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Helmet interface for ventilation likely superior in acute hypoxemic respiratory failure
For adults with acute hypoxemic respiratory failure (AHRF), treatment using a helmet interface is likely superior to a face mask interface, according to a systematic review of recent randomized controlled trials examining different noninvasive oxygenation strategies for AHRF treatment.
The COVID-19 pandemic has underscored the benefits of optimizing noninvasive strategies to avoid unnecessary intubation. Intubation may be avoided in patients with AHRF through noninvasive oxygenation strategies, including high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) and noninvasive bilevel ventilation, noted Tyler Pitre, MD, department of medicine, McMaster University, Hamilton, Ont., and colleagues. CPAP and bilevel ventilation can be delivered through different interfaces, most commonly face mask or helmet. While research has shown noninvasive strategies to be associated with reductions in risk for invasive mechanical ventilation, mortality assessments and analyses comparing specific modalities (i.e., CPAP vs. bilevel ventilation) have been limited. The incremental reduction in diaphragmatic effort and improved gas exchange demonstrated for bilevel ventilation compared with CPAP in COPD patients suggests that responses in AHRF may differ for CPAP and bilevel ventilation, state Dr. Pitre and colleagues. On the other hand, the increased drive pressure of bilevel ventilation may compound patient self-induced lung injury with concomitant lung inflammation and need for prolonged respiratory support. New evidence from several large, high quality randomized controlled trials (RCTs) in COVID-19-related AHRF offered an opportunity to reassess comparative efficacies, the researchers noted.
The retrospective study encompassed RCTs with all types of AHRF, including COVID-19 related, with a total of 7,046 patients whose median age was 59.4 years (61.4% were males). Thirty of the 36 RCTs reported on mortality (6,114 patients and 1,539 deaths). The study’s analysis showed with moderate certainty that helmet CPAP reduces mortality (231 fewer deaths per 1,000 [95% confidence interval (CI), 126-273]) while the 63 fewer deaths per 1,000 (95% CI, 15-102) indicated with low certainty that HFNC may reduce mortality compared with standard oxygen therapy (SOT). The analysis showed also that face mask bilevel (36 fewer deaths per 1,000 [84.0 fewer to 24.0 more]) and helmet bilevel ventilation (129.0 fewer deaths per 1,000 [195.0 to 24.0 fewer]) may reduce death compared with SOT (all low certainty). The mortality benefit for face mask CPAP compared with SOT was uncertain (very low certainty) (9 fewer deaths per 1,000 [81 fewer deaths to 84 more]). For helmet CPAP vs. HFNC ventilation, the mortality benefit had moderate certainty (198.1 fewer events per 1,000 [95% CI, 69.75-248.31].
Mechanical ventilation and ICU duration
The authors found that HFNC probably reduces the need for invasive mechanical ventilation (103.5 fewer events per 1,000 [40.5-157.5 fewer]; moderate certainty). Helmet bilevel ventilation and helmet CPAP may reduce the duration of ICU stay compared with SOT (both low certainty) at (4.84 days fewer [95% CI 2.33 to 16 7.36 days fewer]) and (1.74 days fewer [95% CI 4.49 fewer to 1.01 more]), respectively. Also, SOT may be more comfortable than face mask noninvasive ventilation (NIV) and no different in comfort compared with HFNC (both low certainty).
“Helmet noninvasive ventilation interfaces is probably effective in acute hypoxic respiratory failure and is superior to face mask interfaces. All modalities including HFNC probably reduce the risk of need for invasive mechanical ventilation,” the researchers wrote.
“This meta-analysis shows that helmet noninvasive ventilation is effective in reducing death, and need for invasive mechanical ventilation based on a moderate certainty of evidence,” Shyamsunder Subramanian, MD, chief, division of pulmonary critical care and sleep medicine, Sutter Health, Tracy, Calif., said in an interview. “It is premature based on the results of this meta-analysis to conclude that guideline changes are needed. Use of helmet based ventilation remains limited in scope. We need appropriately designed prospective trials across multiple centers to get sufficient rigor of scientific evidence before any change in guidelines or practice recommendations can be formulated about the appropriate use of helmet NIV in acute respiratory failure.”
The researchers cited the relative heterogeneity of the population included in this analysis as a study limitation.
Dr. Pitre and Dr. Subramanian disclosed that they have no relevant conflicts of interest.
For adults with acute hypoxemic respiratory failure (AHRF), treatment using a helmet interface is likely superior to a face mask interface, according to a systematic review of recent randomized controlled trials examining different noninvasive oxygenation strategies for AHRF treatment.
The COVID-19 pandemic has underscored the benefits of optimizing noninvasive strategies to avoid unnecessary intubation. Intubation may be avoided in patients with AHRF through noninvasive oxygenation strategies, including high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) and noninvasive bilevel ventilation, noted Tyler Pitre, MD, department of medicine, McMaster University, Hamilton, Ont., and colleagues. CPAP and bilevel ventilation can be delivered through different interfaces, most commonly face mask or helmet. While research has shown noninvasive strategies to be associated with reductions in risk for invasive mechanical ventilation, mortality assessments and analyses comparing specific modalities (i.e., CPAP vs. bilevel ventilation) have been limited. The incremental reduction in diaphragmatic effort and improved gas exchange demonstrated for bilevel ventilation compared with CPAP in COPD patients suggests that responses in AHRF may differ for CPAP and bilevel ventilation, state Dr. Pitre and colleagues. On the other hand, the increased drive pressure of bilevel ventilation may compound patient self-induced lung injury with concomitant lung inflammation and need for prolonged respiratory support. New evidence from several large, high quality randomized controlled trials (RCTs) in COVID-19-related AHRF offered an opportunity to reassess comparative efficacies, the researchers noted.
The retrospective study encompassed RCTs with all types of AHRF, including COVID-19 related, with a total of 7,046 patients whose median age was 59.4 years (61.4% were males). Thirty of the 36 RCTs reported on mortality (6,114 patients and 1,539 deaths). The study’s analysis showed with moderate certainty that helmet CPAP reduces mortality (231 fewer deaths per 1,000 [95% confidence interval (CI), 126-273]) while the 63 fewer deaths per 1,000 (95% CI, 15-102) indicated with low certainty that HFNC may reduce mortality compared with standard oxygen therapy (SOT). The analysis showed also that face mask bilevel (36 fewer deaths per 1,000 [84.0 fewer to 24.0 more]) and helmet bilevel ventilation (129.0 fewer deaths per 1,000 [195.0 to 24.0 fewer]) may reduce death compared with SOT (all low certainty). The mortality benefit for face mask CPAP compared with SOT was uncertain (very low certainty) (9 fewer deaths per 1,000 [81 fewer deaths to 84 more]). For helmet CPAP vs. HFNC ventilation, the mortality benefit had moderate certainty (198.1 fewer events per 1,000 [95% CI, 69.75-248.31].
Mechanical ventilation and ICU duration
The authors found that HFNC probably reduces the need for invasive mechanical ventilation (103.5 fewer events per 1,000 [40.5-157.5 fewer]; moderate certainty). Helmet bilevel ventilation and helmet CPAP may reduce the duration of ICU stay compared with SOT (both low certainty) at (4.84 days fewer [95% CI 2.33 to 16 7.36 days fewer]) and (1.74 days fewer [95% CI 4.49 fewer to 1.01 more]), respectively. Also, SOT may be more comfortable than face mask noninvasive ventilation (NIV) and no different in comfort compared with HFNC (both low certainty).
“Helmet noninvasive ventilation interfaces is probably effective in acute hypoxic respiratory failure and is superior to face mask interfaces. All modalities including HFNC probably reduce the risk of need for invasive mechanical ventilation,” the researchers wrote.
“This meta-analysis shows that helmet noninvasive ventilation is effective in reducing death, and need for invasive mechanical ventilation based on a moderate certainty of evidence,” Shyamsunder Subramanian, MD, chief, division of pulmonary critical care and sleep medicine, Sutter Health, Tracy, Calif., said in an interview. “It is premature based on the results of this meta-analysis to conclude that guideline changes are needed. Use of helmet based ventilation remains limited in scope. We need appropriately designed prospective trials across multiple centers to get sufficient rigor of scientific evidence before any change in guidelines or practice recommendations can be formulated about the appropriate use of helmet NIV in acute respiratory failure.”
The researchers cited the relative heterogeneity of the population included in this analysis as a study limitation.
Dr. Pitre and Dr. Subramanian disclosed that they have no relevant conflicts of interest.
For adults with acute hypoxemic respiratory failure (AHRF), treatment using a helmet interface is likely superior to a face mask interface, according to a systematic review of recent randomized controlled trials examining different noninvasive oxygenation strategies for AHRF treatment.
The COVID-19 pandemic has underscored the benefits of optimizing noninvasive strategies to avoid unnecessary intubation. Intubation may be avoided in patients with AHRF through noninvasive oxygenation strategies, including high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) and noninvasive bilevel ventilation, noted Tyler Pitre, MD, department of medicine, McMaster University, Hamilton, Ont., and colleagues. CPAP and bilevel ventilation can be delivered through different interfaces, most commonly face mask or helmet. While research has shown noninvasive strategies to be associated with reductions in risk for invasive mechanical ventilation, mortality assessments and analyses comparing specific modalities (i.e., CPAP vs. bilevel ventilation) have been limited. The incremental reduction in diaphragmatic effort and improved gas exchange demonstrated for bilevel ventilation compared with CPAP in COPD patients suggests that responses in AHRF may differ for CPAP and bilevel ventilation, state Dr. Pitre and colleagues. On the other hand, the increased drive pressure of bilevel ventilation may compound patient self-induced lung injury with concomitant lung inflammation and need for prolonged respiratory support. New evidence from several large, high quality randomized controlled trials (RCTs) in COVID-19-related AHRF offered an opportunity to reassess comparative efficacies, the researchers noted.
The retrospective study encompassed RCTs with all types of AHRF, including COVID-19 related, with a total of 7,046 patients whose median age was 59.4 years (61.4% were males). Thirty of the 36 RCTs reported on mortality (6,114 patients and 1,539 deaths). The study’s analysis showed with moderate certainty that helmet CPAP reduces mortality (231 fewer deaths per 1,000 [95% confidence interval (CI), 126-273]) while the 63 fewer deaths per 1,000 (95% CI, 15-102) indicated with low certainty that HFNC may reduce mortality compared with standard oxygen therapy (SOT). The analysis showed also that face mask bilevel (36 fewer deaths per 1,000 [84.0 fewer to 24.0 more]) and helmet bilevel ventilation (129.0 fewer deaths per 1,000 [195.0 to 24.0 fewer]) may reduce death compared with SOT (all low certainty). The mortality benefit for face mask CPAP compared with SOT was uncertain (very low certainty) (9 fewer deaths per 1,000 [81 fewer deaths to 84 more]). For helmet CPAP vs. HFNC ventilation, the mortality benefit had moderate certainty (198.1 fewer events per 1,000 [95% CI, 69.75-248.31].
Mechanical ventilation and ICU duration
The authors found that HFNC probably reduces the need for invasive mechanical ventilation (103.5 fewer events per 1,000 [40.5-157.5 fewer]; moderate certainty). Helmet bilevel ventilation and helmet CPAP may reduce the duration of ICU stay compared with SOT (both low certainty) at (4.84 days fewer [95% CI 2.33 to 16 7.36 days fewer]) and (1.74 days fewer [95% CI 4.49 fewer to 1.01 more]), respectively. Also, SOT may be more comfortable than face mask noninvasive ventilation (NIV) and no different in comfort compared with HFNC (both low certainty).
“Helmet noninvasive ventilation interfaces is probably effective in acute hypoxic respiratory failure and is superior to face mask interfaces. All modalities including HFNC probably reduce the risk of need for invasive mechanical ventilation,” the researchers wrote.
“This meta-analysis shows that helmet noninvasive ventilation is effective in reducing death, and need for invasive mechanical ventilation based on a moderate certainty of evidence,” Shyamsunder Subramanian, MD, chief, division of pulmonary critical care and sleep medicine, Sutter Health, Tracy, Calif., said in an interview. “It is premature based on the results of this meta-analysis to conclude that guideline changes are needed. Use of helmet based ventilation remains limited in scope. We need appropriately designed prospective trials across multiple centers to get sufficient rigor of scientific evidence before any change in guidelines or practice recommendations can be formulated about the appropriate use of helmet NIV in acute respiratory failure.”
The researchers cited the relative heterogeneity of the population included in this analysis as a study limitation.
Dr. Pitre and Dr. Subramanian disclosed that they have no relevant conflicts of interest.
FROM CHEST
General, abdominal obesity linked to chronic respiratory illness
A recent Swedish study found that both abdominal and general obesity were independently associated with respiratory illnesses, including asthma and self-reported chronic obstructive pulmonary disease.
Relationships between respiratory conditions with characterized obesity types in adults were assessed using self-report surveys from participants originally enrolled in the European Community Respiratory Health Survey (ECRHS) investigating asthma, allergy, and risk factors. The Respiratory Health in Northern Europe (RHINE) III provides a second follow-up substudy of ECRHS focused on two forms of obesity associated with respiratory illnesses.
Obesity is a characteristic risk factor linked to respiratory ailments such as asthma and COPD. High body mass index (BMI) and waist circumference (WC) provide quantitative measurements for defining conditions of comprehensive general and abdominal obesity, respectively.
Although both types of obesity have been associated with asthma incidence, studies on their independent impact on this disease have been limited. Previous reports on abdominal obesity associated with asthma have been inconsistent when considering sexes in the analysis. Additionally, COPD and related outcomes differed between abdominal and general obesity, indicating a need to discover whether self-reported WC abdominal obesity and BMI-based general obesity are independently associated with respiratory symptoms, early- and late-onset asthma, COPD, chronic bronchitis, rhinitis, and sex, Marta A. Kisiel, MD, PhD, of the department of environmental and occupational medicine, Uppsala University, Sweden, and colleagues write.
In a prospective study published in the journal Respiratory Medicine, the researchers report on a cross-sectional investigation of responses to a questionnaire similar to one utilized 10 years earlier in the RHINE II study. Questions required simple yes/no responses that covered asthma, respiratory symptoms, allergic rhinitis, chronic bronchitis, and COPD. Additional requested information included age of asthma onset, potential confounding variables of age, smoking, physical activity, and highest education level, weight and height for BMI calculation, and WC measurement with instructions and a provided tape measure.
The population of the RHINE III study conducted from 2010 to 2012 was composed of 12,290 participants (53% response frequency) obtained from a total of seven research centers located in five northern European countries. Obesity categorization classified 1,837 (6.7%) participants as generally obese based on a high BMI ≥ 30 kg/m2 and 4,261 (34.7%) as abdominally obese by WC measurements of ≥ 102 cm for men and ≥ 88 cm for women. Of the 4,261 total participants, 1,669 met both general and abdominal obesity criteria. Mean age was in the low 50s range and the obese population consisted of more women than men.
Simple linear regression revealed that BMI and WC were highly correlated, and both were associated with tested respiratory conditions when adjusted for confounding variables. Differences with respect to WC and BMI were independently associated with most of the examined respiratory conditions when WC was adjusted for BMI and vice versa. Neither early-onset asthma nor allergic rhinitis were associated with WC, BMI, or abdominal or general obesity.
An independent association of abdominal obesity (with or without general obesity) was found to occur with respiratory symptoms, asthma, late-onset asthma, and chronic bronchitis.
After adjusting for abdominal obesity, general obesity showed an independent and significant association with respiratory symptoms, asthma, adult-onset asthma, and COPD. An analysis stratified by sex indicated a significant association of abdominal and general obesity with asthma in women presented as an odds ratio of 1.56 (95% confidence interval, 1.30-1.87) and 1.95 (95% CI, 1.56-2.43), respectively, compared with men, with an OR of 1.22 (95% CI, 0.97-3.17) and 1.28 (95% CI, 0.97-1.68), respectively. The association of abdominal and general obesity with COPD was also stronger in women, compared with men.
The researchers conclude that “both general and abdominal obesity [were], independent of each other, associated with respiratory symptoms in adults.” There is also a distinct difference between women and men for the association of self-reported asthma and COPD with abdominal and general obesity.
The large randomly selected sample size of participants from research centers located in five northern European countries was considered a major strength of this study as it permitted simultaneous adjustment for multiple potential confounders. Several limitations were acknowledged, including absence of data on obstructive respiratory disease severity, WC measurements not being performed by trained staff, and self-reported height and weight measurements.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A recent Swedish study found that both abdominal and general obesity were independently associated with respiratory illnesses, including asthma and self-reported chronic obstructive pulmonary disease.
Relationships between respiratory conditions with characterized obesity types in adults were assessed using self-report surveys from participants originally enrolled in the European Community Respiratory Health Survey (ECRHS) investigating asthma, allergy, and risk factors. The Respiratory Health in Northern Europe (RHINE) III provides a second follow-up substudy of ECRHS focused on two forms of obesity associated with respiratory illnesses.
Obesity is a characteristic risk factor linked to respiratory ailments such as asthma and COPD. High body mass index (BMI) and waist circumference (WC) provide quantitative measurements for defining conditions of comprehensive general and abdominal obesity, respectively.
Although both types of obesity have been associated with asthma incidence, studies on their independent impact on this disease have been limited. Previous reports on abdominal obesity associated with asthma have been inconsistent when considering sexes in the analysis. Additionally, COPD and related outcomes differed between abdominal and general obesity, indicating a need to discover whether self-reported WC abdominal obesity and BMI-based general obesity are independently associated with respiratory symptoms, early- and late-onset asthma, COPD, chronic bronchitis, rhinitis, and sex, Marta A. Kisiel, MD, PhD, of the department of environmental and occupational medicine, Uppsala University, Sweden, and colleagues write.
In a prospective study published in the journal Respiratory Medicine, the researchers report on a cross-sectional investigation of responses to a questionnaire similar to one utilized 10 years earlier in the RHINE II study. Questions required simple yes/no responses that covered asthma, respiratory symptoms, allergic rhinitis, chronic bronchitis, and COPD. Additional requested information included age of asthma onset, potential confounding variables of age, smoking, physical activity, and highest education level, weight and height for BMI calculation, and WC measurement with instructions and a provided tape measure.
The population of the RHINE III study conducted from 2010 to 2012 was composed of 12,290 participants (53% response frequency) obtained from a total of seven research centers located in five northern European countries. Obesity categorization classified 1,837 (6.7%) participants as generally obese based on a high BMI ≥ 30 kg/m2 and 4,261 (34.7%) as abdominally obese by WC measurements of ≥ 102 cm for men and ≥ 88 cm for women. Of the 4,261 total participants, 1,669 met both general and abdominal obesity criteria. Mean age was in the low 50s range and the obese population consisted of more women than men.
Simple linear regression revealed that BMI and WC were highly correlated, and both were associated with tested respiratory conditions when adjusted for confounding variables. Differences with respect to WC and BMI were independently associated with most of the examined respiratory conditions when WC was adjusted for BMI and vice versa. Neither early-onset asthma nor allergic rhinitis were associated with WC, BMI, or abdominal or general obesity.
An independent association of abdominal obesity (with or without general obesity) was found to occur with respiratory symptoms, asthma, late-onset asthma, and chronic bronchitis.
After adjusting for abdominal obesity, general obesity showed an independent and significant association with respiratory symptoms, asthma, adult-onset asthma, and COPD. An analysis stratified by sex indicated a significant association of abdominal and general obesity with asthma in women presented as an odds ratio of 1.56 (95% confidence interval, 1.30-1.87) and 1.95 (95% CI, 1.56-2.43), respectively, compared with men, with an OR of 1.22 (95% CI, 0.97-3.17) and 1.28 (95% CI, 0.97-1.68), respectively. The association of abdominal and general obesity with COPD was also stronger in women, compared with men.
The researchers conclude that “both general and abdominal obesity [were], independent of each other, associated with respiratory symptoms in adults.” There is also a distinct difference between women and men for the association of self-reported asthma and COPD with abdominal and general obesity.
The large randomly selected sample size of participants from research centers located in five northern European countries was considered a major strength of this study as it permitted simultaneous adjustment for multiple potential confounders. Several limitations were acknowledged, including absence of data on obstructive respiratory disease severity, WC measurements not being performed by trained staff, and self-reported height and weight measurements.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A recent Swedish study found that both abdominal and general obesity were independently associated with respiratory illnesses, including asthma and self-reported chronic obstructive pulmonary disease.
Relationships between respiratory conditions with characterized obesity types in adults were assessed using self-report surveys from participants originally enrolled in the European Community Respiratory Health Survey (ECRHS) investigating asthma, allergy, and risk factors. The Respiratory Health in Northern Europe (RHINE) III provides a second follow-up substudy of ECRHS focused on two forms of obesity associated with respiratory illnesses.
Obesity is a characteristic risk factor linked to respiratory ailments such as asthma and COPD. High body mass index (BMI) and waist circumference (WC) provide quantitative measurements for defining conditions of comprehensive general and abdominal obesity, respectively.
Although both types of obesity have been associated with asthma incidence, studies on their independent impact on this disease have been limited. Previous reports on abdominal obesity associated with asthma have been inconsistent when considering sexes in the analysis. Additionally, COPD and related outcomes differed between abdominal and general obesity, indicating a need to discover whether self-reported WC abdominal obesity and BMI-based general obesity are independently associated with respiratory symptoms, early- and late-onset asthma, COPD, chronic bronchitis, rhinitis, and sex, Marta A. Kisiel, MD, PhD, of the department of environmental and occupational medicine, Uppsala University, Sweden, and colleagues write.
In a prospective study published in the journal Respiratory Medicine, the researchers report on a cross-sectional investigation of responses to a questionnaire similar to one utilized 10 years earlier in the RHINE II study. Questions required simple yes/no responses that covered asthma, respiratory symptoms, allergic rhinitis, chronic bronchitis, and COPD. Additional requested information included age of asthma onset, potential confounding variables of age, smoking, physical activity, and highest education level, weight and height for BMI calculation, and WC measurement with instructions and a provided tape measure.
The population of the RHINE III study conducted from 2010 to 2012 was composed of 12,290 participants (53% response frequency) obtained from a total of seven research centers located in five northern European countries. Obesity categorization classified 1,837 (6.7%) participants as generally obese based on a high BMI ≥ 30 kg/m2 and 4,261 (34.7%) as abdominally obese by WC measurements of ≥ 102 cm for men and ≥ 88 cm for women. Of the 4,261 total participants, 1,669 met both general and abdominal obesity criteria. Mean age was in the low 50s range and the obese population consisted of more women than men.
Simple linear regression revealed that BMI and WC were highly correlated, and both were associated with tested respiratory conditions when adjusted for confounding variables. Differences with respect to WC and BMI were independently associated with most of the examined respiratory conditions when WC was adjusted for BMI and vice versa. Neither early-onset asthma nor allergic rhinitis were associated with WC, BMI, or abdominal or general obesity.
An independent association of abdominal obesity (with or without general obesity) was found to occur with respiratory symptoms, asthma, late-onset asthma, and chronic bronchitis.
After adjusting for abdominal obesity, general obesity showed an independent and significant association with respiratory symptoms, asthma, adult-onset asthma, and COPD. An analysis stratified by sex indicated a significant association of abdominal and general obesity with asthma in women presented as an odds ratio of 1.56 (95% confidence interval, 1.30-1.87) and 1.95 (95% CI, 1.56-2.43), respectively, compared with men, with an OR of 1.22 (95% CI, 0.97-3.17) and 1.28 (95% CI, 0.97-1.68), respectively. The association of abdominal and general obesity with COPD was also stronger in women, compared with men.
The researchers conclude that “both general and abdominal obesity [were], independent of each other, associated with respiratory symptoms in adults.” There is also a distinct difference between women and men for the association of self-reported asthma and COPD with abdominal and general obesity.
The large randomly selected sample size of participants from research centers located in five northern European countries was considered a major strength of this study as it permitted simultaneous adjustment for multiple potential confounders. Several limitations were acknowledged, including absence of data on obstructive respiratory disease severity, WC measurements not being performed by trained staff, and self-reported height and weight measurements.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The breathtaking effects of climate change
To see the harmful effects of climate change firsthand, you need look no farther than the nearest pulmonary clinic.
The causes and effects are unmistakable: pollen storms leading to allergy sufferers flooding into allergists’ offices; rising air pollution levels increasing risk for obstructive airway diseases, cardiopulmonary complications, and non–small cell lung cancer; melting snowpacks and atmospheric rivers inundating neighborhoods and leaving moldy debris and incipient fungal infections in their wake.
“The reason why we think climate change is going to change the type of disease patterns and the severity of illness that we see in patients with respiratory diseases is that it changes a lot of the environment as well as the exposures,” said Bathmapriya Balakrishnan, BMedSci, BMBS, from the section of Pulmonary, Critical Care, and Sleep Medicine in the department of medicine at West Virginia University, Morgantown.
“What we’re going to see is not just new diseases but also exacerbation of chronic diseases, things like asthma [and] COPD. And there’s also concern that patients who are otherwise healthy, because they now have more exposures that are due to climate change, can then develop these diseases,” she said in an interview.
Ms. Balakrishnan is the lead author of a comprehensive, evidence-based review focused on the effects of climate change and air pollution across the spectrum of pulmonary disorders. The review is published online ahead of print in the journal Chest.
“ To inform health care providers of evidence-based methods and improve patient counselling, further research regarding measures that limit exposure is needed. Empowering patients with resources to monitor air quality and minimize exposure is a key preventative measure for decreasing morbidity and mortality while improving quality of life,” Ms. Balakrishnan and colleagues write.
Similarly, in a statement on the effects of climate change on respiratory health, the American Public Health Association succinctly summarized the problem: “Warmer temperatures lead to an increase in pollutants and allergens. Poor air quality leads to reduced lung function, increased risk of asthma complications, heart attacks, heart failure, and death. Air pollution and allergens are the main exposures affecting lung and heart health in this changing climate.”
Early spring
Stanley Fineman, MD, MBA, a past president of the American College of Allergy, Asthma, & Immunology and an allergist in private practice in Atlanta, has seen firsthand how global warming and an earlier start to spring allergy season is affecting his patients.
“The season, at least in our area metro Atlanta, started earlier and has been lasting longer. The pollen counts are very high,” he told this news organization.
“In February we started seeing pollen counts over 1,000 [grams per cubic meter], which is unheard of, and in March about half the days we counted levels that were over 1,000, which is also unheard of. In April it was over 1,000 almost half the days.”
Dr. Fineman and colleagues both in Atlanta and across the country have reported sharp increases in the proportion of new adult patients and in existing patients who have experienced exacerbation of previously mild disease.
“Probably what’s happened is that they may have had some allergic sensitivity that resulted in milder manifestations, but this year they’re getting major manifestations,” Dr. Fineman said.
In a 2014 article in the journal European Respiratory Review, Gennaro D’Amato, MD, from High Speciality Hospital Antonio Cardarelli, Naples, Italy, and colleagues outlined the main effects of climate on pollen levels: “1) an increase in plant growth and faster plant growth; 2) an increase in the amount of pollen produced by each plant; 3) an increase in the amount of allergenic proteins contained in pollen; 4) an increase in the start time of plant growth and, therefore, the start of pollen production; 5) an earlier and longer pollen season; 6) change in the geospatial distribution of pollen, that is plant ranges and long-distance atmospheric transport moving polewards,” they write.
Bad air
In addition to pollen, the ambient air in many places is increasingly becoming saturated with bioallergenic proteins such as bacteria, viruses, animal dander, insects, molds, and plant species, Ms. Balakrishnan and colleagues noted, adding that “atmospheric levels of carbon dioxide have also been found to increase pollen productivity. These changes result in greater over-the-counter medication use, emergency department visits, and outpatient visits for respiratory illnesses.”
The rash of violent storms that has washed over much of the United States in recent months is also likely to increase the incidence of so-called “thunderstorm asthma,” caused when large quantities of respirable particulate matter are released before or during a thunderstorm.
Air pollution from the burning of carbon-based fuels and from wildfires sparked by hotter and drier conditions increase airborne particulate matter that can seriously exacerbate asthma, COPD, and other obstructive airway conditions.
In addition, as previously reported by Medscape, exposure to particulate matter has been implicated as a possible cause of non–small cell lung cancer in persons who have never smoked.
Critical care challenges
Among the myriad other effects of climate change postulated in evidence enumerated by Ms. Balakrishnan and colleagues are chest infections and pleural diseases, such as aspergillosis infections that occur after catastrophic flooding; increased incidence of Mycobacterium avium complex infections and hypersensitivity pneumonitis; increased demands on critical care specialists from natural disasters; pollution-induced cardiac arrest; and heat prostration and heat stroke from increasingly prevalent heat waves.
The reviewers also examined evidence suggesting links between climate change and pulmonary hypertension, interstitial lung disease, sleep disorders, and occupational pulmonary disorders.
Power to the patients
“Pulmonologists should counsel patients on ways to minimize outdoor and indoor pollution, using tight-fitting respirators and home air-purifying systems without encroaching on patients’ beliefs and choices,” the authors advise.
“Empowering patients with resources to monitor air quality daily, in inclement weather, and during disasters would help minimize exposure and thus improve overall health. The pulmonologist can play an important role in emphasizing the impact of climate change on pulmonary disorders during patient care encounters,” they write.
Ms. Balakrishan adds that another important mitigation measure that can be taken today is education.
“In medical school we don’t really learn about the impact of climate change – at least in my generation of physicians, climate change or global warming weren’t part of the medical curriculum – but now I think that there’s a lot of advocacy work being done by medical students who actually want more education on climate change and its effects on pulmonary diseases,” she said.
The study by Ms. Balakrishnan and colleagues was unfunded. Ms. Balakrishnan reports no relevant financial relationships. Co-author Mary-Beth Scholand, MD, has received personal fees from serving on advisory boards and speakers bureaus for Genentech, Boehringer Ingelheim, Veracyte, and United Therapeutics. Co-author Sean Callahan, MD, has received personal fees for serving on advisory boards for Gilead and Boehringer Ingelheim. Dr. Fineman reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
To see the harmful effects of climate change firsthand, you need look no farther than the nearest pulmonary clinic.
The causes and effects are unmistakable: pollen storms leading to allergy sufferers flooding into allergists’ offices; rising air pollution levels increasing risk for obstructive airway diseases, cardiopulmonary complications, and non–small cell lung cancer; melting snowpacks and atmospheric rivers inundating neighborhoods and leaving moldy debris and incipient fungal infections in their wake.
“The reason why we think climate change is going to change the type of disease patterns and the severity of illness that we see in patients with respiratory diseases is that it changes a lot of the environment as well as the exposures,” said Bathmapriya Balakrishnan, BMedSci, BMBS, from the section of Pulmonary, Critical Care, and Sleep Medicine in the department of medicine at West Virginia University, Morgantown.
“What we’re going to see is not just new diseases but also exacerbation of chronic diseases, things like asthma [and] COPD. And there’s also concern that patients who are otherwise healthy, because they now have more exposures that are due to climate change, can then develop these diseases,” she said in an interview.
Ms. Balakrishnan is the lead author of a comprehensive, evidence-based review focused on the effects of climate change and air pollution across the spectrum of pulmonary disorders. The review is published online ahead of print in the journal Chest.
“ To inform health care providers of evidence-based methods and improve patient counselling, further research regarding measures that limit exposure is needed. Empowering patients with resources to monitor air quality and minimize exposure is a key preventative measure for decreasing morbidity and mortality while improving quality of life,” Ms. Balakrishnan and colleagues write.
Similarly, in a statement on the effects of climate change on respiratory health, the American Public Health Association succinctly summarized the problem: “Warmer temperatures lead to an increase in pollutants and allergens. Poor air quality leads to reduced lung function, increased risk of asthma complications, heart attacks, heart failure, and death. Air pollution and allergens are the main exposures affecting lung and heart health in this changing climate.”
Early spring
Stanley Fineman, MD, MBA, a past president of the American College of Allergy, Asthma, & Immunology and an allergist in private practice in Atlanta, has seen firsthand how global warming and an earlier start to spring allergy season is affecting his patients.
“The season, at least in our area metro Atlanta, started earlier and has been lasting longer. The pollen counts are very high,” he told this news organization.
“In February we started seeing pollen counts over 1,000 [grams per cubic meter], which is unheard of, and in March about half the days we counted levels that were over 1,000, which is also unheard of. In April it was over 1,000 almost half the days.”
Dr. Fineman and colleagues both in Atlanta and across the country have reported sharp increases in the proportion of new adult patients and in existing patients who have experienced exacerbation of previously mild disease.
“Probably what’s happened is that they may have had some allergic sensitivity that resulted in milder manifestations, but this year they’re getting major manifestations,” Dr. Fineman said.
In a 2014 article in the journal European Respiratory Review, Gennaro D’Amato, MD, from High Speciality Hospital Antonio Cardarelli, Naples, Italy, and colleagues outlined the main effects of climate on pollen levels: “1) an increase in plant growth and faster plant growth; 2) an increase in the amount of pollen produced by each plant; 3) an increase in the amount of allergenic proteins contained in pollen; 4) an increase in the start time of plant growth and, therefore, the start of pollen production; 5) an earlier and longer pollen season; 6) change in the geospatial distribution of pollen, that is plant ranges and long-distance atmospheric transport moving polewards,” they write.
Bad air
In addition to pollen, the ambient air in many places is increasingly becoming saturated with bioallergenic proteins such as bacteria, viruses, animal dander, insects, molds, and plant species, Ms. Balakrishnan and colleagues noted, adding that “atmospheric levels of carbon dioxide have also been found to increase pollen productivity. These changes result in greater over-the-counter medication use, emergency department visits, and outpatient visits for respiratory illnesses.”
The rash of violent storms that has washed over much of the United States in recent months is also likely to increase the incidence of so-called “thunderstorm asthma,” caused when large quantities of respirable particulate matter are released before or during a thunderstorm.
Air pollution from the burning of carbon-based fuels and from wildfires sparked by hotter and drier conditions increase airborne particulate matter that can seriously exacerbate asthma, COPD, and other obstructive airway conditions.
In addition, as previously reported by Medscape, exposure to particulate matter has been implicated as a possible cause of non–small cell lung cancer in persons who have never smoked.
Critical care challenges
Among the myriad other effects of climate change postulated in evidence enumerated by Ms. Balakrishnan and colleagues are chest infections and pleural diseases, such as aspergillosis infections that occur after catastrophic flooding; increased incidence of Mycobacterium avium complex infections and hypersensitivity pneumonitis; increased demands on critical care specialists from natural disasters; pollution-induced cardiac arrest; and heat prostration and heat stroke from increasingly prevalent heat waves.
The reviewers also examined evidence suggesting links between climate change and pulmonary hypertension, interstitial lung disease, sleep disorders, and occupational pulmonary disorders.
Power to the patients
“Pulmonologists should counsel patients on ways to minimize outdoor and indoor pollution, using tight-fitting respirators and home air-purifying systems without encroaching on patients’ beliefs and choices,” the authors advise.
“Empowering patients with resources to monitor air quality daily, in inclement weather, and during disasters would help minimize exposure and thus improve overall health. The pulmonologist can play an important role in emphasizing the impact of climate change on pulmonary disorders during patient care encounters,” they write.
Ms. Balakrishan adds that another important mitigation measure that can be taken today is education.
“In medical school we don’t really learn about the impact of climate change – at least in my generation of physicians, climate change or global warming weren’t part of the medical curriculum – but now I think that there’s a lot of advocacy work being done by medical students who actually want more education on climate change and its effects on pulmonary diseases,” she said.
The study by Ms. Balakrishnan and colleagues was unfunded. Ms. Balakrishnan reports no relevant financial relationships. Co-author Mary-Beth Scholand, MD, has received personal fees from serving on advisory boards and speakers bureaus for Genentech, Boehringer Ingelheim, Veracyte, and United Therapeutics. Co-author Sean Callahan, MD, has received personal fees for serving on advisory boards for Gilead and Boehringer Ingelheim. Dr. Fineman reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
To see the harmful effects of climate change firsthand, you need look no farther than the nearest pulmonary clinic.
The causes and effects are unmistakable: pollen storms leading to allergy sufferers flooding into allergists’ offices; rising air pollution levels increasing risk for obstructive airway diseases, cardiopulmonary complications, and non–small cell lung cancer; melting snowpacks and atmospheric rivers inundating neighborhoods and leaving moldy debris and incipient fungal infections in their wake.
“The reason why we think climate change is going to change the type of disease patterns and the severity of illness that we see in patients with respiratory diseases is that it changes a lot of the environment as well as the exposures,” said Bathmapriya Balakrishnan, BMedSci, BMBS, from the section of Pulmonary, Critical Care, and Sleep Medicine in the department of medicine at West Virginia University, Morgantown.
“What we’re going to see is not just new diseases but also exacerbation of chronic diseases, things like asthma [and] COPD. And there’s also concern that patients who are otherwise healthy, because they now have more exposures that are due to climate change, can then develop these diseases,” she said in an interview.
Ms. Balakrishnan is the lead author of a comprehensive, evidence-based review focused on the effects of climate change and air pollution across the spectrum of pulmonary disorders. The review is published online ahead of print in the journal Chest.
“ To inform health care providers of evidence-based methods and improve patient counselling, further research regarding measures that limit exposure is needed. Empowering patients with resources to monitor air quality and minimize exposure is a key preventative measure for decreasing morbidity and mortality while improving quality of life,” Ms. Balakrishnan and colleagues write.
Similarly, in a statement on the effects of climate change on respiratory health, the American Public Health Association succinctly summarized the problem: “Warmer temperatures lead to an increase in pollutants and allergens. Poor air quality leads to reduced lung function, increased risk of asthma complications, heart attacks, heart failure, and death. Air pollution and allergens are the main exposures affecting lung and heart health in this changing climate.”
Early spring
Stanley Fineman, MD, MBA, a past president of the American College of Allergy, Asthma, & Immunology and an allergist in private practice in Atlanta, has seen firsthand how global warming and an earlier start to spring allergy season is affecting his patients.
“The season, at least in our area metro Atlanta, started earlier and has been lasting longer. The pollen counts are very high,” he told this news organization.
“In February we started seeing pollen counts over 1,000 [grams per cubic meter], which is unheard of, and in March about half the days we counted levels that were over 1,000, which is also unheard of. In April it was over 1,000 almost half the days.”
Dr. Fineman and colleagues both in Atlanta and across the country have reported sharp increases in the proportion of new adult patients and in existing patients who have experienced exacerbation of previously mild disease.
“Probably what’s happened is that they may have had some allergic sensitivity that resulted in milder manifestations, but this year they’re getting major manifestations,” Dr. Fineman said.
In a 2014 article in the journal European Respiratory Review, Gennaro D’Amato, MD, from High Speciality Hospital Antonio Cardarelli, Naples, Italy, and colleagues outlined the main effects of climate on pollen levels: “1) an increase in plant growth and faster plant growth; 2) an increase in the amount of pollen produced by each plant; 3) an increase in the amount of allergenic proteins contained in pollen; 4) an increase in the start time of plant growth and, therefore, the start of pollen production; 5) an earlier and longer pollen season; 6) change in the geospatial distribution of pollen, that is plant ranges and long-distance atmospheric transport moving polewards,” they write.
Bad air
In addition to pollen, the ambient air in many places is increasingly becoming saturated with bioallergenic proteins such as bacteria, viruses, animal dander, insects, molds, and plant species, Ms. Balakrishnan and colleagues noted, adding that “atmospheric levels of carbon dioxide have also been found to increase pollen productivity. These changes result in greater over-the-counter medication use, emergency department visits, and outpatient visits for respiratory illnesses.”
The rash of violent storms that has washed over much of the United States in recent months is also likely to increase the incidence of so-called “thunderstorm asthma,” caused when large quantities of respirable particulate matter are released before or during a thunderstorm.
Air pollution from the burning of carbon-based fuels and from wildfires sparked by hotter and drier conditions increase airborne particulate matter that can seriously exacerbate asthma, COPD, and other obstructive airway conditions.
In addition, as previously reported by Medscape, exposure to particulate matter has been implicated as a possible cause of non–small cell lung cancer in persons who have never smoked.
Critical care challenges
Among the myriad other effects of climate change postulated in evidence enumerated by Ms. Balakrishnan and colleagues are chest infections and pleural diseases, such as aspergillosis infections that occur after catastrophic flooding; increased incidence of Mycobacterium avium complex infections and hypersensitivity pneumonitis; increased demands on critical care specialists from natural disasters; pollution-induced cardiac arrest; and heat prostration and heat stroke from increasingly prevalent heat waves.
The reviewers also examined evidence suggesting links between climate change and pulmonary hypertension, interstitial lung disease, sleep disorders, and occupational pulmonary disorders.
Power to the patients
“Pulmonologists should counsel patients on ways to minimize outdoor and indoor pollution, using tight-fitting respirators and home air-purifying systems without encroaching on patients’ beliefs and choices,” the authors advise.
“Empowering patients with resources to monitor air quality daily, in inclement weather, and during disasters would help minimize exposure and thus improve overall health. The pulmonologist can play an important role in emphasizing the impact of climate change on pulmonary disorders during patient care encounters,” they write.
Ms. Balakrishan adds that another important mitigation measure that can be taken today is education.
“In medical school we don’t really learn about the impact of climate change – at least in my generation of physicians, climate change or global warming weren’t part of the medical curriculum – but now I think that there’s a lot of advocacy work being done by medical students who actually want more education on climate change and its effects on pulmonary diseases,” she said.
The study by Ms. Balakrishnan and colleagues was unfunded. Ms. Balakrishnan reports no relevant financial relationships. Co-author Mary-Beth Scholand, MD, has received personal fees from serving on advisory boards and speakers bureaus for Genentech, Boehringer Ingelheim, Veracyte, and United Therapeutics. Co-author Sean Callahan, MD, has received personal fees for serving on advisory boards for Gilead and Boehringer Ingelheim. Dr. Fineman reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Improving swallowing may mitigate COPD exacerbations
Dysphagia treatment may be a way to reduce risk for chronic obstructive pulmonary disease (COPD) exacerbations, according to Yoshitaka Oku, MD, of Hyogo Medical University, Nishinomiya, Japan.
Gastroesophageal regurgitation disease (GERD) is known to be associated with exacerbations in COPD, but previous studies have shown little impact of standard GERD therapy on COPD exacerbations. However, additional research indicates that delayed swallowing contributes to COPD exacerbations, as reported in a research review.
In an article published recently in Respiratory Physiology & Neurobiology,
Swallowing disorder (dysphagia) is a common comorbidity in patients with COPD and has been reported at a 17%-20% greater prevalence in those with COPD, compared with controls, the researchers said.
Patients with COPD have altered swallowing behavior because of several factors, including decreased maximal laryngeal elevation, Dr. Oku said. Individuals with COPD “are also prone to laryngeal penetration and aspiration when swallowing large volumes of liquid and tend to follow an inspiratory-swallow-expiratory (I-SW-E) pattern when swallowing large volumes,” he explained.
Dr. Oku conducted prospective studies to investigate the impact of breathing-swallowing discoordination on COPD exacerbation. He found that discoordination in swallowing patterns and the inability to produce airway protective mechanism (such as the I-SW-E pattern) may contribute to more frequent aspirations and more frequent exacerbations.
Dr. Oku also examined whether CPAP and bilevel positive airway pressure (BiPAP) might affect breathing-swallowing coordination in healthy controls and patients with COPD. They found a decrease in breathing-swallowing coordination with CPAP, but not BiPAP, in both controls and stable COPD patients. “During BiPAP, a brief negative flow associated with relaxation of the pharyngeal constrictor muscle triggers inspiratory support, which results in the SW-I pattern,” Dr. Oku noted.
Dr. Oku also wrote that interferential current stimulation (IFC) has been used to stimulate muscles. Studies of transcutaneous electrical sensory stimulation using IFC (IFC-TESS) as an intervention to improve swallowing have shown some success, and also may improve airway protection.
“However, its safety and efficacy in patients with COPD remains unknown,” he wrote. Dr. Oku conducted a study of stable COPD patients and found that repeated salivary swallow test (RSST) scores improved significantly after an IFC-TESS intervention.
Breathing-swallowing discoordination may be an early indicator of swallowing disorder in COPD, and interventions can improve these disorders, Dr. Oku added. However, more research is needed to explore whether interventions to improve dysphagia reduce the frequency of exacerbations in COPD patients, he concluded.
The study was supported by a grant from JSPS KAKENHI. Dr. Oku serves as a senior managing director at EuSense Medical Co.
A version of this article originally appeared on Medscape.com.
Dysphagia treatment may be a way to reduce risk for chronic obstructive pulmonary disease (COPD) exacerbations, according to Yoshitaka Oku, MD, of Hyogo Medical University, Nishinomiya, Japan.
Gastroesophageal regurgitation disease (GERD) is known to be associated with exacerbations in COPD, but previous studies have shown little impact of standard GERD therapy on COPD exacerbations. However, additional research indicates that delayed swallowing contributes to COPD exacerbations, as reported in a research review.
In an article published recently in Respiratory Physiology & Neurobiology,
Swallowing disorder (dysphagia) is a common comorbidity in patients with COPD and has been reported at a 17%-20% greater prevalence in those with COPD, compared with controls, the researchers said.
Patients with COPD have altered swallowing behavior because of several factors, including decreased maximal laryngeal elevation, Dr. Oku said. Individuals with COPD “are also prone to laryngeal penetration and aspiration when swallowing large volumes of liquid and tend to follow an inspiratory-swallow-expiratory (I-SW-E) pattern when swallowing large volumes,” he explained.
Dr. Oku conducted prospective studies to investigate the impact of breathing-swallowing discoordination on COPD exacerbation. He found that discoordination in swallowing patterns and the inability to produce airway protective mechanism (such as the I-SW-E pattern) may contribute to more frequent aspirations and more frequent exacerbations.
Dr. Oku also examined whether CPAP and bilevel positive airway pressure (BiPAP) might affect breathing-swallowing coordination in healthy controls and patients with COPD. They found a decrease in breathing-swallowing coordination with CPAP, but not BiPAP, in both controls and stable COPD patients. “During BiPAP, a brief negative flow associated with relaxation of the pharyngeal constrictor muscle triggers inspiratory support, which results in the SW-I pattern,” Dr. Oku noted.
Dr. Oku also wrote that interferential current stimulation (IFC) has been used to stimulate muscles. Studies of transcutaneous electrical sensory stimulation using IFC (IFC-TESS) as an intervention to improve swallowing have shown some success, and also may improve airway protection.
“However, its safety and efficacy in patients with COPD remains unknown,” he wrote. Dr. Oku conducted a study of stable COPD patients and found that repeated salivary swallow test (RSST) scores improved significantly after an IFC-TESS intervention.
Breathing-swallowing discoordination may be an early indicator of swallowing disorder in COPD, and interventions can improve these disorders, Dr. Oku added. However, more research is needed to explore whether interventions to improve dysphagia reduce the frequency of exacerbations in COPD patients, he concluded.
The study was supported by a grant from JSPS KAKENHI. Dr. Oku serves as a senior managing director at EuSense Medical Co.
A version of this article originally appeared on Medscape.com.
Dysphagia treatment may be a way to reduce risk for chronic obstructive pulmonary disease (COPD) exacerbations, according to Yoshitaka Oku, MD, of Hyogo Medical University, Nishinomiya, Japan.
Gastroesophageal regurgitation disease (GERD) is known to be associated with exacerbations in COPD, but previous studies have shown little impact of standard GERD therapy on COPD exacerbations. However, additional research indicates that delayed swallowing contributes to COPD exacerbations, as reported in a research review.
In an article published recently in Respiratory Physiology & Neurobiology,
Swallowing disorder (dysphagia) is a common comorbidity in patients with COPD and has been reported at a 17%-20% greater prevalence in those with COPD, compared with controls, the researchers said.
Patients with COPD have altered swallowing behavior because of several factors, including decreased maximal laryngeal elevation, Dr. Oku said. Individuals with COPD “are also prone to laryngeal penetration and aspiration when swallowing large volumes of liquid and tend to follow an inspiratory-swallow-expiratory (I-SW-E) pattern when swallowing large volumes,” he explained.
Dr. Oku conducted prospective studies to investigate the impact of breathing-swallowing discoordination on COPD exacerbation. He found that discoordination in swallowing patterns and the inability to produce airway protective mechanism (such as the I-SW-E pattern) may contribute to more frequent aspirations and more frequent exacerbations.
Dr. Oku also examined whether CPAP and bilevel positive airway pressure (BiPAP) might affect breathing-swallowing coordination in healthy controls and patients with COPD. They found a decrease in breathing-swallowing coordination with CPAP, but not BiPAP, in both controls and stable COPD patients. “During BiPAP, a brief negative flow associated with relaxation of the pharyngeal constrictor muscle triggers inspiratory support, which results in the SW-I pattern,” Dr. Oku noted.
Dr. Oku also wrote that interferential current stimulation (IFC) has been used to stimulate muscles. Studies of transcutaneous electrical sensory stimulation using IFC (IFC-TESS) as an intervention to improve swallowing have shown some success, and also may improve airway protection.
“However, its safety and efficacy in patients with COPD remains unknown,” he wrote. Dr. Oku conducted a study of stable COPD patients and found that repeated salivary swallow test (RSST) scores improved significantly after an IFC-TESS intervention.
Breathing-swallowing discoordination may be an early indicator of swallowing disorder in COPD, and interventions can improve these disorders, Dr. Oku added. However, more research is needed to explore whether interventions to improve dysphagia reduce the frequency of exacerbations in COPD patients, he concluded.
The study was supported by a grant from JSPS KAKENHI. Dr. Oku serves as a senior managing director at EuSense Medical Co.
A version of this article originally appeared on Medscape.com.
Asthma tied to increased risk for multiple cancers
People with asthma have an elevated risk for a variety of cancers other than lung cancer, including melanoma as well as blood, kidney, and ovarian cancers, new research suggests.
But, the authors found, treatment with an inhaled steroid may lower that risk, perhaps by keeping inflammation in check.
“Using real-world data, our study is the first to provide evidence of a positive association between asthma and cancer risk in United States patients,” Yi Guo, PhD, with the University of Florida, Gainesville, said in a news release.
The study was published online in Cancer Medicine.
The relationship between chronic inflammation and cancer remains a key area of exploration in cancer etiology. Data show that the risk for developing cancer is higher in patients with chronic inflammatory diseases, and patients with asthma have complex and chronic inflammation. However, prior studies exploring a possible link between asthma and cancer have yielded mixed results.
To investigate further, Dr. Guo and colleagues analyzed electronic health records and claims data in the OneFlorida+ clinical research network for roughly 90,000 adults with asthma and a matched cohort of about 270,000 adults without asthma.
Multivariable analysis revealed that adults with asthma were more likely to develop cancer, compared with peers without asthma (hazard ratio, 1.36), the investigators found.
Adults with asthma had an elevated cancer risk for five of the 13 cancers assessed, including melanoma (HR, 1.98), ovarian cancer (HR, 1.88), lung cancer (HR, 1.56), kidney cancer (HR, 1.48), and blood cancer (HR, 1.26).
Compared with adults without asthma, those with asthma who did not treat it with an inhaled steroid had a more pronounced overall cancer risk, compared with those who were on an inhaled steroid (HR, 1.60 vs. 1.11).
For specific cancer types, the risk was elevated for nine of 13 cancers in patients with asthma not taking an inhaled steroid: prostate (HR, 1.50), lung (HR, 1.74), colorectal (HR, 1.51), blood (HR, 1.44), melanoma (HR, 2.05), corpus uteri (HR, 1.76), kidney (HR, 1.52), ovarian (HR, 2.31), and cervical (HR, 1.46).
In contrast, in patients with asthma who did use an inhaled steroid, an elevated cancer risk was observed for only two cancers, lung cancer (HR, 1.39) and melanoma (HR, 1.92), suggesting a potential protective effect of inhaled steroid use on cancer, the researchers said.
Although prior studies have shown a protective effect of inhaled steroid use on some cancers, potentially by reducing inflammation, the “speculative nature of chronic inflammation (asthma as a common example) as a driver for pan-cancer development requires more investigation,” Dr. Guo and colleagues cautioned.
And because of the observational nature of the current study, Dr. Guo’s team stressed that these findings do not prove a causal relationship between asthma and cancer.
“More in-depth studies using real-word data are needed to further explore the causal mechanisms of asthma on cancer risk,” the researchers concluded.
Funding for the study was provided in part by grants to the researchers from the National Institutes of Health, National Cancer Institute, National Institute on Aging, and the Centers for Disease Control and Prevention. This project was supported by the Cancer Informatics Shared Resource in the University of Florida Health Cancer Center. The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
People with asthma have an elevated risk for a variety of cancers other than lung cancer, including melanoma as well as blood, kidney, and ovarian cancers, new research suggests.
But, the authors found, treatment with an inhaled steroid may lower that risk, perhaps by keeping inflammation in check.
“Using real-world data, our study is the first to provide evidence of a positive association between asthma and cancer risk in United States patients,” Yi Guo, PhD, with the University of Florida, Gainesville, said in a news release.
The study was published online in Cancer Medicine.
The relationship between chronic inflammation and cancer remains a key area of exploration in cancer etiology. Data show that the risk for developing cancer is higher in patients with chronic inflammatory diseases, and patients with asthma have complex and chronic inflammation. However, prior studies exploring a possible link between asthma and cancer have yielded mixed results.
To investigate further, Dr. Guo and colleagues analyzed electronic health records and claims data in the OneFlorida+ clinical research network for roughly 90,000 adults with asthma and a matched cohort of about 270,000 adults without asthma.
Multivariable analysis revealed that adults with asthma were more likely to develop cancer, compared with peers without asthma (hazard ratio, 1.36), the investigators found.
Adults with asthma had an elevated cancer risk for five of the 13 cancers assessed, including melanoma (HR, 1.98), ovarian cancer (HR, 1.88), lung cancer (HR, 1.56), kidney cancer (HR, 1.48), and blood cancer (HR, 1.26).
Compared with adults without asthma, those with asthma who did not treat it with an inhaled steroid had a more pronounced overall cancer risk, compared with those who were on an inhaled steroid (HR, 1.60 vs. 1.11).
For specific cancer types, the risk was elevated for nine of 13 cancers in patients with asthma not taking an inhaled steroid: prostate (HR, 1.50), lung (HR, 1.74), colorectal (HR, 1.51), blood (HR, 1.44), melanoma (HR, 2.05), corpus uteri (HR, 1.76), kidney (HR, 1.52), ovarian (HR, 2.31), and cervical (HR, 1.46).
In contrast, in patients with asthma who did use an inhaled steroid, an elevated cancer risk was observed for only two cancers, lung cancer (HR, 1.39) and melanoma (HR, 1.92), suggesting a potential protective effect of inhaled steroid use on cancer, the researchers said.
Although prior studies have shown a protective effect of inhaled steroid use on some cancers, potentially by reducing inflammation, the “speculative nature of chronic inflammation (asthma as a common example) as a driver for pan-cancer development requires more investigation,” Dr. Guo and colleagues cautioned.
And because of the observational nature of the current study, Dr. Guo’s team stressed that these findings do not prove a causal relationship between asthma and cancer.
“More in-depth studies using real-word data are needed to further explore the causal mechanisms of asthma on cancer risk,” the researchers concluded.
Funding for the study was provided in part by grants to the researchers from the National Institutes of Health, National Cancer Institute, National Institute on Aging, and the Centers for Disease Control and Prevention. This project was supported by the Cancer Informatics Shared Resource in the University of Florida Health Cancer Center. The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
People with asthma have an elevated risk for a variety of cancers other than lung cancer, including melanoma as well as blood, kidney, and ovarian cancers, new research suggests.
But, the authors found, treatment with an inhaled steroid may lower that risk, perhaps by keeping inflammation in check.
“Using real-world data, our study is the first to provide evidence of a positive association between asthma and cancer risk in United States patients,” Yi Guo, PhD, with the University of Florida, Gainesville, said in a news release.
The study was published online in Cancer Medicine.
The relationship between chronic inflammation and cancer remains a key area of exploration in cancer etiology. Data show that the risk for developing cancer is higher in patients with chronic inflammatory diseases, and patients with asthma have complex and chronic inflammation. However, prior studies exploring a possible link between asthma and cancer have yielded mixed results.
To investigate further, Dr. Guo and colleagues analyzed electronic health records and claims data in the OneFlorida+ clinical research network for roughly 90,000 adults with asthma and a matched cohort of about 270,000 adults without asthma.
Multivariable analysis revealed that adults with asthma were more likely to develop cancer, compared with peers without asthma (hazard ratio, 1.36), the investigators found.
Adults with asthma had an elevated cancer risk for five of the 13 cancers assessed, including melanoma (HR, 1.98), ovarian cancer (HR, 1.88), lung cancer (HR, 1.56), kidney cancer (HR, 1.48), and blood cancer (HR, 1.26).
Compared with adults without asthma, those with asthma who did not treat it with an inhaled steroid had a more pronounced overall cancer risk, compared with those who were on an inhaled steroid (HR, 1.60 vs. 1.11).
For specific cancer types, the risk was elevated for nine of 13 cancers in patients with asthma not taking an inhaled steroid: prostate (HR, 1.50), lung (HR, 1.74), colorectal (HR, 1.51), blood (HR, 1.44), melanoma (HR, 2.05), corpus uteri (HR, 1.76), kidney (HR, 1.52), ovarian (HR, 2.31), and cervical (HR, 1.46).
In contrast, in patients with asthma who did use an inhaled steroid, an elevated cancer risk was observed for only two cancers, lung cancer (HR, 1.39) and melanoma (HR, 1.92), suggesting a potential protective effect of inhaled steroid use on cancer, the researchers said.
Although prior studies have shown a protective effect of inhaled steroid use on some cancers, potentially by reducing inflammation, the “speculative nature of chronic inflammation (asthma as a common example) as a driver for pan-cancer development requires more investigation,” Dr. Guo and colleagues cautioned.
And because of the observational nature of the current study, Dr. Guo’s team stressed that these findings do not prove a causal relationship between asthma and cancer.
“More in-depth studies using real-word data are needed to further explore the causal mechanisms of asthma on cancer risk,” the researchers concluded.
Funding for the study was provided in part by grants to the researchers from the National Institutes of Health, National Cancer Institute, National Institute on Aging, and the Centers for Disease Control and Prevention. This project was supported by the Cancer Informatics Shared Resource in the University of Florida Health Cancer Center. The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Using ABIM’s Longitudinal Knowledge Assessment (LKA®) for your advantage
The American Board of Internal Medicine’s (ABIM) Longitudinal Knowledge Assessment (LKA®) has entered its second year of availability, and was launched in January 2023 for the disciplines of pulmonary disease and critical care medicine, as well as infectious disease. If you are due for an ABIM assessment in 2023 in pulmonary disease or critical care medicine, the deadline to enroll in LKA is June 30, 2023.
Many diplomates—including myself—are taking advantage of the flexibility offered by the LKA to maintain certification in one or more specialties. Others are using it to regain certifications that they allowed to lapse. Both scenarios offer a lower-stakes and less time-intensive route to maintaining or recertifying that also promotes relevant and timely learning in a given discipline. Remember that you can still choose to take the traditional 10-year Maintenance of Certification (MOC) exam in any discipline if you feel that works better for you than the LKA.
Detailed information about the LKA and how it works, as well as a walkthrough video and FAQs, are available on ABIM’s website. Following are some suggestions based on the experience of physicians who are currently enrolled in the LKA.
Take it one day at a time
With 30 questions released each quarter, the LKA is designed to be manageable and work with your schedule. You could take one question a day or every few days over the course of the quarter or you can choose to do all 30 in one sitting—whatever works for you. Each correct answer also earns you 0.2 MOC points, meaning that over time, you could potentially achieve all of your required MOC points through the LKA alone.
Don’t forget your time bank
Every question has a 4-minute time limit, but if you need more time to think through a question or look up a resource, you can draw from a 30-minute extra time bank that renews each year. On average, physicians answer most questions in less than 2 minutes.
Use resources
The LKA is essentially “open book,” meaning you can use any resource to help with a question except for another physician. Some physicians cite online sites or hard copy medical references as reliable resources, and CHEST offers additional resources that can be helpful, as well.
Set up your work area for success
Many physicians report using two screens or two devices while taking the LKA—one with the LKA platform open to answer questions and one for looking up resources. Questions involving viewing of media will prompt you when a larger screen may be helpful.
Consider the cost savings
The LKA is included in your annual MOC fee for each certificate you maintain at no additional cost. If you use the LKA to meet your MOC assessment requirement, you don’t need to take the traditional 10-year MOC exam or pay an additional exam fee.
Gauge areas of strength and weakness
Most questions on the LKA will give you rationale and feedback after you’ve answered, allowing you to brush up on knowledge gaps. In addition, you’ll receive interim quarterly score reports starting after your fifth quarter of participation showing your current score relative to the passing standard, including areas where you might need to focus more study.
Regain lapsed certification
The LKA is a simple and lower-stakes way to regain certification in a specialty that has lapsed, though it should be noted that you must complete your 5-year LKA cycle and achieve a passing score for the certificate to become active again. In the meantime, you can use the LKA to refresh your knowledge of current information in that specialty.
Ask about disability accommodations
ABIM offers some accommodations for the LKA in compliance with Title III of the Americans with Disabilities Act (ADA) for individuals with documented disabilities who demonstrate a need for accommodation. Physicians requesting special testing accommodations under the ADA can submit a request on ABIM’s website.
If you’re due for an assessment in 2023, and you haven’t looked into the LKA yet, now is the time: the second quarter closes on June 30, 2023, and you will not be able to enroll after that date. Sign in to your ABIM Physician Portal to see if you are eligible and visit ABIM.org/LKA to learn more.
The American Board of Internal Medicine’s (ABIM) Longitudinal Knowledge Assessment (LKA®) has entered its second year of availability, and was launched in January 2023 for the disciplines of pulmonary disease and critical care medicine, as well as infectious disease. If you are due for an ABIM assessment in 2023 in pulmonary disease or critical care medicine, the deadline to enroll in LKA is June 30, 2023.
Many diplomates—including myself—are taking advantage of the flexibility offered by the LKA to maintain certification in one or more specialties. Others are using it to regain certifications that they allowed to lapse. Both scenarios offer a lower-stakes and less time-intensive route to maintaining or recertifying that also promotes relevant and timely learning in a given discipline. Remember that you can still choose to take the traditional 10-year Maintenance of Certification (MOC) exam in any discipline if you feel that works better for you than the LKA.
Detailed information about the LKA and how it works, as well as a walkthrough video and FAQs, are available on ABIM’s website. Following are some suggestions based on the experience of physicians who are currently enrolled in the LKA.
Take it one day at a time
With 30 questions released each quarter, the LKA is designed to be manageable and work with your schedule. You could take one question a day or every few days over the course of the quarter or you can choose to do all 30 in one sitting—whatever works for you. Each correct answer also earns you 0.2 MOC points, meaning that over time, you could potentially achieve all of your required MOC points through the LKA alone.
Don’t forget your time bank
Every question has a 4-minute time limit, but if you need more time to think through a question or look up a resource, you can draw from a 30-minute extra time bank that renews each year. On average, physicians answer most questions in less than 2 minutes.
Use resources
The LKA is essentially “open book,” meaning you can use any resource to help with a question except for another physician. Some physicians cite online sites or hard copy medical references as reliable resources, and CHEST offers additional resources that can be helpful, as well.
Set up your work area for success
Many physicians report using two screens or two devices while taking the LKA—one with the LKA platform open to answer questions and one for looking up resources. Questions involving viewing of media will prompt you when a larger screen may be helpful.
Consider the cost savings
The LKA is included in your annual MOC fee for each certificate you maintain at no additional cost. If you use the LKA to meet your MOC assessment requirement, you don’t need to take the traditional 10-year MOC exam or pay an additional exam fee.
Gauge areas of strength and weakness
Most questions on the LKA will give you rationale and feedback after you’ve answered, allowing you to brush up on knowledge gaps. In addition, you’ll receive interim quarterly score reports starting after your fifth quarter of participation showing your current score relative to the passing standard, including areas where you might need to focus more study.
Regain lapsed certification
The LKA is a simple and lower-stakes way to regain certification in a specialty that has lapsed, though it should be noted that you must complete your 5-year LKA cycle and achieve a passing score for the certificate to become active again. In the meantime, you can use the LKA to refresh your knowledge of current information in that specialty.
Ask about disability accommodations
ABIM offers some accommodations for the LKA in compliance with Title III of the Americans with Disabilities Act (ADA) for individuals with documented disabilities who demonstrate a need for accommodation. Physicians requesting special testing accommodations under the ADA can submit a request on ABIM’s website.
If you’re due for an assessment in 2023, and you haven’t looked into the LKA yet, now is the time: the second quarter closes on June 30, 2023, and you will not be able to enroll after that date. Sign in to your ABIM Physician Portal to see if you are eligible and visit ABIM.org/LKA to learn more.
The American Board of Internal Medicine’s (ABIM) Longitudinal Knowledge Assessment (LKA®) has entered its second year of availability, and was launched in January 2023 for the disciplines of pulmonary disease and critical care medicine, as well as infectious disease. If you are due for an ABIM assessment in 2023 in pulmonary disease or critical care medicine, the deadline to enroll in LKA is June 30, 2023.
Many diplomates—including myself—are taking advantage of the flexibility offered by the LKA to maintain certification in one or more specialties. Others are using it to regain certifications that they allowed to lapse. Both scenarios offer a lower-stakes and less time-intensive route to maintaining or recertifying that also promotes relevant and timely learning in a given discipline. Remember that you can still choose to take the traditional 10-year Maintenance of Certification (MOC) exam in any discipline if you feel that works better for you than the LKA.
Detailed information about the LKA and how it works, as well as a walkthrough video and FAQs, are available on ABIM’s website. Following are some suggestions based on the experience of physicians who are currently enrolled in the LKA.
Take it one day at a time
With 30 questions released each quarter, the LKA is designed to be manageable and work with your schedule. You could take one question a day or every few days over the course of the quarter or you can choose to do all 30 in one sitting—whatever works for you. Each correct answer also earns you 0.2 MOC points, meaning that over time, you could potentially achieve all of your required MOC points through the LKA alone.
Don’t forget your time bank
Every question has a 4-minute time limit, but if you need more time to think through a question or look up a resource, you can draw from a 30-minute extra time bank that renews each year. On average, physicians answer most questions in less than 2 minutes.
Use resources
The LKA is essentially “open book,” meaning you can use any resource to help with a question except for another physician. Some physicians cite online sites or hard copy medical references as reliable resources, and CHEST offers additional resources that can be helpful, as well.
Set up your work area for success
Many physicians report using two screens or two devices while taking the LKA—one with the LKA platform open to answer questions and one for looking up resources. Questions involving viewing of media will prompt you when a larger screen may be helpful.
Consider the cost savings
The LKA is included in your annual MOC fee for each certificate you maintain at no additional cost. If you use the LKA to meet your MOC assessment requirement, you don’t need to take the traditional 10-year MOC exam or pay an additional exam fee.
Gauge areas of strength and weakness
Most questions on the LKA will give you rationale and feedback after you’ve answered, allowing you to brush up on knowledge gaps. In addition, you’ll receive interim quarterly score reports starting after your fifth quarter of participation showing your current score relative to the passing standard, including areas where you might need to focus more study.
Regain lapsed certification
The LKA is a simple and lower-stakes way to regain certification in a specialty that has lapsed, though it should be noted that you must complete your 5-year LKA cycle and achieve a passing score for the certificate to become active again. In the meantime, you can use the LKA to refresh your knowledge of current information in that specialty.
Ask about disability accommodations
ABIM offers some accommodations for the LKA in compliance with Title III of the Americans with Disabilities Act (ADA) for individuals with documented disabilities who demonstrate a need for accommodation. Physicians requesting special testing accommodations under the ADA can submit a request on ABIM’s website.
If you’re due for an assessment in 2023, and you haven’t looked into the LKA yet, now is the time: the second quarter closes on June 30, 2023, and you will not be able to enroll after that date. Sign in to your ABIM Physician Portal to see if you are eligible and visit ABIM.org/LKA to learn more.
Relearning old lessons from a new disease: Prolonged noninvasive respiratory support for hypoxemic respiratory failure can harm patients
The threshold for abandoning supportive measures and initiating invasive mechanical ventilation (IMV) in patients with respiratory failure is unclear. Noninvasive respiratory support (RS) devices, such as high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV), are tools used to support patients in distress prior to failure and the need for IMV. However, prolonged RS in patients who ultimately require IMV can be harmful.
As the COVID-19 pandemic evolved, ICUs around the world were overrun by patients with varying degrees of respiratory failure. With this novel pathogen came novel approaches to management. Here we will review data available prior to the pandemic and relate them to emerging evidence on prolonged RS in patients with COVID-19. We believe it is time to acknowledge that prolonged RS in patients who ultimately require IMV is likely deleterious. Increased awareness and care to avoid this situation (often meaning earlier intubation) should be implemented in clinical practice.
Excessive tidal volume delivered during IMV can lead to lung injury. Though this principle is widely accepted, the recognition that the same physiology holds in a spontaneously breathing patient receiving RS has been slow to take hold. In the presence of a high respiratory drive injury from overdistension and large transpulmonary pressure, swings can occur with or without IMV. An excellent review summarizing the existing evidence of this risk was published years before the COVID-19 pandemic (Brochard L, et al. AJRCCM. 2017;195[4]:438).
A number of pre-COVID-19 publications focused on examining this topic in clinical practice deserve specific mention. A study of respiratory mechanics in patients on NIV found it was nearly impossible to meet traditional targets for lung protective tidal volumes. Those patients who progressed to IMV had higher expired tidal volumes (Carteaux G, et al. Crit Care Med. 2016;44[2]:282). A large systematic review and metanalysis including more than 11,000 immunocompromised patients found delayed intubation led to increased mortality (Dumas G, et al. AJRCCM. 2021;204[2]:187). This study did not specifically implicate RS days and patient self-induced lung injury as factors driving the excess mortality; another smaller propensity-matched retrospective analysis of patients in the ICU supported with HFNC noted a 65% reduction in mortality among patients intubated after less than vs greater than 48 hours on HFNC who ultimately required IMV (Kang B, et al. Intensive Care Med. 2015;41[4]:623).
Despite this and other existing evidence regarding the hazards of prolonged RS prior to IMV, COVID-19’s burden on the health care system dramatically changed the way hypoxemic respiratory failure is managed in the ICU. Anecdotally, during the height of the pandemic, it was commonplace to encounter patients with severe COVID-19 supported with very high RS settings for days or often weeks. Occasionally, RS may have stabilized breathing mechanics. However, it was often our experience that among those patients supported with RS for extended periods prior to IMV lung compliance was poor, lung recovery did not occur, and prognosis was dismal. Various factors, including early reports of high mortality among patients with COVID-19 supported with IMV, resulted in reliance on RS as a means for delaying or avoiding IMV. Interestingly, a propensity-matched study of more than 2,700 patients found that prolonged RS was associated with significantly higher in-hospital mortality but despite this finding, the practice increased over the course of the pandemic (Riera J, et al. Eur Respir J. 2023;61[3]:2201426). Further, a prospective study comparing outcomes between patients intubated within 48 hours for COVID-19-related respiratory failure to those intubated later found a greater risk of in-hospital mortality and worse long-term outpatient lung function testing (in survivors) in the latter group.
It has previously been postulated that longer duration of IMV prior to the initiation of extracorporeal membrane oxygenation (ECMO) support in patients with hypoxemic respiratory failure may contribute to worse overall ECMO-related outcomes. This supposition is based on the principle that ECMO protects the lung by reducing ventilatory drive, tidal volume, and transpulmonary pressure swings. Several studies have documented an increase in mortality in patients supported with ECMO for COVID-19-related respiratory failure over the course of the pandemic. These investigators have noted that time to cannulation, but not IMV days (possibly reflecting duration of RS), correlates with worse ECMO outcomes (Ahmad Q, et al. ASAIO J. 2022;68[2]:171; Barbaro R, et al. Lancet. 2021;398[10307]:1230). We wonder if this reflects greater attention to low tidal volume ventilation during IMV but lack of awareness of or the inability to prevent injurious ventilation during prolonged RS. We view this as an important area for future research that may aid in patient selection in the ongoing effort to improve COVID-19-related ECMO outcomes.
The COVID-19 pandemic remains a significant burden on the health care system. Changes in care necessitated by the crisis produced innovations with the potential to rapidly improve outcomes. Notably though, it also has resulted in negative changes in response to a new pathogen that are hard to reconcile with physiologic principles. Evidence before and since the emergence of COVID-19 suggests prolonged RS prior to IMV is potentially harmful. It is critical for clinicians to recognize this principle and take steps to mitigate this problem in patients where a positive response to RS is not demonstrated in a timely manner.
Drs. Wilson and Chandel are with the Department of Pulmonary and Critical Care, Walter Reed National Military Medical Center, Washington, DC.
The threshold for abandoning supportive measures and initiating invasive mechanical ventilation (IMV) in patients with respiratory failure is unclear. Noninvasive respiratory support (RS) devices, such as high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV), are tools used to support patients in distress prior to failure and the need for IMV. However, prolonged RS in patients who ultimately require IMV can be harmful.
As the COVID-19 pandemic evolved, ICUs around the world were overrun by patients with varying degrees of respiratory failure. With this novel pathogen came novel approaches to management. Here we will review data available prior to the pandemic and relate them to emerging evidence on prolonged RS in patients with COVID-19. We believe it is time to acknowledge that prolonged RS in patients who ultimately require IMV is likely deleterious. Increased awareness and care to avoid this situation (often meaning earlier intubation) should be implemented in clinical practice.
Excessive tidal volume delivered during IMV can lead to lung injury. Though this principle is widely accepted, the recognition that the same physiology holds in a spontaneously breathing patient receiving RS has been slow to take hold. In the presence of a high respiratory drive injury from overdistension and large transpulmonary pressure, swings can occur with or without IMV. An excellent review summarizing the existing evidence of this risk was published years before the COVID-19 pandemic (Brochard L, et al. AJRCCM. 2017;195[4]:438).
A number of pre-COVID-19 publications focused on examining this topic in clinical practice deserve specific mention. A study of respiratory mechanics in patients on NIV found it was nearly impossible to meet traditional targets for lung protective tidal volumes. Those patients who progressed to IMV had higher expired tidal volumes (Carteaux G, et al. Crit Care Med. 2016;44[2]:282). A large systematic review and metanalysis including more than 11,000 immunocompromised patients found delayed intubation led to increased mortality (Dumas G, et al. AJRCCM. 2021;204[2]:187). This study did not specifically implicate RS days and patient self-induced lung injury as factors driving the excess mortality; another smaller propensity-matched retrospective analysis of patients in the ICU supported with HFNC noted a 65% reduction in mortality among patients intubated after less than vs greater than 48 hours on HFNC who ultimately required IMV (Kang B, et al. Intensive Care Med. 2015;41[4]:623).
Despite this and other existing evidence regarding the hazards of prolonged RS prior to IMV, COVID-19’s burden on the health care system dramatically changed the way hypoxemic respiratory failure is managed in the ICU. Anecdotally, during the height of the pandemic, it was commonplace to encounter patients with severe COVID-19 supported with very high RS settings for days or often weeks. Occasionally, RS may have stabilized breathing mechanics. However, it was often our experience that among those patients supported with RS for extended periods prior to IMV lung compliance was poor, lung recovery did not occur, and prognosis was dismal. Various factors, including early reports of high mortality among patients with COVID-19 supported with IMV, resulted in reliance on RS as a means for delaying or avoiding IMV. Interestingly, a propensity-matched study of more than 2,700 patients found that prolonged RS was associated with significantly higher in-hospital mortality but despite this finding, the practice increased over the course of the pandemic (Riera J, et al. Eur Respir J. 2023;61[3]:2201426). Further, a prospective study comparing outcomes between patients intubated within 48 hours for COVID-19-related respiratory failure to those intubated later found a greater risk of in-hospital mortality and worse long-term outpatient lung function testing (in survivors) in the latter group.
It has previously been postulated that longer duration of IMV prior to the initiation of extracorporeal membrane oxygenation (ECMO) support in patients with hypoxemic respiratory failure may contribute to worse overall ECMO-related outcomes. This supposition is based on the principle that ECMO protects the lung by reducing ventilatory drive, tidal volume, and transpulmonary pressure swings. Several studies have documented an increase in mortality in patients supported with ECMO for COVID-19-related respiratory failure over the course of the pandemic. These investigators have noted that time to cannulation, but not IMV days (possibly reflecting duration of RS), correlates with worse ECMO outcomes (Ahmad Q, et al. ASAIO J. 2022;68[2]:171; Barbaro R, et al. Lancet. 2021;398[10307]:1230). We wonder if this reflects greater attention to low tidal volume ventilation during IMV but lack of awareness of or the inability to prevent injurious ventilation during prolonged RS. We view this as an important area for future research that may aid in patient selection in the ongoing effort to improve COVID-19-related ECMO outcomes.
The COVID-19 pandemic remains a significant burden on the health care system. Changes in care necessitated by the crisis produced innovations with the potential to rapidly improve outcomes. Notably though, it also has resulted in negative changes in response to a new pathogen that are hard to reconcile with physiologic principles. Evidence before and since the emergence of COVID-19 suggests prolonged RS prior to IMV is potentially harmful. It is critical for clinicians to recognize this principle and take steps to mitigate this problem in patients where a positive response to RS is not demonstrated in a timely manner.
Drs. Wilson and Chandel are with the Department of Pulmonary and Critical Care, Walter Reed National Military Medical Center, Washington, DC.
The threshold for abandoning supportive measures and initiating invasive mechanical ventilation (IMV) in patients with respiratory failure is unclear. Noninvasive respiratory support (RS) devices, such as high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV), are tools used to support patients in distress prior to failure and the need for IMV. However, prolonged RS in patients who ultimately require IMV can be harmful.
As the COVID-19 pandemic evolved, ICUs around the world were overrun by patients with varying degrees of respiratory failure. With this novel pathogen came novel approaches to management. Here we will review data available prior to the pandemic and relate them to emerging evidence on prolonged RS in patients with COVID-19. We believe it is time to acknowledge that prolonged RS in patients who ultimately require IMV is likely deleterious. Increased awareness and care to avoid this situation (often meaning earlier intubation) should be implemented in clinical practice.
Excessive tidal volume delivered during IMV can lead to lung injury. Though this principle is widely accepted, the recognition that the same physiology holds in a spontaneously breathing patient receiving RS has been slow to take hold. In the presence of a high respiratory drive injury from overdistension and large transpulmonary pressure, swings can occur with or without IMV. An excellent review summarizing the existing evidence of this risk was published years before the COVID-19 pandemic (Brochard L, et al. AJRCCM. 2017;195[4]:438).
A number of pre-COVID-19 publications focused on examining this topic in clinical practice deserve specific mention. A study of respiratory mechanics in patients on NIV found it was nearly impossible to meet traditional targets for lung protective tidal volumes. Those patients who progressed to IMV had higher expired tidal volumes (Carteaux G, et al. Crit Care Med. 2016;44[2]:282). A large systematic review and metanalysis including more than 11,000 immunocompromised patients found delayed intubation led to increased mortality (Dumas G, et al. AJRCCM. 2021;204[2]:187). This study did not specifically implicate RS days and patient self-induced lung injury as factors driving the excess mortality; another smaller propensity-matched retrospective analysis of patients in the ICU supported with HFNC noted a 65% reduction in mortality among patients intubated after less than vs greater than 48 hours on HFNC who ultimately required IMV (Kang B, et al. Intensive Care Med. 2015;41[4]:623).
Despite this and other existing evidence regarding the hazards of prolonged RS prior to IMV, COVID-19’s burden on the health care system dramatically changed the way hypoxemic respiratory failure is managed in the ICU. Anecdotally, during the height of the pandemic, it was commonplace to encounter patients with severe COVID-19 supported with very high RS settings for days or often weeks. Occasionally, RS may have stabilized breathing mechanics. However, it was often our experience that among those patients supported with RS for extended periods prior to IMV lung compliance was poor, lung recovery did not occur, and prognosis was dismal. Various factors, including early reports of high mortality among patients with COVID-19 supported with IMV, resulted in reliance on RS as a means for delaying or avoiding IMV. Interestingly, a propensity-matched study of more than 2,700 patients found that prolonged RS was associated with significantly higher in-hospital mortality but despite this finding, the practice increased over the course of the pandemic (Riera J, et al. Eur Respir J. 2023;61[3]:2201426). Further, a prospective study comparing outcomes between patients intubated within 48 hours for COVID-19-related respiratory failure to those intubated later found a greater risk of in-hospital mortality and worse long-term outpatient lung function testing (in survivors) in the latter group.
It has previously been postulated that longer duration of IMV prior to the initiation of extracorporeal membrane oxygenation (ECMO) support in patients with hypoxemic respiratory failure may contribute to worse overall ECMO-related outcomes. This supposition is based on the principle that ECMO protects the lung by reducing ventilatory drive, tidal volume, and transpulmonary pressure swings. Several studies have documented an increase in mortality in patients supported with ECMO for COVID-19-related respiratory failure over the course of the pandemic. These investigators have noted that time to cannulation, but not IMV days (possibly reflecting duration of RS), correlates with worse ECMO outcomes (Ahmad Q, et al. ASAIO J. 2022;68[2]:171; Barbaro R, et al. Lancet. 2021;398[10307]:1230). We wonder if this reflects greater attention to low tidal volume ventilation during IMV but lack of awareness of or the inability to prevent injurious ventilation during prolonged RS. We view this as an important area for future research that may aid in patient selection in the ongoing effort to improve COVID-19-related ECMO outcomes.
The COVID-19 pandemic remains a significant burden on the health care system. Changes in care necessitated by the crisis produced innovations with the potential to rapidly improve outcomes. Notably though, it also has resulted in negative changes in response to a new pathogen that are hard to reconcile with physiologic principles. Evidence before and since the emergence of COVID-19 suggests prolonged RS prior to IMV is potentially harmful. It is critical for clinicians to recognize this principle and take steps to mitigate this problem in patients where a positive response to RS is not demonstrated in a timely manner.
Drs. Wilson and Chandel are with the Department of Pulmonary and Critical Care, Walter Reed National Military Medical Center, Washington, DC.
Plasma monitoring supports earlier osimertinib treatment in lung cancer patients
Previous studies have suggested that molecular progression of disease in patients with EGFR-mutant NSCLC, as measured by sequential plasma EGFR T790M, may precede radiological progression, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).
However, the impact of these measures on timing of treatment changes and patient outcomes has not been examined, wrote Jordi Remon, MD, of Paris (France)–Saclay University and colleagues, in Annals of Oncology.
The European Organization for Research Treatment and Cancer Lung Cancer Group designed a phase 2 clinical trial known as APPLE to evaluate the use of sequential plasma EGFR T790M and determine the optimal sequencing for gefitinib and osimertinib in patients with EGFR-mutant NSCLC.
The researchers reported results from two randomized arms of the APPLE trial. In arm B, 52 patients received gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation, based on the cobas EGFR test v2 (a real-time PCR test), or progression of disease based on Response Evaluation Criteria in Solid Tumors (RECIST). In arm C, 51 patients received gefitinib until disease progression based on RECIST. Both arms then switched to osimertinib. Patients randomized to a third arm (arm A) received osimertinib upfront until progression of disease based on RECIST, and they were not included in the current study.
The primary endpoint was progression-free survival (PFS) while receiving osimertinib at 18 months in patients who were originally randomized to gefitinib, then switched to osimertinib at the emergence of circulating tumor DNA. Secondary endpoints included PFS, overall response rate, overall survival, and brain PFS.
Patients entered the study between November 2017 and February 2020. A total of 75% and 65% of those in arms B and C, respectively, were female, approximately 65% had the mutation EGFR Del19, and approximately one-third had baseline brain metastases. In arm B, 17% of patients switched to osimertinib based on the emergence of ctDNA T790M mutation before progressive disease based on RECIST. The median time to molecular disease progression was 266 days.
More patients in arm B met the primary endpoint of PFS while receiving osimertinib at 18 months (67.2%) than in arm C (53.5%), after a median follow-up of 30 months.
As for secondary endpoints, the median PFS in the two arms was 22.0 months and 20.2 months, respectively. Median overall survival was 42.8 months in arm C and was not reached in arm B. The median brain PFS was 24.4 months for arm B and 21.4 months for arm C.
The benefits seen in the osimertinib patients may be due in part to the timing of the switch to correspond with molecular or radiological disease progression, the researchers wrote in their discussion.
In the future, more research is needed to determine whether molecular monitoring may impact patients’ outcomes, compared with monitoring based on radiological progression, they said.
The findings were limited by several factors, mainly the rapid evolution in the treatment landscape of EGFR-mutant NSCLC, the researchers noted.
Osimertinib is currently considered the preferred first-line treatment by most physicians, they said. “The APPLE trial is the first prospective study supporting the role of dynamic adaptive strategies based on ctDNA monitoring in patients with EGFR-mutant advanced NSCLC.”
The study was supported by AstraZeneca. Lead author Dr. Remon had no financial conflicts to disclose. Corresponding author Dr. Dziadziuszko disclosed honoraria for consultancy or lectures from AstraZeneca, Roche, Novartis, MSD, Takeda, Pfizer, Amgen, and Bristol-Myers Squibb.
Previous studies have suggested that molecular progression of disease in patients with EGFR-mutant NSCLC, as measured by sequential plasma EGFR T790M, may precede radiological progression, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).
However, the impact of these measures on timing of treatment changes and patient outcomes has not been examined, wrote Jordi Remon, MD, of Paris (France)–Saclay University and colleagues, in Annals of Oncology.
The European Organization for Research Treatment and Cancer Lung Cancer Group designed a phase 2 clinical trial known as APPLE to evaluate the use of sequential plasma EGFR T790M and determine the optimal sequencing for gefitinib and osimertinib in patients with EGFR-mutant NSCLC.
The researchers reported results from two randomized arms of the APPLE trial. In arm B, 52 patients received gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation, based on the cobas EGFR test v2 (a real-time PCR test), or progression of disease based on Response Evaluation Criteria in Solid Tumors (RECIST). In arm C, 51 patients received gefitinib until disease progression based on RECIST. Both arms then switched to osimertinib. Patients randomized to a third arm (arm A) received osimertinib upfront until progression of disease based on RECIST, and they were not included in the current study.
The primary endpoint was progression-free survival (PFS) while receiving osimertinib at 18 months in patients who were originally randomized to gefitinib, then switched to osimertinib at the emergence of circulating tumor DNA. Secondary endpoints included PFS, overall response rate, overall survival, and brain PFS.
Patients entered the study between November 2017 and February 2020. A total of 75% and 65% of those in arms B and C, respectively, were female, approximately 65% had the mutation EGFR Del19, and approximately one-third had baseline brain metastases. In arm B, 17% of patients switched to osimertinib based on the emergence of ctDNA T790M mutation before progressive disease based on RECIST. The median time to molecular disease progression was 266 days.
More patients in arm B met the primary endpoint of PFS while receiving osimertinib at 18 months (67.2%) than in arm C (53.5%), after a median follow-up of 30 months.
As for secondary endpoints, the median PFS in the two arms was 22.0 months and 20.2 months, respectively. Median overall survival was 42.8 months in arm C and was not reached in arm B. The median brain PFS was 24.4 months for arm B and 21.4 months for arm C.
The benefits seen in the osimertinib patients may be due in part to the timing of the switch to correspond with molecular or radiological disease progression, the researchers wrote in their discussion.
In the future, more research is needed to determine whether molecular monitoring may impact patients’ outcomes, compared with monitoring based on radiological progression, they said.
The findings were limited by several factors, mainly the rapid evolution in the treatment landscape of EGFR-mutant NSCLC, the researchers noted.
Osimertinib is currently considered the preferred first-line treatment by most physicians, they said. “The APPLE trial is the first prospective study supporting the role of dynamic adaptive strategies based on ctDNA monitoring in patients with EGFR-mutant advanced NSCLC.”
The study was supported by AstraZeneca. Lead author Dr. Remon had no financial conflicts to disclose. Corresponding author Dr. Dziadziuszko disclosed honoraria for consultancy or lectures from AstraZeneca, Roche, Novartis, MSD, Takeda, Pfizer, Amgen, and Bristol-Myers Squibb.
Previous studies have suggested that molecular progression of disease in patients with EGFR-mutant NSCLC, as measured by sequential plasma EGFR T790M, may precede radiological progression, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).
However, the impact of these measures on timing of treatment changes and patient outcomes has not been examined, wrote Jordi Remon, MD, of Paris (France)–Saclay University and colleagues, in Annals of Oncology.
The European Organization for Research Treatment and Cancer Lung Cancer Group designed a phase 2 clinical trial known as APPLE to evaluate the use of sequential plasma EGFR T790M and determine the optimal sequencing for gefitinib and osimertinib in patients with EGFR-mutant NSCLC.
The researchers reported results from two randomized arms of the APPLE trial. In arm B, 52 patients received gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation, based on the cobas EGFR test v2 (a real-time PCR test), or progression of disease based on Response Evaluation Criteria in Solid Tumors (RECIST). In arm C, 51 patients received gefitinib until disease progression based on RECIST. Both arms then switched to osimertinib. Patients randomized to a third arm (arm A) received osimertinib upfront until progression of disease based on RECIST, and they were not included in the current study.
The primary endpoint was progression-free survival (PFS) while receiving osimertinib at 18 months in patients who were originally randomized to gefitinib, then switched to osimertinib at the emergence of circulating tumor DNA. Secondary endpoints included PFS, overall response rate, overall survival, and brain PFS.
Patients entered the study between November 2017 and February 2020. A total of 75% and 65% of those in arms B and C, respectively, were female, approximately 65% had the mutation EGFR Del19, and approximately one-third had baseline brain metastases. In arm B, 17% of patients switched to osimertinib based on the emergence of ctDNA T790M mutation before progressive disease based on RECIST. The median time to molecular disease progression was 266 days.
More patients in arm B met the primary endpoint of PFS while receiving osimertinib at 18 months (67.2%) than in arm C (53.5%), after a median follow-up of 30 months.
As for secondary endpoints, the median PFS in the two arms was 22.0 months and 20.2 months, respectively. Median overall survival was 42.8 months in arm C and was not reached in arm B. The median brain PFS was 24.4 months for arm B and 21.4 months for arm C.
The benefits seen in the osimertinib patients may be due in part to the timing of the switch to correspond with molecular or radiological disease progression, the researchers wrote in their discussion.
In the future, more research is needed to determine whether molecular monitoring may impact patients’ outcomes, compared with monitoring based on radiological progression, they said.
The findings were limited by several factors, mainly the rapid evolution in the treatment landscape of EGFR-mutant NSCLC, the researchers noted.
Osimertinib is currently considered the preferred first-line treatment by most physicians, they said. “The APPLE trial is the first prospective study supporting the role of dynamic adaptive strategies based on ctDNA monitoring in patients with EGFR-mutant advanced NSCLC.”
The study was supported by AstraZeneca. Lead author Dr. Remon had no financial conflicts to disclose. Corresponding author Dr. Dziadziuszko disclosed honoraria for consultancy or lectures from AstraZeneca, Roche, Novartis, MSD, Takeda, Pfizer, Amgen, and Bristol-Myers Squibb.
FROM ANNALS OF ONCOLOGY
New drugs in primary care: Lessons learned from COVID-19
SAN DIEGO – – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.
Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.
Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
Understanding the mechanism of action
Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.
“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.
“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.
Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.
Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.
Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.
When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.
Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.
“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.
Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
Effective in real world, but less so than in clinical trials
The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.
A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
Many drug-drug interactions, but they can be managed
Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.
To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.
This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.
To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:
- Prescribe an alternative COVID therapy.
- Temporarily withhold concomitant medication if clinically appropriate.
- Adjust the dose of concomitant medication and monitor for adverse effects.
Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
Important considerations
Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.
He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.
Dr. Smetana and Dr. Kiefl reported no disclosures.
SAN DIEGO – – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.
Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.
Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
Understanding the mechanism of action
Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.
“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.
“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.
Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.
Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.
Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.
When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.
Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.
“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.
Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
Effective in real world, but less so than in clinical trials
The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.
A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
Many drug-drug interactions, but they can be managed
Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.
To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.
This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.
To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:
- Prescribe an alternative COVID therapy.
- Temporarily withhold concomitant medication if clinically appropriate.
- Adjust the dose of concomitant medication and monitor for adverse effects.
Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
Important considerations
Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.
He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.
Dr. Smetana and Dr. Kiefl reported no disclosures.
SAN DIEGO – – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.
Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.
Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
Understanding the mechanism of action
Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.
“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.
“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.
Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.
Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.
Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.
When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.
Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.
“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.
Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
Effective in real world, but less so than in clinical trials
The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.
A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
Many drug-drug interactions, but they can be managed
Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.
To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.
This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.
To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:
- Prescribe an alternative COVID therapy.
- Temporarily withhold concomitant medication if clinically appropriate.
- Adjust the dose of concomitant medication and monitor for adverse effects.
Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
Important considerations
Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.
He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.
Dr. Smetana and Dr. Kiefl reported no disclosures.
AT INTERNAL MEDICINE 2023
New clues to how air pollution fuels lung cancer in nonsmokers
“This work adds to our understanding of the mechanism by which air pollutants promote the earliest stages of lung cancer, particularly in people who have never smoked,” William Hill, PhD, co–first author and postdoctoral researcher at the Francis Crick Institute, London, told this news organization.
The study, which assessed human lung samples and mouse cancer models, was published online in Nature.
Although smoking remains the chief risk factor for lung cancer, outdoor air pollution causes roughly 1 in 10 cases of lung cancer in the United Kingdom, according to Cancer Research UK. In 2019, about 300,000 lung cancer deaths around the world were attributed to exposure to ambient particulate matter measuring ≤ 2.5 mcm (PM2.5).
While the link between air pollution and lung cancer is well known, the mechanism that explains this link has been harder to pinpoint.
One theory is that environmental carcinogens such as tobacco smoke and UV light cause mutations by damaging DNA directly. However, recent data have hinted that that may not be the case.
In the current study, Dr. Hill and colleagues proposed that, rather than act on DNA directly, air pollutants might promote inflammatory changes in the lung tissue that wake up inactive cancer-causing mutations, which accumulate naturally in these cells as people age. This idea lines up with a decades-old theory of cancer promotion, according to which tumorigenesis is a two-step process: The initial step induces mutations in healthy cells, after which a promoter step triggers cancer development.
The study team focused on epidermal growth factor receptor (EGFR)–driven lung cancer, which is more common in never-smokers and light smokers, and on environmental particulate matter measuring ≤ 2.5 mcm (PM2.5), which is fine enough to travel into the lungs and is associated with lung cancer risk.
Dr. Hill and colleagues analyzed data from over 400,000 people in three countries. They compared rates of EGFR-mutant lung cancer cases in areas with different levels of PM2.5 pollution. The team found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in England, South Korea, and Taiwan.
The researchers then studied genetically engineered mouse models of lung adenocarcinoma to determine whether particulate matter exposure could trigger the development of lung tumors. In these functional mouse models, air pollutants led to an influx of macrophages in the lung and the release of interleukin-1beta, a key mediator of the inflammatory response.
This process ultimately “fuels tumorigenesis,” the study team concluded.
The team also found that treatment with an anti-interleukin-1beta antibody during PM2.5 exposure reduced lung cancer promotion by air pollutants.
A detailed mutational profiling of histologically normal lung tissue from 295 individuals revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively.
Overall, “our data suggest a mechanistic and causative link between air pollutants and lung cancer,” the study team wrote.
The study demonstrates that air pollution rouses cells in the lung that carry cancer-causing mutations, “encouraging them to grow and potentially form tumors,” Dr. Hill said. “Understanding the biology could help identify high-risk individuals and, in the future, may open avenues to prevent cancer caused by breathing polluted air.”
In a related article in Nature, Allan Balmain, PhD, of the University of California, San Francisco, said these results have “major implications for how to think about cancer prevention.”
“There is presently nothing that can be done to remove the mutated cells that accumulate in normal tissues, but if there is a promotion stage that influences the rate of cancer development, then inhibition of this stage might be an effective way to prevent cancer,” Dr. Balmain said.
Another prevention option, Dr. Hill noted, is to reduce the levels of air pollution. “Our study provides a mandate for the reduction of PM2.5 emissions globally,” he said.
Dr. Hill also believes the findings may extend beyond lung cancer.
“It’s possible that this inflammatory pathway could be involved in other types of cancer and that it could be triggered by other environmental carcinogens,” he said. “But further research is needed to find out which other environmental carcinogens might trigger this pathway, as well as which other parts of the body this may occur in.”
Funding for the study was provided by Cancer Research UK, the European Research Council, the Francis Crick Institute, the Mark Foundation, the Lung Cancer Research Foundation, Rosetrees Trust, and the Ruth Strauss Foundation. A complete list of author disclosures is available with the original article. Dr. Balmain has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“This work adds to our understanding of the mechanism by which air pollutants promote the earliest stages of lung cancer, particularly in people who have never smoked,” William Hill, PhD, co–first author and postdoctoral researcher at the Francis Crick Institute, London, told this news organization.
The study, which assessed human lung samples and mouse cancer models, was published online in Nature.
Although smoking remains the chief risk factor for lung cancer, outdoor air pollution causes roughly 1 in 10 cases of lung cancer in the United Kingdom, according to Cancer Research UK. In 2019, about 300,000 lung cancer deaths around the world were attributed to exposure to ambient particulate matter measuring ≤ 2.5 mcm (PM2.5).
While the link between air pollution and lung cancer is well known, the mechanism that explains this link has been harder to pinpoint.
One theory is that environmental carcinogens such as tobacco smoke and UV light cause mutations by damaging DNA directly. However, recent data have hinted that that may not be the case.
In the current study, Dr. Hill and colleagues proposed that, rather than act on DNA directly, air pollutants might promote inflammatory changes in the lung tissue that wake up inactive cancer-causing mutations, which accumulate naturally in these cells as people age. This idea lines up with a decades-old theory of cancer promotion, according to which tumorigenesis is a two-step process: The initial step induces mutations in healthy cells, after which a promoter step triggers cancer development.
The study team focused on epidermal growth factor receptor (EGFR)–driven lung cancer, which is more common in never-smokers and light smokers, and on environmental particulate matter measuring ≤ 2.5 mcm (PM2.5), which is fine enough to travel into the lungs and is associated with lung cancer risk.
Dr. Hill and colleagues analyzed data from over 400,000 people in three countries. They compared rates of EGFR-mutant lung cancer cases in areas with different levels of PM2.5 pollution. The team found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in England, South Korea, and Taiwan.
The researchers then studied genetically engineered mouse models of lung adenocarcinoma to determine whether particulate matter exposure could trigger the development of lung tumors. In these functional mouse models, air pollutants led to an influx of macrophages in the lung and the release of interleukin-1beta, a key mediator of the inflammatory response.
This process ultimately “fuels tumorigenesis,” the study team concluded.
The team also found that treatment with an anti-interleukin-1beta antibody during PM2.5 exposure reduced lung cancer promotion by air pollutants.
A detailed mutational profiling of histologically normal lung tissue from 295 individuals revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively.
Overall, “our data suggest a mechanistic and causative link between air pollutants and lung cancer,” the study team wrote.
The study demonstrates that air pollution rouses cells in the lung that carry cancer-causing mutations, “encouraging them to grow and potentially form tumors,” Dr. Hill said. “Understanding the biology could help identify high-risk individuals and, in the future, may open avenues to prevent cancer caused by breathing polluted air.”
In a related article in Nature, Allan Balmain, PhD, of the University of California, San Francisco, said these results have “major implications for how to think about cancer prevention.”
“There is presently nothing that can be done to remove the mutated cells that accumulate in normal tissues, but if there is a promotion stage that influences the rate of cancer development, then inhibition of this stage might be an effective way to prevent cancer,” Dr. Balmain said.
Another prevention option, Dr. Hill noted, is to reduce the levels of air pollution. “Our study provides a mandate for the reduction of PM2.5 emissions globally,” he said.
Dr. Hill also believes the findings may extend beyond lung cancer.
“It’s possible that this inflammatory pathway could be involved in other types of cancer and that it could be triggered by other environmental carcinogens,” he said. “But further research is needed to find out which other environmental carcinogens might trigger this pathway, as well as which other parts of the body this may occur in.”
Funding for the study was provided by Cancer Research UK, the European Research Council, the Francis Crick Institute, the Mark Foundation, the Lung Cancer Research Foundation, Rosetrees Trust, and the Ruth Strauss Foundation. A complete list of author disclosures is available with the original article. Dr. Balmain has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“This work adds to our understanding of the mechanism by which air pollutants promote the earliest stages of lung cancer, particularly in people who have never smoked,” William Hill, PhD, co–first author and postdoctoral researcher at the Francis Crick Institute, London, told this news organization.
The study, which assessed human lung samples and mouse cancer models, was published online in Nature.
Although smoking remains the chief risk factor for lung cancer, outdoor air pollution causes roughly 1 in 10 cases of lung cancer in the United Kingdom, according to Cancer Research UK. In 2019, about 300,000 lung cancer deaths around the world were attributed to exposure to ambient particulate matter measuring ≤ 2.5 mcm (PM2.5).
While the link between air pollution and lung cancer is well known, the mechanism that explains this link has been harder to pinpoint.
One theory is that environmental carcinogens such as tobacco smoke and UV light cause mutations by damaging DNA directly. However, recent data have hinted that that may not be the case.
In the current study, Dr. Hill and colleagues proposed that, rather than act on DNA directly, air pollutants might promote inflammatory changes in the lung tissue that wake up inactive cancer-causing mutations, which accumulate naturally in these cells as people age. This idea lines up with a decades-old theory of cancer promotion, according to which tumorigenesis is a two-step process: The initial step induces mutations in healthy cells, after which a promoter step triggers cancer development.
The study team focused on epidermal growth factor receptor (EGFR)–driven lung cancer, which is more common in never-smokers and light smokers, and on environmental particulate matter measuring ≤ 2.5 mcm (PM2.5), which is fine enough to travel into the lungs and is associated with lung cancer risk.
Dr. Hill and colleagues analyzed data from over 400,000 people in three countries. They compared rates of EGFR-mutant lung cancer cases in areas with different levels of PM2.5 pollution. The team found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in England, South Korea, and Taiwan.
The researchers then studied genetically engineered mouse models of lung adenocarcinoma to determine whether particulate matter exposure could trigger the development of lung tumors. In these functional mouse models, air pollutants led to an influx of macrophages in the lung and the release of interleukin-1beta, a key mediator of the inflammatory response.
This process ultimately “fuels tumorigenesis,” the study team concluded.
The team also found that treatment with an anti-interleukin-1beta antibody during PM2.5 exposure reduced lung cancer promotion by air pollutants.
A detailed mutational profiling of histologically normal lung tissue from 295 individuals revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively.
Overall, “our data suggest a mechanistic and causative link between air pollutants and lung cancer,” the study team wrote.
The study demonstrates that air pollution rouses cells in the lung that carry cancer-causing mutations, “encouraging them to grow and potentially form tumors,” Dr. Hill said. “Understanding the biology could help identify high-risk individuals and, in the future, may open avenues to prevent cancer caused by breathing polluted air.”
In a related article in Nature, Allan Balmain, PhD, of the University of California, San Francisco, said these results have “major implications for how to think about cancer prevention.”
“There is presently nothing that can be done to remove the mutated cells that accumulate in normal tissues, but if there is a promotion stage that influences the rate of cancer development, then inhibition of this stage might be an effective way to prevent cancer,” Dr. Balmain said.
Another prevention option, Dr. Hill noted, is to reduce the levels of air pollution. “Our study provides a mandate for the reduction of PM2.5 emissions globally,” he said.
Dr. Hill also believes the findings may extend beyond lung cancer.
“It’s possible that this inflammatory pathway could be involved in other types of cancer and that it could be triggered by other environmental carcinogens,” he said. “But further research is needed to find out which other environmental carcinogens might trigger this pathway, as well as which other parts of the body this may occur in.”
Funding for the study was provided by Cancer Research UK, the European Research Council, the Francis Crick Institute, the Mark Foundation, the Lung Cancer Research Foundation, Rosetrees Trust, and the Ruth Strauss Foundation. A complete list of author disclosures is available with the original article. Dr. Balmain has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.