User login
Exacerbation history found flawed as COPD risk predictor
Clinical guidelines recommend use of exacerbation history in choosing therapies to predict the risk for chronic obstructive pulmonary disease exacerbations, but an analysis of data from three different clinical studies has found that exacerbation history alone is not the most accurate risk-prediction tool – and that it may even cause harm in some situations.
“Our results present a cautionary tale for the potential risk of harm to patients when naively applying risk stratification algorithms across different clinical settings,” lead author Joseph Khoa Ho, PharmD, a master’s candidate in pharmaceutical sciences at the University of British Columbia, Vancouver, told this news organization.
he said. “However, the prediction models required re-evaluation and setting-specific recalibration in order to yield higher clinical utility.”
The study, known as IMPACT, analyzed three trials that enrolled 4,107 patients at varying levels of moderate or severe exacerbation risks: the placebo arm of the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421); the Long-term Oxygen Treatment Trial (LOTT; N = 595); and the placebo arm of the Towards a Revolution in COPD Health trial (TORCH; N = 1,091). The exacerbation risks were low, medium, and high in the three respective trials.
The study, published online in the journal CHEST, compared the performance of three risk-stratification algorithms: exacerbation history; the model that Loes C.M. Bertens, PhD, and colleagues in the Netherlands developed in 2013; and the latest version of the Acute COPD Exacerbation Prediction Tool, known as ACCEPT.
Results of the analysis
The study used area under the curve (AUC), a method of evaluating effectiveness or efficiency, to compare performance of the prediction algorithms. ACCEPT outperformed exacerbation history and the Bertens algorithm in all the LOTT (medium risk) and TORCH (high risk) samples, both of which were statistically significant. In SUMMIT (low risk), Bertens and ACCEPT outperformed exacerbation history, which was statistically significant.
The AUC for exacerbation history alone in predicting future exacerbations in SUMMIT, LOTT, and TORCH was 0.59 (95% confidence interval, 0.57-0.61), 0.63 (95% CI, 0.59-0.67), and 0.65 (95% CI, 0.63-0.68), respectively. Bertens had a higher AUC, compared with exacerbation history alone in SUMMIT (increase of 0.10, P < .001) and TORCH (increase of 0.05, P < .001), but not in LOTT (increase of 0.01, P = .84).
ACCEPT had higher AUC, compared with exacerbation history alone in all study samples, by 0.08 (P < .001), 0.07 (P = .001) and 0.10 (P < .001), respectively. Compared with Bertens, ACCEPT had higher AUC by 0.06 (P = .001) in LOTT and 0.05 (P < .001) in TORCH, whereas the AUCs were not different in SUMMIT (change of –0.02, P = .16).
Study rationale
Senior author Mohsen Sadatsafavi, MD, PhD, associate professor of pharmaceutical sciences at the University of British Columbia, told this news organization that this study was inspired by a study in cardiology earlier in 2022 that found that the performance of the multitude of risk-prediction tools used to evaluate cardiovascular disease risk can vary widely if they’re not calibrated for new patient populations.
“The main finding was that exacerbation history alone can be harmful even if it is applied at different risk levels,” Dr. Sadatsafavi said of the IMPACT study. “No algorithm could be universally applicable, but exacerbation history has a very high chance of being worse than not doing any risk stratification at all and simply giving medication to all patients.”
Exacerbation history was considered harmful because it generated a lower net benefit than the either Bertens or ACCEPT, the IMPACT study found.
The benefit of the two risk-prediction tools is that they can be recalibrated, Dr. Sadatsafavi said. “You don’t have that luxury with exacerbation history, because it’s just a fixed positive or negative history,” he said. “We need to be quite cognizant of the difference in lung attacks in different populations and the fact that exacerbation history has very different performance in different groups and might be harmful when applied in certain populations. We suggest the use of the risk-stratification tools as a better proper statistical model.”
Expert comment
“As the authors point out, current guidelines for COPD management recommend preventive exacerbation therapy considering the patient’s exacerbation history,” Mary Jo S. Farmer, MD, PhD, assistant professor at the University of Massachusetts Chan Medical School-Baystate, Worcester, said via email. “However, this strategy has demonstrated harm in some situations.”
She noted that the multivariable prediction models were more accurate than exacerbation history alone for predicting 12-month risk of moderate/severe COPD exacerbations but that no algorithm was superior in clinical utility across all samples.
“The authors conclude that the highest accuracy of a risk prediction model can be achieved when the model is recalibrated based on the baseline exacerbation risk of the study population in question,” Dr. Farmer added.
The study received funding from the Canadian Institutes of Health Research. Dr. Ho, Dr. Sadatsafavi, and Dr. Farmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinical guidelines recommend use of exacerbation history in choosing therapies to predict the risk for chronic obstructive pulmonary disease exacerbations, but an analysis of data from three different clinical studies has found that exacerbation history alone is not the most accurate risk-prediction tool – and that it may even cause harm in some situations.
“Our results present a cautionary tale for the potential risk of harm to patients when naively applying risk stratification algorithms across different clinical settings,” lead author Joseph Khoa Ho, PharmD, a master’s candidate in pharmaceutical sciences at the University of British Columbia, Vancouver, told this news organization.
he said. “However, the prediction models required re-evaluation and setting-specific recalibration in order to yield higher clinical utility.”
The study, known as IMPACT, analyzed three trials that enrolled 4,107 patients at varying levels of moderate or severe exacerbation risks: the placebo arm of the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421); the Long-term Oxygen Treatment Trial (LOTT; N = 595); and the placebo arm of the Towards a Revolution in COPD Health trial (TORCH; N = 1,091). The exacerbation risks were low, medium, and high in the three respective trials.
The study, published online in the journal CHEST, compared the performance of three risk-stratification algorithms: exacerbation history; the model that Loes C.M. Bertens, PhD, and colleagues in the Netherlands developed in 2013; and the latest version of the Acute COPD Exacerbation Prediction Tool, known as ACCEPT.
Results of the analysis
The study used area under the curve (AUC), a method of evaluating effectiveness or efficiency, to compare performance of the prediction algorithms. ACCEPT outperformed exacerbation history and the Bertens algorithm in all the LOTT (medium risk) and TORCH (high risk) samples, both of which were statistically significant. In SUMMIT (low risk), Bertens and ACCEPT outperformed exacerbation history, which was statistically significant.
The AUC for exacerbation history alone in predicting future exacerbations in SUMMIT, LOTT, and TORCH was 0.59 (95% confidence interval, 0.57-0.61), 0.63 (95% CI, 0.59-0.67), and 0.65 (95% CI, 0.63-0.68), respectively. Bertens had a higher AUC, compared with exacerbation history alone in SUMMIT (increase of 0.10, P < .001) and TORCH (increase of 0.05, P < .001), but not in LOTT (increase of 0.01, P = .84).
ACCEPT had higher AUC, compared with exacerbation history alone in all study samples, by 0.08 (P < .001), 0.07 (P = .001) and 0.10 (P < .001), respectively. Compared with Bertens, ACCEPT had higher AUC by 0.06 (P = .001) in LOTT and 0.05 (P < .001) in TORCH, whereas the AUCs were not different in SUMMIT (change of –0.02, P = .16).
Study rationale
Senior author Mohsen Sadatsafavi, MD, PhD, associate professor of pharmaceutical sciences at the University of British Columbia, told this news organization that this study was inspired by a study in cardiology earlier in 2022 that found that the performance of the multitude of risk-prediction tools used to evaluate cardiovascular disease risk can vary widely if they’re not calibrated for new patient populations.
“The main finding was that exacerbation history alone can be harmful even if it is applied at different risk levels,” Dr. Sadatsafavi said of the IMPACT study. “No algorithm could be universally applicable, but exacerbation history has a very high chance of being worse than not doing any risk stratification at all and simply giving medication to all patients.”
Exacerbation history was considered harmful because it generated a lower net benefit than the either Bertens or ACCEPT, the IMPACT study found.
The benefit of the two risk-prediction tools is that they can be recalibrated, Dr. Sadatsafavi said. “You don’t have that luxury with exacerbation history, because it’s just a fixed positive or negative history,” he said. “We need to be quite cognizant of the difference in lung attacks in different populations and the fact that exacerbation history has very different performance in different groups and might be harmful when applied in certain populations. We suggest the use of the risk-stratification tools as a better proper statistical model.”
Expert comment
“As the authors point out, current guidelines for COPD management recommend preventive exacerbation therapy considering the patient’s exacerbation history,” Mary Jo S. Farmer, MD, PhD, assistant professor at the University of Massachusetts Chan Medical School-Baystate, Worcester, said via email. “However, this strategy has demonstrated harm in some situations.”
She noted that the multivariable prediction models were more accurate than exacerbation history alone for predicting 12-month risk of moderate/severe COPD exacerbations but that no algorithm was superior in clinical utility across all samples.
“The authors conclude that the highest accuracy of a risk prediction model can be achieved when the model is recalibrated based on the baseline exacerbation risk of the study population in question,” Dr. Farmer added.
The study received funding from the Canadian Institutes of Health Research. Dr. Ho, Dr. Sadatsafavi, and Dr. Farmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinical guidelines recommend use of exacerbation history in choosing therapies to predict the risk for chronic obstructive pulmonary disease exacerbations, but an analysis of data from three different clinical studies has found that exacerbation history alone is not the most accurate risk-prediction tool – and that it may even cause harm in some situations.
“Our results present a cautionary tale for the potential risk of harm to patients when naively applying risk stratification algorithms across different clinical settings,” lead author Joseph Khoa Ho, PharmD, a master’s candidate in pharmaceutical sciences at the University of British Columbia, Vancouver, told this news organization.
he said. “However, the prediction models required re-evaluation and setting-specific recalibration in order to yield higher clinical utility.”
The study, known as IMPACT, analyzed three trials that enrolled 4,107 patients at varying levels of moderate or severe exacerbation risks: the placebo arm of the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421); the Long-term Oxygen Treatment Trial (LOTT; N = 595); and the placebo arm of the Towards a Revolution in COPD Health trial (TORCH; N = 1,091). The exacerbation risks were low, medium, and high in the three respective trials.
The study, published online in the journal CHEST, compared the performance of three risk-stratification algorithms: exacerbation history; the model that Loes C.M. Bertens, PhD, and colleagues in the Netherlands developed in 2013; and the latest version of the Acute COPD Exacerbation Prediction Tool, known as ACCEPT.
Results of the analysis
The study used area under the curve (AUC), a method of evaluating effectiveness or efficiency, to compare performance of the prediction algorithms. ACCEPT outperformed exacerbation history and the Bertens algorithm in all the LOTT (medium risk) and TORCH (high risk) samples, both of which were statistically significant. In SUMMIT (low risk), Bertens and ACCEPT outperformed exacerbation history, which was statistically significant.
The AUC for exacerbation history alone in predicting future exacerbations in SUMMIT, LOTT, and TORCH was 0.59 (95% confidence interval, 0.57-0.61), 0.63 (95% CI, 0.59-0.67), and 0.65 (95% CI, 0.63-0.68), respectively. Bertens had a higher AUC, compared with exacerbation history alone in SUMMIT (increase of 0.10, P < .001) and TORCH (increase of 0.05, P < .001), but not in LOTT (increase of 0.01, P = .84).
ACCEPT had higher AUC, compared with exacerbation history alone in all study samples, by 0.08 (P < .001), 0.07 (P = .001) and 0.10 (P < .001), respectively. Compared with Bertens, ACCEPT had higher AUC by 0.06 (P = .001) in LOTT and 0.05 (P < .001) in TORCH, whereas the AUCs were not different in SUMMIT (change of –0.02, P = .16).
Study rationale
Senior author Mohsen Sadatsafavi, MD, PhD, associate professor of pharmaceutical sciences at the University of British Columbia, told this news organization that this study was inspired by a study in cardiology earlier in 2022 that found that the performance of the multitude of risk-prediction tools used to evaluate cardiovascular disease risk can vary widely if they’re not calibrated for new patient populations.
“The main finding was that exacerbation history alone can be harmful even if it is applied at different risk levels,” Dr. Sadatsafavi said of the IMPACT study. “No algorithm could be universally applicable, but exacerbation history has a very high chance of being worse than not doing any risk stratification at all and simply giving medication to all patients.”
Exacerbation history was considered harmful because it generated a lower net benefit than the either Bertens or ACCEPT, the IMPACT study found.
The benefit of the two risk-prediction tools is that they can be recalibrated, Dr. Sadatsafavi said. “You don’t have that luxury with exacerbation history, because it’s just a fixed positive or negative history,” he said. “We need to be quite cognizant of the difference in lung attacks in different populations and the fact that exacerbation history has very different performance in different groups and might be harmful when applied in certain populations. We suggest the use of the risk-stratification tools as a better proper statistical model.”
Expert comment
“As the authors point out, current guidelines for COPD management recommend preventive exacerbation therapy considering the patient’s exacerbation history,” Mary Jo S. Farmer, MD, PhD, assistant professor at the University of Massachusetts Chan Medical School-Baystate, Worcester, said via email. “However, this strategy has demonstrated harm in some situations.”
She noted that the multivariable prediction models were more accurate than exacerbation history alone for predicting 12-month risk of moderate/severe COPD exacerbations but that no algorithm was superior in clinical utility across all samples.
“The authors conclude that the highest accuracy of a risk prediction model can be achieved when the model is recalibrated based on the baseline exacerbation risk of the study population in question,” Dr. Farmer added.
The study received funding from the Canadian Institutes of Health Research. Dr. Ho, Dr. Sadatsafavi, and Dr. Farmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL CHEST
Comorbidities and the prognosis of chronic obstructive pulmonary disease
Strict control of comorbidities in patients with chronic obstructive pulmonary disease decreases exacerbations and morbimortality, and avoids readmissions. An increasing number of women have the disease, which progresses differently in women than in men and even has different comorbidities.
said Belén Alonso, MD, PhD, coordinator of the COPD Working Group of the Spanish Society of Internal Medicine. Up to 73 comorbidities associated with chronic obstructive pulmonary disease have been described. Dr. Alonso made these remarks during her presentation at the Comorbidities in Chronic Obstructive Pulmonary Disease Panel, which took place during the 43rd Conference of the Spanish Society of Internal Medicine (SEMI), in Gijón, Spain.
According to the scientific society’s press release, moderator María Gómez Antúnez, MD, stated, “The correct approach and treatment of these comorbidities is fundamental to improve the quality of life of the patient, decrease exacerbations, avoid readmissions, and decrease morbimortality in people with chronic obstructive pulmonary disease.”
The different works published, two of them by the SEMI COPD Working Group (ECCO and ESMI studies), indicate that the main comorbidities of patients with that pneumopathy are arterial hypertension, dyslipidemia, diabetes, heart failure, atrial fibrillation, ischemic heart disease, chronic kidney disease, peripheral arterial disease, and osteoporosis. Chronic hepatopathy, pulmonary neoplasm, depression, and cerebrovascular disease are less common.
73 comorbidities described
Dr. Alonso told this news organization, “Of those 73 comorbidities, some of the lesser known or less attention grabbing, according to a paper that we brought to the panel, include sleep disorders that encompass insomnia, nightmares, night terrors, sleep apneas, or hypopneas. Other lesser-known comorbidities related to cognitive decline, with patterns that reflect that up to 60% [of patients] may have some degree of deterioration, involve the disease phase, hypoxemia, or degree of inflammation. On the other hand, it has also been associated with Parkinson’s disease and gastroesophageal reflux, among many more that arise from the cardiovascular sphere.”
One paper reveals that more than 78% of patients with chronic obstructive pulmonary disease have one associated comorbidity, almost 69% have two, and 47.9% have three.
“Based on gender, comorbidities are different. In women, it is well observed that anxiety, depression, and osteoporosis are more common. However, hypertension, ischemic heart disease, and diabetes are more common in men with chronic obstructive pulmonary disease,” she stated.
“The pulmonary disease in question also progresses differently in men and women. In women, onset is at younger ages – between 40 and 50 years – and in men, after 50. Likewise, it appears that the disease progresses more quickly, which coincides with a worse quality of life (since dyspnea is tolerated less) and exceeds the anatomical differences, where hormonal influences play a dominant role,” Dr. Alonso stressed.
Reciprocal prognosis
Dr. Alonso stated, “The prognostic importance of comorbidities in the disease is reciprocal. In other words, if there are comorbidities that we do not look for or treat, they are going to have a negative influence on the chronic obstructive pulmonary disease. The disease will progress more and elevate the risk of exacerbations (the most important prognostic factor of that disease). In turn, if we are not treating the disease well, not only pharmacologically, it will have negative repercussions on the comorbidities. It will progress and have negative connotations, such as diabetes or ischemic heart disease.”
The aforementioned ECCO and ESMI studies include patients in internal medicine with exacerbations where the most common comorbidities have been mapped out, although there is also extensive research on comorbidities in patients who are admitted to departments other than internal medicine. “With regard to prognostic implications, our working group very clearly observed the comorbidities and the comorbidome, that solar system that appears so much in medical conferences and forums, which implies that proximity to the center of that solar system is related more to mortality, anxiety, depression, and breast cancer. Other pathologies, such as ischemic heart disease or dyslipidemia, are outside of that territory of greater risk, in which we have been more pioneering than other groups,” said Dr. Alonso.
The current trend is that the age of these patients is increasing, and there are more and more women with this pathology. According to the latest report from the Ministry of Health on respiratory diseases, the prevalence of chronic obstructive pulmonary disease among the population 40 years and older is around 33.9 cases per 1,000 inhabitants, more than twice as common in men than in women (47.7 vs. 21.3). Prevalence increases with age after 40 years progressively until reaching the greatest frequency in the 80- to 84-year-old age group.
In 2019, the number of deaths due to chronic obstructive pulmonary disease in Spain was 13,808 (9,907 men and 3,901 women), with a crude mortality rate of 29.3 deaths per 100,000 inhabitants. This toll decreased in comparison with that of 2018. Chronic obstructive pulmonary disease causes 2.5 times more deaths in men than in women. From 2001 to 2019, mortality due to that pathology declined by 43% in men and women. The decrease was almost 50% in men and 33% in women.
Overlap syndrome prevalent
Javier Sánchez Lora, MD, of the internal medicine department of the Virgen de la Victoria de Málaga University Clinical Hospital, discussed chronic obstructive pulmonary disease and sleep disorders. More concretely, he spoke about overlap syndrome: chronic obstructive pulmonary disease plus obstructive sleep apnea. According to the international consensus document on obstructive sleep apnea, the diagnosis requires an apnea-hypopnea index (AHI) equal to or greater than 15 per hour or equal to or greater than 5. The patient must also have one or more of the following factors: excessive daytime sleepiness, sleep that is not restful, excessive fatigue, and deterioration in quality of life related to sleep and not justified by other causes.
“The overlap syndrome affects 3%-66% of chronic obstructive pulmonary diseases and 7%-55% of obstructive sleep apnea,” said Dr. Sánchez Lora. This syndrome has important effects on different systems: at the cardiovascular level (arterial and pulmonary hypertension, heart failure, stroke, arrhythmias, ischemic heart disease, pulmonary thromboembolism), metabolic (insulin resistance, diabetes, metabolic syndrome), neurocognitive (dementia, depression), and neoplastic (lung, pancreas, esophagus) effects.
“These patients have a worse prognosis than those that have these pathologies alone. During sleep, they experience more frequent episodes of oxygen desaturation and they have a longer total period of sleep with hypoxemia and hypercapnia than those with obstructive apnea alone without chronic obstructive pulmonary disease,” said Dr. Sánchez Lora.
The apneic events of patients with the syndrome have a more profound hypoxemia and more arrhythmias, in addition to them being more susceptible to developing pulmonary hypertension than those with chronic obstructive pulmonary disease or sleep apnea alone. “The good news is that in patients with overlap, the use of ventilation with positive pressure reduces all causes of hospitalization and the visits to the emergency room, as well as the moderate and severe exacerbations of the disease.”
Dr. Sánchez Lora referred to a series of recommendations in clinical practice for the diagnosis and treatment of overlap syndrome: screening, combined therapy of hygienic-dietary measures, and the use of continuous positive respiratory pressure. Oxygen therapy to correct isolated nocturnal desaturations has not shown benefits in survival, although a benefit trial of symptoms attributed to nocturnal hypoxemia in patients with significant comorbidity can be conducted.
Underdiagnosis
“During the panel, we also spoke about the importance that as part of internal medicine we need to make an effort to reduce the underdiagnosis of chronic pulmonary disease and its comorbidities. Specialists in internal medicine need to become aware that this pathology is not only pulmonary, but also multisystemic, complex, heterogenous, and very variable even in the same patient,” said Dr. Sánchez Lora.
Dr. Alonso said, “Regarding the importance of diagnosis of this disease, we continue with an underdiagnosis greater than 70% for men and 80% for women. Secondly, we need to actively seek out the comorbidities associated with chronic obstructive pulmonary disease, even taking advantage of the admission of these patients with exacerbations, which are undesired and common.
“Regarding ongoing trials, we have a study that started during the COVID-19 pandemic, ADEG-EPOC, that involves the adaptation to and impact of severe and very severe exacerbations in patients admitted to our departments,” the specialist indicated.
“In the group, we are also planning to publish an updated agreement, which we already made in 2014, on the most common and important comorbidities associated with chronic obstructive pulmonary disease.” The agreement discusses the 20 most important comorbidities. In addition, the 2023 Gold Guide, which appeared in November 2022, includes a new chapter on updated treatment and the latest developments.
In the last 5 years, Dr. Alonso has collaborated with Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, Ferrer, Fresenius Kabi, GSK, Nestlé, Novo Nordisk, Nutricia, and Menarini. Dr. Sánchez Lora has collaborated with AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, GSK, and Menarini.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
Strict control of comorbidities in patients with chronic obstructive pulmonary disease decreases exacerbations and morbimortality, and avoids readmissions. An increasing number of women have the disease, which progresses differently in women than in men and even has different comorbidities.
said Belén Alonso, MD, PhD, coordinator of the COPD Working Group of the Spanish Society of Internal Medicine. Up to 73 comorbidities associated with chronic obstructive pulmonary disease have been described. Dr. Alonso made these remarks during her presentation at the Comorbidities in Chronic Obstructive Pulmonary Disease Panel, which took place during the 43rd Conference of the Spanish Society of Internal Medicine (SEMI), in Gijón, Spain.
According to the scientific society’s press release, moderator María Gómez Antúnez, MD, stated, “The correct approach and treatment of these comorbidities is fundamental to improve the quality of life of the patient, decrease exacerbations, avoid readmissions, and decrease morbimortality in people with chronic obstructive pulmonary disease.”
The different works published, two of them by the SEMI COPD Working Group (ECCO and ESMI studies), indicate that the main comorbidities of patients with that pneumopathy are arterial hypertension, dyslipidemia, diabetes, heart failure, atrial fibrillation, ischemic heart disease, chronic kidney disease, peripheral arterial disease, and osteoporosis. Chronic hepatopathy, pulmonary neoplasm, depression, and cerebrovascular disease are less common.
73 comorbidities described
Dr. Alonso told this news organization, “Of those 73 comorbidities, some of the lesser known or less attention grabbing, according to a paper that we brought to the panel, include sleep disorders that encompass insomnia, nightmares, night terrors, sleep apneas, or hypopneas. Other lesser-known comorbidities related to cognitive decline, with patterns that reflect that up to 60% [of patients] may have some degree of deterioration, involve the disease phase, hypoxemia, or degree of inflammation. On the other hand, it has also been associated with Parkinson’s disease and gastroesophageal reflux, among many more that arise from the cardiovascular sphere.”
One paper reveals that more than 78% of patients with chronic obstructive pulmonary disease have one associated comorbidity, almost 69% have two, and 47.9% have three.
“Based on gender, comorbidities are different. In women, it is well observed that anxiety, depression, and osteoporosis are more common. However, hypertension, ischemic heart disease, and diabetes are more common in men with chronic obstructive pulmonary disease,” she stated.
“The pulmonary disease in question also progresses differently in men and women. In women, onset is at younger ages – between 40 and 50 years – and in men, after 50. Likewise, it appears that the disease progresses more quickly, which coincides with a worse quality of life (since dyspnea is tolerated less) and exceeds the anatomical differences, where hormonal influences play a dominant role,” Dr. Alonso stressed.
Reciprocal prognosis
Dr. Alonso stated, “The prognostic importance of comorbidities in the disease is reciprocal. In other words, if there are comorbidities that we do not look for or treat, they are going to have a negative influence on the chronic obstructive pulmonary disease. The disease will progress more and elevate the risk of exacerbations (the most important prognostic factor of that disease). In turn, if we are not treating the disease well, not only pharmacologically, it will have negative repercussions on the comorbidities. It will progress and have negative connotations, such as diabetes or ischemic heart disease.”
The aforementioned ECCO and ESMI studies include patients in internal medicine with exacerbations where the most common comorbidities have been mapped out, although there is also extensive research on comorbidities in patients who are admitted to departments other than internal medicine. “With regard to prognostic implications, our working group very clearly observed the comorbidities and the comorbidome, that solar system that appears so much in medical conferences and forums, which implies that proximity to the center of that solar system is related more to mortality, anxiety, depression, and breast cancer. Other pathologies, such as ischemic heart disease or dyslipidemia, are outside of that territory of greater risk, in which we have been more pioneering than other groups,” said Dr. Alonso.
The current trend is that the age of these patients is increasing, and there are more and more women with this pathology. According to the latest report from the Ministry of Health on respiratory diseases, the prevalence of chronic obstructive pulmonary disease among the population 40 years and older is around 33.9 cases per 1,000 inhabitants, more than twice as common in men than in women (47.7 vs. 21.3). Prevalence increases with age after 40 years progressively until reaching the greatest frequency in the 80- to 84-year-old age group.
In 2019, the number of deaths due to chronic obstructive pulmonary disease in Spain was 13,808 (9,907 men and 3,901 women), with a crude mortality rate of 29.3 deaths per 100,000 inhabitants. This toll decreased in comparison with that of 2018. Chronic obstructive pulmonary disease causes 2.5 times more deaths in men than in women. From 2001 to 2019, mortality due to that pathology declined by 43% in men and women. The decrease was almost 50% in men and 33% in women.
Overlap syndrome prevalent
Javier Sánchez Lora, MD, of the internal medicine department of the Virgen de la Victoria de Málaga University Clinical Hospital, discussed chronic obstructive pulmonary disease and sleep disorders. More concretely, he spoke about overlap syndrome: chronic obstructive pulmonary disease plus obstructive sleep apnea. According to the international consensus document on obstructive sleep apnea, the diagnosis requires an apnea-hypopnea index (AHI) equal to or greater than 15 per hour or equal to or greater than 5. The patient must also have one or more of the following factors: excessive daytime sleepiness, sleep that is not restful, excessive fatigue, and deterioration in quality of life related to sleep and not justified by other causes.
“The overlap syndrome affects 3%-66% of chronic obstructive pulmonary diseases and 7%-55% of obstructive sleep apnea,” said Dr. Sánchez Lora. This syndrome has important effects on different systems: at the cardiovascular level (arterial and pulmonary hypertension, heart failure, stroke, arrhythmias, ischemic heart disease, pulmonary thromboembolism), metabolic (insulin resistance, diabetes, metabolic syndrome), neurocognitive (dementia, depression), and neoplastic (lung, pancreas, esophagus) effects.
“These patients have a worse prognosis than those that have these pathologies alone. During sleep, they experience more frequent episodes of oxygen desaturation and they have a longer total period of sleep with hypoxemia and hypercapnia than those with obstructive apnea alone without chronic obstructive pulmonary disease,” said Dr. Sánchez Lora.
The apneic events of patients with the syndrome have a more profound hypoxemia and more arrhythmias, in addition to them being more susceptible to developing pulmonary hypertension than those with chronic obstructive pulmonary disease or sleep apnea alone. “The good news is that in patients with overlap, the use of ventilation with positive pressure reduces all causes of hospitalization and the visits to the emergency room, as well as the moderate and severe exacerbations of the disease.”
Dr. Sánchez Lora referred to a series of recommendations in clinical practice for the diagnosis and treatment of overlap syndrome: screening, combined therapy of hygienic-dietary measures, and the use of continuous positive respiratory pressure. Oxygen therapy to correct isolated nocturnal desaturations has not shown benefits in survival, although a benefit trial of symptoms attributed to nocturnal hypoxemia in patients with significant comorbidity can be conducted.
Underdiagnosis
“During the panel, we also spoke about the importance that as part of internal medicine we need to make an effort to reduce the underdiagnosis of chronic pulmonary disease and its comorbidities. Specialists in internal medicine need to become aware that this pathology is not only pulmonary, but also multisystemic, complex, heterogenous, and very variable even in the same patient,” said Dr. Sánchez Lora.
Dr. Alonso said, “Regarding the importance of diagnosis of this disease, we continue with an underdiagnosis greater than 70% for men and 80% for women. Secondly, we need to actively seek out the comorbidities associated with chronic obstructive pulmonary disease, even taking advantage of the admission of these patients with exacerbations, which are undesired and common.
“Regarding ongoing trials, we have a study that started during the COVID-19 pandemic, ADEG-EPOC, that involves the adaptation to and impact of severe and very severe exacerbations in patients admitted to our departments,” the specialist indicated.
“In the group, we are also planning to publish an updated agreement, which we already made in 2014, on the most common and important comorbidities associated with chronic obstructive pulmonary disease.” The agreement discusses the 20 most important comorbidities. In addition, the 2023 Gold Guide, which appeared in November 2022, includes a new chapter on updated treatment and the latest developments.
In the last 5 years, Dr. Alonso has collaborated with Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, Ferrer, Fresenius Kabi, GSK, Nestlé, Novo Nordisk, Nutricia, and Menarini. Dr. Sánchez Lora has collaborated with AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, GSK, and Menarini.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
Strict control of comorbidities in patients with chronic obstructive pulmonary disease decreases exacerbations and morbimortality, and avoids readmissions. An increasing number of women have the disease, which progresses differently in women than in men and even has different comorbidities.
said Belén Alonso, MD, PhD, coordinator of the COPD Working Group of the Spanish Society of Internal Medicine. Up to 73 comorbidities associated with chronic obstructive pulmonary disease have been described. Dr. Alonso made these remarks during her presentation at the Comorbidities in Chronic Obstructive Pulmonary Disease Panel, which took place during the 43rd Conference of the Spanish Society of Internal Medicine (SEMI), in Gijón, Spain.
According to the scientific society’s press release, moderator María Gómez Antúnez, MD, stated, “The correct approach and treatment of these comorbidities is fundamental to improve the quality of life of the patient, decrease exacerbations, avoid readmissions, and decrease morbimortality in people with chronic obstructive pulmonary disease.”
The different works published, two of them by the SEMI COPD Working Group (ECCO and ESMI studies), indicate that the main comorbidities of patients with that pneumopathy are arterial hypertension, dyslipidemia, diabetes, heart failure, atrial fibrillation, ischemic heart disease, chronic kidney disease, peripheral arterial disease, and osteoporosis. Chronic hepatopathy, pulmonary neoplasm, depression, and cerebrovascular disease are less common.
73 comorbidities described
Dr. Alonso told this news organization, “Of those 73 comorbidities, some of the lesser known or less attention grabbing, according to a paper that we brought to the panel, include sleep disorders that encompass insomnia, nightmares, night terrors, sleep apneas, or hypopneas. Other lesser-known comorbidities related to cognitive decline, with patterns that reflect that up to 60% [of patients] may have some degree of deterioration, involve the disease phase, hypoxemia, or degree of inflammation. On the other hand, it has also been associated with Parkinson’s disease and gastroesophageal reflux, among many more that arise from the cardiovascular sphere.”
One paper reveals that more than 78% of patients with chronic obstructive pulmonary disease have one associated comorbidity, almost 69% have two, and 47.9% have three.
“Based on gender, comorbidities are different. In women, it is well observed that anxiety, depression, and osteoporosis are more common. However, hypertension, ischemic heart disease, and diabetes are more common in men with chronic obstructive pulmonary disease,” she stated.
“The pulmonary disease in question also progresses differently in men and women. In women, onset is at younger ages – between 40 and 50 years – and in men, after 50. Likewise, it appears that the disease progresses more quickly, which coincides with a worse quality of life (since dyspnea is tolerated less) and exceeds the anatomical differences, where hormonal influences play a dominant role,” Dr. Alonso stressed.
Reciprocal prognosis
Dr. Alonso stated, “The prognostic importance of comorbidities in the disease is reciprocal. In other words, if there are comorbidities that we do not look for or treat, they are going to have a negative influence on the chronic obstructive pulmonary disease. The disease will progress more and elevate the risk of exacerbations (the most important prognostic factor of that disease). In turn, if we are not treating the disease well, not only pharmacologically, it will have negative repercussions on the comorbidities. It will progress and have negative connotations, such as diabetes or ischemic heart disease.”
The aforementioned ECCO and ESMI studies include patients in internal medicine with exacerbations where the most common comorbidities have been mapped out, although there is also extensive research on comorbidities in patients who are admitted to departments other than internal medicine. “With regard to prognostic implications, our working group very clearly observed the comorbidities and the comorbidome, that solar system that appears so much in medical conferences and forums, which implies that proximity to the center of that solar system is related more to mortality, anxiety, depression, and breast cancer. Other pathologies, such as ischemic heart disease or dyslipidemia, are outside of that territory of greater risk, in which we have been more pioneering than other groups,” said Dr. Alonso.
The current trend is that the age of these patients is increasing, and there are more and more women with this pathology. According to the latest report from the Ministry of Health on respiratory diseases, the prevalence of chronic obstructive pulmonary disease among the population 40 years and older is around 33.9 cases per 1,000 inhabitants, more than twice as common in men than in women (47.7 vs. 21.3). Prevalence increases with age after 40 years progressively until reaching the greatest frequency in the 80- to 84-year-old age group.
In 2019, the number of deaths due to chronic obstructive pulmonary disease in Spain was 13,808 (9,907 men and 3,901 women), with a crude mortality rate of 29.3 deaths per 100,000 inhabitants. This toll decreased in comparison with that of 2018. Chronic obstructive pulmonary disease causes 2.5 times more deaths in men than in women. From 2001 to 2019, mortality due to that pathology declined by 43% in men and women. The decrease was almost 50% in men and 33% in women.
Overlap syndrome prevalent
Javier Sánchez Lora, MD, of the internal medicine department of the Virgen de la Victoria de Málaga University Clinical Hospital, discussed chronic obstructive pulmonary disease and sleep disorders. More concretely, he spoke about overlap syndrome: chronic obstructive pulmonary disease plus obstructive sleep apnea. According to the international consensus document on obstructive sleep apnea, the diagnosis requires an apnea-hypopnea index (AHI) equal to or greater than 15 per hour or equal to or greater than 5. The patient must also have one or more of the following factors: excessive daytime sleepiness, sleep that is not restful, excessive fatigue, and deterioration in quality of life related to sleep and not justified by other causes.
“The overlap syndrome affects 3%-66% of chronic obstructive pulmonary diseases and 7%-55% of obstructive sleep apnea,” said Dr. Sánchez Lora. This syndrome has important effects on different systems: at the cardiovascular level (arterial and pulmonary hypertension, heart failure, stroke, arrhythmias, ischemic heart disease, pulmonary thromboembolism), metabolic (insulin resistance, diabetes, metabolic syndrome), neurocognitive (dementia, depression), and neoplastic (lung, pancreas, esophagus) effects.
“These patients have a worse prognosis than those that have these pathologies alone. During sleep, they experience more frequent episodes of oxygen desaturation and they have a longer total period of sleep with hypoxemia and hypercapnia than those with obstructive apnea alone without chronic obstructive pulmonary disease,” said Dr. Sánchez Lora.
The apneic events of patients with the syndrome have a more profound hypoxemia and more arrhythmias, in addition to them being more susceptible to developing pulmonary hypertension than those with chronic obstructive pulmonary disease or sleep apnea alone. “The good news is that in patients with overlap, the use of ventilation with positive pressure reduces all causes of hospitalization and the visits to the emergency room, as well as the moderate and severe exacerbations of the disease.”
Dr. Sánchez Lora referred to a series of recommendations in clinical practice for the diagnosis and treatment of overlap syndrome: screening, combined therapy of hygienic-dietary measures, and the use of continuous positive respiratory pressure. Oxygen therapy to correct isolated nocturnal desaturations has not shown benefits in survival, although a benefit trial of symptoms attributed to nocturnal hypoxemia in patients with significant comorbidity can be conducted.
Underdiagnosis
“During the panel, we also spoke about the importance that as part of internal medicine we need to make an effort to reduce the underdiagnosis of chronic pulmonary disease and its comorbidities. Specialists in internal medicine need to become aware that this pathology is not only pulmonary, but also multisystemic, complex, heterogenous, and very variable even in the same patient,” said Dr. Sánchez Lora.
Dr. Alonso said, “Regarding the importance of diagnosis of this disease, we continue with an underdiagnosis greater than 70% for men and 80% for women. Secondly, we need to actively seek out the comorbidities associated with chronic obstructive pulmonary disease, even taking advantage of the admission of these patients with exacerbations, which are undesired and common.
“Regarding ongoing trials, we have a study that started during the COVID-19 pandemic, ADEG-EPOC, that involves the adaptation to and impact of severe and very severe exacerbations in patients admitted to our departments,” the specialist indicated.
“In the group, we are also planning to publish an updated agreement, which we already made in 2014, on the most common and important comorbidities associated with chronic obstructive pulmonary disease.” The agreement discusses the 20 most important comorbidities. In addition, the 2023 Gold Guide, which appeared in November 2022, includes a new chapter on updated treatment and the latest developments.
In the last 5 years, Dr. Alonso has collaborated with Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, Ferrer, Fresenius Kabi, GSK, Nestlé, Novo Nordisk, Nutricia, and Menarini. Dr. Sánchez Lora has collaborated with AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, GSK, and Menarini.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
The latest on ERS/ATS lung function interpretation guidelines and bronchodilator testing
The European Respiratory Society (ERS) and the American Thoracic Society (ATS) just published an updated technical standard on lung function interpretation. It’s impossible to review in its entirety without more space, so I’ll settle for covering what the authors say about bronchodilator testing. But before I do that, it’s worth reviewing what we think we know about having a patient perform spirometry, inhale a bronchodilator, and then repeat it. This is colloquially referred to as pre- and postbronchodilator testing.
Administering a bronchodilator and measuring changes in lung function seems simple and intuitive. It is biologically plausible that improvement would predict treatment response. It should allow for phenotyping airway diseases and quantifying exacerbation risk. It is easy to perform and can be done in the clinic. But in practice it falls short of its purpose, in part because of technical factors but also because it doesn’t really have a purpose.
The last interpretative strategies document from the ERS/ATS was published in 2005. Reading it many years ago, I was struck by the contrast between our reliance on bronchodilator response and its lack of standardization. It seemed that there was none. After making statements like, “There is no consensus on what constitutes reversibility in subjects with airflow obstruction” and “There is no consensus on how a bronchodilator response should be expressed, the variables to be used, and finally, the kind, dose, and inhalation mode of bronchodilator agent,” the 2005 ERS/ATS authors suggest using the criteria most clinicians are familiar with: A change of 12% and 200 cc in FEV1 or FVC marks a “significant” bronchodilator response. Four puffs of albuterol (100 mcg each for a total of 400 mcg) with a 15- to 20-minute wait before repeat spirometry is also suggested.
The 2005 iteration acknowledges that a significant bronchodilator response isn’t a very accurate predictor of, well, anything. It doesn’t reliably differentiate COPD from asthma and it’s never been as sensitive as bronchoprovocation testing for diagnosing airway reactivity. The absence of a significant bronchodilator response does not preclude a 2-month trial of the same medicine used to test for response. Given these problems with standardization and accuracy, I was left wondering why anyone bothers ordering the test at all.
In my own practice, I continued to order, conduct, and interpret bronchodilator response according to the suggestions made by the ERS/ATS in 2005 when trying to diagnose asthma. I recognized that a nonsignificant response meant nothing, but bronchodilator response testing was easier to obtain than bronchoprovocation at my hospital. It was a matter of convenience for me and the patient. According to the Global Initiative for Asthma (GINA) Guidelines, a significant bronchodilator response conducted and interpreted as recommended by the ERS/ATS 2005 standard provides objective confirmation of asthma in the presence of characteristic clinical symptoms.
The headline from the ERS/ATS 2022 Technical Standard is that the 12% and 200-cc criteria suggested in 2005 are being retired. Why? Well, much of the variability in the 2005 criteria is explained by height, age, sex, and baseline lung function. These factors obscure change related to intrinsic airway abnormalities. Instead, the authors suggest using a threshold change in the predicted values of FEV1 and FVC to determine a significant response. Because predicted values incorporate age, height, and sex, the impact from these variables is minimized. Using a percent predicted (PPD) threshold will also minimize the effect from the inverse relationship between measured values and bronchodilator response.
A 10% change in the PPD value for either FEV1 or FVC constitutes a significant bronchodilator response. Ten percent was chosen because it represents the statistically defined upper limit of normal response; and a greater than 8% change in bronchodilator response is associated with mortality, implying that values above this threshold connote disease. The technical standard seems to be on solid ground here; the rationale is mathematically appropriate and evidence based. The new definition will certainly improve precision.
There’s really no progress on accuracy, though. There are no comments on the protocol to be followed or clinical indications. The reader is referred to the ERS/ATS 2019 technical statement on standardization of spirometry. The statement on standardization is short on details, too, and refers the reader to an online supplement for a suggested protocol. The suggested protocol is identical to that suggested in 2005.
In summary, not a lot is different in the world of bronchodilator response testing. The definition is different now, and though it’s likely to be more precise, we still don’t know enough about accuracy. It’s nice to know that the new criteria will predict mortality, but in clinical practice we don’t use the test for that purpose. The 2022 technical standard acknowledges this and other limitations in a “future directions” paragraph. Perhaps we’ll know more when the next iteration is published.
Dr. Holley is a professor of medicine at Uniformed Services University of the Health Sciences. Bethesda, Md., and a pulmonary medicine/critical care physician at MedStar Washington Hospital Center, Washington. He reported conflicts of interest with Metapharm and the American College of Chest Physicians. A version of this article first appeared on Medscape.com.
The European Respiratory Society (ERS) and the American Thoracic Society (ATS) just published an updated technical standard on lung function interpretation. It’s impossible to review in its entirety without more space, so I’ll settle for covering what the authors say about bronchodilator testing. But before I do that, it’s worth reviewing what we think we know about having a patient perform spirometry, inhale a bronchodilator, and then repeat it. This is colloquially referred to as pre- and postbronchodilator testing.
Administering a bronchodilator and measuring changes in lung function seems simple and intuitive. It is biologically plausible that improvement would predict treatment response. It should allow for phenotyping airway diseases and quantifying exacerbation risk. It is easy to perform and can be done in the clinic. But in practice it falls short of its purpose, in part because of technical factors but also because it doesn’t really have a purpose.
The last interpretative strategies document from the ERS/ATS was published in 2005. Reading it many years ago, I was struck by the contrast between our reliance on bronchodilator response and its lack of standardization. It seemed that there was none. After making statements like, “There is no consensus on what constitutes reversibility in subjects with airflow obstruction” and “There is no consensus on how a bronchodilator response should be expressed, the variables to be used, and finally, the kind, dose, and inhalation mode of bronchodilator agent,” the 2005 ERS/ATS authors suggest using the criteria most clinicians are familiar with: A change of 12% and 200 cc in FEV1 or FVC marks a “significant” bronchodilator response. Four puffs of albuterol (100 mcg each for a total of 400 mcg) with a 15- to 20-minute wait before repeat spirometry is also suggested.
The 2005 iteration acknowledges that a significant bronchodilator response isn’t a very accurate predictor of, well, anything. It doesn’t reliably differentiate COPD from asthma and it’s never been as sensitive as bronchoprovocation testing for diagnosing airway reactivity. The absence of a significant bronchodilator response does not preclude a 2-month trial of the same medicine used to test for response. Given these problems with standardization and accuracy, I was left wondering why anyone bothers ordering the test at all.
In my own practice, I continued to order, conduct, and interpret bronchodilator response according to the suggestions made by the ERS/ATS in 2005 when trying to diagnose asthma. I recognized that a nonsignificant response meant nothing, but bronchodilator response testing was easier to obtain than bronchoprovocation at my hospital. It was a matter of convenience for me and the patient. According to the Global Initiative for Asthma (GINA) Guidelines, a significant bronchodilator response conducted and interpreted as recommended by the ERS/ATS 2005 standard provides objective confirmation of asthma in the presence of characteristic clinical symptoms.
The headline from the ERS/ATS 2022 Technical Standard is that the 12% and 200-cc criteria suggested in 2005 are being retired. Why? Well, much of the variability in the 2005 criteria is explained by height, age, sex, and baseline lung function. These factors obscure change related to intrinsic airway abnormalities. Instead, the authors suggest using a threshold change in the predicted values of FEV1 and FVC to determine a significant response. Because predicted values incorporate age, height, and sex, the impact from these variables is minimized. Using a percent predicted (PPD) threshold will also minimize the effect from the inverse relationship between measured values and bronchodilator response.
A 10% change in the PPD value for either FEV1 or FVC constitutes a significant bronchodilator response. Ten percent was chosen because it represents the statistically defined upper limit of normal response; and a greater than 8% change in bronchodilator response is associated with mortality, implying that values above this threshold connote disease. The technical standard seems to be on solid ground here; the rationale is mathematically appropriate and evidence based. The new definition will certainly improve precision.
There’s really no progress on accuracy, though. There are no comments on the protocol to be followed or clinical indications. The reader is referred to the ERS/ATS 2019 technical statement on standardization of spirometry. The statement on standardization is short on details, too, and refers the reader to an online supplement for a suggested protocol. The suggested protocol is identical to that suggested in 2005.
In summary, not a lot is different in the world of bronchodilator response testing. The definition is different now, and though it’s likely to be more precise, we still don’t know enough about accuracy. It’s nice to know that the new criteria will predict mortality, but in clinical practice we don’t use the test for that purpose. The 2022 technical standard acknowledges this and other limitations in a “future directions” paragraph. Perhaps we’ll know more when the next iteration is published.
Dr. Holley is a professor of medicine at Uniformed Services University of the Health Sciences. Bethesda, Md., and a pulmonary medicine/critical care physician at MedStar Washington Hospital Center, Washington. He reported conflicts of interest with Metapharm and the American College of Chest Physicians. A version of this article first appeared on Medscape.com.
The European Respiratory Society (ERS) and the American Thoracic Society (ATS) just published an updated technical standard on lung function interpretation. It’s impossible to review in its entirety without more space, so I’ll settle for covering what the authors say about bronchodilator testing. But before I do that, it’s worth reviewing what we think we know about having a patient perform spirometry, inhale a bronchodilator, and then repeat it. This is colloquially referred to as pre- and postbronchodilator testing.
Administering a bronchodilator and measuring changes in lung function seems simple and intuitive. It is biologically plausible that improvement would predict treatment response. It should allow for phenotyping airway diseases and quantifying exacerbation risk. It is easy to perform and can be done in the clinic. But in practice it falls short of its purpose, in part because of technical factors but also because it doesn’t really have a purpose.
The last interpretative strategies document from the ERS/ATS was published in 2005. Reading it many years ago, I was struck by the contrast between our reliance on bronchodilator response and its lack of standardization. It seemed that there was none. After making statements like, “There is no consensus on what constitutes reversibility in subjects with airflow obstruction” and “There is no consensus on how a bronchodilator response should be expressed, the variables to be used, and finally, the kind, dose, and inhalation mode of bronchodilator agent,” the 2005 ERS/ATS authors suggest using the criteria most clinicians are familiar with: A change of 12% and 200 cc in FEV1 or FVC marks a “significant” bronchodilator response. Four puffs of albuterol (100 mcg each for a total of 400 mcg) with a 15- to 20-minute wait before repeat spirometry is also suggested.
The 2005 iteration acknowledges that a significant bronchodilator response isn’t a very accurate predictor of, well, anything. It doesn’t reliably differentiate COPD from asthma and it’s never been as sensitive as bronchoprovocation testing for diagnosing airway reactivity. The absence of a significant bronchodilator response does not preclude a 2-month trial of the same medicine used to test for response. Given these problems with standardization and accuracy, I was left wondering why anyone bothers ordering the test at all.
In my own practice, I continued to order, conduct, and interpret bronchodilator response according to the suggestions made by the ERS/ATS in 2005 when trying to diagnose asthma. I recognized that a nonsignificant response meant nothing, but bronchodilator response testing was easier to obtain than bronchoprovocation at my hospital. It was a matter of convenience for me and the patient. According to the Global Initiative for Asthma (GINA) Guidelines, a significant bronchodilator response conducted and interpreted as recommended by the ERS/ATS 2005 standard provides objective confirmation of asthma in the presence of characteristic clinical symptoms.
The headline from the ERS/ATS 2022 Technical Standard is that the 12% and 200-cc criteria suggested in 2005 are being retired. Why? Well, much of the variability in the 2005 criteria is explained by height, age, sex, and baseline lung function. These factors obscure change related to intrinsic airway abnormalities. Instead, the authors suggest using a threshold change in the predicted values of FEV1 and FVC to determine a significant response. Because predicted values incorporate age, height, and sex, the impact from these variables is minimized. Using a percent predicted (PPD) threshold will also minimize the effect from the inverse relationship between measured values and bronchodilator response.
A 10% change in the PPD value for either FEV1 or FVC constitutes a significant bronchodilator response. Ten percent was chosen because it represents the statistically defined upper limit of normal response; and a greater than 8% change in bronchodilator response is associated with mortality, implying that values above this threshold connote disease. The technical standard seems to be on solid ground here; the rationale is mathematically appropriate and evidence based. The new definition will certainly improve precision.
There’s really no progress on accuracy, though. There are no comments on the protocol to be followed or clinical indications. The reader is referred to the ERS/ATS 2019 technical statement on standardization of spirometry. The statement on standardization is short on details, too, and refers the reader to an online supplement for a suggested protocol. The suggested protocol is identical to that suggested in 2005.
In summary, not a lot is different in the world of bronchodilator response testing. The definition is different now, and though it’s likely to be more precise, we still don’t know enough about accuracy. It’s nice to know that the new criteria will predict mortality, but in clinical practice we don’t use the test for that purpose. The 2022 technical standard acknowledges this and other limitations in a “future directions” paragraph. Perhaps we’ll know more when the next iteration is published.
Dr. Holley is a professor of medicine at Uniformed Services University of the Health Sciences. Bethesda, Md., and a pulmonary medicine/critical care physician at MedStar Washington Hospital Center, Washington. He reported conflicts of interest with Metapharm and the American College of Chest Physicians. A version of this article first appeared on Medscape.com.
Double CF combination safe, effective in 1- to 2-year-olds
In children with cystic fibrosis (CF) and homozygous for the F508 mutation, the combination of lumacaftor and ivacaftor appears generally safe, and biomarker data suggest its efficacy, according to results from a new open-label phase 3 trial.
In September, the Food and Drug Administration approved lumacaftor/ivacaftor for patients aged 1 years and above. Waiting in the wings is the triple combination of elexacaftor, tezacaftor, and ivacaftor (ETI), which is available for patients with at least one copy of the F508 mutation aged 6 and over. ETI is also being tested in younger patients.
One driving factor for early treatment is countering the malnutrition that can occur among CF patients because of poor pancreatic insufficiency and chronic inflammation. “We’ve known for many years that (being) at or above average body weight and height predict better lung function. And we’ve known for quite a while that the height-for-age percentile, in preschool years, actually predicts your lung function later, and how long you’re going to live, so nutrition is incredibly important,” said study author Susanna McColley, MD, in an interview. It’s also difficult to use lung function tests in young children, since even adults can find them challenging, she said.
“FEV1 [forced expiratory volume in 1 second] is the strongest predictor of survival, and then nutrition is the highest predictor of FEV1, so that’s kind of the construct. They had similar improvement in the functional measures of their pancreas and in the measures of inflammation in the gut. I think the story here is that starting a modulator early has a likelihood to have positive health effects that go forward. We can’t say that from the data in the paper. It’s a 24-week study, but looking at the pancreatic and intestinal functioning and also the fact that there was a decrease in sweat chloride is important,” said Dr. McColley, who is a professor of pediatrics in pulmonary and sleep medicine at Northwestern University, Chicago.
The study adds more evidence that earlier treatment in CF may lead to better outcomes, but the digestive improvements are an overlooked factor, according to Dr. McColley. “Even with early treatment, and even with pancreatic enzymes and supplements taken to digest food, it’s a huge burden. When they come in and say that digestion seems better, there is less bloating, things like that, these are the things that aren’t captured so much in the clinical trial data, but they’re meaningful to families,” she said.
Single-agent ivacaftor is available for children as young as 4 months, but is limited to patients with the G551D gating mutation. Most young children with CF can only be treated for symptoms.
The lack of new safety signals in the new study is reassuring, and the research presents some hope to young children who are not yet eligible to receive ETI, according to Carlos Milla, MD, who is a pediatric pulmonary physician at Stanford (Calif.) University. “We already know that the next version of this drug is much more efficacious, the triple-combination therapy. It’s a little bit like we’re falling behind when it comes to treating these young kids because we are offering right now what we know is a less effective drug as opposed to the ones that are available now down to age 6, and hopefully sometime soon down to age 2. It’s better [than] to have no treatment at all, so it’s a good start,” said Dr. Milla.
“I think this is a great bridge for babies while they’re waiting to grow up to be old enough to get [triple combination therapy] and will prevent some of the complications until they can get the even more highly effective therapy in the future,” said Jennifer Taylor-Cousar, MD, who was asked to comment on the study. Dr. Taylor-Cousar is codirector of the Adult CF Program at National Jewish Health, Denver.
She also noted that the therapy could rapidly become more important. Since the approval of elexacaftor/tezacaftor/ivacaftor in 2019, pregnancies in women with CF have increased markedly. There were 310 such pregnancies in 2019, and 675 in 2020 after the combination became generally available in November of 2019. Many of the resulting babies had false-negative CF diagnoses because the mother was taking the triple combination and the medication crossed the placenta and prevented disease progression. The drugs are present in breast milk, but when breastfeeding isn’t possible, newborns are left without a therapeutic option. “There was no approval for babies who had two copies of F508. This helps tremendously with that albeit small population, although I suspect it may grow larger over the upcoming years as we continue to see so many pregnancies in women with CF because they are so much healthier,” said Dr. Taylor-Cousar.
The study was a phase 3, open-label trial with a cohort aged 18-24 months (cohort 1, n = 14) and another aged 12-18 months (cohort 2, n = 46). Participants received a 15-day treatment with a dose based on weight at screening. Participants then underwent a 24-week treatment period with a dose determined by pharmacokinetic data collected during the initial treatment, the authors wrote in the American Journal of Respiratory and Critical Care Medicine.
A total of 95.7% of children experienced adverse events during the 24-week treatment period; 52.2% of events were mild, and 39.1% were moderate. The most frequent adverse events were cough (34.8%), infective exacerbation of CF (21.7%), pyrexia (21.7%), and vomiting (17.4%); 10.9% had elevations of alanine aminotransferase and/or aspartate aminotransferase higher than three times the upper limit of normal, and one (2.2%) had concentrations of both high enough that the study drug was discontinued.
There were significant reductions in sweat chloride concentration at week 24, suggesting strong efficacy (–29.1 mmol/L; 95% confidence interval, –34.8 to –23.4 mmol/L). Body mass, weight, and length remained normal during the 24-week treatment period, and there were trends towards improvement in biomarkers of pancreatic function and intestinal inflammation, including fecal elastase-1 (+73.1mcg/g; 95% CI, 29.40-116.80 mcg/g), serum immunoreactive trypsinogen (–295.50 mcg/g; 95% CI, –416.60 to –174.50 mcg/g), and fecal calprotectin (–106.63 mg/kg; 95% CI, –180.60 to –32.66 mg/kg)
Dr. McColley, Dr. Taylor-Cousar, and Dr. Milla have no relevant financial disclosures. The study was funded by Merck.
In children with cystic fibrosis (CF) and homozygous for the F508 mutation, the combination of lumacaftor and ivacaftor appears generally safe, and biomarker data suggest its efficacy, according to results from a new open-label phase 3 trial.
In September, the Food and Drug Administration approved lumacaftor/ivacaftor for patients aged 1 years and above. Waiting in the wings is the triple combination of elexacaftor, tezacaftor, and ivacaftor (ETI), which is available for patients with at least one copy of the F508 mutation aged 6 and over. ETI is also being tested in younger patients.
One driving factor for early treatment is countering the malnutrition that can occur among CF patients because of poor pancreatic insufficiency and chronic inflammation. “We’ve known for many years that (being) at or above average body weight and height predict better lung function. And we’ve known for quite a while that the height-for-age percentile, in preschool years, actually predicts your lung function later, and how long you’re going to live, so nutrition is incredibly important,” said study author Susanna McColley, MD, in an interview. It’s also difficult to use lung function tests in young children, since even adults can find them challenging, she said.
“FEV1 [forced expiratory volume in 1 second] is the strongest predictor of survival, and then nutrition is the highest predictor of FEV1, so that’s kind of the construct. They had similar improvement in the functional measures of their pancreas and in the measures of inflammation in the gut. I think the story here is that starting a modulator early has a likelihood to have positive health effects that go forward. We can’t say that from the data in the paper. It’s a 24-week study, but looking at the pancreatic and intestinal functioning and also the fact that there was a decrease in sweat chloride is important,” said Dr. McColley, who is a professor of pediatrics in pulmonary and sleep medicine at Northwestern University, Chicago.
The study adds more evidence that earlier treatment in CF may lead to better outcomes, but the digestive improvements are an overlooked factor, according to Dr. McColley. “Even with early treatment, and even with pancreatic enzymes and supplements taken to digest food, it’s a huge burden. When they come in and say that digestion seems better, there is less bloating, things like that, these are the things that aren’t captured so much in the clinical trial data, but they’re meaningful to families,” she said.
Single-agent ivacaftor is available for children as young as 4 months, but is limited to patients with the G551D gating mutation. Most young children with CF can only be treated for symptoms.
The lack of new safety signals in the new study is reassuring, and the research presents some hope to young children who are not yet eligible to receive ETI, according to Carlos Milla, MD, who is a pediatric pulmonary physician at Stanford (Calif.) University. “We already know that the next version of this drug is much more efficacious, the triple-combination therapy. It’s a little bit like we’re falling behind when it comes to treating these young kids because we are offering right now what we know is a less effective drug as opposed to the ones that are available now down to age 6, and hopefully sometime soon down to age 2. It’s better [than] to have no treatment at all, so it’s a good start,” said Dr. Milla.
“I think this is a great bridge for babies while they’re waiting to grow up to be old enough to get [triple combination therapy] and will prevent some of the complications until they can get the even more highly effective therapy in the future,” said Jennifer Taylor-Cousar, MD, who was asked to comment on the study. Dr. Taylor-Cousar is codirector of the Adult CF Program at National Jewish Health, Denver.
She also noted that the therapy could rapidly become more important. Since the approval of elexacaftor/tezacaftor/ivacaftor in 2019, pregnancies in women with CF have increased markedly. There were 310 such pregnancies in 2019, and 675 in 2020 after the combination became generally available in November of 2019. Many of the resulting babies had false-negative CF diagnoses because the mother was taking the triple combination and the medication crossed the placenta and prevented disease progression. The drugs are present in breast milk, but when breastfeeding isn’t possible, newborns are left without a therapeutic option. “There was no approval for babies who had two copies of F508. This helps tremendously with that albeit small population, although I suspect it may grow larger over the upcoming years as we continue to see so many pregnancies in women with CF because they are so much healthier,” said Dr. Taylor-Cousar.
The study was a phase 3, open-label trial with a cohort aged 18-24 months (cohort 1, n = 14) and another aged 12-18 months (cohort 2, n = 46). Participants received a 15-day treatment with a dose based on weight at screening. Participants then underwent a 24-week treatment period with a dose determined by pharmacokinetic data collected during the initial treatment, the authors wrote in the American Journal of Respiratory and Critical Care Medicine.
A total of 95.7% of children experienced adverse events during the 24-week treatment period; 52.2% of events were mild, and 39.1% were moderate. The most frequent adverse events were cough (34.8%), infective exacerbation of CF (21.7%), pyrexia (21.7%), and vomiting (17.4%); 10.9% had elevations of alanine aminotransferase and/or aspartate aminotransferase higher than three times the upper limit of normal, and one (2.2%) had concentrations of both high enough that the study drug was discontinued.
There were significant reductions in sweat chloride concentration at week 24, suggesting strong efficacy (–29.1 mmol/L; 95% confidence interval, –34.8 to –23.4 mmol/L). Body mass, weight, and length remained normal during the 24-week treatment period, and there were trends towards improvement in biomarkers of pancreatic function and intestinal inflammation, including fecal elastase-1 (+73.1mcg/g; 95% CI, 29.40-116.80 mcg/g), serum immunoreactive trypsinogen (–295.50 mcg/g; 95% CI, –416.60 to –174.50 mcg/g), and fecal calprotectin (–106.63 mg/kg; 95% CI, –180.60 to –32.66 mg/kg)
Dr. McColley, Dr. Taylor-Cousar, and Dr. Milla have no relevant financial disclosures. The study was funded by Merck.
In children with cystic fibrosis (CF) and homozygous for the F508 mutation, the combination of lumacaftor and ivacaftor appears generally safe, and biomarker data suggest its efficacy, according to results from a new open-label phase 3 trial.
In September, the Food and Drug Administration approved lumacaftor/ivacaftor for patients aged 1 years and above. Waiting in the wings is the triple combination of elexacaftor, tezacaftor, and ivacaftor (ETI), which is available for patients with at least one copy of the F508 mutation aged 6 and over. ETI is also being tested in younger patients.
One driving factor for early treatment is countering the malnutrition that can occur among CF patients because of poor pancreatic insufficiency and chronic inflammation. “We’ve known for many years that (being) at or above average body weight and height predict better lung function. And we’ve known for quite a while that the height-for-age percentile, in preschool years, actually predicts your lung function later, and how long you’re going to live, so nutrition is incredibly important,” said study author Susanna McColley, MD, in an interview. It’s also difficult to use lung function tests in young children, since even adults can find them challenging, she said.
“FEV1 [forced expiratory volume in 1 second] is the strongest predictor of survival, and then nutrition is the highest predictor of FEV1, so that’s kind of the construct. They had similar improvement in the functional measures of their pancreas and in the measures of inflammation in the gut. I think the story here is that starting a modulator early has a likelihood to have positive health effects that go forward. We can’t say that from the data in the paper. It’s a 24-week study, but looking at the pancreatic and intestinal functioning and also the fact that there was a decrease in sweat chloride is important,” said Dr. McColley, who is a professor of pediatrics in pulmonary and sleep medicine at Northwestern University, Chicago.
The study adds more evidence that earlier treatment in CF may lead to better outcomes, but the digestive improvements are an overlooked factor, according to Dr. McColley. “Even with early treatment, and even with pancreatic enzymes and supplements taken to digest food, it’s a huge burden. When they come in and say that digestion seems better, there is less bloating, things like that, these are the things that aren’t captured so much in the clinical trial data, but they’re meaningful to families,” she said.
Single-agent ivacaftor is available for children as young as 4 months, but is limited to patients with the G551D gating mutation. Most young children with CF can only be treated for symptoms.
The lack of new safety signals in the new study is reassuring, and the research presents some hope to young children who are not yet eligible to receive ETI, according to Carlos Milla, MD, who is a pediatric pulmonary physician at Stanford (Calif.) University. “We already know that the next version of this drug is much more efficacious, the triple-combination therapy. It’s a little bit like we’re falling behind when it comes to treating these young kids because we are offering right now what we know is a less effective drug as opposed to the ones that are available now down to age 6, and hopefully sometime soon down to age 2. It’s better [than] to have no treatment at all, so it’s a good start,” said Dr. Milla.
“I think this is a great bridge for babies while they’re waiting to grow up to be old enough to get [triple combination therapy] and will prevent some of the complications until they can get the even more highly effective therapy in the future,” said Jennifer Taylor-Cousar, MD, who was asked to comment on the study. Dr. Taylor-Cousar is codirector of the Adult CF Program at National Jewish Health, Denver.
She also noted that the therapy could rapidly become more important. Since the approval of elexacaftor/tezacaftor/ivacaftor in 2019, pregnancies in women with CF have increased markedly. There were 310 such pregnancies in 2019, and 675 in 2020 after the combination became generally available in November of 2019. Many of the resulting babies had false-negative CF diagnoses because the mother was taking the triple combination and the medication crossed the placenta and prevented disease progression. The drugs are present in breast milk, but when breastfeeding isn’t possible, newborns are left without a therapeutic option. “There was no approval for babies who had two copies of F508. This helps tremendously with that albeit small population, although I suspect it may grow larger over the upcoming years as we continue to see so many pregnancies in women with CF because they are so much healthier,” said Dr. Taylor-Cousar.
The study was a phase 3, open-label trial with a cohort aged 18-24 months (cohort 1, n = 14) and another aged 12-18 months (cohort 2, n = 46). Participants received a 15-day treatment with a dose based on weight at screening. Participants then underwent a 24-week treatment period with a dose determined by pharmacokinetic data collected during the initial treatment, the authors wrote in the American Journal of Respiratory and Critical Care Medicine.
A total of 95.7% of children experienced adverse events during the 24-week treatment period; 52.2% of events were mild, and 39.1% were moderate. The most frequent adverse events were cough (34.8%), infective exacerbation of CF (21.7%), pyrexia (21.7%), and vomiting (17.4%); 10.9% had elevations of alanine aminotransferase and/or aspartate aminotransferase higher than three times the upper limit of normal, and one (2.2%) had concentrations of both high enough that the study drug was discontinued.
There were significant reductions in sweat chloride concentration at week 24, suggesting strong efficacy (–29.1 mmol/L; 95% confidence interval, –34.8 to –23.4 mmol/L). Body mass, weight, and length remained normal during the 24-week treatment period, and there were trends towards improvement in biomarkers of pancreatic function and intestinal inflammation, including fecal elastase-1 (+73.1mcg/g; 95% CI, 29.40-116.80 mcg/g), serum immunoreactive trypsinogen (–295.50 mcg/g; 95% CI, –416.60 to –174.50 mcg/g), and fecal calprotectin (–106.63 mg/kg; 95% CI, –180.60 to –32.66 mg/kg)
Dr. McColley, Dr. Taylor-Cousar, and Dr. Milla have no relevant financial disclosures. The study was funded by Merck.
FROM THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Dapper homolog 2 shows promise for pulmonary fibrosis
Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.
Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.
Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.
In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.
The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.
They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.
The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.
“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.
More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.
“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.
The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.
Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.
Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.
Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.
In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.
The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.
They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.
The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.
“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.
More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.
“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.
The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.
Dapper homolog 2 attenuated pulmonary fibrosis development and suppressed glycosis in myofibroblasts, suggesting potential as a therapeutic target for idiopathic pulmonary fibrosis, based on data from mouse models.
Idiopathic pulmonary fibrosis (IPF) remains a challenge with poor prognosis, and current therapeutic options are limited, wrote Xiaofan Lai, of Sun Yat-sen University, Guangzhou, China, and colleagues. Previous studies suggest that myofibroblasts are key contributors to fibrosis in IPF, they said.
Dishevelled-associated antagonist of beta-catenin 2 (DACT2) is an antagonist in the DACT gene family and associated with tissue development and injury, but its function and potential therapeutic role in IPF has not been explored; specifically, “whether DACT2 participates in the dysregulated glycolysis of myofibroblasts remains unknown,” they said.
In a study published in the International Journal of Biological Macromolecules, the researchers examined adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression in experimental pulmonary fibrosis using mouse models.
The researchers injected AAV6 vectors into the lungs of mice to overexpress DACT2. The DACT2 overexpression “effectively attenuated both bleomycin-induced and AdTGF-beta-1-induced pulmonary fibrosis murine models in vivo, as evidenced by the alleviation of myofibroblast differentiation and collagen accumulation,” they said.
They found that overexpression of DACT2 was associated with glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level, and lactate levels of myofibroblasts.
The researchers also conducted in vitro experiments in which they treated lung fibroblasts with cycloheximide (CHX), a protein synthesis inhibitor. These experiments showed that DACT2 inhibited differentiation of lung myofibroblasts by downregulating lactate dehydrogenase A (LDHA), which caused suppression of glycolysis in myofibroblasts.
“Aerobic glycolysis is an important method of energy generation, and several studies have shown that enhanced glycolysis facilitates the progression of pulmonary fibrosis,” the researchers wrote in their discussion.
More research is needed outside of mouse models and in vitro studies, but the current study is the first known to explore the relationship between DACT2 and LDHA in pulmonary fibrosis, and the results provide evidence of the potential benefits of DACT2 in treating lung disorders, the researchers wrote.
“We hope this research will lay the theoretical foundation for finding novel therapeutics to alleviate or reverse the development of pulmonary fibrosis and other chronic lung disorders,” they concluded.
The study was supported by the National Natural Science Foundation of China and the Regional Joint Fund-Youth Fund projects of Guangdong Province. The researchers had no financial conflicts to disclose.
FROM THE INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Fat-free mass index tied to outcomes in underweight COPD patients
Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.
Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.
However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.
In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.
Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).
Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.
Notably, after adjusting for multiple variables, after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.
However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).
Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.
The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.
However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.
The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.
Mr. Machado disclosed financial support from ZonMW.
A version of this article first appeared on Medscape.com.
Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.
Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.
However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.
In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.
Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).
Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.
Notably, after adjusting for multiple variables, after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.
However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).
Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.
The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.
However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.
The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.
Mr. Machado disclosed financial support from ZonMW.
A version of this article first appeared on Medscape.com.
Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.
Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.
However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.
In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.
Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).
Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.
Notably, after adjusting for multiple variables, after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.
However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).
Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.
The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.
However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.
The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.
Mr. Machado disclosed financial support from ZonMW.
A version of this article first appeared on Medscape.com.
From the Journal CHEST
A doctor saves a drowning family in a dangerous river
Is There a Doctor in the House? is a new series telling these stories.
I live on the Maumee River in Ohio, about 50 yards from the water. I had an early quit time and came home to meet my wife for lunch. Afterward, I went up to my barn across the main road to tinker around. It was a nice day out, so my wife had opened some windows. Suddenly, she heard screaming from the river. It did not sound like fun.
She ran down to the river’s edge and saw a dad and three boys struggling in the water. She phoned me screaming: “They’re drowning! They’re drowning!” I jumped in my truck and drove up our driveway through the yard right down to the river.
My wife was on the phone with 911 at that point, and I could see them about 75-100 yards out. The dad had two of the boys clinging around his neck. They were going under the water and coming up and going under again. The other boy was just floating nearby, face down, motionless.
I threw my shoes and scrubs off and started to walk towards the water. My wife screamed at me, “You’re not going in there!” I said, “I’m not going to stand here and watch this. It’s not going to happen.”
I’m not a kid anymore, but I was a high school swimmer, and to this day I work out all the time. I felt like I had to try something. So, I went in the water despite my wife yelling and I swam towards them.
What happens when you get in that deep water is that you panic. You can’t hear anyone because of the rapids, and your instinct is to swim back towards where you went in, which is against the current. Unless you’re a very strong swimmer, you’re just wasting your time, swimming in place.
But these guys weren’t trying to go anywhere. Dad was just trying to stay up and keep the boys alive. He was in about 10 feet of water. What they didn’t see or just didn’t know: About 20 yards upstream from that deep water is a little island.
When I got to them, I yelled at the dad to move towards the island, “Go backwards! Go back!” I flipped the boy over who wasn’t moving. He was the oldest of the three, around 10 or 11 years old. When I turned him over, he was blue and wasn’t breathing. I put my fingers on his neck and didn’t feel a pulse.
So, I’m treading water, holding him. I put an arm behind his back and started doing chest compressions on him. I probably did a dozen to 15 compressions – nothing. I thought, I’ve got to get some air in this kid. So, I gave him two deep breaths and then started doing compressions again. I know ACLS and CPR training would say we don’t do that anymore. But I couldn’t just sit there and give up. Shortly after that, he coughed out a large amount of water and started breathing.
The dad and the other two boys had made it to the island. So, I started moving towards it with the boy. It was a few minutes before he regained consciousness. Of course, he was unaware of what had happened. He started to scream, because here’s this strange man holding him. But he was breathing. That’s all I cared about.
When we got to the island, I saw that my neighbor downstream had launched his canoe. He’s a retired gentleman who lives next to me, a very physically fit man. He started rolling as hard as he could towards us, against the stream. I kind of gave him a thumbs up, like, “we’re safe now. We’re standing.” We loaded the kids and the dad in the canoe and made it back against the stream to the parking lot where they went in.
All this took probably 10 or 15 minutes, and by then the paramedics were there. Life Flight had been dispatched up by my barn where there’s room to land. So, they drove up there in the ambulance. The boy I revived was flown to the hospital. The others went in the ambulance.
I know all the ED docs, so I talked to somebody later who, with permission from the family, said they were all doing fine. They were getting x-rays on the boy’s lungs. And then I heard the dad and two boys were released that night. The other boy I worked on was observed overnight and discharged the following morning.
Four or 5 days later, I heard from their pediatrician, who also had permission to share. He sent me a very nice note through Epic that he had seen the boys. Besides some mental trauma, they were all healthy and doing fine.
The family lives in the area and the kids go to school 5 miles from my house. So, the following weekend they came over. It was Father’s Day, which was kind of cool. They brought me some flowers and candy and a card the boys had drawn to thank me.
I learned that the dad had brought the boys to the fishing site. They were horsing around in knee deep water. One of the boys walked off a little way and didn’t realize there was a drop off. He went in, and of course the dad went after him, and the other two followed.
I said to the parents: “Look, things like this happen for a reason. People like your son are saved and go on in this world because they’ve got special things to do. I can’t wait to see what kind of man he becomes.”
Two or 3 months later, it was football season, and I got at a message from the dad saying their son was playing football on Saturday at the school. He wondered if I could drop by. So, I kind of snuck over and watched, but I didn’t go say hi. There’s trauma there, and I didn’t want them to have to relive that.
I’m very fortunate that I exercise every day and I know how to do CPR and swim. And thank God the boy was floating when I got to him, or I never would’ve found him. The Maumee River is known as the “muddy Maumee.” You can’t see anything under the water.
Depending on the time of year, the river can be almost dry or overflowing into the parking lot with the current rushing hard. If it had been like that, I wouldn’t have considered going in. And they wouldn’t they have been there in the first place. They’d have been a mile downstream.
I took a risk. I could have gone out there and had the dad and two other kids jump on top of me. Then we all would have been in trouble. But like I told my wife, I couldn’t stand there and watch it. I’m just not that person.
I think it was also about being a dad myself and having grandkids now. Doctor or no doctor, I felt like I was in reasonably good shape and I had to go in there to help. This dad was trying his butt off, but three little kids is too many. You can’t do that by yourself. They were not going to make it.
I go to the hospital and I save lives as part of my job, and I don’t even come home and talk about it. But this is a whole different thing. Being able to save someone’s life when put in this situation is very gratifying. It’s a tremendous feeling. There’s a reason that young man is here today, and I’ll be watching for great things from him.
A version of this article first appeared on Medscape.com.
Daniel Cassavar, MD, is a cardiologist with ProMedica in Perrysburg, Ohio.
Is There a Doctor in the House? is a new series telling these stories.
I live on the Maumee River in Ohio, about 50 yards from the water. I had an early quit time and came home to meet my wife for lunch. Afterward, I went up to my barn across the main road to tinker around. It was a nice day out, so my wife had opened some windows. Suddenly, she heard screaming from the river. It did not sound like fun.
She ran down to the river’s edge and saw a dad and three boys struggling in the water. She phoned me screaming: “They’re drowning! They’re drowning!” I jumped in my truck and drove up our driveway through the yard right down to the river.
My wife was on the phone with 911 at that point, and I could see them about 75-100 yards out. The dad had two of the boys clinging around his neck. They were going under the water and coming up and going under again. The other boy was just floating nearby, face down, motionless.
I threw my shoes and scrubs off and started to walk towards the water. My wife screamed at me, “You’re not going in there!” I said, “I’m not going to stand here and watch this. It’s not going to happen.”
I’m not a kid anymore, but I was a high school swimmer, and to this day I work out all the time. I felt like I had to try something. So, I went in the water despite my wife yelling and I swam towards them.
What happens when you get in that deep water is that you panic. You can’t hear anyone because of the rapids, and your instinct is to swim back towards where you went in, which is against the current. Unless you’re a very strong swimmer, you’re just wasting your time, swimming in place.
But these guys weren’t trying to go anywhere. Dad was just trying to stay up and keep the boys alive. He was in about 10 feet of water. What they didn’t see or just didn’t know: About 20 yards upstream from that deep water is a little island.
When I got to them, I yelled at the dad to move towards the island, “Go backwards! Go back!” I flipped the boy over who wasn’t moving. He was the oldest of the three, around 10 or 11 years old. When I turned him over, he was blue and wasn’t breathing. I put my fingers on his neck and didn’t feel a pulse.
So, I’m treading water, holding him. I put an arm behind his back and started doing chest compressions on him. I probably did a dozen to 15 compressions – nothing. I thought, I’ve got to get some air in this kid. So, I gave him two deep breaths and then started doing compressions again. I know ACLS and CPR training would say we don’t do that anymore. But I couldn’t just sit there and give up. Shortly after that, he coughed out a large amount of water and started breathing.
The dad and the other two boys had made it to the island. So, I started moving towards it with the boy. It was a few minutes before he regained consciousness. Of course, he was unaware of what had happened. He started to scream, because here’s this strange man holding him. But he was breathing. That’s all I cared about.
When we got to the island, I saw that my neighbor downstream had launched his canoe. He’s a retired gentleman who lives next to me, a very physically fit man. He started rolling as hard as he could towards us, against the stream. I kind of gave him a thumbs up, like, “we’re safe now. We’re standing.” We loaded the kids and the dad in the canoe and made it back against the stream to the parking lot where they went in.
All this took probably 10 or 15 minutes, and by then the paramedics were there. Life Flight had been dispatched up by my barn where there’s room to land. So, they drove up there in the ambulance. The boy I revived was flown to the hospital. The others went in the ambulance.
I know all the ED docs, so I talked to somebody later who, with permission from the family, said they were all doing fine. They were getting x-rays on the boy’s lungs. And then I heard the dad and two boys were released that night. The other boy I worked on was observed overnight and discharged the following morning.
Four or 5 days later, I heard from their pediatrician, who also had permission to share. He sent me a very nice note through Epic that he had seen the boys. Besides some mental trauma, they were all healthy and doing fine.
The family lives in the area and the kids go to school 5 miles from my house. So, the following weekend they came over. It was Father’s Day, which was kind of cool. They brought me some flowers and candy and a card the boys had drawn to thank me.
I learned that the dad had brought the boys to the fishing site. They were horsing around in knee deep water. One of the boys walked off a little way and didn’t realize there was a drop off. He went in, and of course the dad went after him, and the other two followed.
I said to the parents: “Look, things like this happen for a reason. People like your son are saved and go on in this world because they’ve got special things to do. I can’t wait to see what kind of man he becomes.”
Two or 3 months later, it was football season, and I got at a message from the dad saying their son was playing football on Saturday at the school. He wondered if I could drop by. So, I kind of snuck over and watched, but I didn’t go say hi. There’s trauma there, and I didn’t want them to have to relive that.
I’m very fortunate that I exercise every day and I know how to do CPR and swim. And thank God the boy was floating when I got to him, or I never would’ve found him. The Maumee River is known as the “muddy Maumee.” You can’t see anything under the water.
Depending on the time of year, the river can be almost dry or overflowing into the parking lot with the current rushing hard. If it had been like that, I wouldn’t have considered going in. And they wouldn’t they have been there in the first place. They’d have been a mile downstream.
I took a risk. I could have gone out there and had the dad and two other kids jump on top of me. Then we all would have been in trouble. But like I told my wife, I couldn’t stand there and watch it. I’m just not that person.
I think it was also about being a dad myself and having grandkids now. Doctor or no doctor, I felt like I was in reasonably good shape and I had to go in there to help. This dad was trying his butt off, but three little kids is too many. You can’t do that by yourself. They were not going to make it.
I go to the hospital and I save lives as part of my job, and I don’t even come home and talk about it. But this is a whole different thing. Being able to save someone’s life when put in this situation is very gratifying. It’s a tremendous feeling. There’s a reason that young man is here today, and I’ll be watching for great things from him.
A version of this article first appeared on Medscape.com.
Daniel Cassavar, MD, is a cardiologist with ProMedica in Perrysburg, Ohio.
Is There a Doctor in the House? is a new series telling these stories.
I live on the Maumee River in Ohio, about 50 yards from the water. I had an early quit time and came home to meet my wife for lunch. Afterward, I went up to my barn across the main road to tinker around. It was a nice day out, so my wife had opened some windows. Suddenly, she heard screaming from the river. It did not sound like fun.
She ran down to the river’s edge and saw a dad and three boys struggling in the water. She phoned me screaming: “They’re drowning! They’re drowning!” I jumped in my truck and drove up our driveway through the yard right down to the river.
My wife was on the phone with 911 at that point, and I could see them about 75-100 yards out. The dad had two of the boys clinging around his neck. They were going under the water and coming up and going under again. The other boy was just floating nearby, face down, motionless.
I threw my shoes and scrubs off and started to walk towards the water. My wife screamed at me, “You’re not going in there!” I said, “I’m not going to stand here and watch this. It’s not going to happen.”
I’m not a kid anymore, but I was a high school swimmer, and to this day I work out all the time. I felt like I had to try something. So, I went in the water despite my wife yelling and I swam towards them.
What happens when you get in that deep water is that you panic. You can’t hear anyone because of the rapids, and your instinct is to swim back towards where you went in, which is against the current. Unless you’re a very strong swimmer, you’re just wasting your time, swimming in place.
But these guys weren’t trying to go anywhere. Dad was just trying to stay up and keep the boys alive. He was in about 10 feet of water. What they didn’t see or just didn’t know: About 20 yards upstream from that deep water is a little island.
When I got to them, I yelled at the dad to move towards the island, “Go backwards! Go back!” I flipped the boy over who wasn’t moving. He was the oldest of the three, around 10 or 11 years old. When I turned him over, he was blue and wasn’t breathing. I put my fingers on his neck and didn’t feel a pulse.
So, I’m treading water, holding him. I put an arm behind his back and started doing chest compressions on him. I probably did a dozen to 15 compressions – nothing. I thought, I’ve got to get some air in this kid. So, I gave him two deep breaths and then started doing compressions again. I know ACLS and CPR training would say we don’t do that anymore. But I couldn’t just sit there and give up. Shortly after that, he coughed out a large amount of water and started breathing.
The dad and the other two boys had made it to the island. So, I started moving towards it with the boy. It was a few minutes before he regained consciousness. Of course, he was unaware of what had happened. He started to scream, because here’s this strange man holding him. But he was breathing. That’s all I cared about.
When we got to the island, I saw that my neighbor downstream had launched his canoe. He’s a retired gentleman who lives next to me, a very physically fit man. He started rolling as hard as he could towards us, against the stream. I kind of gave him a thumbs up, like, “we’re safe now. We’re standing.” We loaded the kids and the dad in the canoe and made it back against the stream to the parking lot where they went in.
All this took probably 10 or 15 minutes, and by then the paramedics were there. Life Flight had been dispatched up by my barn where there’s room to land. So, they drove up there in the ambulance. The boy I revived was flown to the hospital. The others went in the ambulance.
I know all the ED docs, so I talked to somebody later who, with permission from the family, said they were all doing fine. They were getting x-rays on the boy’s lungs. And then I heard the dad and two boys were released that night. The other boy I worked on was observed overnight and discharged the following morning.
Four or 5 days later, I heard from their pediatrician, who also had permission to share. He sent me a very nice note through Epic that he had seen the boys. Besides some mental trauma, they were all healthy and doing fine.
The family lives in the area and the kids go to school 5 miles from my house. So, the following weekend they came over. It was Father’s Day, which was kind of cool. They brought me some flowers and candy and a card the boys had drawn to thank me.
I learned that the dad had brought the boys to the fishing site. They were horsing around in knee deep water. One of the boys walked off a little way and didn’t realize there was a drop off. He went in, and of course the dad went after him, and the other two followed.
I said to the parents: “Look, things like this happen for a reason. People like your son are saved and go on in this world because they’ve got special things to do. I can’t wait to see what kind of man he becomes.”
Two or 3 months later, it was football season, and I got at a message from the dad saying their son was playing football on Saturday at the school. He wondered if I could drop by. So, I kind of snuck over and watched, but I didn’t go say hi. There’s trauma there, and I didn’t want them to have to relive that.
I’m very fortunate that I exercise every day and I know how to do CPR and swim. And thank God the boy was floating when I got to him, or I never would’ve found him. The Maumee River is known as the “muddy Maumee.” You can’t see anything under the water.
Depending on the time of year, the river can be almost dry or overflowing into the parking lot with the current rushing hard. If it had been like that, I wouldn’t have considered going in. And they wouldn’t they have been there in the first place. They’d have been a mile downstream.
I took a risk. I could have gone out there and had the dad and two other kids jump on top of me. Then we all would have been in trouble. But like I told my wife, I couldn’t stand there and watch it. I’m just not that person.
I think it was also about being a dad myself and having grandkids now. Doctor or no doctor, I felt like I was in reasonably good shape and I had to go in there to help. This dad was trying his butt off, but three little kids is too many. You can’t do that by yourself. They were not going to make it.
I go to the hospital and I save lives as part of my job, and I don’t even come home and talk about it. But this is a whole different thing. Being able to save someone’s life when put in this situation is very gratifying. It’s a tremendous feeling. There’s a reason that young man is here today, and I’ll be watching for great things from him.
A version of this article first appeared on Medscape.com.
Daniel Cassavar, MD, is a cardiologist with ProMedica in Perrysburg, Ohio.
How to have a safer and more joyful holiday season
This holiday season, I am looking forward to spending some time with family, as I have in the past. As I have chatted with others, many friends are looking forward to events that are potentially larger and potentially returning to prepandemic type gatherings.
Gathering is important and can bring joy, sense of community, and love to the lives of many. Unfortunately, the risks associated with gathering are not over. as our country faces many cases of respiratory syncytial virus (RSV), COVID-19, and influenza at the same time.
During the first week of December, cases of influenza were rising across the country1 and were rising faster than in previous years. Although getting the vaccine is an important method of influenza prevention and is recommended for everyone over the age of 6 months with rare exception, many have not gotten their vaccine this year.
Influenza
Thus far, “nearly 50% of reported flu-associated hospitalizations in women of childbearing age have been in women who are pregnant.” We are seeing this at a time with lower-than-average uptake of influenza vaccine leaving both the pregnant persons and their babies unprotected. In addition to utilizing vaccines as prevention, isolating when ill, cleaning surfaces, and practicing good hand hygiene can all decrease transmission.
RSV
In addition to rises of influenza, there are currently high rates of RSV in various parts of the country. Prior to 2020, RSV typically started in the fall and peaked in the winter months. However, since the pandemic, the typical seasonal pattern has not returned, and it is unclear when it will. Although RSV hits the very young, the old, and the immunocompromised the most, RSV can infect anyone. Unfortunately, we do not currently have a vaccine for everyone against this virus. Prevention of transmission includes, as with flu, isolating when ill, cleaning surfaces, and washing hands.2
COVID-19
Of course, the effects of the COVID-19 pandemic are also still here as well. During the first week of December, the CDC reported rising cases of COVID across the country. Within the past few months, there have been several developments, though, for protection. There are now bivalent vaccines available as either third doses or booster doses approved for all persons over 6 months of age. As of the first week of December, only 13.5% of those aged 5 and over had received an updated booster.
There is currently wider access to rapid testing, including at-home testing, which can allow individuals to identify if COVID positive. Additionally, there is access to medication to decrease the likelihood of severe disease – though this does not take the place of vaccinations.
If anyone does test positive for COVID, they should follow the most recent quarantine guidelines including wearing a well-fitted mask when they do begin returning to activities.3
With rising cases of all three of these viruses, some may be asking how we can safely gather. There are several things to consider and do to enjoy our events. The first thing everyone can do is to receive updated vaccinations for both influenza and COVID-19 if eligible. Although it may take some time to be effective, vaccination is still one of our most effective methods of disease prevention and is important this winter season. Vaccinations can also help decrease the risk of severe disease.
Although many have stopped masking, as cases rise, it is time to consider masking particularly when community levels of any of these viruses are high. Masks help with preventing and spreading more than just COVID-19. Using them can be especially important for those going places such as stores and to large public gatherings and when riding on buses, planes, or trains.
In summary
Preventing exposure by masking can help keep individuals healthy prior to celebrating the holidays with others. With access to rapid testing, it makes sense to consider testing prior to gathering with friends and family. Most importantly, although we all are looking forward to spending time with our loved ones, it is important to stay home if not feeling well. Following these recommendations will allow us to have a safer and more joyful holiday season.
Dr. Wheat is a family physician at Erie Family Health Center and program director of Northwestern University’s McGaw Family Medicine residency program, both in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].
References
1. Centers for Disease Control and Prevention. Influenza (flu). [Online] Dec. 1, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/flu/index.htm.
2. Respiratory syncytial virus. Respiratory syncytial virus infection (RSV). [Online] Oct. 28, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/rsv/index.html.
3. COVID-19. [Online] Dec. 7, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/coronavirus/2019-ncov/index.html.
This holiday season, I am looking forward to spending some time with family, as I have in the past. As I have chatted with others, many friends are looking forward to events that are potentially larger and potentially returning to prepandemic type gatherings.
Gathering is important and can bring joy, sense of community, and love to the lives of many. Unfortunately, the risks associated with gathering are not over. as our country faces many cases of respiratory syncytial virus (RSV), COVID-19, and influenza at the same time.
During the first week of December, cases of influenza were rising across the country1 and were rising faster than in previous years. Although getting the vaccine is an important method of influenza prevention and is recommended for everyone over the age of 6 months with rare exception, many have not gotten their vaccine this year.
Influenza
Thus far, “nearly 50% of reported flu-associated hospitalizations in women of childbearing age have been in women who are pregnant.” We are seeing this at a time with lower-than-average uptake of influenza vaccine leaving both the pregnant persons and their babies unprotected. In addition to utilizing vaccines as prevention, isolating when ill, cleaning surfaces, and practicing good hand hygiene can all decrease transmission.
RSV
In addition to rises of influenza, there are currently high rates of RSV in various parts of the country. Prior to 2020, RSV typically started in the fall and peaked in the winter months. However, since the pandemic, the typical seasonal pattern has not returned, and it is unclear when it will. Although RSV hits the very young, the old, and the immunocompromised the most, RSV can infect anyone. Unfortunately, we do not currently have a vaccine for everyone against this virus. Prevention of transmission includes, as with flu, isolating when ill, cleaning surfaces, and washing hands.2
COVID-19
Of course, the effects of the COVID-19 pandemic are also still here as well. During the first week of December, the CDC reported rising cases of COVID across the country. Within the past few months, there have been several developments, though, for protection. There are now bivalent vaccines available as either third doses or booster doses approved for all persons over 6 months of age. As of the first week of December, only 13.5% of those aged 5 and over had received an updated booster.
There is currently wider access to rapid testing, including at-home testing, which can allow individuals to identify if COVID positive. Additionally, there is access to medication to decrease the likelihood of severe disease – though this does not take the place of vaccinations.
If anyone does test positive for COVID, they should follow the most recent quarantine guidelines including wearing a well-fitted mask when they do begin returning to activities.3
With rising cases of all three of these viruses, some may be asking how we can safely gather. There are several things to consider and do to enjoy our events. The first thing everyone can do is to receive updated vaccinations for both influenza and COVID-19 if eligible. Although it may take some time to be effective, vaccination is still one of our most effective methods of disease prevention and is important this winter season. Vaccinations can also help decrease the risk of severe disease.
Although many have stopped masking, as cases rise, it is time to consider masking particularly when community levels of any of these viruses are high. Masks help with preventing and spreading more than just COVID-19. Using them can be especially important for those going places such as stores and to large public gatherings and when riding on buses, planes, or trains.
In summary
Preventing exposure by masking can help keep individuals healthy prior to celebrating the holidays with others. With access to rapid testing, it makes sense to consider testing prior to gathering with friends and family. Most importantly, although we all are looking forward to spending time with our loved ones, it is important to stay home if not feeling well. Following these recommendations will allow us to have a safer and more joyful holiday season.
Dr. Wheat is a family physician at Erie Family Health Center and program director of Northwestern University’s McGaw Family Medicine residency program, both in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].
References
1. Centers for Disease Control and Prevention. Influenza (flu). [Online] Dec. 1, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/flu/index.htm.
2. Respiratory syncytial virus. Respiratory syncytial virus infection (RSV). [Online] Oct. 28, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/rsv/index.html.
3. COVID-19. [Online] Dec. 7, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/coronavirus/2019-ncov/index.html.
This holiday season, I am looking forward to spending some time with family, as I have in the past. As I have chatted with others, many friends are looking forward to events that are potentially larger and potentially returning to prepandemic type gatherings.
Gathering is important and can bring joy, sense of community, and love to the lives of many. Unfortunately, the risks associated with gathering are not over. as our country faces many cases of respiratory syncytial virus (RSV), COVID-19, and influenza at the same time.
During the first week of December, cases of influenza were rising across the country1 and were rising faster than in previous years. Although getting the vaccine is an important method of influenza prevention and is recommended for everyone over the age of 6 months with rare exception, many have not gotten their vaccine this year.
Influenza
Thus far, “nearly 50% of reported flu-associated hospitalizations in women of childbearing age have been in women who are pregnant.” We are seeing this at a time with lower-than-average uptake of influenza vaccine leaving both the pregnant persons and their babies unprotected. In addition to utilizing vaccines as prevention, isolating when ill, cleaning surfaces, and practicing good hand hygiene can all decrease transmission.
RSV
In addition to rises of influenza, there are currently high rates of RSV in various parts of the country. Prior to 2020, RSV typically started in the fall and peaked in the winter months. However, since the pandemic, the typical seasonal pattern has not returned, and it is unclear when it will. Although RSV hits the very young, the old, and the immunocompromised the most, RSV can infect anyone. Unfortunately, we do not currently have a vaccine for everyone against this virus. Prevention of transmission includes, as with flu, isolating when ill, cleaning surfaces, and washing hands.2
COVID-19
Of course, the effects of the COVID-19 pandemic are also still here as well. During the first week of December, the CDC reported rising cases of COVID across the country. Within the past few months, there have been several developments, though, for protection. There are now bivalent vaccines available as either third doses or booster doses approved for all persons over 6 months of age. As of the first week of December, only 13.5% of those aged 5 and over had received an updated booster.
There is currently wider access to rapid testing, including at-home testing, which can allow individuals to identify if COVID positive. Additionally, there is access to medication to decrease the likelihood of severe disease – though this does not take the place of vaccinations.
If anyone does test positive for COVID, they should follow the most recent quarantine guidelines including wearing a well-fitted mask when they do begin returning to activities.3
With rising cases of all three of these viruses, some may be asking how we can safely gather. There are several things to consider and do to enjoy our events. The first thing everyone can do is to receive updated vaccinations for both influenza and COVID-19 if eligible. Although it may take some time to be effective, vaccination is still one of our most effective methods of disease prevention and is important this winter season. Vaccinations can also help decrease the risk of severe disease.
Although many have stopped masking, as cases rise, it is time to consider masking particularly when community levels of any of these viruses are high. Masks help with preventing and spreading more than just COVID-19. Using them can be especially important for those going places such as stores and to large public gatherings and when riding on buses, planes, or trains.
In summary
Preventing exposure by masking can help keep individuals healthy prior to celebrating the holidays with others. With access to rapid testing, it makes sense to consider testing prior to gathering with friends and family. Most importantly, although we all are looking forward to spending time with our loved ones, it is important to stay home if not feeling well. Following these recommendations will allow us to have a safer and more joyful holiday season.
Dr. Wheat is a family physician at Erie Family Health Center and program director of Northwestern University’s McGaw Family Medicine residency program, both in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].
References
1. Centers for Disease Control and Prevention. Influenza (flu). [Online] Dec. 1, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/flu/index.htm.
2. Respiratory syncytial virus. Respiratory syncytial virus infection (RSV). [Online] Oct. 28, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/rsv/index.html.
3. COVID-19. [Online] Dec. 7, 2022. [Cited: 2022 Dec 10.] https://www.cdc.gov/coronavirus/2019-ncov/index.html.
Cardiac injury caused by COVID-19 less common than thought
The study examined cardiac MRI scans in 31 patients before and after having COVID-19 infection and found no new evidence of myocardial injury in the post-COVID scans relative to the pre-COVID scans.
“To the best of our knowledge this is the first cardiac MRI study to assess myocardial injury pre- and post-COVID-19,” the authors stated.
They say that while this study cannot rule out the possibility of rare events of COVID-19–induced myocardial injury, “the complete absence of de novo late gadolinium enhancement lesions after COVID-19 in this cohort indicates that outside special circumstances, COVID-19–induced myocardial injury may be much less common than suggested by previous studies.”
The study was published online in JACC: Cardiovascular Imaging.
Coauthor Till F. Althoff, MD, Cardiovascular Institute, Clínic–University Hospital Barcelona, said in an interview that previous reports have found a high rate of cardiac lesions in patients undergoing imaging after having had COVID-19 infection.
“In some reports, this has been as high as 80% of patients even though they have not had severe COVID disease. These reports have been interpreted as showing the majority of patients have some COVID-induced cardiac damage, which is an alarming message,” he commented.
However, he pointed out that the patients in these reports did not undergo a cardiac MRI scan before they had COVID-19 so it wasn’t known whether these cardiac lesions were present before infection or not.
To try and gain more accurate information, the current study examined cardiac MRI scans in the same patients before and after they had COVID-19.
The researchers, from an arrhythmia unit, made use of the fact that all their patients have cardiac MRI data, so they used their large registry of patients in whom cardiac MRI had been performed, and cross referenced this to a health care database to identify those patients who had confirmed COVID-19 after they obtaining a cardiac scan at the arrhythmia unit. They then conducted another cardiac MRI scan in the 31 patients identified a median of 5 months after their COVID-19 infection.
“These 31 patients had a cardiac MRI scan pre-COVID and post COVID using exactly the same scanner with identical sequences, so the scans were absolutely comparable,” Dr. Althoff noted.
Of these 31 patients, 7 had been hospitalized at the time of acute presentation with COVID-19, of whom 2 required intensive care. Most patients (29) had been symptomatic, but none reported cardiac symptoms.
Results showed that, on the post–COVID-19 scan, late gadolinium enhancement lesions indicative of residual myocardial injury were encountered in 15 of the 31 patients (48%), which the researchers said is in line with previous reports.
However, intraindividual comparison with the pre–COVID-19 cardiac MRI scans showed all these lesions were preexisting with identical localization, pattern, and transmural distribution, and thus not COVID-19 related.
Quantitative analyses, performed independently, detected no increase in the size of individual lesions nor in the global left ventricular late gadolinium enhancement extent.
Comparison of pre- and post COVID-19 imaging sequences did not show any differences in ventricular functional or structural parameters.
“While this study only has 31 patients, the fact that we are conducting intra-individual comparisons, which rules out bias, means that we don’t need a large number of patients for reliable results,” Dr. Althoff said.
“These types of lesions are normal to see. We know that individuals without cardiac disease have these types of lesions, and they are not necessarily an indication of any specific pathology. I was kind of surprised by the interpretation of previous data, which is why we did the current study,” he added.
Dr. Althoff acknowledged that some cardiac injury may have been seen if much larger numbers of patients had been included. “But I think we can say from this data that COVID-induced cardiac damage is much less of an issue than we may have previously thought,” he added.
He also noted that most of the patients in this study had mild COVID-19, so the results cannot be extrapolated to severe COVID-19 infection.
However, Dr. Althoff pointed out that all the patients already had atrial fibrillation, so would have been at higher risk of cardiac injury from COVID-19.
“These patients had preexisting cardiac risk factors, and thus they would have been more susceptible to both a more severe course of COVID and an increased risk of myocardial damage due to COVID. The fact that we don’t find any myocardial injury due to COVID in this group is even more reassuring. The general population will be at even lower risk,” he commented.
“I think we can say that, in COVID patients who do not have any cardiac symptoms, our study suggests that the incidence of cardiac injury is very low,” Dr. Althoff said.
“Even in patients with severe COVID and myocardial involvement reflected by increased troponin levels, I wouldn’t be sure that they have any residual cardiac injury. While it has been reported that cardiac lesions have been found in such patients, pre-COVID MRI scans were not available so we don’t know if they were there before,” he added.
“We do not know the true incidence of cardiac injury after COVID, but I think we can say from this data that it is definitely not anywhere near the 40%-50% or even greater that some of the previous reports have suggested,” he stated.
Dr. Althoff suggested that, based on these data, some of the recommendations based on previous reports such the need for follow-up cardiac scans and caution about partaking in sports again after COVID-19 infection, are probably not necessary.
“Our data suggest that these concerns are unfounded, and we need to step back a bit and stop alarming patients about the risk of cardiac damage after COVID,” he said. “Yes, if patients have cardiac symptoms during or after COVID infection they should get checked out, but I do not think we need to do a cardiac risk assessment in patients without cardiac symptoms in COVID.”
This work is supported in part by grants from Instituto de Salud Carlos III, the Spanish government, Madrid, and Fundació la Marató de TV3 in Catalonia. Dr. Althoff has received research grants for investigator-initiated trials from Biosense Webster.
A version of this article first appeared on Medscape.com.
The study examined cardiac MRI scans in 31 patients before and after having COVID-19 infection and found no new evidence of myocardial injury in the post-COVID scans relative to the pre-COVID scans.
“To the best of our knowledge this is the first cardiac MRI study to assess myocardial injury pre- and post-COVID-19,” the authors stated.
They say that while this study cannot rule out the possibility of rare events of COVID-19–induced myocardial injury, “the complete absence of de novo late gadolinium enhancement lesions after COVID-19 in this cohort indicates that outside special circumstances, COVID-19–induced myocardial injury may be much less common than suggested by previous studies.”
The study was published online in JACC: Cardiovascular Imaging.
Coauthor Till F. Althoff, MD, Cardiovascular Institute, Clínic–University Hospital Barcelona, said in an interview that previous reports have found a high rate of cardiac lesions in patients undergoing imaging after having had COVID-19 infection.
“In some reports, this has been as high as 80% of patients even though they have not had severe COVID disease. These reports have been interpreted as showing the majority of patients have some COVID-induced cardiac damage, which is an alarming message,” he commented.
However, he pointed out that the patients in these reports did not undergo a cardiac MRI scan before they had COVID-19 so it wasn’t known whether these cardiac lesions were present before infection or not.
To try and gain more accurate information, the current study examined cardiac MRI scans in the same patients before and after they had COVID-19.
The researchers, from an arrhythmia unit, made use of the fact that all their patients have cardiac MRI data, so they used their large registry of patients in whom cardiac MRI had been performed, and cross referenced this to a health care database to identify those patients who had confirmed COVID-19 after they obtaining a cardiac scan at the arrhythmia unit. They then conducted another cardiac MRI scan in the 31 patients identified a median of 5 months after their COVID-19 infection.
“These 31 patients had a cardiac MRI scan pre-COVID and post COVID using exactly the same scanner with identical sequences, so the scans were absolutely comparable,” Dr. Althoff noted.
Of these 31 patients, 7 had been hospitalized at the time of acute presentation with COVID-19, of whom 2 required intensive care. Most patients (29) had been symptomatic, but none reported cardiac symptoms.
Results showed that, on the post–COVID-19 scan, late gadolinium enhancement lesions indicative of residual myocardial injury were encountered in 15 of the 31 patients (48%), which the researchers said is in line with previous reports.
However, intraindividual comparison with the pre–COVID-19 cardiac MRI scans showed all these lesions were preexisting with identical localization, pattern, and transmural distribution, and thus not COVID-19 related.
Quantitative analyses, performed independently, detected no increase in the size of individual lesions nor in the global left ventricular late gadolinium enhancement extent.
Comparison of pre- and post COVID-19 imaging sequences did not show any differences in ventricular functional or structural parameters.
“While this study only has 31 patients, the fact that we are conducting intra-individual comparisons, which rules out bias, means that we don’t need a large number of patients for reliable results,” Dr. Althoff said.
“These types of lesions are normal to see. We know that individuals without cardiac disease have these types of lesions, and they are not necessarily an indication of any specific pathology. I was kind of surprised by the interpretation of previous data, which is why we did the current study,” he added.
Dr. Althoff acknowledged that some cardiac injury may have been seen if much larger numbers of patients had been included. “But I think we can say from this data that COVID-induced cardiac damage is much less of an issue than we may have previously thought,” he added.
He also noted that most of the patients in this study had mild COVID-19, so the results cannot be extrapolated to severe COVID-19 infection.
However, Dr. Althoff pointed out that all the patients already had atrial fibrillation, so would have been at higher risk of cardiac injury from COVID-19.
“These patients had preexisting cardiac risk factors, and thus they would have been more susceptible to both a more severe course of COVID and an increased risk of myocardial damage due to COVID. The fact that we don’t find any myocardial injury due to COVID in this group is even more reassuring. The general population will be at even lower risk,” he commented.
“I think we can say that, in COVID patients who do not have any cardiac symptoms, our study suggests that the incidence of cardiac injury is very low,” Dr. Althoff said.
“Even in patients with severe COVID and myocardial involvement reflected by increased troponin levels, I wouldn’t be sure that they have any residual cardiac injury. While it has been reported that cardiac lesions have been found in such patients, pre-COVID MRI scans were not available so we don’t know if they were there before,” he added.
“We do not know the true incidence of cardiac injury after COVID, but I think we can say from this data that it is definitely not anywhere near the 40%-50% or even greater that some of the previous reports have suggested,” he stated.
Dr. Althoff suggested that, based on these data, some of the recommendations based on previous reports such the need for follow-up cardiac scans and caution about partaking in sports again after COVID-19 infection, are probably not necessary.
“Our data suggest that these concerns are unfounded, and we need to step back a bit and stop alarming patients about the risk of cardiac damage after COVID,” he said. “Yes, if patients have cardiac symptoms during or after COVID infection they should get checked out, but I do not think we need to do a cardiac risk assessment in patients without cardiac symptoms in COVID.”
This work is supported in part by grants from Instituto de Salud Carlos III, the Spanish government, Madrid, and Fundació la Marató de TV3 in Catalonia. Dr. Althoff has received research grants for investigator-initiated trials from Biosense Webster.
A version of this article first appeared on Medscape.com.
The study examined cardiac MRI scans in 31 patients before and after having COVID-19 infection and found no new evidence of myocardial injury in the post-COVID scans relative to the pre-COVID scans.
“To the best of our knowledge this is the first cardiac MRI study to assess myocardial injury pre- and post-COVID-19,” the authors stated.
They say that while this study cannot rule out the possibility of rare events of COVID-19–induced myocardial injury, “the complete absence of de novo late gadolinium enhancement lesions after COVID-19 in this cohort indicates that outside special circumstances, COVID-19–induced myocardial injury may be much less common than suggested by previous studies.”
The study was published online in JACC: Cardiovascular Imaging.
Coauthor Till F. Althoff, MD, Cardiovascular Institute, Clínic–University Hospital Barcelona, said in an interview that previous reports have found a high rate of cardiac lesions in patients undergoing imaging after having had COVID-19 infection.
“In some reports, this has been as high as 80% of patients even though they have not had severe COVID disease. These reports have been interpreted as showing the majority of patients have some COVID-induced cardiac damage, which is an alarming message,” he commented.
However, he pointed out that the patients in these reports did not undergo a cardiac MRI scan before they had COVID-19 so it wasn’t known whether these cardiac lesions were present before infection or not.
To try and gain more accurate information, the current study examined cardiac MRI scans in the same patients before and after they had COVID-19.
The researchers, from an arrhythmia unit, made use of the fact that all their patients have cardiac MRI data, so they used their large registry of patients in whom cardiac MRI had been performed, and cross referenced this to a health care database to identify those patients who had confirmed COVID-19 after they obtaining a cardiac scan at the arrhythmia unit. They then conducted another cardiac MRI scan in the 31 patients identified a median of 5 months after their COVID-19 infection.
“These 31 patients had a cardiac MRI scan pre-COVID and post COVID using exactly the same scanner with identical sequences, so the scans were absolutely comparable,” Dr. Althoff noted.
Of these 31 patients, 7 had been hospitalized at the time of acute presentation with COVID-19, of whom 2 required intensive care. Most patients (29) had been symptomatic, but none reported cardiac symptoms.
Results showed that, on the post–COVID-19 scan, late gadolinium enhancement lesions indicative of residual myocardial injury were encountered in 15 of the 31 patients (48%), which the researchers said is in line with previous reports.
However, intraindividual comparison with the pre–COVID-19 cardiac MRI scans showed all these lesions were preexisting with identical localization, pattern, and transmural distribution, and thus not COVID-19 related.
Quantitative analyses, performed independently, detected no increase in the size of individual lesions nor in the global left ventricular late gadolinium enhancement extent.
Comparison of pre- and post COVID-19 imaging sequences did not show any differences in ventricular functional or structural parameters.
“While this study only has 31 patients, the fact that we are conducting intra-individual comparisons, which rules out bias, means that we don’t need a large number of patients for reliable results,” Dr. Althoff said.
“These types of lesions are normal to see. We know that individuals without cardiac disease have these types of lesions, and they are not necessarily an indication of any specific pathology. I was kind of surprised by the interpretation of previous data, which is why we did the current study,” he added.
Dr. Althoff acknowledged that some cardiac injury may have been seen if much larger numbers of patients had been included. “But I think we can say from this data that COVID-induced cardiac damage is much less of an issue than we may have previously thought,” he added.
He also noted that most of the patients in this study had mild COVID-19, so the results cannot be extrapolated to severe COVID-19 infection.
However, Dr. Althoff pointed out that all the patients already had atrial fibrillation, so would have been at higher risk of cardiac injury from COVID-19.
“These patients had preexisting cardiac risk factors, and thus they would have been more susceptible to both a more severe course of COVID and an increased risk of myocardial damage due to COVID. The fact that we don’t find any myocardial injury due to COVID in this group is even more reassuring. The general population will be at even lower risk,” he commented.
“I think we can say that, in COVID patients who do not have any cardiac symptoms, our study suggests that the incidence of cardiac injury is very low,” Dr. Althoff said.
“Even in patients with severe COVID and myocardial involvement reflected by increased troponin levels, I wouldn’t be sure that they have any residual cardiac injury. While it has been reported that cardiac lesions have been found in such patients, pre-COVID MRI scans were not available so we don’t know if they were there before,” he added.
“We do not know the true incidence of cardiac injury after COVID, but I think we can say from this data that it is definitely not anywhere near the 40%-50% or even greater that some of the previous reports have suggested,” he stated.
Dr. Althoff suggested that, based on these data, some of the recommendations based on previous reports such the need for follow-up cardiac scans and caution about partaking in sports again after COVID-19 infection, are probably not necessary.
“Our data suggest that these concerns are unfounded, and we need to step back a bit and stop alarming patients about the risk of cardiac damage after COVID,” he said. “Yes, if patients have cardiac symptoms during or after COVID infection they should get checked out, but I do not think we need to do a cardiac risk assessment in patients without cardiac symptoms in COVID.”
This work is supported in part by grants from Instituto de Salud Carlos III, the Spanish government, Madrid, and Fundació la Marató de TV3 in Catalonia. Dr. Althoff has received research grants for investigator-initiated trials from Biosense Webster.
A version of this article first appeared on Medscape.com.
FROM JACC: CARDIOVASCULAR IMAGING
Scientists use mRNA technology for universal flu vaccine
Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through.
It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable.
“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.”
A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus.
It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics.
“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.”
That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says.
Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.
Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died.
The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall.
Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions.
“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.
But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.
A version of this article first appeared on WebMD.com.
Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through.
It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable.
“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.”
A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus.
It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics.
“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.”
That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says.
Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.
Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died.
The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall.
Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions.
“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.
But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.
A version of this article first appeared on WebMD.com.
Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through.
It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable.
“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.”
A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus.
It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics.
“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.”
That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says.
Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.
Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died.
The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall.
Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions.
“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.
But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.
A version of this article first appeared on WebMD.com.
FROM SCIENCE