Daily Respiratory Research Analysis
Three high-impact studies advance respiratory health: a Bangladeshi prospective cohort links betel quid use to higher respiratory and COPD mortality independent of smoking; a national Moldovan analysis shows alarming baseline and acquired resistance to fluoroquinolones, bedaquiline, and linezolid driving MDR/RR-TB treatment failure; and a population-based Catalan cohort demonstrates sustained protection of nirsevimab against severe RSV outcomes across two seasons without rebound severity.
Summary
Three high-impact studies advance respiratory health: a Bangladeshi prospective cohort links betel quid use to higher respiratory and COPD mortality independent of smoking; a national Moldovan analysis shows alarming baseline and acquired resistance to fluoroquinolones, bedaquiline, and linezolid driving MDR/RR-TB treatment failure; and a population-based Catalan cohort demonstrates sustained protection of nirsevimab against severe RSV outcomes across two seasons without rebound severity.
Research Themes
- Behavioral risk factors and respiratory mortality
- Antimicrobial resistance in tuberculosis and treatment failure
- Respiratory virus immunoprophylaxis effectiveness in real-world settings
Selected Articles
1. Association Between Betel Quid Consumption and Respiratory Disease Mortality in a Prospective Bangladeshi Cohort.
In a 20,033-participant prospective cohort in Bangladesh, betel quid use was associated with higher respiratory disease mortality, especially COPD, with a clear dose-response and effects persisting in women and never-smokers. The population attributable fraction for COPD deaths due to betel use was 16.3%, underscoring substantial public health implications.
Impact: This study identifies a prevalent, modifiable exposure linked to excess COPD and respiratory mortality independent of smoking, providing strong evidence to inform prevention policies in South and Southeast Asia and beyond.
Clinical Implications: Clinicians should screen for betel quid use, counsel cessation, and incorporate it into COPD risk assessment, especially for women and never-smokers. Public health programs should target betel cessation alongside tobacco control.
Key Findings
- Ever betel quid use increased respiratory disease mortality (HR 1.38; 95% CI 1.13–1.69).
- COPD mortality was higher among betel users (HR 1.56; 95% CI 1.19–2.05) with dose-response: low vs high consumption HRs 1.46 and 2.47.
- Associations persisted in women (HR 3.63) and never-smokers (HR 3.44); population attributable fraction for COPD deaths due to betel use was 16.3%.
Methodological Strengths
- Large, long-term prospective cohort with standardized data collection and multivariable Cox modeling.
- Robust dose-response analyses and subgroup evaluations (women, never-smokers).
Limitations
- Self-reported betel use may introduce misclassification; intensity metrics may be imperfect.
- Residual confounding and limited generalizability beyond the study region are possible.
Future Directions: Evaluate biological mechanisms linking betel constituents to COPD pathogenesis; implement and trial cessation interventions; expand to multi-country cohorts to assess generalizability.
BACKGROUND: Betel quid is a widely consumed substance that has been associated with higher mortality and increased risk of several diseases. RESEARCH QUESTION: Is betel quid use associated with increased respiratory disease mortality, particularly in COPD? STUDY DESIGN AND METHODS: A prospective cohort included 20,033 individuals 18 to 75 years of age living in Araihazar, Bangladesh. A total of 476 deaths resulting from respiratory disease were recorded during follow-up between October 2000 and April 2024. Data on baseline demographics, lifestyle factors, and betel nut use were ascertained using standardized questionnaires. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations between betel consumption practices and the risk of death due to respiratory disease while adjusting for age, BMI, educational attainment, sex, and cigarette smoking history. RESULTS: Cohort members who had ever consumed betel were at increased risk of death due to respiratory disease (HR, 1.38; 95% CI, 1.13-1.69), including COPD (HR, 1.56; 95% CI, 1.19- 2.05) but not lung cancer (HR, 1.24; 95% CI, 0.81-1.89). We observed a dose-response relationship between indicators of betel use intensity and COPD mortality; compared with those who never used betel, the HR was 1.46 (95% CI, 1.10-1.94) and 2.47 (95% CI, 1.64-3.74) for those who did use betel with low and high levels of consumption, respectively. The association did not differ appreciably by other characteristics and remained apparent in female individuals (HR, 3.63; 95% CI, 2.01-6.59) and people who have never smoked (HR, 3.44; 95% CI, 1.85-6.39). The population attributable fraction for betel use was 16.3% for deaths from COPD. INTERPRETATION: Betel quid consumption was associated with increased mortality from respiratory disease, including COPD, in this cohort. Efforts to bolster clinical and public awareness are warranted to help combat the global health emergency posed by betel quid consumption.
2. High rates of acquired resistance to fluoroquinolones, bedaquiline, and linezolid in patients failing treatment against drug-resistant tuberculosis in the Republic of Moldova.
National surveillance data from Moldova show that treatment failure in MDR/RR-TB is strongly driven by high baseline and acquired resistance to fluoroquinolones, bedaquiline, and linezolid. Acquired resistance occurred in 39.6% of failures (notably bedaquiline 30.9%), with baseline FQ resistance (OR 4.7) and any acquired Group A resistance (OR 63.5) associated with failure.
Impact: Highlights rapidly emerging resistance to cornerstone second-line anti-TB agents in a high-burden setting, with direct implications for regimen design, surveillance, and stewardship to avert extensively drug-resistant TB.
Clinical Implications: Routine baseline and serial DST for Group A drugs, adherence support, and rapid regimen modification are critical. Programs should enhance pharmacovigilance for bedaquiline and linezolid resistance and consider individualized regimens guided by timely DST.
Key Findings
- Treatment failure occurred in 5.3% (55/1034) with 67.1% success.
- Baseline resistance was markedly higher in failures vs successes: FQs 66.7% vs 18.3%, bedaquiline 12.5% vs 0.6%, linezolid 25.0% vs 0.6% (all p < 0.0001).
- Acquired resistance in failures: any 39.6%; bedaquiline 30.9%, linezolid 16.7%, FQs 25.0%; baseline FQ resistance (OR 4.7) and any acquired Group A resistance (OR 63.5) were strongly associated with failure.
Methodological Strengths
- Nationwide cohort leveraging surveillance data with both baseline and follow-up DST.
- Multivariable modeling quantifying associations with treatment failure.
Limitations
- Retrospective design with potential missing data and unmeasured confounders (e.g., adherence, PK variability).
- Generalizability may be limited to similar high-burden settings.
Future Directions: Implement prospective resistance surveillance with rapid DST and adherence monitoring; evaluate modified regimens and companion diagnostics to mitigate emergence of resistance.
OBJECTIVES: Mycobacterium tuberculosis with rifampicin resistance ranks among the four critical antimicrobial-resistant pathogens needing priority attention as identified by the World Health Organization (WHO) in 2024. Our objective was to identify the causes of treatment failure in patients diagnosed with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) in a nationwide cohort in the Republic of Moldova, a WHO high-burden country of MDR/RR-TB. METHODS: A retrospective cohort study analysed national tuberculosis surveillance data (2021-2022) on patients diagnosed with MDR/RR-TB with available baseline and follow-up drug susceptibility testing for WHO group A drugs. Treatment failure was defined as the absence of sputum culture conversion after 6 months. Logistic regression was used to identify risk factors associated with treatment failure. RESULTS: Of 1034 patients initiating MDR/RR-TB treatment, 55 (5.3%) experienced treatment failure, whereas 693 (67.1%) were successfully treated. Baseline resistance to WHO group A drugs was significantly higher in patients with treatment failure than in those with successful outcomes: fluoroquinolones (32/48 [66.7%] vs. 86/471 [18.3%]; p < 0.0001), bedaquiline (6/42 [12.5%] vs. 3/468 [0.6%]; p < 0.0001), and linezolid (12/48 [25.0%] vs. 3/468 [0.6%]; p < 0.0001). Acquired resistance occurred in 19 of 48 (39.6%) of those failing treatment, but none with successful outcomes, particularly to bedaquiline 13 of 42 (30.9%), linezolid 6 of 36 (16.7%), and fluoroquinolones 4 of 16 (25.0%). Baseline fluoroquinolone resistance (OR, 4.7; 95% CI, 2.0-11.2) and acquired resistance to any WHO group A drug (OR, 63.5; 95% CI, 7.7-8311.7) were associated with treatment failure. DISCUSSION: Although frequencies of treatment failure in MDR/RR-TB are low on bedaquiline-containing treatment regimens, we find alarmingly high rates of baseline and acquired drug resistance to key second-line anti-TB drugs as a driver for treatment failure in MDR/RR-TB. Strengthening resistance monitoring, improving adherence, and optimizing individualized regimens are urgently needed to prevent the emergence of extensively drug-resistant TB in high-burden settings of MDR/RR-TB.
3. Impact of nirsevimab immunoprophylaxis on respiratory syncytial virus-related outcomes in hospital and primary care after two consecutive seasons: a population-based retrospective cohort study in infants in their second year of life in Catalonia, Spain.
In a population-based cohort of 51,154 Catalan infants, nirsevimab immunization was associated with markedly lower RSV-related hospitalizations and PICU admissions over two seasons, with no evidence of rebound severity in season two. Primary care RSV infections were slightly higher in season two among immunized infants but without increased severe outcomes.
Impact: Provides robust real-world effectiveness and safety signals across consecutive seasons, informing infant RSV immunization policy and addressing concerns regarding disease rebound.
Clinical Implications: Supports broad infant nirsevimab rollout prior to first RSV season with monitoring across seasons; reinforces prioritization for hospitalization prevention without evidence for rebound severity.
Key Findings
- Among 51,154 infants, 89.9% received nirsevimab prior to or during the first season.
- By study end, RSV-related hospital admissions were 9.57 vs 35.56 per 1,000 (RR 0.27), and PICU admissions 1.90 vs 9.08 per 1,000 (RR 0.21) for immunized vs non-immunized.
- Primary care RSV infection rates were not significantly different (RR 0.81), and no significant differences in aHR across outcomes during the second season were observed.
Methodological Strengths
- Population-based design with very large sample and inverse probability-weighted Kaplan–Meier estimation.
- Assessment across two consecutive seasons with multiple clinically relevant outcomes.
Limitations
- Retrospective observational design with potential residual confounding and differential care-seeking.
- Non-randomized immunization; aHRs in season two were not statistically significant.
Future Directions: Evaluate durability, waning, and optimal timing across diverse settings; integrate genomic surveillance for RSV to monitor strain effects; economic evaluations to inform policy.
UNLABELLED: To analyse the effect of nirsevimab immunoprophylaxis on RSV-associated outcomes after two consecutive epidemic seasons in infants born and Living in Catalonia, Spain. We conducted a population-based retrospective cohort study including all infants born in Catalonia between April 2023 and March 2024. We established two cohorts (immunised with nirsevimab and non-immunised). We estimated adjusted cumulative incidences (CInc) curves for RSV-associated hospital admissions, paediatric intensive care unit (PICU) admissions, emergency department (ED) visits for bronchiolitis, and RSV infections and bronchiolitis registered in primary care from October 2023 to mid-February 2025 using inverse probability-weighted Kaplan-Meier methods. Marginal risk differences and risk ratios (RR) with 95% confidence intervals (95%CI) were calculated at the end of the first RSV season (January 15, 2024), beginning of the second season (October 1, 2024), and end of the second season (February 16, 2025). As a secondary analysis, we estimated adjusted hazard ratios (aHR) during the second RSV season (October 2024 to mid-February 2025) using Cox proportional hazard models. Among 51,154 infants, 45,971 (89.9%) were immunised with nirsevimab just before or during their first RSV season. After two RSV seasons, the CInc of severe outcomes remained substantially lower in the immunised group. By the end of the study period, the CInc of hospital admissions was 9.57 per 1,000 infants (95%CI: 7.92-11.20) in the immunised group and 35.56 per 1,000 (95%CI: 25.69-47.58) in the control group (RR: 0.27, 95%CI: 0.20-0.40); and for PICU admissions, 1.90 vs. 9.08 per 1,000 (RR: 0.21, 95%CI: 0.11-0.48). Primary care infection rates were also lower in the immunised group (13.78 vs. 16.96 per 1,000), although the difference was not statistically significant (RR: 0.81, 95%CI: 0.57-1.29). No statistically significant differences were observed in aHR across any outcomes during the second season. CONCLUSION: After two consecutive epidemic seasons, nirsevimab immunization provides protection against severe RSV-associated outcomes, with a significant reduction observed during the first season without increasing the risk of severe disease during the second. WHAT IS KNOWN: • Nirsevimab, a long-acting monoclonal antibody, was approved in 2023 to prevent severe respiratory syncytial virus (RSV) infections in the first seasonal exposure to the virus. • It has demonstrated high effectiveness in real-world studies in preventing RSV-associated hospital admissions in infants during their first season. WHAT IS NEW: • Our study provides evidence that nirsevimab reduces severe RSV-associated outcomes during the first season without increasing the risk of more severe disease in the second season. • After two years we still found lower rates of hospital and PICU admissions in the nirsevimab group, despite a slightly increased RSV infection rate among immunised infants during the second season, but with reduced severity.