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The Cochrane Database of Systematic... Feb 2021Interstitial lung disease (ILD) is characterised by reduced functional capacity, dyspnoea and exercise-induced hypoxia. Pulmonary rehabilitation is often used to improve... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Interstitial lung disease (ILD) is characterised by reduced functional capacity, dyspnoea and exercise-induced hypoxia. Pulmonary rehabilitation is often used to improve symptoms, health-related quality of life and functional status in other chronic lung conditions. There is accumulating evidence for comparable effects of pulmonary rehabilitation in people with ILD. However, further information is needed to clarify the long-term benefit and to strengthen the rationale for pulmonary rehabilitation to be incorporated into standard clinical management of people with ILD. This review updates the results reported in 2014.
OBJECTIVES
To determine whether pulmonary rehabilitation in people with ILD has beneficial effects on exercise capacity, symptoms, quality of life and survival compared with no pulmonary rehabilitation in people with ILD. To assess the safety of pulmonary rehabilitation in people with ILD.
SEARCH METHODS
We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO) and PEDro from inception to April 2020. We searched the reference lists of relevant studies, international clinical trial registries and respiratory conference abstracts to look for qualifying studies.
SELECTION CRITERIA
We included randomised controlled trials and quasi-randomised controlled trials in which pulmonary rehabilitation was compared with no pulmonary rehabilitation or with other therapy in people with ILD of any origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias. We contacted study authors to request missing data and information regarding adverse effects. We specified a priori subgroup analyses for participants with idiopathic pulmonary fibrosis (IPF) and participants with severe lung disease (low diffusing capacity or desaturation during exercise). There were insufficient data to perform the prespecified subgroup analysis for type of exercise training modality.
MAIN RESULTS
For this update, we included an additional 12 studies resulting in a total of 21 studies. We included 16 studies in the meta-analysis (356 participants undertook pulmonary rehabilitation and 319 were control participants). The mean age of participants ranged from 36 to 72 years and included people with ILD of varying aetiology, sarcoidosis or IPF (with mean transfer factor of carbon dioxide (TLCO) % predicted ranging from 37% to 63%). Most pulmonary rehabilitation programmes were conducted in an outpatient setting, with a small number conducted in home-based, inpatient or tele-rehabilitation settings. The duration of pulmonary rehabilitation ranged from three to 48 weeks. There was a moderate risk of bias due to the absence of outcome assessor blinding and intention-to-treat analyses and the inadequate reporting of randomisation and allocation procedures in 60% of the studies. Pulmonary rehabilitation probably improves the six-minute walk distance (6MWD) with mean difference (MD) of 40.07 metres, 95% confidence interval (CI) 32.70 to 47.44; 585 participants; moderate-certainty evidence). There may be improvements in peak workload (MD 9.04 watts, 95% CI 6.07 to 12.0; 159 participants; low-certainty evidence), peak oxygen consumption (MD 1.28 mL/kg/minute, 95% CI 0.51 to 2.05; 94 participants; low-certainty evidence) and maximum ventilation (MD 7.21 L/minute, 95% CI 4.10 to 10.32; 94 participants; low-certainty evidence). In the subgroup of participants with IPF, there were comparable improvements in 6MWD (MD 37.25 metres, 95% CI 26.16 to 48.33; 278 participants; moderate-certainty evidence), peak workload (MD 9.94 watts, 95% CI 6.39 to 13.49; low-certainty evidence), VO (oxygen uptake) peak (MD 1.45 mL/kg/minute, 95% CI 0.51 to 2.40; low-certainty evidence) and maximum ventilation (MD 9.80 L/minute, 95% CI 6.06 to 13.53; 62 participants; low-certainty evidence). The effect of pulmonary rehabilitation on maximum heart rate was uncertain. Pulmonary rehabilitation may reduce dyspnoea in participants with ILD (standardised mean difference (SMD) -0.36, 95% CI -0.58 to -0.14; 348 participants; low-certainty evidence) and in the IPF subgroup (SMD -0.41, 95% CI -0.74 to -0.09; 155 participants; low-certainty evidence). Pulmonary rehabilitation probably improves health-related quality of life: there were improvements in all four domains of the Chronic Respiratory Disease Questionnaire (CRQ) and the St George's Respiratory Questionnaire (SGRQ) for participants with ILD and for the subgroup of people with IPF. The improvement in SGRQ Total score was -9.29 for participants with ILD (95% CI -11.06 to -7.52; 478 participants; moderate-certainty evidence) and -7.91 for participants with IPF (95% CI -10.55 to -5.26; 194 participants; moderate-certainty evidence). Five studies reported longer-term outcomes, with improvements in exercise capacity, dyspnoea and health-related quality of life still evident six to 12 months following the intervention period (6MWD: MD 32.43, 95% CI 15.58 to 49.28; 297 participants; moderate-certainty evidence; dyspnoea: MD -0.29, 95% CI -0.49 to -0.10; 335 participants; SGRQ Total score: MD -4.93, 95% CI -7.81 to -2.06; 240 participants; low-certainty evidence). In the subgroup of participants with IPF, there were improvements at six to 12 months following the intervention for dyspnoea and SGRQ Impact score. The effect of pulmonary rehabilitation on survival at long-term follow-up is uncertain. There were insufficient data to allow examination of the impact of disease severity or exercise training modality. Ten studies provided information on adverse events; however, there were no adverse events reported during rehabilitation. Four studies reported the death of one pulmonary rehabilitation participant; however, all four studies indicated this death was unrelated to the intervention received.
AUTHORS' CONCLUSIONS
Pulmonary rehabilitation can be performed safely in people with ILD. Pulmonary rehabilitation probably improves functional exercise capacity, dyspnoea and quality of life in the short term, with benefits also probable in IPF. Improvements in functional exercise capacity, dyspnoea and quality of life were sustained longer term. Dyspnoea and quality of life may be sustained in people with IPF. The certainty of evidence was low to moderate, due to inadequate reporting of methods, the lack of outcome assessment blinding and heterogeneity in some results. Further well-designed randomised trials are needed to determine the optimal exercise prescription, and to investigate ways to promote longer-lasting improvements, particularly for people with IPF.
Topics: Adult; Aged; Dyspnea; Exercise; Exercise Tolerance; Humans; Lung Diseases, Interstitial; Middle Aged; Quality of Life
PubMed: 34559419
DOI: 10.1002/14651858.CD006322.pub4 -
Children (Basel, Switzerland) Mar 2023Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) is a new CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) modulator treatment, used over the last few years,... (Review)
Review
Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) is a new CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) modulator treatment, used over the last few years, which has shown an improvement in different clinical outcomes in patients with cystic fibrosis (CF). The objective of this study was a systematic research of the literature on the efficacy and safety of this CFTR modulator on patients with CF. A search of Pubmed was conducted for randomized clinical trials and observational studies published from 2012 to September 2022. The included full manuscripts comprised nine clinical trials and 16 observational studies, whose participants were aged ≥12 years or were children 6-11 years old with at least one Phe508del mutation and/or advanced lung disease (ALD). These studies reported that ELX/TEZ/IVA has a significant positive effect on the lung function of patients with CF, by ameliorating parameters such as FEV, LCI, pulmonary exacerbations or sweat chloride concentration, increasing BMI and improving quality of their life. Its role in cystic fibrosis-related diabetes (CFRD) is not yet clear. It was found that this new CFTR modulator has an overall favorable safety profile, with mild to moderate adverse events. Further studies are needed for a deeper understanding of the impact of CFTR modulators on other CF manifestations, or the possibility of treating with ELX/TEZ/IVA CF patients with rare CFTR mutations.
PubMed: 36980112
DOI: 10.3390/children10030554 -
BMC Pulmonary Medicine Dec 2021Research questions To compare the efficacy of nintedanib and pirfenidone in the treatment of progressive pulmonary fibrosis; and to compare the efficacy of anti-fibrotic... (Comparative Study)
Comparative Study Meta-Analysis
Efficacy of antifibrotic drugs, nintedanib and pirfenidone, in treatment of progressive pulmonary fibrosis in both idiopathic pulmonary fibrosis (IPF) and non-IPF: a systematic review and meta-analysis.
BACKGROUND
Research questions To compare the efficacy of nintedanib and pirfenidone in the treatment of progressive pulmonary fibrosis; and to compare the efficacy of anti-fibrotic therapy (grouping nintedanib and pirfenidone together) in patients with IPF versus patients with progressive lung fibrosis not classified as IPF.
STUDY DESIGN AND METHODS
A search of databases including MEDLINE, EMBASE, PubMed, and clinicaltrials.gov was conducted. Studies were included if they were randomised controlled trials of pirfenidone or nintedanib in adult patients with IPF or non-IPF patients, and with extractable data on mortality or decline in forced vital capacity (FVC). Random effects meta-analyses were performed on changes in FVC and where possible on mortality in the selected studies.
RESULTS
13 trials of antifibrotic therapy were pooled in a meta-analysis (with pirfenidone and nintedanib considered together as anti-fibrotic therapy). The change in FVC was expressed as a standardised difference to allow pooling of percentage and absolute changes. The mean effect size in the IPF studies was - 0.305 (SE 0.043) (p < 0.001) and in the non-IPF studies the figures were - 0.307 (SE 0.063) (p < 0.001). There was no evidence of any difference between the two groups for standardised rate of FVC decline (p = 0.979). Pooling IPF and non-IPF showed a significant reduction in mortality, with mean risk ratio of 07.01 in favour of antifibrotic therapy (p = 0.008). A separate analysis restricted to non-IPF did not show a significant reduction in mortality (risk ratio 0.908 (0.547 to 1.508), p = 0.71.
INTERPRETATION
Anti-fibrotic therapy offers protection against the rate of decline in FVC in progressive lung fibrosis, with similar efficacy shown between the two anti-fibrotic agents currently in clinical use. There was no significant difference in efficacy of antifibrotic therapy whether the underlying condition was IPF or non-IPF with progressive fibrosis, supporting the hypothesis of a common pathogenesis. The data in this analysis was insufficient to be confident about a reduction in mortality in non-IPF with anti-fibrotic therapy. Trial Registration PROSPERO, registration number CRD42021266046.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antifibrotic Agents; Cause of Death; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pulmonary Fibrosis; Pyridones; Treatment Outcome
PubMed: 34895203
DOI: 10.1186/s12890-021-01783-1 -
Aging Cell Jul 2023Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains... (Meta-Analysis)
Meta-Analysis Review
Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta-analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health-related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR-Egger, weighted median, MR-PRESSO, and multivariate MR. Meta-analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non-GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length.
Topics: Humans; Mendelian Randomization Analysis; Arthritis, Rheumatoid; Glioma; Hypertension; Telomere; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 37232505
DOI: 10.1111/acel.13874 -
BMJ Open Respiratory Research Jun 2023Interstitial lung disease (ILD) is a collective term representing a diverse group of pulmonary fibrotic and inflammatory conditions. Due to the diversity of ILD... (Review)
Review
Interstitial lung disease (ILD) is a collective term representing a diverse group of pulmonary fibrotic and inflammatory conditions. Due to the diversity of ILD conditions, paucity of guidance and updates to diagnostic criteria over time, it has been challenging to precisely determine ILD incidence and prevalence. This systematic review provides a synthesis of published data at a global level and highlights gaps in the current knowledge base. Medline and Embase databases were searched systematically for studies reporting incidence and prevalence of various ILDs. Randomised controlled trials, case reports and conference abstracts were excluded. 80 studies were included, the most described subgroup was autoimmune-related ILD, and the most studied conditions were rheumatoid arthritis (RA)-associated ILD, systemic sclerosis associated (SSc) ILD and idiopathic pulmonary fibrosis (IPF). The prevalence of IPF was mostly established using healthcare datasets, whereas the prevalence of autoimmune ILD tended to be reported in smaller autoimmune cohorts. The prevalence of IPF ranged from 7 to 1650 per 100 000 persons. Prevalence of SSc ILD and RA ILD ranged from 26.1% to 88.1% and 0.6% to 63.7%, respectively. Significant heterogeneity was observed in the reported incidence of various ILD subtypes. This review demonstrates the challenges in establishing trends over time across regions and highlights a need to standardise ILD diagnostic criteria.PROSPERO registration number: CRD42020203035.
Topics: Humans; Prevalence; Incidence; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis; Arthritis, Rheumatoid
PubMed: 37308252
DOI: 10.1136/bmjresp-2022-001291 -
International Journal of Molecular... Apr 2023Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use... (Review)
Review
Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use worldwide. These drugs have been shown to reduce the rate of decline in forced vital capacity and the risk of acute exacerbation among patients with idiopathic pulmonary fibrosis. Recent data suggest that different interstitial lung diseases with a progressive pulmonary fibrosis phenotype can share similar pathogenetic and biological pathways and could be amenable to antifibrotic therapies. Indeed, historical management strategies in interstitial lung disease have failed to identify potential treatments once progression has occurred despite available drugs. In this systematic review, we summarized data on the efficacy of pirfenidone and nintedanib in interstitial lung diseases other than idiopathic pulmonary fibrosis as well as ongoing and upcoming clinical trials. We identify two well-designed trials regarding nintedanib demonstrating the efficacy of this drug in slowing disease progression in patients with interstitial lung diseases other than idiopathic pulmonary fibrosis. On the other hand, results on the use of pirfenidone in interstitial lung diseases other than idiopathic pulmonary fibrosis should be interpreted with more caution on the basis of trial limitations. Several randomized control trials are underway to improve the quality of evidence in the interstitial lung disease field.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Indoles; Pyridones; Treatment Outcome
PubMed: 37175556
DOI: 10.3390/ijms24097849 -
American Journal of Respiratory Cell... Mar 2023Microorganisms colonize the human body. The lungs and respiratory tract, previously believed to be sterile, harbor diverse microbial communities and the genomes of...
Microorganisms colonize the human body. The lungs and respiratory tract, previously believed to be sterile, harbor diverse microbial communities and the genomes of bacteria (bacteriome), viruses (virome), and fungi (mycobiome). Recent advances in amplicon and shotgun metagenomic sequencing technologies and data-analyzing methods have greatly aided the identification and characterization of microbial populations from airways. The respiratory microbiome has been shown to play roles in human health and disease and is an area of rapidly emerging interest in pulmonary medicine. In this review, we provide updated information in the field by focusing on four lung conditions, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis. We evaluate gut, oral, and upper airway microbiomes and how they contribute to lower airway flora. The discussion is followed by a systematic review of the lower airway microbiome in health and disease. We conclude with promising research avenues and implications for evolving therapeutics.
Topics: Humans; Lung; Asthma; Pulmonary Disease, Chronic Obstructive; Microbiota; Cystic Fibrosis
PubMed: 36476129
DOI: 10.1165/rcmb.2022-0208TR -
Journal of Thoracic Disease Mar 2020Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with significant dyspnea and limited exercise capacity. This systematic review aimed to... (Review)
Review
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with significant dyspnea and limited exercise capacity. This systematic review aimed to synthesize evidence of exercise interventions during pulmonary rehabilitation that aim to improve exercise capacity, dyspnea, and health-related quality of life (HRQL) in IPF patients.
METHODS
Searches were performed in MEDLINE, Embase, CENTRAL, SPORTDiscus, PubMed and PEDro from inception to January 2019 using search terms for: (I) participants: 'IPF or interstitial lung disease'; (II) interventions: 'aerobic training or resistance training or respiratory muscle training'; and (III) outcomes: 'exercise capacity or dyspnea or health-related quality of life'. Two reviewers independently screened titles, abstracts and full texts to identify eligible studies. Methodological quality of studies was assessed using the Downs and Black checklist and meta-analyses were performed.
RESULTS
Of 1,677 articles identified, 14 were included (four randomized controlled trials and 10 prospective pre-post design studies) that examined 362 patients receiving training and 95 control subjects. Exercise capacity was measured with the 6-minute walk distance, peak oxygen consumption, peak work rate, or endurance time for constant work rate cycling, which increased after exercise [aerobic exercise; aerobic and breathing exercises; aerobic and inspiratory muscle training (IMT) exercises] compared to the control groups. Dyspnea scores improved after aerobic and breathing exercises. HRQL also improved after aerobic exercise training alone or combined with breathing exercises. Aerobic training alone or combined with IMT or breathing exercises improved exercise capacity.
CONCLUSIONS
Breathing exercises appears to complement exercise training towards improved dyspnea and HRQL in patients with IPF.
PubMed: 32274173
DOI: 10.21037/jtd.2019.12.27 -
The Cochrane Database of Systematic... Aug 2022Physical activity (including exercise) may form an important part of regular care for people with cystic fibrosis (CF). This is an update of a previously published... (Review)
Review
BACKGROUND
Physical activity (including exercise) may form an important part of regular care for people with cystic fibrosis (CF). This is an update of a previously published review.
OBJECTIVES
To assess the effects of physical activity interventions on exercise capacity by peak oxygen uptake, lung function by forced expiratory volume in one second (FEV), health-related quality of life (HRQoL) and further important patient-relevant outcomes in people with cystic fibrosis (CF).
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The most recent search was on 3 March 2022. We also searched two ongoing trials registers: clinicaltrials.gov, most recently on 4 March 2022; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), most recently on 16 March 2022. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs comparing physical activity interventions of any type and a minimum intervention duration of two weeks with conventional care (no physical activity intervention) in people with CF.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected RCTs for inclusion, assessed methodological quality and extracted data. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 24 parallel RCTs (875 participants). The number of participants in the studies ranged from nine to 117, with a wide range of disease severity. The studies' age demographics varied: in two studies, all participants were adults; in 13 studies, participants were 18 years and younger; in one study, participants were 15 years and older; in one study, participants were 12 years and older; and seven studies included all age ranges. The active training programme lasted up to and including six months in 14 studies, and longer than six months in the remaining 10 studies. Of the 24 included studies, seven implemented a follow-up period (when supervision was withdrawn, but participants were still allowed to exercise) ranging from one to 12 months. Studies employed differing levels of supervision: in 12 studies, training was supervised; in 11 studies, it was partially supervised; and in one study, training was unsupervised. The quality of the included studies varied widely. This Cochrane Review shows that, in studies with an active training programme lasting over six months in people with CF, physical activity probably has a positive effect on exercise capacity when compared to no physical activity (usual care) (mean difference (MD) 1.60, 95% confidence interval (CI) 0.16 to 3.05; 6 RCTs, 348 participants; moderate-certainty evidence). The magnitude of improvement in exercise capacity is interpreted as small, although study results were heterogeneous. Physical activity interventions may have no effect on lung function (forced expiratory volume in one second (FEV) % predicted) (MD 2.41, 95% CI ‒0.49 to 5.31; 6 RCTs, 367 participants), HRQoL physical functioning (MD 2.19, 95% CI ‒3.42 to 7.80; 4 RCTs, 247 participants) and HRQoL respiratory domain (MD ‒0.05, 95% CI ‒3.61 to 3.51; 4 RCTs, 251 participants) at six months and longer (low-certainty evidence). One study (117 participants) reported no differences between the physical activity and control groups in the number of participants experiencing a pulmonary exacerbation by six months (incidence rate ratio 1.28, 95% CI 0.85 to 1.94) or in the time to first exacerbation over 12 months (hazard ratio 1.34, 95% CI 0.65 to 2.80) (both high-certainty evidence); and no effects of physical activity on diabetic control (after 1 hour: MD ‒0.04 mmol/L, 95% CI ‒1.11 to 1.03; 67 participants; after 2 hours: MD ‒0.44 mmol/L, 95% CI ‒1.43 to 0.55; 81 participants; moderate-certainty evidence). We found no difference between groups in the number of adverse events over six months (odds ratio 6.22, 95% CI 0.72 to 53.40; 2 RCTs, 156 participants; low-certainty evidence). For other time points (up to and including six months and during a follow-up period with no active intervention), the effects of physical activity versus control were similar to those reported for the outcomes above. However, only three out of seven studies adding a follow-up period with no active intervention (ranging between one and 12 months) reported on the primary outcomes of changes in exercise capacity and lung function, and one on HRQoL. These data must be interpreted with caution. Altogether, given the heterogeneity of effects across studies, the wide variation in study quality and lack of information on clinically meaningful changes for several outcome measures, we consider the overall certainty of evidence on the effects of physical activity interventions on exercise capacity, lung function and HRQoL to be low to moderate.
AUTHORS' CONCLUSIONS
Physical activity interventions for six months and longer likely improve exercise capacity when compared to no training (moderate-certainty evidence). Current evidence shows little or no effect on lung function and HRQoL (low-certainty evidence). Over recent decades, physical activity has gained increasing interest and is already part of multidisciplinary care offered to most people with CF. Adverse effects of physical activity appear rare and there is no reason to actively discourage regular physical activity and exercise. The benefits of including physical activity in an individual's regular care may be influenced by the type and duration of the activity programme as well as individual preferences for and barriers to physical activity. Further high-quality and sufficiently-sized studies are needed to comprehensively assess the benefits of physical activity and exercise in people with CF, particularly in the new era of CF medicine.
Topics: Adolescent; Adult; Cystic Fibrosis; Exercise; Forced Expiratory Volume; Humans; Quality of Life
PubMed: 35943025
DOI: 10.1002/14651858.CD002768.pub5 -
The European Respiratory Journal Apr 2023Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe... (Review)
Review
BACKGROUND
Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.
METHODS
COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.
RESULTS
Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).
CONCLUSIONS
This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
Topics: Child; Humans; Adult; Quality of Life; Reproducibility of Results; Disease Progression; Asthma; Outcome Assessment, Health Care; Anti-Asthmatic Agents
PubMed: 36229046
DOI: 10.1183/13993003.00606-2022