When is Lung Biopsy Useful for Diagnosing ANCA-Associated Vasculitis? Insights From a Multi-Center Retrospective Analysis

Authors: M Sonoda, et al.

This retrospective study evaluated the usefulness of lung biopsy for diagnosing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Medical records of patients who underwent bronchoscopic lung biopsy at two Japanese centres between 2003 and 2024 were reviewed. Clinical, radiological, pathological findings, and biopsy-related complications were assessed. A total of 31 patients with suspected AAV underwent transbronchial lung biopsy (TBLB). These patients had characteristic findings such as alveolar haemorrhage, ANCA positivity, and suspected extrapulmonary vasculitic lesions involving the nasal mucosa, kidneys, or skin. Histological confirmation through TBLB was achieved in 4 patients, including 1 case each of GPA and EGPA, and 2 cases of MPA. All confirmed cases showed distinct pulmonary nodules, masses, or interstitial infiltrates related to AAV. An additional 17 patients were ultimately diagnosed with AAV through extrapulmonary tissue biopsy (13 patients) or clinical diagnosis (4 patients). No major biopsy-related complications, including massive bleeding or pneumothorax, were reported following TBLB.

Overall, the study suggests that lung biopsy may help diagnose AAV in selected patients with characteristic clinical features and clear pulmonary lesions.

Mapping Longitudinal FVC and DLCO Trajectories across Medication Regimens in Interstitial Pneumonia with Autoimmune Features

Authors: D C Gomez Manjarres, et al.

This retrospective cohort study evaluated the effects of antifibrotics, immunosuppression, and combination therapy in patients with Interstitial Pneumonia with Autoimmune Features (IPAF), including fibrotic and non-fibrotic subtypes. The study included 159 patients treated at the University of Florida. The mean age was 69.2±10.2 years, 52.2% were male, and 81.1% were White. Baseline mean forced vital capacity (FVC) was 69.4±18.6%, while diffusing capacity for carbon monoxide (DLCO) was 43.2±17.9%. Dyspnoea (70.2%) and cough (52.8%) were the most common symptoms. Overall mortality was highest in patients receiving prednisone/mycophenolate/azathioprine (42.2%) and immunosuppression plus antifibrotic therapy (45.8%). Across treatment groups, fibrotic status was not significantly associated with annual change in FVC percentage (p>0.05). However, patients receiving antifibrotics showed a trend toward slower FVC decline (β ≈ +8% per year; p=0.053). Median survival was generally similar between fibrotic and non-fibrotic IPAF across treatment groups. Kaplan-Meier analysis suggested numerically lower early survival in fibrotic IPAF patients receiving combination therapy, although this was not statistically significant (χ²=2.91; p=0.088).

Overall, the study showed variable disease trajectories and treatment responses in IPAF, highlighting the heterogeneity of the condition.

Small Airway Disease in Interstitial Lung Disease is Common and Correlates with Disease Severity

Authors: O Freund, et al.

This prospective observational study evaluated the prevalence and clinical significance of small airway disease (SAD) in patients with interstitial lung disease (ILD) using impulse oscillometry (IOS). A total of 94 patients with ILD completed IOS, pulmonary function tests, and six-minute walking test (6MWT). The median age was 70 years, 44% were female, and 74% had fibrotic ILD. The most common ILD subtypes were connective tissue disease-related ILD (32%) and hypersensitivity pneumonitis (22%). SAD was identified in 46 patients (49%) based on frequency dependence of resistance (R5-20) >0.1 kPa/L/s or area under the reactance curve (AX) >1.0 kPa/L. SAD was not associated with baseline characteristics, fibrosis, or ILD subtype. However, patients with SAD had worse lung function and exercise capacity compared with those without SAD. Median forced vital capacity (FVC) was lower in patients with SAD (74% vs 84% predicted; p<0.01), as were total lung capacity (75% vs 86% predicted; p=0.04) and diffusing capacity for carbon monoxide (DLCO) (48% vs 54% predicted; p=0.02). Exercise capacity was also reduced, with lower median 6MWT distance (413 vs 465 meters; p=0.01). Among patients with fibrotic ILD, progressive pulmonary fibrosis in the previous year was more common in those with SAD (60% vs 18%; p<0.001), along with greater DLCO decline and worsening radiologic findings and symptoms. Higher AX and R5-20 values were associated with air-trapping or mosaic attenuation on chest computed tomography (CT), but not with honeycombing or traction bronchiectasis.

Overall, the study showed that SAD is common in ILD and is associated with worse disease severity and functional impairment.

Quantitative CT Parameters Predict ILA Progression

Authors: J Kropski, et al.

This study evaluated whether quantitative computed tomography (qCT) metrics could help predict progression from interstitial lung abnormalities (ILA) to interstitial lung disease (ILD). The analysis included deidentified chest CT datasets from Vanderbilt University Medical Center (VUMC) and Weill Cornell Medical Center (WCMC). The VUMC cohort included first-degree relatives of patients with familial pulmonary fibrosis undergoing serial high-resolution CT scans, while the WCMC cohort included patients with incidentally detected ILA who underwent follow-up imaging. A total of 369 subjects from VUMC and 82 subjects from WCMC were included. ILD developed in 8 participants from the VUMC cohort and 7 from the WCMC cohort. Mean age was 53.7 years in VUMC and 70.3 years in WCMC. Median follow-up duration was 38 months and 18.5 months, respectively. Several qCT parameters in the VUMC cohort showed significant or trend-level associations with ILD-free survival, including airway tortuosity, pulmonary vessel fractal dimension, fibrosis volume, vessel volume, airway wall area, airway volume, airway radius, and percentage of lung voxels with attenuation >−600 Hounsfield units (HU). In the WCMC cohort, quantitative emphysema score was significantly associated with ILD risk. Hazard ratio estimates for 8 of 11 features associated with ILD risk in the VUMC cohort showed similar directional trends in the WCMC cohort.

Overall, the findings suggest that qCT measures of airway, vascular, and parenchymal abnormalities may help identify individuals with ILA who are at increased risk of developing ILD.

Predictors of Treatment Response to Antifibrotic Therapy in Patients With Idiopathic Pulmonary Fibrosis

Authors: T Kishaba, et al.

This retrospective study evaluated baseline predictors of response to antifibrotic therapy in patients with idiopathic pulmonary fibrosis (IPF). The analysis included 47 patients diagnosed with IPF between 2012 and 2020 who received antifibrotic therapy for at least 3 months and underwent baseline and follow-up pulmonary function tests (PFTs). The cohort included 32 men and 15 women, with a mean age of 74.3 years. Overall, 63.8% were ever-smokers. Disease deterioration within 1 year was defined as worsening symptoms, radiologic progression, or an absolute decline in forced vital capacity (FVC) of ≥5%. Baseline pulmonary function showed mean percent predicted peak expiratory flow (%PEF) of 77.9%, total lung capacity (%TLC) of 73.9%, forced vital capacity (%FVC) of 72.2%, and diffusing capacity for carbon monoxide (%DLco) of 63.7%. High-resolution computed tomography (HRCT) patterns were classified as definite usual interstitial pneumonia (UIP) in 20 patients, probable UIP in 19, and indeterminate in 8. Lower baseline %PEF (odds ratio [OR] 0.977; p=0.097) and %TLC (OR 0.953; p=0.071) were associated with clinical deterioration within 1 year. Patients with preserved %PEF and %TLC tended to have a slower rate of functional decline. During a median follow-up of 24 months, median survival was 47 months.

Overall, the findings suggest that lower baseline %PEF and %TLC may help identify patients with IPF who are more likely to experience poorer response to antifibrotic therapy.

Comparative Evaluation of Survival Outcomes and Safety Between Nintedanib and Pirfenidone in Idiopathic Pulmonary Fibrosis: Systematic Review and Meta-Analysis

Authors: M Hasson, et al.

This systematic review and meta-analysis compared the efficacy and safety of nintedanib and pirfenidone in patients with idiopathic pulmonary fibrosis (IPF). The analysis included 33 studies published between 2016 and 2025, involving more than 7,400 patients with IPF. Most studies were retrospective or cohort-based, with follow-up durations ranging from 12 months to over 5 years. Standard antifibrotic doses were used across studies. Analysis of 9 studies evaluating survival showed no significant difference between nintedanib and pirfenidone (hazard ratio [HR] 1.24; 95% confidence interval [CI], 0.91–1.69; p=0.18). Similarly, pooled data from 12 studies showed no significant difference in all-cause mortality (odds ratio [OR] 0.98; 95% CI, 0.73–1.31; p=0.87). Treatment modifications were common but not significantly different between therapies (OR 1.37; 95% CI, 0.94–2.00; p=0.11). However, dose reductions occurred significantly more often (OR 2.27; 95% CI, 1.66–3.11; p=0.0026). Adverse events were also significantly more frequent overall with antifibrotic therapy (OR 1.68; 95% CI, 1.27–2.21; p=0.0003).

Overall, the meta-analysis showed that nintedanib and pirfenidone provide comparable survival and mortality outcomes in IPF, although both therapies are associated with frequent adverse events and treatment adjustments.

Associations Between Changes in HRCT Scores and Transplant-Free Survival in Patients With Progressive Pulmonary Fibrosis

Authors: A C Swaminathan, et al.

This study evaluated whether changes in radiographic fibrosis on high-resolution computed tomography (HRCT) could predict outcomes in patients with progressive pulmonary fibrosis (PPF). The analysis included 138 patients with PPF enrolled in the ILD-PRO Registry. All patients had interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis and had undergone at least two HRCT scans. A machine learning algorithm was used to quantify total ILD burden (QILD score) and extent of lung fibrosis (QLF score). The median age was 66 years, 63% were female, and median follow-up was 23.4 months. During follow-up, 49 patients (35.5%) died or underwent lung transplant. The median time between HRCT scans was 12.1 months. Each 5% absolute increase in quantitative lung fibrosis (QLF) score was associated with a 47% higher risk of death or lung transplant (hazard ratio [HR] 1.47; 95% confidence interval [CI], 1.34–1.62). Similar findings were observed for increases in total ILD burden (QILD score; HR 1.45; 95% CI, 1.29–1.63). These associations remained significant even after adjusting for changes in forced vital capacity (FVC) percent predicted.

Overall, increasing radiographic fibrosis on serial HRCT scans was associated with worse transplant-free survival in patients with PPF, independent of lung function decline.

Associations Between Ground Glass Opacity, Fibrosis and Lung Function in Idiopathic Pulmonary Fibrosis

Authors: K R Kirov, et al.

This study evaluated the relationship between ground glass opacities (GGO), fibrosis on high-resolution computed tomography (HRCT), and lung function changes in treatment-naive patients with idiopathic pulmonary fibrosis (IPF). The analysis included HRCT scans from 377 patients enrolled in the PROFILE study. Using an artificial intelligence-based imaging model, scans were segmented into GGO and fibrosis components. Patients were categorized as fibrosis-rich (277 patients) or GGO-rich (100 patients) based on the predominant imaging pattern. Fibrosis-rich patients had lower mean forced vital capacity (FVC) compared with GGO-rich patients. Baseline FVC showed a moderate correlation with fibrosis percentage in fibrosis-rich patients and a weak correlation with GGO percentage in GGO-rich patients. At 6 months, changes in GGO percentage showed a significant association with FVC change in 34 patients with follow-up scans (r=-0.66; p<0.001; adjusted R²=0.42). However, no association was observed between 12-month FVC change and 12-month GGO change. Changes in fibrosis percentage were not associated with FVC change at 6 months. However, at 12 months, fibrosis progression was significantly associated with worsening FVC in 40 patients (r=-0.38; p=0.014; adjusted R²=0.12).

Overall, the findings suggest that short-term lung function changes in IPF may be influenced by changes in GGO, while longer-term decline appears to be driven by fibrosis progression.

Comparison of Clinical and Radiological Features in Patients with Pulmonary Fibrosis and Telomere Lengths

Authors: R A Raghu, et al.

This retrospective single-centre study evaluated clinical and high-resolution computed tomography (HRCT) features in patients with pulmonary fibrosis (PF) with short telomeres (ST) compared with normal telomere length (NT). The study included 24 patients with PF who progressed to require lung transplantation and underwent genetic testing before transplantation. Of these, 15 patients had short telomeres. The median age at diagnosis was 53 years, and 75% of patients were male. Baseline lung function before transplantation showed a mean forced vital capacity (FVC) of 1.98 L (47.3% predicted) and mean diffusing capacity for carbon monoxide (DLCO) of 37.9%, with no significant differences between the ST and NT groups. Patients with ST were more likely to have a diagnosis of idiopathic pulmonary fibrosis (IPF) based on 2022 guideline criteria compared with patients with NT (12/15 vs 3/9; p=0.036). A combined pleuro-parenchymal fibroelastosis-usual interstitial pneumonia (PPFE-UIP) pattern on HRCT was observed more frequently in patients with ST than NT (40% vs 12.5%), although this difference was not statistically significant (p=0.191). Segment 4 liver hypoplasia was also more common in the ST group, but this finding did not reach statistical significance.

Overall, the study suggests that PF patients with short telomeres more commonly have IPF, and combined PPFE-UIP patterns may potentially be associated with short telomeres.

Evolving Interstitial Lung Disease (ILD): From Hypersensitivity Pneumonitis Mimic to Connective Tissue Disease-ILD

Authors: A Ahmed Shaikh, et al.

This case report describes a 59-year-old woman who presented with progressive dyspnea, cough, hand swelling, pleuritic chest pain, lower extremity edema, and joint stiffness after exposure to dust, mold, and mouse droppings while cleaning an old house. Initial chest computed tomography angiography (CTA) showed multifocal interstitial infiltrates without pulmonary embolism, and cardiac evaluation was normal. Due to the environmental exposure, hypersensitivity pneumonitis (HP) or organizing pneumonia was initially suspected. The patient received steroids and antibiotics without improvement. Initial interstitial lung disease (ILD) evaluation showed mildly elevated C-reactive protein (2.9 mg/dL), while autoimmune and myositis panels were negative. Rheumatologic evaluation did not identify a defined connective tissue disease (CTD). Serial high-resolution computed tomography (HRCT) scans demonstrated persistent peribronchial and basilar opacities without improvement, leading to treatment with mycophenolate mofetil for suspected CTD-associated ILD (CTD-ILD). Follow-up serologic testing at a tertiary center later revealed antinuclear antibody (ANA) positivity at 1:80 with cytoplasmic speckled pattern and anti-SSA-52 positivity, suggesting evolving myositis-spectrum or amyopathic CTD-ILD.

Overall, this case highlights that ILD may be the first and only manifestation of evolving CTD-ILD, and that repeat clinical and serologic reassessment may be important in patients with persistent ILD despite standard therapy.

Estimating Further Progression Risk in PPF to Support Antifibrotic Decisions

Authors: T Niitsu, et al.

This multicenter retrospective study developed and externally validated a prediction model to estimate 24-month progression risk in patients with progressive pulmonary fibrosis (PPF) receiving standard therapy without antifibrotics. The development cohort included 223 patients from Osaka University Hospital, while the external validation cohort included 236 patients from Osaka Prefectural Toneyama Medical Center. PPF was defined according to the 2022 proposed criteria. In the validation cohort, 105 of 236 patients (44.5%) experienced progression events within 24 months. The prediction model used routinely available clinical variables and evaluated progression risk while treating death as a competing event. In external validation, the model demonstrated a 2-year area under the curve (AUC) of 0.72 (95% confidence interval [CI], 0.55–0.90). After recalibration, the 2-year Brier score improved from 0.098 to 0.080, indicating better risk calibration. Decision curve analysis showed that the model provided greater net clinical benefit than a “treat-all” antifibrotic strategy at higher decision thresholds. At a threshold of 0.60, the model achieved an estimated net benefit increase of approximately 43.8 per 100 patients while reducing unnecessary antifibrotic treatment by around 29 per 100 patients. Time-varying effects were observed for forced vital capacity (FVC) and Krebs von den Lungen-6 (KL-6), suggesting that progression risk may change over time.

Overall, the model provided reasonable 24-month risk stratification in PPF and may help guide decisions regarding antifibrotic therapy initiation.

Treatment Patterns and Survival Outcomes of Patients with Interstitial Lung Disease and Myositis Specific Antibodies: A Single Center Retrospective Study

Authors: J Major, et al.

This retrospective cohort study evaluated patients with interstitial lung disease (ILD) and myositis-specific antibodies (MSA) at Henry Ford Health, comparing patients with myositis-associated ILD (M-ILD) and idiopathic ILD with MSA (I-ILD-w/MSA). A total of 126 patients were included, with 62% female and a mean age of 59.8 years. Following specialist evaluation, 53 patients were diagnosed with idiopathic inflammatory myopathy-associated ILD (M-ILD), while 73 were classified as I-ILD-w/MSA. Compared with I-ILD-w/MSA, patients with M-ILD were younger at presentation (53.6 vs 63.7 years; p<0.05) and more frequently had positive Jo-1 antibodies (58.5% vs 10.5%; p<0.05). Positive NXP antibodies were more common in I-ILD-w/MSA (20.5% vs 5.7%; p<0.05). Lung biopsy was performed in similar proportions in both groups. Nonspecific interstitial pneumonia (NSIP) was more common in M-ILD (45.3% vs 20.5%; p<0.05). At 6-month follow-up, patients with M-ILD had lower dyspnea scores, improved forced vital capacity (FVC) percentage (+3.9% vs -0.6%; p<0.05), and higher diffusing capacity for carbon monoxide (DLCO) percentage (53.7% vs 43%; p<0.05). Patients with M-ILD also received corticosteroids (75.5% vs 53.4%; p<0.05) and immunomodulators (69.8% vs 37%; p<0.05) more frequently than patients with I-ILD-w/MSA. Kaplan-Meier analysis showed longer median survival in M-ILD compared with I-ILD-w/MSA (73.2 vs 45.4 months; p<0.05).

Overall, the study found that patients with M-ILD were younger, received more immunomodulatory therapy, and had better survival outcomes than patients with I-ILD-w/MSA.

ATS 2026, May15 –20, Orlando, Florida.