Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fHP.

A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls.

MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73-27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP.

These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition.

Workplace exposures are widely known to cause specific occupational diseases such as silicosis and asbestosis, but they also can contribute substantially to causation of common respiratory diseases. In 2019, the American Thoracic Society (ATS) and the European Respiratory Society (ERS) published a joint statement on the occupational burden of respiratory diseases. Our aim on this narrative review is to summarise the most recent evidence published after the ATS/ERS statement as well as to provide information on traditional occupational lung diseases that can be useful for clinicians and researchers.

Newer publications confirm the findings of the ATS/ERS statement on the role of workplace exposure in contributing to the aetiology of the respiratory diseases considered in this review (asthma, COPD, chronic bronchitis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, infectious pneumonia). Except for COPD, chronic bronchitis and infectious pneumonia, the number of publications in the last 5 years for the other diseases is limited. For traditional occupational lung diseases such as silicosis and asbestosis, there are old as well as novel sources of exposure and their burden continues to be relevant, especially in developing countries.

Occupational exposure remains an important risk factor for airways and interstitial lung diseases, causing occupational lung diseases and contributing substantially in the aetiology of common respiratory diseases. This information is critical for public health professionals formulating effective preventive strategies but also for clinicians in patient care. Effective action requires shared knowledge among clinicians, researchers, public health professionals, and policy makers.

Purpose of the research: transbronchial lung cryobiopsy has been recently accepted as a valid and less invasive alternative to surgical lung biopsy. The purpose of this randomized controlled study was to evaluate, for the first time, the quality and safety of biopsy specimens obtained by using the new disposable 1.7-mm cryoprobe compared with the standard re-usable 1.9 mm cryoprobe in the diagnosis of diffuse parenchymal lung diseases. Methods: 60 consecutive patients were prospectively enrolled and randomly assigned to two different groups: 1.9 mm (group A) and 1.7 mm (group B); primary endpoints were pathological and multidisciplinary diagnostic yield, sample size and complication rate. Principal results: the pathological diagnostic yield of cryobiopsy was 100% in group A and 93.3% in group B (p = 0.718); cryobiopsy median diameter was 6.8 mm in group A and 6.7 mm in group B (p = 0,5241). Pneumothorax occurred in 9 patients in group A and 10 in group B (p = 0.951); mild-to-moderate bleeding in 7 cases and 9 cases in group A and B respectively (p = 0.559). No death or severe adverse events were observed. Conclusions: there was no statistically significant difference between the two groups, regarding diagnostic yield, adverse events and sampling adequacy.

Systemic sclerosis (SSc) is a rare immune-mediated connective tissue disease with high morbidity and mortality. Interstitial lung disease (ILD) is now the leading cause of death for patients with SSc. While several therapeutic agents have been approved for SSc-ILD, opportunities remain for a personalized medicine approach to improve patient outcomes. The purpose of this narrative review is to summarize the current state of personalized medicine for SSc-ILD and future directions to facilitate earlier diagnosis, disease stratification, prognostication, and determination of treatment response. We also review opportunities for personalized medicine approaches within clinical trial design for SSc-ILD.

The management of SSc-ILD remains challenging due to its variable clinical course and current deficits in predicting which individuals will develop progressive pulmonary fibrosis. There have additionally been many challenges in clinical trial design due to limitations in enrichment strategies. Emerging data suggest that serum, radiologic, and other novel biomarkers could be utilized to assess disease activity and treatment response on an individual level.

Personalized medicine is emerging as a way to address unmet challenges in SSc-ILD and has applicability for identifying stratifying, prognostic, and therapeutic markers for routine clinical care and clinical trial design.

Cough is a prevalent symptom in patients with interstitial lung disease (ILD), often significantly impacting quality of life (QoL). However, there is limited data on cough's burden and its effects on QoL in patients with progressive pulmonary fibrosis (PPF).

This study aimed to evaluate the impact of cough burden on QoL among a cohort of patients with PPF.

This multicenter, cross-sectional cohort study focused on PPF. Cough severity and its impact on QoL were assessed using the Visual Analogue Scale (VAS) and Leicester Cough Questionnaire (LCQ) scores.

Of the 248 patients included, 136 (54.8 %) had PPF due to rheumatic diseases, and 193 (77.8 %) reported experiencing cough. Patients with fibrotic nonspecific interstitial pneumonia had the highest cough frequency (p = 0.019). Correlations between cough measures and other variables were generally weak. The mean total LCQ score was 16.1 ± 4.7, with correlations between age and LCQ sub-scores. LCQ total scores positively correlated with FVC (%) (r = 0.202, p = 0.002), DLCO (%) (r = 0.255, p < 0.001), and 6MWT distance (r = 0.277, p = 0.001). VAS scores showed a negative correlation with DLCO, FVC (%), FVC (L), and 6MWT distance. No factor was significantly associated with cough presence in logistic regression, but longer antifibrotic treatment duration and higher LCQ scores were linked to lower VAS scores in linear regression.

Cough is highly prevalent in PPF patients and significantly impacts health-related QoL, underscoring the need for targeted management of this symptom in PPF.

To assess the effectiveness and safety of the antifibrotic drug nintedanib in rheumatoid arthritis (RA)-related interstitial lung disease (ILD) and a progressive phenotype in clinical practice.

National Spanish multicenter study of RA-ILD patients to whom nintedanib was added due to progressive fibrosing ILD. Outcome variables were effectiveness, retention rate and safety. Forced vital capacity (FVC) evolution was the primary endpoint. A comparative study between our cohort and those RA-ILD patients included in the INBUILD trial (n = 89, 42 treated with nintedanib) was performed.

A total of 74 patients (31 women/43 men) were collected, mean age of 69.3 ± 8.8 years. Median [IQR] ILD duration up to antifibrotic initiation was 51 [22-77.5] months. Besides corticosteroids (n = 54), nintedanib was used combined with cDMARD (n = 21), bDMARD (n = 46) and/or JAKi (n = 4) and monotherapy (n = 3). Mean FVC one year before nintedanib start was 81.9 ± 21.2 (% pred.), whilst mean baseline FVC was 73.7 ± 22.5 (% pred.). After a median follow-up of 15 [10-22, 4-9] months, no significant decline in mean FVC or DLCO values was observed. Moreover, the evolution of DLCO and FVC significantly differed from a predictive model that assumed their changes without the drug. The retention rate with nintedanib was 78.4 %. During the follow up, 16.7 % of patients showed ILD progression or progressive pulmonary fibrosis. Gastrointestinal adverse events were the most common reason for nintedanib discontinuation. Compared with INBUILD trial, patients from clinical practice were older, had a higher tobacco exposure, time since ILD diagnosis was longer and treatment with combined immunosuppressants was more frequent. However, baseline mean values of FVC and DLCO were similar in both groups.

Nintedanib seems to be effective and relatively safe in progressive fibrosing RA-ILD despite clinical differences with the INBUILD trial.

Laryngopharyngeal reflux plays an important role in respiratory diseases such as chronic cough, asthma, chronic obstructive pulmonary disease, interstitial lung disease, and lung transplantation, among others. In cases of refractory chronic cough, reflux testing (hypopharyngeal-esophageal multichannel intraluminal impedance with dual-PH sensor and high-resolution esophageal manometry) will assist the clinician in determining whether additional reflux treatment steps should be undertaken. It is important to consider all mechanisms of reflux pathophysiology to yield the optimal result in the management of a patient with chronic respiratory disease.

Pulmonary high attenuation may be caused by calcification or ossification, both of which are common phenomena with distinct pathogeneses, histologies, and radiologic appearances. Pulmonary calcification is divided into metastatic pulmonary calcification (MPC), caused by systemic hypercalcemia, and dystrophic pulmonary calcification (DPC), caused by local lung injury. MPC often demonstrates diffuse calcified nodules, which can be subtle and amorphous on CT images, with associated sandlike, fine ground-glass, or consolidative opacities. Conversely, DPC often appears nodular and is localized to areas of lung injury and thus is associated with other signs of lung damage, such as prior infection, fibrosis, or scarring. In contrast to calcification, pulmonary ossification is not a consequence of a localized or systemic metabolic abnormality but instead is found in the setting of chronic lung disease, which induces fibroblast-to-osteoblast transformation and bone deposition. Pulmonary ossification can be divided into nodular (NPO) and dendriform (DPO) patterns. NPO often appears as multiple small well-defined round nodules that are uniform in size and appearance. NPO classically is seen with chronic venous congestion in a subpleural predominant distribution and increasingly is recognized in pathologic findings in the setting of fibrosing interstitial lung disease (ILD). DPO appears more commonly as peripheral irregular branching opacities and can be seen with ILD. Additionally, pulmonary calcification or ossification can occur in association with protein deposition disease, including pulmonary amyloidosis, or in benign neoplasms or metastatic malignancies. Pulmonary alveolar microlithiasis is a distinct entity relating to phosphate metabolism. Pulmonary calcification and ossification can provide insight into patients' underlying disease processes and clinical context for radiologic study interpretation. ©RSNA, 2025 Supplemental material is available for this article.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) presents with variable severity and progression, highlighting the need for effective tools to identify patients at risk. Although CT imaging plays a vital role in the management of RA-ILD, there is a lack of objective methods to predict disease progression. This study investigates the association between semi-quantitative and quantitative CT scoring methods and disease progression in early-stage RA-ILD.

This observational study analyzed baseline and the first technically evaluable follow-up CT scans of patients who met the 2010 ACR/EULAR classification criteria for RA and were diagnosed with ILD. Only patients with ≤ 5 years between baseline and follow-up scans were included. Semi-quantitative assessments were conducted using the Goh and Warrick scoring systems, while quantitative analyses utilized Vitrea software to measure mean lung attenuation (MLA) and low-, medium-, and high-density lung volumes. Progression risk factors were evaluated using binary logistic regression, with progression defined by changes in CT parameters over time.

A total of 77 RA-ILD patients (45 females, 32 males) were included, with a median follow-up period of 20 months (interquartile range: 7.4-46 months). Disease progression was observed in 34 patients (44.2%). Baseline medium-density volume (MDV), follow-up mean lung attenuation (MLA), and low-density volume (LDV) differed significantly between the progression and non-progression groups (p < 0.05). Quantitative CT parameters demonstrated strong correlations with both the Goh and Warrick scoring systems. Binary logistic regression analysis identified the usual interstitial pneumonia (UIP) pattern on baseline imaging as the only independent predictor of disease progression (odds ratio: 3.1; 95% confidence interval: 1.1-12.4).

In this study of early-stage RA-ILD patients, only the usual interstitial pneumonia (UIP) pattern on baseline HRCT independently predicted disease progression. Neither semi-quantitative scores nor quantitative CT parameters were predictive of progression. However, quantitative CT metrics demonstrated strong correlations with traditional scoring systems, supporting their utility in objectively assessing disease extent.

Pulmonary fibrosis (PF) is sexually dimorphic, with a relatively high prevalence and severity in males; however, the mechanism remains unclear. Our study revealed pronounced sexual dimorphism of immune cell genes in the lung, among which grancalcin (GCA) showed profound sex differences. GCA was produced by lung-infiltrating bone marrow macrophages triggered by heightened inflammation in the lung. However, a unique HTR2C+ alveolar macrophage population enriched in female lungs metabolically reprogramed bone marrow-derived macrophages and constrained local GCA amplification. As a novel chemokine, GCA bound to protein tyrosine phosphatase receptor type T (PTPRT) in Th17 cells and facilitated pathogenic lung infiltration by activating the ROCK1-MLC pathway, thus aggravating lung fibrosis. Notably, both GCA and Th17 cells abundantly accumulated in lung biopsies from male PF patients but not in those from female patients. GCA-neutralizing antibodies in combination with pirfenidone, a prescribed medication for treating fibrosis, provided superior effectiveness and survival rates against PF compared with treatment with pirfenidone alone. Overall, our findings reveal that sex-biased lung fibrosis is shaped by lung immune-regulatory units, which could be targeted to limit lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by complex aetiologies involving the accumulation of inflammatory cells, such as macrophages, in the alveoli. This process is driven by uncontrolled extracellular matrix (ECM) deposition and the development of fibrous connective tissues. Here, we observed that the mRNA expression of Ffar1, the gene encoding G protein-coupled receptor 40 (GPR40), is repressed, while Cd36 is increased in the bronchoalveolar lavage fluid (BALF), which is predominantly composed of alveolar macrophages, of IPF patients. Furthermore, the GPR40 protein was found to be largely adhered to macrophages and was pathologically downregulated in the lungs of bleomycin (BLM)-induced PF model mice (PF mice) compared with those of control mice. Specific knockdown of GPR40 in pulmonary macrophages by adeno-associated virus 9-F4/80-shGPR40 (AAV9-shGPR40) exacerbated the fibrotic phenotype in the PF mice, and activation of GPR40 by its determined agonist compound SC (1,3-dihydroxy-8-methoxy-9H-xanthen-9-one) effectively protected the PF mice from pathological exacerbation. Moreover, Ffar1 or Cd36 gene knockout mouse-based assays were performed to explore the mechanism underlying the regulation of GPR40 activation in pulmonary macrophages with compound SC as a probe. We found that compound SC mitigated pulmonary fibrosis progression by preventing M2 macrophage polarization from exerting profibrotic effects through the GPR40/PKD1/CD36 axis. Our results strongly support the therapeutic potential of targeting intrinsic GPR40 activation in pulmonary macrophages for IPF and highlight the potential of compound SC in treating this disease.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible fatal disease, the prevalence of which has been increasing in recent years. Nonradiographic and noninvasive early diagnosis of pulmonary fibrosis could improve prognosis but is a formidable challenge. As one of the fundamental microenvironmental parameters, viscosity is relevant to various pathological states, such as acute inflammation. Nevertheless, the potential biological roles of viscosity during the IPF process have been relatively underexplored. To address this issue, herein, we developed a new viscosity-responsive probe (JZ-2), which displayed high sensitivity and selectivity for viscosity, as well as excellent characteristics for targeting mitochondria. JZ-2 was successfully applied to map the changes in mitochondrial viscosity in cells caused by various stimuli, such as nystatin and lipopolysaccharide. Besides, JZ-2 was capable of differentiating cancer cells from normal cells and even tissues. More importantly, JZ-2 has been demonstrated to be sufficiently sensitive for tumor detection and early identification of IPF in vivo, revealing a significant increase in the viscosity of lung fibrosis tissues. Thus, JZ-2 is expected to be a swift and reliable diagnostic modality for the prediction of IPF progression in clinical settings.

The role of chronic inflammation in non-idiopathic pulmonary fibrosis fibrotic interstitial lung disease (non-IPF f-ILD) remains unclear, with varied responses to anti-inflammatory or immunosuppressive therapy. A reliable predictor for guiding treatment response may enhance clinical decision-making and minimize adverse treatment effects. We hypothesized that elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) may be associated with improved treatment response.

Our retrospective cohort study compared treatment response to anti-inflammatory therapy in patients with non-IPF f-ILD stratified by baseline CRP and ESR levels. Treatment response was defined as: (1) relative increase in percent predicted forced vital capacity (FVC%) ≥ 5% in 6 months or ≥ 10% in 12 months; or (2) no change or any increase in FVC% if FVC% decline was noted prior to treatment. Logistic regression was used to delineate outcome predictors with FVC% change over time assessed with linear mixed effects models.

Of 832 non-IPF f-ILD patients screened, 167 received anti-inflammatory therapy and baseline inflammatory marker testing stratified into high vs. low-to-normal groups (104 vs. 63, respectively). Median age was 64 years, and 57% were diagnosed with a systemic autoimmune rheumatic disease (SARD). Treatment response was greater in those with elevated inflammatory markers (56% vs. 35%; OR 2.45 [1.243-4.828] P = 0.010) even after adjustment for a priori covariables. SARD diagnosis was associated with treatment response (OR 2.90 [1.45-5.81] P = 0.003), independent of inflammatory marker level. A positive FVC% slope was observed in treated patients with initially elevated inflammatory markers (P = 0.003).

Patients with non-IPF f-ILD and elevated inflammatory markers appear to be more responsive to anti-inflammatory therapy with slower FVC decline over time. These findings suggest baseline serum ESR and CRP may be feasible and reliable predictors of treatment response in certain subgroups.

This study explores the relationship between health-related physical fitness and depressive states in adolescents and examines the influence of gender, age, and parental education.

A stratified and cluster sampling method selected 689 students (grades 7, 8, 10, and 11) from a Beijing middle school. After screening, 441 adolescents (12-18 years, 55.3% male) were included. Measurements included body composition (BMI), cardiopulmonary fitness (vital capacity), muscular strength/endurance (grip strength, sit-ups, standing long jump), and flexibility (sit-and-reach). Depressive states were assessed using the depression subscale of the Achenbach Youth Self-Report Scale (YSR). Data were analyzed using SPSS 24.0 with descriptive statistics, stratified analysis, and Pearson correlation.

Cardiopulmonary fitness was significantly negatively correlated with depressive states (r = -0.346, p < 0.001), while grip strength showed a weak positive correlation with depression (r = 0.137, p = 0.003). Standing long jump exhibited a slight positive correlation with depression scores (r = 0.114, p < 0.05), but the effect size was negligible. BMI, sit-ups, and sit-and-reach showed no significant correlation with depression scores (p > 0.05). Stratified analysis revealed that females aged 15-18 had significantly higher depression scores than their male counterparts (p < 0.001) and were negatively correlated with cardiopulmonary fitness (r = -0.32, p = 0.002). Grip strength in males significantly increased with age (r = 0.62, p < 0.001), while in females, it stabilized after age 15 and showed no significant correlation with depression (p > 0.05).

Cardiopulmonary fitness is a key factor in adolescent mental health, with a stronger impact than muscular strength. Late-adolescent females are at higher depression risk, likely due to lower cardiopulmonary fitness and increased stress. Findings highlight the need for interventions improving cardiopulmonary fitness to support adolescent mental health.

we aimed to evaluate lung ultrasound (LUS) and oxygen desaturation as markers for the severity of diffuse parenchymal lung disease (DPLD), specifically the fibrotic subtypes, and correlate the findings with high-resolution computed tomography (HRCT) and other physiologic parameters.

A case-control study was conducted recruiting 31 DPLD patients and 20 age-matched healthy controls from our institution. All participants had a spirometry, HRCT, 6-minute walk test (6MWT), echocardiography and full-night cardio-respiratory polygraph. LUS for B-line quantification and pleural examination was performed on 6 zones bilaterally.

Compared to controls, patients had a statistically significant higher total number of B-lines, lower 6MWT nadir O2 and lower nadir nocturnal oxygen saturation (SpO2). Among patients; fibrotic DPLD (58.1%) had more B-lines, pleural irregularities with or without fragmentation, higher Warrick scores and lower 6MWT nadir SpO2 (p = 0.01, 0.008, < 0.005, 0.03 respectively). There was a statistically significant positive correlation between LUS findings and Warrick score that inversely correlated with the forced vital capacity (FVC)% predicted (p < 0.001). A score of LUS findings, 6MWT nadir SpO2 and time spent with SpO2 < 90% (T90) ≥2 points had a sensitivity of 91.7% and specificity of 66.7% in predicting severe fibrotic DPLD (area under curve (AUC)= 0.832, CI95% = 0.723-0.941, p = 0.001).

The number of B-lines and pleural irregularities in LUS, nocturnal desaturation and exercise desaturation can play a role as markers of DPLD severity.

To develop a new high-resolution (HR)CT abnormalities quantification tool (CVILDES) for interstitial lung diseases (ILDs) based on the nnU-Net network structure and to determine whether the quantitative parameters derived from this new software could offer a reliable and precise assessment in a clinical setting that is in line with expert visual evaluation.

HRCT scans from 83 cases of ILDs and 20 cases of other diffuse lung diseases were labeled section by section by multiple radiologists and were used as training data for developing a deep learning model based on nnU-Net, employing a supervised learning approach. For clinical validation, a cohort including 51 cases of interstitial pneumonia with autoimmune features (IPAF) and 14 cases of idiopathic pulmonary fibrosis (IPF) had CT parenchymal patterns evaluated quantitatively with CVILDES and by visual evaluation. Subsequently, we assessed the correlation of the two methodologies for ILD features quantification. Furthermore, the correlation between the quantitative results derived from the two methods and pulmonary function parameters (DLCO%, FVC%, and FEV%) was compared.

All CT data were successfully quantified using CVILDES. CVILDES-quantified results (total ILD extent, ground-glass opacity, consolidation, reticular pattern and honeycombing) showed a strong correlation with visual evaluation and were numerically close to the visual evaluation results (r = 0.64-0.89, p < 0.0001), particularly for the extent of fibrosis (r = 0.82, p < 0.0001). As judged by correlation with pulmonary function parameters, CVILDES quantification was comparable or even superior to visual evaluation.

nnU-Net-based CVILDES was comparable to visual evaluation for ILD abnormalities quantification.

Question Visual assessment of ILD on HRCT is time-consuming and exhibits poor inter-observer agreement, making it challenging to accurately evaluate the therapeutic efficacy. Findings nnU-Net-based Computer vision-based ILD evaluation system (CVILDES) accurately segmented and quantified the HRCT features of ILD, and results were comparable to visual evaluation. Clinical relevance This study developed a new tool that has the potential to be applied in the quantitative assessment of ILD.

The diagnostic evaluation of interstitial lung diseases (ILDs) remains challenging due to their heterogeneous etiologies and overlapping clinical and radiographic patterns. A confident diagnosis often necessitates histopathological sampling, particularly when high-resolution computed tomography and serologic assessments are inconclusive. While surgical lung biopsy (SLB) has long been considered the diagnostic gold standard, its invasiveness, associated morbidity, and limited feasibility in high-risk patients have driven the pursuit of less invasive alternatives. Here, we review the current applications, diagnostic yield, procedural techniques, and complications of several bronchoscopic modalities. Bronchoalveolar lavage (BAL) aids in characterizing inflammatory profiles and differentiating among conditions such as hypersensitivity pneumonitis, sarcoidosis, and eosinophilic pneumonia. Endobronchial biopsies (EBBs) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) are valuable in diagnosing granulomatous diseases with lymphadenopathy. Transbronchial lung biopsy (TBLB) is effective for peribronchial and centrilobular diseases but is limited by small sample size and tissue distortion. Transbronchial lung cryobiopsy (TBC) enables acquisition of larger, well-preserved parenchymal tissue samples from the peripheral lung. Over recent years, studies have demonstrated that TBC, when interpreted within a multidisciplinary discussion (MDD), achieves diagnostic concordance rates with SLB exceeding 75%, and up to 95% in cases where high diagnostic confidence is reached. When performed in experienced centers using standardized protocols, TBC is considered a viable first-line histopathologic tool in the diagnostic evaluation of ILD. Adequate training and standardization of the TBC procedure are needed to ensure low complication rates and a high yield.

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic interstitial lung disease characterized by irreversible loss of lung function and a poor prognosis. Type I collagen, a major component of the extracellular matrix, plays a central role in the pathogenesis of fibrosis and is considered a key molecular target for therapeutic intervention. While current anti-fibrotic therapies demonstrate limited efficacy in slowing disease progression, their clinical impact remains suboptimal due to poor pharmacokinetic properties and non-curative therapy. Moreover, the development of effective anti-fibrotic agents targeting collagen synthesis is hindered by the absence of robust, cost-effective, high-throughput drug screening platforms. In this study, we established a novel screening system designed to identify small molecules that inhibit the expression of the COL1A2 gene, which encodes type I collagen. Utilizing this system, we screened a library of natural and synthetic compounds developed at Nagasaki University and identified lamellarin D as a potent inhibitor of COL1A2 expression and subsequent type I collagen production. These findings suggest that lamellarin D, through its unique molecular mechanism, may serve as the foundation for the development of a new class of IPF treatments aimed at targeting the underlying fibrotic processes.

The contribution of forced oscillation technique (FOT), also called oscillometry, in diagnosis and follow-up of progressive pulmonary fibrosis (PPF) is not yet established. The aims of this monocentric retrospective study were to compare the FOT profile between patients suffering from PPF and stable non-idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs), to look for a correlation between oscillometry and conventional function tests currently used for PPF follow-up and functional definition (forced vital capacity (FVC) and diffusing lung capacity (DLCO)) and correlation with ILD severity according to FVC. Compared to non-IPF stable ILDs (n = 96), PPF patients (n = 45) showed lower median resistance at 5Hz (Xrs5) values (during inspiratory phase: 0.31 versus -0.39 cmH2O/(L/sec), p = 0.019595). Xrs5 also showed moderate correlation with FVC and DLCO. Finally, among all ILDs (n = 160), Xrs5 showed correlation with disease severity according to FVC. These results suggest that, in conjunction with conventional pulmonary function tests, FOT could be an interesting tool to predict progressive course of fibrosing non-IPF ILDs. Its exact contribution to PPF diagnosis and follow-up needs to be determined by a prospective approach.

Pulmonary fibrosis (PF) is a life-threatening interstitial lung disease, characterized by excessive fibroblast activation and collagen deposition, leading to progressive pulmonary function decline and limited therapeutic efficacy. Here, the inhalable, myofibroblast-targeted, and pH-responsive liposomes (FL-NI) were developed for effective codelivery of nintedanib, a mainstream antifibrotic drug in clinic, and siIL11, a small interfering RNA that silences the key profibrosis cytokine IL-11. Notably, FL-NI achieved a 117.8% increase in pulmonary drug delivery by noninvasive inhalation and a 71.5% increase in delivery specifically to fibroblast activation protein-positive myofibroblasts while reducing nonspecific immune cell and epithelial uptake by 29.8 and 55.8%, respectively. The accurate inhalation codelivery of nintedanib and siIL11 into myofibroblasts achieved synergistic effects, effectively enhanced myofibroblast deactivation, reduced pathological collagen deposition by 50.8%, and promoted epithelial tissue repair. FL-NI remodeled the aberrant immune microenvironment without inducing systemic toxicities. Therefore, this work demonstrated the notable potential for this pluripotent strategy for improving PF outcomes and its promising clinical translation.

Desquamative interstitial pneumonia (DIP), a rare type of idiopathic interstitial pneumonia (IIP), is smoking-related. However, some cases of DIP can also occur in non-smokers with autoimmune disorders. The diagnosis of DIP requires an invasive surgical lung biopsy, therefore, identifying a non-invasive diagnostic biomarker for DIP is crucial. This study aimed to elucidate autoantibodies specific for DIP and evaluate their diagnostic utility. Autoantibodies in the sera of patients with DIP were screened using immunoprecipitation. The common proteins recognized by autoantibodies in patients with DIP were identified using mass spectrometry and enzyme-linked immunosorbent assay (ELISA), and compared to other types of interstitial lung diseases (ILD) and pulmonary diseases. Several characteristic proteins commonly recognized by the sera of patients with DIP were revealed using immunoprecipitation and these proteins were identified as annexin A (ANXA) proteins using mass spectrometry. Using ELISA, autoantibodies to several ANXA were detected more frequently and specifically in DIP compared with those with other types of ILDs and pulmonary diseases. In particular, anti-ANXA4 antibodies had a sensitivity of 52.6 % and specificity of 99 % for DIP compared with those of other types of ILD. Therefore, anti-ANXAs antibodies, especially anti-ANXA4, could be a candidate diagnostic biomarker for DIP.

Lungs are among the most affected organs in systemic sclerosis (SSc), with interstitial lung disease (ILD) being a leading cause of mortality. Biomarkers are increasingly explored for predicting SSc-ILD detection and progression. This study evaluates the roles of Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and peroxiredoxin-4 (PRDX-4) in diagnosing SSc-ILD and monitoring progression.

A total of 89 individuals (61 SSc patients and 28 healthy volunteers) were included. SSc patients were grouped based on pulmonary function tests and high-resolution computed tomography findings to determine SSc-ILD presence. Patients with SSc-ILD were further categorized by progressive pulmonary fibrosis (PPF) presence based on 2022 guidelines. Serum KL-6, SP-D, and PRDX-4 levels were measured using the Enzyme-Linked Immuno-Sorbent Assay method.

Of the 61 SSc patients, 34 (55.7%) had ILD. Serum KL-6 and PRDX-4 levels were significantly higher in SSc-ILD patients (p = 0.004 and p = 0.012, respectively). KL-6, SP-D, and PRDX-4 levels were elevated in the PPF group compared to stable disease (p = 0.001). PRDX-4 showed the highest diagnostic performance for PPF (AUC: 0.936, sensitivity: 85.7%, specificity: 85%).

KL-6 is a well-established biomarker for SSc-ILD, but PRDX-4 offers superior diagnostic accuracy, especially in identifying PPF.

Pulmonary fibrosis (PF) is a chronic and progressive lung disease with fatal consequences. The study of PF is challenging due to the complex mechanism involved, the need to understand the heterogeneity and spatial organization within lung tissues. In this study, we investigate the metabolic heterogeneity between two forms of lung fibrosis: idiopathic pulmonary fibrosis (IPF) and silicosis, using advanced spatially-resolved metabolomics techniques. Employing high-resolution mass spectrometry imaging, we spatially mapped and identified over 260 metabolites in lung tissue sections from mouse models of IPF and silicosis. Histological analysis confirmed fibrosis in both models, with distinct pathological features: alveolar destruction and collagen deposition in IPF, and nodule formation in silicosis. Metabolomic analysis revealed significant differences between IPF and silicosis in key metabolic pathways, including phospholipid metabolism, purine/pyrimidine metabolism, and the TCA cycle. Notably, phosphocholine was elevated in silicosis but reduced in IPF, while carnitine levels decreased in both conditions. Additionally, glycolytic activity was increased in both models, but TCA cycle intermediates showed opposing trends. These findings highlight the spatial metabolic heterogeneity of PF and suggest potential metabolic targets for therapeutic intervention. Further investigation into the regulatory mechanisms behind these metabolic shifts may open new avenues for fibrosis treatment.

Genomic classifier might serve as a biomarker for disease progression in fibrotic interstitial lung disease https://bit.ly/3YuGjoF.

Real-world data on lung function course of patients with progressive pulmonary fibrosis (PPF) treated with anti-fibrotic medication are limited. We evaluated forced vital capacity (FVC) decline in patients with PPF and idiopathic pulmonary fibrosis (IPF) who started anti-fibrotic treatment.

This was a nationwide multi-centre registry study in 16 hospitals throughout the Netherlands. Patients treated with anti-fibrotic medication, with at least two in-hospital pulmonary function tests before and after the initiation of anti-fibrotic treatment, were included. Linear mixed-effects modelling was used to analyse lung function trajectories 1 year before and after the start of anti-fibrotic treatment.

Data from 538 patients (n = 142 with PPF, n = 396 with IPF) were analysed. In PPF, the mean annualised FVC decline was 412 mL (95% confidence interval [CI]: 308-517 mL) before the initiation of anti-fibrotic treatment, and 18 mL (95% CI: 9-124 mL) in the first year after. The corresponding declines for IPF were 158 mL (95% CI: 78-239 mL) and 38 mL (95% CI: 24-101 mL). In both groups, treatment significantly slowed down FVC decline, although the change was larger in the PPF group (p = 0.0006). In the first year after treatment initiation, 23.9% of patients with PPF and 28.0% with IPF had disease progression.

The FVC decline significantly slowed after the initiation of treatment for both IPF and PPF. Nevertheless, a significant proportion of patients exhibited disease progression, despite the start of anti-fibrotic treatment. Early identification of these patients is crucial for treatment adaptations and inclusion in clinical trials.

The 6-min walk test (6MWT), used to monitor disease progression or exacerbation in interstitial lung disease, faces challenges such as requiring a 30-m walking path and difficulty assessing patients with gait disturbance. The 1-min sit-to-stand test (1STST) offers a convenient alternative, potentially addressing these issues. Despite its advantages, the effectiveness of the 1STST in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) still needs to be explored. We assessed 1STST's ability to detect exercise-induced desaturation in a randomized, crossover trial involving patients with IPF or PPF.

Participants were divided into group A (6MWT to 1STST) and B (1STST to 6MWT), with a 30-min rest period between the tests. The primary endpoint was the difference in nadir oxygen saturation (SpO2) between the groups throughout the study. Secondary endpoints included the percentage of participants with a nadir SpO₂ <88% during the tests, a decline of ≥4% in SpO2, and the variation in Borg scores post-tests.

Twenty-three participants (91.3% male; mean age ± standard deviation: 77.2 ± 7.4 years) diagnosed with IPF and PPF were enrolled in this study. The difference in nadir SpO2 between the 1STST and 6MWT was 1.14% (95% confidence interval: -0.18, 2.48), with the 95% confidence intervals falling within the predefined equivalence range. No significant differences were observed in the secondary endpoints.

The results suggest that the 1STST is as effective as the 6MWT in detecting desaturation in patients with IPF and PPF.

This study was registered on the website of the Japan Registry of Clinical Trials (jRCT1032230037; URL: https://jrct.niph.go.jp/).

Although idiopathic pulmonary fibrosis (IPF) is a type of idiopathic interstitial pneumonia (IIP), it is different from other IIPs. IPF also differs from interstitial lung disease (ILD) with known causes, including connective tissue disease, exposure, cysts and/or airspace filling disease, and sarcoidosis. More than 90% of IPFs demonstrate progressive disease. Non-IPF ILD has been classified as progressive pulmonary fibrosis on the basis of disease behavior (progressive disease that gets worse over time) as opposed to classification based on cause and/or morphologic characteristics. Progressive fibrosis predictors in ILD include demographic characteristics, underlying connective tissue disease, more extensive disease at CT, honeycombing and usual interstitial pneumonia (UIP) pattern at CT, and greater impairment of lung function. Hypersensitivity pneumonitis (HP), a type of ILD, is separated into fibrotic and nonfibrotic types. Extensive peribronchiolar metaplasia supports the diagnosis of fibrotic HP over UIP, as does predominantly peribronchiolar disease with relative subpleural sparing at CT. Interstitial lung abnormality (ILA) is incidentally identified at CT; thus, ILA is under radiologist purview. Subpleural fibrotic ILA is a prognostic imaging biomarker, predictive of worse prognosis. Photon-counting CT can provide high spatial resolutions of up to 125 μm (in-plane) and 200 μm (through-plane) for improved evaluation of abnormalities.

The optimal treatment modality for interstitial lung disease (ILD) associated with anti-aminoacyl-tRNA synthetase (ARS) antibodies remains controversial. This study aimed to compare the efficacy and safety of pulse corticosteroid therapy with that of conventional corticosteroid therapy in patients with anti-ARS ILD.

This retrospective cohort study included 62 patients with anti-ARS ILD. Patients were divided into two groups: Those who received pulse corticosteroid therapy (500-1000 mg of methylprednisolone intravenously for three days) and those who received conventional corticosteroid therapy. Primary outcomes included initial treatment response at one year and disease recurrence. Secondary outcomes were alterations in pulmonary function tests, KL-6 levels, prednisolone dose, and adverse events.

Both the pulse corticosteroid therapy group and the conventional therapy group had similar rates of initial treatment improvement (90.3 % vs. 77.4 %, p = 0.301), with no significant differences in recurrence-free survival. Improvements in pulmonary function tests were comparable between the two groups. At 12 months, the mean daily prednisolone dose was 3.9 mg in the pulse therapy group compared with 6.0 mg in the conventional therapy group. The pulse corticosteroid therapy group also experienced fewer adverse events (25.8 % vs. 61.3 %, p = 0.010).

Pulse corticosteroid therapy provides similar treatment efficacy, earlier reduction in corticosteroid dosage, and a lower incidence of adverse events compared to conventional therapy in patients with anti-ARS ILD. These findings highlight the potential benefit of a steroid-sparing strategy, suggesting that pulse corticosteroid therapy may be considered an effective and safer option in managing this condition.

Fibrotic interstitial lung disease (ILD) is associated with high morbidity and mortality. Patients often exhibit impaired nutritional status and alterations in body composition, such as dynapenia and sarcopenia, which correlate with poor pulmonary function, reduced exercise tolerance and diminished quality of life. However, the impact of dynapenia and sarcopenia on prognosis has not been examined extensively in ILD patients. We assessed the impact of dynapenia and sarcopenia as risk factors for mortality and their prevalence in ILD.

Prospective cohort study. ILD was classified into idiopathic pulmonary fibrosis (IPF), connective tissue disease-related ILD (CTD-ILD) and chronic hypersensitivity pneumonitis (CHP). Patients over 18 years old with a confirmed diagnosis of ILD were included, while those with diagnoses of cancer, human immunodeficiency virus and neurological disease were excluded. Dynapenia and sarcopenia were determined according to EWGSOP2 criteria.

Ninety-eight ILD patients were included; 33.66% had IPF, 47.96% had CTD-ILD, and 18.37% had CHP. The mean age was 63.89 ± 12.02 years; 37.76% were male. The risk factors associated with mortality included dynapenia (HR: 2.04, 95% CI: 1.10-3.77, p = 0.022), sarcopenia (HR: 1.88, 95% CI; 1.00-3.33, p = 0.049) and exercise tolerance (HR: 0.99, 95% CI; 0.99-0.99, p = 0.023), adjusted for confounding variables. The prevalence of dynapenia was 45% in ILD; 51% in IPF, 35% in CTD-ILD and 61% in CHP. The prevalence of sarcopenia was 29%; both IPF (39%) and CHP (50%) had a higher prevalence of sarcopenia than CTD-ILD (14%).

Sarcopenia and dynapenia are independent risk factors for mortality in ILD.

Quantitative CT imaging may be a useful predictor of outcome in rheumatoid arthritis-related interstitial lung disease (RA-ILD).

What is the utility of deep learning-based lung fibrosis quantitation on CT imaging in assessing disease severity, predicting mortality, and identifying progression in RA-ILD?

CT scans on a primary cohort of 289 patients and a validation cohort of 50 individuals with RA-ILD were assessed quantitatively by using the data-driven texture analysis (DTA) method. We examined associations between quantitative scores for extent of lung fibrosis and pulmonary function and survival.

DTA fibrosis score at baseline showed moderate negative correlation with FVC percent predicted (primary cohort rho = -0.55; validation cohort rho = -0.50; both, P < .001), and diffusing capacity for carbon monoxide percent predicted (primary cohort rho = -0.67; validation cohort rho = -0.65; both, P < .001). Longitudinal change in DTA fibrosis score was associated with changes in FVC and diffusing capacity for carbon monoxide in the primary cohort (rho = -0.46 and rho = -0.43, respectively; both, P < .001). Cox multivariable models adjusted for potentially influential variables showed that the baseline DTA fibrosis score was significantly associated with mortality risk (primary cohort hazard ratio [HR], 1.04 [95% CI, 1.03-1.05; P < .001]; validation cohort HR, 1.06 [95% CI, 1.01-1.11; P = .026]). In the primary cohort, the increase in DTA fibrosis score on sequential scans was associated with increased risk of mortality (HR, 1.04; 95% CI, 1.01-1.06; P = .003) independent of baseline DTA extent.

In 2 cohorts of patients with RA-ILD, quantitative assessment of lung fibrosis on CT imaging was associated with worse lung function at baseline and risk of mortality. Increase in DTA-derived lung fibrosis score on sequential scans was associated with subsequent risk of mortality. Quantitative CT imaging should be considered for use as a clinical and research outcome assessment tool in RA-ILD.