Pulmonology

Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.

RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.

In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.

At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.

Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).

In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”

Case courtesy A.Prof Frank Gaillard, Radiopaedia.org, rID: 12274

In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.

The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.

“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.

The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.

Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.

RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.

In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.

At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.

Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).

In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”

Case courtesy A.Prof Frank Gaillard, Radiopaedia.org, rID: 12274

In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.

The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.

“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.

The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.

Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.

RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.

In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.

At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.

Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).

In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”

Case courtesy A.Prof Frank Gaillard, Radiopaedia.org, rID: 12274

In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.

The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.

“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.

The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.

Study Overview

Objective. To examine the trend of noninvasive and invasive mechanical ventilation at the end of life from 2000 to 2017.

Design. Observational population-based cohort study.

Setting and participants. The study was a population-based cohort study to examine the use of noninvasive and invasive mechanical ventilation among decedents. The study included a random 20% sample of Medicare beneficiaries older than 65 years who were hospitalized in the last 30 days of life and died between January 1, 2000, and December 31, 2017, except for the period October 1, 2015, to December 31, 2015, when the transition from International Classification of Diseases, Ninth Revision (ICD-9) to ICD-10 occurred. Beneficiaries with the primary admitting diagnosis of cardiac arrest or with preexisting tracheostomy were excluded because of expected requirements for ventilatory support. The sample included a total of 2,470,735 Medicare beneficiaries; mean age was 82.2 years, and 54.8% were female. Primary admitting diagnosis codes were used to identify 3 subcohorts: congestive heart failure, chronic obstructive pulmonary disease, and cancer; a fourth subcohort of dementia was identified using the primary admitting diagnosis code or the first 9 secondary diagnosis codes.

Main outcome measures. The study used procedure codes to identify the use of noninvasive ventilation, invasive mechanical ventilation, or none among decedents who were hospitalized in the last 30 days of life. Descriptive statistics to characterize variables by year of hospitalization and ventilatory support were calculated, and the rates of noninvasive and invasive mechanical ventilation use were tabulated. Other outcomes of interest include site of death (in-hospital death), hospice enrollment at death, and hospice enrollment in the last 3 days of life as measures of end-of- life care use. Multivariable logistic regressions were used to examine noninvasive and invasive mechanical ventilation use among decedents, and time trends were examined, with the pattern of use in year 2000 as reference. Subgroup analysis with the subcohort of patients with different diagnoses were conducted to examine trends.

Main results. From 2000 to 2017, 16.3% of decedents had invasive mechanical ventilation, 3.7% had noninvasive ventilation, and 1.0% had both noninvasive and invasive ventilation during their hospital stay. Compared to the reference year 2000, there was a 9-fold increase in noninvasive ventilation use, from 0.8% to 7.1% in 2017, and invasive mechanical ventilation use also increased slightly, from 15.0% to 18.5%. Compared to year 2000, decedents were 2.63 times and 1.04 times (adjusted odds ratio [OR]) more likely to receive noninvasive ventilation and invasive mechanical ventilation, respectively, in 2005, 7.87 times and 1.39 times more likely in 2011, and 11.84 times and 1.63 times more likely in 2017.

Subgroup analysis showed that for congestive heart failure and chronic obstructive pulmonary disease, the increase in noninvasive ventilation use mirrored the trend observed for the overall population, but the use of invasive mechanical ventilation did not increase from 2000 to 2017, with a rate of use of 11.1% versus 7.8% (adjusted OR, 1.07; 95% confidence interval [CI], 0.95-1.19) for congestive heart failure and 17.4% vs 13.2% (OR 1.03, 95% CI, 0.88-1.21) for chronic obstructive pulmonary disease. For the cancer and dementia subgroups, the increase in noninvasive ventilation use from 2000 to 2017 was accompanied by an increase in the use of invasive mechanical ventilation, with a rate of 6.2% versus 7.4% (OR, 1.40; 95% CI, 1.26-1.55) for decedents with cancer and a rate of 5.7% versus 6.2% (OR, 1.28; 95% CI, 1.17-1.41) for decedents with dementia. For other measures of end-of-life care, noninvasive ventilation use when compared to invasive mechanical ventilation use was associated with lower rates of in-hospital (acute care) deaths (50.3% vs 76.7%), hospice enrollment in the last 3 days of life (late hospice enrollment; 57.7% vs 63.0%), and higher rates of hospice enrollment at death (41.3% vs 20.0%).

Conclusion. There was an increase in the use of noninvasive ventilation from 2000 through 2017 among Medicare beneficiaries who died. The findings also suggest that the use of invasive mechanical ventilation did not increase among decedents with congestive heart failure and chronic obstructive pulmonary disease but increased among decedents with cancer and dementia.

 

 

Commentary

Noninvasive ventilation offers an alternative to invasive mechanical ventilation for providing ventilatory support for respiratory failure, and may offer benefits as it could avert adverse effects associated with invasive mechanical ventilation, particularly in the management of respiratory failure due to congestive heart failure and chronic obstructive pulmonary disease.¹ There is evidence for potential benefits of use of noninvasive ventilation in other clinical scenarios, such as pneumonia in older adults with comorbidities, though its clinical utility is not as well established for other diseases.²

As noninvasive ventilation is introduced into clinical practice, it is not surprising that over the period of the study (2000 to 2017) that its use increased substantially. Advance directives that involve discussion of life-sustaining treatments, including in scenarios with respiratory failure, may also result in physician orders that specify whether an individual desires invasive mechanical ventilation versus other medical treatments, including noninvasive ventilation.^3,4 By examining the temporal trends of use of noninvasive and invasive ventilation, this study reveals that invasive mechanical ventilation use among decedents with dementia and cancer has increased, despite increases in the use of noninvasive ventilation. It is important to understand further what would explain these temporal trends and whether the use of noninvasive and also invasive mechanical ventilation at the end of life represents appropriate care with clear goals or whether it may represent overuse. It is also less clear in the end-of-life care scenario what the goals of treatment with noninvasive ventilation would be, especially if it does not avert the use of invasive mechanical ventilation.

The study includes decedents only, thus limiting the ability to draw conclusions about clinically appropriate care.⁵ Further studies should examine a cohort of patients who have serious and life-threatening illness to examine the trends and potential effects of noninvasive ventilation on outcomes and utilization, as individuals who have improved and survived would not be included in this present decedent cohort.

Applications for Clinical Practice

This study highlights changes in the use of noninvasive and invasive ventilation over time and the different trends seen among subgroups with different diagnoses. For older adults with serious comorbid illness such as dementia, it is especially important to have discussions on advance directives so that care at the end of life is concordant with the patient’s wishes and that unnecessary, burdensome care can be averted. Further studies to understand and define the appropriate use of noninvasive and invasive mechanical ventilation for older adults with significant comorbidities who have serious, life-threatening illness are needed to ensure appropriate clinical treatment at the end of life.

–William W. Hung, MD, MPH

Study Overview

Objective. To examine the trend of noninvasive and invasive mechanical ventilation at the end of life from 2000 to 2017.

Design. Observational population-based cohort study.

Setting and participants. The study was a population-based cohort study to examine the use of noninvasive and invasive mechanical ventilation among decedents. The study included a random 20% sample of Medicare beneficiaries older than 65 years who were hospitalized in the last 30 days of life and died between January 1, 2000, and December 31, 2017, except for the period October 1, 2015, to December 31, 2015, when the transition from International Classification of Diseases, Ninth Revision (ICD-9) to ICD-10 occurred. Beneficiaries with the primary admitting diagnosis of cardiac arrest or with preexisting tracheostomy were excluded because of expected requirements for ventilatory support. The sample included a total of 2,470,735 Medicare beneficiaries; mean age was 82.2 years, and 54.8% were female. Primary admitting diagnosis codes were used to identify 3 subcohorts: congestive heart failure, chronic obstructive pulmonary disease, and cancer; a fourth subcohort of dementia was identified using the primary admitting diagnosis code or the first 9 secondary diagnosis codes.

Main outcome measures. The study used procedure codes to identify the use of noninvasive ventilation, invasive mechanical ventilation, or none among decedents who were hospitalized in the last 30 days of life. Descriptive statistics to characterize variables by year of hospitalization and ventilatory support were calculated, and the rates of noninvasive and invasive mechanical ventilation use were tabulated. Other outcomes of interest include site of death (in-hospital death), hospice enrollment at death, and hospice enrollment in the last 3 days of life as measures of end-of- life care use. Multivariable logistic regressions were used to examine noninvasive and invasive mechanical ventilation use among decedents, and time trends were examined, with the pattern of use in year 2000 as reference. Subgroup analysis with the subcohort of patients with different diagnoses were conducted to examine trends.

Main results. From 2000 to 2017, 16.3% of decedents had invasive mechanical ventilation, 3.7% had noninvasive ventilation, and 1.0% had both noninvasive and invasive ventilation during their hospital stay. Compared to the reference year 2000, there was a 9-fold increase in noninvasive ventilation use, from 0.8% to 7.1% in 2017, and invasive mechanical ventilation use also increased slightly, from 15.0% to 18.5%. Compared to year 2000, decedents were 2.63 times and 1.04 times (adjusted odds ratio [OR]) more likely to receive noninvasive ventilation and invasive mechanical ventilation, respectively, in 2005, 7.87 times and 1.39 times more likely in 2011, and 11.84 times and 1.63 times more likely in 2017.

Subgroup analysis showed that for congestive heart failure and chronic obstructive pulmonary disease, the increase in noninvasive ventilation use mirrored the trend observed for the overall population, but the use of invasive mechanical ventilation did not increase from 2000 to 2017, with a rate of use of 11.1% versus 7.8% (adjusted OR, 1.07; 95% confidence interval [CI], 0.95-1.19) for congestive heart failure and 17.4% vs 13.2% (OR 1.03, 95% CI, 0.88-1.21) for chronic obstructive pulmonary disease. For the cancer and dementia subgroups, the increase in noninvasive ventilation use from 2000 to 2017 was accompanied by an increase in the use of invasive mechanical ventilation, with a rate of 6.2% versus 7.4% (OR, 1.40; 95% CI, 1.26-1.55) for decedents with cancer and a rate of 5.7% versus 6.2% (OR, 1.28; 95% CI, 1.17-1.41) for decedents with dementia. For other measures of end-of-life care, noninvasive ventilation use when compared to invasive mechanical ventilation use was associated with lower rates of in-hospital (acute care) deaths (50.3% vs 76.7%), hospice enrollment in the last 3 days of life (late hospice enrollment; 57.7% vs 63.0%), and higher rates of hospice enrollment at death (41.3% vs 20.0%).

Conclusion. There was an increase in the use of noninvasive ventilation from 2000 through 2017 among Medicare beneficiaries who died. The findings also suggest that the use of invasive mechanical ventilation did not increase among decedents with congestive heart failure and chronic obstructive pulmonary disease but increased among decedents with cancer and dementia.

 

 

Commentary

Noninvasive ventilation offers an alternative to invasive mechanical ventilation for providing ventilatory support for respiratory failure, and may offer benefits as it could avert adverse effects associated with invasive mechanical ventilation, particularly in the management of respiratory failure due to congestive heart failure and chronic obstructive pulmonary disease.¹ There is evidence for potential benefits of use of noninvasive ventilation in other clinical scenarios, such as pneumonia in older adults with comorbidities, though its clinical utility is not as well established for other diseases.²

As noninvasive ventilation is introduced into clinical practice, it is not surprising that over the period of the study (2000 to 2017) that its use increased substantially. Advance directives that involve discussion of life-sustaining treatments, including in scenarios with respiratory failure, may also result in physician orders that specify whether an individual desires invasive mechanical ventilation versus other medical treatments, including noninvasive ventilation.^3,4 By examining the temporal trends of use of noninvasive and invasive ventilation, this study reveals that invasive mechanical ventilation use among decedents with dementia and cancer has increased, despite increases in the use of noninvasive ventilation. It is important to understand further what would explain these temporal trends and whether the use of noninvasive and also invasive mechanical ventilation at the end of life represents appropriate care with clear goals or whether it may represent overuse. It is also less clear in the end-of-life care scenario what the goals of treatment with noninvasive ventilation would be, especially if it does not avert the use of invasive mechanical ventilation.

The study includes decedents only, thus limiting the ability to draw conclusions about clinically appropriate care.⁵ Further studies should examine a cohort of patients who have serious and life-threatening illness to examine the trends and potential effects of noninvasive ventilation on outcomes and utilization, as individuals who have improved and survived would not be included in this present decedent cohort.

Applications for Clinical Practice

This study highlights changes in the use of noninvasive and invasive ventilation over time and the different trends seen among subgroups with different diagnoses. For older adults with serious comorbid illness such as dementia, it is especially important to have discussions on advance directives so that care at the end of life is concordant with the patient’s wishes and that unnecessary, burdensome care can be averted. Further studies to understand and define the appropriate use of noninvasive and invasive mechanical ventilation for older adults with significant comorbidities who have serious, life-threatening illness are needed to ensure appropriate clinical treatment at the end of life.

–William W. Hung, MD, MPH

Study Overview

Objective. To examine the trend of noninvasive and invasive mechanical ventilation at the end of life from 2000 to 2017.

Design. Observational population-based cohort study.

Setting and participants. The study was a population-based cohort study to examine the use of noninvasive and invasive mechanical ventilation among decedents. The study included a random 20% sample of Medicare beneficiaries older than 65 years who were hospitalized in the last 30 days of life and died between January 1, 2000, and December 31, 2017, except for the period October 1, 2015, to December 31, 2015, when the transition from International Classification of Diseases, Ninth Revision (ICD-9) to ICD-10 occurred. Beneficiaries with the primary admitting diagnosis of cardiac arrest or with preexisting tracheostomy were excluded because of expected requirements for ventilatory support. The sample included a total of 2,470,735 Medicare beneficiaries; mean age was 82.2 years, and 54.8% were female. Primary admitting diagnosis codes were used to identify 3 subcohorts: congestive heart failure, chronic obstructive pulmonary disease, and cancer; a fourth subcohort of dementia was identified using the primary admitting diagnosis code or the first 9 secondary diagnosis codes.

Main outcome measures. The study used procedure codes to identify the use of noninvasive ventilation, invasive mechanical ventilation, or none among decedents who were hospitalized in the last 30 days of life. Descriptive statistics to characterize variables by year of hospitalization and ventilatory support were calculated, and the rates of noninvasive and invasive mechanical ventilation use were tabulated. Other outcomes of interest include site of death (in-hospital death), hospice enrollment at death, and hospice enrollment in the last 3 days of life as measures of end-of- life care use. Multivariable logistic regressions were used to examine noninvasive and invasive mechanical ventilation use among decedents, and time trends were examined, with the pattern of use in year 2000 as reference. Subgroup analysis with the subcohort of patients with different diagnoses were conducted to examine trends.

Main results. From 2000 to 2017, 16.3% of decedents had invasive mechanical ventilation, 3.7% had noninvasive ventilation, and 1.0% had both noninvasive and invasive ventilation during their hospital stay. Compared to the reference year 2000, there was a 9-fold increase in noninvasive ventilation use, from 0.8% to 7.1% in 2017, and invasive mechanical ventilation use also increased slightly, from 15.0% to 18.5%. Compared to year 2000, decedents were 2.63 times and 1.04 times (adjusted odds ratio [OR]) more likely to receive noninvasive ventilation and invasive mechanical ventilation, respectively, in 2005, 7.87 times and 1.39 times more likely in 2011, and 11.84 times and 1.63 times more likely in 2017.

Subgroup analysis showed that for congestive heart failure and chronic obstructive pulmonary disease, the increase in noninvasive ventilation use mirrored the trend observed for the overall population, but the use of invasive mechanical ventilation did not increase from 2000 to 2017, with a rate of use of 11.1% versus 7.8% (adjusted OR, 1.07; 95% confidence interval [CI], 0.95-1.19) for congestive heart failure and 17.4% vs 13.2% (OR 1.03, 95% CI, 0.88-1.21) for chronic obstructive pulmonary disease. For the cancer and dementia subgroups, the increase in noninvasive ventilation use from 2000 to 2017 was accompanied by an increase in the use of invasive mechanical ventilation, with a rate of 6.2% versus 7.4% (OR, 1.40; 95% CI, 1.26-1.55) for decedents with cancer and a rate of 5.7% versus 6.2% (OR, 1.28; 95% CI, 1.17-1.41) for decedents with dementia. For other measures of end-of-life care, noninvasive ventilation use when compared to invasive mechanical ventilation use was associated with lower rates of in-hospital (acute care) deaths (50.3% vs 76.7%), hospice enrollment in the last 3 days of life (late hospice enrollment; 57.7% vs 63.0%), and higher rates of hospice enrollment at death (41.3% vs 20.0%).

Conclusion. There was an increase in the use of noninvasive ventilation from 2000 through 2017 among Medicare beneficiaries who died. The findings also suggest that the use of invasive mechanical ventilation did not increase among decedents with congestive heart failure and chronic obstructive pulmonary disease but increased among decedents with cancer and dementia.

 

 

Commentary

Noninvasive ventilation offers an alternative to invasive mechanical ventilation for providing ventilatory support for respiratory failure, and may offer benefits as it could avert adverse effects associated with invasive mechanical ventilation, particularly in the management of respiratory failure due to congestive heart failure and chronic obstructive pulmonary disease.¹ There is evidence for potential benefits of use of noninvasive ventilation in other clinical scenarios, such as pneumonia in older adults with comorbidities, though its clinical utility is not as well established for other diseases.²

As noninvasive ventilation is introduced into clinical practice, it is not surprising that over the period of the study (2000 to 2017) that its use increased substantially. Advance directives that involve discussion of life-sustaining treatments, including in scenarios with respiratory failure, may also result in physician orders that specify whether an individual desires invasive mechanical ventilation versus other medical treatments, including noninvasive ventilation.^3,4 By examining the temporal trends of use of noninvasive and invasive ventilation, this study reveals that invasive mechanical ventilation use among decedents with dementia and cancer has increased, despite increases in the use of noninvasive ventilation. It is important to understand further what would explain these temporal trends and whether the use of noninvasive and also invasive mechanical ventilation at the end of life represents appropriate care with clear goals or whether it may represent overuse. It is also less clear in the end-of-life care scenario what the goals of treatment with noninvasive ventilation would be, especially if it does not avert the use of invasive mechanical ventilation.

The study includes decedents only, thus limiting the ability to draw conclusions about clinically appropriate care.⁵ Further studies should examine a cohort of patients who have serious and life-threatening illness to examine the trends and potential effects of noninvasive ventilation on outcomes and utilization, as individuals who have improved and survived would not be included in this present decedent cohort.

Applications for Clinical Practice

This study highlights changes in the use of noninvasive and invasive ventilation over time and the different trends seen among subgroups with different diagnoses. For older adults with serious comorbid illness such as dementia, it is especially important to have discussions on advance directives so that care at the end of life is concordant with the patient’s wishes and that unnecessary, burdensome care can be averted. Further studies to understand and define the appropriate use of noninvasive and invasive mechanical ventilation for older adults with significant comorbidities who have serious, life-threatening illness are needed to ensure appropriate clinical treatment at the end of life.

–William W. Hung, MD, MPH

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

New findings suggest that monoclonal antibodies used to treat RA could improve severe COVID-19 outcomes, including risk for death.

Given within 24 hours of critical illness, tocilizumab (Actemra) was associated with a median of 10 days free of respiratory and cardiovascular support up to day 21, the primary outcome. Similarly, sarilumab (Kevzara) was linked to a median of 11 days. In contrast, the usual care control group experienced zero such days in the hospital.

However, the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) trial comes with a caveat. The preprint findings have not yet been peer reviewed and “should not be used to guide clinical practice,” the authors stated.

The results were published online Jan. 7 in MedRxiv.

Nevertheless, the trial also revealed a mortality benefit associated with the two interleukin-6 antagonists. The hospital mortality rate was 22% with sarilumab, 28% with tocilizumab, and almost 36% with usual care.

“That’s a big change in survival. They are both lifesaving drugs,” lead coinvestigator Anthony Gordon, an Imperial College London professor of anesthesia and critical care, commented in a recent  story by Reuters.
 

Consider the big picture

“What I think is important is ... this is one of many trials,” Paul Auwaerter, MD, MBA, said in an interview. Many other studies looking at monoclonal antibody therapy for people with COVID-19 were halted because they did not show improvement.

One exception is the EMPACTA trial, which suggested that tocilizumab was effective if given before a person becomes ill enough to be placed on a ventilator, said Dr. Auwaerter, clinical director of the division of infectious diseases at Johns Hopkins Medicine and a contributor to this news organization. “It appeared to reduce the need for mechanical ventilation or death.”

“These two trials are the first randomized, prospective trials that show a benefit on a background of others which have not,” Dr. Auwaerter added.
 

Interim findings

The REMAP-CAP investigators randomly assigned adults within 24 hours of critical care for COVID-19 to 8 mg/kg tocilizumab, 400 mg sarilumab, or usual care at 113 sites in six countries. There were 353 participants in the tocilizumab arm, 48 in the sarilumab group, and 402 in the control group.

Compared with the control group, the 10 days free of organ support in the tocilizumab cohort was associated with an adjusted odds ratio of 1.64 (95% confidence interval, 1.25-2.14). The 11 days free of organ support in the sarilumab cohort was likewise superior to control (adjusted odds ratio, 1.76; 95% CI, 1.17-2.91).

“All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists,” the authors note. These endpoints included 90-day survival, time to intensive care unit discharge, and hospital discharge.
 

Cautious optimism?

“The results were quite impressive – having 10 or 11 fewer days in the ICU, compared to standard of care,” Deepa Gotur, MD, said in an interview. “Choosing the right patient population and providing the anti-IL-6 treatment at the right time would be the key here.”

In addition to not yet receiving peer review, an open-label design, a relatively short follow-up of 21 days, and steroids becoming standard of care about halfway through the trial are potential limitations, said Dr. Gotur, an intensivist at Houston Methodist Hospital and associate professor of clinical medicine at Weill Cornell Medicine, New York.

“This is an interesting study,” Carl J. Fichtenbaum, MD, professor of clinical medicine at the University of Cincinnati, said in a comment.

Additional detail on how many participants in each group received steroids is warranted, Dr. Fichtenbaum said. “The analysis did not carefully adjust for the use of steroids that might have influenced outcomes.”

Dr. Fichtenbaum said it’s important to look at what is distinctive about REMAP-CAP because “there are several other studies showing opposite results.”

Dr. Gotur was an investigator on a previous study evaluating tocilizumab for patients already on mechanical ventilation. “One of the key differences between this and other studies is that they included more of the ICU population,” she said. “They also included patients within 24 hours of requiring organ support, cardiac, as well as respiratory support.” Some other research included less-acute patients, including all comers into the ED who required oxygen and received tocilizumab.

The prior studies also evaluated cytokine or inflammatory markers. In contrast, REMAP-CAP researchers “looked at organ failure itself ... which I think makes sense,” Dr. Gotur said.

Cytokine release syndrome can cause organ damage or organ failure, she added, “but these markers are all over the place. I’ve seen patients who are very, very sick despite having a low [C-reactive protein] or IL-6 level.”
 

Backing from the British

Citing the combined 24% decrease in the risk for death associated with these agents in the REMAP-CAP trial, the U.K. government announced Jan. 7 it will work to make tocilizumab and sarilumab available to citizens with severe COVID-19.

Experts in the United Kingdom shared their perspectives on the REMAP-CAP interim findings through the U.K. Science Media Centre.

“There are few treatments for severe COVID-19,” said Robin Ferner, MD, honorary professor of clinical pharmacology at the University of Birmingham (England) and honorary consultant physician at City Hospital Birmingham. “If the published data from REMAP-CAP are supported by further studies, this suggests that two IL-6 receptor antagonists can reduce the death rate in the most severely ill patients.”

Dr. Ferner added that the findings are not a “magic cure,” however. He pointed out that of 401 patients given the drugs, 109 died, and with standard treatment, 144 out of 402 died.

Peter Horby, MD, PhD, was more optimistic. “It is great to see a positive result at a time that we really need good news and more tools to fight COVID. This is great achievement for REMAP-CAP,” he said.

“We hope to soon have results from RECOVERY on the effect of tocilizumab in less severely ill patients in the hospital,” said Dr. Horby, cochief investigator of the RECOVERY trial and professor of emerging infectious diseases at the Centre for Tropical Medicine and Global Health at the University of Oxford (England).

Stephen Evans, BA, MSc, FRCP, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said, “This is a high-quality trial, and although published as a preprint, is of much higher quality than many non–peer-reviewed papers.”

Dr. Evans also noted the addition of steroid therapy for many participants. “Partway through the trial, the RECOVERY trial findings showed that the corticosteroid drug dexamethasone had notable mortality benefits. Consequently, quite a number of the patients in this trial had also received a corticosteroid.”

“It does look as though these drugs give some additional benefit beyond that given by dexamethasone,” he added.

Awaiting peer review

“We need to wait for the final results and ensure it was adequately powered with enough observations to make us confident in the results,” Dr. Fichtenbaum said.

“We in the United States have to step back and look at the entire set of studies and also, for this particular one, REMAP-CAP, to be in a peer-reviewed publication,” Dr. Auwaerter said. Preprints are often released “in the setting of the pandemic, where there may be important findings, especially if they impact mortality or severity of illness.”

“We need to make sure these findings, as outlined, hold up,” he said.

In the meantime, Dr. Auwaerter added, “Exactly how this will fit in is unclear. But it’s important to me as another potential drug that can help our critically ill patients.”

The REMAP-CAP study is ongoing and updated results will be provided online.

Dr. Auwaerter disclosed that he is a consultant for EMD Serono and a member of the data monitoring safety board for Humanigen. Dr. Gotur, Dr. Fichtenbaum, Dr. Ferner, and Dr. Evans disclosed no relevant financial relationships. Dr. Horby reported that Oxford University receives funding for the RECOVERY trial from U.K. Research and Innovation and the National Institute for Health Research. Roche Products and Sanofi supported REMAP-CAP through provision of tocilizumab and sarilumab in the United Kingdom.

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

New findings suggest that monoclonal antibodies used to treat RA could improve severe COVID-19 outcomes, including risk for death.

Given within 24 hours of critical illness, tocilizumab (Actemra) was associated with a median of 10 days free of respiratory and cardiovascular support up to day 21, the primary outcome. Similarly, sarilumab (Kevzara) was linked to a median of 11 days. In contrast, the usual care control group experienced zero such days in the hospital.

However, the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) trial comes with a caveat. The preprint findings have not yet been peer reviewed and “should not be used to guide clinical practice,” the authors stated.

The results were published online Jan. 7 in MedRxiv.

Nevertheless, the trial also revealed a mortality benefit associated with the two interleukin-6 antagonists. The hospital mortality rate was 22% with sarilumab, 28% with tocilizumab, and almost 36% with usual care.

“That’s a big change in survival. They are both lifesaving drugs,” lead coinvestigator Anthony Gordon, an Imperial College London professor of anesthesia and critical care, commented in a recent  story by Reuters.
 

Consider the big picture

“What I think is important is ... this is one of many trials,” Paul Auwaerter, MD, MBA, said in an interview. Many other studies looking at monoclonal antibody therapy for people with COVID-19 were halted because they did not show improvement.

One exception is the EMPACTA trial, which suggested that tocilizumab was effective if given before a person becomes ill enough to be placed on a ventilator, said Dr. Auwaerter, clinical director of the division of infectious diseases at Johns Hopkins Medicine and a contributor to this news organization. “It appeared to reduce the need for mechanical ventilation or death.”

“These two trials are the first randomized, prospective trials that show a benefit on a background of others which have not,” Dr. Auwaerter added.
 

Interim findings

The REMAP-CAP investigators randomly assigned adults within 24 hours of critical care for COVID-19 to 8 mg/kg tocilizumab, 400 mg sarilumab, or usual care at 113 sites in six countries. There were 353 participants in the tocilizumab arm, 48 in the sarilumab group, and 402 in the control group.

Compared with the control group, the 10 days free of organ support in the tocilizumab cohort was associated with an adjusted odds ratio of 1.64 (95% confidence interval, 1.25-2.14). The 11 days free of organ support in the sarilumab cohort was likewise superior to control (adjusted odds ratio, 1.76; 95% CI, 1.17-2.91).

“All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists,” the authors note. These endpoints included 90-day survival, time to intensive care unit discharge, and hospital discharge.
 

Cautious optimism?

“The results were quite impressive – having 10 or 11 fewer days in the ICU, compared to standard of care,” Deepa Gotur, MD, said in an interview. “Choosing the right patient population and providing the anti-IL-6 treatment at the right time would be the key here.”

In addition to not yet receiving peer review, an open-label design, a relatively short follow-up of 21 days, and steroids becoming standard of care about halfway through the trial are potential limitations, said Dr. Gotur, an intensivist at Houston Methodist Hospital and associate professor of clinical medicine at Weill Cornell Medicine, New York.

“This is an interesting study,” Carl J. Fichtenbaum, MD, professor of clinical medicine at the University of Cincinnati, said in a comment.

Additional detail on how many participants in each group received steroids is warranted, Dr. Fichtenbaum said. “The analysis did not carefully adjust for the use of steroids that might have influenced outcomes.”

Dr. Fichtenbaum said it’s important to look at what is distinctive about REMAP-CAP because “there are several other studies showing opposite results.”

Dr. Gotur was an investigator on a previous study evaluating tocilizumab for patients already on mechanical ventilation. “One of the key differences between this and other studies is that they included more of the ICU population,” she said. “They also included patients within 24 hours of requiring organ support, cardiac, as well as respiratory support.” Some other research included less-acute patients, including all comers into the ED who required oxygen and received tocilizumab.

The prior studies also evaluated cytokine or inflammatory markers. In contrast, REMAP-CAP researchers “looked at organ failure itself ... which I think makes sense,” Dr. Gotur said.

Cytokine release syndrome can cause organ damage or organ failure, she added, “but these markers are all over the place. I’ve seen patients who are very, very sick despite having a low [C-reactive protein] or IL-6 level.”
 

Backing from the British

Citing the combined 24% decrease in the risk for death associated with these agents in the REMAP-CAP trial, the U.K. government announced Jan. 7 it will work to make tocilizumab and sarilumab available to citizens with severe COVID-19.

Experts in the United Kingdom shared their perspectives on the REMAP-CAP interim findings through the U.K. Science Media Centre.

“There are few treatments for severe COVID-19,” said Robin Ferner, MD, honorary professor of clinical pharmacology at the University of Birmingham (England) and honorary consultant physician at City Hospital Birmingham. “If the published data from REMAP-CAP are supported by further studies, this suggests that two IL-6 receptor antagonists can reduce the death rate in the most severely ill patients.”

Dr. Ferner added that the findings are not a “magic cure,” however. He pointed out that of 401 patients given the drugs, 109 died, and with standard treatment, 144 out of 402 died.

Peter Horby, MD, PhD, was more optimistic. “It is great to see a positive result at a time that we really need good news and more tools to fight COVID. This is great achievement for REMAP-CAP,” he said.

“We hope to soon have results from RECOVERY on the effect of tocilizumab in less severely ill patients in the hospital,” said Dr. Horby, cochief investigator of the RECOVERY trial and professor of emerging infectious diseases at the Centre for Tropical Medicine and Global Health at the University of Oxford (England).

Stephen Evans, BA, MSc, FRCP, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said, “This is a high-quality trial, and although published as a preprint, is of much higher quality than many non–peer-reviewed papers.”

Dr. Evans also noted the addition of steroid therapy for many participants. “Partway through the trial, the RECOVERY trial findings showed that the corticosteroid drug dexamethasone had notable mortality benefits. Consequently, quite a number of the patients in this trial had also received a corticosteroid.”

“It does look as though these drugs give some additional benefit beyond that given by dexamethasone,” he added.

Awaiting peer review

“We need to wait for the final results and ensure it was adequately powered with enough observations to make us confident in the results,” Dr. Fichtenbaum said.

“We in the United States have to step back and look at the entire set of studies and also, for this particular one, REMAP-CAP, to be in a peer-reviewed publication,” Dr. Auwaerter said. Preprints are often released “in the setting of the pandemic, where there may be important findings, especially if they impact mortality or severity of illness.”

“We need to make sure these findings, as outlined, hold up,” he said.

In the meantime, Dr. Auwaerter added, “Exactly how this will fit in is unclear. But it’s important to me as another potential drug that can help our critically ill patients.”

The REMAP-CAP study is ongoing and updated results will be provided online.

Dr. Auwaerter disclosed that he is a consultant for EMD Serono and a member of the data monitoring safety board for Humanigen. Dr. Gotur, Dr. Fichtenbaum, Dr. Ferner, and Dr. Evans disclosed no relevant financial relationships. Dr. Horby reported that Oxford University receives funding for the RECOVERY trial from U.K. Research and Innovation and the National Institute for Health Research. Roche Products and Sanofi supported REMAP-CAP through provision of tocilizumab and sarilumab in the United Kingdom.

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

New findings suggest that monoclonal antibodies used to treat RA could improve severe COVID-19 outcomes, including risk for death.

Given within 24 hours of critical illness, tocilizumab (Actemra) was associated with a median of 10 days free of respiratory and cardiovascular support up to day 21, the primary outcome. Similarly, sarilumab (Kevzara) was linked to a median of 11 days. In contrast, the usual care control group experienced zero such days in the hospital.

However, the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) trial comes with a caveat. The preprint findings have not yet been peer reviewed and “should not be used to guide clinical practice,” the authors stated.

The results were published online Jan. 7 in MedRxiv.

Nevertheless, the trial also revealed a mortality benefit associated with the two interleukin-6 antagonists. The hospital mortality rate was 22% with sarilumab, 28% with tocilizumab, and almost 36% with usual care.

“That’s a big change in survival. They are both lifesaving drugs,” lead coinvestigator Anthony Gordon, an Imperial College London professor of anesthesia and critical care, commented in a recent  story by Reuters.
 

Consider the big picture

“What I think is important is ... this is one of many trials,” Paul Auwaerter, MD, MBA, said in an interview. Many other studies looking at monoclonal antibody therapy for people with COVID-19 were halted because they did not show improvement.

One exception is the EMPACTA trial, which suggested that tocilizumab was effective if given before a person becomes ill enough to be placed on a ventilator, said Dr. Auwaerter, clinical director of the division of infectious diseases at Johns Hopkins Medicine and a contributor to this news organization. “It appeared to reduce the need for mechanical ventilation or death.”

“These two trials are the first randomized, prospective trials that show a benefit on a background of others which have not,” Dr. Auwaerter added.
 

Interim findings

The REMAP-CAP investigators randomly assigned adults within 24 hours of critical care for COVID-19 to 8 mg/kg tocilizumab, 400 mg sarilumab, or usual care at 113 sites in six countries. There were 353 participants in the tocilizumab arm, 48 in the sarilumab group, and 402 in the control group.

Compared with the control group, the 10 days free of organ support in the tocilizumab cohort was associated with an adjusted odds ratio of 1.64 (95% confidence interval, 1.25-2.14). The 11 days free of organ support in the sarilumab cohort was likewise superior to control (adjusted odds ratio, 1.76; 95% CI, 1.17-2.91).

“All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists,” the authors note. These endpoints included 90-day survival, time to intensive care unit discharge, and hospital discharge.
 

Cautious optimism?

“The results were quite impressive – having 10 or 11 fewer days in the ICU, compared to standard of care,” Deepa Gotur, MD, said in an interview. “Choosing the right patient population and providing the anti-IL-6 treatment at the right time would be the key here.”

In addition to not yet receiving peer review, an open-label design, a relatively short follow-up of 21 days, and steroids becoming standard of care about halfway through the trial are potential limitations, said Dr. Gotur, an intensivist at Houston Methodist Hospital and associate professor of clinical medicine at Weill Cornell Medicine, New York.

“This is an interesting study,” Carl J. Fichtenbaum, MD, professor of clinical medicine at the University of Cincinnati, said in a comment.

Additional detail on how many participants in each group received steroids is warranted, Dr. Fichtenbaum said. “The analysis did not carefully adjust for the use of steroids that might have influenced outcomes.”

Dr. Fichtenbaum said it’s important to look at what is distinctive about REMAP-CAP because “there are several other studies showing opposite results.”

Dr. Gotur was an investigator on a previous study evaluating tocilizumab for patients already on mechanical ventilation. “One of the key differences between this and other studies is that they included more of the ICU population,” she said. “They also included patients within 24 hours of requiring organ support, cardiac, as well as respiratory support.” Some other research included less-acute patients, including all comers into the ED who required oxygen and received tocilizumab.

The prior studies also evaluated cytokine or inflammatory markers. In contrast, REMAP-CAP researchers “looked at organ failure itself ... which I think makes sense,” Dr. Gotur said.

Cytokine release syndrome can cause organ damage or organ failure, she added, “but these markers are all over the place. I’ve seen patients who are very, very sick despite having a low [C-reactive protein] or IL-6 level.”
 

Backing from the British

Citing the combined 24% decrease in the risk for death associated with these agents in the REMAP-CAP trial, the U.K. government announced Jan. 7 it will work to make tocilizumab and sarilumab available to citizens with severe COVID-19.

Experts in the United Kingdom shared their perspectives on the REMAP-CAP interim findings through the U.K. Science Media Centre.

“There are few treatments for severe COVID-19,” said Robin Ferner, MD, honorary professor of clinical pharmacology at the University of Birmingham (England) and honorary consultant physician at City Hospital Birmingham. “If the published data from REMAP-CAP are supported by further studies, this suggests that two IL-6 receptor antagonists can reduce the death rate in the most severely ill patients.”

Dr. Ferner added that the findings are not a “magic cure,” however. He pointed out that of 401 patients given the drugs, 109 died, and with standard treatment, 144 out of 402 died.

Peter Horby, MD, PhD, was more optimistic. “It is great to see a positive result at a time that we really need good news and more tools to fight COVID. This is great achievement for REMAP-CAP,” he said.

“We hope to soon have results from RECOVERY on the effect of tocilizumab in less severely ill patients in the hospital,” said Dr. Horby, cochief investigator of the RECOVERY trial and professor of emerging infectious diseases at the Centre for Tropical Medicine and Global Health at the University of Oxford (England).

Stephen Evans, BA, MSc, FRCP, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said, “This is a high-quality trial, and although published as a preprint, is of much higher quality than many non–peer-reviewed papers.”

Dr. Evans also noted the addition of steroid therapy for many participants. “Partway through the trial, the RECOVERY trial findings showed that the corticosteroid drug dexamethasone had notable mortality benefits. Consequently, quite a number of the patients in this trial had also received a corticosteroid.”

“It does look as though these drugs give some additional benefit beyond that given by dexamethasone,” he added.

Awaiting peer review

“We need to wait for the final results and ensure it was adequately powered with enough observations to make us confident in the results,” Dr. Fichtenbaum said.

“We in the United States have to step back and look at the entire set of studies and also, for this particular one, REMAP-CAP, to be in a peer-reviewed publication,” Dr. Auwaerter said. Preprints are often released “in the setting of the pandemic, where there may be important findings, especially if they impact mortality or severity of illness.”

“We need to make sure these findings, as outlined, hold up,” he said.

In the meantime, Dr. Auwaerter added, “Exactly how this will fit in is unclear. But it’s important to me as another potential drug that can help our critically ill patients.”

The REMAP-CAP study is ongoing and updated results will be provided online.

Dr. Auwaerter disclosed that he is a consultant for EMD Serono and a member of the data monitoring safety board for Humanigen. Dr. Gotur, Dr. Fichtenbaum, Dr. Ferner, and Dr. Evans disclosed no relevant financial relationships. Dr. Horby reported that Oxford University receives funding for the RECOVERY trial from U.K. Research and Innovation and the National Institute for Health Research. Roche Products and Sanofi supported REMAP-CAP through provision of tocilizumab and sarilumab in the United Kingdom.

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

Three-quarters of patients hospitalized with COVID-19 were still experiencing at least one symptom of the infection 6 months after being discharged, according to a follow-up study involving 1,733 patients.

“Patients with COVID-19 had symptoms of fatigue or muscle weakness, sleep difficulties, and anxiety or depression,” and those with “more severe illness during their hospital stay had increasingly impaired pulmonary diffusion capacities and abnormal chest imaging manifestations,” Chaolin Huang, MD, of Jin Yin-tan Hospital in Wuhan, China, and associates wrote in the Lancet.

Fatigue or muscle weakness, reported by 63% of patients, was the most common symptom, followed by sleep difficulties, hair loss, and smell disorder. Altogether, 76% of those examined 6 months after discharge from Jin Yin-tan hospital – the first designated for patients with COVID-19 in Wuhan – reported at least one symptom, they said.

Symptoms were more common in women than men: 81% vs. 73% had at least one symptom, and 66% vs. 59% had fatigue or muscle weakness. Women were also more likely than men to report anxiety or depression at follow-up: 28% vs. 18% (23% overall), the investigators said.

Patients with the most severe COVID-19 were 2.4 times as likely to report any symptom later, compared with those who had the least severe levels of infection. Among the 349 participants who completed a lung function test at follow-up, lung diffusion impairment was seen in 56% of those with the most severe illness and 22% of those with the lowest level, Dr. Huang and associates reported.

In a different subset of 94 patients from whom plasma samples were collected, the “seropositivity and median titres of the neutralising antibodies were significantly lower than at the acute phase,” raising concern for reinfection, they said.

The results of the study, the investigators noted, “support that those with severe disease need post-discharge care. Longer follow-up studies in a larger population are necessary to understand the full spectrum of health consequences from COVID-19.”

[email protected]

Three-quarters of patients hospitalized with COVID-19 were still experiencing at least one symptom of the infection 6 months after being discharged, according to a follow-up study involving 1,733 patients.

“Patients with COVID-19 had symptoms of fatigue or muscle weakness, sleep difficulties, and anxiety or depression,” and those with “more severe illness during their hospital stay had increasingly impaired pulmonary diffusion capacities and abnormal chest imaging manifestations,” Chaolin Huang, MD, of Jin Yin-tan Hospital in Wuhan, China, and associates wrote in the Lancet.

Fatigue or muscle weakness, reported by 63% of patients, was the most common symptom, followed by sleep difficulties, hair loss, and smell disorder. Altogether, 76% of those examined 6 months after discharge from Jin Yin-tan hospital – the first designated for patients with COVID-19 in Wuhan – reported at least one symptom, they said.

Symptoms were more common in women than men: 81% vs. 73% had at least one symptom, and 66% vs. 59% had fatigue or muscle weakness. Women were also more likely than men to report anxiety or depression at follow-up: 28% vs. 18% (23% overall), the investigators said.

Patients with the most severe COVID-19 were 2.4 times as likely to report any symptom later, compared with those who had the least severe levels of infection. Among the 349 participants who completed a lung function test at follow-up, lung diffusion impairment was seen in 56% of those with the most severe illness and 22% of those with the lowest level, Dr. Huang and associates reported.

In a different subset of 94 patients from whom plasma samples were collected, the “seropositivity and median titres of the neutralising antibodies were significantly lower than at the acute phase,” raising concern for reinfection, they said.

The results of the study, the investigators noted, “support that those with severe disease need post-discharge care. Longer follow-up studies in a larger population are necessary to understand the full spectrum of health consequences from COVID-19.”

[email protected]

Three-quarters of patients hospitalized with COVID-19 were still experiencing at least one symptom of the infection 6 months after being discharged, according to a follow-up study involving 1,733 patients.

“Patients with COVID-19 had symptoms of fatigue or muscle weakness, sleep difficulties, and anxiety or depression,” and those with “more severe illness during their hospital stay had increasingly impaired pulmonary diffusion capacities and abnormal chest imaging manifestations,” Chaolin Huang, MD, of Jin Yin-tan Hospital in Wuhan, China, and associates wrote in the Lancet.

Fatigue or muscle weakness, reported by 63% of patients, was the most common symptom, followed by sleep difficulties, hair loss, and smell disorder. Altogether, 76% of those examined 6 months after discharge from Jin Yin-tan hospital – the first designated for patients with COVID-19 in Wuhan – reported at least one symptom, they said.

Symptoms were more common in women than men: 81% vs. 73% had at least one symptom, and 66% vs. 59% had fatigue or muscle weakness. Women were also more likely than men to report anxiety or depression at follow-up: 28% vs. 18% (23% overall), the investigators said.

Patients with the most severe COVID-19 were 2.4 times as likely to report any symptom later, compared with those who had the least severe levels of infection. Among the 349 participants who completed a lung function test at follow-up, lung diffusion impairment was seen in 56% of those with the most severe illness and 22% of those with the lowest level, Dr. Huang and associates reported.

In a different subset of 94 patients from whom plasma samples were collected, the “seropositivity and median titres of the neutralising antibodies were significantly lower than at the acute phase,” raising concern for reinfection, they said.

The results of the study, the investigators noted, “support that those with severe disease need post-discharge care. Longer follow-up studies in a larger population are necessary to understand the full spectrum of health consequences from COVID-19.”

[email protected]

Patients with asthma–chronic obstructive pulmonary disease overlap (ACO) experienced a higher burden of disease than patients with either asthma or COPD alone, a recent study has found.

Approximately 20% of chronic obstructive airway disease cases are ACO, but data on these patients are limited, as they are often excluded from clinical trials, wrote Sarah A. Hiles, MD, of the University of Newcastle (Australia) and colleagues.

“Comparing the burden of eosinophilic ACO, eosinophilic severe asthma, and eosinophilic COPD may also help contextualize findings from phenotype-targeted treatments in different diagnostic groups, such as the limited success of anti-IL [interleukin]–5 monoclonal antibodies as therapy in eosinophilic COPD,” they said.

In a cross-sectional, observational study published in Respirology the researchers recruited patients aged 18 years and older with a confirmed diagnosis of COPD only (153) severe asthma only (64), or ACO (106). Patients were assessed for demographic and clinical factors including health-related quality of life, past-year exacerbation, and other indicators of disease burden. In addition, patients were identified as having eosinophilic airway disease based on a blood eosinophil count of at least 0.3x109/L.

Overall, eosinophilic airway disease was present in 41% of the patients; 55%, 44%, and 29% for those with ACO, severe asthma, and COPD, respectively. Reports of poor health-related quality of life and past-year exacerbations were similar for eosinophilic patients across all three conditions.

However, patients with eosinophilic ACO experienced significantly more past-year exacerbations, notably those requiring oral corticosteroids, compared with patients with asthma alone. In addition, the cumulative number of past-year exacerbations in patient with eosinophilic disease was 164 in those with ACO, compared with severe asthma alone (44) and COPD alone (59).

Patients with ACO also had significantly higher disease burden based on the St. George’s Respiratory Questionnaire (SGRQ), which assessed functional limitation. “For 100 patients, the cumulative SGRQ score attributable to eosinophilic airways disease in ACO was 2,872.8, which was higher than in severe asthma (1,942.5) or COPD (1,638.1),” the researchers said.

The study was limited by several factors including the cross-sectional design and use of a single measurement to classify eosinophilia, the researchers noted. “The non-eosinophilic group likely included a mix of patients with treated eosinophilia and patients without eosinophilia, regardless of treatment, which is a limitation to consider when interpreting the disease burden estimates in this group,” they added.

However, the results add to the understanding of blood eosinophils in airway disease and the study “supports eosinophilia as a phenotype that spans across disease labels of severe asthma and COPD, and their overlap,” they concluded.

The study was supported by AstraZeneca; lead author Dr. Hiles received a salary through a grant from AstraZeneca to the University of Newcastle while conducting the study. Other coauthors disclosed relationships with companies including AstraZeneca, GlaxoSmithKline, Menarini, and Novartis.

Patients with asthma–chronic obstructive pulmonary disease overlap (ACO) experienced a higher burden of disease than patients with either asthma or COPD alone, a recent study has found.

Approximately 20% of chronic obstructive airway disease cases are ACO, but data on these patients are limited, as they are often excluded from clinical trials, wrote Sarah A. Hiles, MD, of the University of Newcastle (Australia) and colleagues.

“Comparing the burden of eosinophilic ACO, eosinophilic severe asthma, and eosinophilic COPD may also help contextualize findings from phenotype-targeted treatments in different diagnostic groups, such as the limited success of anti-IL [interleukin]–5 monoclonal antibodies as therapy in eosinophilic COPD,” they said.

In a cross-sectional, observational study published in Respirology the researchers recruited patients aged 18 years and older with a confirmed diagnosis of COPD only (153) severe asthma only (64), or ACO (106). Patients were assessed for demographic and clinical factors including health-related quality of life, past-year exacerbation, and other indicators of disease burden. In addition, patients were identified as having eosinophilic airway disease based on a blood eosinophil count of at least 0.3x109/L.

Overall, eosinophilic airway disease was present in 41% of the patients; 55%, 44%, and 29% for those with ACO, severe asthma, and COPD, respectively. Reports of poor health-related quality of life and past-year exacerbations were similar for eosinophilic patients across all three conditions.

However, patients with eosinophilic ACO experienced significantly more past-year exacerbations, notably those requiring oral corticosteroids, compared with patients with asthma alone. In addition, the cumulative number of past-year exacerbations in patient with eosinophilic disease was 164 in those with ACO, compared with severe asthma alone (44) and COPD alone (59).

Patients with ACO also had significantly higher disease burden based on the St. George’s Respiratory Questionnaire (SGRQ), which assessed functional limitation. “For 100 patients, the cumulative SGRQ score attributable to eosinophilic airways disease in ACO was 2,872.8, which was higher than in severe asthma (1,942.5) or COPD (1,638.1),” the researchers said.

The study was limited by several factors including the cross-sectional design and use of a single measurement to classify eosinophilia, the researchers noted. “The non-eosinophilic group likely included a mix of patients with treated eosinophilia and patients without eosinophilia, regardless of treatment, which is a limitation to consider when interpreting the disease burden estimates in this group,” they added.

However, the results add to the understanding of blood eosinophils in airway disease and the study “supports eosinophilia as a phenotype that spans across disease labels of severe asthma and COPD, and their overlap,” they concluded.

The study was supported by AstraZeneca; lead author Dr. Hiles received a salary through a grant from AstraZeneca to the University of Newcastle while conducting the study. Other coauthors disclosed relationships with companies including AstraZeneca, GlaxoSmithKline, Menarini, and Novartis.

Patients with asthma–chronic obstructive pulmonary disease overlap (ACO) experienced a higher burden of disease than patients with either asthma or COPD alone, a recent study has found.

Approximately 20% of chronic obstructive airway disease cases are ACO, but data on these patients are limited, as they are often excluded from clinical trials, wrote Sarah A. Hiles, MD, of the University of Newcastle (Australia) and colleagues.

“Comparing the burden of eosinophilic ACO, eosinophilic severe asthma, and eosinophilic COPD may also help contextualize findings from phenotype-targeted treatments in different diagnostic groups, such as the limited success of anti-IL [interleukin]–5 monoclonal antibodies as therapy in eosinophilic COPD,” they said.

In a cross-sectional, observational study published in Respirology the researchers recruited patients aged 18 years and older with a confirmed diagnosis of COPD only (153) severe asthma only (64), or ACO (106). Patients were assessed for demographic and clinical factors including health-related quality of life, past-year exacerbation, and other indicators of disease burden. In addition, patients were identified as having eosinophilic airway disease based on a blood eosinophil count of at least 0.3x109/L.

Overall, eosinophilic airway disease was present in 41% of the patients; 55%, 44%, and 29% for those with ACO, severe asthma, and COPD, respectively. Reports of poor health-related quality of life and past-year exacerbations were similar for eosinophilic patients across all three conditions.

However, patients with eosinophilic ACO experienced significantly more past-year exacerbations, notably those requiring oral corticosteroids, compared with patients with asthma alone. In addition, the cumulative number of past-year exacerbations in patient with eosinophilic disease was 164 in those with ACO, compared with severe asthma alone (44) and COPD alone (59).

Patients with ACO also had significantly higher disease burden based on the St. George’s Respiratory Questionnaire (SGRQ), which assessed functional limitation. “For 100 patients, the cumulative SGRQ score attributable to eosinophilic airways disease in ACO was 2,872.8, which was higher than in severe asthma (1,942.5) or COPD (1,638.1),” the researchers said.

The study was limited by several factors including the cross-sectional design and use of a single measurement to classify eosinophilia, the researchers noted. “The non-eosinophilic group likely included a mix of patients with treated eosinophilia and patients without eosinophilia, regardless of treatment, which is a limitation to consider when interpreting the disease burden estimates in this group,” they added.

However, the results add to the understanding of blood eosinophils in airway disease and the study “supports eosinophilia as a phenotype that spans across disease labels of severe asthma and COPD, and their overlap,” they concluded.

The study was supported by AstraZeneca; lead author Dr. Hiles received a salary through a grant from AstraZeneca to the University of Newcastle while conducting the study. Other coauthors disclosed relationships with companies including AstraZeneca, GlaxoSmithKline, Menarini, and Novartis.

Background: COPD is a highly morbid disease, and there is a need for a better understanding of the true prevalence. Little is known regarding overdiagnosis of COPD. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), airflow limitation by spirometry is a key criteria for diagnosis.

Overdiagnosis of COPD was noted to be more prevalent in high-income countries than they were in low- to middle-income countries (4.9% versus 1.9% of the participants sampled).

The self-reporting of the diagnosis of COPD is a limitation of the study because it may have artificially inflated the rate of false positives.

Bottom line: Patient-reported diagnoses of COPD should be taken with a degree of caution because of high rates of overdiagnosis and overtreatment.

Citation: Sator L et al. Overdiagnosis of COPD in subjects with unobstructed spirometry. Chest. 2019 Aug;156(2):277-88.

Dr. Gordon is a hospitalist at Maine Medical Center in Portland.

Background: COPD is a highly morbid disease, and there is a need for a better understanding of the true prevalence. Little is known regarding overdiagnosis of COPD. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), airflow limitation by spirometry is a key criteria for diagnosis.

Overdiagnosis of COPD was noted to be more prevalent in high-income countries than they were in low- to middle-income countries (4.9% versus 1.9% of the participants sampled).

The self-reporting of the diagnosis of COPD is a limitation of the study because it may have artificially inflated the rate of false positives.

Bottom line: Patient-reported diagnoses of COPD should be taken with a degree of caution because of high rates of overdiagnosis and overtreatment.

Citation: Sator L et al. Overdiagnosis of COPD in subjects with unobstructed spirometry. Chest. 2019 Aug;156(2):277-88.

Dr. Gordon is a hospitalist at Maine Medical Center in Portland.

Background: COPD is a highly morbid disease, and there is a need for a better understanding of the true prevalence. Little is known regarding overdiagnosis of COPD. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), airflow limitation by spirometry is a key criteria for diagnosis.

Overdiagnosis of COPD was noted to be more prevalent in high-income countries than they were in low- to middle-income countries (4.9% versus 1.9% of the participants sampled).

The self-reporting of the diagnosis of COPD is a limitation of the study because it may have artificially inflated the rate of false positives.

Bottom line: Patient-reported diagnoses of COPD should be taken with a degree of caution because of high rates of overdiagnosis and overtreatment.

Citation: Sator L et al. Overdiagnosis of COPD in subjects with unobstructed spirometry. Chest. 2019 Aug;156(2):277-88.

Dr. Gordon is a hospitalist at Maine Medical Center in Portland.

Inhaled treprostinil improved the exercise capacity of patients with pulmonary hypertension attributable to interstitial lung disease and was associated with some additional clinical benefits, according to a new study published in the New England Journal of Medicine.

To investigate treprostinil therapy for pulmonary hypertension in this subset of patients with lung disease, Aaron Waxman, MD, PhD, of Brigham and Women’s Hospital in Boston, and his fellow researchers launched the multicenter, randomized, double-blind, placebo-controlled INCREASE trial. They assigned 163 patients to the inhaled treprostinil group – administered via an ultrasonic, pulsed-delivery nebulizer over 16 weeks – and 163 patients to the placebo group. Their average age was 66.5 years, 73% were white, and 47% were female

At baseline, the mean 6-minute walk distance (6MWD) for all patients was 259.6 m. After 16 weeks, the treprostinil group gained a mean of 21.08 m in 6MWD, and the placebo group lost 10.04 m. The least-squares mean difference between the groups from baseline in the 6MWD was 31.12 m (95% confidence interval, 16.85-45.39; P < .001). After sensitivity analysis with multiple imputation, the difference remained significant at 30.97 m (95% CI, 16.53-45.41; P < .001).

In a comparison of N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels from baseline to 16 weeks, the treprostinil group saw a decrease of 15% while the placebo group’s levels increased by 46% (treatment ratio 0.58; 95% CI, 0.47-0.72; P < .001). Clinical worsening occurred in 37 patients (23%) in the treprostinil group and 54 patients (33%) in the placebo group (hazard ratio, 0.61; 95% CI, 0.40-0.92; P = .04), while serious adverse events occurred in 23.3% of the patients on treprostinil and 25.8% of the patients on placebo. There was no significant difference between groups in patient-reported quality of life, as assessed via the St. George’s Respiratory Questionnaire.

“There was no guarantee that this was going to work in this condition,” said Adriano Tonelli, MD, of the department of pulmonary medicine at the Cleveland Clinic, in an interview. “Several small studies have tried different medications, for pulmonary hypertension or otherwise, in patients with interstitial lung disease with minimal effect, if any. Given that all the prior studies were not categorically positive, the expectation, at least on my end, was that we needed to wait and see.” Dr. Tonelli and coauthors published a post hoc analysis of inhaled treprostinil studied in the TRIUMPH and BEAT trials.

Next steps: Assess clinical outcomes after inhaled treprostinil

Although the results of this study by Waxman et al, are encouraging, and the need for a treatment in this type of pulmonary hypertension is very real, more narrowing down will be needed to confirm the benefits of inhaled treprostinil, wrote Darren B. Taichman, MD, PhD, of the University of Pennsylvania in an accompanying editorial. He wrote, “After all, patients and physicians may reason, ‘It can’t hurt.’ Unfortunately, however, it could. Therapies approved for pulmonary arterial hypertension have been studied in patients with [ILD]-associated pulmonary hypertension and have shown inconsistent results, with some studies showing no benefit or suggesting harm.”

While the 6MWD has been used as an end point in previous drug trials for pulmonary arterial hypertension, Dr. Taichman wrote that improvements in such a variable were “probably too modest to be unequivocally consequential for many patients.” To confirm the benefits – and detriments – of treatments like inhaled treprostinil, it’s time for studies to focus on clinical end points, he stated, including hospitalizations, disease progression, and death.

He also highlighted the disparity between a treatment that led to increased walk distance and decreased clinical worsening yet did not register an improvement in health-related quality of life. He noted that the oft-cited minimal clinically important difference for 6MWD is approximately 30 m – similar to the difference recorded here. That said, he wrote, “prevention of deterioration is not to be ignored, even if it does not make a patient feel better.”

Regarding quality of life, Dr. Tonelli observed that this questionnaire, standard fare in respiratory research, may not have been perfectly suited for this particular study.

“You have to put it in the context of, ‘How good is the questionnaire to capture a difference in this particular disease over a 16-week period?’ ” he said. “It might not be sensitive enough to capture a significant change. The questionnaire was not developed for pulmonary hypertension in interstitial lung disease, of course. It was developed more generically. It may not capture all that you need to show significance.”

The investigators acknowledged the study’s other potential limitations, including a short duration, a notable percentage of patients who discontinued the trial early, and the fact that clinical worsening and exacerbation of disease were investigator reported and not confirmed by an independent committee.

As for next steps in assessing pulmonary hypertension treatments, Dr. Tonelli pointed to the direction of future research. “The other big study that needs to come out in our field, and I believe it’s being worked on, is inhaled treprostinil in pulmonary hypertension due to chronic obstructive pulmonary disease [COPD],” he said. “That’s a major unmet need; the COPD population is larger than the population for interstitial lung disease, and one would wonder whether inhaled treprostinil would benefit those patients as well. At the moment, we have no treatments for that condition. In the future, a COPD study will be needed.”

The study was supported by United Therapeutics. Author disclosures are listed on the New England Journal of Medicine website.

Inhaled treprostinil improved the exercise capacity of patients with pulmonary hypertension attributable to interstitial lung disease and was associated with some additional clinical benefits, according to a new study published in the New England Journal of Medicine.

To investigate treprostinil therapy for pulmonary hypertension in this subset of patients with lung disease, Aaron Waxman, MD, PhD, of Brigham and Women’s Hospital in Boston, and his fellow researchers launched the multicenter, randomized, double-blind, placebo-controlled INCREASE trial. They assigned 163 patients to the inhaled treprostinil group – administered via an ultrasonic, pulsed-delivery nebulizer over 16 weeks – and 163 patients to the placebo group. Their average age was 66.5 years, 73% were white, and 47% were female

At baseline, the mean 6-minute walk distance (6MWD) for all patients was 259.6 m. After 16 weeks, the treprostinil group gained a mean of 21.08 m in 6MWD, and the placebo group lost 10.04 m. The least-squares mean difference between the groups from baseline in the 6MWD was 31.12 m (95% confidence interval, 16.85-45.39; P < .001). After sensitivity analysis with multiple imputation, the difference remained significant at 30.97 m (95% CI, 16.53-45.41; P < .001).

In a comparison of N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels from baseline to 16 weeks, the treprostinil group saw a decrease of 15% while the placebo group’s levels increased by 46% (treatment ratio 0.58; 95% CI, 0.47-0.72; P < .001). Clinical worsening occurred in 37 patients (23%) in the treprostinil group and 54 patients (33%) in the placebo group (hazard ratio, 0.61; 95% CI, 0.40-0.92; P = .04), while serious adverse events occurred in 23.3% of the patients on treprostinil and 25.8% of the patients on placebo. There was no significant difference between groups in patient-reported quality of life, as assessed via the St. George’s Respiratory Questionnaire.

“There was no guarantee that this was going to work in this condition,” said Adriano Tonelli, MD, of the department of pulmonary medicine at the Cleveland Clinic, in an interview. “Several small studies have tried different medications, for pulmonary hypertension or otherwise, in patients with interstitial lung disease with minimal effect, if any. Given that all the prior studies were not categorically positive, the expectation, at least on my end, was that we needed to wait and see.” Dr. Tonelli and coauthors published a post hoc analysis of inhaled treprostinil studied in the TRIUMPH and BEAT trials.

Next steps: Assess clinical outcomes after inhaled treprostinil

Although the results of this study by Waxman et al, are encouraging, and the need for a treatment in this type of pulmonary hypertension is very real, more narrowing down will be needed to confirm the benefits of inhaled treprostinil, wrote Darren B. Taichman, MD, PhD, of the University of Pennsylvania in an accompanying editorial. He wrote, “After all, patients and physicians may reason, ‘It can’t hurt.’ Unfortunately, however, it could. Therapies approved for pulmonary arterial hypertension have been studied in patients with [ILD]-associated pulmonary hypertension and have shown inconsistent results, with some studies showing no benefit or suggesting harm.”

While the 6MWD has been used as an end point in previous drug trials for pulmonary arterial hypertension, Dr. Taichman wrote that improvements in such a variable were “probably too modest to be unequivocally consequential for many patients.” To confirm the benefits – and detriments – of treatments like inhaled treprostinil, it’s time for studies to focus on clinical end points, he stated, including hospitalizations, disease progression, and death.

He also highlighted the disparity between a treatment that led to increased walk distance and decreased clinical worsening yet did not register an improvement in health-related quality of life. He noted that the oft-cited minimal clinically important difference for 6MWD is approximately 30 m – similar to the difference recorded here. That said, he wrote, “prevention of deterioration is not to be ignored, even if it does not make a patient feel better.”

Regarding quality of life, Dr. Tonelli observed that this questionnaire, standard fare in respiratory research, may not have been perfectly suited for this particular study.

“You have to put it in the context of, ‘How good is the questionnaire to capture a difference in this particular disease over a 16-week period?’ ” he said. “It might not be sensitive enough to capture a significant change. The questionnaire was not developed for pulmonary hypertension in interstitial lung disease, of course. It was developed more generically. It may not capture all that you need to show significance.”

The investigators acknowledged the study’s other potential limitations, including a short duration, a notable percentage of patients who discontinued the trial early, and the fact that clinical worsening and exacerbation of disease were investigator reported and not confirmed by an independent committee.

As for next steps in assessing pulmonary hypertension treatments, Dr. Tonelli pointed to the direction of future research. “The other big study that needs to come out in our field, and I believe it’s being worked on, is inhaled treprostinil in pulmonary hypertension due to chronic obstructive pulmonary disease [COPD],” he said. “That’s a major unmet need; the COPD population is larger than the population for interstitial lung disease, and one would wonder whether inhaled treprostinil would benefit those patients as well. At the moment, we have no treatments for that condition. In the future, a COPD study will be needed.”

The study was supported by United Therapeutics. Author disclosures are listed on the New England Journal of Medicine website.

Inhaled treprostinil improved the exercise capacity of patients with pulmonary hypertension attributable to interstitial lung disease and was associated with some additional clinical benefits, according to a new study published in the New England Journal of Medicine.

To investigate treprostinil therapy for pulmonary hypertension in this subset of patients with lung disease, Aaron Waxman, MD, PhD, of Brigham and Women’s Hospital in Boston, and his fellow researchers launched the multicenter, randomized, double-blind, placebo-controlled INCREASE trial. They assigned 163 patients to the inhaled treprostinil group – administered via an ultrasonic, pulsed-delivery nebulizer over 16 weeks – and 163 patients to the placebo group. Their average age was 66.5 years, 73% were white, and 47% were female

At baseline, the mean 6-minute walk distance (6MWD) for all patients was 259.6 m. After 16 weeks, the treprostinil group gained a mean of 21.08 m in 6MWD, and the placebo group lost 10.04 m. The least-squares mean difference between the groups from baseline in the 6MWD was 31.12 m (95% confidence interval, 16.85-45.39; P < .001). After sensitivity analysis with multiple imputation, the difference remained significant at 30.97 m (95% CI, 16.53-45.41; P < .001).

In a comparison of N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels from baseline to 16 weeks, the treprostinil group saw a decrease of 15% while the placebo group’s levels increased by 46% (treatment ratio 0.58; 95% CI, 0.47-0.72; P < .001). Clinical worsening occurred in 37 patients (23%) in the treprostinil group and 54 patients (33%) in the placebo group (hazard ratio, 0.61; 95% CI, 0.40-0.92; P = .04), while serious adverse events occurred in 23.3% of the patients on treprostinil and 25.8% of the patients on placebo. There was no significant difference between groups in patient-reported quality of life, as assessed via the St. George’s Respiratory Questionnaire.

“There was no guarantee that this was going to work in this condition,” said Adriano Tonelli, MD, of the department of pulmonary medicine at the Cleveland Clinic, in an interview. “Several small studies have tried different medications, for pulmonary hypertension or otherwise, in patients with interstitial lung disease with minimal effect, if any. Given that all the prior studies were not categorically positive, the expectation, at least on my end, was that we needed to wait and see.” Dr. Tonelli and coauthors published a post hoc analysis of inhaled treprostinil studied in the TRIUMPH and BEAT trials.

Next steps: Assess clinical outcomes after inhaled treprostinil

Although the results of this study by Waxman et al, are encouraging, and the need for a treatment in this type of pulmonary hypertension is very real, more narrowing down will be needed to confirm the benefits of inhaled treprostinil, wrote Darren B. Taichman, MD, PhD, of the University of Pennsylvania in an accompanying editorial. He wrote, “After all, patients and physicians may reason, ‘It can’t hurt.’ Unfortunately, however, it could. Therapies approved for pulmonary arterial hypertension have been studied in patients with [ILD]-associated pulmonary hypertension and have shown inconsistent results, with some studies showing no benefit or suggesting harm.”

While the 6MWD has been used as an end point in previous drug trials for pulmonary arterial hypertension, Dr. Taichman wrote that improvements in such a variable were “probably too modest to be unequivocally consequential for many patients.” To confirm the benefits – and detriments – of treatments like inhaled treprostinil, it’s time for studies to focus on clinical end points, he stated, including hospitalizations, disease progression, and death.

He also highlighted the disparity between a treatment that led to increased walk distance and decreased clinical worsening yet did not register an improvement in health-related quality of life. He noted that the oft-cited minimal clinically important difference for 6MWD is approximately 30 m – similar to the difference recorded here. That said, he wrote, “prevention of deterioration is not to be ignored, even if it does not make a patient feel better.”

Regarding quality of life, Dr. Tonelli observed that this questionnaire, standard fare in respiratory research, may not have been perfectly suited for this particular study.

“You have to put it in the context of, ‘How good is the questionnaire to capture a difference in this particular disease over a 16-week period?’ ” he said. “It might not be sensitive enough to capture a significant change. The questionnaire was not developed for pulmonary hypertension in interstitial lung disease, of course. It was developed more generically. It may not capture all that you need to show significance.”

The investigators acknowledged the study’s other potential limitations, including a short duration, a notable percentage of patients who discontinued the trial early, and the fact that clinical worsening and exacerbation of disease were investigator reported and not confirmed by an independent committee.

As for next steps in assessing pulmonary hypertension treatments, Dr. Tonelli pointed to the direction of future research. “The other big study that needs to come out in our field, and I believe it’s being worked on, is inhaled treprostinil in pulmonary hypertension due to chronic obstructive pulmonary disease [COPD],” he said. “That’s a major unmet need; the COPD population is larger than the population for interstitial lung disease, and one would wonder whether inhaled treprostinil would benefit those patients as well. At the moment, we have no treatments for that condition. In the future, a COPD study will be needed.”

The study was supported by United Therapeutics. Author disclosures are listed on the New England Journal of Medicine website.

Background: Corticosteroids in the setting of an acute exacerbation of improve COPD symptoms but do not affect the decline in lung function, rate of repeat exacerbations after a month, or mortality. There is concern regarding the cumulative adverse effects over time. Limited prior research suggests that a patient’s blood eosinophil count may be useful for determining the necessity of steroids for treatment of exacerbation.

The primary outcome of days alive and out of the hospital within 14 days after recruitment was similar between groups (9 days; P = .34), along with the secondary outcome of treatment failure (26%; P = .90). Importantly, the cumulative steroid dose in the eosinophilia-guided group was lower than that of the control group at days 5, 30, and 90 (P less than or equal to .0002). Additionally, the control arm had worsening of baseline diabetes within 30 days and was more likely to require antibiotics for infections within 90 days.

Although not statistically significant, a trend was noted toward increased readmission for COPD exacerbations or death at 30 days in the eosinophilia-guided group (25% vs. 17% of control; P = .10). Future work will need to further study this trend.

Bottom line: Eosinophilia-guided treatment of COPD exacerbations reduced the cumulative exposure of steroid therapy, thereby decreasing side effects, although further study of safety profile is warranted.

Citation: Sivapalan P et al. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): A multicenter, randomized, controlled, open-label, non-inferiority trial. Lancet Respir Med. 2019 Aug;7(8): 699-709.

Dr. Dupuis is a hospitalist at Maine Medical Center in Portland.

Background: Corticosteroids in the setting of an acute exacerbation of improve COPD symptoms but do not affect the decline in lung function, rate of repeat exacerbations after a month, or mortality. There is concern regarding the cumulative adverse effects over time. Limited prior research suggests that a patient’s blood eosinophil count may be useful for determining the necessity of steroids for treatment of exacerbation.

The primary outcome of days alive and out of the hospital within 14 days after recruitment was similar between groups (9 days; P = .34), along with the secondary outcome of treatment failure (26%; P = .90). Importantly, the cumulative steroid dose in the eosinophilia-guided group was lower than that of the control group at days 5, 30, and 90 (P less than or equal to .0002). Additionally, the control arm had worsening of baseline diabetes within 30 days and was more likely to require antibiotics for infections within 90 days.

Although not statistically significant, a trend was noted toward increased readmission for COPD exacerbations or death at 30 days in the eosinophilia-guided group (25% vs. 17% of control; P = .10). Future work will need to further study this trend.

Bottom line: Eosinophilia-guided treatment of COPD exacerbations reduced the cumulative exposure of steroid therapy, thereby decreasing side effects, although further study of safety profile is warranted.

Citation: Sivapalan P et al. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): A multicenter, randomized, controlled, open-label, non-inferiority trial. Lancet Respir Med. 2019 Aug;7(8): 699-709.

Dr. Dupuis is a hospitalist at Maine Medical Center in Portland.

Background: Corticosteroids in the setting of an acute exacerbation of improve COPD symptoms but do not affect the decline in lung function, rate of repeat exacerbations after a month, or mortality. There is concern regarding the cumulative adverse effects over time. Limited prior research suggests that a patient’s blood eosinophil count may be useful for determining the necessity of steroids for treatment of exacerbation.

The primary outcome of days alive and out of the hospital within 14 days after recruitment was similar between groups (9 days; P = .34), along with the secondary outcome of treatment failure (26%; P = .90). Importantly, the cumulative steroid dose in the eosinophilia-guided group was lower than that of the control group at days 5, 30, and 90 (P less than or equal to .0002). Additionally, the control arm had worsening of baseline diabetes within 30 days and was more likely to require antibiotics for infections within 90 days.

Although not statistically significant, a trend was noted toward increased readmission for COPD exacerbations or death at 30 days in the eosinophilia-guided group (25% vs. 17% of control; P = .10). Future work will need to further study this trend.

Bottom line: Eosinophilia-guided treatment of COPD exacerbations reduced the cumulative exposure of steroid therapy, thereby decreasing side effects, although further study of safety profile is warranted.

Citation: Sivapalan P et al. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): A multicenter, randomized, controlled, open-label, non-inferiority trial. Lancet Respir Med. 2019 Aug;7(8): 699-709.

Dr. Dupuis is a hospitalist at Maine Medical Center in Portland.