Daily Respiratory Research Analysis

BACKGROUND AND AIMS: Randomized trials of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) in patients with cardiovascular disease have not detected reduced risk of major adverse cardiovascular and cerebrovascular events (MACCEs). This study tested whether the cardiovascular benefit of CPAP occurs preferentially in high-risk OSA, characterized by greater OSA-related heart rate acceleration or hypoxaemia. METHODS: In a post hoc analysis of pooled Randomized Intervention with Continuous Positive Airway Pressure in Coronary Artery Disease and Obstructive Sleep Apnoea, Impact of Continuous Positive Airway Pressure on Patients with Acute Coronary Syndrome and Nonsleepy Obstructive Sleep Apnoea, and Sleep Apnoea Cardiovascular Endpoints Study randomized trials; outcomes were stratified by high-risk OSA status, defined by heart rate response following OSA respiratory events >9.4 b.p.m. (third tertile) or oxygen desaturation area under baseline (hypoxic burden) > 87.1% min/h (third tertile). Cox mixed models quantified the CPAP treatment effect on MACCE (including cardiovascular mortality, myocardial infarction, and stroke) within high-risk OSA and the difference vs low-risk status (primary test). Secondary analyses examined participants without excessive sleepiness (Epworth <11 points) or without increased blood pressure (systolic/diastolic <140/90 mmHg). RESULTS: In 3549 participants, 16.6% and 16.3% reached the MACCE endpoint with CPAP (n = 1778) and usual care (n = 1771), respectively. The CPAP treatment effect was greater in participants with vs without high-risk OSA [interaction hazard ratio (iHR) .69, 95% confidence interval (CI) .50-.95, Pinteraction = .024; Nhigh-risk = 1832]. The differential effect was stronger in those without excessive sleepiness (iHR .59, 95% CI .41-.84; Nhigh-risk = 1509), or without increased blood pressure (iHR .54, 95% CI .36-.81; Nhigh-risk = 1244). Continuous positive airway pressure benefits in high-risk OSA were observed alongside harm in low-risk OSA. CONCLUSIONS: Continuous positive airway pressure preferentially improves cardiovascular outcomes in high-risk OSA, while harm in low-risk OSA may counteract this effect. These findings provide a pathway to identify patients likely to benefit.

IMPORTANCE: Pulmonary rehabilitation (PR) improves exercise tolerance, symptom burden, and health-related quality of life for people with chronic respiratory conditions. However, demand for PR outstrips supply. Traditionally, PR has been delivered using specialist, gym-based exercise equipment. OBJECTIVE: To investigate whether PR using minimal equipment (PR-min) is noninferior to PR using specialist gym exercise equipment (PR-gym). DESIGN, SETTINGS, AND PARTICIPANTS: This parallel, 2-group, assessor- and statistician-blinded, noninferiority randomized clinical trial compared PR-min with PR-gym. Eligible participants were people with chronic respiratory disease referred for PR to the Regional Pulmonary Rehabilitation Unit in northwest London, UK. Recruitment occurred from October 15, 2018, to December 21, 2021, with a final follow-up to December 14, 2022. Randomization was by an independent web-based system using minimization with 1:1 allocation. Data analysis was performed from May 2023 to January 2025. INTERVENTIONS: Both PR programs comprised 2 in-person, outpatient supervised sessions per week for 8 weeks. PR-min used minimal equipment (eg, walking circuit and body weight exercises), whereas PR-gym used specialist exercise equipment (eg, treadmills and weights machines). MAIN OUTCOMES AND MEASURES: The primary outcome was change in incremental shuttle walk (ISW) distance after PR (ie, at 8 weeks; with a predefined noninferiority margin of -24 m). Secondary outcomes included dyspnea, health-related quality of life, costs, and adverse events. RESULTS: A total of 436 participants (median [IQR] age, 71.7 [63.2-77.7] years; 239 [54.8%] male) were enrolled, with 218 randomized to PR-min and 218 to PR-gym. At 8 weeks, PR-min (n = 136) and PR-gym (n = 130) demonstrated significant improvements in ISW distance with no significant between-group difference in ISW distance change (mean, 1.7 m; 1-sided 97.5% CI lower bound, -16.8), which was within the -24-m noninferiority margin. The intention-to-treat analysis and a robust range of sensitivity analyses all demonstrated that PR-min was noninferior to PR-gym. Similar findings were observed for dyspnea and health-related quality of life. No excess adverse events or costs were seen with intervention. CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that PR-min demonstrated noninferiority to PR-gym for exercise capacity, dyspnea, and health-related quality of life. PR-min can expand the number of settings where PR can be provided, thus improving patient accessibility. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16196765.

BACKGROUND: Randomised controlled studies evaluating vitamin D supplementation in pregnancy or early childhood for preventing childhood asthma have yielded inconclusive results. Previous systematic reviews of vitamin D for asthma prevention focused on studies comparing vitamin D to placebo or studies intervening in pregnancy, limiting the body of evidence. OBJECTIVES: Primary: to evaluate the efficacy of any vitamin D supplementation and high-dose vitamin D supplementation in early life, including the prenatal period, for preventing asthma in children. Secondary: to assess the efficacy of vitamin D supplementation: • for preventing asthma in children at risk of vitamin D deficiency at the start of the trial or whose mothers were at risk; • by intervention timing and the cumulative dose administered; • in preventing factors associated with early childhood asthma, including atopic dermatitis, respiratory tract infections, sensitisation to allergens, and airway inflammation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and the Cochrane Airways and Skin Trial Registers. We checked the reference lists of relevant systematic reviews and meta-analyses. We contacted authors to obtain additional study information as needed. Date of last search: October 2023. SELECTION CRITERIA: We included randomised controlled studies comparing higher versus lower/standard dose vitamin D (≤ 400 international units (IU)/day) or any vitamin D versus placebo/no treatment in generally healthy pregnant or lactating women or children up to five years of age that evaluated childhood asthma, wheeze, atopic dermatitis, airway infections, allergic sensitisation, and airway inflammation. We excluded trials recruiting populations with pre-existing conditions. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodological procedures, including using Cochrane's Screen4Me workflow. We considered participants rather than events as the unit of analysis, performed fixed-effect meta-analysis, and reported risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) for four comparisons: (1) any vitamin D versus placebo/no supplementation in pregnant or breastfeeding women; (2) any vitamin D versus placebo/no supplementation in infants or children; (3) high versus low/standard dose vitamin D in pregnant or breastfeeding women; (4) high versus low/standard dose vitamin D in infants or children. Our outcomes were: asthma, wheeze, atopic dermatitis, airway infections, allergic sensitisation, airway inflammation, and adverse events. We narratively described results that could not be meta-analysed. We used the Cochrane risk of bias tool (RoB) to assess bias in the studies. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 18 studies involving a total of 10,611 participants, of which 16 contributed data to meta-analyses. Studies were conducted around the world, with most taking place in higher-income countries. The dose and frequency of vitamin D ranged from 200 IU/day to 100,000 IU bolus quarterly, and the duration of supplementation ranged from 28 days to two years. Comparison 1. Any vitamin D versus placebo/no supplementation in pregnant or breastfeeding women (4 studies) Compared to placebo or no supplementation, any vitamin D given to pregnant or breastfeeding women may reduce the risk of early childhood asthma (RR 0.17, 95% CI 0.05 to 0.61; 1 study, 236 participants; low-certainty evidence) and likely has little to no effect on childhood airway infections (RR 1.00, 95% CI 0.97 to 1.04; 3 studies, 1564 participants; moderate-certainty evidence). The evidence is very uncertain for wheeze, atopic dermatitis, allergic sensitisation, airway inflammation, or adverse events. Comparison 2. Any vitamin D versus placebo/no supplementation in infants or children (5 studies) Compared to placebo or no supplementation, any vitamin D given to infants or children may have little to no effect on childhood wheeze (RR 0.89, 95% CI 0.68 to 1.16; 2 studies, 431 participants; low-certainty evidence), atopic dermatitis (RR 1.01, 95% CI 0.80 to 1.28; 2 studies, 448 participants; low-certainty evidence), airway infections (RR 0.92, 95% CI 0.83 to 1.01; 2 studies, 500 participants; low-certainty evidence), allergic sensitisation (RR 2.25, 95% CI 0.60 to 8.50; 1 study, 228 participants; low-certainty evidence), or airway inflammation measured by eosinophil counts (RR 1.06, 95% CI 0.65 to 1.74; 1 study, 226 participants; low-certainty evidence). The evidence is very uncertain for asthma and adverse events. Comparison 3. High versus low/standard dose vitamin D in pregnant or breastfeeding women (4 studies) Compared to low/standard dose, high-dose vitamin D given to pregnant or breastfeeding women likely reduces the risk of childhood wheeze (RR 0.79, 95% CI 0.64 to 0.98; 3 studies, 1439 participants; moderate-certainty evidence), but likely results in little to no difference in childhood asthma, although the direction and magnitude of effect is similar to that for wheeze (RR 0.81, 95% CI 0.63 to 1.04; 2 studies, 1355 participants; moderate-certainty evidence). Compared to low/standard dose, high-dose vitamin D in pregnancy likely has little to no effect on childhood atopic dermatitis (RR 0.91, 95% CI 0.75 to 1.11; 3 studies, 1439 participants; moderate-certainty evidence), airway infections (RR 0.95, 95% CI 0.82 to 1.11; 3 studies, 1441 participants; moderate-certainty evidence), or allergic sensitisation (RR 1.01, 95% CI 0.87 to 1.18; 2 studies, 1110 participants; moderate-certainty evidence). The evidence is very uncertain for adverse events. No studies evaluated airway inflammation. Comparison 4. High versus low/standard dose vitamin D in infants or children (7 studies) Compared to low/standard dose, high-dose vitamin D given to infants or children may slightly reduce airway infections (RR 0.94, 95% CI 0.90 to 0.98; 6 studies, 2385 participants; low-certainty evidence) but may have little to no effect on atopic dermatitis (RR 0.76, 95% CI 0.55 to 1.05; 1 study, 769 participants; low-certainty evidence). The evidence is very uncertain for asthma, wheeze, allergic sensitisation, and adverse events. No studies evaluated airway inflammation. AUTHORS' CONCLUSIONS: Evidence supporting a protective effect of vitamin D supplementation in early life, including the prenatal period, on childhood asthma is limited. Moderate-certainty evidence suggests that high-dose vitamin D in pregnancy likely helps prevent childhood wheeze. Evidence for the effects of vitamin D in early childhood on asthma or wheeze is less certain. Additional high-quality studies, especially in infants and children, are needed to establish with any certainty the effects of vitamin D supplementation on childhood asthma and associated factors.