Pulmonology

Extracorporeal membrane oxygen support appears to be beneficial in patients with advanced interstitial lung disease (ILD), according to a new meta-analysis. Specifically, among patients undergoing ECMO as a bridge to transplant, mortality was lower with venoarterial (VA) ECMO than with venovenous (VV) ECMO, although the confidence in the finding was low.

ECMO has been used increasingly in ILD patients over the past 10-15 years for acute decompensation as well as a bridge to lung transplant, according to Prasanth Balasubramanian, MD, but clinical evidence for its use is limited to case series or short-term retrospective studies. “We don’t have robust evidence on whether it really helps with the outcome, and which mode is better, so that’s why we decided to do a study on this,” said Dr. Balasubramanian, who is a fellow in pulmonary critical care at Mayo Clinic (Jacksonville, Fla.). He presented the new research at the annual meeting of the American College of Chest Physicians (CHEST).

The results were encouraging, according to the study’s lead author Pramod Guru, MD. “I think what we take from this analysis is that ECMO should not be considered as a contraindication for people you are considering for lung transplant. If we have this population of people who are very sick, but we have the opportunity to solve them with VA ECMO and then give the transplantation possibly, that may be the way,” said Dr. Guru, who is a critical care specialist at Mayo Clinic, Jacksonville, Fla. He acknowledged that more work needs to be done to determine whether VA or VV is best in specific patient populations.

The meta-analysis included 18 studies with a total of 1,341 patients, who were a mean age of 55.89 years and 61.08% of whom were male. Most procedures (75.3%) were VV. The overall mortality was 52.6%, including 59.7% for VV ECMO and 34.2% for VA ECMO. The survival difference did not reach statistical significance (odds ratio, 0.48; P = .11). There was also no significant difference in survival between patients who underwent ECMO and those who did not undergo ECMO (OR, 0.48; P = .43).

The researchers also analyzed 13 studies with 1,002 patients that looked at ECMO as a bridge to transplant (mean age, 52.1; 52.2% male; 49.3% VV, 31.1% VA, 32.4% cardiopulmonary bypass). Mortality was lower in the VA group than in the VV group (odds ratio, 0.62; P = .04).

“VA ECMO is generally for sicker patients, so it’s odd that the patients who are on the more aggressive support had lower mortality. But it’s good, it says it works,” said Chris Carroll, MD, an intensivist at the University of Florida, Jacksonville, who was asked to comment on the study.

The finding may also be an artifact of bias in the retrospective data, according to Joshua Diamond, MD, who comoderated the session where the study was presented. He noted age, physical function, and illness severity, among other factors can play a role in decision-making. “I have a feeling that what you’re seeing is a very carefully selected patient population as opposed to a true mortality benefit with VA versus VV ECMO,” said Dr. Diamond, who is associate medical director of the Penn Lung Transplant Program in Philadelphia.

Another weakness of the study is that ECMO techniques and devices have changed over time, making some of the older data less relevant to current practice. Overall Dr. Diamond described the study as interesting, but “I’d like to see a bit more granularity of data to figure out who makes or doesn’t make a good candidate,” said Dr. Diamond.

Patients with ILD undergoing ECMO as a bridge to transplant had a higher 1-year posttransplant mortality than patients with other causes for transplant (OR, 1.78; P<.01). However, this finding relied on two retrospective studies using the UNOS database at different time points (2001-2012 and 2015-2020), leading to potential confounders and risk of bias.

Dr. Balasubramanian recognized the limitations of the analysis. “We do think that further prospective studies comparing various modalities would be essential, although it would be challenging,” he said.

Nevertheless, Dr. Guru said that his own center is changing its patient selection criteria for ECMO and will begin to collect prospective data: “I would say that in 12 months we’ll have our own data to support what we are doing.”

The study can also inform patients and family who are trying to make a potential end-of-life decision about pursuing aggressive ECMO therapy. “This study says that if you choose to pursue that more aggressive therapy, you may still have a good outcome. A patient might say, ‘Why am I going to go through all this? Is it just prolonging my death, or is there a chance of saving my life? I think what this study shows is that it does have potential of saving their life,” said Dr. Carroll.

Dr. Balasubramanian, Dr. Guru, and Dr. Carroll have no relevant financial disclosures.

Extracorporeal membrane oxygen support appears to be beneficial in patients with advanced interstitial lung disease (ILD), according to a new meta-analysis. Specifically, among patients undergoing ECMO as a bridge to transplant, mortality was lower with venoarterial (VA) ECMO than with venovenous (VV) ECMO, although the confidence in the finding was low.

ECMO has been used increasingly in ILD patients over the past 10-15 years for acute decompensation as well as a bridge to lung transplant, according to Prasanth Balasubramanian, MD, but clinical evidence for its use is limited to case series or short-term retrospective studies. “We don’t have robust evidence on whether it really helps with the outcome, and which mode is better, so that’s why we decided to do a study on this,” said Dr. Balasubramanian, who is a fellow in pulmonary critical care at Mayo Clinic (Jacksonville, Fla.). He presented the new research at the annual meeting of the American College of Chest Physicians (CHEST).

The results were encouraging, according to the study’s lead author Pramod Guru, MD. “I think what we take from this analysis is that ECMO should not be considered as a contraindication for people you are considering for lung transplant. If we have this population of people who are very sick, but we have the opportunity to solve them with VA ECMO and then give the transplantation possibly, that may be the way,” said Dr. Guru, who is a critical care specialist at Mayo Clinic, Jacksonville, Fla. He acknowledged that more work needs to be done to determine whether VA or VV is best in specific patient populations.

The meta-analysis included 18 studies with a total of 1,341 patients, who were a mean age of 55.89 years and 61.08% of whom were male. Most procedures (75.3%) were VV. The overall mortality was 52.6%, including 59.7% for VV ECMO and 34.2% for VA ECMO. The survival difference did not reach statistical significance (odds ratio, 0.48; P = .11). There was also no significant difference in survival between patients who underwent ECMO and those who did not undergo ECMO (OR, 0.48; P = .43).

The researchers also analyzed 13 studies with 1,002 patients that looked at ECMO as a bridge to transplant (mean age, 52.1; 52.2% male; 49.3% VV, 31.1% VA, 32.4% cardiopulmonary bypass). Mortality was lower in the VA group than in the VV group (odds ratio, 0.62; P = .04).

“VA ECMO is generally for sicker patients, so it’s odd that the patients who are on the more aggressive support had lower mortality. But it’s good, it says it works,” said Chris Carroll, MD, an intensivist at the University of Florida, Jacksonville, who was asked to comment on the study.

The finding may also be an artifact of bias in the retrospective data, according to Joshua Diamond, MD, who comoderated the session where the study was presented. He noted age, physical function, and illness severity, among other factors can play a role in decision-making. “I have a feeling that what you’re seeing is a very carefully selected patient population as opposed to a true mortality benefit with VA versus VV ECMO,” said Dr. Diamond, who is associate medical director of the Penn Lung Transplant Program in Philadelphia.

Another weakness of the study is that ECMO techniques and devices have changed over time, making some of the older data less relevant to current practice. Overall Dr. Diamond described the study as interesting, but “I’d like to see a bit more granularity of data to figure out who makes or doesn’t make a good candidate,” said Dr. Diamond.

Patients with ILD undergoing ECMO as a bridge to transplant had a higher 1-year posttransplant mortality than patients with other causes for transplant (OR, 1.78; P<.01). However, this finding relied on two retrospective studies using the UNOS database at different time points (2001-2012 and 2015-2020), leading to potential confounders and risk of bias.

Dr. Balasubramanian recognized the limitations of the analysis. “We do think that further prospective studies comparing various modalities would be essential, although it would be challenging,” he said.

Nevertheless, Dr. Guru said that his own center is changing its patient selection criteria for ECMO and will begin to collect prospective data: “I would say that in 12 months we’ll have our own data to support what we are doing.”

The study can also inform patients and family who are trying to make a potential end-of-life decision about pursuing aggressive ECMO therapy. “This study says that if you choose to pursue that more aggressive therapy, you may still have a good outcome. A patient might say, ‘Why am I going to go through all this? Is it just prolonging my death, or is there a chance of saving my life? I think what this study shows is that it does have potential of saving their life,” said Dr. Carroll.

Dr. Balasubramanian, Dr. Guru, and Dr. Carroll have no relevant financial disclosures.

Extracorporeal membrane oxygen support appears to be beneficial in patients with advanced interstitial lung disease (ILD), according to a new meta-analysis. Specifically, among patients undergoing ECMO as a bridge to transplant, mortality was lower with venoarterial (VA) ECMO than with venovenous (VV) ECMO, although the confidence in the finding was low.

ECMO has been used increasingly in ILD patients over the past 10-15 years for acute decompensation as well as a bridge to lung transplant, according to Prasanth Balasubramanian, MD, but clinical evidence for its use is limited to case series or short-term retrospective studies. “We don’t have robust evidence on whether it really helps with the outcome, and which mode is better, so that’s why we decided to do a study on this,” said Dr. Balasubramanian, who is a fellow in pulmonary critical care at Mayo Clinic (Jacksonville, Fla.). He presented the new research at the annual meeting of the American College of Chest Physicians (CHEST).

The results were encouraging, according to the study’s lead author Pramod Guru, MD. “I think what we take from this analysis is that ECMO should not be considered as a contraindication for people you are considering for lung transplant. If we have this population of people who are very sick, but we have the opportunity to solve them with VA ECMO and then give the transplantation possibly, that may be the way,” said Dr. Guru, who is a critical care specialist at Mayo Clinic, Jacksonville, Fla. He acknowledged that more work needs to be done to determine whether VA or VV is best in specific patient populations.

The meta-analysis included 18 studies with a total of 1,341 patients, who were a mean age of 55.89 years and 61.08% of whom were male. Most procedures (75.3%) were VV. The overall mortality was 52.6%, including 59.7% for VV ECMO and 34.2% for VA ECMO. The survival difference did not reach statistical significance (odds ratio, 0.48; P = .11). There was also no significant difference in survival between patients who underwent ECMO and those who did not undergo ECMO (OR, 0.48; P = .43).

The researchers also analyzed 13 studies with 1,002 patients that looked at ECMO as a bridge to transplant (mean age, 52.1; 52.2% male; 49.3% VV, 31.1% VA, 32.4% cardiopulmonary bypass). Mortality was lower in the VA group than in the VV group (odds ratio, 0.62; P = .04).

“VA ECMO is generally for sicker patients, so it’s odd that the patients who are on the more aggressive support had lower mortality. But it’s good, it says it works,” said Chris Carroll, MD, an intensivist at the University of Florida, Jacksonville, who was asked to comment on the study.

The finding may also be an artifact of bias in the retrospective data, according to Joshua Diamond, MD, who comoderated the session where the study was presented. He noted age, physical function, and illness severity, among other factors can play a role in decision-making. “I have a feeling that what you’re seeing is a very carefully selected patient population as opposed to a true mortality benefit with VA versus VV ECMO,” said Dr. Diamond, who is associate medical director of the Penn Lung Transplant Program in Philadelphia.

Another weakness of the study is that ECMO techniques and devices have changed over time, making some of the older data less relevant to current practice. Overall Dr. Diamond described the study as interesting, but “I’d like to see a bit more granularity of data to figure out who makes or doesn’t make a good candidate,” said Dr. Diamond.

Patients with ILD undergoing ECMO as a bridge to transplant had a higher 1-year posttransplant mortality than patients with other causes for transplant (OR, 1.78; P<.01). However, this finding relied on two retrospective studies using the UNOS database at different time points (2001-2012 and 2015-2020), leading to potential confounders and risk of bias.

Dr. Balasubramanian recognized the limitations of the analysis. “We do think that further prospective studies comparing various modalities would be essential, although it would be challenging,” he said.

Nevertheless, Dr. Guru said that his own center is changing its patient selection criteria for ECMO and will begin to collect prospective data: “I would say that in 12 months we’ll have our own data to support what we are doing.”

The study can also inform patients and family who are trying to make a potential end-of-life decision about pursuing aggressive ECMO therapy. “This study says that if you choose to pursue that more aggressive therapy, you may still have a good outcome. A patient might say, ‘Why am I going to go through all this? Is it just prolonging my death, or is there a chance of saving my life? I think what this study shows is that it does have potential of saving their life,” said Dr. Carroll.

Dr. Balasubramanian, Dr. Guru, and Dr. Carroll have no relevant financial disclosures.

Hospitalized patients with both asthma and eosinophilic esophagitis (EoE) were a younger average age than those hospitalized with asthma alone, according to a new analysis of data from HCA Healthcare.

Not much work has been done on the overlap between the two conditions, both of which are believed to be driven by the action of both eosinophils and helper T cells, according to Linda Pham, DO, who presented the research at the annual meeting of the American College of Chest Physicians (CHEST).

“I have a colleague who is interested in GI and he’s really interested in EOE. We thought it would be nice to look at those populations of patients to see if there’s a correlation between them aside from just the atopic disease,” said Dr. Pham, who is an internal medicine resident at Riverside (Calif.) Community Hospital.

The findings underscore the need for assessing individual patient risk. “Having another concomitant disease like EoE, or maybe like atopic dermatitis, might cause you to have more severe [asthma] exacerbations causing you to go into the hospital more. I think if patients have more of these diseases, doctors can be more cognizant that they need to really be on top of treatment and make sure that [their patients] are aware of themselves so that if their symptoms exacerbate, they can go to the hospital and seek care,” said Dr. Pham.

The study was a retrospective analysis of 3,678,812 patients with asthma and 5,823 patients with both EoE and asthma. The data was drawn from 185 HCA hospitals, with records between 2016 and 2021.

The incidence of both asthma and asthma with EoE remained stable between 2016 and 2021. Dr. Pham pointed out that there are good methods to diagnose both conditions, which suggests that existing treatments are effective enough to be limiting the need for emergency treatment, according to Dr. Pham.

Among patients hospitalized with asthma alone, 72.55% were female, while 27.45% were male (P < .001). The numbers were much more evenly split among those with asthma and EoE, at 51.78% and 48.22%, respectively. The differing gender statistics aren’t easy to explain. “It’s not quite clear whether it’s because they just have more severe symptoms, or if it is other factors causing women to seek care more than their male counterparts. It could be personal biases, or it could be the asthma itself that is more severe in women,” said Dr. Pham.

When they broke down the analysis by sex, the researchers found that male EoE patients without asthma were a mean value of 5.517 years older than male EoE patients with asthma, and the mean difference was 5.480 years in female patients (P < .001 for both).

Although the direct cause of earlier hospitalization among patients with concomitant EoE and asthma is unclear, Dr. Pham speculated that the combination of atopic diseases may be leading to a stronger inflammatory response.

It remains to be seen if a similar relationship occurs with other atopic diseases, and future research could examine other factors. “I think it’d be good to look at not just age and gender, but BMI and occupation, things like that,” said Dr. Pham.

The study was of particular interest to Michelle Robertson, MD, who was in the audience. She is the director for clinical services at the Airborne Hazards and Burn Pits Center of Excellence at the New Jersey War-Related Illness and Injury Study Center. “We see a significant number of [veterans] who have been diagnosed with both asthma and eosinophilic esophagitis, and our thinking is that that is likely related to some of the military exposures: In particular, [what the] deployed veterans encountered in the Gulf War, [such as] the smoke from burn pits, sand and dust storms, and smoke from oil well fires. Our thinking is that the particulate matter, the PM 2.5, the very, very tiny particles, may be either sensitizing the lung area and/or esophagus and predisposing them to having those symptoms when they return home,” said Dr. Robertson, in an interview.

Particles in this size range may be able to bypass the protected areas of the nose and the lungs to reach the alveoli, where they could potentially interfere with the transfer of air between the lungs and the rest of the body, which could in turn lead to a variety of inflammatory conditions, according to Dr. Robertson.

She noted that particle exposure varies with a soldier’s wartime occupation, with higher exposures among mechanics and burn pit managers, for example. However, the highest levels of exposure do not predict later illness, which is a natural prompt for future research. “The second part of this whole pathophysiology is susceptibility. Is there something about those people that do get sick that makes them more susceptible than folks that don’t, even though they both have the same jobs?”

Dr. Pham and Dr. Robertson have no relevant financial disclosures.
 

Hospitalized patients with both asthma and eosinophilic esophagitis (EoE) were a younger average age than those hospitalized with asthma alone, according to a new analysis of data from HCA Healthcare.

Not much work has been done on the overlap between the two conditions, both of which are believed to be driven by the action of both eosinophils and helper T cells, according to Linda Pham, DO, who presented the research at the annual meeting of the American College of Chest Physicians (CHEST).

“I have a colleague who is interested in GI and he’s really interested in EOE. We thought it would be nice to look at those populations of patients to see if there’s a correlation between them aside from just the atopic disease,” said Dr. Pham, who is an internal medicine resident at Riverside (Calif.) Community Hospital.

The findings underscore the need for assessing individual patient risk. “Having another concomitant disease like EoE, or maybe like atopic dermatitis, might cause you to have more severe [asthma] exacerbations causing you to go into the hospital more. I think if patients have more of these diseases, doctors can be more cognizant that they need to really be on top of treatment and make sure that [their patients] are aware of themselves so that if their symptoms exacerbate, they can go to the hospital and seek care,” said Dr. Pham.

The study was a retrospective analysis of 3,678,812 patients with asthma and 5,823 patients with both EoE and asthma. The data was drawn from 185 HCA hospitals, with records between 2016 and 2021.

The incidence of both asthma and asthma with EoE remained stable between 2016 and 2021. Dr. Pham pointed out that there are good methods to diagnose both conditions, which suggests that existing treatments are effective enough to be limiting the need for emergency treatment, according to Dr. Pham.

Among patients hospitalized with asthma alone, 72.55% were female, while 27.45% were male (P < .001). The numbers were much more evenly split among those with asthma and EoE, at 51.78% and 48.22%, respectively. The differing gender statistics aren’t easy to explain. “It’s not quite clear whether it’s because they just have more severe symptoms, or if it is other factors causing women to seek care more than their male counterparts. It could be personal biases, or it could be the asthma itself that is more severe in women,” said Dr. Pham.

When they broke down the analysis by sex, the researchers found that male EoE patients without asthma were a mean value of 5.517 years older than male EoE patients with asthma, and the mean difference was 5.480 years in female patients (P < .001 for both).

Although the direct cause of earlier hospitalization among patients with concomitant EoE and asthma is unclear, Dr. Pham speculated that the combination of atopic diseases may be leading to a stronger inflammatory response.

It remains to be seen if a similar relationship occurs with other atopic diseases, and future research could examine other factors. “I think it’d be good to look at not just age and gender, but BMI and occupation, things like that,” said Dr. Pham.

The study was of particular interest to Michelle Robertson, MD, who was in the audience. She is the director for clinical services at the Airborne Hazards and Burn Pits Center of Excellence at the New Jersey War-Related Illness and Injury Study Center. “We see a significant number of [veterans] who have been diagnosed with both asthma and eosinophilic esophagitis, and our thinking is that that is likely related to some of the military exposures: In particular, [what the] deployed veterans encountered in the Gulf War, [such as] the smoke from burn pits, sand and dust storms, and smoke from oil well fires. Our thinking is that the particulate matter, the PM 2.5, the very, very tiny particles, may be either sensitizing the lung area and/or esophagus and predisposing them to having those symptoms when they return home,” said Dr. Robertson, in an interview.

Particles in this size range may be able to bypass the protected areas of the nose and the lungs to reach the alveoli, where they could potentially interfere with the transfer of air between the lungs and the rest of the body, which could in turn lead to a variety of inflammatory conditions, according to Dr. Robertson.

She noted that particle exposure varies with a soldier’s wartime occupation, with higher exposures among mechanics and burn pit managers, for example. However, the highest levels of exposure do not predict later illness, which is a natural prompt for future research. “The second part of this whole pathophysiology is susceptibility. Is there something about those people that do get sick that makes them more susceptible than folks that don’t, even though they both have the same jobs?”

Dr. Pham and Dr. Robertson have no relevant financial disclosures.
 

Hospitalized patients with both asthma and eosinophilic esophagitis (EoE) were a younger average age than those hospitalized with asthma alone, according to a new analysis of data from HCA Healthcare.

Not much work has been done on the overlap between the two conditions, both of which are believed to be driven by the action of both eosinophils and helper T cells, according to Linda Pham, DO, who presented the research at the annual meeting of the American College of Chest Physicians (CHEST).

“I have a colleague who is interested in GI and he’s really interested in EOE. We thought it would be nice to look at those populations of patients to see if there’s a correlation between them aside from just the atopic disease,” said Dr. Pham, who is an internal medicine resident at Riverside (Calif.) Community Hospital.

The findings underscore the need for assessing individual patient risk. “Having another concomitant disease like EoE, or maybe like atopic dermatitis, might cause you to have more severe [asthma] exacerbations causing you to go into the hospital more. I think if patients have more of these diseases, doctors can be more cognizant that they need to really be on top of treatment and make sure that [their patients] are aware of themselves so that if their symptoms exacerbate, they can go to the hospital and seek care,” said Dr. Pham.

The study was a retrospective analysis of 3,678,812 patients with asthma and 5,823 patients with both EoE and asthma. The data was drawn from 185 HCA hospitals, with records between 2016 and 2021.

The incidence of both asthma and asthma with EoE remained stable between 2016 and 2021. Dr. Pham pointed out that there are good methods to diagnose both conditions, which suggests that existing treatments are effective enough to be limiting the need for emergency treatment, according to Dr. Pham.

Among patients hospitalized with asthma alone, 72.55% were female, while 27.45% were male (P < .001). The numbers were much more evenly split among those with asthma and EoE, at 51.78% and 48.22%, respectively. The differing gender statistics aren’t easy to explain. “It’s not quite clear whether it’s because they just have more severe symptoms, or if it is other factors causing women to seek care more than their male counterparts. It could be personal biases, or it could be the asthma itself that is more severe in women,” said Dr. Pham.

When they broke down the analysis by sex, the researchers found that male EoE patients without asthma were a mean value of 5.517 years older than male EoE patients with asthma, and the mean difference was 5.480 years in female patients (P < .001 for both).

Although the direct cause of earlier hospitalization among patients with concomitant EoE and asthma is unclear, Dr. Pham speculated that the combination of atopic diseases may be leading to a stronger inflammatory response.

It remains to be seen if a similar relationship occurs with other atopic diseases, and future research could examine other factors. “I think it’d be good to look at not just age and gender, but BMI and occupation, things like that,” said Dr. Pham.

The study was of particular interest to Michelle Robertson, MD, who was in the audience. She is the director for clinical services at the Airborne Hazards and Burn Pits Center of Excellence at the New Jersey War-Related Illness and Injury Study Center. “We see a significant number of [veterans] who have been diagnosed with both asthma and eosinophilic esophagitis, and our thinking is that that is likely related to some of the military exposures: In particular, [what the] deployed veterans encountered in the Gulf War, [such as] the smoke from burn pits, sand and dust storms, and smoke from oil well fires. Our thinking is that the particulate matter, the PM 2.5, the very, very tiny particles, may be either sensitizing the lung area and/or esophagus and predisposing them to having those symptoms when they return home,” said Dr. Robertson, in an interview.

Particles in this size range may be able to bypass the protected areas of the nose and the lungs to reach the alveoli, where they could potentially interfere with the transfer of air between the lungs and the rest of the body, which could in turn lead to a variety of inflammatory conditions, according to Dr. Robertson.

She noted that particle exposure varies with a soldier’s wartime occupation, with higher exposures among mechanics and burn pit managers, for example. However, the highest levels of exposure do not predict later illness, which is a natural prompt for future research. “The second part of this whole pathophysiology is susceptibility. Is there something about those people that do get sick that makes them more susceptible than folks that don’t, even though they both have the same jobs?”

Dr. Pham and Dr. Robertson have no relevant financial disclosures.
 

HONOLULU – The diversity of species in the sputum of patients undergoing therapy for nontuberculosis mycobacterial pulmonary disease (NTM-PD) could be a marker for treatment efficacy, authors of a small prospective study suggest.

Neil Osterweil/MDedge

Among 14 patients treated for NTM-PD, 7 of whom had treatment-refractory disease and 7 of whom had microbiological cures after antibiotic therapy, the diversity of the microbiome in sputum was greater for those patients who were cured, indicating that the variety of species found in sputum during treatment could help clinicians evaluate the efficacy of therapy and guide patient management, said Noeul Kang, MD, PhD, from Samsung Medical Center in Seoul, South Korea.

“What we found was that in NTM-PD patients, the sputum of the patients who remained in long-time stabilization without recurrence exhibited higher microbiome diversity than that of treatment-refractory patients, and several genera were identified in the samples of the cured group. We hope to do more research on this, and we are planning to compare the patients who have never been treated with those who respond to treatment,” she said at the annual meeting of the American College of Chest Physicians (CHEST).
 

NTM-PD on the rise

The incidence and prevalence of NTM-PD in both South Korea and the United States have been rising steadily since 2007, with the highest incidence occurring among those 65 and older.

“NTM-PD is becoming a global burden,” Dr. Kang said.

Across the world the most commonly occurring organisms in NTM-PD patients are Mycobacterium avium complex (MAC), with other mycobacteria species varying in frequency by region.

Outcomes of treatment differ according to the etiologic organism, with M. avium complex infections being successfully treated in about 60% of patients, compared with 70% of patients’ infections with the M. abscessus massiliense, and 30%-40% of infections yielding to antibiotics in patients with M. abscessus abscessus, Dr. Kang said.

To compare the characteristics of the sputum microbiota of NTM-PD patients based on their treatment outcomes, Dr. Kang and colleagues looked at sputum from all patients with NTM-PD who agreed to provide samples at their center from 2018 through 2022.

After excluding those who did not receive antibiotics, those who were on treatment but did not have refractory disease, and those who were lost to follow-up or whose samples did not pass quality control, they identified seven patients who had microbiological cures, and seven whose disease remained refractory to treatment.

They defined culture conversion at three or more consecutive negative sputum cultures after treatment, collected at least 4 weeks apart, and microbiological cures at maintenance of multiple consecutive negative cultures without any positive cultures of the causative species from respiratory samples.

Infections were deemed to be refractory if there were sustained positive cultures from respiratory samples of causative NTM species after at least 1 year of antibiotic therapy.
 

Diversity analysis

Samples from 8 of the 14 participants had M. abscessus-PD, with the proportion higher among those who had a sustained microbiological cure (71.4% vs. 42.9%).

At baseline, patients with refractory disease were found to have significantly lower alpha diversity, a measure of microbial diversity within a single sample, compared with those whose infections were cured (P = .025).

In addition, samples at 6-month follow-up from those with baseline ­refractory infections ­had differences in the species level of beta-diversity (that is, differences among samples), compared with both baseline and follow-up samples from the cured group (P = .022 and .024, respectively).

The investigators also used linear discriminant analysis to look at taxonomic biomarkers, and observed that several species were more abundant in samples from the microbiological cure group than from the refractory disease group (P < .05) These species included organisms in the Streptococcus pneumoniae group, Prevotella melaninogenica, and Haemophilus parahaemolyticus group.
 

Promising start

A pulmonologist who was not involved in the study commented in an interview that, although the findings need further study, the microbiome of sputum samples has the potential for predictive value.

“I think this will be clinically useful, actually, if we’re able to identify and diagnose patients with MAC disease and then we identify their sputum microbiome, it might give us an idea whether these patients are more sensitive or refractory to treatment,” said Muhammad U. Khawar, MD, from the University of Cincinnati.

Dr. Khawar moderated the session where Dr. Kang reported her data.

The investigators did not report a funding source. Dr. Kang and Dr. Khawar reported that they had no relevant disclosures.
 

HONOLULU – The diversity of species in the sputum of patients undergoing therapy for nontuberculosis mycobacterial pulmonary disease (NTM-PD) could be a marker for treatment efficacy, authors of a small prospective study suggest.

Neil Osterweil/MDedge

Among 14 patients treated for NTM-PD, 7 of whom had treatment-refractory disease and 7 of whom had microbiological cures after antibiotic therapy, the diversity of the microbiome in sputum was greater for those patients who were cured, indicating that the variety of species found in sputum during treatment could help clinicians evaluate the efficacy of therapy and guide patient management, said Noeul Kang, MD, PhD, from Samsung Medical Center in Seoul, South Korea.

“What we found was that in NTM-PD patients, the sputum of the patients who remained in long-time stabilization without recurrence exhibited higher microbiome diversity than that of treatment-refractory patients, and several genera were identified in the samples of the cured group. We hope to do more research on this, and we are planning to compare the patients who have never been treated with those who respond to treatment,” she said at the annual meeting of the American College of Chest Physicians (CHEST).
 

NTM-PD on the rise

The incidence and prevalence of NTM-PD in both South Korea and the United States have been rising steadily since 2007, with the highest incidence occurring among those 65 and older.

“NTM-PD is becoming a global burden,” Dr. Kang said.

Across the world the most commonly occurring organisms in NTM-PD patients are Mycobacterium avium complex (MAC), with other mycobacteria species varying in frequency by region.

Outcomes of treatment differ according to the etiologic organism, with M. avium complex infections being successfully treated in about 60% of patients, compared with 70% of patients’ infections with the M. abscessus massiliense, and 30%-40% of infections yielding to antibiotics in patients with M. abscessus abscessus, Dr. Kang said.

To compare the characteristics of the sputum microbiota of NTM-PD patients based on their treatment outcomes, Dr. Kang and colleagues looked at sputum from all patients with NTM-PD who agreed to provide samples at their center from 2018 through 2022.

After excluding those who did not receive antibiotics, those who were on treatment but did not have refractory disease, and those who were lost to follow-up or whose samples did not pass quality control, they identified seven patients who had microbiological cures, and seven whose disease remained refractory to treatment.

They defined culture conversion at three or more consecutive negative sputum cultures after treatment, collected at least 4 weeks apart, and microbiological cures at maintenance of multiple consecutive negative cultures without any positive cultures of the causative species from respiratory samples.

Infections were deemed to be refractory if there were sustained positive cultures from respiratory samples of causative NTM species after at least 1 year of antibiotic therapy.
 

Diversity analysis

Samples from 8 of the 14 participants had M. abscessus-PD, with the proportion higher among those who had a sustained microbiological cure (71.4% vs. 42.9%).

At baseline, patients with refractory disease were found to have significantly lower alpha diversity, a measure of microbial diversity within a single sample, compared with those whose infections were cured (P = .025).

In addition, samples at 6-month follow-up from those with baseline ­refractory infections ­had differences in the species level of beta-diversity (that is, differences among samples), compared with both baseline and follow-up samples from the cured group (P = .022 and .024, respectively).

The investigators also used linear discriminant analysis to look at taxonomic biomarkers, and observed that several species were more abundant in samples from the microbiological cure group than from the refractory disease group (P < .05) These species included organisms in the Streptococcus pneumoniae group, Prevotella melaninogenica, and Haemophilus parahaemolyticus group.
 

Promising start

A pulmonologist who was not involved in the study commented in an interview that, although the findings need further study, the microbiome of sputum samples has the potential for predictive value.

“I think this will be clinically useful, actually, if we’re able to identify and diagnose patients with MAC disease and then we identify their sputum microbiome, it might give us an idea whether these patients are more sensitive or refractory to treatment,” said Muhammad U. Khawar, MD, from the University of Cincinnati.

Dr. Khawar moderated the session where Dr. Kang reported her data.

The investigators did not report a funding source. Dr. Kang and Dr. Khawar reported that they had no relevant disclosures.
 

HONOLULU – The diversity of species in the sputum of patients undergoing therapy for nontuberculosis mycobacterial pulmonary disease (NTM-PD) could be a marker for treatment efficacy, authors of a small prospective study suggest.

Neil Osterweil/MDedge

Among 14 patients treated for NTM-PD, 7 of whom had treatment-refractory disease and 7 of whom had microbiological cures after antibiotic therapy, the diversity of the microbiome in sputum was greater for those patients who were cured, indicating that the variety of species found in sputum during treatment could help clinicians evaluate the efficacy of therapy and guide patient management, said Noeul Kang, MD, PhD, from Samsung Medical Center in Seoul, South Korea.

“What we found was that in NTM-PD patients, the sputum of the patients who remained in long-time stabilization without recurrence exhibited higher microbiome diversity than that of treatment-refractory patients, and several genera were identified in the samples of the cured group. We hope to do more research on this, and we are planning to compare the patients who have never been treated with those who respond to treatment,” she said at the annual meeting of the American College of Chest Physicians (CHEST).
 

NTM-PD on the rise

The incidence and prevalence of NTM-PD in both South Korea and the United States have been rising steadily since 2007, with the highest incidence occurring among those 65 and older.

“NTM-PD is becoming a global burden,” Dr. Kang said.

Across the world the most commonly occurring organisms in NTM-PD patients are Mycobacterium avium complex (MAC), with other mycobacteria species varying in frequency by region.

Outcomes of treatment differ according to the etiologic organism, with M. avium complex infections being successfully treated in about 60% of patients, compared with 70% of patients’ infections with the M. abscessus massiliense, and 30%-40% of infections yielding to antibiotics in patients with M. abscessus abscessus, Dr. Kang said.

To compare the characteristics of the sputum microbiota of NTM-PD patients based on their treatment outcomes, Dr. Kang and colleagues looked at sputum from all patients with NTM-PD who agreed to provide samples at their center from 2018 through 2022.

After excluding those who did not receive antibiotics, those who were on treatment but did not have refractory disease, and those who were lost to follow-up or whose samples did not pass quality control, they identified seven patients who had microbiological cures, and seven whose disease remained refractory to treatment.

They defined culture conversion at three or more consecutive negative sputum cultures after treatment, collected at least 4 weeks apart, and microbiological cures at maintenance of multiple consecutive negative cultures without any positive cultures of the causative species from respiratory samples.

Infections were deemed to be refractory if there were sustained positive cultures from respiratory samples of causative NTM species after at least 1 year of antibiotic therapy.
 

Diversity analysis

Samples from 8 of the 14 participants had M. abscessus-PD, with the proportion higher among those who had a sustained microbiological cure (71.4% vs. 42.9%).

At baseline, patients with refractory disease were found to have significantly lower alpha diversity, a measure of microbial diversity within a single sample, compared with those whose infections were cured (P = .025).

In addition, samples at 6-month follow-up from those with baseline ­refractory infections ­had differences in the species level of beta-diversity (that is, differences among samples), compared with both baseline and follow-up samples from the cured group (P = .022 and .024, respectively).

The investigators also used linear discriminant analysis to look at taxonomic biomarkers, and observed that several species were more abundant in samples from the microbiological cure group than from the refractory disease group (P < .05) These species included organisms in the Streptococcus pneumoniae group, Prevotella melaninogenica, and Haemophilus parahaemolyticus group.
 

Promising start

A pulmonologist who was not involved in the study commented in an interview that, although the findings need further study, the microbiome of sputum samples has the potential for predictive value.

“I think this will be clinically useful, actually, if we’re able to identify and diagnose patients with MAC disease and then we identify their sputum microbiome, it might give us an idea whether these patients are more sensitive or refractory to treatment,” said Muhammad U. Khawar, MD, from the University of Cincinnati.

Dr. Khawar moderated the session where Dr. Kang reported her data.

The investigators did not report a funding source. Dr. Kang and Dr. Khawar reported that they had no relevant disclosures.
 

HONOLULU – Patients with acute respiratory distress syndrome (ARDS) and coexisting pulmonary hypertension (PH) are significantly more likely to have longer and more costly hospital stays and to die in-hospital than patients with ARDS without PH, results of a retrospective study suggest.

Among more than 156,000 hospitalized patients with ARDS, 16.8% of whom also had a diagnosis of PH, the presence of PH was associated with about a 50% higher risk for in-hospital mortality and a 37% higher risk for longer hospital stays. In addition, the presence of PH was associated with nearly $20,000 of higher hospital expenditures, reported Kaushik Kumar, MBBS, at the annual meeting of the American College of Chest Physicians (CHEST).

“Clinicians should be vigilant in identifying and managing pulmonary hypertension in ARDS patients,” Dr. Kumar, a resident in internal medicine at Medstar Health, Baltimore, said in an oral abstract presentation.

He added that PH has the potential to serve as an indicator of disease severity for patients with ARDS.
 

National database

PH is a frequent complication of ARDS, likely related to a combination of pulmonary vasoconstriction, thromboembolism, and interstitial edema, he said.

To test their hypothesis that the presence of PH in patients with ARDS is associated with worse outcomes, Dr. Kumar and colleagues drew on the National Inpatient Sample database for information on adults aged 18 years and older who had been diagnosed with ARDS with or without PH.

They identified a total of 156,687 patients of whom 26,324 (16.8%) also had been diagnosed with PH. Among the cohort with PH, there were higher proportions of older patients, women, and patients with multiple comorbidities.

The in-hospital mortality rate was 36.8% among patients with PH, compared with 24.6% among those without. The mean length of stay was also longer among patients with PH, at 12 days versus 10 days.

In an unadjusted analysis, mean total hospital charges for patients with ARDS and PH were $210,165, versus $160,683 for patients with ARDS who did not have PH.

In an analysis in which the investigators controlled for age, sex, index admission length of stay, insurance status, and comorbidities, in-hospital mortality for patients with PH remained significantly higher, with an odds ratio of 1.52 (P < .001). PH was also significantly associated with longer length of stay (odds ratio, 1.37; P < .001) and higher total hospital costs, with a mean difference of $19,406.

Dr. Kumar said that the findings underscore the importance of a tailored approach to managing patients with ARDS, especially in the presence of PH.

The investigators plan further studies to assess the role of PH-targeted therapies, to examine the role of sepsis and right ventricular failure and to explore the long-term impact of PH among ARDS survivors, including effects with respect to pulmonary function, quality of life, and long-term morbidity.
 

Potential to inform practice

A pulmonologist who was not involved in the study said in an interview that the findings of the trial suggest that PH may have a greater influence on mortality than is currently understood and that further investigations into this association could change practice in the future.

“I think it would be very important for us to understand if that is going to change our outlook on how ARDS is managed. It’s possible that some of the interventions that we give people who don’t have pulmonary hypertension, for example, increasing the airway pressure in order to minimize oxygenation, may have a detrimental effect on the pulmonary vasculature,” said Timothy Morris, MD, medical director of the pulmonary and exercise lab and professor of medicine at the University of California, San Diego.

“I think it’s a little bit premature to say that this should guide management now, but it’s certainly an interesting question that may end up changing practice in the future,” said Dr. Morris, who was moderator of the session in which Dr. Kumar presented the data.

The study was supported by the Agency for Healthcare Research and Quality and Medstar Health Research Institute. Dr. Kumar and Dr. Morris have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

HONOLULU – Patients with acute respiratory distress syndrome (ARDS) and coexisting pulmonary hypertension (PH) are significantly more likely to have longer and more costly hospital stays and to die in-hospital than patients with ARDS without PH, results of a retrospective study suggest.

Among more than 156,000 hospitalized patients with ARDS, 16.8% of whom also had a diagnosis of PH, the presence of PH was associated with about a 50% higher risk for in-hospital mortality and a 37% higher risk for longer hospital stays. In addition, the presence of PH was associated with nearly $20,000 of higher hospital expenditures, reported Kaushik Kumar, MBBS, at the annual meeting of the American College of Chest Physicians (CHEST).

“Clinicians should be vigilant in identifying and managing pulmonary hypertension in ARDS patients,” Dr. Kumar, a resident in internal medicine at Medstar Health, Baltimore, said in an oral abstract presentation.

He added that PH has the potential to serve as an indicator of disease severity for patients with ARDS.
 

National database

PH is a frequent complication of ARDS, likely related to a combination of pulmonary vasoconstriction, thromboembolism, and interstitial edema, he said.

To test their hypothesis that the presence of PH in patients with ARDS is associated with worse outcomes, Dr. Kumar and colleagues drew on the National Inpatient Sample database for information on adults aged 18 years and older who had been diagnosed with ARDS with or without PH.

They identified a total of 156,687 patients of whom 26,324 (16.8%) also had been diagnosed with PH. Among the cohort with PH, there were higher proportions of older patients, women, and patients with multiple comorbidities.

The in-hospital mortality rate was 36.8% among patients with PH, compared with 24.6% among those without. The mean length of stay was also longer among patients with PH, at 12 days versus 10 days.

In an unadjusted analysis, mean total hospital charges for patients with ARDS and PH were $210,165, versus $160,683 for patients with ARDS who did not have PH.

In an analysis in which the investigators controlled for age, sex, index admission length of stay, insurance status, and comorbidities, in-hospital mortality for patients with PH remained significantly higher, with an odds ratio of 1.52 (P < .001). PH was also significantly associated with longer length of stay (odds ratio, 1.37; P < .001) and higher total hospital costs, with a mean difference of $19,406.

Dr. Kumar said that the findings underscore the importance of a tailored approach to managing patients with ARDS, especially in the presence of PH.

The investigators plan further studies to assess the role of PH-targeted therapies, to examine the role of sepsis and right ventricular failure and to explore the long-term impact of PH among ARDS survivors, including effects with respect to pulmonary function, quality of life, and long-term morbidity.
 

Potential to inform practice

A pulmonologist who was not involved in the study said in an interview that the findings of the trial suggest that PH may have a greater influence on mortality than is currently understood and that further investigations into this association could change practice in the future.

“I think it would be very important for us to understand if that is going to change our outlook on how ARDS is managed. It’s possible that some of the interventions that we give people who don’t have pulmonary hypertension, for example, increasing the airway pressure in order to minimize oxygenation, may have a detrimental effect on the pulmonary vasculature,” said Timothy Morris, MD, medical director of the pulmonary and exercise lab and professor of medicine at the University of California, San Diego.

“I think it’s a little bit premature to say that this should guide management now, but it’s certainly an interesting question that may end up changing practice in the future,” said Dr. Morris, who was moderator of the session in which Dr. Kumar presented the data.

The study was supported by the Agency for Healthcare Research and Quality and Medstar Health Research Institute. Dr. Kumar and Dr. Morris have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

HONOLULU – Patients with acute respiratory distress syndrome (ARDS) and coexisting pulmonary hypertension (PH) are significantly more likely to have longer and more costly hospital stays and to die in-hospital than patients with ARDS without PH, results of a retrospective study suggest.

Among more than 156,000 hospitalized patients with ARDS, 16.8% of whom also had a diagnosis of PH, the presence of PH was associated with about a 50% higher risk for in-hospital mortality and a 37% higher risk for longer hospital stays. In addition, the presence of PH was associated with nearly $20,000 of higher hospital expenditures, reported Kaushik Kumar, MBBS, at the annual meeting of the American College of Chest Physicians (CHEST).

“Clinicians should be vigilant in identifying and managing pulmonary hypertension in ARDS patients,” Dr. Kumar, a resident in internal medicine at Medstar Health, Baltimore, said in an oral abstract presentation.

He added that PH has the potential to serve as an indicator of disease severity for patients with ARDS.
 

National database

PH is a frequent complication of ARDS, likely related to a combination of pulmonary vasoconstriction, thromboembolism, and interstitial edema, he said.

To test their hypothesis that the presence of PH in patients with ARDS is associated with worse outcomes, Dr. Kumar and colleagues drew on the National Inpatient Sample database for information on adults aged 18 years and older who had been diagnosed with ARDS with or without PH.

They identified a total of 156,687 patients of whom 26,324 (16.8%) also had been diagnosed with PH. Among the cohort with PH, there were higher proportions of older patients, women, and patients with multiple comorbidities.

The in-hospital mortality rate was 36.8% among patients with PH, compared with 24.6% among those without. The mean length of stay was also longer among patients with PH, at 12 days versus 10 days.

In an unadjusted analysis, mean total hospital charges for patients with ARDS and PH were $210,165, versus $160,683 for patients with ARDS who did not have PH.

In an analysis in which the investigators controlled for age, sex, index admission length of stay, insurance status, and comorbidities, in-hospital mortality for patients with PH remained significantly higher, with an odds ratio of 1.52 (P < .001). PH was also significantly associated with longer length of stay (odds ratio, 1.37; P < .001) and higher total hospital costs, with a mean difference of $19,406.

Dr. Kumar said that the findings underscore the importance of a tailored approach to managing patients with ARDS, especially in the presence of PH.

The investigators plan further studies to assess the role of PH-targeted therapies, to examine the role of sepsis and right ventricular failure and to explore the long-term impact of PH among ARDS survivors, including effects with respect to pulmonary function, quality of life, and long-term morbidity.
 

Potential to inform practice

A pulmonologist who was not involved in the study said in an interview that the findings of the trial suggest that PH may have a greater influence on mortality than is currently understood and that further investigations into this association could change practice in the future.

“I think it would be very important for us to understand if that is going to change our outlook on how ARDS is managed. It’s possible that some of the interventions that we give people who don’t have pulmonary hypertension, for example, increasing the airway pressure in order to minimize oxygenation, may have a detrimental effect on the pulmonary vasculature,” said Timothy Morris, MD, medical director of the pulmonary and exercise lab and professor of medicine at the University of California, San Diego.

“I think it’s a little bit premature to say that this should guide management now, but it’s certainly an interesting question that may end up changing practice in the future,” said Dr. Morris, who was moderator of the session in which Dr. Kumar presented the data.

The study was supported by the Agency for Healthcare Research and Quality and Medstar Health Research Institute. Dr. Kumar and Dr. Morris have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Diffuse Lung & Transplant Network

Pulmonary Physiology & Rehabilitation Section

Pulmonary arterial hypertension (PH) and more recently interstitial lung disease (ILD) trials use the 6-minute walk test (6MWT) as a primary outcome due to its ability to conveniently capture a patient’s functional capacity and quality of life. However, interpreting the 6MWT in complex and diverse diseases, such as ILD, presents significant challenges.

A recent article (Harari, et al. Eur Respir Rev. 2022 Aug 23;31(165):220087. doi: 10.1183/16000617.0087-2022) advocates for further research to determine the optimal use of the 6MWT as a clinical endpoint in ILD trials. A decline in 6MWT can represent progression of ILD; ILD-related PH; or musculoskeletal, hematologic, or cardiac etiologies related to the underlying cause of ILD.

To enhance sensitivity, the authors endorse the inclusion of additional parameters in the analysis, possibly as a composite outcome. This would involve integrating the oxygen desaturation profile, dyspnea scores, and heart rate recovery with changes in the 6MWT-distance. They propose this composite measure could serve as a primary endpoint when the study intervention’s impact on clinical performance – either improvement or stabilization of ILD or ILD-related PH – is clearly defined. The prognostic significance of these additional parameters in patients with ILD, however, requires further investigation.

Inter-test reliability requires a standardized 6MWT, as previously proposed for this population (Lancaster, et al. Contemporary Clin Trials. 2021;Nov 25,2020). The standardized test protocol that includes continuous pulse oximetry and heart rate measurement, oxygen titration, and end of test guidelines, will reduce variability and boost reproducibility.

In light of recent advancements in the affordability, convenience, and portability of oxygen consumption (VO2) gas analyzers, we believe that incorporating Vo2 measurements into the 6MWT is a needed incremental improvement. This integration will help define the disease process, its impact on patient performance, and clinical prognosis. Future work should focus on understanding how to effectively estimate Vo2 in combination with a standardized 6MWT to make this test a reliable clinical outcome in trials.

Ruchicka Sangani, MD, Section Fellow-in-Training

Saqib Baig, MD, Section Member-at-Large
 

Diffuse Lung & Transplant Network

Pulmonary Physiology & Rehabilitation Section

Pulmonary arterial hypertension (PH) and more recently interstitial lung disease (ILD) trials use the 6-minute walk test (6MWT) as a primary outcome due to its ability to conveniently capture a patient’s functional capacity and quality of life. However, interpreting the 6MWT in complex and diverse diseases, such as ILD, presents significant challenges.

A recent article (Harari, et al. Eur Respir Rev. 2022 Aug 23;31(165):220087. doi: 10.1183/16000617.0087-2022) advocates for further research to determine the optimal use of the 6MWT as a clinical endpoint in ILD trials. A decline in 6MWT can represent progression of ILD; ILD-related PH; or musculoskeletal, hematologic, or cardiac etiologies related to the underlying cause of ILD.

To enhance sensitivity, the authors endorse the inclusion of additional parameters in the analysis, possibly as a composite outcome. This would involve integrating the oxygen desaturation profile, dyspnea scores, and heart rate recovery with changes in the 6MWT-distance. They propose this composite measure could serve as a primary endpoint when the study intervention’s impact on clinical performance – either improvement or stabilization of ILD or ILD-related PH – is clearly defined. The prognostic significance of these additional parameters in patients with ILD, however, requires further investigation.

Inter-test reliability requires a standardized 6MWT, as previously proposed for this population (Lancaster, et al. Contemporary Clin Trials. 2021;Nov 25,2020). The standardized test protocol that includes continuous pulse oximetry and heart rate measurement, oxygen titration, and end of test guidelines, will reduce variability and boost reproducibility.

In light of recent advancements in the affordability, convenience, and portability of oxygen consumption (VO2) gas analyzers, we believe that incorporating Vo2 measurements into the 6MWT is a needed incremental improvement. This integration will help define the disease process, its impact on patient performance, and clinical prognosis. Future work should focus on understanding how to effectively estimate Vo2 in combination with a standardized 6MWT to make this test a reliable clinical outcome in trials.

Ruchicka Sangani, MD, Section Fellow-in-Training

Saqib Baig, MD, Section Member-at-Large
 

Diffuse Lung & Transplant Network

Pulmonary Physiology & Rehabilitation Section

Pulmonary arterial hypertension (PH) and more recently interstitial lung disease (ILD) trials use the 6-minute walk test (6MWT) as a primary outcome due to its ability to conveniently capture a patient’s functional capacity and quality of life. However, interpreting the 6MWT in complex and diverse diseases, such as ILD, presents significant challenges.

A recent article (Harari, et al. Eur Respir Rev. 2022 Aug 23;31(165):220087. doi: 10.1183/16000617.0087-2022) advocates for further research to determine the optimal use of the 6MWT as a clinical endpoint in ILD trials. A decline in 6MWT can represent progression of ILD; ILD-related PH; or musculoskeletal, hematologic, or cardiac etiologies related to the underlying cause of ILD.

To enhance sensitivity, the authors endorse the inclusion of additional parameters in the analysis, possibly as a composite outcome. This would involve integrating the oxygen desaturation profile, dyspnea scores, and heart rate recovery with changes in the 6MWT-distance. They propose this composite measure could serve as a primary endpoint when the study intervention’s impact on clinical performance – either improvement or stabilization of ILD or ILD-related PH – is clearly defined. The prognostic significance of these additional parameters in patients with ILD, however, requires further investigation.

Inter-test reliability requires a standardized 6MWT, as previously proposed for this population (Lancaster, et al. Contemporary Clin Trials. 2021;Nov 25,2020). The standardized test protocol that includes continuous pulse oximetry and heart rate measurement, oxygen titration, and end of test guidelines, will reduce variability and boost reproducibility.

In light of recent advancements in the affordability, convenience, and portability of oxygen consumption (VO2) gas analyzers, we believe that incorporating Vo2 measurements into the 6MWT is a needed incremental improvement. This integration will help define the disease process, its impact on patient performance, and clinical prognosis. Future work should focus on understanding how to effectively estimate Vo2 in combination with a standardized 6MWT to make this test a reliable clinical outcome in trials.

Ruchicka Sangani, MD, Section Fellow-in-Training

Saqib Baig, MD, Section Member-at-Large
 

An investigation into associations between serum phosphate levels and in-hospital mortality risk among patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) found significantly higher in-hospital mortality among AECOPD patients with high serum phosphate levels. The finding, according to Siqi Li et al. in a preproof HELIYON article, suggests that hyperphosphatemia may be a high-risk factor for AECOPD-related in-hospital mortality.

Phosphorus is key to several physiological processes, among them energy metabolism, bone mineralization, membrane transport, and intracellular signaling. Li et al. pointed out that in patients with multiple diseases, hyperphosphatemia is associated with increased mortality. In the development of COPD specifically, acute exacerbations have been shown in several recent studies to be an important adverse event conferring heightened mortality risk. Despite many efforts, AECOPD mortality rates remain high, making identification of potential factors, Li et al. stated, crucial for improving outcomes in high-risk patients.

The electronic Intensive Care Unit Collaborative Research Database (eICU-CRD) holds data associated with over 200,000 patient stays, providing a large sample size for research studies. To determine the relationship between serum phosphate and in-hospital mortality in AECOPD patients, investigators analyzed data from a total of 1,199 AECOPD patients (mean age, 68 years; ~55% female) enrolled in eICU-CRD and divided them into three groups according to serum phosphate level tertiles: lowest tertile (serum phosphate ≤ 3.0 mg/dL, n = 445), median tertile (serum phosphate > 3.0 mg/dL and ≤ 4.0 mg/dL, n = 378), and highest tertile (serum phosphate > 4.0 mg/dL, n = 376). The Li et al. study’s primary outcome was all-cause in-hospital mortality, defined as survival to hospital discharge. Secondary outcomes included length of stay (LOS) in the intensive care unit (ICU), LOS in the hospital, and all-cause ICU mortality.

The Li et al. analysis of patient characteristics showed that patients in the highest tertile of serum phosphate had significantly higher body mass index (BMI) (P < .001), lower temperature (P < .001), lower heart rate (P < .001), lower mean arterial blood pressure (P = .011), higher creatinine (P < .001), higher potassium (P < .001), higher sequential organ failure assessment (SOFA) (P < .001), higher acute physiology and chronic health evaluation (APACHE IV) (P < .001), and higher ICU mortality (P < .001). Also, patients with higher serum phosphate levels were more likely to receive renal replacement therapy (RRT) (P < .001) and vasoactive drugs (P = .003) than those in the lower serum phosphate group. Such differences were also observed for age (P = .021), calcium level (P = .023), sodium level (P = .039), hypertension (P = .014), coronary artery disease (P = .004), diabetes (P = .017), and chronic kidney disease (P < .001). No significant differences were observed for gender, respiration rate, SpO₂, white blood cell count, hemoglobin, platelets, cirrhosis, stroke, ventilation, LOS in ICU, and LOS in hospital (P > .05).

A univariate logistic regression analysis performed to determine the relationship between serum phosphate level and risk of in-hospital mortality revealed that higher serum phosphate level correlated with increased in-hospital mortality (odds ratio, 1.30; 95% confidence interval, 1.16-1.46; P < .001).

Li et al. posited that several mechanisms may explain increased mortality at higher serum phosphate levels in AECOPD patients: increased serum phosphate induces vascular calcification and endothelial dysfunction, leading to organ dysfunction; hyperphosphatemia causes oxidative stress, cell apoptosis, and inflammation, all of which are involved in the pathogenesis of AECOPD, and a higher phosphate diet exacerbates aging and lung emphysema phenotypes; restriction of phosphate intake and absorption relieves these phenotypes and alveolar destruction, which might contribute to the development of AECOPD.

Li et al. concluded: “Reducing serum phosphate levels may be a therapeutic strategy to improve prognosis of AECOPD patients.”

“This large retrospective analysis on eICU database in the U.S. revealed elevated serum phosphate levels with increased in-hospital mortality among patients experiencing acute exacerbation of COPD,” commented Dharani Narendra, MD, assistant professor in medicine, at Baylor College of Medicine, Houston. “This association, previously observed in various chronic conditions including COPD, particularly in men, is now noted to apply to both genders, irrespective of chronic kidney disease. The study also hints at potential mechanisms for elevated phosphate levels, such as inflammation, oxidative stress, and cell apoptosis in AECOPD, as well as a high-phosphate diet.”

She told this news organization also, “It remains imperative to ascertain whether treating hyperphosphatemia or implementing dietary phosphate restrictions can reduce mortality or prevent AECOPD episodes. These demand additional clinical trials to establish a definitive cause-and-effect relationship and to guide potential treatment and prevention strategies.”

Noting study limitations, Li et al. stated that many variables, such as smoking, exacerbation frequency, severity, PH, PaO₂, PaCO₂, and lactate, were not included in this study owing to more than 20% missing values.

This work was supported by the National Natural Science Foundation of China, Scientific Research Fund of Hunan Provincial Education Department, Hunan Provincial Natural Science Foundation, and Special fund for rehabilitation medicine of the National Clinical Research Center for Geriatric Disorders Clinical Research Fund. The authors declare no competing interests.
 

An investigation into associations between serum phosphate levels and in-hospital mortality risk among patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) found significantly higher in-hospital mortality among AECOPD patients with high serum phosphate levels. The finding, according to Siqi Li et al. in a preproof HELIYON article, suggests that hyperphosphatemia may be a high-risk factor for AECOPD-related in-hospital mortality.

Phosphorus is key to several physiological processes, among them energy metabolism, bone mineralization, membrane transport, and intracellular signaling. Li et al. pointed out that in patients with multiple diseases, hyperphosphatemia is associated with increased mortality. In the development of COPD specifically, acute exacerbations have been shown in several recent studies to be an important adverse event conferring heightened mortality risk. Despite many efforts, AECOPD mortality rates remain high, making identification of potential factors, Li et al. stated, crucial for improving outcomes in high-risk patients.

The electronic Intensive Care Unit Collaborative Research Database (eICU-CRD) holds data associated with over 200,000 patient stays, providing a large sample size for research studies. To determine the relationship between serum phosphate and in-hospital mortality in AECOPD patients, investigators analyzed data from a total of 1,199 AECOPD patients (mean age, 68 years; ~55% female) enrolled in eICU-CRD and divided them into three groups according to serum phosphate level tertiles: lowest tertile (serum phosphate ≤ 3.0 mg/dL, n = 445), median tertile (serum phosphate > 3.0 mg/dL and ≤ 4.0 mg/dL, n = 378), and highest tertile (serum phosphate > 4.0 mg/dL, n = 376). The Li et al. study’s primary outcome was all-cause in-hospital mortality, defined as survival to hospital discharge. Secondary outcomes included length of stay (LOS) in the intensive care unit (ICU), LOS in the hospital, and all-cause ICU mortality.

The Li et al. analysis of patient characteristics showed that patients in the highest tertile of serum phosphate had significantly higher body mass index (BMI) (P < .001), lower temperature (P < .001), lower heart rate (P < .001), lower mean arterial blood pressure (P = .011), higher creatinine (P < .001), higher potassium (P < .001), higher sequential organ failure assessment (SOFA) (P < .001), higher acute physiology and chronic health evaluation (APACHE IV) (P < .001), and higher ICU mortality (P < .001). Also, patients with higher serum phosphate levels were more likely to receive renal replacement therapy (RRT) (P < .001) and vasoactive drugs (P = .003) than those in the lower serum phosphate group. Such differences were also observed for age (P = .021), calcium level (P = .023), sodium level (P = .039), hypertension (P = .014), coronary artery disease (P = .004), diabetes (P = .017), and chronic kidney disease (P < .001). No significant differences were observed for gender, respiration rate, SpO₂, white blood cell count, hemoglobin, platelets, cirrhosis, stroke, ventilation, LOS in ICU, and LOS in hospital (P > .05).

A univariate logistic regression analysis performed to determine the relationship between serum phosphate level and risk of in-hospital mortality revealed that higher serum phosphate level correlated with increased in-hospital mortality (odds ratio, 1.30; 95% confidence interval, 1.16-1.46; P < .001).

Li et al. posited that several mechanisms may explain increased mortality at higher serum phosphate levels in AECOPD patients: increased serum phosphate induces vascular calcification and endothelial dysfunction, leading to organ dysfunction; hyperphosphatemia causes oxidative stress, cell apoptosis, and inflammation, all of which are involved in the pathogenesis of AECOPD, and a higher phosphate diet exacerbates aging and lung emphysema phenotypes; restriction of phosphate intake and absorption relieves these phenotypes and alveolar destruction, which might contribute to the development of AECOPD.

Li et al. concluded: “Reducing serum phosphate levels may be a therapeutic strategy to improve prognosis of AECOPD patients.”

“This large retrospective analysis on eICU database in the U.S. revealed elevated serum phosphate levels with increased in-hospital mortality among patients experiencing acute exacerbation of COPD,” commented Dharani Narendra, MD, assistant professor in medicine, at Baylor College of Medicine, Houston. “This association, previously observed in various chronic conditions including COPD, particularly in men, is now noted to apply to both genders, irrespective of chronic kidney disease. The study also hints at potential mechanisms for elevated phosphate levels, such as inflammation, oxidative stress, and cell apoptosis in AECOPD, as well as a high-phosphate diet.”

She told this news organization also, “It remains imperative to ascertain whether treating hyperphosphatemia or implementing dietary phosphate restrictions can reduce mortality or prevent AECOPD episodes. These demand additional clinical trials to establish a definitive cause-and-effect relationship and to guide potential treatment and prevention strategies.”

Noting study limitations, Li et al. stated that many variables, such as smoking, exacerbation frequency, severity, PH, PaO₂, PaCO₂, and lactate, were not included in this study owing to more than 20% missing values.

This work was supported by the National Natural Science Foundation of China, Scientific Research Fund of Hunan Provincial Education Department, Hunan Provincial Natural Science Foundation, and Special fund for rehabilitation medicine of the National Clinical Research Center for Geriatric Disorders Clinical Research Fund. The authors declare no competing interests.
 

An investigation into associations between serum phosphate levels and in-hospital mortality risk among patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) found significantly higher in-hospital mortality among AECOPD patients with high serum phosphate levels. The finding, according to Siqi Li et al. in a preproof HELIYON article, suggests that hyperphosphatemia may be a high-risk factor for AECOPD-related in-hospital mortality.

Phosphorus is key to several physiological processes, among them energy metabolism, bone mineralization, membrane transport, and intracellular signaling. Li et al. pointed out that in patients with multiple diseases, hyperphosphatemia is associated with increased mortality. In the development of COPD specifically, acute exacerbations have been shown in several recent studies to be an important adverse event conferring heightened mortality risk. Despite many efforts, AECOPD mortality rates remain high, making identification of potential factors, Li et al. stated, crucial for improving outcomes in high-risk patients.

The electronic Intensive Care Unit Collaborative Research Database (eICU-CRD) holds data associated with over 200,000 patient stays, providing a large sample size for research studies. To determine the relationship between serum phosphate and in-hospital mortality in AECOPD patients, investigators analyzed data from a total of 1,199 AECOPD patients (mean age, 68 years; ~55% female) enrolled in eICU-CRD and divided them into three groups according to serum phosphate level tertiles: lowest tertile (serum phosphate ≤ 3.0 mg/dL, n = 445), median tertile (serum phosphate > 3.0 mg/dL and ≤ 4.0 mg/dL, n = 378), and highest tertile (serum phosphate > 4.0 mg/dL, n = 376). The Li et al. study’s primary outcome was all-cause in-hospital mortality, defined as survival to hospital discharge. Secondary outcomes included length of stay (LOS) in the intensive care unit (ICU), LOS in the hospital, and all-cause ICU mortality.

The Li et al. analysis of patient characteristics showed that patients in the highest tertile of serum phosphate had significantly higher body mass index (BMI) (P < .001), lower temperature (P < .001), lower heart rate (P < .001), lower mean arterial blood pressure (P = .011), higher creatinine (P < .001), higher potassium (P < .001), higher sequential organ failure assessment (SOFA) (P < .001), higher acute physiology and chronic health evaluation (APACHE IV) (P < .001), and higher ICU mortality (P < .001). Also, patients with higher serum phosphate levels were more likely to receive renal replacement therapy (RRT) (P < .001) and vasoactive drugs (P = .003) than those in the lower serum phosphate group. Such differences were also observed for age (P = .021), calcium level (P = .023), sodium level (P = .039), hypertension (P = .014), coronary artery disease (P = .004), diabetes (P = .017), and chronic kidney disease (P < .001). No significant differences were observed for gender, respiration rate, SpO₂, white blood cell count, hemoglobin, platelets, cirrhosis, stroke, ventilation, LOS in ICU, and LOS in hospital (P > .05).

A univariate logistic regression analysis performed to determine the relationship between serum phosphate level and risk of in-hospital mortality revealed that higher serum phosphate level correlated with increased in-hospital mortality (odds ratio, 1.30; 95% confidence interval, 1.16-1.46; P < .001).

Li et al. posited that several mechanisms may explain increased mortality at higher serum phosphate levels in AECOPD patients: increased serum phosphate induces vascular calcification and endothelial dysfunction, leading to organ dysfunction; hyperphosphatemia causes oxidative stress, cell apoptosis, and inflammation, all of which are involved in the pathogenesis of AECOPD, and a higher phosphate diet exacerbates aging and lung emphysema phenotypes; restriction of phosphate intake and absorption relieves these phenotypes and alveolar destruction, which might contribute to the development of AECOPD.

Li et al. concluded: “Reducing serum phosphate levels may be a therapeutic strategy to improve prognosis of AECOPD patients.”

“This large retrospective analysis on eICU database in the U.S. revealed elevated serum phosphate levels with increased in-hospital mortality among patients experiencing acute exacerbation of COPD,” commented Dharani Narendra, MD, assistant professor in medicine, at Baylor College of Medicine, Houston. “This association, previously observed in various chronic conditions including COPD, particularly in men, is now noted to apply to both genders, irrespective of chronic kidney disease. The study also hints at potential mechanisms for elevated phosphate levels, such as inflammation, oxidative stress, and cell apoptosis in AECOPD, as well as a high-phosphate diet.”

She told this news organization also, “It remains imperative to ascertain whether treating hyperphosphatemia or implementing dietary phosphate restrictions can reduce mortality or prevent AECOPD episodes. These demand additional clinical trials to establish a definitive cause-and-effect relationship and to guide potential treatment and prevention strategies.”

Noting study limitations, Li et al. stated that many variables, such as smoking, exacerbation frequency, severity, PH, PaO₂, PaCO₂, and lactate, were not included in this study owing to more than 20% missing values.

This work was supported by the National Natural Science Foundation of China, Scientific Research Fund of Hunan Provincial Education Department, Hunan Provincial Natural Science Foundation, and Special fund for rehabilitation medicine of the National Clinical Research Center for Geriatric Disorders Clinical Research Fund. The authors declare no competing interests.
 

Inhalers, nebulizers, antibiotics, and steroids – these are some of the most common tools in our pulmonary arsenal that we deploy on a daily basis. But, there is no treatment more fundamental to a pulmonary practitioner than oxygen. So how is it that something that naturally occurs and comprises 21% of ambient air has become so medicalized?

It is difficult (perhaps impossible) to find a pulmonologist or a hospitalist who has not included the phrase “obtain ambulatory saturation to qualify the patient for home oxygen” in at least one of their progress notes on a daily basis. Chronic obstructive pulmonary disease (COPD) is the most common reason for the prescription of long-term oxygen therapy (LTOT), a large industry tightly regulated by the Centers for Medicare & Medicaid Services (CMS).

The evidence for the use of LTOT in patients with COPD dates back to two seminal papers published in 1980 and 1981. The British Medical Research Council Working Party conducted the BMRC trial, in which 87 patients with a Pao2 of 40 mm Hg to 60 mm Hg, CO2 retention, and a history of congestive heart failure were randomized to treatment with 15 hours per day of home oxygen therapy, starting at 2 L and titrating to Pao2 of 60 mm Hg vs. standard therapy without oxygen (Lancet. 1981;1[8222]:681-6). There was an impressive 22% mortality benefit at 3 years.

Another study published around the same time, the Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease (NOTT) trial (Ann Intern Med. 1980;93[3]:391-8) directly compared continuous 24-hour to nocturnal home oxygen therapy in patients with COPD and severe hypoxemia with a Pao2 less than 55 mm Hg. Again, there was an impressive mortality benefit in favor of continuous home oxygen with a 9% and 18% mortality difference at 1 and 2 years of enrollment, respectively.

Afterward, it became universally accepted dogma that patients with COPD and severe hypoxemia stood to substantially benefit from LTOT. For years, it was the only therapy associated with a mortality reduction. The LOTT study (Albert RK, et al. N Engl J Med. 2016;375[17]:1617-27) included 768 patients with stable COPD and a resting or nocturnal Spo2 of 89% to93%, as well as patients with moderate exercise-induced desaturation (Spo2 of greater than or equal to 80% and less than 90% for greater than or equal to 10 seconds during the 6-minute walk test). Half of these patients received oxygen for 24 hours per day, during sleep, or during exercise (depending on when desaturation would occur) and half received no oxygen. There was no difference in time to death or first hospitalization or in rates of hospitalization or exacerbation. There was also no difference between groups in quality of life, lung function, or distance walked in 6 minutes.

The INOX (Lacasse Y, et al. N Engl J Med. 2020;383[12]:1129-38) trial, in which 243 patients with oxygen saturation less than 90% for at least 30% of the night were assigned to receive nocturnal vs sham oxygen, found similar results. There was no difference in the composite outcome of all-cause mortality and progression to 24-7 oxygen requirement (according to the criteria originally defined by NOTT). A 2022 systematic review and meta-analysis including six studies designed to assess the role of LTOT in patients with COPD and moderate desaturation, including LOTT and INOX, found no benefit to providing LTOT (Lacasse Y, et al. Lancet Respir Med. 2022;10[11]:1029-37).

Based on these studies, a resting Spo2 of 88% seems to be the threshold below which LTOT improves outcomes. CMS lists four classes of patients eligible for LTOT: (1) Patients with Pao2 < 55 mm Hg or pulse oximetry less than or equal to 88% at rest or (2) during sleep or (3) during exercise, and (4) patients with Pao2 > 55 mm Hg but less than or equal to 59 mm Hg or pulse oximetry of 89% who have lower extremity edema, evidence of pulmonary hypertension, or erythrocythemia (Centers for Medicare & Medicaid Services. Medicare Coverage Database. 2021;100-103:240.2. These criteria reflect the inclusion criteria of the BMRC trial and NOTT.

COPD management has changed significantly in the 40 years since NOTT was published. In the early 1980s, standard of care included an inhaled beta-agonist and oral theophylline. We now prescribe a regimen of modern-day inhaler combinations, which can lead to a mortality benefit in the correct population. Additionally, rates of smoking are markedly lower now than they were in 1980. In the Minnesota Heart Survey, the prevalence of being an ever-smoking man or woman in 1980 compared with 2009 dropped from 71.6% and 54.7% to 44.2% and 39.6%, respectively (Filion KB, et al. Am J Public Health. 2012;102[4]:705-13). Treatment of common comorbid conditions has also dramatically improved.

A report containing all fee-for-service data published in 2021 by CMS reported oxygen therapy accounted for 9.8% of all DME costs covered by CMS and totaled approximately $800,000,000 (Centers for Medicare & Medicaid Services. FFS Data. 2021. This represents a significant financial burden to our health system and government.

Two of the eligible groups per CMS (those with isolated ambulatory or nocturnal hypoxemia) do not benefit from LTOT in RCTs. The other two groups are eligible based on trial data from a small number of patients who were studied more than 40 years ago. These facts raise serious questions about the cost-efficacy of LTOT.

So where does this leave us?

There are significant barriers to repeating large randomized oxygen trials. Due to broad inclusion criteria for LTOT by CMS, there are undoubtedly many people prescribed LTOT for whom there is minimal to no benefit. Patients often feel restricted in their mobility and may feel isolated being tethered to medical equipment. It is good practice to think about LTOT the same way we do any other therapy we provide - as a medicine with associated risks, benefits, and costs.

Despite its ubiquity, oxygen remains an important therapeutic tool. Still, choosing wisely means recognizing that not all patients who qualify for LTOT by CMS criteria will benefit.

Drs. Kreisel and Sonti are with the Division of Pulmonary, Critical Care, and Sleep Medicine, MedStar Georgetown University Hospital, Washington, DC.

Inhalers, nebulizers, antibiotics, and steroids – these are some of the most common tools in our pulmonary arsenal that we deploy on a daily basis. But, there is no treatment more fundamental to a pulmonary practitioner than oxygen. So how is it that something that naturally occurs and comprises 21% of ambient air has become so medicalized?

It is difficult (perhaps impossible) to find a pulmonologist or a hospitalist who has not included the phrase “obtain ambulatory saturation to qualify the patient for home oxygen” in at least one of their progress notes on a daily basis. Chronic obstructive pulmonary disease (COPD) is the most common reason for the prescription of long-term oxygen therapy (LTOT), a large industry tightly regulated by the Centers for Medicare & Medicaid Services (CMS).

The evidence for the use of LTOT in patients with COPD dates back to two seminal papers published in 1980 and 1981. The British Medical Research Council Working Party conducted the BMRC trial, in which 87 patients with a Pao2 of 40 mm Hg to 60 mm Hg, CO2 retention, and a history of congestive heart failure were randomized to treatment with 15 hours per day of home oxygen therapy, starting at 2 L and titrating to Pao2 of 60 mm Hg vs. standard therapy without oxygen (Lancet. 1981;1[8222]:681-6). There was an impressive 22% mortality benefit at 3 years.

Another study published around the same time, the Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease (NOTT) trial (Ann Intern Med. 1980;93[3]:391-8) directly compared continuous 24-hour to nocturnal home oxygen therapy in patients with COPD and severe hypoxemia with a Pao2 less than 55 mm Hg. Again, there was an impressive mortality benefit in favor of continuous home oxygen with a 9% and 18% mortality difference at 1 and 2 years of enrollment, respectively.

Afterward, it became universally accepted dogma that patients with COPD and severe hypoxemia stood to substantially benefit from LTOT. For years, it was the only therapy associated with a mortality reduction. The LOTT study (Albert RK, et al. N Engl J Med. 2016;375[17]:1617-27) included 768 patients with stable COPD and a resting or nocturnal Spo2 of 89% to93%, as well as patients with moderate exercise-induced desaturation (Spo2 of greater than or equal to 80% and less than 90% for greater than or equal to 10 seconds during the 6-minute walk test). Half of these patients received oxygen for 24 hours per day, during sleep, or during exercise (depending on when desaturation would occur) and half received no oxygen. There was no difference in time to death or first hospitalization or in rates of hospitalization or exacerbation. There was also no difference between groups in quality of life, lung function, or distance walked in 6 minutes.

The INOX (Lacasse Y, et al. N Engl J Med. 2020;383[12]:1129-38) trial, in which 243 patients with oxygen saturation less than 90% for at least 30% of the night were assigned to receive nocturnal vs sham oxygen, found similar results. There was no difference in the composite outcome of all-cause mortality and progression to 24-7 oxygen requirement (according to the criteria originally defined by NOTT). A 2022 systematic review and meta-analysis including six studies designed to assess the role of LTOT in patients with COPD and moderate desaturation, including LOTT and INOX, found no benefit to providing LTOT (Lacasse Y, et al. Lancet Respir Med. 2022;10[11]:1029-37).

Based on these studies, a resting Spo2 of 88% seems to be the threshold below which LTOT improves outcomes. CMS lists four classes of patients eligible for LTOT: (1) Patients with Pao2 < 55 mm Hg or pulse oximetry less than or equal to 88% at rest or (2) during sleep or (3) during exercise, and (4) patients with Pao2 > 55 mm Hg but less than or equal to 59 mm Hg or pulse oximetry of 89% who have lower extremity edema, evidence of pulmonary hypertension, or erythrocythemia (Centers for Medicare & Medicaid Services. Medicare Coverage Database. 2021;100-103:240.2. These criteria reflect the inclusion criteria of the BMRC trial and NOTT.

COPD management has changed significantly in the 40 years since NOTT was published. In the early 1980s, standard of care included an inhaled beta-agonist and oral theophylline. We now prescribe a regimen of modern-day inhaler combinations, which can lead to a mortality benefit in the correct population. Additionally, rates of smoking are markedly lower now than they were in 1980. In the Minnesota Heart Survey, the prevalence of being an ever-smoking man or woman in 1980 compared with 2009 dropped from 71.6% and 54.7% to 44.2% and 39.6%, respectively (Filion KB, et al. Am J Public Health. 2012;102[4]:705-13). Treatment of common comorbid conditions has also dramatically improved.

A report containing all fee-for-service data published in 2021 by CMS reported oxygen therapy accounted for 9.8% of all DME costs covered by CMS and totaled approximately $800,000,000 (Centers for Medicare & Medicaid Services. FFS Data. 2021. This represents a significant financial burden to our health system and government.

Two of the eligible groups per CMS (those with isolated ambulatory or nocturnal hypoxemia) do not benefit from LTOT in RCTs. The other two groups are eligible based on trial data from a small number of patients who were studied more than 40 years ago. These facts raise serious questions about the cost-efficacy of LTOT.

So where does this leave us?

There are significant barriers to repeating large randomized oxygen trials. Due to broad inclusion criteria for LTOT by CMS, there are undoubtedly many people prescribed LTOT for whom there is minimal to no benefit. Patients often feel restricted in their mobility and may feel isolated being tethered to medical equipment. It is good practice to think about LTOT the same way we do any other therapy we provide - as a medicine with associated risks, benefits, and costs.

Despite its ubiquity, oxygen remains an important therapeutic tool. Still, choosing wisely means recognizing that not all patients who qualify for LTOT by CMS criteria will benefit.

Drs. Kreisel and Sonti are with the Division of Pulmonary, Critical Care, and Sleep Medicine, MedStar Georgetown University Hospital, Washington, DC.

Inhalers, nebulizers, antibiotics, and steroids – these are some of the most common tools in our pulmonary arsenal that we deploy on a daily basis. But, there is no treatment more fundamental to a pulmonary practitioner than oxygen. So how is it that something that naturally occurs and comprises 21% of ambient air has become so medicalized?

It is difficult (perhaps impossible) to find a pulmonologist or a hospitalist who has not included the phrase “obtain ambulatory saturation to qualify the patient for home oxygen” in at least one of their progress notes on a daily basis. Chronic obstructive pulmonary disease (COPD) is the most common reason for the prescription of long-term oxygen therapy (LTOT), a large industry tightly regulated by the Centers for Medicare & Medicaid Services (CMS).

The evidence for the use of LTOT in patients with COPD dates back to two seminal papers published in 1980 and 1981. The British Medical Research Council Working Party conducted the BMRC trial, in which 87 patients with a Pao2 of 40 mm Hg to 60 mm Hg, CO2 retention, and a history of congestive heart failure were randomized to treatment with 15 hours per day of home oxygen therapy, starting at 2 L and titrating to Pao2 of 60 mm Hg vs. standard therapy without oxygen (Lancet. 1981;1[8222]:681-6). There was an impressive 22% mortality benefit at 3 years.

Another study published around the same time, the Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease (NOTT) trial (Ann Intern Med. 1980;93[3]:391-8) directly compared continuous 24-hour to nocturnal home oxygen therapy in patients with COPD and severe hypoxemia with a Pao2 less than 55 mm Hg. Again, there was an impressive mortality benefit in favor of continuous home oxygen with a 9% and 18% mortality difference at 1 and 2 years of enrollment, respectively.

Afterward, it became universally accepted dogma that patients with COPD and severe hypoxemia stood to substantially benefit from LTOT. For years, it was the only therapy associated with a mortality reduction. The LOTT study (Albert RK, et al. N Engl J Med. 2016;375[17]:1617-27) included 768 patients with stable COPD and a resting or nocturnal Spo2 of 89% to93%, as well as patients with moderate exercise-induced desaturation (Spo2 of greater than or equal to 80% and less than 90% for greater than or equal to 10 seconds during the 6-minute walk test). Half of these patients received oxygen for 24 hours per day, during sleep, or during exercise (depending on when desaturation would occur) and half received no oxygen. There was no difference in time to death or first hospitalization or in rates of hospitalization or exacerbation. There was also no difference between groups in quality of life, lung function, or distance walked in 6 minutes.

The INOX (Lacasse Y, et al. N Engl J Med. 2020;383[12]:1129-38) trial, in which 243 patients with oxygen saturation less than 90% for at least 30% of the night were assigned to receive nocturnal vs sham oxygen, found similar results. There was no difference in the composite outcome of all-cause mortality and progression to 24-7 oxygen requirement (according to the criteria originally defined by NOTT). A 2022 systematic review and meta-analysis including six studies designed to assess the role of LTOT in patients with COPD and moderate desaturation, including LOTT and INOX, found no benefit to providing LTOT (Lacasse Y, et al. Lancet Respir Med. 2022;10[11]:1029-37).

Based on these studies, a resting Spo2 of 88% seems to be the threshold below which LTOT improves outcomes. CMS lists four classes of patients eligible for LTOT: (1) Patients with Pao2 < 55 mm Hg or pulse oximetry less than or equal to 88% at rest or (2) during sleep or (3) during exercise, and (4) patients with Pao2 > 55 mm Hg but less than or equal to 59 mm Hg or pulse oximetry of 89% who have lower extremity edema, evidence of pulmonary hypertension, or erythrocythemia (Centers for Medicare & Medicaid Services. Medicare Coverage Database. 2021;100-103:240.2. These criteria reflect the inclusion criteria of the BMRC trial and NOTT.

COPD management has changed significantly in the 40 years since NOTT was published. In the early 1980s, standard of care included an inhaled beta-agonist and oral theophylline. We now prescribe a regimen of modern-day inhaler combinations, which can lead to a mortality benefit in the correct population. Additionally, rates of smoking are markedly lower now than they were in 1980. In the Minnesota Heart Survey, the prevalence of being an ever-smoking man or woman in 1980 compared with 2009 dropped from 71.6% and 54.7% to 44.2% and 39.6%, respectively (Filion KB, et al. Am J Public Health. 2012;102[4]:705-13). Treatment of common comorbid conditions has also dramatically improved.

A report containing all fee-for-service data published in 2021 by CMS reported oxygen therapy accounted for 9.8% of all DME costs covered by CMS and totaled approximately $800,000,000 (Centers for Medicare & Medicaid Services. FFS Data. 2021. This represents a significant financial burden to our health system and government.

Two of the eligible groups per CMS (those with isolated ambulatory or nocturnal hypoxemia) do not benefit from LTOT in RCTs. The other two groups are eligible based on trial data from a small number of patients who were studied more than 40 years ago. These facts raise serious questions about the cost-efficacy of LTOT.

So where does this leave us?

There are significant barriers to repeating large randomized oxygen trials. Due to broad inclusion criteria for LTOT by CMS, there are undoubtedly many people prescribed LTOT for whom there is minimal to no benefit. Patients often feel restricted in their mobility and may feel isolated being tethered to medical equipment. It is good practice to think about LTOT the same way we do any other therapy we provide - as a medicine with associated risks, benefits, and costs.

Despite its ubiquity, oxygen remains an important therapeutic tool. Still, choosing wisely means recognizing that not all patients who qualify for LTOT by CMS criteria will benefit.

Drs. Kreisel and Sonti are with the Division of Pulmonary, Critical Care, and Sleep Medicine, MedStar Georgetown University Hospital, Washington, DC.

In a real-world study of asthma patients, treatment with biologics following an exacerbation was associated with better health care utilization outcomes.

The data fill a gap, according to Sushan Gupta, MD, who presented the results at the annual meeting of the American College of Chest Physicians. “There’s some ample real-world data that shows that biologics reduce the incidence of asthma exacerbation, but the data regarding what happens after an exacerbation is still lacking, especially real-world data,” said Dr. Gupta, who is a resident at Carle Foundation Hospital in Champaign, Ill.

The findings were encouraging. “Patients with severe asthma on biologics fare well even after an exacerbation event, which includes a reduced incidence of hospitalization, ICU admission, and need for mechanical ventilation. We did not have any patient in the biologic group that required intubation, so that is pretty significant as compared to other patients who did not receive biologics,” said Dr. Gupta.

The results weren’t surprising, but underscore the benefits of biologics, according to Brittany Duchene, MD, who moderated the session where the results were presented. “I think it reinforced that they’re really good drugs,” said Dr. Duchene, who is a pulmonary critical care physician at Northeastern Vermont Regional Hospital, St. Johnsbury.

Although the study was retrospective, it suggests that the threshold for initiating biologics could potentially be lowered for patients with uncontrolled asthma despite adequate use of inhalers, according to Dr. Gupta. “Should that threshold be lower, and would that improve the overall morbidity and eventually the health care cost of utilization? Our study does not prove any of those data, but moving forward that data will also come out.”

Dr. Duchene noted that the accumulating scientific and clinical data for biologics is “really, really strong.” She also speculated that biologics could be used increasingly in the acute setting, which she admitted is a controversial topic. “I think there’s going to be a lot more push to early initiation, and you can see from the [new] study that it decreased a lot of hospitalizations.”

Dr. Gupta emphasized the need for prospective studies, and Dr. Duchene agreed that any such change would need to be patient centric, considering the diversity of available biologics. “It depends what their true issue is. The broader the biologic [mechanism of action], probably the more success you’ll have. I’ve found there’s not a pure allergic or a pure eosinophilic asthma patient. They’re usually more a combination.”

Some key questions remain about biologics treatment, especially in the long term. These include when a patient should be switched from one biologic to another, and whether biologic treatment should be continued over the patient’s lifetime and potential long-term side effects. “I think that data is still evolving and will come to us with time,” said Dr. Gupta.

The researchers analyzed retrospective data from 316 asthma patients treated with biologics and 9,645 treated with nonbiologic therapy between February 2018 and February 2023 at a tertiary care teaching hospital in the Midwest. There was a higher proportion of females in the biologics (69.7%) and nonbiologics groups (63.8%, P = .032), but there was no significant difference in the proportion of Whites in the biologics and nonbiologics groups (78.2% vs. 74.3%, P = .103).

The lack of a difference in racial groups was a surprise, according to Dr. Duchene, especially since other studies have noted disparities in biologic therapy among asthma patients.

Among the biologics group, 0.9% were hospitalized during the study period, compared with 6.5% of the nonbiologics group (P = .00006). They also had fewer ICU visits (0.3% vs. 1.8%; P = .04).

Dr. Gupta’s team attempted to subdivide the data by individual biologic, but there was no statistical significance in outcomes between biologics, perhaps because of the relatively small sample size.

Dr. Gupta noted that his group’s results are generally similar to other studies, including a U.S. study that found a decrease in exacerbation rates after staring or switching biologics and a slightly higher prevalence of biologics use among White patients (77% of biologic users versus 71% of nonbiologics users). A study in southwestern England found fewer ED visits and hospitalizations among patients on biologics.

Dr. Gupta and Dr. Duchene have no relevant financial disclosures.
 

In a real-world study of asthma patients, treatment with biologics following an exacerbation was associated with better health care utilization outcomes.

The data fill a gap, according to Sushan Gupta, MD, who presented the results at the annual meeting of the American College of Chest Physicians. “There’s some ample real-world data that shows that biologics reduce the incidence of asthma exacerbation, but the data regarding what happens after an exacerbation is still lacking, especially real-world data,” said Dr. Gupta, who is a resident at Carle Foundation Hospital in Champaign, Ill.

The findings were encouraging. “Patients with severe asthma on biologics fare well even after an exacerbation event, which includes a reduced incidence of hospitalization, ICU admission, and need for mechanical ventilation. We did not have any patient in the biologic group that required intubation, so that is pretty significant as compared to other patients who did not receive biologics,” said Dr. Gupta.

The results weren’t surprising, but underscore the benefits of biologics, according to Brittany Duchene, MD, who moderated the session where the results were presented. “I think it reinforced that they’re really good drugs,” said Dr. Duchene, who is a pulmonary critical care physician at Northeastern Vermont Regional Hospital, St. Johnsbury.

Although the study was retrospective, it suggests that the threshold for initiating biologics could potentially be lowered for patients with uncontrolled asthma despite adequate use of inhalers, according to Dr. Gupta. “Should that threshold be lower, and would that improve the overall morbidity and eventually the health care cost of utilization? Our study does not prove any of those data, but moving forward that data will also come out.”

Dr. Duchene noted that the accumulating scientific and clinical data for biologics is “really, really strong.” She also speculated that biologics could be used increasingly in the acute setting, which she admitted is a controversial topic. “I think there’s going to be a lot more push to early initiation, and you can see from the [new] study that it decreased a lot of hospitalizations.”

Dr. Gupta emphasized the need for prospective studies, and Dr. Duchene agreed that any such change would need to be patient centric, considering the diversity of available biologics. “It depends what their true issue is. The broader the biologic [mechanism of action], probably the more success you’ll have. I’ve found there’s not a pure allergic or a pure eosinophilic asthma patient. They’re usually more a combination.”

Some key questions remain about biologics treatment, especially in the long term. These include when a patient should be switched from one biologic to another, and whether biologic treatment should be continued over the patient’s lifetime and potential long-term side effects. “I think that data is still evolving and will come to us with time,” said Dr. Gupta.

The researchers analyzed retrospective data from 316 asthma patients treated with biologics and 9,645 treated with nonbiologic therapy between February 2018 and February 2023 at a tertiary care teaching hospital in the Midwest. There was a higher proportion of females in the biologics (69.7%) and nonbiologics groups (63.8%, P = .032), but there was no significant difference in the proportion of Whites in the biologics and nonbiologics groups (78.2% vs. 74.3%, P = .103).

The lack of a difference in racial groups was a surprise, according to Dr. Duchene, especially since other studies have noted disparities in biologic therapy among asthma patients.

Among the biologics group, 0.9% were hospitalized during the study period, compared with 6.5% of the nonbiologics group (P = .00006). They also had fewer ICU visits (0.3% vs. 1.8%; P = .04).

Dr. Gupta’s team attempted to subdivide the data by individual biologic, but there was no statistical significance in outcomes between biologics, perhaps because of the relatively small sample size.

Dr. Gupta noted that his group’s results are generally similar to other studies, including a U.S. study that found a decrease in exacerbation rates after staring or switching biologics and a slightly higher prevalence of biologics use among White patients (77% of biologic users versus 71% of nonbiologics users). A study in southwestern England found fewer ED visits and hospitalizations among patients on biologics.

Dr. Gupta and Dr. Duchene have no relevant financial disclosures.
 

In a real-world study of asthma patients, treatment with biologics following an exacerbation was associated with better health care utilization outcomes.

The data fill a gap, according to Sushan Gupta, MD, who presented the results at the annual meeting of the American College of Chest Physicians. “There’s some ample real-world data that shows that biologics reduce the incidence of asthma exacerbation, but the data regarding what happens after an exacerbation is still lacking, especially real-world data,” said Dr. Gupta, who is a resident at Carle Foundation Hospital in Champaign, Ill.

The findings were encouraging. “Patients with severe asthma on biologics fare well even after an exacerbation event, which includes a reduced incidence of hospitalization, ICU admission, and need for mechanical ventilation. We did not have any patient in the biologic group that required intubation, so that is pretty significant as compared to other patients who did not receive biologics,” said Dr. Gupta.

The results weren’t surprising, but underscore the benefits of biologics, according to Brittany Duchene, MD, who moderated the session where the results were presented. “I think it reinforced that they’re really good drugs,” said Dr. Duchene, who is a pulmonary critical care physician at Northeastern Vermont Regional Hospital, St. Johnsbury.

Although the study was retrospective, it suggests that the threshold for initiating biologics could potentially be lowered for patients with uncontrolled asthma despite adequate use of inhalers, according to Dr. Gupta. “Should that threshold be lower, and would that improve the overall morbidity and eventually the health care cost of utilization? Our study does not prove any of those data, but moving forward that data will also come out.”

Dr. Duchene noted that the accumulating scientific and clinical data for biologics is “really, really strong.” She also speculated that biologics could be used increasingly in the acute setting, which she admitted is a controversial topic. “I think there’s going to be a lot more push to early initiation, and you can see from the [new] study that it decreased a lot of hospitalizations.”

Dr. Gupta emphasized the need for prospective studies, and Dr. Duchene agreed that any such change would need to be patient centric, considering the diversity of available biologics. “It depends what their true issue is. The broader the biologic [mechanism of action], probably the more success you’ll have. I’ve found there’s not a pure allergic or a pure eosinophilic asthma patient. They’re usually more a combination.”

Some key questions remain about biologics treatment, especially in the long term. These include when a patient should be switched from one biologic to another, and whether biologic treatment should be continued over the patient’s lifetime and potential long-term side effects. “I think that data is still evolving and will come to us with time,” said Dr. Gupta.

The researchers analyzed retrospective data from 316 asthma patients treated with biologics and 9,645 treated with nonbiologic therapy between February 2018 and February 2023 at a tertiary care teaching hospital in the Midwest. There was a higher proportion of females in the biologics (69.7%) and nonbiologics groups (63.8%, P = .032), but there was no significant difference in the proportion of Whites in the biologics and nonbiologics groups (78.2% vs. 74.3%, P = .103).

The lack of a difference in racial groups was a surprise, according to Dr. Duchene, especially since other studies have noted disparities in biologic therapy among asthma patients.

Among the biologics group, 0.9% were hospitalized during the study period, compared with 6.5% of the nonbiologics group (P = .00006). They also had fewer ICU visits (0.3% vs. 1.8%; P = .04).

Dr. Gupta’s team attempted to subdivide the data by individual biologic, but there was no statistical significance in outcomes between biologics, perhaps because of the relatively small sample size.

Dr. Gupta noted that his group’s results are generally similar to other studies, including a U.S. study that found a decrease in exacerbation rates after staring or switching biologics and a slightly higher prevalence of biologics use among White patients (77% of biologic users versus 71% of nonbiologics users). A study in southwestern England found fewer ED visits and hospitalizations among patients on biologics.

Dr. Gupta and Dr. Duchene have no relevant financial disclosures.
 

HONOLULU – There’s new evidence to support a practice that many pulmonologists have been doing empirically anyway: namely, reducing the dose of the antifibrotic medication nintedanib (Ofev) for patients with idiopathic pulmonary fibrosis (IPF) who can’t tolerate the full 150-mg twice-daily dose.

An analysis of data from a large administrative claims database showed that there were no significant differences in either all-cause mortality or hospitalization rates between patients with IPF treated at the full 150-mg twice-daily dose and those treated with a reduced twice-daily dose of 100 mg nintedanib.

Although the results need to be confirmed by additional prospective and registry studies, they suggest that patients with IPF can still fare just as well with a reduced-dose nintedanib regimen, ideally with fewer gastrointestinal side effects such as diarrhea, reported Andrew Limper, MD, of the Mayo Clinic in Rochester, Minn.

“At least on this preliminary data you could ... rest assured,” Dr. Limper told his colleagues in an oral abstract session at the American College of Chest Physicians (CHEST) 2023 annual meeting.

“This is not definitive proof, I’m not making more out of this than it is, but we all put people on 100 mg twice daily because their guts don’t tolerate it; they live in the bathroom and they don’t want to live that way,” Dr. Limper said.
 

Hard to take

Nintedanib is approved in the United States for the treatment of IPF, chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype, and systemic sclerosis-associated ILD. For IPF, the standard dose established in randomized clinical trials is 150 mg twice daily.

However, nintedanib is associated with a number of side effects, including hepatic and other gastrointestinal toxicities, arterial thromboembolic events, and proteinuria within the nephrotic range. As a result, clinicians often reduce the dose to 100 mg twice daily, but there is a lack of data to indicate whether it’s safe to do so or if efficacy will be compromised.

To see whether dose reductions might result in poorer outcomes for patients with IPF, Dr. Limper and colleagues analyzed data from the OptumLabs Data Warehouse, a large administrative claims database, to compare outcomes for patients treated with IPF at either the 150-mg or 100-mg twice-daily doses.

They used propensity-score matching to account for differences among individuals according to age, sex, race/ethnicity, residence, insurance type, additional medication use, oxygen use, smoking status, health care use, and comorbidities. The final cohort included 346 patients in each dosing group.

There was no difference between the dosing groups for the primary outcome of all-cause mortality at 18 months, with a nonsignificant hazard ratio of 0.65 (P = .313), and no significant difference over 24 months in risk of hospitalization, with a hazard ratio of 0.98 (P = .899).

“This is not randomized controlled data; I doubt that [nintedanib maker Boehringer Ingelheim] is ever going to do a 150 vs. 100 milligram head-to-head trial, but it does give us some ground to start to look at this,” Dr. Limper said.
 

Not so sure

Session comoderator Misbah Baqir, MBBS, also from the Mayo Clinic, told this news organization that she would need to see more data from prospective studies using endpoints other than mortality before she could be convinced that nintedanib dose reductions do not adversely affect efficacy. She was not involved in the study.

“I feel that the endpoint should be different, either it should be forced vital capacity change, quality of life, or something else. The problem with a database study is that you don’t have everything in it. You have to play with what you have, and you don’t have forced vital capacity. You have to go into the charts to get it,” she said.

It would be more helpful to objectively compare, for example, diarrhea episodes or other adverse events to see whether they were significantly reduced with the 100-mg dose, she added.

In an interview, Dr. Limper said that he and his colleagues plan to gather additional observational data including the newly available Medicare fee-for-service data set, registry data, and other sources.

“If we get all of that, and it really still looks compelling – and that’s an if – then I think that would be the foothold to go back to the manufacturer and say, ‘Hey, maybe you ought to think about doing a prospective trial to prove it with lung function and other endpoints such as 6-minute walks,’ ” he said.

The study was supported by a grant from Three Lakes Foundation. Dr. Limper and Dr. Baqir have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

HONOLULU – There’s new evidence to support a practice that many pulmonologists have been doing empirically anyway: namely, reducing the dose of the antifibrotic medication nintedanib (Ofev) for patients with idiopathic pulmonary fibrosis (IPF) who can’t tolerate the full 150-mg twice-daily dose.

An analysis of data from a large administrative claims database showed that there were no significant differences in either all-cause mortality or hospitalization rates between patients with IPF treated at the full 150-mg twice-daily dose and those treated with a reduced twice-daily dose of 100 mg nintedanib.

Although the results need to be confirmed by additional prospective and registry studies, they suggest that patients with IPF can still fare just as well with a reduced-dose nintedanib regimen, ideally with fewer gastrointestinal side effects such as diarrhea, reported Andrew Limper, MD, of the Mayo Clinic in Rochester, Minn.

“At least on this preliminary data you could ... rest assured,” Dr. Limper told his colleagues in an oral abstract session at the American College of Chest Physicians (CHEST) 2023 annual meeting.

“This is not definitive proof, I’m not making more out of this than it is, but we all put people on 100 mg twice daily because their guts don’t tolerate it; they live in the bathroom and they don’t want to live that way,” Dr. Limper said.
 

Hard to take

Nintedanib is approved in the United States for the treatment of IPF, chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype, and systemic sclerosis-associated ILD. For IPF, the standard dose established in randomized clinical trials is 150 mg twice daily.

However, nintedanib is associated with a number of side effects, including hepatic and other gastrointestinal toxicities, arterial thromboembolic events, and proteinuria within the nephrotic range. As a result, clinicians often reduce the dose to 100 mg twice daily, but there is a lack of data to indicate whether it’s safe to do so or if efficacy will be compromised.

To see whether dose reductions might result in poorer outcomes for patients with IPF, Dr. Limper and colleagues analyzed data from the OptumLabs Data Warehouse, a large administrative claims database, to compare outcomes for patients treated with IPF at either the 150-mg or 100-mg twice-daily doses.

They used propensity-score matching to account for differences among individuals according to age, sex, race/ethnicity, residence, insurance type, additional medication use, oxygen use, smoking status, health care use, and comorbidities. The final cohort included 346 patients in each dosing group.

There was no difference between the dosing groups for the primary outcome of all-cause mortality at 18 months, with a nonsignificant hazard ratio of 0.65 (P = .313), and no significant difference over 24 months in risk of hospitalization, with a hazard ratio of 0.98 (P = .899).

“This is not randomized controlled data; I doubt that [nintedanib maker Boehringer Ingelheim] is ever going to do a 150 vs. 100 milligram head-to-head trial, but it does give us some ground to start to look at this,” Dr. Limper said.
 

Not so sure

Session comoderator Misbah Baqir, MBBS, also from the Mayo Clinic, told this news organization that she would need to see more data from prospective studies using endpoints other than mortality before she could be convinced that nintedanib dose reductions do not adversely affect efficacy. She was not involved in the study.

“I feel that the endpoint should be different, either it should be forced vital capacity change, quality of life, or something else. The problem with a database study is that you don’t have everything in it. You have to play with what you have, and you don’t have forced vital capacity. You have to go into the charts to get it,” she said.

It would be more helpful to objectively compare, for example, diarrhea episodes or other adverse events to see whether they were significantly reduced with the 100-mg dose, she added.

In an interview, Dr. Limper said that he and his colleagues plan to gather additional observational data including the newly available Medicare fee-for-service data set, registry data, and other sources.

“If we get all of that, and it really still looks compelling – and that’s an if – then I think that would be the foothold to go back to the manufacturer and say, ‘Hey, maybe you ought to think about doing a prospective trial to prove it with lung function and other endpoints such as 6-minute walks,’ ” he said.

The study was supported by a grant from Three Lakes Foundation. Dr. Limper and Dr. Baqir have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

HONOLULU – There’s new evidence to support a practice that many pulmonologists have been doing empirically anyway: namely, reducing the dose of the antifibrotic medication nintedanib (Ofev) for patients with idiopathic pulmonary fibrosis (IPF) who can’t tolerate the full 150-mg twice-daily dose.

An analysis of data from a large administrative claims database showed that there were no significant differences in either all-cause mortality or hospitalization rates between patients with IPF treated at the full 150-mg twice-daily dose and those treated with a reduced twice-daily dose of 100 mg nintedanib.

Although the results need to be confirmed by additional prospective and registry studies, they suggest that patients with IPF can still fare just as well with a reduced-dose nintedanib regimen, ideally with fewer gastrointestinal side effects such as diarrhea, reported Andrew Limper, MD, of the Mayo Clinic in Rochester, Minn.

“At least on this preliminary data you could ... rest assured,” Dr. Limper told his colleagues in an oral abstract session at the American College of Chest Physicians (CHEST) 2023 annual meeting.

“This is not definitive proof, I’m not making more out of this than it is, but we all put people on 100 mg twice daily because their guts don’t tolerate it; they live in the bathroom and they don’t want to live that way,” Dr. Limper said.
 

Hard to take

Nintedanib is approved in the United States for the treatment of IPF, chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype, and systemic sclerosis-associated ILD. For IPF, the standard dose established in randomized clinical trials is 150 mg twice daily.

However, nintedanib is associated with a number of side effects, including hepatic and other gastrointestinal toxicities, arterial thromboembolic events, and proteinuria within the nephrotic range. As a result, clinicians often reduce the dose to 100 mg twice daily, but there is a lack of data to indicate whether it’s safe to do so or if efficacy will be compromised.

To see whether dose reductions might result in poorer outcomes for patients with IPF, Dr. Limper and colleagues analyzed data from the OptumLabs Data Warehouse, a large administrative claims database, to compare outcomes for patients treated with IPF at either the 150-mg or 100-mg twice-daily doses.

They used propensity-score matching to account for differences among individuals according to age, sex, race/ethnicity, residence, insurance type, additional medication use, oxygen use, smoking status, health care use, and comorbidities. The final cohort included 346 patients in each dosing group.

There was no difference between the dosing groups for the primary outcome of all-cause mortality at 18 months, with a nonsignificant hazard ratio of 0.65 (P = .313), and no significant difference over 24 months in risk of hospitalization, with a hazard ratio of 0.98 (P = .899).

“This is not randomized controlled data; I doubt that [nintedanib maker Boehringer Ingelheim] is ever going to do a 150 vs. 100 milligram head-to-head trial, but it does give us some ground to start to look at this,” Dr. Limper said.
 

Not so sure

Session comoderator Misbah Baqir, MBBS, also from the Mayo Clinic, told this news organization that she would need to see more data from prospective studies using endpoints other than mortality before she could be convinced that nintedanib dose reductions do not adversely affect efficacy. She was not involved in the study.

“I feel that the endpoint should be different, either it should be forced vital capacity change, quality of life, or something else. The problem with a database study is that you don’t have everything in it. You have to play with what you have, and you don’t have forced vital capacity. You have to go into the charts to get it,” she said.

It would be more helpful to objectively compare, for example, diarrhea episodes or other adverse events to see whether they were significantly reduced with the 100-mg dose, she added.

In an interview, Dr. Limper said that he and his colleagues plan to gather additional observational data including the newly available Medicare fee-for-service data set, registry data, and other sources.

“If we get all of that, and it really still looks compelling – and that’s an if – then I think that would be the foothold to go back to the manufacturer and say, ‘Hey, maybe you ought to think about doing a prospective trial to prove it with lung function and other endpoints such as 6-minute walks,’ ” he said.

The study was supported by a grant from Three Lakes Foundation. Dr. Limper and Dr. Baqir have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Nirmatrelvir-ritonavir (Paxlovid) is associated with a reduced risk for death or hospitalization in the most extremely vulnerable patients with COVID-19, new research suggests.

In a cohort study from British Columbia that included nearly 7,000 patients with COVID-19, nirmatrelvir-ritonavir was associated with a 2.5% reduction in risk for death or emergency hospitalization in clinically extremely vulnerable (CEV) patients who were severely immunocompromised. No significant benefit was observed in patients who were not immunocompromised.

“This finding could help substantially limit unnecessary use of nirmatrelvir and ritonavir in older, otherwise healthy individuals,” lead author Colin R. Dormuth, ScD, associate professor of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, told this news organization. “Another finding that was surprising and might help place the role of nirmatrelvir and ritonavir in context is that even in severely immunocompromised individuals who did not take [the drug], the risk of death or hospitalization with COVID-19 was less than 4% in our study population.”

The study was published online in JAMA Network Open.
 

Who benefits?

The investigators analyzed medical records for 6,866 patients in British Columbia (median age, 70 years; 57% women) who presented between Feb. 1, 2022, and Feb. 3, 2023. Eligible patients belonged to one of four higher-risk groups who received priority for COVID-19 vaccination.

Two groups included CEV patients who were severely (CEV1) or moderately (CEV2) immunocompromised. The CEV3 group was not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group included higher-risk patients who were not in one of the other groups, such as unvaccinated patients older than age 70 years.

The investigators matched treated patients to untreated patients in the same vulnerability group according to age, sex, and month of infection. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.

Treatment with nirmatrelvir-ritonavir was associated with statistically significant relative reductions in the primary outcome, compared with no treatment, for patients in the CEV1 (risk difference, −2.5%) and CEV2 (RD, −1.7%) groups. In the CEV3 group, the RD of −1.3% was not statistically significant. In the EXEL group, treatment was associated with a higher risk for the primary outcome (RD, 1.0%), but the result was not statistically significant.

The results were “robust across sex and older vs. younger age,” the authors note. “No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.”

The combination of nirmatrelvir-ritonavir was approved for use in Canada based on interim efficacy and safety data from the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, said Dr. Dormuth.

British Columbia’s eligibility criteria for nirmatrelvir-ritonavir coverage differ substantially from the criteria for participants in the EPIC-HR trial, he noted. Those patients were unvaccinated, had no natural immunity from a previous COVID-19 infection, and were infected with COVID-19 variants that were different from those now circulating. The current study was prompted by the need to look at a broader population of individuals in British Columbia with varying risks of complications from COVID-19 infection.

Before the study, a common view was that patients aged 70 and older would benefit from the drug, said Dr. Dormuth. “Our study, which accounted for medical conditions related to an individual’s vulnerability to complications, showed that older age on its own was not a reason to use nirmatrelvir and ritonavir once relevant medical conditions were taken into consideration.”

The researchers are working on a study to identify with greater specificity which comorbid conditions are most associated with nirmatrelvir-ritonavir effectiveness, he added. “It could be that a relatively small number of conditions can be used to identify most individuals who would benefit from the drug.”
 

‘Signal toward benefit’

Commenting on the findings for this news organization, Abhijit Duggal, MD, vice chair of critical care at the Cleveland Clinic, who was not involved in this study, said, “I’m always very wary when we look at observational data and we start saying the effectiveness is not really as high as was seen in other studies. We are seeing an effect with all these studies that seems to be in the right direction.

“Having said that,” he added, “is the effect going to be potentially more in patients at higher risk? Absolutely. I think these postmarket studies are really showing that after vaccination, if someone does get infected, this is a secondary option available to us that can prevent progression of the disease, which would likely be more severe in immunocompromised patients.”

Dr. Duggal was a coinvestigator on a recent study of more than 68,000 patients that showed that nirmatrelvir-ritonavir or molnupiravir was associated with reductions in mortality and hospitalization in nonhospitalized patients infected with the Omicron variant, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.

“In all groups, there was a signal toward benefit,” said Dr. Duggal. “These studies tell us that these drugs do remain valid options. But their use needs to be discussed on a case-by-case basis with patients we feel are deteriorating or at a higher risk because of underlying disease processes.”

The study was supported by funding from the British Columbia Ministry of Health. Dr. Dormuth and Dr. Duggal report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Nirmatrelvir-ritonavir (Paxlovid) is associated with a reduced risk for death or hospitalization in the most extremely vulnerable patients with COVID-19, new research suggests.

In a cohort study from British Columbia that included nearly 7,000 patients with COVID-19, nirmatrelvir-ritonavir was associated with a 2.5% reduction in risk for death or emergency hospitalization in clinically extremely vulnerable (CEV) patients who were severely immunocompromised. No significant benefit was observed in patients who were not immunocompromised.

“This finding could help substantially limit unnecessary use of nirmatrelvir and ritonavir in older, otherwise healthy individuals,” lead author Colin R. Dormuth, ScD, associate professor of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, told this news organization. “Another finding that was surprising and might help place the role of nirmatrelvir and ritonavir in context is that even in severely immunocompromised individuals who did not take [the drug], the risk of death or hospitalization with COVID-19 was less than 4% in our study population.”

The study was published online in JAMA Network Open.
 

Who benefits?

The investigators analyzed medical records for 6,866 patients in British Columbia (median age, 70 years; 57% women) who presented between Feb. 1, 2022, and Feb. 3, 2023. Eligible patients belonged to one of four higher-risk groups who received priority for COVID-19 vaccination.

Two groups included CEV patients who were severely (CEV1) or moderately (CEV2) immunocompromised. The CEV3 group was not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group included higher-risk patients who were not in one of the other groups, such as unvaccinated patients older than age 70 years.

The investigators matched treated patients to untreated patients in the same vulnerability group according to age, sex, and month of infection. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.

Treatment with nirmatrelvir-ritonavir was associated with statistically significant relative reductions in the primary outcome, compared with no treatment, for patients in the CEV1 (risk difference, −2.5%) and CEV2 (RD, −1.7%) groups. In the CEV3 group, the RD of −1.3% was not statistically significant. In the EXEL group, treatment was associated with a higher risk for the primary outcome (RD, 1.0%), but the result was not statistically significant.

The results were “robust across sex and older vs. younger age,” the authors note. “No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.”

The combination of nirmatrelvir-ritonavir was approved for use in Canada based on interim efficacy and safety data from the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, said Dr. Dormuth.

British Columbia’s eligibility criteria for nirmatrelvir-ritonavir coverage differ substantially from the criteria for participants in the EPIC-HR trial, he noted. Those patients were unvaccinated, had no natural immunity from a previous COVID-19 infection, and were infected with COVID-19 variants that were different from those now circulating. The current study was prompted by the need to look at a broader population of individuals in British Columbia with varying risks of complications from COVID-19 infection.

Before the study, a common view was that patients aged 70 and older would benefit from the drug, said Dr. Dormuth. “Our study, which accounted for medical conditions related to an individual’s vulnerability to complications, showed that older age on its own was not a reason to use nirmatrelvir and ritonavir once relevant medical conditions were taken into consideration.”

The researchers are working on a study to identify with greater specificity which comorbid conditions are most associated with nirmatrelvir-ritonavir effectiveness, he added. “It could be that a relatively small number of conditions can be used to identify most individuals who would benefit from the drug.”
 

‘Signal toward benefit’

Commenting on the findings for this news organization, Abhijit Duggal, MD, vice chair of critical care at the Cleveland Clinic, who was not involved in this study, said, “I’m always very wary when we look at observational data and we start saying the effectiveness is not really as high as was seen in other studies. We are seeing an effect with all these studies that seems to be in the right direction.

“Having said that,” he added, “is the effect going to be potentially more in patients at higher risk? Absolutely. I think these postmarket studies are really showing that after vaccination, if someone does get infected, this is a secondary option available to us that can prevent progression of the disease, which would likely be more severe in immunocompromised patients.”

Dr. Duggal was a coinvestigator on a recent study of more than 68,000 patients that showed that nirmatrelvir-ritonavir or molnupiravir was associated with reductions in mortality and hospitalization in nonhospitalized patients infected with the Omicron variant, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.

“In all groups, there was a signal toward benefit,” said Dr. Duggal. “These studies tell us that these drugs do remain valid options. But their use needs to be discussed on a case-by-case basis with patients we feel are deteriorating or at a higher risk because of underlying disease processes.”

The study was supported by funding from the British Columbia Ministry of Health. Dr. Dormuth and Dr. Duggal report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Nirmatrelvir-ritonavir (Paxlovid) is associated with a reduced risk for death or hospitalization in the most extremely vulnerable patients with COVID-19, new research suggests.

In a cohort study from British Columbia that included nearly 7,000 patients with COVID-19, nirmatrelvir-ritonavir was associated with a 2.5% reduction in risk for death or emergency hospitalization in clinically extremely vulnerable (CEV) patients who were severely immunocompromised. No significant benefit was observed in patients who were not immunocompromised.

“This finding could help substantially limit unnecessary use of nirmatrelvir and ritonavir in older, otherwise healthy individuals,” lead author Colin R. Dormuth, ScD, associate professor of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, told this news organization. “Another finding that was surprising and might help place the role of nirmatrelvir and ritonavir in context is that even in severely immunocompromised individuals who did not take [the drug], the risk of death or hospitalization with COVID-19 was less than 4% in our study population.”

The study was published online in JAMA Network Open.
 

Who benefits?

The investigators analyzed medical records for 6,866 patients in British Columbia (median age, 70 years; 57% women) who presented between Feb. 1, 2022, and Feb. 3, 2023. Eligible patients belonged to one of four higher-risk groups who received priority for COVID-19 vaccination.

Two groups included CEV patients who were severely (CEV1) or moderately (CEV2) immunocompromised. The CEV3 group was not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group included higher-risk patients who were not in one of the other groups, such as unvaccinated patients older than age 70 years.

The investigators matched treated patients to untreated patients in the same vulnerability group according to age, sex, and month of infection. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.

Treatment with nirmatrelvir-ritonavir was associated with statistically significant relative reductions in the primary outcome, compared with no treatment, for patients in the CEV1 (risk difference, −2.5%) and CEV2 (RD, −1.7%) groups. In the CEV3 group, the RD of −1.3% was not statistically significant. In the EXEL group, treatment was associated with a higher risk for the primary outcome (RD, 1.0%), but the result was not statistically significant.

The results were “robust across sex and older vs. younger age,” the authors note. “No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.”

The combination of nirmatrelvir-ritonavir was approved for use in Canada based on interim efficacy and safety data from the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, said Dr. Dormuth.

British Columbia’s eligibility criteria for nirmatrelvir-ritonavir coverage differ substantially from the criteria for participants in the EPIC-HR trial, he noted. Those patients were unvaccinated, had no natural immunity from a previous COVID-19 infection, and were infected with COVID-19 variants that were different from those now circulating. The current study was prompted by the need to look at a broader population of individuals in British Columbia with varying risks of complications from COVID-19 infection.

Before the study, a common view was that patients aged 70 and older would benefit from the drug, said Dr. Dormuth. “Our study, which accounted for medical conditions related to an individual’s vulnerability to complications, showed that older age on its own was not a reason to use nirmatrelvir and ritonavir once relevant medical conditions were taken into consideration.”

The researchers are working on a study to identify with greater specificity which comorbid conditions are most associated with nirmatrelvir-ritonavir effectiveness, he added. “It could be that a relatively small number of conditions can be used to identify most individuals who would benefit from the drug.”
 

‘Signal toward benefit’

Commenting on the findings for this news organization, Abhijit Duggal, MD, vice chair of critical care at the Cleveland Clinic, who was not involved in this study, said, “I’m always very wary when we look at observational data and we start saying the effectiveness is not really as high as was seen in other studies. We are seeing an effect with all these studies that seems to be in the right direction.

“Having said that,” he added, “is the effect going to be potentially more in patients at higher risk? Absolutely. I think these postmarket studies are really showing that after vaccination, if someone does get infected, this is a secondary option available to us that can prevent progression of the disease, which would likely be more severe in immunocompromised patients.”

Dr. Duggal was a coinvestigator on a recent study of more than 68,000 patients that showed that nirmatrelvir-ritonavir or molnupiravir was associated with reductions in mortality and hospitalization in nonhospitalized patients infected with the Omicron variant, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.

“In all groups, there was a signal toward benefit,” said Dr. Duggal. “These studies tell us that these drugs do remain valid options. But their use needs to be discussed on a case-by-case basis with patients we feel are deteriorating or at a higher risk because of underlying disease processes.”

The study was supported by funding from the British Columbia Ministry of Health. Dr. Dormuth and Dr. Duggal report no relevant financial relationships.

A version of this article appeared on Medscape.com.