Tomoyuki Fujisawa

Objective: Thyroid dysfunction has been increasingly reported after the coronavirus disease 2019 (COVID‐19) pandemic. To date, no population‐based study has examined this association using more than 10 million matched pairs. We compared the risk of documented thyroid outcomes after COVID‐19 with that after influenza during the Omicron‐predominant period. Methods: We conducted a nationwide retrospective cohort study using the Japanese National Database of Health Insurance Claims, including patients with COVID‐19 between January 2022 and March 2023, and those with influenza between September 2017 and March 2023. Individuals with pre‐existing thyroid disease were excluded. After 1:1 propensity score matching, 24,173,646 pairs were analysed. Database‐recorded outcomes assessed within 90 days of documented COVID‐19 infection included diagnoses of thyrotoxicosis, hypothyroidism and subacute thyroiditis, as well as initiation of antithyroid drugs (ATDs) and thyroid hormone replacement therapy (THRT). Results: Among database‐recorded outcomes, COVID‐19 was associated with higher risks of thyrotoxicosis diagnosis (risk ratio [RR], 1.08), hypothyroidism diagnosis (RR, 1.12), ATD initiation (RR, 1.06) and THRT initiation (RR, 1.22) than influenza, but not subacute thyroiditis diagnosis. Age‐stratified analyses showed markedly higher risks in individuals aged 0–19 years for thyrotoxicosis diagnosis (RR, 1.38) and ATD initiation (RR, 1.77). Conclusions: In this nationwide cohort, COVID‐19 was associated with higher risks of database‐recorded diagnoses of thyrotoxicosis and hypothyroidism than influenza during the Omicron‐predominant period. The strongest association was observed for thyrotoxicosis diagnosis and ATD initiation in younger individuals, underscoring the importance of post–COVID‐19 thyroid monitoring in adolescents and young adults.

Background: Progressive pulmonary fibrosis (PPF) has a poor prognosis, with optimal treatment strategies remaining undefined. We previously reported favorable 24-week outcomes with upfront triple combination therapy (nintedanib, tacrolimus, prednisolone) in treatment-naïve PPF patients. Here we report 52-week outcomes for the same trial (TOP-ILD). Methods: This prospective, multicenter, single-arm study enrolled 34 treatment-naïve PPF patients. Patients received prednisolone (10 mg daily) and tacrolimus (trough of 5–10 ng·mL ⁻¹ ) from day 1, and nintedanib (150 mg twice daily) from day 8. Treatment persistence, lung function changes, safety, overall survival, and time to treatment failure were assessed. Treatment failure was defined as a relative forced vital capacity (FVC) decline of ≥10% predicted, a relative diffusing capacity of the lung for carbon monoxide (DLCO) decline of ≥15% predicted, acute exacerbation, or death. Results: Twenty-nine (85.3%) patients maintained triple therapy at 52 weeks. The annual rate of FVC change was +1.8±10.7%. Overall survival was 93.9%, the cumulative acute exacerbation rate was 3.0%, and the treatment failure rate was 53.7%. Treatment failure was mostly due to DLCO decline (76.5% of cases). Baseline predictors included a higher mMRC dyspnea score (HR=1.63, p=0.032), lower oxygen saturation (HR=0.73, p=0.044), and higher eosinophil percentage in bronchoalveolar lavage fluid (HR=1.11, p=0.049). Safety remained manageable. Conclusions: Upfront triple combination therapy may support sustained disease stabilization with high treatment persistence in treatment-naïve PPF patients, and baseline dyspnea, hypoxemia, and BALF eosinophilia may predict treatment failure. These exploratory findings from a single-arm study are hypothesis-generating and require confirmation in controlled trials.

Background: Immune checkpoint inhibitors (ICIs) have fundamentally changed cancer treatment, but ICI-related pneumonitis (ICI-P) remains a major clinical concern. Although numerous studies have reported its incidence and risk factors, the retrospective nature of these studies makes accurate assessment difficult in a real-world clinical setting. Patients and Methods: This prospective multicenter observational study enrolled patients with advanced or recurrent thoracic malignancies treated with nivolumab, pembrolizumab, or atezolizumab. Thoracic high-resolution computed tomography (HRCT) examinations were performed at the start of ICI therapy and at the onset of ICI-P. The primary endpoint was ICI-P incidence. The secondary endpoints included evaluation of risk factors, with a focus on the lung lesions present at ICI initiation. Fine-Gray analyses with 3 models were used to identify risk factors. Results: Among 614 eligible patients, 78 (12.7%) developed ICI-P. During a median observation period of 14.4 months, 29 patients developed grade ≥3 pneumonitis and 7 patients died owing to ICI-P. In the multivariable Fine-Gray analyses, independent risk factors for ICI-P included heavy smoking history (>50 pack-years; subdistribution hazard ratio [SHR], 1.90; 95% confidence interval [CI], 1.17-3.10), baseline interstitial lung abnormalities (ILAs; SHR, 3.42; 95% CI, 2.05-5.71), use of PD-1 inhibitors (SHR, 2.15; 95% CI, 1.28-3.63), and immunochemotherapy (SHR, 2.16; 95% CI, 1.17-3.98). Conclusion: In this prospective real-world cohort, the incidence of ICI-P was relatively high, and ILAs detected by HRCT, heavy smoking history, and treatment with a PD-1 inhibitor alone or in combination with cytotoxic chemotherapy were identified as independent risk factors.

Rationale: Early prediction of lung function decline remains challenging in idiopathic pulmonary fibrosis (IPF) and fibrotic interstitial lung diseases (ILDs). We evaluated whether oxygen desaturation during the 6-min walk test (6MWT) predicts forced vital capacity (FVC) decline and long-term outcomes. Methods: We analysed data from two independent cohorts: the nationwide Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry and an external IPF cohort (K-Junko Study). Hazard ratios (HRs) were estimated for each 6MWT parameter to identify variables associated with FVC decline and to determine optimal thresholds. Sensitivity analyses were conducted using Fine–Gray models. The performance of the predictive model was assessed using calibration plots and the concordance index (C-index). Results: In the JIPS IPF (n=457) and K-Junko IPF (n=318) cohorts, a peripheral oxygen saturation ( S pO ₂ ) change of ≤−6 percentage points during the 6MWT independently predicted a decline in FVC of ≥5 percentage points in both cohorts (JIPS HR 1.292; K-Junko HR 1.480). Moreover, S pO ₂ change during the 6MWT was significantly associated with FVC change in the subsequent year, and this association persisted over 5 consecutive years in JIPS IPF cohort. The nomogram demonstrated moderate discrimination (C-index: 0.619 (training) and 0.632 (validation)) and fair calibration. A composite profile meeting all three criteria (FVC ≥80%, S pO ₂ change >−6 percentage points, 6-min walk distance (6MWD) ≥420 m) identified patients with favourable transplant-free survival. In the JIPS non-IPF fibrotic ILD cohort (n=387), S pO ₂ change remained the sole independent predictor of an FVC decline of ≥5 percentage points (HR 1.350). Conclusion: S pO ₂ change during the 6MWT predicts FVC decline and outcomes across fibrotic ILD; its incorporation into routine assessment may enable earlier risk stratification and facilitate timely intervention.

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 dyspnoea scale but a weak or no correlation with pulmonary function test parameters and ILD aetiology. 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.

A 64‐year‐old man with a mild cough presented with abnormal chest imaging with centrilobular ground‐glass opacities in the upper lobes, peribronchovascular and subpleural consolidation and small nodules. Bronchoalveolar lavage fluid (BALF) lacked foamy macrophages, transbronchial lung cryobiopsy revealed features consistent with amiodarone‐induced interstitial pneumonia, including vacuolization of type II alveolar epithelial cells, lymphoid follicle formation and granulation tissue. After discontinuation of amiodarone, the patient's symptoms and radiographic abnormalities improved. This case highlights that the absence of foamy macrophages in BALF should not preclude amiodarone‐induced pneumonia, and that histological evaluation plays a pivotal role in establishing an accurate diagnosis.

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.