European Respiratory Journal最新文献

Background: COPD has high mortality, compounded by comorbid cardiovascular disease. We investigated two ECG markers, Cardiac Infarction Injury Score (CIIS) and P pulmonale, as prognostic tools for adverse cardiopulmonary events in COPD.

Methods: This was a p ost hoc analysis of the IMPACT trial. Outcomes included odds (odds ratio, 95% confidence intervals) of adverse cardiopulmonary events stratified by CIIS threshold (<20 versus ≥20) and P pulmonale (baseline). Events included all-cause death, hospitalisation or death, cardiovascular adverse event of special interest, severe COPD exacerbations, and moderate/severe COPD exacerbations. We also assessed the effects of fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol or umeclidinium/vilanterol based on CIIS and P pulmonale.

Results: We included 9448 patients. Patients with CIIS ≥20 (versus CIIS <20) had greater odds of all-cause death (OR 1.73, 95% CI 1.27-2.37, p<0.001), hospitalisation or death (OR 1.33, 95% CI 1.17-1.50, p<0.001), cardiovascular adverse event of special interest (OR 1.27, 95% CI 1.08-1.48, p<0.005), severe COPD exacerbations (OR 1.41, 95% CI 1.21-1.64, p<0.001) and moderate/severe COPD exacerbations (OR 1.25, 95% CI 1.13-1.40, p<0.001). Patients with P pulmonale (versus without) had greater odds of all-cause death (OR 2.25, 95% CI 1.54-3.29, p<0.001), hospitalisation or death (OR 1.51, 95% CI 1.28-1.79, p<0.001), severe COPD exacerbations (OR 2.00, 95% CI 1.65-2.41, p<0.001) and moderate/severe COPD exacerbations (OR 1.25, 95% CI 1.08-1.46, p<0.001). A combined model demonstrated that patients with CIIS ≥20 and P pulmonale had increased risk of all-cause death (OR 3.38, 95% CI 1.23-9.30, p=0.019), hospitalisation or death (OR 1.61, 95% CI 1.14-2.22, p=0.004) and rate of severe COPD exacerbations (OR 1.89, 95% CI 1.22-2.91, p=0.004) and moderate/severe COPD exacerbations (OR 1.25, 95% CI 1.00-1.56, p=0.046). The risk of all-cause death and cardiovascular adverse events of special interest was reduced with fluticasone furoate/umeclidinium/vilanterol versus umeclidinium/vilanterol in patients with CIIS ≥20, but not CIIS <20.

Conclusions: These findings suggest the potential clinical relevance of CIIS and P pulmonale as risk indicators for adverse cardiopulmonary events in COPD.

Background: Cough severity represents an important end-point to assess the impact of therapies for patients with refractory chronic cough (RCC). Our objective was to develop a new patient-reported outcome measure addressing cough severity in patients with RCC.

Methods: Phase 1 (item generation): a systematic survey, focus groups and expert consultation generated 51 items. Phase 2 (item reduction): from a list of 51 items, 100 patients identified those they had experienced in the previous year and rated their importance on a 5-point scale. The McMaster Cough Severity Questionnaire (MCSQ) included items reported to occur most frequently and that had the highest importance scores. Patient feedback on the MCSQ led to elimination of redundant items. Another 100 patients completed the MCSQ, from which we performed an exploratory factor analysis and a Rasch analysis to further refine items on the MCSQ.

Results: Previous publications report on the details of Phase 1. Phase 2 led to selection of 15 items from the initial 51. Patient feedback on the 15 items led to elimination of five redundant items. An exploratory factor analysis of the 10-item MCSQ led to the selection of two domains, and the elimination of one item that demonstrated cross-loading and another that had high inter-item correlations. A Rasch analysis of the 8-item MCSQ confirmed that the response options functioned in a logically progressive manner and that no items exhibited differential item functioning. The final 8-item MCSQ has a 1-week recall period and includes two domains (intensity and frequency). The 8-item MCSQ had high internal consistency (Cronbach's α=0.89), proved able to distinguish different levels of cough severity (person separation index 0.89) and demonstrated high cross-sectional convergent validity (Pearson's correlation 0.76, 95% CI 0.66-0.83) with the 100-mm cough severity visual analogue scale.

Conclusions: Initial evidence supports the validity of the MCSQ, an 8-item instrument measuring cough severity in patients with RCC. Future studies should evaluate its properties in measuring change over time.

Background: Recurrent respiratory papillomatosis (RRP) is a rare respiratory disease primarily caused by chronic human papillomavirus (HPV) infection of serotypes 6 and 11. It manifests in childhood (juvenile-onset recurrent respiratory papillomatosis [JoRRP]) and adulthood (adult-onset recurrent respiratory papillomatosis [AoRRP]), leading to progressive obstruction by papillomas in the upper airway and occasionally in the lower respiratory tract (LRT), including the lungs, with a potential for malignant transformation. This study aimed to delineate the characteristics of JoRRP and AoRRP with LRT involvement in adulthood.

Methods: A multicenter French-speaking cohort study was conducted, coupled with a comprehensive literature review of clinical, histological, therapeutic, and prognostic features associated with RRP-LRT.

Results: Among the 122 with LRT involvement with LRT involvement analyzed, 55 (45%) had JoRRP and 67 (55%) had AoRRP. The mean age at diagnosis was 4 years for JoRRP and 54 years for AoRRP. Ear, nose, and throat involvement was observed in all JoRRP cases and in 34 AoRRP cases (51%). Lung involvement occurred in 47 JoRRP cases (85%) and in ten AoRRP cases (15%). Malignant transformation to squamous cell carcinoma in the trachea (n=6) or lung (n=36) was observed in 42 patients (34%). Factors associated with lung involvement included JoRRP, repeated debulking, and malignant transformation; the only factor associated with malignant transformation was lung involvement. Overall mortality was 16%, with JoRRP, lung involvement, and malignant transformation identified as risk factors for death.

Conclusion: This study highlights the prevalence of lung involvement and malignant transformation in RRP with LRT and advocates for targeted screening measures and preventive therapeutic strategies.

Background: Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung disease (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through adverse drug reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs.

Methods: This retrospective study included cases registered in the FPVD from 1 January 1985 to 1 April 2022 which had ADRs coded in MedDRA with a High-Level Group Term "Lower respiratory tract disorders (excluding obstruction and infection)" involving patients aged ≥18 years.

Results: We analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and death ensued in 13.3%. Males accounted for 54.4% of the cases. Median (range) age was 69 (18-103) years. The most prevalent ADRs were "Interstitial lung disease" (51.0%), "Pulmonary oedema" (acute/non-acute) (15.6%) and "Pulmonary fibrosis" (10.5%). Anti-cancer drugs (31.2%) and cardiovascular drugs (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%).

Conclusion: This study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify the diseases properly and discontinue the culprit drug urgently.

Pulmonary fibrosis (PF) is the most prevalent and severe form of end-stage interstitial lung disease. Macrophages are crucial players in inflammation-induced PF, but the mechanisms driving macrophage polarization and their specific roles in PF pathogenesis remain poorly understood. Here, we demonstrate that both YAP and TAZ are activated in lung macrophages from patients with PF as well as in mice with bleomycin-induced PF. Myeloid-specific Yap/Taz deletion resulted in reduced recruitment of monocyte-derived alveolar macrophages (Mo-AMs), impaired inflammatory responses, decreased PF, and enhanced alveolar epithelial cell regeneration following bleomycin treatment. Conversely, the expression of a constitutively active YAP mutant (YAP^5SA) exacerbated bleomycin-induced PF by increasing Mo-AM recruitment, elevating expression of proinflammatory and profibrotic markers, and impairing alveolar epithelial cell regeneration. We demonstrate that YAP/TAZ-CCL2 signaling plays a crucial role in bleomycin-induced PF, as blocking CCL2 with a neutralizing antibody effectively abrogated the YAP^5SA-induced recruitment of Mo-AMs, inflammatory and fibrotic responses. Additionally, we reveal that the YAP/TAZ-MBD2-TGFβ1-pSMAD2 signaling axis is crucial not only for profibrotic macrophage polarization but also for their crosstalk with lung fibroblasts, driving the fibroblast-to-myofibroblast transition. Collectively, these findings suggest that targeting aberrant YAP/TAZ activity to modulate inflammatory and fibrotic response could be a promising strategy for the prevention and treatment of PF.

Introduction: Global migration has increased in recent decades due to war, conflict, persecutions, and natural disasters, but also secondary to increased opportunities related to work or study. Migrants' risk of tuberculosis (TB) differs by reasons for migration, socioeconomic status, mode of travel and TB risk in transit, TB incidence and healthcare provision in country of origin. Despite advances in TB care for migrants and new treatment strategies, decisions for the management of migrants at risk of TB often rely on expert opinions, rather than clinical evidence.

Methods: A systematic literature search was conducted, studies were mapped to different recommendation groups and included studies were synthesized by meta-analysis where appropriate. Current evidence on diagnosis of active TB in migrants entering the European Union /European Economic Area (EU/EEA) &UK including the clinical presentation and diagnostic delay, treatment outcomes of drug susceptible TB, prevalence and treatment outcomes of multidrug/rifampicin-resistant (MDR/RR)-TB and TB/HIV co-infection was summarised. A consensus process was used based on the evidence.

Results: We document a higher vulnerability of migrants for TB, including an increased risk of extrapulmonary TB, MDR/RR-TB, TB/HIV co-infection and worse TB treatment outcomes compared to host populations. Consensus recommendations include screening of migrants for TB/ latent TB infection (LTBI) according to country data; a minimal package for TB care in drug susceptible and MDR/RR-TB; implementation of migrant-sensitive strategies; free healthcare and preventive treatment for migrants with HIV co-infection.

Conclusion: Dedicated care for TB prevention and treatment in migrant populations within the EU/EEA &UK is essential.

Objective: To compare the effectiveness and safety of tofacitinib (TOF) versus calcineurin inhibitor (CNI) as initial immunosuppressive regimen for anti-melanoma differentiation-associated gene 5-positive dermatomyositis with interstitial lung disease (MDA5+DM-ILD).

Methods: Adult Chinese patients with newly-diagnosed MDA5+DM-ILD (ILD course<3 months) from five tertiary referral centres between April 2014 and January 2023 were included for this retrospective cohort study. The primary effectiveness endpoint was lung transplantation-free survival within 1 year. Propensity score-based inverse probability of treatment weighting (IPTW) was applied for adjustment in this real-world study.

Results: In the eligible cohort, a total of 94 (32.4%) and 105 (46.7%) patients died or underwent lung transplantation within 1 year in the TOF group (n=290) and the CNI group (n=225), respectively. After adjustment by IPTW, patients' lung transplantation-free survival rate within 1 year was significantly higher in the TOF group compared to the CNI group (log-rank p=0.013). Multivariable Cox analysis performed in the IPTW dataset revealed the hazard ratio of TOF versus CNI for 1-year survival was 0.72 (95% CI, 0.56 to 0.94, p=0.013). The adjusted difference of survival rate was 9.3% (95%CI 2.8% to 15.8%). Alternative analytic strategies yielded consistent results in sensitivity analyses. Patients less than 60 years old, without RPILD, or with baseline PaO₂/FiO₂ ≥300 mmHg might benefit more from TOF. Opportunistic infection was the major treatment-related serious adverse event, with generally comparable incidence (42.4% versus 45.3%).

Conclusion: In this large multi-centre cohort study, tofacitinib showed significantly more benefits for 1-year lung transplantation-free survival than calcineurin inhibitors in MDA5+DM-ILD.