Background Clinically important deterioration (CID) has been used to assess chronic obstructive pulmonary disease (COPD) progression by time-to-first-event analysis. However, this does not reveal the clinical importance of the CID components. The win ratio may provide a complementary assessment by comparing outcomes according to a prespecified hierarchy. We reanalysed data from the Tie-COPD studywith win ratio to assess the overall treatment benefit associated with tiotropium in patients with mild-to-moderate COPD.Methods In this exploratory post hoc study, the unmatched win ratio method was applied to the outcomes observed in the Tie-COPD study comparing 18 µg tiotropium with placebo in patients with mild-to-moderate COPD over 24 months. CID was defined as an occurrence of moderate-to-severe exacerbation, an increase of ≥2 units in COPD Assessment Test (CAT) score or a decrease of ≥100 mL in the forced expiratory volume in 1 s (FEV1). We evaluated the win ratio across all possible hierarchies of CID components. Exploratory inverse-probability-of-censoring weighted (IPCW), and covariate-adjusted IPCW (CovIPCW) analyses were performed to account for censoring. Subgroup analyses were performed with stratification by sex, smoking status, Global Initiative for Chronic Obstructive Lung Disease stage, CAT score and modified Medical Research Council score at baseline.Results Of the 841 randomised patients, 771 were included in the full analysis set (tiotropium=388; placebo=383). With the clinical hierarchy of CID defined by FEV1, exacerbation and CAT, the win ratio was 2.26 (95% CI 1.87 to 2.73, p<0.001), and the net benefit was 0.35 (95% CI 0.27 to 0.44, p<0.001). Win ratios were greater than 1 across all hierarchies, subgroups and censoring-adjusted analyses. No treatment-by-subgroup interaction was detected (all p for interaction >0.05).Conclusions In this exploratory post hoc analysis, tiotropium was associated with a greater overall treatment benefit than placebo in patients with mild-to-moderate COPD. This benefit was also observed in patients with mild disease or fewer respiratory symptoms. The direction of the findings was consistent across alternative CID hierarchies and censoring-adjusted analyses.Trial registration number NCT01455129.
Rationale Long-term survival after lung transplant is limited by chronic lung allograft dysfunction (CLAD). Oscillometry is a novel pulmonary function technique that complements spirometry. We hypothesise that oscillometry and spirometry at 3 months post-transplant are associated with CLAD.Methods Double lung transplant recipients (n=280) were enrolled from 2017 to 2020 for oscillometry at the first post-transplant spirometry. We excluded re-transplantation and patients missing 3-month oscillometry-spirometry data. Patients who died within 3 years where a CLAD diagnosis was ascertained were included. We used Mann-Whitney U and Pearson’s χ2 tests for group comparisons, logistic regression to assess the associations of spirometry and oscillometry with CLAD, and receiver operating characteristic curves to identify the threshold values for CLAD.Results At 3 years post-transplant, 129 were alive and CLAD-free while 75 patients had CLAD. Preoperative and perioperative characteristics were similar except for higher body mass index in the CLAD group. At 3 months, CLAD patients had lower forced expiratory volume in 1 s (%FEV1) and FEV1/FVC (forced vital capacity), and worst lung mechanics with high R5 (resistance at 5 Hz), low X5 (reactance at 5 Hz) and high AX (area of reactance). %FEV1, FEV1/FVC, R5 and R5−19 (difference in resistance from 5 to 19 Hz), X5, X5 z-score and AX were independently associated with CLAD. A composite metric of %FEV1, FEV1/FVC, R5 z-score, R5−19 and AX provided the strongest association with CLAD.Conclusions The 3-month composite spirometry-oscillometry score post-transplant provides risk stratification of CLAD. Patients at risk can be monitored closely, to enable earlier interventions and minimise progression to CLAD.
Background Identifying progression in fibrotic interstitial lung disease (f-ILD) is essential for treatment decisions and prognostication. Quantitative CT (qCT) may improve detection of progressive pulmonary fibrosis (PPF). We evaluated whether routine qCT enhances identification of disease progression.Methods We conducted a retrospective observational study of patients presenting to an ILD service over 2 years. Patients with f-ILD who underwent two CT scans within 24 months prior to ILD multidisciplinary team (ILD-MDT) review were included. CTs were initially reported by a mixed pool of radiologists and subsequently reviewed by an expert thoracic radiologist at ILD-MDT. The contextflow ADVANCE Chest CT was used to quantify lung abnormalities.The cohort was divided 70:30 into derivation and validation sets, stratified by ILD-MDT-defined progression. In the derivation cohort, optimal qCT thresholds were defined using Youden’s index and applied to the validation cohort to assess detection of previously unreported progression.Results 127/502 patients met inclusion criteria and were stratified into derivation (n=89) and validation (n=38) cohorts. In the derivation cohort, a 0.39% increase in combined honeycombing and reticulation yielded an AUC of 0.64 for identifying progression.In the validation cohort, this threshold achieved sensitivity and specificity of 0.71 for PPF detection. Although 27/38 (71.1%) patients were initially reported as stable or without comment on progression, 12/27 (44.4%) were later classified as having radiological progression at ILD-MDT. Of these discordant cases, qCT correctly identified progression in 10/12 (83.3%).Discussion This study demonstrates that qCT may assist the non-specialist radiologist in identifying fibrotic disease progression enabling earlier access to appropriate treatment.
Background Obesity is a chronic inflammatory and metabolic condition implicated in the pathogenesis of several fibrotic diseases. However, population-based evidence regarding the association between obesity and the risk of idiopathic pulmonary fibrosis (IPF) remains limited.Methods This is a nationwide population-based cohort study using the National Health Information Database of South Korea. Adults aged ≥20 years who participated in the National Health Screening Program in 2012 were included. Individuals with prevalent IPF or those diagnosed within 1 year after baseline were excluded. Obesity was assessed using body mass index (BMI ≥25 kg/m² by Asian criteria) and waist circumference (WC). Incident IPF was defined by insurance claims with the International Classification of Diseases, 10th Revision code J84.1 in conjunction with registration in the Rare Intractable Diseases programme.Results Among 4 788 202 participants followed for a mean of 10.15 years, 1 591 830 (33.2%) were classified as obese. Higher BMI was associated with an increased risk of IPF in a dose–response manner after multivariable adjustment. Compared with participants with BMI 18.5–22.9 kg/m², adjusted HRs for IPF were 1.25 (95% CI 1.16 to 1.35) for BMI 23–24.9 kg/m², 1.55 (95% CI 1.45 to 1.66) for BMI 25–29.9 kg/m² and 1.66 (95% CI 1.42 to 1.94) for BMI ≥30 kg/m². In contrast, underweight individuals (BMI <18.5 kg/m²) had a lower risk of IPF. WC demonstrated a similar trend, with higher values independently associated with increased IPF risk.Conclusions In this large nationwide cohort, both general and abdominal obesity were independently associated with an increased risk of incident IPF. These findings provide population-based evidence supporting a potential role of increased adiposity in IPF pathogenesis.
Introduction Chronic obstructive pulmonary disease (COPD) has a heterogeneous clinical and immunological presentation. Although proportions of group 1 innate lymphoid cells (ILC1) in peripheral blood were shown to correlate with COPD severity, no analysis of ILC subsets in relation to clinical outcomes has been performed yet. Our aim was to explore the relationship between clinical phenotype clusters and ILC subsets in COPD.Methods 24 patients with COPD were included in this explorative cross-sectional study. Forced expiratory volume in 1 s (FEV1), diffusion capacity for carbon monoxide, COPD Assessment Test (CAT) and body mass index (BMI) values were collected. Clinical clusters were defined, ILC populations in peripheral blood were quantified and characterised by flow cytometry. Data were analysed using a combination of multiple factor and principal component analysis.Results First, we identified three clinical clusters. C1 (n=12) had low FEV1 and BMI values and the highest disease burden, as determined by CAT. C2 (n=11) comprised older patients with increased BMI and the most pack-years. C3 (n=11) had the highest FEV1 values and fewer exacerbations. Based on leucocyte differentiation and phenotypic characterisation of ILC subsets, two immunological clusters of patients with COPD were identified. C1, the most severe COPD group, was associated with reduced frequencies of circulating ILCs with a potentially inflammatory phenotype.Conclusions The finding that clinical clusters of patients with COPD were strongly associated with peripheral blood immunophenotype and ILC profile suggests a role for ILCs in disease course and may have relevance for the development of personalised therapies.
