European Respiratory Journal最新文献

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

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

Methods: This cross-sectional study analysed data from 139 cannabis-smoking participants categorised by joint-year exposure (low: ≤5; moderate: >5-20; high: >20 joint-years) and 57 never-smokers. We evaluated respiratory symptom questionnaire scores, lung function measurements, chest computed tomography and hyperpolarised ¹²⁹Xenon 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 cell cultures, we quantified epithelial mucin 5AC (MUC5AC) protein and correlated its expression with clinical outcomes.

Results: Among cannabis-smoking participants (48% male, 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 forced expiratory volume in 1 s to forced vital capacity ratio, lower forced expiratory flow at 25-75% of the forced vital capacity, more radiographic emphysema and more ventilation abnormalities than never-smokers. Airway epithelial brushings from cannabis-smoking participants demonstrated an increased type 2 immune response, decreased type 17 immune response and higher MUC5AC gene expression than non-cannabis-smoking participants. 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.

Background: Nontuberculous mycobacteria (NTM) are associated with chronic and challenging infections, particularly pulmonary disease (NTM-PD). While clinical guidelines provide treatment recommendations for the most common disease-causing species, they offer limited guidance on managing treatment failures. This study aims to develop a consensus-based decision-making framework for addressing treatment failure in NTM-PD.

Methods: A panel of 16 international experts used the e-Delphi method to address gaps in NTM-PD management. Initial statements were derived from an open-ended questionnaire, supported by a prior systematic review. Iterative rounds of expert evaluation were conducted until a consensus was reached on treatment failure definitions, decision-making criteria, therapeutic strategies and supportive care measures.

Results: Consensus defined treatment failure as the absence of culture conversion after 6 months of appropriate antimycobacterial therapy, while clinical and radiological deterioration were considered additional but non-mandatory criteria. Treatment intensification or de-escalation decisions were based on patient preferences, clinical status, comorbidities, disease severity, antibiotic tolerance, resistance patterns and previous treatment history. Treatment intensification highlighted the necessity for personalised multidrug antibiotic regimens. De-escalation strategies focus on delivering optimal, patient-centred supportive care while minimising pharmacological adverse effects, by opting for simplified antibiotic regimens, intermittent antibiotic courses for symptomatic control or the cessation of antimicrobial therapy.

Conclusion: This study offers a structured approach to managing treatment failure in NTM-PD, addressing patient selection, treatment intensification, de-escalation and supportive care, while championing individualised strategies. Future research should concentrate on validating predictive factors for treatment response, refining therapeutic regimens and investigating host-directed therapies to enhance patient outcomes.