A survey and stakeholder group prioritised key systematic review questions in airways disease.

Objective: Priority setting is important for healthcare research. The Cochrane Airways Group wanted to prioritise topics for systematic reviews across all chronic respiratory diseases with limited resources and according to latest Cochrane policy.The objective was to prioritise 10 reviews of importance to the public (patients, carers, healthcare professionals and researchers) from a patient survey. Study design and setting: We convened a stakeholder group of patients, carers, healthcare professionals and representatives from charities. We conducted an online survey to collect uncertainties about the treatment and management of respiratory disease from the public. Uncertainties were ranked by the stakeholder group, and scoping searches refined the uncertainties into systematic review questions. Results: We received 147 survey responses. We removed duplicates and blank responses and asked the stakeholder group to rank 100 uncertainties. The first round of voting produced a list of 29 topics and the second round resulted in 12 uncertainties. These uncertainties were scoped with literature searches and teased out further into systematic review topics. We identified 3 Cochrane reviews to update, 8 new review topics, and 3 evidence gaps. Conclusion: We successfully convened a stakeholder group and prioritised a list of uncertainties in the treatment and management of airways diseases that had been identified by patients and the public.

Tailored or adapted interventions for adults with chronic obstructive pulmonary disease and at least one other long-term condition: a mixed methods review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by shortness of breath, cough and recurrent exacerbations. People with COPD often live with one or more co-existing long-term health conditions (comorbidities). People with more severe COPD often have a higher number of comorbidities, putting them at greater risk of morbidity and mortality. OBJECTIVES: To assess the effectiveness of any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention for people with COPD and one or more common comorbidities (quantitative data, RCTs) in terms of the following outcomes: Quality of life, exacerbations, functional status, all-cause and respiratory-related hospital admissions, mortality, pain, and depression and anxiety. To assess the effectiveness of an adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more common comorbidities (quantitative data, RCTs) compared to usual care in terms of the following outcomes: Quality of life, exacerbations, functional status, all-cause and respiratory-related hospital admissions, mortality, pain, and depression and anxiety. To identify emerging themes that describe the views and experiences of patients, carers and healthcare professionals when receiving or providing care to manage multimorbidities (qualitative data). SEARCH METHODS: We searched multiple databases including the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, and CINAHL, to identify relevant randomised and qualitative studies. We also searched trial registries and conducted citation searches. The latest search was conducted in January 2021. SELECTION CRITERIA: Eligible randomised controlled trials (RCTs) compared a) any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention, or b) any adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more comorbidities, compared to usual care. We included qualitative studies or mixed-methods studies to identify themes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for analysis of the RCTs. We used Cochrane's risk of bias tool for the RCTs and the CASP checklist for the qualitative studies. We planned to use the Mixed Methods Appraisal tool (MMAT) to assess the risk of bias in mixed-methods studies, but we found none. We used GRADE and CERQual to assess the quality of the quantitative and qualitative evidence respectively. The primary outcome measures for this review were quality of life and exacerbations. MAIN RESULTS: Quantitative studies We included seven studies (1197 participants) in the quantitative analyses, with interventions including telemonitoring, pulmonary rehabilitation, treatment optimisation, water-based exercise training and case management. Interventions were either compared with usual care or with an active comparator (such as land-based exercise training). Duration of trials ranged from 4 to 52 weeks. Mean age of participants ranged from 64 to 72 years and COPD severity ranged from mild to very severe. Trials included either people with COPD and a specific comorbidity (including cardiovascular disease, metabolic syndrome, lung cancer, head or neck cancer, and musculoskeletal conditions), or with one or more comorbidities of any type. Overall, we judged the evidence presented to be of moderate to very low certainty (GRADE), mainly due to the methodological quality of included trials and imprecision of effect estimates. Intervention versus usual care Quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) total score may improve with tailored pulmonary rehabilitation compared to usual care at 52 weeks (mean difference (MD) -10.85, 95% confidence interval (CI) -12.66 to -9.04; 1 study, 70 participants; low-certainty evidence). Tailored pulmonary rehabilitation is likely to improve COPD assessment test (CAT) scores compared with usual care at 52 weeks (MD -8.02, 95% CI -9.44 to -6.60; 1 study, 70 participants, moderate-certainty evidence) and with a multicomponent telehealth intervention at 52 weeks (MD -6.90, 95% CI -9.56 to -4.24; moderate-certainty evidence). Evidence is uncertain about effects of pharmacotherapy optimisation or telemonitoring interventions on CAT improvement compared with usual care. There may be little to no difference in the number of people experiencing exacerbations, or mean exacerbations with case management compared with usual care (OR 1.09, 95% CI 0.75 to 1.57; 1 study, 470 participants; very low-certainty evidence). For secondary outcomes, six-minute walk distance (6MWD) may improve with pulmonary rehabilitation, water-based exercise or multicomponent interventions at 38 to 52 weeks (low-certainty evidence). A multicomponent intervention may result in fewer people being admitted to hospital at 17 weeks, although there may be little to no difference in a telemonitoring intervention. There may be little to no difference between intervention and usual care for mortality. Intervention versus active comparator We included one study comparing water-based and land-based exercise (30 participants). We found no evidence for quality of life or exacerbations. There may be little to no difference between water- and land-based exercise for 6MWD (MD 5 metres, 95% CI -22 to 32; 38 participants; very low-certainty evidence). Qualitative studies One nested qualitative study (21 participants) explored perceptions and experiences of people with COPD and long-term conditions, and of researchers and health professionals who were involved in an RCT of telemonitoring equipment. Several themes were identified, including health status, beliefs and concerns, reliability of equipment, self-efficacy, perceived ease of use, factors affecting usefulness and perceived usefulness, attitudes and intention, self-management and changes in healthcare use. We judged the qualitative evidence presented as of very low certainty overall. AUTHORS' CONCLUSIONS: Owing to a paucity of eligible trials, as well as diversity in the intervention type, comorbidities and the outcome measures reported, we were unable to provide a robust synthesis of data. Pulmonary rehabilitation or multicomponent interventions may improve quality of life and functional status (6MWD), but the evidence is too limited to draw a robust conclusion. The key take-home message from this review is the lack of data from RCTs on treatments for people living with COPD and comorbidities. Given the variation in number and type of comorbidity(s) an individual may have, and severity of COPD, larger studies reporting individual patient data are required to determine these effects.

Antibiotics for exacerbations of asthma.

BACKGROUND: Asthma is a chronic respiratory condition that affects over 300 million adults and children worldwide. It is characterised by wheeze, cough, chest tightness, and shortness of breath. Symptoms typically are intermittent and may worsen over a short time, leading to an exacerbation. Asthma exacerbations can be serious, leading to hospitalisation or even death in rare cases. Exacerbations may be treated by increasing an individual's usual medication and providing additional medication, such as oral steroids. Although antibiotics are sometimes included in the treatment regimen, bacterial infections are thought to be responsible for only a minority of exacerbations, and current guidance states that antibiotics should be reserved for cases in which clear signs, symptoms, or laboratory test results are suggestive of bacterial infection. OBJECTIVES: To determine the efficacy and safety of antibiotics in the treatment of asthma exacerbations. SEARCH METHODS: We searched the Cochrane Airways Trials Register, which contains records compiled from multiple electronic and handsearched resources. We also searched trial registries and reference lists of primary studies. We conducted the most recent search in October 2017. SELECTION CRITERIA: We included studies comparing antibiotic therapy for asthma exacerbations in adults or children versus placebo or usual care not involving an antibiotic. We allowed studies including any type of antibiotic, any dose, and any duration, providing the aim was to treat the exacerbation. We included parallel studies of any duration conducted in any setting and planned to include cluster trials. We excluded cross-over trials. We included studies reported as full-text articles, those published as abstracts only, and unpublished data. DATA COLLECTION AND ANALYSIS: At least two review authors screened the search results for eligible studies. We extracted outcome data, assessed risk of bias in duplicate, and resolved discrepancies by involving another review author. We analysed dichotomous data as odds ratios (ORs) or risk differences (RDs), and continuous data as mean differences (MDs), all with a fixed-effect model. We described skewed data narratively. We graded the results and presented evidence in 'Summary of findings' tables for each comparison. Primary outcomes were intensive care unit/high dependence unit (ICU/HDU) admission, duration of symptoms/exacerbations, and all adverse events. Seconday outcomes were mortality, length of hospital admission, relapse after index presentation, and peak expiratory flow rate (PEFR). MAIN RESULTS: Six studies met our inclusion criteria and included a total of 681 adults and children with exacerbations of asthma. Mean age in the three studies in adults ranged from 36.2 to 41.2 years. The three studies in children applied varied inclusion criteria, ranging from one to 18 years of age. Five studies explicitly excluded participants with obvious signs and symptoms of bacterial infection (i.e. those clearly meeting current guidance to receive antibiotics). Four studies investigated macrolide antibiotics, and two studies investigated penicillin (amoxicillin and ampicillin) antibiotics; both studies using penicillin were conducted over 35 years ago. Five studies compared antibiotics versus placebo, and one was open-label. Study follow-up ranged from one to twelve weeks. Trials were of varied methodological quality, and we were able to perform only limited meta-analysis.None of the included trials reported ICU/HDU admission, although one participant in the placebo group of a study including children with status asthmaticus experienced a respiratory arrest and was ventilated. Four studies reported asthma symptoms, but we were able to combine results for only two macrolide studies of 416 participants; the MD in diary card symptom score was -0.34 (95% confidence interval (CI) -0.60 to -0.08), with lower scores (on a 7 point scale) denoting improved symptoms. Two macrolide studies reported symptom-free days. One study of 255 adults authors reported the percentage of symptom-free days at 10 days as 16% in the antibiotic group and 8% in the placebo group. In a further study of 40 children study authors reported significantly more symptom-free days at all time points in the antibiotic group compared with the usual care group. The same study reported the duration in days of the index asthma exacerbation, again favouring the antibiotic group. One study of a penicillin including 69 participants reported asthma symptoms at hospital discharge; the between-group difference for both studies was reported as non-significant.We combined data for serious adverse events from three studies involving 502 participants, but events were rare; the three trials reported only 10 events: five in the antibiotic group and five in the placebo group. We combined data for all adverse events (AEs) from three studies, but the effect estimate is imprecise (OR 0.99, 95% CI 0.69 to 1.43). No deaths were reported in any of the included studies.Two studies investigating penicillins reported admission duration; neither study reported a between-group difference. In one study (263 participants) of macrolides, two participants in each arm were reported as experiencing a relapse, defined as a further exacerbation, by the six-week time points. We combined PEFR endpoint results at 10 days for two macrolide studies; the result favoured antibiotics over placebo (MD 23.42 L/min, 95% CI 5.23 to 41.60). One study in children reported the maximum peak flow recorded during the follow-up period, favouring the clarithromycin group, but the confidence interval includes no difference (MD 38.80, 95% CI -11.19 to 88.79).Grading of outcomes ranged from moderate to very low quality, with quality of outcomes downgraded for suspicion of publication bias, indirectness, imprecision, and poor methodological quality of studies. AUTHORS' CONCLUSIONS: We found limited evidence that antibiotics given at the time of an asthma exacerbation may improve symptoms and PEFR at follow-up compared with standard care or placebo. However, findings were inconsistent across the six heterogeneous studies included, two of the studies were conducted over 30 years ago and most of the participants included in this review were recruited from emergency departments, limiting the applicability of findings to this population. Therefore we have limited confidence in the results. We found insufficient evidence about several patient-important outcomes (e.g. hospital admission) to form conclusions. We were unable to rule out a difference between groups in terms of all adverse events, but serious adverse events were rare.