Daily Respiratory Research Analysis

BACKGROUND: Despite a substantial reduction in the use of solid fuels for cooking worldwide, exposure to household air pollution (HAP) remains a leading global risk factor, contributing considerably to the burden of disease. We present a comprehensive analysis of spatial patterns and temporal trends in exposure and attributable disease from 1990 to 2021, featuring substantial methodological updates compared with previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study, including improved exposure estimations accounting for specific fuel types. METHODS: We estimated HAP exposure and trends and attributable burden for cataract, chronic obstructive pulmonary disease, ischaemic heart disease, lower respiratory infections, tracheal cancer, bronchus cancer, lung cancer, stroke, type 2 diabetes, and causes mediated via adverse reproductive outcomes for 204 countries and territories from 1990 to 2021. We first estimated the mean fuel type-specific concentrations (in μg/m FINDINGS: In 2021, 2·67 billion (95% uncertainty interval [UI] 2·63-2·71) people, 33·8% (95% UI 33·2-34·3) of the global population, were exposed to HAP from all sources at a mean concentration of 84·2 μg/m INTERPRETATION: Although the burden attributable to HAP has decreased considerably, HAP remains a substantial risk factor, especially in sub-Saharan Africa and south Asia. Our comprehensive estimates of HAP exposure and attributable burden offer a robust and reliable resource for health policy makers and practitioners to precisely target and tailor health interventions. Given the persistent and substantial impact of HAP in many regions and countries, it is imperative to accelerate efforts to transition under-resourced communities to cleaner household energy sources. Such initiatives are crucial for mitigating health risks and promoting sustainable development, ultimately improving the quality of life and health outcomes for millions of people. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Data regarding the effect of positive airway pressure (PAP) therapy for obstructive sleep apnoea (OSA) on all-cause mortality are inconsistent. We aimed to conduct a systematic review and meta-analysis to test the hypothesis that PAP therapy is associated with reduced all-cause and cardiovascular mortality in people with OSA. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from database inception to Aug 22, 2023 (updated Sept 9, 2024), with no language or geographical restrictions. Reference lists of eligible studies and recent conference abstracts (2022-23) were also reviewed. We included outpatient studies (randomised controlled trials [RCTs] or confounder-adjusted, non-randomised controlled studies [NRCSs]) assessing the incidence of all-cause mortality, cardiovascular mortality, or both in adults (aged ≥18 years) with OSA who were treated versus not treated with PAP; other study types and studies that evaluated only PAP adherence were excluded. Abstracts of all retrieved publications were independently screened by two of three researchers (BS, SRB, and KCW), with disagreements resolved by adjudication from another researcher (SHM). The AutoLit feature of the Nested Knowledge platform was used for the review and data-extraction phases. We analysed each log-transformed hazard ratio (HR) and SE using a linear random-effects model to estimate overall HRs and 95% CIs. To evaluate the risk of bias, we used the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa Scale for NRCSs. This study was registered with PROSPERO, CRD42023456627. FINDINGS: Of 5484 records identified by our search, 435 were assessed for eligibility and 30 studies were included in the systematic review and meta-analysis (ten RCTs and 20 NRCSs). These studies included 1 175 615 participants, of whom 905 224 (77%) were male and 270 391 (23%) were female (SE 1·9), with a mean age of 59·5 (SE 1·4) years and a mean follow-up of 5·1 (0·5) years. The risk of bias was low to moderate. The risk of all-cause mortality (HR 0·63, 95% CI 0·56-0·72; p<0·0001) and cardiovascular mortality (0·45, 0·29-0·72; p<0·0001) was significantly lower in the PAP group than in the no-PAP group, and the clinically relevant benefit of PAP therapy increased with use. INTERPRETATION: Our results are consistent with a potentially beneficial effect of PAP therapy on all-cause and cardiovascular mortality in patients with OSA. Patients should be made aware of this effect of their treatment, which could result in greater acceptance of treatment initiation and greater adherence, leading to a higher likelihood of improved outcomes. FUNDING: ResMed.

Molecular changes underlying the persistent health effects after SARS-CoV-2 infection remain poorly understood. To discern the gene regulatory landscape in the upper respiratory tract of COVID-19 patients, we performed enzymatic DNA methylome and single-cell RNA sequencing in nasal cells of COVID-19 patients (n = 19, scRNA-seq n = 14) and controls (n = 14, scRNA-seq n = 10). In addition, we resampled a subset of these patients for transcriptome analyses at 3 (n = 7) and 12 months (n = 5) post infection and followed the expression of differentially regulated genes over time. Genome-wide DNA methylation analysis revealed 3112 differentially methylated regions between COVID-19 patients and controls. Hypomethylated regions affected immune regulatory genes, while hypermethylated regions were associated with genes governing ciliary function. These genes were not only downregulated in the acute phase of the disease but sustained repressed up to 12 months post infection in ciliated cells. Validation in an independent cohort collected 6 months post infection (n  = 15) indicated symptom-dependent transcriptional repression of ciliary genes. We therefore propose that hypermethylation observed in the acute phase may exert a long-term effect on gene expression, possibly contributing to post-acute COVID-19 sequelae.