European Respiratory Journal最新文献

Background: The 6-min walk test (6MWT) provides an assessment of patient function and has been employed in interstitial lung disease clinical trials as an end-point. The ISABELA studies were two replicate randomised controlled trials of idiopathic pulmonary fibrosis (IPF) that included a regimented 6MWT protocol. The goal of this study was to combine 6MWT components into a pragmatic, easy to apply, composite clinical prediction score.

Methods: 6MWT parameters associated with time to death or respiratory hospitalisation in the ISABELA studies were integrated into a single composite score. This score was then validated in an external cohort.

Results: There were 1251 patients in the derivation set with 83 respiratory-related hospitalisations and 21 deaths observed after 48 weeks. After multivariable analysis, four parameters were independently predictive of outcomes: Borg dyspnoea score, oxygen flow rate, oxygen saturation nadir and the 6-min walk distance. A pragmatic model, termed the ODDS (oxygen, distance, dyspnoea, saturation) was then developed. This performed better than the individual parameters alone with an area under the curve (AUC) of 0.797, 0.781 and 0.766 for events at 12, 24 and 48 weeks, respectively. The ODDS model was similarly accurate when applied to the external validation set (n=295) at 48 weeks (AUC 0.758, 95% CI 0.688-0.825).

Conclusion: The 6MWT imparts important prognostic information which is best captured by combining constituent variables in a composite score system. The ODDS model might find utility in the clinical setting as well as in IPF studies where it can be used to risk-stratify patients for outcomes.

Background: Longitudinal data addressing the impact of asthma severity on mortality are lacking. We aimed to explore all-cause and cause-specific mortality according to asthma severity.

Methods: The present registry-based cohort study is based on Danish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. Adult patients with severe asthma were matched on age and sex to 10 patients with mild-to-moderate asthma and followed from 2000-2020. Patients with chronic obstructive pulmonary disease (COPD) diagnosed prior to inclusion were excluded. Absolute and relative measures of all-cause and cause-specific mortality were compared between severe and mild-to-moderate asthma.

Results: We included 11 811 and 118 810 patients with severe and mild-to-moderate asthma, respectively. All-cause mortality was significantly higher in patients with severe asthma compared to patients with mild-to-moderate asthma, both in absolute measures of the cumulative mortality [34% (95% CI: 32, 35) versus 20% (19, 20), p<0.001] after 20 years of follow-up and in relative measures [hazard ratio (HR)=1.99 (1.90, 2.09), p<0.001]. The HR of all-cause mortality was attenuated after adjustment for oral corticosteroid (OCS) use [HR=1.30 (95% CI: 1.23, 1.37, p<0.001)] and T2 inflammatory markers [HR=1.34 (1.09, 1.64), p<0.001]. The increased cumulative mortality risk was mainly due to respiratory diseases [12.6% (95% CI:11.7, 13.6) versus 3.3% (3.2, 3.5), p<0.001] with cancer [7.5% (95% CI: 6.8, 8.3) versus 5.9% (5.7, 6.2), p<0.001 ] and cardiovascular diseases [4.7% (95% CI: 4.1, 5.3) versus 3.8% (3.6, 4.0), p<0.001] also contributing. Though rare, the relative risk of asthma-related deaths was three-fold in severe asthma patients [HR=2.95 (2.08, 4.18), p<0.001].

Conclusions: In this nationwide cohort, severe asthma was associated with a significantly higher mortality risk compared to mild-to-moderate asthma. The increased risk was primarily driven by respiratory-related deaths, with OCS use and T2 inflammation as contributing mortality risk factors.

Background: The growing popularity of cannabis smoking in an era of legalization has prompted concerns about respiratory health.

Objective: To investigate clinical and airway epithelial transcriptomic features associated with cannabis smoking.

Methods: This cross-sectional study analyzed 139 cannabis-smoking participants categorized by joint-year exposure (low: ≤5; moderate: >5-20; high: >20), and 57 never-smokers. We evaluated respiratory symptom questionnaire scores, lung function measurements, and chest computed tomography and hyperpolarized ¹²⁹Xe pulmonary magnetic resonance imaging measurements across groups. We compared the expression of immune response signatures and mucin genes in airway epithelial brushings collected from bronchoscopy. Using air-liquid interface (ALI) cell cultures, we quantified epithelial MUC5AC protein and correlated its expression with clinical outcomes.

Results: Among cannabis-smoking individuals (48% male and median age of 27 years), 84% reported current or former cigarette smoking or vaping. Cannabis-smoking groups reported worse respiratory symptoms than never-smokers. High joint-year cannabis-smoking participants showed lower pre-bronchodilator FEV₁/FVC and FEF_25-75, more radiographic emphysema, and more ventilation abnormalities than never-smokers. Airway epithelial brushings from cannabis-smoking individuals demonstrated increased type 2 immune response, decreased type 17 immune response, and higher MUC5AC gene expression than non-cannabis-smoking individuals. Epithelial MUC5AC protein expression in cell cultures correlated with worse clinical outcomes and imaging abnormalities.

Conclusions: Cannabis smoking, particularly at high exposures, is associated with worse respiratory symptoms, lower lung function, functional imaging abnormalities, and dysregulated immune responses in the airway epithelium. These observations suggest respiratory harm associated with cannabis smoking and underscore the concerns for future respiratory morbidities related to persistent cannabis use.