Respirology最新文献

Background and objective: We determined the impact of genetic susceptibility and its interaction with smoking and air pollution on the risk of developing lung adenocarcinoma.

Methods: This retrospective case-control study utilised data from Taiwan Precision Medicine Initiative (TPMI) project conducted between June 2019 and November 2022. The study population consisted of lung adenocarcinoma patients and 1:4 age-, gender-, and index year-matched non-lung cancer controls. We analysed polygenic risk scores (PRS), smoking status, as well as PM_2.5 and PM₁₀ exposures.

Results: A total of 681 lung adenocarcinoma patients and 2724 non-lung cancer participants were included. PRS was significantly higher among lung adenocarcinoma patients than controls (p < 0.001). Overall, a higher PRS was associated with a higher risk of lung adenocarcinoma. A high PM_2.5 exposure was associated with a higher risk of lung adenocarcinoma (OR 1.88 [95% CI 1.12-3.14], p = 0.0163) among never-smokers with low genetic risk. Never-smokers with a higher genetic risk were associated with a higher OR for lung adenocarcinoma with the highest OR among Q4 participants with high PM_2.5 exposure (4.97 [95% CI 3.10-7.97], p < 0.001). There was no significant impact of PM_2.5 exposure among individuals with higher genetic risks. Similar phenomena were observed in the PM₁₀ analyses. There were no significant correlations of PRS with risk of lung adenocarcinoma among smokers.

Conclusion: PRS significantly predicted lung adenocarcinoma incident cases in a dose-dependent manner among never-smokers. The PRS effect was not noted in smokers. The results were consistent among participants exposed to different air pollution levels.

Background and objective: While short-term weight changes are known to influence obstructive sleep apnoea (OSA), the impact of body mass index (BMI) changes over the life course has been poorly documented. We examined the association between BMI trajectories from childhood to middle age and adult OSA, 10 years later.

Methods: Five BMI trajectories were previously identified in the population-based cohort Tasmanian Longitudinal Health Study (TAHS), using eight time-point BMI from age 5 to 43 years. The primary outcome was probable OSA at 53 years, defined using STOP-Bang questionnaire, with Berlin and OSA-50 questionnaires used to ensure consistency of findings. Clinically significant diagnosed OSA was defined as self-reported medical diagnosis or mild OSA with symptoms or moderate-to-severe OSA, using type-4 sleep studies. Associations were examined using multivariable logistic regression.

Results: Compared with the average BMI trajectory, the child average-increasing (aOR = 5.28, 95% CI 3.38-8.27) and persistently high trajectories (aOR = 3.73, 2.06-6.74) were associated with increased risk of probable OSA. These associations were consistent when using clinically significant diagnosed OSA (child average-increasing trajectory: aOR = 2.95, 1.30-6.72; high trajectory: aOR = 2.23, 0.82-6.09). Individuals belonging to the low trajectory were less likely than the average trajectory to have OSA. Notably, the child high-decreasing trajectory was not associated with OSA.

Conclusion: Physicians and the public should be aware of the potential risk of OSA in middle-aged adults when BMI is high or continuously increasing from childhood to mid-40s. Obese children who subsequently lose weight were not at higher risk of OSA in middle age-a novel and key finding.

Background and objective: Symptom-based questionnaires and handheld lung function devices are widely used for COPD case finding, but the optimal combination remains unclear. This study aimed to compare the diagnostic accuracy (DA) of various combinations of handheld lung function devices and questionnaires and develop a COPD case-finding strategy.

Methods: This cross-sectional, prospective, observational study enrolled participants aged ≥ 40 years with respiratory symptoms and ≥ 10 smoking pack-years. Participants completed three questionnaires (COPD diagnostic questionnaire [CDQ], lung function questionnaire; COPD Population Screener) and 2 handheld lung function devices (peak flow meter, microspirometer), followed by spirometry to confirm COPD (post-bronchodilation FEV₁/FVC < 0.7). DA is assessed using the area under the ROC curve (AUROC).

Results: Among 224 participants, COPD incidence was 29%. Individually, handheld devices showed significantly higher DA than questionnaires (AUROC 0.678-0.69 for questionnaires vs. 0.807 for peak expiratory flow rate [PEFR] and 0.888 for FEV₁/FEV₆; all pairwise p < 0.05). FEV₁/FEV₆-based combinations outperformed PEFR-based combinations (all n = 224; AUROC 0.897-0.903 vs. 0.810-0.818; p < 0.05). The CDQ and FEV₁/FEV₆ combination reached the highest DA (AUROC 0.903). FEV₁/FEV₆ < 0.76 was the optimal cutoff value. A two-staged strategy (sensitivity/specificity 0.82/0.84) was proposed: low-risk participants (CDQ ≤ 13) need no further testing; middle-risk (CDQ 14-26) should undergo FEV₁/FEV₆; and high-risk (CDQ ≥ 27) and middle-risk with FEV₁/FEV₆ < 0.76 require confirmatory spirometry. This approach would reduce misdiagnoses and save costs and time compared to FEV₁/FEV₆ alone.

Conclusion: FEV₁/FEV₆ and CDQ combination achieves the highest DA. A two-staged, risk-stratified strategy combining CDQ and FEV₁/FEV₆ can be accurate and cost-effective to detect at-risk, undiagnosed COPD subjects. External validation is required.

Background and objective: An imbalanced fat and muscle mass ratio might impact exacerbation of chronic obstructive pulmonary disease (COPD). We investigated the association of visceral fat-to-muscle ratio (VMR) with severe COPD exacerbation requiring hospitalisation.

Methods: This prospective cohort study in COPD patients was performed along with the Xinjiang Multi-Ethnic Cohort study between May 2018 and December 2023. Baseline VMR was calculated from visceral fat area and muscle mass measured by bioelectrical impedance analysis. Numbers of COPD exacerbation hospitalizations were monitored. Associations between various variables and exacerbation were assessed by logistics regression and Zero-inflated Poisson regression analyses.

Results: A total of 631 COPD patients were included, with 186 (29.48%) and 304 (48.18%) severe COPD exacerbation within 1 and 5 years, respectively. Compared with body mass index and other obesity indicators, VMR had stronger associations with severe exacerbation. A higher VMR was associated with increased risks of 1-year and 5-year exacerbation (odds ratio [OR] = 1.34 and 1.44, respectively). The subgroup female and overweight individuals showed a strong association (female OR = 1.89 and 1.99, overweight OR = 1.80 and 1.88, for 1 and 5-year exacerbation, respectively). The number of COPD exacerbation increased by 46% for each one-point VMR increase. These results remained unchanged in the sensitivity analyses after removing underweight patients or smoke influence, as well as in the competing risk analysis when considering other causes for death.

Conclusion: VMR was a risk factors of severe COPD exacerbation. Proactive assessment of VMR might be helpful to guide management of COPD patients.

Background and objective: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a poor prognosis. Antifibrotics slow the decline of pulmonary function after 12-months, but limited studies have examined the role of circulatory biomarkers in antifibrotic treated IPF patients.

Methods: Serum from 98 IPF participants, from the Australian Idiopathic Pulmonary Fibrosis Registry were collected at four time-points over 1 year post-antifibrotic treatment and analysed as two separate cohorts. Patients were stratified as progressive, if they experienced ≥ 10% decline in FVC or ≥ 15% decline in DLCO or were deceased within 1 year of treatment initiation: or otherwise as stable. Ten molecules of interest were measured by ELISAs in patient serum.

Results: Baseline MMP7 levels were higher in progressive than stable patients in Cohort 1 (p = 0.02) and Cohort 2 (p = 0.0002). Baseline MMP7 levels also best differentiated progressive from stable patients (Cohort 1, AUC = 0.74, p = 0.02; Cohort 2, AUC = 0.81, p = 0.0003). Regression analysis of the combined cohort showed that elevated MMP7 levels predicted 12-month progression (OR = 1.530, p = 0.010) and increased risk of overall mortality (HR = 1.268, p = 0.002). LASSO regression identified a multi-biomarker panel (MMP7, ICAM-1, CHI3L1, CA125) that differentiated progression more accurately than MMP7 alone. Furthermore, GAP combined with MMP7, ICAM-1, CCL18 and SP-D was more predictive of 3-year mortality than GAP alone.

Conclusion: MMP7 along with a multi-biomarker and GAP panel can predict IPF progression and mortality, with the potential for optimising management.

Background and objective: Previous observational studies reported a complex relationship between snoring and coronary artery disease (CAD). We aimed to estimate the causal associations between snoring and CAD among East Asian people, and the effects independent of BMI.

Methods: Based on 497,250 adults from China Kadoorie Biobank (CKB), we performed a conventional prospective analysis between snoring and CAD outcomes, using the multivariable Cox regression. We also leveraged genome-wide association (GWAS) summary statistics of snoring and BMI from CKB (n = 100,626, 47,208 snorers) and CAD outcomes from Biobank of Japan (BBJ, 5891-25,892 cases, 142,336-168,186 controls). Single-variable and multivariable two-sample bi-directional Mendelian randomization (MR) analyses were performed.

Results: During a median follow-up of 12.32 years, 48,997 participants developed CAD. Snoring and habitual snoring were associated with incident CAD and myocardial infarction (MI), habitual snoring was also associated with stable angina pectoris (SAP). The HRs (95% CIs) of habitual snoring were 1.06 (1.04, 1.08), 1.06 (1.04, 1.08) and 1.14 (1.03, 1.25). The associations remained among non-adiposity participants. Genetically predicted habitual snoring was associated with CAD and MI, the corresponding IVW-ORs (95% CIs) were 1.09 (1.005, 1.19) and 1.15 (1.05, 1.25). Further adjusted BMI, habitual snoring retained independent effects on MI and CAD, and showed impact on SAP (1.09 [1.01, 1.17]). No reverse associations were observed between CADs on snoring traits.

Conclusion: Habitual snoring elevated the risks of total CAD, MI and SAP. The causal associations were independent of BMI. These findings indicated that snoring intervention might contribute to the decrease of CAD risk among Asians.

Background and objective: Fibrotic interstitial lung disease (ILD) is associated with high morbidity and mortality. Patients often exhibit impaired nutritional status and alterations in body composition, such as dynapenia and sarcopenia, which correlate with poor pulmonary function, reduced exercise tolerance and diminished quality of life. However, the impact of dynapenia and sarcopenia on prognosis has not been examined extensively in ILD patients. We assessed the impact of dynapenia and sarcopenia as risk factors for mortality and their prevalence in ILD.

Methods: Prospective cohort study. ILD was classified into idiopathic pulmonary fibrosis (IPF), connective tissue disease-related ILD (CTD-ILD) and chronic hypersensitivity pneumonitis (CHP). Patients over 18 years old with a confirmed diagnosis of ILD were included, while those with diagnoses of cancer, human immunodeficiency virus and neurological disease were excluded. Dynapenia and sarcopenia were determined according to EWGSOP2 criteria.

Results: Ninety-eight ILD patients were included; 33.66% had IPF, 47.96% had CTD-ILD, and 18.37% had CHP. The mean age was 63.89 ± 12.02 years; 37.76% were male. The risk factors associated with mortality included dynapenia (HR: 2.04, 95% CI: 1.10-3.77, p = 0.022), sarcopenia (HR: 1.88, 95% CI; 1.00-3.33, p = 0.049) and exercise tolerance (HR: 0.99, 95% CI; 0.99-0.99, p = 0.023), adjusted for confounding variables. The prevalence of dynapenia was 45% in ILD; 51% in IPF, 35% in CTD-ILD and 61% in CHP. The prevalence of sarcopenia was 29%; both IPF (39%) and CHP (50%) had a higher prevalence of sarcopenia than CTD-ILD (14%).

Conclusion: Sarcopenia and dynapenia are independent risk factors for mortality in ILD.

Background and objective: A disintegrin and metalloprotease 33 (ADAM33) is associated with asthma susceptibility, and its genetic variations impact susceptibility and disease severity. However, the mechanisms remain unclear. This study aimed to investigate ADAM33 single nucleotide polymorphisms (SNPs) in childhood asthma susceptibility and explore their regulatory mechanisms.

Methods: Eleven selected SNPs in ADAM33 were genotyped and identified the association with asthma susceptibility. In the validation cohort, we measured plasma sADAM33 levels and compared them with disease severity among children with different SNP genotypes. Computational predictions identified miRNAs targeting the SNP, and the impact of the SNP on miRNA regulation was confirmed using a dual luciferase reporter system. Finally, we validated the regulatory role of miRNAs on ADAM33 expression using an in vitro model with upregulated ADAM33 expression.

Results: Only rs3918400 was associated with asthma susceptibility. In the validation cohort, children with allergic asthma exhibited higher plasma sADAM33 levels. Among asthmatic children, those with the rs3918400 CT/TT genotype had higher sADAM33 levels, poorer asthma control, more severe airway hyper-responsiveness, lower FEV₁% and higher dust mite-specific IgE activity compared to those with the CC genotype. miR-3928-5p bound strongly to the rs3918400 C allele and effectively reduced ADAM33 protein expression in CC genotype cells. However, the binding affinity of miR-3928-5p to the T allele was weaker, resulting in diminished negative regulation of protein expression.

Conclusion: The rs3918400 SNP affects the negative regulation of ADAM33 by miR-3928-5p, potentially participating in a complex interplay of processes related to childhood asthma susceptibility.