European Respiratory Journal最新文献

The complex pathogenic relationships between idiopathic pulmonary fibrosis (IPF) and its usually associated comorbidities remain poorly understood. While evidence suggests that some comorbidities may directly influence the development or progression of IPF or vice versa, whether these associations are causal or arise independently due to shared risk factors, such as aging, smoking, lifestyle, and genetic susceptibility, is still uncertain. Some comorbidities, such as metabolic syndromes, gastro-esophageal reflux disease, and obstructive sleep apnea, precede the development of IPF. In contrast, others, like pulmonary hypertension or lung cancer, often become apparent after its onset or during its progression. These timing patterns suggest a directional relationship in their associations. The issue is further complicated by the fact that patients often have multiple comorbidities, which may interact and exacerbate one another, creating a vicious cycle. To clarify these correlations, some studies have used causal inference methods (e.g., Mendelian randomisation) and exploration of underlying mechanisms; however, these efforts have not yet generated conclusive insights. In this review, we provide a general overview of the relationship between IPF and its comorbidities, emphasizing the pathogenic mechanisms underlying each comorbidity, potential shared pathobiology with IPF, and, when available, causal insights from Mendelian randomisation studies.

Background: Adherence to continuous positive airway pressure (CPAP) for obstructive sleep apnoea (OSA) continues to be low with high termination rates. Alternative therapies to CPAP are needed. Our objective was to compare objective adherence to CPAP and mandibular advancement splints (MAS) and to evaluate their effectiveness, and additionally to identify treatment usage patterns and the clinical effectiveness of having both therapies.

Methods: This multicentre, double-randomised, three-phase trial (titration/crossover/observation) was conducted at three Canadian universities. Eligible participants were treatment-naïve with mild-to-severe OSA. The primary outcome was objectively measured adherence (hours per night) during the crossover phase. Secondary outcomes included efficacy during the crossover phase; adherence during the observational phase; and patient-centred outcomes, blood pressure and side-effects during the crossover and observational phases. Duration of the crossover and observational phase was 2.5 and 6 months, respectively.

Results: 81 participants were enrolled in the first randomisation. 79 entered the adaptation/titration phase (mean±sd age 52.3±10.8 years; 58 males), 73 entered the crossover phase (included in the intention-to-treat analysis) and 64 completed the observational phase. Mean objective adherence over 1 month: MAS showed higher adherence than CPAP, 6.0 versus 5.3 h·night^-1 (difference 0.7 (95% CI 0.3-1.2) h·night^-1; p<0.001). Mean CPAP-MAS difference in efficacy: 10.4 (95% CI 7.8-13.0) events·h^-1; p<0.001. During the observational phase 55% (35 out of 64) of participants chose to alternate therapies. All treatments led to substantial improvement in patient-centred outcomes.

Conclusions: Despite the higher efficacy of CPAP and higher adherence to MAS, both demonstrate comparable clinical effectiveness on patient-centred outcomes. Having both CPAP and MAS can improve long-term management of OSA.

Background: Asthma attacks are heterogeneous. It is not known whether the response to oral corticosteroids (OCS) in acute asthma varies according to type-2 (T2) inflammatory biomarkers, blood eosinophil count (BEC) and exhaled nitric oxide (FeNO). We aim to explore the relationship between T2 biomarkers and response to OCS in acute asthma.

Methods: We conducted a longitudinal observational study of people experiencing an asthma attack evaluated before and after a 7-day OCS course. The primary outcome was post-bronchodilator (BD) FEV₁ change according to ordinal BEC-FeNO 3-group categories (T2-Low/Low, BEC <0.15×10⁹ cells·L^-1 and FeNO <25 ppb; T2-High/High, BEC ≥0.30×10⁹ cells·L^-1 and FeNO ≥35 ppb and T2-Mid, not meeting Low/Low-High/High criteria). A key secondary outcome was the Asthma Control Questionnaire (ACQ-5) change. Exploratory outcomes included OCS-attributable adverse events.

Results: Fifty-three people were enrolled with 16 (30%) T2-Low/Low, 27 (51%) T2-Mid and 10 (19%) T2-High/High asthma attacks. Post-BD FEV₁ changes increased with combined BEC-FeNO elevation (p-for-interaction=0.007), peaking in the T2-High/High phenotype (0.390±0.512L, p-for-trend<0.0001). Conversely, T2-Low/Low attacked achieved nonsignificant FEV₁ changes (0.017±0.153L). In univariable and multivariable analyses, only ordinal BEC-FeNO stratification - not symptoms nor FEV₁ - was a predictor of subsequent post-BD FEV₁ improvement. All patients improved ACQ-5, numerically peaking in the T2-High/High phenotype (-1.58±0.60, p-for-trend=0.08). All groups experienced similar OCS-attributable adverse events, with n=33 (62%) participants reporting ≥1 event.

Conclusions: We found that objective improvement following OCS is confined to T2-High/High events. As in chronic asthma, greater T2 burden identifies a distinct clinical and therapeutic trajectory, whereas OCS-related adverse events are uniformly distributed.