Stopping versus continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study).

BACKGROUND: The long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use. METHODS: COMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicentre study. Patients who had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692) and received continuous mepolizumab treatment for ≥3 years were randomised 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks. Primary end-point: time to first clinically significant exacerbation; secondary end-points: time to first exacerbation requiring hospitalisation/emergency department visit, time to decrease in asthma control (≥0.5-point increase in Asthma Control Questionnaire-5 score from COMET baseline) and blood eosinophil count ratio to COMET baseline. Safety was assessed. RESULTS: Patients stopping (n=151) versus continuing (n=144) mepolizumab had significantly shorter times to first clinically significant exacerbation (hazard ratio 1.61, 95% CI 1.17-2.22; p=0.004) and decrease in asthma control (hazard ratio 1.52, 95% CI 1.13-2.02; p=0.005), and higher blood eosinophil counts at week 52 (270 versus 40 cells·µL-1; ratio (stopping versus continuing) 6.19, 95% CI 4.89-7.83; p<0.001). Differences in efficacy outcomes between groups were observed when assessed from week 12 (16 weeks after last mepolizumab dose). Exacerbations requiring hospitalisation/emergency department visit were rare. Adverse events in patients continuing mepolizumab were consistent with previous studies. For patients who stopped mepolizumab, the safety profile was consistent with other eosinophilic asthma populations. CONCLUSION: Patients who stopped mepolizumab had an increase in exacerbations and reduced asthma control versus those who continued.

Factors Affecting Health Literacy as Related to Asthma and COPD Management: Learning from Patient and Health Care Professional Viewpoints.

BACKGROUND: Studies have identified health literacy (HL) as an important determinant of asthma and chronic obstructive pulmonary disease (COPD) management. There are, however, limited data on patients' and health care professionals (HCPs') insights about the link between HL and management of asthma and COPD. OBJECTIVE: The aim of this study was to elicit patients' and HCPs' perspectives with respect to factors affecting HL in the context of asthma and COPD management. METHODS: A total of 16 semi-structured focus groups (10 in English and 6 in French) with patients with asthma or COPD (n = 93) and 45 interviews with HCPs, researchers, and policymakers were conducted between June 2015 and April 2017. Participants were asked to share their perspectives with respect to five predefined HL domains-accessing, understanding, evaluating, communicating, and using health-related information-in relation to disease self-management practices. Data were analyzed qualitatively, using a content analysis approach. KEY RESULTS: Most patients and HCPs reflected on factors hampering HL in relation to asthma and COPD management. Thoughts such as "not having enough time during medical consultations," "not receiving consistent messages from different health care professionals," and "language or cultural differences" were frequently mentioned by both patients and HCPs. CONCLUSIONS: We identified multiple factors affecting communication between patients and HCPs as it relates to the self-management of their disease. These included inconsistent messages from different providers, limited consultation time, use of technical language, failure to account for cultural differences, and reduced health literacy, especially as it related to written communication. Future interventions that aim to enhance HL skills in the context of asthma and COPD self-management should consider these issues. [HLRP: Health Literacy Research and Practice. 2021;5(3):e179-e193.] Plain Language Summary: The current study advances the health literacy (HL) knowledge base by adding patients' and health care professionals' valuable insights on factors that hamper or facilitate HL in relation to asthma and chronic obstructive pulmonary disease (COPD) management. An important insight from this study is that receiving conflicting information from different health care professional's hampers HL in patients with asthma and/or COPD.

Exploring PI3Kδ Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled Trials.

Background: Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD). Objective: To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD. Methods: In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg). Endpoints included induced sputum at various time points before and during treatment for the measurement of transcriptomics (primary endpoint), inflammatory mediators, functional respiratory imaging (FRI), and spirometry. Results: In stable COPD patients, the use of nemiralisib was associated with alterations in sputum neutrophil transcriptomics suggestive of an improvement in migration phenotype; however, the same nemiralisib-evoked effects were not observed in AECOPD. Inhibition of sputum inflammatory mediators was also observed in stable but not AECOPD patients. In contrast, a placebo-corrected improvement in forced expiratory volume in 1 sec of 136 mL (95% Credible Intervals -46, 315mL) with a probability that the true treatment ratio was >0% (Pr(θ>0)) of 93% was observed in AECOPD. However, FRI endpoints remained unchanged. Conclusion: We provide evidence for nemiralisib-evoked changes in neutrophil migration phenotype in stable COPD but not AECOPD, despite improving lung function in the latter group. We conclude that induced sputum can be used for measuring evidence of alteration of neutrophil phenotype in stable patients, and our study provides a data set of the sputum transcriptomic changes during recovery from AECOPD.

Ultrasound Evaluation of the Quadriceps Muscle Contractile Index in Patients with Stable Chronic Obstructive Pulmonary Disease: Relationships with Clinical Symptoms, Disease Severity and Diaphragm Contractility.

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with changes in the composition and function of peripheral and respiratory muscles, which can negatively impact quality of life. Ultrasonography can provide a non-invasive evaluation of the integrity of both peripheral muscles and diaphragm, but its use in patients with COPD is still being investigated. We aimed at evaluating the relationship between quadriceps size, using ultrasonography and symptoms, lung function and diaphragm contractility in a cohort of patients with COPD. Methods: COPD patients were prospectively recruited and ultrasonography of the dominant quadriceps and of the diaphragm was performed. Quadriceps size was evaluated using three measurements: 1) cross-sectional area of the rectus femoris (Qcsa), 2) thickness (Qthick) and 3) contractile index (Qci), defined as the ratio of quadriceps thickness/total anterior thigh thickness. Diaphragm contractility was evaluated using thickening fraction (TFdi). Clinical characteristics and number of moderate-to-severe exacerbations in the previous year were retrieved from medical files. Dyspnea (mMRC scale) and disease impact on health status (COPD Assessment Test (CAT)) were measured at inclusion. Fat-free mass index (FFMI) was assessed using bioelectrical impedance. Results: Forty patients were recruited (20 males, mean age and FEV1 66±6 years and 49±17%predicted, respectively). Mean Qcsa, Qthick and Qci were 336±145 mm2, 1.55±0.53 cm and 64±16%, respectively, and mean TFdi was 91±36%. Qci was significantly correlated with FFMI (rho=0.59, p=0.001), TFdi (rho=0.41, p=0.008), FEV1 (rho=0.43, p=0.001) but not with age (rho=0.18, p=0.28). Qci was significantly correlated to CAT score (rho=-0.47, p=0.002), even when controlled for FEV1, and was lower in patients with an mMRC score ≥2 (55±15 vs 70±14%, p=0.002). Qcsa and Qci were significantly lower in patients with frequent exacerbations. In a multiple linear regression analysis that included age, gender, FFMI, FEV1 and TFdi, only FFMI and TFdi were found to be significantly related to lower Qci values. Conclusion: In patients with COPD, ultrasound evaluation of the quadriceps contractile index is feasible and related to disease severity, clinical symptoms, exacerbation history and diaphragm contractility. As such, it may provide a novel tool for the evaluation of the severity and burden of the disease in this population. Further studies are required to better delineate its potential role as a prognostic marker in this population.

Asthma and COPD patients' perceived link between health literacy core domains and self-management of their condition.

OBJECTIVE: Health literacy (HL) is a person's ability to practically apply a wide range of cognitive and non-cognitive skills, to make health-related decisions. Currently, no tool applies all HL core domains to capture necessary data to measures HL in adult asthma and COPD patients. We endeavored to develop a comprehensive, function-based tool that adequately and accurately measures HL skills of this patient population. We explored the perspectives of patients related to each core HL domain, with an emphasis on self-management practices. METHODS: Sixteen focus groups were conducted (n = 93; 40 asthma and 53 COPD) across Canada. Data was analyzed using NVivo12. RESULTS: Thirteen subthemes were identified within five HL domains: (a) access: active access; passive access; lack of access; (b) understanding: how to improve understanding; (c) trustworthiness; relevancy and validity of information: pre- and post- application of information; (d) communication: barriers to proper communication; (e) application of information: making health decisions. CONCLUSIONS: Participants provided valuable insight in terms of disease management topics and corresponding items to include in our HL tool. PRACTICE IMPLICATIONS: Involvement of patients from initial stage allowed us to develop a tool that will serve as a first ever developed HL tool for asthma and COPD patient group.

Effects of Pursed Lip Breathing on Exercise Capacity and Dyspnea in Patients With Interstitial Lung Disease: A RANDOMIZED, CROSSOVER STUDY.

BACKGROUND: Although mainly described in patients with chronic obstructive pulmonary disease, pursed lip breathing (PLB) could prove useful in patients with interstitial lung disease (ILD) by improving exertional tachypnea and respiratory control. This prospective, randomized, crossover trial aimed at evaluating the impact of PLB on dyspnea and walking distance in ILD patients. METHODS: ILD patients with total lung capacity of <80% predicted were randomized to 6-min walk tests using either PLB or usual breathing. Patients were crossed over for the second 6-min walk tests and served as their own controls. Ventilatory and metabolic variables were recorded using a portable metabolic cart and were compared at 1-min intervals. RESULTS: Thirty-five patients were included (mean forced vital capacity of 64 ± 10% predicted). Use of PLB resulted in lower mean respiratory rates and larger tidal volumes (both P < .001), worsened dyspnea ratings (post-6-min walk test Borg score: 5.2 ± 2.6 vs 4.2 ± 2.3, P < .001), and walking distance (403 ± 102 m vs 429 ± 93 m, P < .001). Twenty-nine patients (83%) described PLB as less comfortable than usual breathing. Both groups had similar total ventilation and oxygen saturation (all P > .05), but PLB resulted in higher mean oxygen uptake (13.9 ± 3.6 vs 12.9 ± 3.2 mL/kg/min, P = .02), even when corrected for walking distance (P < .001). CONCLUSION: In ILD patients, acute exposure to PLB did not improve exertional dyspnea, walking distance, or gas exchange, and was associated with higher metabolic demands than usual breathing. These results cast doubt on the usefulness of this technique in ILD patients and should be taken into account when tailoring pulmonary rehabilitation programs to this population.

Dose omission to shorten methacholine challenge testing: clinical consequences of the use of a 10% fall in FEV1 threshold.

INTRODUCTION: In methacholine challenge testing (MCT), skipping a methacholine dose is suggested if FEV1 falls by < 5%. Using a larger threshold may further shorten test duration, but data supporting this hypothesis is lacking. We evaluated the safety and consequences of using a 10% FEV1 fall as threshold to skip the next dose of methacholine in patients undergoing MCT. METHODS: We reviewed MCTs performed in our center in 2017-2018. A ≤ 10% FEV1 fall allowed the omission of the next methacholine dose. Patients of interest were those in which a dose was skipped after a previous FEV1 fall outside the usual range (5-10%, termed "skip5-10%"). Adverse events [AE; mild: > 1 nebulized salbutamol dose (2.5 mg) to reach basal FEV1, palpitations; severe: hypoxemia and/or need for medical attention or intervention] were compared in the skip5-10% group and others. Regression analysis was used to identify predictors of AE. RESULTS: 208 MCTs were analysed (135 males, age 52 ± 15 years). Skip5-10% occurred 111 times in 90 tests. Prevalence of AE was 5% and all were mild. Patients who developed AEs had lower FEV1, FVC and FEV1/FVC ratio, and higher lung volume values (all p < 0.05), but similar prevalence of skip5-10% (36 vs. 44%, p = 0.64). Overall, MCTs in which at least one skip5-10% occurred had a lower mean number of doses (3.1 ± 0.6 vs. 3.5 ± 1.3 doses, p = 0.007). Baseline residual volume was independently related to the development of AEs (OR 1.05, 95% CI 1.01-1.10, p = 0.01), but not the presence of a skip5-10%, even when the skipped dose directly led to the reaching of PC20 (OR 5.40, 95% CI 0.73-39.22, p = 0.10). CONCLUSION: Omitting a methacholine dose based on a ≤ 10% fall in FEV1 occurs frequently and has the potential to shorten test duration. AE are rare, but patients with worse baseline lung function and gas trapping are at increased risk of mild side effects.

Pilot project: Physiologic responses to a high-intensity active video game with COPD patients-Tools for home rehabilitation.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a respiratory condition that causes a significant deterioration of the quality of life. However, exercise can improve the quality of life for COPD patients and it is for this reason previous study observed the effects of active video games to increase exercise. Using motion capture devices with short bursts of exercise never been tried with COPD patients. OBJECTIVES: The objective was to observe the feasibility of using this device safely and easily with COPD patients. METHODS: A total of 14 participants (8 men, 69 ± 6 years, 6 women, 74 ± 6 years), with a moderate to severe COPD diagnosis performed exercise games (Shape-Up, Ubisoft, Mtl) adapted under supervision. Gaming sessions of 10-15 min duration were composed of four games of about 1.5 min separated by rest. RESULTS: Average and peak minute ventilation, and METs peak were, respectively: Stunt Run game (lifting knees on spot) 25.3 ± 6.8, 33.5 ± 8.2 L/min and 4.2 ± 1.5 METs; Arctic Punch game (punching targets): 23.1 ± 5.6, 31.8 ± 9.8 L/min and 3.7 ± 1.2 METs; To the Core game (core twist), 22.2 ± 7.3, 29.2 ± 9.9 L/min and 3.3 ± 1.1 METs; and Squat me to the Moon game (sitting to standing), 27.8 ± 6.7, 36.8 ± 11.1 L/min and 4.4 ± 1.1 METs. CONCLUSION: Knowing the pleasure reported by the participants, the safety, and the ability to use it with assistance, it seems that the games could be a good tool in order for COPD patients to exercise at home. However, further investigation needs to be completed in order to observe the benefits in comparison to a traditional training program.

Stair-Climbing Capacity as a Marker of Improvement Following Pulmonary Rehabilitation.

PURPOSE: The aim of this study was to explore the potential and safety of a stair-climbing test as a tool to monitor improvement following pulmonary rehabilitation (PR) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Stair-climbing capacity was assessed in 139 patients with COPD before and after a comprehensive 8-week PR program, which included stair-climbing training. Stair-climbing capacity was assessed as the total number of flights of stairs climbed without stopping. A constant work rate endurance test (CET) was also performed before and after PR. Change in stair-climbing after PR (Δstairs) was compared and correlated to the change in endurance time (ΔCET) and, for 40 patients, to the change in COPD assessment test (ΔCAT) score. RESULTS: Most patients had moderate to severe COPD (mean forced expiratory volume in 1 second = 54% ± 20% predicted). Stair-climbing capacity, endurance time, and CAT score improved after PR (2.8 ± 1.4 vs 8.3 ± 3.3 flights, 408 ± 272 vs 717 ± 415 seconds, and 20.0 ± 6.4 vs 17.6 ± 6.6 units, respectively; P value for all < .001). Δstairs was moderately correlated to ΔCET (r = 0.49; P < .001) and well correlated to ΔCAT (r = -0.71; P < .001). Patients with greater change in Δstairs had better baseline resting lung function and aerobic capacity. No adverse events were reported during stair-climbing. CONCLUSION: Stair-climbing is responsive to training in patients with COPD and is correlated to the change in CAT score following PR. Although the test requires further standardization, it could eventually be used as a simple and safe way to assess improvement following interventions in COPD.