Respirology最新文献

Background and objective: Tracheobronchial amyloidosis is a rare disease. This study aimed to assess the clinical presentation, radiological findings, bronchoscopic features, pathological findings and management approach at a national respiratory centre in China.

Methods: We retrospectively analysed biopsy-confirmed tracheobronchial amyloidosis cases from 2018 to 2023 using electronic medical records. Data on demographics, clinical manifestations, investigational findings, management and prognosis were analysed.

Results: Six patients (2 women and 4 men, mean age 55.5 years) were diagnosed with tracheobronchial amyloidosis. Common symptoms included cough, sputum and dyspnoea. None of the patients had evidence of extra-pulmonary amyloidosis. Diagnosis was confirmed via tracheobronchial biopsy. Precursor proteins included AL-λ and AL-κ in 2 patients, AL-κ and ATTR in one patient. The median delay from symptoms onset to diagnosis was 18 months while computerised tomography (CT) imaging expediated diagnosis of tracheobronchial amyloidosis, with a median time from CT thorax to diagnostic bronchoscopy of 2 days in four cases, with two cases lacking detailed information on the date of the initial CT. Treatments included bronchoscopic intervention in three patients and observation in three patients.

Conclusions: Patients with tracheobronchial amyloidosis often present with symptoms resembling those of other airway disorders. Considering this condition in differential diagnosis is crucial when standard treatments fail. Chest CT facilitates prompt referral for diagnostic bronchoscopy. No curative therapy is currently available.

Background and objectives: Rheumatoid arthritis (RA) is a systemic autoimmune disease that is often complicated by interstitial lung disease (ILD), one of its most severe extra-articular manifestations. However, whether RA causally contributes to ILD development remains unclear.

Methods: We conducted a two-sample Mendelian randomization (MR) analysis to investigate whether RA has a causal effect on ILD. MR uses genetic variants associated with RA as instrumental variables to infer causality and minimize confounding. Genetic instruments for RA were obtained from a large European GWAS (ebi-a-GCST002318; 14,361 cases and 42,923 controls). The ILD outcome data were derived from FinnGen (finn-b-ILD, 1969 ILD cases and 196,986 controls), and autoimmune-related codes were explicitly excluded to minimize phenotypic overlap. MR analyses were performed using inverse variance weighting (IVW), MR-Egger regression, weighted median, mode-based methods, and MR-PRESSO to assess causality, heterogeneity, and pleiotropy.

Results: The MR analysis identified 52 RA-related single nucleotide polymorphisms (SNPs) (p < 5 × 10^-8), which were selected as instrumental variables. The IVW method revealed a significant causal effect of RA on ILD risk, with an odds ratio (OR) of 1.155 (95% confidence interval [CI]: 1.083-1.232, p = 1.04E-05). Directionally consistent results were obtained from weighted median and mode-based methods. The MR-Egger regression showed no evidence of directional pleiotropy (intercept = 0.014, p = 0.147), and Cochran's Q test detected no significant heterogeneity (IVW Q = 45.424, p = 0.694). Furthermore, the MR-PRESSO global test did not detect horizontal pleiotropy (p = 0.26), and no outlier SNPs were identified. Leave-one-out analysis indicated that no single SNP disproportionately influenced the overall estimate. The funnel plot showed a symmetrical distribution, suggesting no evidence of directional pleiotropy or influential bias.

Conclusion: This MR study provides robust genetic evidence supporting a potential causal relationship between RA and increased risk of ILD. These findings highlight the need for increased clinical vigilance, including early respiratory screening and monitoring in RA patients-particularly those at high risk-to facilitate timely detection and management of ILD.

Background and objectives: Anti-GM-CSF autoantibodies (GMAbs) are essential biomarkers for diagnosing autoimmune pulmonary alveolar proteinosis (APAP). While enzyme-linked immunosorbent assay (ELISA) is commonly used, it is time-consuming and requires specialised equipment. We developed a novel immunochromatographic test (ICT) for rapid detection of GMAbs in clinical settings.

Methods: ICT was designed using a gold colloid aggregation method. The test line intensity was calibrated to be close to the ELISA cutoff of 1.65 U/mL using polyclonal anti-GM-CSF antibodies purified from the pooled patient sera. Validation was performed in 211 APAP and 171 non-APAP cases. The sensitivity, specificity, and correlation with ELISA were assessed.

Results: Using known concentrations of serum from APAP patients, the grey zone concentration, which was difficult to judge by visual inspection, was found to be below 3.5 U/mL. In serological diagnosis of 211 cases with APAP and 171 cases with non-APAP lung diseases, the sensitivity and specificity by five examiners were 100% and 98.8%, respectively. When the GMAbs positive serum was serially diluted, the end point dilution titre showed a strong correlation overall (ρ = 0.93) with the antibody concentration determined by the conventional ELISA method, but the correlation was weaker in the low concentration range below 60 U/mL (ρ = 0.67), suggesting that the accuracy of ICT was reduced in the lower concentration range.

Conclusion: This ICT offers a practical alternative to ELISA for APAP serological diagnosis. It enables rapid testing in clinical settings and supports the implementation of GM-CSF inhalation therapy.

Background and objectives: The increasing complexity of interstitial lung disease (ILD) related to cancer-targeted monoclonal antibodies (mAbs) has emerged as a significant clinical concern. Thus, this study aimed to investigate reporting signals of four ILD subtypes detected with cancer-targeted mAbs.

Methods: This global pharmacovigilance study conducted disproportionality analyses to detect signals of ILD subtypes reported with cancer-targeted mAbs. ILD subtypes were classified into eight categories according to previous studies, of which four with a low number of reports were excluded. Five cancer-targeted monoclonal antibodies (VEGF/VEGFR, CD20, PD-1/PD-L1, HER2, and EGFR inhibitors) were included according to ATC code (L01F). Reporting signals were evaluated using reporting odds ratio (ROR) with 95% CI and information component (IC) with IC₀₂₅.

Results: Interstitial pneumonitis and pulmonary fibrosis showed significant disproportionate reporting signals across all drugs. Notably, interstitial pneumonitis showed significant signals with EGFR inhibitors (ROR, 47.46 [95% CI, 44.67-50.42]; IC, 5.47 [IC_0.25, 5.37]) and PD-1/PD-L1 inhibitors (45.20 [43.49-46.97]; 5.36 [5.30]), while pulmonary fibrosis showed higher signals with CD20 inhibitors (12.71 [11.30-14.31]; 3.61 [3.42]). Organising pneumonia exhibited significant signals with PD-1/PD-L1 inhibitors (ROR, 44.48 [95% CI, 39.05-50.67]; IC, 5.26 [IC_0.25, 5.04]), followed by CD20 (17.45 [13.88-21.94]; 3.95 [3.57]), and HER2 (15.95 [11.88-21.40]; 3.76 [3.26]), with the strongest signal observed with PD-1/PD-L1 inhibitors. Eosinophilic pneumonia showed significant signals with all drugs except CD20 inhibitors.

Conclusions: Although causal inference cannot be drawn, this global disproportionality study highlights reporting signals between cancer-targeted mAbs and ILD subtypes, underscoring the importance of strengthening adverse event reporting systems before and after mAb administration.

Background and objective: The impact of lipid abnormalities on right heart function and outcomes in pre-capillary pulmonary hypertension (precPH) remains unclear. This study investigates how lipid profile alterations influence right heart function, strain, and prognosis in precPH patients.

Methods: From June 2013 to December 2023, 394 precPH patients were prospectively enrolled. Clinical data, cardiac MRI-derived right heart systolic function, and strain parameters were compared among groups based on lipid profiles. The optimal cut-off values of lipid profiles were determined using the maximally selected rank statistics. Prognostic analyses were conducted using Cox regression and Kaplan-Meier survival methods.

Results: During a median follow-up of 36 months, 18.8% of patients died. Low-density lipoprotein cholesterol (LDL-C) < 1.93 mmol/L and high-density lipoprotein cholesterol (HDL-C) < 0.82 mmol/L were associated with increased mortality risks (2.51-fold and 2.65-fold, respectively). Multivariate analysis confirmed decreased LDL-C (HR 1.853, 95% CI 1.102-3.115, p = 0.02) and decreased HDL-C (HR 2.019, 95% CI 1.131-3.603, p = 0.02) as independent prognostic indicators. A decrease in either cholesterol subtype predicted worse outcomes (Log-rank p = 0.003). Incorporation of LDL-C and HDL-C enhanced prognostic accuracy of the ESC model (χ²: 50.8 to 60.5, p = 0.007; 50.8 to 66.0, p < 0.001) and ESC-CMR model (χ²: 59.3 to 66.0, p = 0.04; 59.3 to 72.7, p = 0.001). HDL-C < 0.82 mmol/L was associated with impaired right ventricular global longitudinal strain (p < 0.001), RV free wall strain (p < 0.001), and right atrial phasic strain (all p < 0.05).

Conclusions: Decreased HDL-C and LDL-C levels independently predict increased mortality in precPH patients. Notably, low HDL-C significantly associates with impaired right heart function and strain.

Trial registration: Chinese Clinical Trial Registry (https://www.

Clinicaltrials: gov; ID: ChiCTR1800019314 and ChiCTR1900025518).