Respiratory Research最新文献

Backgrounds: Anti-MDA5 antibody-positive dermatomyositis (DM) is characterized by the presence of anti-MDA5 antibodies. We aimed to assess longitudinal changes of anti-MDA5 antibody levels and long-term outcomes in 6-month survivors of anti-MDA5 + DM with interstitial lung disease (ILD).

Methods: Anti-MDA5 antibody titers were measured using enzyme-linked immunosorbent assay upon newly diagnosed anti-MDA5 + DM-ILD patients. Patients with follow-up beyond 6 months and at least two anti-MDA5 antibody measurements were subsequently subjected to group-based trajectory analysis by utilizing latent class mixture model. Seroconversion was defined as a change from positive to negative for anti-MDA5 antibodies. Outcome measurements include low disease activity (LDA) status and remission.

Findings: In 6-month survivors, two anti-MDA5 antibody trajectories were identified: "fast seroconvertors" and "slow seroconvertors". The median time to anti-MDA5 seroconversion for fast seroconvertors was 9 (IQR: 5-15) months, whereas slow seroconvertors did not achieve 50% anti-MDA5 seroconversion during the follow-up period. Although with a lower baseline PaO₂/FiO₂ (P = 0.01), along with a lower baseline anti-MDA5 antibody level (P < 0.001), these anti-MDA5 fast seroconvertors had a much higher rate of LDA attainment compared to slow seroconvertors at 12 months (66.0% vs. 37.2%, P < 0.001); as well as a greater proportion of prednisone-free remission by 24 months (16.7% vs. 8.8%, P = 0.02), and drug-free remission by 36 months (10.5% vs. 2.7%, P = 0.006). The relative changes of anti-MDA5 antibody levels at the first three months (ΔMDA5@3m), with a cut-off point of 33.0% reduction, yielded a good predictive value for different seroconvertors with an area under curve of 0.86. Multivariable Cox regression model identified a reduction in ΔMDA5@3m of ≥ 33.0% as an independent favorable factor for achieving LDA (HR 1.96, 95% CI: 1.33-2.90, P < 0.001).

Conclusions: Two distinct trajectories of anti-MDA5 antibody levels among 6-month survivors with anti-MDA5 + DM-ILD have been identified. The long-term outcomes were favorable for those with fast seroconvertors.

Background: Long-term ozone (O₃) exposure is known to be associated with respiratory mortality and hospitalization, but its effects on respiratory morbidity, symptom severity, and quality of life remain undefined.

Methods: This study was conducted using data from the China Pulmonary Health (CPH) study. Respiratory morbidity was measured by the COPD Assessment Test (CAT) scores, the modified Medical Research Council (mMRC) dyspnea scale, and spirometry-defined COPD. Health-related quality of life was also considered. Long-term O₃ exposure was defined as the annual average of daily maximum 8-hour average (MDA8) O₃ concentrations in the year prior to the survey. Logistic and linear regression models were used to explore the association between long-term O₃ exposure and the health outcomes.

Results: Each 10 µg/m³ increase in O₃ was associated with increased odds of CAT ≥ 10 (measured in participants with a post-bronchodilator FEV₁/FVC ratio less than 0.8; OR = 1.09, 95% CI:1.00, 1.18), mMRC ≥ 1 (OR = 1.13, 95% CI:1.04, 1.22), and COPD (OR = 1.11, 95% CI:1.05, 1.17), as well as a 0.55-point decline in SF-12 PCS (95% CI: -0.71, -0.39). Positive associations were also observed for some single CAT items. Female and younger participants were identified as subgroups particularly vulnerable to O₃.

Conclusion: Long-term O₃ exposure was associated with the presence of respiratory symptoms, increased prevalence of spirometry-defined COPD, and poorer quality of life. These findings underscore the importance of raising awareness of the respiratory effects of O₃ exposure and the need for O₃ control.

Trial registration: Not applicable.

Background: Primary Sjögren's syndrome-associated interstitial lung disease (pSS-ILD) shows heterogeneous patterns and variable prognosis. We previously observed elevated serum CA125 in pSS-ILD. This study investigated whether CA125 predicts adverse outcomes in pSS-ILD.

Methods: Data were derived from the ILD-China cohort (ClinicalTrials.gov: NCT04370158). Among enrolled pSS-ILD patients, a total of 395 with follow-up data were included. The adverse outcomes were death or lung transplantation (LTx). Associations were evaluated using Cox proportional hazards models, with restricted cubic splines to assess nonlinearity.

Results: Among 395 patients, 87 experienced adverse outcomes (83 deaths and 4 LTx). CA125 levels were higher in patients with adverse outcomes and were associated with indices of disease severity. In ROC analysis, CA125 showed the highest discrimination among the evaluated biomarkers (AUC 0.764), with a higher AUC than KL-6 (0.580). In multivariable Cox models, higher CA125 modeled as a continuous biomarker was independently associated with adverse outcomes (adjusted HR 1.005 per 1 U/mL increase, 95% CI 1.002-1.007; P < 0.001), corresponding to an approximately 5% higher hazard per 10 U/mL increase. Spline analysis supported a nonlinear relationship between CA125 and hazard.

Conclusions: Higher serum CA125 is independently associated with adverse outcomes in pSS-ILD, with evidence of a nonlinear exposure-hazard relationship. CA125 may aid prognostic assessment in pSS-ILD.

Trial registration: Clinical trials.govs: NCT04370158, Registration date: 30 April 2020.