BACKGROUND AND OBJECTIVE:This study determined contemporary transplant-free survival in fibrotic interstitial lung disease (ILD), identified baseline factors associated with death or transplant, and assessed performance of the ILD-GAP (Gender, Age, Physiology) index in a contemporary cohort. METHODS:Patients with idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (fHP), connective tissue disease-associated ILD (CTD-ILD), or unclassifiable ILD (uILD) prospectively enrolled in the Canadian Registry for Pulmonary Fibrosis were included. Transplant-free survival at 1, 3, and 5 years was estimated overall and by subtype using enrollment as time zero. Cox proportional hazards models evaluated associations between patient characteristics and time to death or transplant. ILD-GAP scores were calculated at 1, 2, and 3 years, and discriminability was assessed with Harrell's C statistic. RESULTS:Among 4236 patients with fibrotic ILD enrolled in the Canadian Registry for Pulmonary Fibrosis (CARE-PF), 31% had IPF, 40% CTD-ILD, 9% fHP, and 20% uILD. Overall transplant-free survival was 91% at 1 year, 72% at 3 years, and 57% at 5 years. Survival was lowest in IPF (87%, 61%, 39%) and highest in CTD-ILD (95%, 81%, 70%). Compared with IPF, CTD-ILD was associated with better 5-year survival after adjustment (hazard ratio 0.64 [0.55-0.76]). ILD-GAP showed moderate discrimination at 1 (C = 0.75), 2 (C = 0.74), and 3 years (C = 0.73). CONCLUSION:In this registry cohort anchored at enrollment, CTD-ILD had superior transplant-free survival versus IPF, and ILD-GAP provided moderate prognostic accuracy.
Multidisciplinary discussion remains the cornerstone of ILD diagnosis and management, with recent advances further strengthening the integration of clinical, radiological, pathological, and molecular information. Updated ILD nomenclature and classification better align disease terminology with underlying morphology and pathobiology. Growing emphasis is being placed on the early detection of ILD and on identifying individuals at high risk of progression among those with interstitial lung abnormalities (ILAs). Emerging multi-omic biomarkers and quantitative imaging techniques are enhancing prognostic stratification and may support future precision medicine approaches. Novel antifibrotic therapies and targeted treatments are expanding therapeutic options beyond IPF, although important unmet needs remain regarding patient selection, treatment response, and disease modification. The integration of clinical, radiological, functional, and molecular information will be fundamental to optimize individualized management and improve long-term outcomes in patients with ILDs.
BACKGROUND AND OBJECTIVE:Prediction of the progressive phenotype from baseline evaluation is challenging due to the variable clinical course of fibrosing interstitial lung disease (ILD). The aim of this study was to evaluate whether the Single Time Point Prediction (STP) score predicts disease progression better than other quantitative scores. METHODS:This is a retrospective two-centre study including patients with ILD other than idiopathic pulmonary fibrosis (IPF). Using an automated quantification system, quantitative lung fibrosis (QLF), quantitative ground-glass opacity (QGG), quantitative ILD (QILD; the sum of reticulation, honeycombing, and ground-glass opacity), quantitative normal lung (QNL), and STP scores were measured. Disease progression (DP) was defined as an absolute decline in forced vital capacity (FVC) ≥ 5% or DLCO ≥ 10% predicted, death or lung transplantation. RESULTS:Of 245 patients, 137 (55.9%) progressed during follow-up (median: 20.4 months). In the Kaplan-Meier analysis, patients with high QGG (≥ 10%), high QILD (≥ 30%), and high STP (≥ 30%) showed shorter DP free survival time than those without. After adjusting for age, sex, FVC, and types of non-IPF ILD, QGG scores ≥ 10%, QILD ≥ 30%, and STP ≥ 30% remained significant predictors of progression (hazard ratio [HR] = 1.71, p = 0.024; HR = 1.73, p = 0.006; and HR = 1.58, p = 0.020, respectively). Furthermore, higher QILD and QGG scores in STP-positive regions were independently associated with increased DP risk, whereas higher QNL in STP-negative regions was associated with lower DP risk. CONCLUSIONS:The STP score is a useful imaging biomarker for predicting DP and, when combined with conventional quantitative CT scores, may improve risk stratification in patients with non-IPF ILD.
BACKGROUND AND OBJECTIVE:Incident airflow limitation is frequently diagnosed at advanced stages. Identifying individuals at risk through primary care spirometry may enable earlier intervention, yet validated, pragmatic frameworks remain lacking. METHODS:We applied a framework of three mutually exclusive spirometric at-risk phenotypes, termed Three-Phenotype Spirometry-Based Identification (hereafter TriSpi), to 6123 participants from two population-based cohorts: KORA (n = 1973, 3-year Follow-up, derivation) and SHIP (n = 4150, 5-year Follow-up, validation). TriSpi+ individuals were defined as meeting criteria for one of the three phenotypes: Early airflow limitation (EAL, FEV1/FVC > 0.7 and < 10th percentile or < 0.7 and > 5th percentile), small airway dysfunction (SAD) defined using FEF50- or FEF75-based thresholds; and preserved-ratio impaired-spirometry (PRISm). Associations with incident airflow limitation were tested using Firth's regression. RESULTS:EAL, PRISm, and SAD (defined using either FEF50 or FEF75-based thresholds) were significantly associated with incident airflow limitation across cohorts and follow-ups. TriSpi+ individuals accounted for 26%-36% of the population, identifying 74%-93% of future cases, while TriSpi+ was associated with a 10-25-fold increase in risk. Negative predictive values exceeded 95% across definitions, and the number needed to screen among TriSpi+ individuals ranged from 7 to 13. EAL showed the strongest individual association (OR up to 53.2), while SAD was more common in younger adults. CONCLUSION:Combining definitions for EAL, PRISm, and SAD enables robust prediction of incident airflow limitation. TriSpi may serve as a scalable, pragmatic approach for early risk stratification in primary care, in absence of post-BD spirometry.
Abstract Introduction Treatment initiation or intensification to prevent exacerbation of chronic obstructive pulmonary disease (COPD) is based on the identification of patients with high exacerbation risk. The commonly used high-risk category of at least 2 moderate or 1 severe exacerbation within the prior 12 months has limited supporting evidence. We aimed to test the discriminative accuracy and assess the clinical utility of various COPD exacerbation categories for predicting future exacerbations. Methods In the COPDGene and NOVELTY cohorts, for each 1-year and 2-year recall periods, we estimated 6 distinct categories of exacerbation frequencies: ≥1 moderate (M1), ≥2 moderate (M2), ≥1 severe (S1), ≥1 moderate and ≥1 severe (M1andS1), ≥1 moderate or ≥ 1 severe (M1orS1), and ≥2 moderate or ≥ 1 severe (M2orS1), each ascertained in 3 ways: within 1 year, in each of 2 consecutive years (suffix E), and over a rolling combined 2-year period (suffix R). We used the area under the receiver operating characteristic curve (AUC) and decision curve analysis to evaluate the discriminative accuracy and clinical utility of these 18 categories for predicting the occurrence of M2orS1 (current standard) in the subsequent year. Results In COPDGene (n = 3,035), for the prediction of future M2orS1, baseline M1orS1R had the highest AUC (0.69, 95%CI 0.67-0.71) vs. baseline M2orS1 (0.66, 95%CI 0.64-0.67; Δ = 0.03;p<0.001). In NOVELTY (n = 3,080), M1orS1R category had the highest AUC (0.87, 95%CI 0.85-0.88) vs. M2orS1 (0.75, 95%CI 0.72-0.77, Δ = 0.12;p<0.001). Decision curve analysis demonstrated that the two-year rolling patterns provided the highest clinical utility across a clinically relevant treatment threshold range of 5% to 30% (Figure). M1orS1R also had the highest AUC for predicting any exacerbation (M1orS1) in both COPDGene (AUC = 0.68, 95%CI 0.66-0.70) and in NOVELTY (AUC = 0.86, 95%CI 0.85-0.88). Conclusions At least 1 moderate or 1 severe exacerbation over the previous 2 years has the highest discrimination and confers the highest clinical utility for predicting high COPD exacerbation risk. Overall, the combination of higher performance of various exacerbation history patterns in terms of their statistical (AUC) and clinical utility (net benefit) indicates that using a two-year recall and a lower threshold for high-risk classification (any moderate/severe events) is superior to the current standard of care. This abstract is funded by: This work was supported by NHLBI R01 HL151421 (SPB and AN), U01 HL089897 and U01 HL089856, by NIH contract 75N92023D00011, and by a Team Grant from the Canadian Institutes of Health Research (PHT 178432). COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion. The NOVELTY study was funded by AstraZeneca.
BACKGROUND AND OBJECTIVE:Pulmonary alveolar proteinosis (PAP) is a rare disease of inappropriate alveolar surfactant accumulation. The study objective was to compare Greece-Türkiye-Cyprus cohorts, followed-up for 20 years. METHODS:Data were retrieved retrospectively by chart review. RESULTS:One hundred and thirty patients, Greece 39, Türkiye 87, Cyprus 4, were included; 115 (89%) autoimmune (a)PAP, 13 (10%) secondary, 1 (1%) hereditary. Abnormal anti-GM-CSF antibody titre was available in 86/115 patients, further analyzed for aPAP. Forty (46%) were male, with median (IQR) age at diagnosis of 40 (31-50) years. At median (IQR) duration of clinical follow-up of 39 (18-78) months, three patients died. Non-survivors had higher rates of cardiovascular disease [67% vs. 5%, p < 0.001], LTOT (67% vs. 13%, p = 0.001), pulmonary fibrosis [67% vs. 5%] and worse functional status at follow-up [FVC% pred 49 (29) vs. 87 (74-97); p = 0.026, DLCO% pred 21 (46) vs. 72 (58-82); p = 0.016]. aPAP patients were stratified by therapy group (no WLL-no i-GM-CSF, WLL alone, i-GMCSF alone and both WLL and iGM-CSF). WLL was more frequently performed in Türkiye and i-GMCSF alone in Greece (p = 0.006). All therapies were effective. No difference was detected on outcome when sole iGM-CSF was compared to WLL alone or in combination with iGM-CSF [deceased/alive 0%/100% vs. 7%/93%, p = 0.491]. Sole iGM-CSF significantly ameliorated clinical and functional parameters of disease severity [DLCO% (p = 0.013), SatO2 (p = 0.002), 6MWT (p = 0.026)]. Across all therapy groups, pulmonary fibrosis eliminated beneficial response to treatment. CONCLUSION:This first real-life comparison of aPAP cohorts originating from three countries showed the non-inferiority of sole iGM-CSF treatment. Fibrosis negatively affects response to treatment and survival.
