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Four-meter gait speed predicts mortality in IPF
SAN DIEGO – Among patients with idiopathic pulmonary fibrosis (IPF), an improvement in 4-meter gait speed with pulmonary rehabilitation is an independent predictor of all-cause mortality at 1 year, suggest results from a multicenter study presented at an international conference of the American Thoracic Society.
In all, 11% of patients died within 1 year of completing pulmonary rehabilitation.
“Mortality is an attractive endpoint in IPF clinical research but requires large sample sizes and long follow-up duration, making clinical trials expensive and challenging to undertake,” lead study author Claire M. Nolan, MSc, said at the conference.
“Consequently, there is much interest in surrogate endpoints of mortality. In the elderly population, a lot of work has been done on performance measures, in particular the 4-meter gait test. It’s a simple test to do from the assessor’s perspective, because you just need a 4-meter corridor and a stopwatch. From the patient’s perspective, they only have to walk at their usual speed, making it feasible in most settings.”
The study by Ms. Nolan, a National Institute for Health Research fellow, and her associates, involved recruiting 90 IPF patients referred to three outpatient pulmonary rehabilitation programs in London. All patients underwent the following assessments before and after 8 weeks of pulmonary rehabilitation: spirometry; Medical Research Council dyspnea score; anthropometry; 4-meter gait speed; incremental shuttle walk test, and King’s Brief Interstitial Lung Disease questionnaire. Ms. Nolan, a respiratory physiotherapist with the Harefield Pulmonary Rehabilitation and Muscle Research Group, Royal Brompton and Harefield NHS Foundation Trust, Harefield, London, and her associates drew from national databases to obtain data on all-cause mortality 1 year following pulmonary rehabilitation.
“We also identified a cutpoint, so if patients improved their walking speed by 0.009 meters per second or above, that was associated with a longer survival time at 1 year (area under the curve of 0.76, for sensitivity of 69.6% and a specificity of 70%; P less than 0.01),” she said.* “Among patients who achieved that cutpoint or exceeded it, only 5% of them died in the 1-year follow-up period, compared with 23% in the group that didn’t achieve that cutpoint. That’s quite a big difference, but this requires external validation in another population.”
To determine the 4-meter gait speed change cut-off that best discriminated between patients who died and survived, the investigators plotted receiver operating characteristic curves. For validation, they conducted a Kaplan-Meier analysis to assess time to death, with significance assessed via the log-rank test. Finally, they used a multivariate Cox proportional hazards model to characterize the relationship between 4-meter gait speed change and all-cause mortality, adjusting for independent predictors of mortality (age, previous respiratory hospitalizations in the past year, forced vital capacity percent predicted) and baseline 4-meter gait speed.
At baseline, 70% of the 90 patients were male, mean age was 74 years, mean forced vital capacity was 72.8% predicted, and mean Medical Research Council dyspnea score was 3. In addition, mean body mass index was 27.2 kg/m2, mean 4-meter gait speed was 0.92 meters per second, mean incremental shuttle walk test measurement was 271 meters, and mean King’s Brief Interstitial Lung Disease total score was 56.4. Following 8 weeks of pulmonary rehabilitation, the patients’ 4-meter gait speed improved significantly by a mean of 0.15 meters per second (P less than .001). All other variables also improved significantly, with the exception of forced vital capacity.
In an interview, Ms. Nolan characterized the results as “one piece of the puzzle in answering whether 4-meter gait speed is a useful test for clinicians and researchers. It needs to be taken in the context of 4-meter gait speed in other populations as well as with what we’re finding in patients with IPF. We know that this test is reliable, valid, and responsive to treatment. Now we know that it has predictive capacity as well.”
During her presentation, she cited potential reasons why change in gait speed is associated with survival. “Firstly, gait speed has been described as a clinical indicator of multisystem well-being and the ‘sixth vital sign,’ ”she said. “Walking ability and speed rely on multiple factors and the integration of many systems, cardiovascular and otherwise. We know that pulmonary rehab has multiple benefits and improves these systems, and it’s plausible that change in gait speed may be a surrogate marker for, say, improvement in exercise capacity or health status. But the precise mechanism requires verification.”
Ms. Nolan acknowledged certain limitations of the study, including the fact that contemporaneous measurement of full lung function testing and pulmonary hypertension diagnosis were not available at the time of the study. “Therefore, we were unable to account for [diffusing capacity of the lung for carbon monoxide] and pulmonary hypertension diagnosis,” she said. “Secondly, we were unable to identify the precise cause of death from the national database of harm and care records, but this corroborates previous data which suggest that it’s difficult to reliably discern if a death is IPF- or non-IPF related. Lastly, we know that the benefits of pulmonary rehab experienced by IPF patients tend to wane after 6 months. It would be interesting to compare the short-term improvements in gait speed that we observed to more sustained improvements, to identify whether this impacts prognostability.”
National Institute for Health Research funded the study. Ms. Nolan reported having no financial disclosures.
*Correction, 5/23/18: An earlier version of this article misstated the 4-meter gait speed cutoff point.
SOURCE: Nolan CM et al. ATS 2018, Abstract A2456.
SAN DIEGO – Among patients with idiopathic pulmonary fibrosis (IPF), an improvement in 4-meter gait speed with pulmonary rehabilitation is an independent predictor of all-cause mortality at 1 year, suggest results from a multicenter study presented at an international conference of the American Thoracic Society.
In all, 11% of patients died within 1 year of completing pulmonary rehabilitation.
“Mortality is an attractive endpoint in IPF clinical research but requires large sample sizes and long follow-up duration, making clinical trials expensive and challenging to undertake,” lead study author Claire M. Nolan, MSc, said at the conference.
“Consequently, there is much interest in surrogate endpoints of mortality. In the elderly population, a lot of work has been done on performance measures, in particular the 4-meter gait test. It’s a simple test to do from the assessor’s perspective, because you just need a 4-meter corridor and a stopwatch. From the patient’s perspective, they only have to walk at their usual speed, making it feasible in most settings.”
The study by Ms. Nolan, a National Institute for Health Research fellow, and her associates, involved recruiting 90 IPF patients referred to three outpatient pulmonary rehabilitation programs in London. All patients underwent the following assessments before and after 8 weeks of pulmonary rehabilitation: spirometry; Medical Research Council dyspnea score; anthropometry; 4-meter gait speed; incremental shuttle walk test, and King’s Brief Interstitial Lung Disease questionnaire. Ms. Nolan, a respiratory physiotherapist with the Harefield Pulmonary Rehabilitation and Muscle Research Group, Royal Brompton and Harefield NHS Foundation Trust, Harefield, London, and her associates drew from national databases to obtain data on all-cause mortality 1 year following pulmonary rehabilitation.
“We also identified a cutpoint, so if patients improved their walking speed by 0.009 meters per second or above, that was associated with a longer survival time at 1 year (area under the curve of 0.76, for sensitivity of 69.6% and a specificity of 70%; P less than 0.01),” she said.* “Among patients who achieved that cutpoint or exceeded it, only 5% of them died in the 1-year follow-up period, compared with 23% in the group that didn’t achieve that cutpoint. That’s quite a big difference, but this requires external validation in another population.”
To determine the 4-meter gait speed change cut-off that best discriminated between patients who died and survived, the investigators plotted receiver operating characteristic curves. For validation, they conducted a Kaplan-Meier analysis to assess time to death, with significance assessed via the log-rank test. Finally, they used a multivariate Cox proportional hazards model to characterize the relationship between 4-meter gait speed change and all-cause mortality, adjusting for independent predictors of mortality (age, previous respiratory hospitalizations in the past year, forced vital capacity percent predicted) and baseline 4-meter gait speed.
At baseline, 70% of the 90 patients were male, mean age was 74 years, mean forced vital capacity was 72.8% predicted, and mean Medical Research Council dyspnea score was 3. In addition, mean body mass index was 27.2 kg/m2, mean 4-meter gait speed was 0.92 meters per second, mean incremental shuttle walk test measurement was 271 meters, and mean King’s Brief Interstitial Lung Disease total score was 56.4. Following 8 weeks of pulmonary rehabilitation, the patients’ 4-meter gait speed improved significantly by a mean of 0.15 meters per second (P less than .001). All other variables also improved significantly, with the exception of forced vital capacity.
In an interview, Ms. Nolan characterized the results as “one piece of the puzzle in answering whether 4-meter gait speed is a useful test for clinicians and researchers. It needs to be taken in the context of 4-meter gait speed in other populations as well as with what we’re finding in patients with IPF. We know that this test is reliable, valid, and responsive to treatment. Now we know that it has predictive capacity as well.”
During her presentation, she cited potential reasons why change in gait speed is associated with survival. “Firstly, gait speed has been described as a clinical indicator of multisystem well-being and the ‘sixth vital sign,’ ”she said. “Walking ability and speed rely on multiple factors and the integration of many systems, cardiovascular and otherwise. We know that pulmonary rehab has multiple benefits and improves these systems, and it’s plausible that change in gait speed may be a surrogate marker for, say, improvement in exercise capacity or health status. But the precise mechanism requires verification.”
Ms. Nolan acknowledged certain limitations of the study, including the fact that contemporaneous measurement of full lung function testing and pulmonary hypertension diagnosis were not available at the time of the study. “Therefore, we were unable to account for [diffusing capacity of the lung for carbon monoxide] and pulmonary hypertension diagnosis,” she said. “Secondly, we were unable to identify the precise cause of death from the national database of harm and care records, but this corroborates previous data which suggest that it’s difficult to reliably discern if a death is IPF- or non-IPF related. Lastly, we know that the benefits of pulmonary rehab experienced by IPF patients tend to wane after 6 months. It would be interesting to compare the short-term improvements in gait speed that we observed to more sustained improvements, to identify whether this impacts prognostability.”
National Institute for Health Research funded the study. Ms. Nolan reported having no financial disclosures.
*Correction, 5/23/18: An earlier version of this article misstated the 4-meter gait speed cutoff point.
SOURCE: Nolan CM et al. ATS 2018, Abstract A2456.
SAN DIEGO – Among patients with idiopathic pulmonary fibrosis (IPF), an improvement in 4-meter gait speed with pulmonary rehabilitation is an independent predictor of all-cause mortality at 1 year, suggest results from a multicenter study presented at an international conference of the American Thoracic Society.
In all, 11% of patients died within 1 year of completing pulmonary rehabilitation.
“Mortality is an attractive endpoint in IPF clinical research but requires large sample sizes and long follow-up duration, making clinical trials expensive and challenging to undertake,” lead study author Claire M. Nolan, MSc, said at the conference.
“Consequently, there is much interest in surrogate endpoints of mortality. In the elderly population, a lot of work has been done on performance measures, in particular the 4-meter gait test. It’s a simple test to do from the assessor’s perspective, because you just need a 4-meter corridor and a stopwatch. From the patient’s perspective, they only have to walk at their usual speed, making it feasible in most settings.”
The study by Ms. Nolan, a National Institute for Health Research fellow, and her associates, involved recruiting 90 IPF patients referred to three outpatient pulmonary rehabilitation programs in London. All patients underwent the following assessments before and after 8 weeks of pulmonary rehabilitation: spirometry; Medical Research Council dyspnea score; anthropometry; 4-meter gait speed; incremental shuttle walk test, and King’s Brief Interstitial Lung Disease questionnaire. Ms. Nolan, a respiratory physiotherapist with the Harefield Pulmonary Rehabilitation and Muscle Research Group, Royal Brompton and Harefield NHS Foundation Trust, Harefield, London, and her associates drew from national databases to obtain data on all-cause mortality 1 year following pulmonary rehabilitation.
“We also identified a cutpoint, so if patients improved their walking speed by 0.009 meters per second or above, that was associated with a longer survival time at 1 year (area under the curve of 0.76, for sensitivity of 69.6% and a specificity of 70%; P less than 0.01),” she said.* “Among patients who achieved that cutpoint or exceeded it, only 5% of them died in the 1-year follow-up period, compared with 23% in the group that didn’t achieve that cutpoint. That’s quite a big difference, but this requires external validation in another population.”
To determine the 4-meter gait speed change cut-off that best discriminated between patients who died and survived, the investigators plotted receiver operating characteristic curves. For validation, they conducted a Kaplan-Meier analysis to assess time to death, with significance assessed via the log-rank test. Finally, they used a multivariate Cox proportional hazards model to characterize the relationship between 4-meter gait speed change and all-cause mortality, adjusting for independent predictors of mortality (age, previous respiratory hospitalizations in the past year, forced vital capacity percent predicted) and baseline 4-meter gait speed.
At baseline, 70% of the 90 patients were male, mean age was 74 years, mean forced vital capacity was 72.8% predicted, and mean Medical Research Council dyspnea score was 3. In addition, mean body mass index was 27.2 kg/m2, mean 4-meter gait speed was 0.92 meters per second, mean incremental shuttle walk test measurement was 271 meters, and mean King’s Brief Interstitial Lung Disease total score was 56.4. Following 8 weeks of pulmonary rehabilitation, the patients’ 4-meter gait speed improved significantly by a mean of 0.15 meters per second (P less than .001). All other variables also improved significantly, with the exception of forced vital capacity.
In an interview, Ms. Nolan characterized the results as “one piece of the puzzle in answering whether 4-meter gait speed is a useful test for clinicians and researchers. It needs to be taken in the context of 4-meter gait speed in other populations as well as with what we’re finding in patients with IPF. We know that this test is reliable, valid, and responsive to treatment. Now we know that it has predictive capacity as well.”
During her presentation, she cited potential reasons why change in gait speed is associated with survival. “Firstly, gait speed has been described as a clinical indicator of multisystem well-being and the ‘sixth vital sign,’ ”she said. “Walking ability and speed rely on multiple factors and the integration of many systems, cardiovascular and otherwise. We know that pulmonary rehab has multiple benefits and improves these systems, and it’s plausible that change in gait speed may be a surrogate marker for, say, improvement in exercise capacity or health status. But the precise mechanism requires verification.”
Ms. Nolan acknowledged certain limitations of the study, including the fact that contemporaneous measurement of full lung function testing and pulmonary hypertension diagnosis were not available at the time of the study. “Therefore, we were unable to account for [diffusing capacity of the lung for carbon monoxide] and pulmonary hypertension diagnosis,” she said. “Secondly, we were unable to identify the precise cause of death from the national database of harm and care records, but this corroborates previous data which suggest that it’s difficult to reliably discern if a death is IPF- or non-IPF related. Lastly, we know that the benefits of pulmonary rehab experienced by IPF patients tend to wane after 6 months. It would be interesting to compare the short-term improvements in gait speed that we observed to more sustained improvements, to identify whether this impacts prognostability.”
National Institute for Health Research funded the study. Ms. Nolan reported having no financial disclosures.
*Correction, 5/23/18: An earlier version of this article misstated the 4-meter gait speed cutoff point.
SOURCE: Nolan CM et al. ATS 2018, Abstract A2456.
AT ATS 2018
Key clinical point: Change in 4-meter gait speed following pulmonary rehabilitation is an independent predictor of all-cause mortality at 1 year in patients with IPF.
Major finding: IPF patients who improved their 4-meter walking speed by 0.009 meters per second or more were more likely to be alive 1 year following pulmonary rehabilitation, compared with those who did not reach that cut point (P less than .01).
Study details: A multicenter study of 90 IPF patients who underwent 8 weeks of pulmonary rehabilitation.
Disclosures: The National Institute for Health Research funded the study. Ms. Nolan reported having no financial disclosures.
Source: Nolan, CM et al. ATS 2018, Abstract A2456.
Most COPD patients on triple therapy can withdraw steroids
SAN DIEGO – In patients on long-term triple therapy and up to one exacerbation in the previous year, the withdrawal of inhaled corticosteroids (ICS) led to a small decrease in lung function that was not clinically important, with no associated difference in the rates of chronic obstructive pulmonary disease (COPD) exacerbations, dyspnea or as-needed bronchodilator use.
Those are key findings from the SUNSET trial, a 26-week, randomized, double-blind, parallel-group multicenter study to assess the efficacy and safety of the switch from long-term triple therapy to indacaterol/glycopyrronium (IND/GLY, 110/50 mcg once daily) or continuation of triple therapy with tiotropium 18 mcg once daily and salmeterol/fluticasone propionate fixed-dose combination 50/500 mcg b.i.d.
Dr. Chapman, director of the asthma and airways clinic at University Health Network, Toronto, noted that relatively few patients with COPD benefit from inhaled steroids. “Given the risk of adverse events (pneumonia, osteoporosis, etc.), we’d rather not give them when they’re not needed,” he said. “Inhaled steroids seem to play only one role in COPD: They tend to reduce exacerbations in the exacerbation-prone COPD patient. That’s about 20% of the COPD population. Despite this, a great many patients end up on triple therapy [long-acting bronchodilators/long-acting muscarinic antagonist (LABA/LAMA) and ICS] needlessly.”
For the study, Dr. Chapman and his associates enrolled 1,053 patients with moderate to severe COPD who’d had no more than one exacerbation in the previous year who had used triple therapy for at least 6 months prior to study inclusion. The primary endpoint of the study was noninferiority on change from baseline in postdose trough forced expiratory volume in 1 second (FEV1) (with a noninferiority margin of –50 mL) after 26 weeks. Exacerbations, health-related quality of life as measured by the St. George’s Respiratory Questionnaire (SGRQ-C), and breathlessness as measures by the Transition Dyspnea Index also were evaluated. Of the 1,053 patients, 527 were randomized to IND/GLY and 526 to triple therapy. Their mean age was 65 years and their mean postbronchodilator FEV1 was 1.6 L.
The researchers found that ICS withdrawal led to a mean reduction in trough FEV1 of –26 mL, which exceeded the noninferiority margin. This difference between treatments on trough FEV1 was driven by the subset of patients with high blood eosinophil counts at baseline (a mean of –68 mL for patients with at least 300 cells/mcL and a mean of –13 mL for patients with fewer than 300 cells/mcL). The two treatments showed similar annualized rates of moderate/severe COPD exacerbations (rate ratio, 1.08) and all (mild/moderate/severe) exacerbations (RR, 1.07). ICS withdrawal led to a small difference in SGRQ-C (1.4 U on week 26), but no differences in Transition Dyspnea Index or use of rescue medication over 26 weeks. Safety and tolerability were balanced across the two treatment groups.
“Although we found no overall increase in exacerbations with ‘de-escalation,’ there were, of course, exacerbations that occurred during the trial,” Dr. Chapman said. “We found that they tended to occur in the minority of patients who had elevated blood eosinophil counts, especially if the counts were elevated persistently (at screening and randomization). The relevant cut-point was blood eosinophil counts above 300/UL. If exacerbations did occur in this easily identifiable subpopulation, they tended to occur early, in the first month after de-escalation. This gives physicians a simply way to identify a population they might exercise caution and a period when careful monitoring is useful.”
He acknowledged certain limitations of the study, including its 6-month duration, which is shorter than most exacerbation studies. “But by recruiting at multiple sites in multiple countries and across seasons, we don’t think this was an importation limitation,” he said. “Of course, like most investigators, I can always think of things I wish I had tracked. My personal hunch is that FeNO [exhaled nitric oxide levels] might offer some useful information but that will be a hunch to explore in another study.”
SUNSET was sponsored by Novartis. Dr. Chapman disclosed that he has received fees for research, consulting and lectures from Novartis, as well as from several other pharmaceutical companies.
dbrunk@mdedge.com
SOURCE: Chapman K et al. ATS 2018 Abstract A1009.
SAN DIEGO – In patients on long-term triple therapy and up to one exacerbation in the previous year, the withdrawal of inhaled corticosteroids (ICS) led to a small decrease in lung function that was not clinically important, with no associated difference in the rates of chronic obstructive pulmonary disease (COPD) exacerbations, dyspnea or as-needed bronchodilator use.
Those are key findings from the SUNSET trial, a 26-week, randomized, double-blind, parallel-group multicenter study to assess the efficacy and safety of the switch from long-term triple therapy to indacaterol/glycopyrronium (IND/GLY, 110/50 mcg once daily) or continuation of triple therapy with tiotropium 18 mcg once daily and salmeterol/fluticasone propionate fixed-dose combination 50/500 mcg b.i.d.
Dr. Chapman, director of the asthma and airways clinic at University Health Network, Toronto, noted that relatively few patients with COPD benefit from inhaled steroids. “Given the risk of adverse events (pneumonia, osteoporosis, etc.), we’d rather not give them when they’re not needed,” he said. “Inhaled steroids seem to play only one role in COPD: They tend to reduce exacerbations in the exacerbation-prone COPD patient. That’s about 20% of the COPD population. Despite this, a great many patients end up on triple therapy [long-acting bronchodilators/long-acting muscarinic antagonist (LABA/LAMA) and ICS] needlessly.”
For the study, Dr. Chapman and his associates enrolled 1,053 patients with moderate to severe COPD who’d had no more than one exacerbation in the previous year who had used triple therapy for at least 6 months prior to study inclusion. The primary endpoint of the study was noninferiority on change from baseline in postdose trough forced expiratory volume in 1 second (FEV1) (with a noninferiority margin of –50 mL) after 26 weeks. Exacerbations, health-related quality of life as measured by the St. George’s Respiratory Questionnaire (SGRQ-C), and breathlessness as measures by the Transition Dyspnea Index also were evaluated. Of the 1,053 patients, 527 were randomized to IND/GLY and 526 to triple therapy. Their mean age was 65 years and their mean postbronchodilator FEV1 was 1.6 L.
The researchers found that ICS withdrawal led to a mean reduction in trough FEV1 of –26 mL, which exceeded the noninferiority margin. This difference between treatments on trough FEV1 was driven by the subset of patients with high blood eosinophil counts at baseline (a mean of –68 mL for patients with at least 300 cells/mcL and a mean of –13 mL for patients with fewer than 300 cells/mcL). The two treatments showed similar annualized rates of moderate/severe COPD exacerbations (rate ratio, 1.08) and all (mild/moderate/severe) exacerbations (RR, 1.07). ICS withdrawal led to a small difference in SGRQ-C (1.4 U on week 26), but no differences in Transition Dyspnea Index or use of rescue medication over 26 weeks. Safety and tolerability were balanced across the two treatment groups.
“Although we found no overall increase in exacerbations with ‘de-escalation,’ there were, of course, exacerbations that occurred during the trial,” Dr. Chapman said. “We found that they tended to occur in the minority of patients who had elevated blood eosinophil counts, especially if the counts were elevated persistently (at screening and randomization). The relevant cut-point was blood eosinophil counts above 300/UL. If exacerbations did occur in this easily identifiable subpopulation, they tended to occur early, in the first month after de-escalation. This gives physicians a simply way to identify a population they might exercise caution and a period when careful monitoring is useful.”
He acknowledged certain limitations of the study, including its 6-month duration, which is shorter than most exacerbation studies. “But by recruiting at multiple sites in multiple countries and across seasons, we don’t think this was an importation limitation,” he said. “Of course, like most investigators, I can always think of things I wish I had tracked. My personal hunch is that FeNO [exhaled nitric oxide levels] might offer some useful information but that will be a hunch to explore in another study.”
SUNSET was sponsored by Novartis. Dr. Chapman disclosed that he has received fees for research, consulting and lectures from Novartis, as well as from several other pharmaceutical companies.
dbrunk@mdedge.com
SOURCE: Chapman K et al. ATS 2018 Abstract A1009.
SAN DIEGO – In patients on long-term triple therapy and up to one exacerbation in the previous year, the withdrawal of inhaled corticosteroids (ICS) led to a small decrease in lung function that was not clinically important, with no associated difference in the rates of chronic obstructive pulmonary disease (COPD) exacerbations, dyspnea or as-needed bronchodilator use.
Those are key findings from the SUNSET trial, a 26-week, randomized, double-blind, parallel-group multicenter study to assess the efficacy and safety of the switch from long-term triple therapy to indacaterol/glycopyrronium (IND/GLY, 110/50 mcg once daily) or continuation of triple therapy with tiotropium 18 mcg once daily and salmeterol/fluticasone propionate fixed-dose combination 50/500 mcg b.i.d.
Dr. Chapman, director of the asthma and airways clinic at University Health Network, Toronto, noted that relatively few patients with COPD benefit from inhaled steroids. “Given the risk of adverse events (pneumonia, osteoporosis, etc.), we’d rather not give them when they’re not needed,” he said. “Inhaled steroids seem to play only one role in COPD: They tend to reduce exacerbations in the exacerbation-prone COPD patient. That’s about 20% of the COPD population. Despite this, a great many patients end up on triple therapy [long-acting bronchodilators/long-acting muscarinic antagonist (LABA/LAMA) and ICS] needlessly.”
For the study, Dr. Chapman and his associates enrolled 1,053 patients with moderate to severe COPD who’d had no more than one exacerbation in the previous year who had used triple therapy for at least 6 months prior to study inclusion. The primary endpoint of the study was noninferiority on change from baseline in postdose trough forced expiratory volume in 1 second (FEV1) (with a noninferiority margin of –50 mL) after 26 weeks. Exacerbations, health-related quality of life as measured by the St. George’s Respiratory Questionnaire (SGRQ-C), and breathlessness as measures by the Transition Dyspnea Index also were evaluated. Of the 1,053 patients, 527 were randomized to IND/GLY and 526 to triple therapy. Their mean age was 65 years and their mean postbronchodilator FEV1 was 1.6 L.
The researchers found that ICS withdrawal led to a mean reduction in trough FEV1 of –26 mL, which exceeded the noninferiority margin. This difference between treatments on trough FEV1 was driven by the subset of patients with high blood eosinophil counts at baseline (a mean of –68 mL for patients with at least 300 cells/mcL and a mean of –13 mL for patients with fewer than 300 cells/mcL). The two treatments showed similar annualized rates of moderate/severe COPD exacerbations (rate ratio, 1.08) and all (mild/moderate/severe) exacerbations (RR, 1.07). ICS withdrawal led to a small difference in SGRQ-C (1.4 U on week 26), but no differences in Transition Dyspnea Index or use of rescue medication over 26 weeks. Safety and tolerability were balanced across the two treatment groups.
“Although we found no overall increase in exacerbations with ‘de-escalation,’ there were, of course, exacerbations that occurred during the trial,” Dr. Chapman said. “We found that they tended to occur in the minority of patients who had elevated blood eosinophil counts, especially if the counts were elevated persistently (at screening and randomization). The relevant cut-point was blood eosinophil counts above 300/UL. If exacerbations did occur in this easily identifiable subpopulation, they tended to occur early, in the first month after de-escalation. This gives physicians a simply way to identify a population they might exercise caution and a period when careful monitoring is useful.”
He acknowledged certain limitations of the study, including its 6-month duration, which is shorter than most exacerbation studies. “But by recruiting at multiple sites in multiple countries and across seasons, we don’t think this was an importation limitation,” he said. “Of course, like most investigators, I can always think of things I wish I had tracked. My personal hunch is that FeNO [exhaled nitric oxide levels] might offer some useful information but that will be a hunch to explore in another study.”
SUNSET was sponsored by Novartis. Dr. Chapman disclosed that he has received fees for research, consulting and lectures from Novartis, as well as from several other pharmaceutical companies.
dbrunk@mdedge.com
SOURCE: Chapman K et al. ATS 2018 Abstract A1009.
REPORTING FROM ATS 2018
Key clinical point: Switching from triple therapy to indacaterol/glycopyrronium (IND/GLY) is effective in COPD patients and avoids long-term exposure to inhaled corticosteroids.
Major finding: ICS withdrawal led to a mean reduction in trough FEV1 of –26 mL, which exceeded the noninferiority margin.
Study details: A randomized trial of COPD patients in which 527 were randomized to IND/GLY and 526 to triple therapy.
Disclosures: SUNSET was sponsored by Novartis. Dr. Chapman disclosed that he has received fees for research, consulting, and lectures from Novartis, as well as from several other pharmaceutical companies.
Source: Chapman K et al. ATS 2018. Abstract A1009.
Palliative care may reduce suicide among lung cancer patients
according to new research that will be presented at an international conference of the American Thoracic Society.
“Suicide is a significant national public health problem, especially among lung cancer patients and among veterans,” said lead author, Donald R. Sullivan, MD, of the division of pulmonary and critical care medicine at Oregon Health & Science University and a member of the OHSU Knight Cancer Institute, in a statement.
The investigators found that veterans who experienced at least one “palliative care encounter” after learning they had lung cancer were 82% less likely to die by suicide (odds ratio, 0.18; 95% confidence interval, 0.07-0.46; P less than .001), when compared with veterans who were diagnosed with lung cancer but did not receive palliative care.
The suicide rate for the advanced-stage lung cancer patients was 200/100,000 patient-years, which was more than five times higher than the suicide rate – adjusted for age, sex, and year – for all veterans using VA health care (37.5/100,000), according to the study abstract.
Of the 20,900 lung cancer patients analyzed, 30 committed suicide. Only six (20%) of the patients who died by suicide had received palliative care. Overall, most patients (18,192 or 87%) in the registry died of lung cancer. Other cancers, heart disease, and chronic obstructive pulmonary disease were some of the other common causes of death for the lung cancer patients, according to the abstract.
While several medical societies recommend palliative care for all patients with advanced-stage lung cancer, there is a gap between those recommendations and practice, noted Dr. Sullivan. “There are many barriers to palliative care, and unfortunately, some are related to clinician referrals. Not all doctors are aware of the benefits of palliative care,” he said in the statement.
Dr. Sullivan added that palliative care should be offered to all patients shortly after receiving a diagnosis of advanced-stage lung cancer.
More details on this study will be presented at the conference on Monday, May 21, at 2:30 p.m. in Room 14 A-B (Mezzanine Level) of the San Diego Convention Center.
according to new research that will be presented at an international conference of the American Thoracic Society.
“Suicide is a significant national public health problem, especially among lung cancer patients and among veterans,” said lead author, Donald R. Sullivan, MD, of the division of pulmonary and critical care medicine at Oregon Health & Science University and a member of the OHSU Knight Cancer Institute, in a statement.
The investigators found that veterans who experienced at least one “palliative care encounter” after learning they had lung cancer were 82% less likely to die by suicide (odds ratio, 0.18; 95% confidence interval, 0.07-0.46; P less than .001), when compared with veterans who were diagnosed with lung cancer but did not receive palliative care.
The suicide rate for the advanced-stage lung cancer patients was 200/100,000 patient-years, which was more than five times higher than the suicide rate – adjusted for age, sex, and year – for all veterans using VA health care (37.5/100,000), according to the study abstract.
Of the 20,900 lung cancer patients analyzed, 30 committed suicide. Only six (20%) of the patients who died by suicide had received palliative care. Overall, most patients (18,192 or 87%) in the registry died of lung cancer. Other cancers, heart disease, and chronic obstructive pulmonary disease were some of the other common causes of death for the lung cancer patients, according to the abstract.
While several medical societies recommend palliative care for all patients with advanced-stage lung cancer, there is a gap between those recommendations and practice, noted Dr. Sullivan. “There are many barriers to palliative care, and unfortunately, some are related to clinician referrals. Not all doctors are aware of the benefits of palliative care,” he said in the statement.
Dr. Sullivan added that palliative care should be offered to all patients shortly after receiving a diagnosis of advanced-stage lung cancer.
More details on this study will be presented at the conference on Monday, May 21, at 2:30 p.m. in Room 14 A-B (Mezzanine Level) of the San Diego Convention Center.
according to new research that will be presented at an international conference of the American Thoracic Society.
“Suicide is a significant national public health problem, especially among lung cancer patients and among veterans,” said lead author, Donald R. Sullivan, MD, of the division of pulmonary and critical care medicine at Oregon Health & Science University and a member of the OHSU Knight Cancer Institute, in a statement.
The investigators found that veterans who experienced at least one “palliative care encounter” after learning they had lung cancer were 82% less likely to die by suicide (odds ratio, 0.18; 95% confidence interval, 0.07-0.46; P less than .001), when compared with veterans who were diagnosed with lung cancer but did not receive palliative care.
The suicide rate for the advanced-stage lung cancer patients was 200/100,000 patient-years, which was more than five times higher than the suicide rate – adjusted for age, sex, and year – for all veterans using VA health care (37.5/100,000), according to the study abstract.
Of the 20,900 lung cancer patients analyzed, 30 committed suicide. Only six (20%) of the patients who died by suicide had received palliative care. Overall, most patients (18,192 or 87%) in the registry died of lung cancer. Other cancers, heart disease, and chronic obstructive pulmonary disease were some of the other common causes of death for the lung cancer patients, according to the abstract.
While several medical societies recommend palliative care for all patients with advanced-stage lung cancer, there is a gap between those recommendations and practice, noted Dr. Sullivan. “There are many barriers to palliative care, and unfortunately, some are related to clinician referrals. Not all doctors are aware of the benefits of palliative care,” he said in the statement.
Dr. Sullivan added that palliative care should be offered to all patients shortly after receiving a diagnosis of advanced-stage lung cancer.
More details on this study will be presented at the conference on Monday, May 21, at 2:30 p.m. in Room 14 A-B (Mezzanine Level) of the San Diego Convention Center.
FROM ATS 2018
EPA proposal on research data to be discussed at ATS meeting
A press conference on the Environmental Protection Agency’s proposed policy on research data will be held at the American Thoracic Society International Conference on Sunday, May 20.
The conference, entitled “Silencing Science: EPA’s Proposed Policy on Research Data,” will occur at 11:15 a.m. Pacific Standard Time in the San Diego Convention Center, Meeting Room 23A (Upper Level).
For information about this press conference, contact Dacia Morris, director of communications and marketing of the ATS, at 212-315-8620.
A press conference on the Environmental Protection Agency’s proposed policy on research data will be held at the American Thoracic Society International Conference on Sunday, May 20.
The conference, entitled “Silencing Science: EPA’s Proposed Policy on Research Data,” will occur at 11:15 a.m. Pacific Standard Time in the San Diego Convention Center, Meeting Room 23A (Upper Level).
For information about this press conference, contact Dacia Morris, director of communications and marketing of the ATS, at 212-315-8620.
A press conference on the Environmental Protection Agency’s proposed policy on research data will be held at the American Thoracic Society International Conference on Sunday, May 20.
The conference, entitled “Silencing Science: EPA’s Proposed Policy on Research Data,” will occur at 11:15 a.m. Pacific Standard Time in the San Diego Convention Center, Meeting Room 23A (Upper Level).
For information about this press conference, contact Dacia Morris, director of communications and marketing of the ATS, at 212-315-8620.
FROM ATS 2018
CHEST® Physician’s preview of ATS 2018
Here is a glimpse of some of the important research that will be presented at this meeting.
The findings of several chronic obstructive pulmonary disease (COPD) drug trials will be discussed during a session entitled “ICS [Inhaled corticosteroids] in COPD: The Pendulum Keeps Swinging,” which is scheduled to occur at 9:15 a.m. in Room 14 A-B (Mezzanine Level). Among the research to be presented are the latest findings of the phase 3 IMPACT study of 10,355 symptomatic COPD patients with a history of moderate to severe exacerbations. This study compared the use of an inhaled therapy that comprised a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the use of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. (Lipson DA et al. N Engl J Med. 2018 Apr 18;378:1671-80). Patients were randomized to receive either a once-daily combination of 100 mcg fluticasone furoate (a corticosteroid); 62.5 mcg of the LAMA, umeclidinium; and 25 mcg of the LABA, vilanterol; or dual inhaled therapy involving either 100 mcg fluticasone furoate plus 25 mcg of vilanterol, or 62.5 mcg of umeclidinium plus 25 mcg of vilanterol for 52 weeks.
One of the updates on this trial is that using the triple therapy significantly reduced on-treatment all-cause mortality over using the LAMA (62.5 mcg of umeclidinium) plus LABA (25 mcg of the vilanterol) dual therapy. Fifty of the patients who received triple therapy died (1.20%), versus 49 patients in the corticosteroid plus LABA group (1.19%) and 30 patients (1.88%) in the LAMA plus LABA group. A 42.1% reduction in risk of all-cause mortality occurred for patients who took the triple therapy, when compared with patients who took the LAMA/LABA combo (95% confidence interval, 11.9%-61.9%; P = .011), according to an abstract on the ATS International Conference’s website.
At the same time on Sunday, researchers will be presenting their research in a session entitled “Sleep Disordered Breathing, Cardiovascular Disease, and Mortality,” in Room 3 (Upper Level) of the convention center. One of the abstracts that will be discussed compared the long-term effectiveness of noninvasive ventilation (NIV) with continuous positive airway pressure (CPAP) in patients with obesity hypoventilation syndrome with severe obstructive sleep apnea. In this multicenter open-label, randomized, controlled trial, Sanchez Quiroga M et al. analyzed the results for 202 patients who used one of the two treatments for at least 3 years. Among this study’s findings were that the mortality rates and the number of cardiovascular events that occurred were similar in the two treatment groups. The mortality rate for patients who used CPAP was 14.7%, compared with 11.3% for the patients who received NIV (adjusted hazard ratio, 0.73; P = .439), and the cardiovascular events per 100 person-years were 5.1 for CPAP and 7.46 for NIV (P = .315). The researchers concluded that both treatments are equally effective for the long term, but that CPAP should be “the preferred treatment modality,” because it’s cheaper and easier to implement.
On Monday morning, researchers will present their findings of the short-term cardiovascular effects of 30 pulmonary arterial hypertension patients’ use of the beta blocker carvedilol, in 3.125 mg doses taken twice a day. Right ventricular systolic pressure (RVSP) decreased by an average of 11 mmHg (P = .003) in this double-blinded, randomized, controlled open-label trial with a 1-week run-in period. Cardiac output decreased by an average of –1.8 L/min (P less than .0001), but RVSP was inversely associated with cardiac output. “Short-term carvedilol could potentially identify a subgroup for long-term therapy based on initial drop in RVSP and heart rate response,” noted Farha SY et al. in their abstract. None of the patients experienced any side effects from taking the drug. More details on this research and other studies on pulmonary hypertension will be presented at 9:15 am in Area B (Hall A-B2, Ground level) of the convention center, in the session entitled “Surf’s Up: Riding the Wave of Clinical Research in Pulmonary Hypertension.”
Look for all of our on-site coverage of the conference at mdedge.com/chestphysician next week.
Here is a glimpse of some of the important research that will be presented at this meeting.
The findings of several chronic obstructive pulmonary disease (COPD) drug trials will be discussed during a session entitled “ICS [Inhaled corticosteroids] in COPD: The Pendulum Keeps Swinging,” which is scheduled to occur at 9:15 a.m. in Room 14 A-B (Mezzanine Level). Among the research to be presented are the latest findings of the phase 3 IMPACT study of 10,355 symptomatic COPD patients with a history of moderate to severe exacerbations. This study compared the use of an inhaled therapy that comprised a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the use of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. (Lipson DA et al. N Engl J Med. 2018 Apr 18;378:1671-80). Patients were randomized to receive either a once-daily combination of 100 mcg fluticasone furoate (a corticosteroid); 62.5 mcg of the LAMA, umeclidinium; and 25 mcg of the LABA, vilanterol; or dual inhaled therapy involving either 100 mcg fluticasone furoate plus 25 mcg of vilanterol, or 62.5 mcg of umeclidinium plus 25 mcg of vilanterol for 52 weeks.
One of the updates on this trial is that using the triple therapy significantly reduced on-treatment all-cause mortality over using the LAMA (62.5 mcg of umeclidinium) plus LABA (25 mcg of the vilanterol) dual therapy. Fifty of the patients who received triple therapy died (1.20%), versus 49 patients in the corticosteroid plus LABA group (1.19%) and 30 patients (1.88%) in the LAMA plus LABA group. A 42.1% reduction in risk of all-cause mortality occurred for patients who took the triple therapy, when compared with patients who took the LAMA/LABA combo (95% confidence interval, 11.9%-61.9%; P = .011), according to an abstract on the ATS International Conference’s website.
At the same time on Sunday, researchers will be presenting their research in a session entitled “Sleep Disordered Breathing, Cardiovascular Disease, and Mortality,” in Room 3 (Upper Level) of the convention center. One of the abstracts that will be discussed compared the long-term effectiveness of noninvasive ventilation (NIV) with continuous positive airway pressure (CPAP) in patients with obesity hypoventilation syndrome with severe obstructive sleep apnea. In this multicenter open-label, randomized, controlled trial, Sanchez Quiroga M et al. analyzed the results for 202 patients who used one of the two treatments for at least 3 years. Among this study’s findings were that the mortality rates and the number of cardiovascular events that occurred were similar in the two treatment groups. The mortality rate for patients who used CPAP was 14.7%, compared with 11.3% for the patients who received NIV (adjusted hazard ratio, 0.73; P = .439), and the cardiovascular events per 100 person-years were 5.1 for CPAP and 7.46 for NIV (P = .315). The researchers concluded that both treatments are equally effective for the long term, but that CPAP should be “the preferred treatment modality,” because it’s cheaper and easier to implement.
On Monday morning, researchers will present their findings of the short-term cardiovascular effects of 30 pulmonary arterial hypertension patients’ use of the beta blocker carvedilol, in 3.125 mg doses taken twice a day. Right ventricular systolic pressure (RVSP) decreased by an average of 11 mmHg (P = .003) in this double-blinded, randomized, controlled open-label trial with a 1-week run-in period. Cardiac output decreased by an average of –1.8 L/min (P less than .0001), but RVSP was inversely associated with cardiac output. “Short-term carvedilol could potentially identify a subgroup for long-term therapy based on initial drop in RVSP and heart rate response,” noted Farha SY et al. in their abstract. None of the patients experienced any side effects from taking the drug. More details on this research and other studies on pulmonary hypertension will be presented at 9:15 am in Area B (Hall A-B2, Ground level) of the convention center, in the session entitled “Surf’s Up: Riding the Wave of Clinical Research in Pulmonary Hypertension.”
Look for all of our on-site coverage of the conference at mdedge.com/chestphysician next week.
Here is a glimpse of some of the important research that will be presented at this meeting.
The findings of several chronic obstructive pulmonary disease (COPD) drug trials will be discussed during a session entitled “ICS [Inhaled corticosteroids] in COPD: The Pendulum Keeps Swinging,” which is scheduled to occur at 9:15 a.m. in Room 14 A-B (Mezzanine Level). Among the research to be presented are the latest findings of the phase 3 IMPACT study of 10,355 symptomatic COPD patients with a history of moderate to severe exacerbations. This study compared the use of an inhaled therapy that comprised a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the use of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. (Lipson DA et al. N Engl J Med. 2018 Apr 18;378:1671-80). Patients were randomized to receive either a once-daily combination of 100 mcg fluticasone furoate (a corticosteroid); 62.5 mcg of the LAMA, umeclidinium; and 25 mcg of the LABA, vilanterol; or dual inhaled therapy involving either 100 mcg fluticasone furoate plus 25 mcg of vilanterol, or 62.5 mcg of umeclidinium plus 25 mcg of vilanterol for 52 weeks.
One of the updates on this trial is that using the triple therapy significantly reduced on-treatment all-cause mortality over using the LAMA (62.5 mcg of umeclidinium) plus LABA (25 mcg of the vilanterol) dual therapy. Fifty of the patients who received triple therapy died (1.20%), versus 49 patients in the corticosteroid plus LABA group (1.19%) and 30 patients (1.88%) in the LAMA plus LABA group. A 42.1% reduction in risk of all-cause mortality occurred for patients who took the triple therapy, when compared with patients who took the LAMA/LABA combo (95% confidence interval, 11.9%-61.9%; P = .011), according to an abstract on the ATS International Conference’s website.
At the same time on Sunday, researchers will be presenting their research in a session entitled “Sleep Disordered Breathing, Cardiovascular Disease, and Mortality,” in Room 3 (Upper Level) of the convention center. One of the abstracts that will be discussed compared the long-term effectiveness of noninvasive ventilation (NIV) with continuous positive airway pressure (CPAP) in patients with obesity hypoventilation syndrome with severe obstructive sleep apnea. In this multicenter open-label, randomized, controlled trial, Sanchez Quiroga M et al. analyzed the results for 202 patients who used one of the two treatments for at least 3 years. Among this study’s findings were that the mortality rates and the number of cardiovascular events that occurred were similar in the two treatment groups. The mortality rate for patients who used CPAP was 14.7%, compared with 11.3% for the patients who received NIV (adjusted hazard ratio, 0.73; P = .439), and the cardiovascular events per 100 person-years were 5.1 for CPAP and 7.46 for NIV (P = .315). The researchers concluded that both treatments are equally effective for the long term, but that CPAP should be “the preferred treatment modality,” because it’s cheaper and easier to implement.
On Monday morning, researchers will present their findings of the short-term cardiovascular effects of 30 pulmonary arterial hypertension patients’ use of the beta blocker carvedilol, in 3.125 mg doses taken twice a day. Right ventricular systolic pressure (RVSP) decreased by an average of 11 mmHg (P = .003) in this double-blinded, randomized, controlled open-label trial with a 1-week run-in period. Cardiac output decreased by an average of –1.8 L/min (P less than .0001), but RVSP was inversely associated with cardiac output. “Short-term carvedilol could potentially identify a subgroup for long-term therapy based on initial drop in RVSP and heart rate response,” noted Farha SY et al. in their abstract. None of the patients experienced any side effects from taking the drug. More details on this research and other studies on pulmonary hypertension will be presented at 9:15 am in Area B (Hall A-B2, Ground level) of the convention center, in the session entitled “Surf’s Up: Riding the Wave of Clinical Research in Pulmonary Hypertension.”
Look for all of our on-site coverage of the conference at mdedge.com/chestphysician next week.
FROM ATS 2018