Background Treatment selection for advanced lung cancer has become increasingly complex with the development of anticancer agents. Generative artificial intelligence (AI) may assist in treatment selection; however, its clinical utility remains unclear. Methods In this simulation study, we evaluated the performance of generative AI models (ChatGPT, Claude, and Copilot) in selecting systemic anticancer treatments using ten virtual advanced lung cancer scenarios. Five scenarios were without complicating factors (basic scenarios) and five involved complex clinical backgrounds (advanced scenarios). Additionally, physicians completed an online questionnaire using the same scenarios. Responses generated by AI and physicians were assessed by two lung cancer specialists and categorized as appropriate or inappropriate treatment recommendations. Results The appropriate response rates of ChatGPT, Claude, and Copilot were 90% (9/10), 70% (7/10), and 80% (8/10) for all scenarios; 100% (5/5), 80% (4/5), and 100% (5/5) for the basic scenarios; and 80% (4/5), 60% (3/5), and 60% (3/5), for the advanced scenarios, respectively. In the questionnaire survey of 88 physicians, the mean appropriate response rate was 88% (775/880 responses) for all scenarios; 95% (417/500 responses) for the basic scenarios; and 81% (358/500 responses) for the advanced scenarios. AI performed well in the basic scenarios, but generated inappropriate recommendations more frequently in the advanced scenarios involving comorbidities or organ dysfunction, mainly because of its failure to recognize or appropriately weigh these risk factors. Conclusion Generative AI may provide clinically appropriate treatment recommendations for advanced lung cancer cases; however, its performance appeared to be lower in complex cases that require clinical judgment.

Background Patients with fibrotic interstitial lung diseases (ILDs) experience impaired health-related quality of life (HRQoL). The King's Brief Interstitial Lung Disease (KBILD) questionnaire was designed to evaluate disease-specific HRQoL; however, its practical application in real-world clinical settings has not been thoroughly investigated. Methods This prospective longitudinal study included 289 patients with fibrotic ILD initiated antifibrotic therapy. Their HRQoL was evaluated using the KBILD questionnaire at baseline, 6 months, and 1 year. A total of 289, 164, and 159 patients completed the KBILD assessment at the aforementioned time points, respectively. The associations between the KBILD scores, clinical parameters, and mortality risk were evaluated. Results The KBILD Total score demonstrated a moderate correlation with dyspnea scale but a weak or no correlation with pulmonary function test parameters and ILD etiology. Interestingly, more than 20% of the patients showed significant improvement (≥5 points) at 6 months and 1 year. A lower baseline KBILD Total score was associated with disease progression and reduced survival, independent of the ILD–gender–age–physiology index. In addition, longitudinal assessment showed that the cross-sectional KBILD Total score at 6 months and 1 year and longitudinal decreases in the KBILD Total score at 1 year were associated with increased mortality risk. Conclusion Antifibrotic therapy has a positive impact on HRQoL in a subset of patients with fibrotic ILDs. Repeated KBILD assessment may aid in monitoring mortality risk, independent of lung function tests.

BACKGROUND:Compared with cytotoxic chemotherapy, the efficacy and safety of immune checkpoint inhibitors (ICIs) for patients with interstitial lung disease and non-small cell lung cancer (ILD-NSCLC) are unclear. METHODS:Data of patients in a Japanese nationwide insurance claims database with ILD-NSCLC who received ICIs (ICI group, n=1748) and those who received only chemotherapy without ICIs (chemotherapy group, n=6362) were extracted. Landmark analyses were performed to compare overall survival (OS) between the two groups. Propensity-score matching was performed to compare 753 patients who received ICI as the first-line treatment (first-ICI group) and 753 from the chemotherapy group with matched backgrounds (matched chemotherapy group). RESULTS:The ICI group had a significantly longer median OS of 19.7 months than the chemotherapy group (9.9 months; HR 0.51, 95% CI 0.47 to 0.54, p<0.001). In landmark analyses at 3, 6, 9 and 12 months, the ICI group had a significantly longer OS than the chemotherapy group (all p<0.001). The incidence of drug-induced ILD (DIILD) was significantly higher in the ICI group than in the chemotherapy group (p<0.001). In the ICI group, there was no significant difference in OS between patients with and without DIILD (p=0.784). A propensity score-matched analysis indicated that the first-ICI group had a significantly longer OS than the matched chemotherapy group (p<0.001). CONCLUSIONS:In patients with ILD-NSCLC, ICIs were associated with significantly longer OS compared with cytotoxic chemotherapy, despite the increased risk of DIILD.

BACKGROUND:Serum Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) are established biomarkers of interstitial lung diseases. However, their utility for differential diagnosis of immune checkpoint inhibitor-related pneumonitis (ICI-P) remains unclear. METHODS:This retrospective observational study included cancer patients who newly developed pulmonary diseases and in whom serum KL-6 and/or SP-D levels were measured at disease onset. RESULTS:Among 200 eligible patients, 77 had ICI-P and 123 had other pulmonary diseases (bacterial pneumonia, n = 64; lymphangitic carcinomatosis, n = 42; pulmonary edema, n = 10; radiation pneumonitis, n = 5; and others, n = 2). Serum KL-6 and SP-D levels were significantly higher in patients with ICI-P than in those without (both p < 0.001). The area under the receiver operating characteristic curve was 0.684 for KL-6 and 0.771 for SP-D. KL-6 ≥500 U/mL showed sensitivity and specificity of 0.623 and 0.705, respectively, and SP-D ≥110 ng/mL showed sensitivity and specificity of 0.693 and 0.769, respectively. When both KL-6 ≥500 U/mL and SP-D ≥110 ng/mL, the sensitivity and specificity were 0.480 and 0.907, respectively. CONCLUSIONS:KL-6 and SP-D may play a supportive role in the differential diagnosis of ICI-P.

This study aimed to assess the clinical utility of serum interferon-lambda 3 (IFN-λ3) as a sequential biomarker for treatment response and disease control in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM)-associated interstitial lung disease (ILD). Serum IFN-λ3 levels were measured in 24 patients with anti-MDA5 antibody-positive DM-ILD at diagnosis and 1 month after initiating immunosuppressive therapy. Patients were categorized into two groups based on clinical outcomes: a good control group (n = 16; survived without relapse for ≥ 1 year) and a poor control group (n = 8; died from ILD progression or relapse within 1 year). Changes in serum IFN-λ3 levels and differences between groups were analyzed. In the good control group, serum IFN-λ3 levels significantly decreased from 94.6 to 12.7 pg/mL (p < 0.001), whereas no significant change was observed in the poor control group (129.0 to 118.8 pg/mL). Furthermore, serum IFN-λ3 levels at 1 month were significantly lower in the good control group than in the poor control group (p = 0.004). Serum IFN-λ3 levels may reflect short-term treatment response and could serve as a useful sequential biomarker for assessing disease control in patients with anti-MDA5 antibody-positive DM-ILD.

No prospective studies have investigated the relationship between nutritional status, tolerability to antifibrotic therapy, and mortality in patients with fibrotic interstitial lung diseases (ILDs). This prospective longitudinal study enrolled 290 consecutive patients with fibrotic ILDs who initiated antifibrotic therapy, including 164 with idiopathic pulmonary fibrosis (IPF) and 126 with non-IPF. Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI). Overall, 106 patients (36.6%) were classified as having malnutrition-related risk (GNRI < 98) at baseline. The prevalence of malnutrition-related risk was comparable between patients with IPF and non-IPF, although it tended to be higher in the non-IPF group than in the IPF group. Patients with malnutrition-related risk showed higher cumulative incidence of antifibrotic therapy discontinuation. Importantly, in both IPF and non-IPF groups, the mortality risk was significantly higher in patients with malnutrition-related risk than in those without. Longitudinally, a lower GNRI at 1 year was associated with shorter survival. In multivariable analyses, baseline malnutrition-related risk was independently associated with increased risk of therapy discontinuation and mortality, even after adjusting for the ILD-gender-age-physiology index. These findings indicate that assessment of nutritional status helps predict antifibrotic therapy tolerability and mortality risk in patients with fibrotic ILD.

BACKGROUND:Mycobacterium avium complex lung disease (MAC-LD) is a chronic pulmonary infection associated with significant long-term morbidity and mortality. The Geriatric Nutritional Risk Index (GNRI) is a simple nutritional indicator derived from serum albumin levels and the actual-to-ideal body weight ratio. Although host nutritional status is thought to influence the prognosis of patients with MAC-LD, the clinical importance of the GNRI in this population remains unclear. METHODS:This multicenter retrospective cohort study included 588 patients diagnosed with MAC-LD between 2006 and 2020. Patients were categorized into four groups according to GNRI: ≥98 (no risk), 92-<98 (low risk), 82-<92 (moderate risk), and <82 (high risk). Furthermore, the association between the GNRI and clinical outcomes was evaluated. RESULTS:The 5-year survival rates in the no-, low-, moderate-, and high-risk groups were 94%, 78%, 65%, and 46%, respectively (p < 0.01). In the multivariable Cox model, a higher-risk group based on GNRI was independently associated with a higher risk of all-cause mortality (hazard ratio 1.89, 95% confidence interval 1.45-2.44), and the GNRI category-based model yielded a Harrell's C-index of 0.888 (95% confidence interval, 0.841-0.920) for all-cause mortality. In the multivariable Fine-Gray model, a higher-risk group based on GNRI was significantly associated with a higher risk of respiratory-related mortality (subdistribution hazard ratio 2.08, 95% CI 1.52-2.86). CONCLUSION:These findings suggest that the GNRI is a useful prognostic marker for all-cause and respiratory-related mortalities in patients with MAC-LD.

Purpose To determine the prevalence of apical scarring-which has recently also been referred to as pleuroparenchymal fibroelastosis (PPFE)-like lesions, a characteristic finding at chest CT in idiopathic PPFE-in apparently healthy individuals, to identify associated clinical features, and to evaluate their progression over time. Materials and Methods This retrospective study included individuals without underlying diseases known to cause PPFE, who underwent comprehensive health checkups including chest CT between April 2014 and March 2015 (cohort 1: n = 1737; cohort 2: n = 1126). Clinical features associated with the presence of apical scarring were analyzed using propensity score matching and logistic regression analysis. Furthermore, in a subset of individuals with available follow-up data, radiologic progression of apical scarring was evaluated over a 4-year period from baseline, and potential risk factors were evaluated using a logistic regression model. Results Among 2863 individuals (median age, 57 years [IQR, 49-65 years]; 2299 male), 158 (5.5%) had apical scarring, with prevalence rates of 1.6%, 3.9%, and 8.1% in individuals aged 20-39 years, 40-59 years, and 60 years and older, respectively. Older age and lower body mass index, body fat, and waist circumference were associated with apical scarring. These findings were consistent in both cohorts. Among the 158 individuals with apical scarring, at least 20 (12.7%) demonstrated radiologic progression over 4 years, which was more common in those with more extensive lesions at baseline (progression rate: grade 1 lesions, 19.2% vs grade 2 lesions, 66.7%; P = .006). Conclusion Among apparently healthy individuals, the prevalence of apical scarring increased with age, and its presence was associated with a lean body habitus. Radiologic progression was observed in some individuals. Keywords: CT, Thorax, Lung, Epidemiology, Apical Cap, Interstitial Lung Disease, PPFE, PPFE-like lesions, Pleuroparenchymal Fibroelastosis Supplemental material is available for this article. © RSNA, 2026.

BACKGROUND:Interstitial lung disease (ILD) comprises a wide range of pulmonary disorders associated with high morbidity and mortality. Although idiopathic pulmonary fibrosis (IPF) has been the focus of much prior research, population-level data covering the full spectrum of ILD in Japan remain limited. METHODS:This retrospective cohort study used the National Database of Health Insurance Claims (NDB) in Japan to identify patients diagnosed with ILD from January 2015 to December 2023. We analyzed annual prevalence, incidence, patient demographics, and survival outcomes overall and by ILD subtypes. RESULTS:A total of 2,758,542 patients with ILD were identified during the study period. ILD prevalence nearly doubled, from 656 per 100,000 population in 2015 to 1301 per 100,000 in 2023, while incidence remained relatively stable (192 per 100,000 in 2015 to 212 per 100,000 in 2023), with a notable decline observed in 2020 (178 per 100,000). Males consistently had higher prevalence and incidence than females. Age and sex distributions differed substantially across ILD subtypes. The overall 5-year survival rate was 59.9 %, with IPF demonstrating the poorest survival (32.1 %). CONCLUSIONS:This nationwide study provides the most comprehensive epidemiological overview of ILD in Japan to date. The insights gained can support evidence-based healthcare planning and help guide priorities for future research and clinical improvements.

In the Phase III TASUKI-52 trial, nivolumab with carboplatin, paclitaxel (CP), plus bevacizumab significantly prolonged progression-free survival (PFS), and resulted in longer overall survival (OS) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). This final analysis evaluated 4-year treatment outcomes in terms of OS, PFS and duration of response (DOR) by investigator assessment and safety, as well as the background characteristics and treatment courses associated with 4-year survivors. Patients were randomized 1:1 to receive nivolumab (n = 275) or placebo (n = 275) in addition to CP plus bevacizumab. With a minimum follow-up of 53.1 months, nivolumab with CP plus bevacizumab continued to show improvement in OS (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.58-0.88) and PFS (HR: 0.61; 95% CI: 0.50-0.74) compared to placebo with CP plus bevacizumab. The 4-year OS rate was 34.7% in the nivolumab arm versus 22.1% in the placebo arm, and the 4-year PFS rate was 13.7% in the nivolumab arm versus 3.3% in the placebo arm. Among 4-year survivors, the median DOR was numerically longer in the nivolumab arm than in the placebo arm (34.7 vs. 13.5 months). No new safety signals were observed. Four-year survival in the nivolumab arm was associated with the absence of bone metastases and age < 65, but not with PD-L1 status and tumor size. In conclusion, treatment with nivolumab demonstrated long-term survival benefit and durable response, which supports nivolumab with CP plus bevacizumab as a first-line treatment option for advanced nonsquamous NSCLC. Trial Registration: ClinicalTrials.gov identifier: NCT03117049.

AIMS:Pulmonary arterial hypertension (PAH) is a syndrome characterized by elevated pulmonary artery pressure. We developed a population pharmacokinetic (PPK) model using combined plasma drug concentration data from Japanese paediatric (<15 years) and adult (≥15 years) patients with PAH to investigate the pharmacokinetic characteristics of PAH treatments (sildenafil, tadalafil, bosentan and ambrisentan). METHODS:PPK analysis was conducted using a nonlinear mixed-effects modelling approach. A one-compartment model was selected as the structural model, and an exponential error model was used to describe interindividual variability. Individual patient clearance (CL), adjusted for bioavailability (F) using Bayesian estimation based on the PPK model, was used to estimate the steady-state plasma concentrations (Css) of the drugs in paediatric and adult patients receiving clinical dosages. RESULTS:PPK analysis was performed on data from 35 paediatric and 16 adult subjects to estimate pharmacokinetic parameters. The population mean CL/F values for sildenafil, tadalafil, bosentan and ambrisentan were estimated at 60.6, 1.76, 8.85 and 0.594 L/h, respectively. Covariates that improved model performance and were incorporated into the final model included the effect of bodyweight on the CL/F of each drug. The estimated Css values for all drugs were 26.0%-72.2% lower in paediatric than in adult patients. CONCLUSIONS:This study clarified the pharmacokinetic parameters and their variability for sildenafil, tadalafil, bosentan and ambrisentan using combined data from Japanese paediatric and adult patients with PAH. The results of Bayesian estimation suggest that at current clinical dosages, plasma concentrations of these drugs may be lower in paediatric than adult patients.

Pulmonary fibrosis is a fatal interstitial lung disease marked by irreversible lung structure destruction. Understanding its molecular mechanisms is essential. Cold-inducible RNA-binding protein (CIRBP), a stress-responsive protein, stabilizes mRNA intracellularly and also acts extracellularly. We previously demonstrated that CIRBP is highly expressed in fibrotic lesions of idiopathic pulmonary fibrosis patients, with elevated serum levels correlating with disease progression and poor prognosis. However, its role in fibrosis remains unclear. We investigated CIRBP’s function using an in vivo bleomycin (BLM)-induced pulmonary fibrosis mouse model via intratracheal administration and an in vitro model with primary lung fibroblasts. CIRBP expression was markedly upregulated in the fibrotic regions of BLM-treated wild-type (WT) mice. CIRBP-deficient mice showed improved survival, reduced fibrosis, lower hydroxyproline content, and decreased expression of α-SMA and fibronectin. Therapeutic administration of C23, a CIRBP-derived inhibitory peptide, significantly suppressed fibrosis and improved survival in WT mice. In vitro, recombinant CIRBP promoted collagen secretion, fibroblast proliferation, and cell migration, which were inhibited by C23. Mechanistically, CIRBP-induced IL-6 production via TLR2 and TLR4, leading to fibroblast activation through autocrine signaling. These effects were suppressed by C23, TLR2/4 inhibitors, or IL-6 neutralization. Our findings identify CIRBP as a novel profibrotic factor and therapeutic target in pulmonary fibrosis.

This novel method for quantitatively measuring the normal upper-lobe lung volume using three-dimensional computed tomography is useful for assessing disease severity and mortality risk in idiopathic pleuroparenchymal fibroelastosis https://bit.ly/4fcRCrj.

Before the introduction of antifibrotic therapy, patients with familial pulmonary fibrosis (FPF) were reported to have a higher mortality risk than those with sporadic disease. Genetic predisposition plays an important role in the development of interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF). The 2023 European Respiratory Society consensus statement defined FPF and recommended antifibrotic drugs for treatment; however, their efficacy in FPF remains unclear. We conducted a retrospective multicohort study of 280 patients with IPF receiving antifibrotic therapy (exploratory cohort, n = 141; validation cohort, n = 139). FPF was defined as fibrotic ILD in at least two first- or second-degree relatives. We examined tolerability, causes of drug discontinuation, incidence of acute exacerbation (AE), and mortality. Among all patients, 45 (16.1

Abstract Purpose Studies on COVID-19 mortality during the Omicron-predominant wave have focused primarily on the inpatient/emergency room setting, and real-world data including both inpatients and outpatients are lacking. Methods Patients diagnosed with COVID-19 (n = 27,440,148) or influenza (n = 8,179,641) from January 2020 to April 2023 were identified using nationwide claims data in Japan. Patients with COVID-19 in the Omicron-predominant wave were compared with their counterparts in earlier waves, and a subset of the former group (May 2022–April 2023) was compared with patients with influenza as controls. Results The mortality rates (average number of deaths/cases per week) of COVID-19 decreased over time, being 2.7% (169/6312), 2.1% (397/18,754), 0.7% (195/28,273), and 0.4% (1613/378,848) in the wild-type–, Alpha-, Delta-, and Omicron-predominant waves, respectively. However, the number of deaths increased substantially in the Omicron-predominant wave, especially among the elderly (e.g., in the Delta- and Omicron-predominant waves, the average numbers of deaths/cases per week were < 1/5527 (< 0.01%) and 4/105,763 (< 0.01%) respectively, in patients aged 0–19, versus 101/925 (10.9%) and 1212/20,771 (5.8%), respectively, in patients aged ≥ 80). The mortality rate was lower for patients with COVID-19 than in those with influenza among those aged ≤ 39 years but higher among those aged ≥ 40 years. Conclusions In the Omicron-predominant wave, the mortality rate of COVID-19 decreased, but the number of patients increased, leading to a substantial increase in the number of deaths, especially among the elderly. The mortality rate of COVID-19 was higher than that of influenza in the elderly but not in the young, highlighting the need for age-specific interventions.

We present a case of alveolar sarcoidosis showing lower lobe-predominant areas of airspace consolidation and ground-glass attenuation on HRCT, mimicking idiopathic interstitial pneumonia (IIP) with spontaneous wandering. Mediastinal lymphadenopathy and uveitis were negative. Surgical lung biopsy revealed multiple non-necrotising granulomas. Alveolar sarcoidosis that mimics IIP without mediastinal lymphadenopathy is rare.

BACKGROUND:Chronological age alone does not adequately capture inter-individual variability in the health status and treatment outcomes of patients with advanced non-small cell lung cancer (NSCLC). Biological age, calculated using routine clinical biomarkers (BioAge), may offer superior prognostic value. PATIENTS AND METHODS:A retrospective analysis was conducted on 138 patients treated with immune checkpoint inhibitors (ICIs; ICI cohort) and 154 ICI-naïve patients treated with chemotherapy (chemotherapy cohort). BioAge was calculated using chronological age and seven clinical biomarkers. BioAge acceleration (BioAgeAccel) was defined as the residual derived from the linear regression of BioAge on chronological age. The Kaplan-Meier method and Cox proportional hazards model were used for survival analyses. In the ICI cohort, associations with immune-related adverse events (irAEs) development were evaluated using competing risk regression. RESULTS:Higher BioAge (≥79.1 years) was independently associated with shorter overall survival (OS) in both cohorts, whereas chronological age (≥75 years) was not. In the ICI cohort, biologically older patients demonstrated significantly worse OS than biologically younger patients, and BioAgeAccel was an independent prognostic factor. However, the BioAgeAccel was not associated with OS in the chemotherapy cohort. No significant associations were observed between BioAge, BioAgeAccel, or chronological age and the risk of irAEs. CONCLUSION:Biological age is a robust prognostic factor for advanced NSCLC. BioAgeAccel has additional prognostic value, particularly in the context of immunotherapy. Incorporating biological age metrics into clinical practice may improve patient stratification and support individualized treatment decisions.

Bronchial asthma is a common disease treated primarily with inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA), yet optimal add-on therapy with long-acting muscarinic antagonists (LAMA) or leukotriene receptor antagonists (LTRA) remains unclear. This multicenter, randomized, open-label phase 2 screening trial compared the efficacy of adding tiotropium (LAMA) versus montelukast (LTRA) to ICS/LABA therapy in adult patients with poorly controlled asthma. Patients were randomly assigned to receive either tiotropium or montelukast for 12 weeks. Primary outcome was the change in forced expiratory volume in 1 second (FEV1), secondary outcomes included changes in asthma control questionnaire (ACQ-5), asthma control test (ACT) scores, and peak expiratory flow (PEF). Ninety-four patients were analyzed. Over 12 weeks, the tiotropium group showed significant improvements in FEV1 and PEF, while the montelukast group showed no improvement in respiratory function. Both groups, however, showed significant improvements in ACQ-5 and ACT. The primary endpoint, change in FEV1 improved similarly in both groups (tiotropium 2.03 ± 0.74 to 2.10 ± 0.72 L vs montelukast 2.08 ± 0.69 to 2.13 ± 0.67 L; p = 0.736), while the tiotropium group exhibited a significantly greater improvement in PEF (tiotropium 5.41 ± 1.85 to 5.92 ± 1.93 L/s vs montelukast 5.58 ± 1.84 to 5.65 ± 1.82 L/s; p = 0.025). Subgroup analysis of patients with allergic rhinitis revealed the ACQ-5 score was significantly improved in the montelukast group (tiotropium 0.94 ± 0.64 to 0.68 ± 0.76 L/s vs montelukast 1.26 ± 1.15 to 0.53 ± 0.86 L/s; p = 0.002). Adding tiotropium to ICS/LABA therapy improves respiratory function, whereas adding montelukast enhances symptom control, particularly in patients with allergic rhinitis. These findings underscore the importance of personalized treatment approaches in asthma management by demonstrating that both tiotropium and montelukast confer distinct benefits according to patient characteristics, while also addressing a significant gap in the literature regarding optimal adjunctive therapies for adult asthma, given the scarcity of studies directly comparing these add-on strategies. Further research is needed to establish definitive guidelines for optimal add-on therapies in asthma.

BACKGROUND:Acute exacerbation (AE) is defined as acute deterioration in the respiratory status that can lead to a fatal outcome. It may occur in various types of interstitial lung disease (ILD). However, its incidence and clinical picture in patients with primary Sjögren's syndrome-associated interstitial lung disease (pSjS-ILD) remain unclear. Therefore, this study aimed to examine the incidence and clinical significance of AE in patients with pSjS-ILD. METHODS:This study included 101 consecutive patients with pSjS-ILD. The clinical findings at diagnosis, AE development, and outcome were analyzed. Furthermore, the prognostic significance of AE was evaluated via Cox proportional-hazards analysis with time-dependent covariates. The Fine-Gray subdistribution hazard model was employed to identify factors associated with AE development. RESULTS:Of the 101 patients, 17 (17 %) developed AE during their clinical course. The cumulative incidence rates of AE were 2.0 %, 11.2 %, and 18.1 % at 1, 5, and 10 years, respectively. Multivariate analysis revealed that AE development was significantly associated with poor prognosis (hazard ratio: 3.69; P = 0.01) as well as age, male sex, and %FVC. Moreover, the serum levels of surfactant protein-D at diagnosis were significantly associated with AE development. Of the 17 patients demonstrating AE, 8 died, with a 60-day post-AE mortality rate of 47 %. The age and serum C-reactive protein level at AE onset were significantly associated with 60-day mortality in patients with AE of pSjS-ILD. CONCLUSION:AE occurs with a certain frequency and is strongly associated with poor outcome in patients with pSjS-ILD.