Pentraxin-3 as a diagnostic and prognostic biomarker in inflammatory lung diseases.

This case report presents a young female patient whose chief complaint was exertional dyspnea. Right heart catheterization confirmed severe pulmonary hypertension. Concurrently, chest CT showed atypical pulmonary parenchymal and interstitial lesions, and pulmonary function tests indicated severe impairment of diffusion capacity. To clarify whether an association existed between the lung disease and pulmonary hypertension, transbronchial lung cryobiopsy was performed, which revealed multinucleated giant cell aggregates within the alveolar spaces, with cholesterol clefts in the cytoplasm of some of them. Together with a 1-year history of pigeon exposure, the final pulmonary diagnosis was extrinsic allergic alveolitis (hypersensitivity pneumonitis).With respect to the pulmonary hypertension, genetic testing showed no significant abnormalities, thereby ruling out heritable pulmonary hypertension. After oral imatinib combined with macitentan was administered, the patient's pulmonary artery pressure gradually decreased and her symptoms recovered well; however, follow-up chest CT and pulmonary function tests showed no apparent improvement. Because the elevated pulmonary artery pressure was inconsistent with the pulmonary disease, the patient was ultimately diagnosed with idiopathic pulmonary hypertension complicated by allergic alveolitis.

Neuromyelitis optica spectrum disorder (NMOSD) is a recurrent demyelinating disease of the central nervous system (CNS)characterized by inflammatory attacks on the CNS. This article reports a 56-year-old male patient admitted with over a year history of shortness of breath, a 2-week history of decreased vision in the right eye, and a 1-week history of hiccups. Physical examination revealed digital clubbing of both hands and bilateral lower lung Velcro rales. The patient had concurrent anti-aquaporin-4 (AQP4) antibody-positive NMOSD, primary Sjögren's syndrome (pSS), and interstitial lung disease (ILD), which were confirmed by characteristic clinical features, serological antibody testing, high-resolution chest CT, cranial and optic nerve MRI, and labial gland biopsy. Treatment included high-dose glucocorticoid pulse therapy combined with efgartigimod for pathogenic autoantibody clearance, inebilizumab targeted therapy, and mycophenolate mofetil (MMF) for long-term immunosuppression. After discharge, sequential maintenance therapy with oral prednisone and MMF tablets was administered. The patient's visual acuity and neurological symptoms improved. At follow-up >2 months after discharge, dyspnea recurred and worsened. After intensifying anti-infective therapy while maintaining the immunomodulatory regimen, the condition was effectively controlled, with follow-up high-resolution CT showing marked resolution of pulmonary interstitial exudates. This case suggests that anti-AQP4 antibodies may co-mediate pathological processes in both the central nervous system and peripheral organs. For patients with anti-AQP4 antibody-positive NMOSD, further screening for ILD or pSS is warranted. Early neurological assessment and antibody screening are crucial, facilitating early diagnosis and individualized treatment under multidisciplinary collaboration.

STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by mutations in TMEM173 gene encoding STING (stimulator of interferon genes). It typically presents in infancy and is mainly characterized by interstitial lung disease, skin rash, and systemic inflammation. This report presents the case of adult-onset SAVI:A 28-year-old male patient was admitted with recurrent episode of cough, expectoration, chest tightness with shortness of breath and erythematous rashes on the extremities, chest, and back.His CT revealed bilateral diffuse fine reticular opacities and irregular reticular shadows, with focal areas of honeycombing. Further inquiry into the family history revealed that the patient's mother had been diagnosed with interstitial lung disease (ILD).Thus, a genetic etiology should be highly suspected.Later, whole-exome sequencing identified a heterozygous mutation in the STING1 gene: c.842G>A (p.R281Q), establishing the diagnosis of SAVI. The patient was subsequently referred to a tertiary care hospital for specialized management. During one year of follow-up, the patient underwent lung transplantation in August 2025 and had since received long-term immunosuppressive therapy for rejection prophylaxis. Cough and expectoration improved markedly, although exertional dyspnea persisted; the cutaneous rash had resolved completely.

Objective: To investigate the predictive value of baseline serum KL-6 levels for acute exacerbation (AE) in patients with fibrotic interstitial lung disease (F-ILD). Methods: A single-center retrospective cohort study was conducted, enrolling 265 patients with fibrotic ILD diagnosed by multidisciplinary team (MDT) at Sichuan Provincial People's Hospital from July 2022 to November 2024, including 118 patients with idiopathic pulmonary fibrosis (IPF) and 147 patients with fibrotic connective tissue disease-associated ILD (CTD-ILD). Baseline data were collected, and the primary endpoint was the occurrence of AE during follow-up. Cox regression analysis was used to identify independent risk factors for AE, and ROC curve analysis was performed to evaluate predictive performance. Results: After a median follow-up of 20 months, 77 patients (29.1%) developed AE. Multivariate Cox regression showed that KL-6≥1 363.5 U/ml (HR=3.928, P<0.001) was an independent risk factor for AE. Baseline KL-6 predicted AE in F-ILD with an AUC of 0.795, and the optimal cutoff value was 1 363.5 U/ml. The combined model (KL-6+CA15-3+CYFRA21-1+DLCO%) achieved an AUC of 0.853. Subgroup analysis revealed that KL-6 had the highest predictive value in IPF patients (AUC=0.820), followed by CTD-ILD patients (AUC=0.774). Conclusion: Baseline serum KL-6 is an independent predictor of AE in patients with F-ILD, demonstrating good risk stratification capability, particularly with optimal performance in IPF.

FFA4 inhibits bleomycin-induced pulmonary fibrosis in mice by suppressing IL-33.

Objective: To understand the etiological diagnosis, triggers for disease recurrence and treatment status of diffuse alveolar hemorrhage (DAH) in Chinese children. Methods: A retrospective cohort study was conducted. Clinical data, including baseline information, laboratory findings, chest imaging findings and treatment regimens were collected from 567 children with DAH admitted to 21 hospitals in China from 2002 to 2021. Cases with immune-related etiologies or undetermined etiological diagnosis were included and divided into two groups based on glucocorticoids treatment duration: ≥3 months group and <3 months group. The study period from January 2002 to December 2021 was divided into two time intervals: 2002-2011 and 2012-2021. The two groups were compared in terms of etiological diagnosis rate, initial and overall immunosuppressant use rate, disease recurrence rate and mortality rate. All group comparisons were performed using the χ² test. Results: Among the 567 children with DAH, 333 were male and 234 were female. The age at onset was 4.0 (2.1, 6.5) years and the follow-up duration was 4.4 (2.4, 7.2) years. A definite etiological diagnosis was established in 107 cases (18.9%), while 460 cases (81.1%) remained without a definite etiological diagnosis. Among the 494 cases (including idiopathic pulmonary hemosiderosis and those with undetermined etiological diagnosis), 389 cases (78.7%) were initially treated with glucocorticoids alone and 45 cases (9.1%) with a combination of glucocorticoids and immunosuppressants. Throughout the treatment, immunosuppressants were used in 132 cases (26.7%). Among the 549 cases (including immune-related cases and those with undetermined etiological diagnosis), 303 cases (55.2%) experienced recurrent exacerbation of the disease. The common triggers included respiratory infection in 193 cases (35.2%), glucocorticoid dose reduction in 103 cases (18.8%) and non-adherence to medication in 66 cases (12.0%). Eight cases were lost to follow-up. The mortality rate was 8.7% (47/541), with causes of death including end-stage lung disease with severe infection in 32 cases (5.9%), severe pulmonary hemorrhage in 12 cases (2.2%) and unknown cause in 3 cases (0.5%). Among those receiving glucocorticoids therapy, 373 cases were in the ≥3 months group and 125 cases in the <3 months group. The mortality rate in the ≥3 months group was lower than that in the <3 months group (P<0.01). There were 92 cases in the 2002-2012 group and 457 cases in the 2012-2021 group. The utilization rates of immunosuppressants in both initial treatment and the entire treatment course for children with immune-related and those with undetermined etiological diagnosis were higher in the 2012-2021 group than in the 2002-2012 group (both P<0.01). Conclusions: In China, pediatric DAH has complex etiologies and a definitive etiological diagnosis remains difficult to establish in some cases. Recurrent exacerbation is common and mainly due to the respiratory infection, glucocorticoids dose reduction and non-adherence to medication. Glucocorticoids remain the primary treatment, with combined use of immunosuppressants in some cases.

With a rapidly expanding human population at advanced ages and age as the main driver for chronic diseases, we face the challenge of understanding tissue aging and devising new therapeutic interventions. Cellular senescence is an important hallmark of all aging tissues and has emerged as a potential key driver of chronic lung diseases, including pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), and asthma. This comprehensive review recapitulates current knowledge of pathways and processes involved in cellular senescence with emphasis on the role of mitochondrial dysfunction and the "4 Ms" (morphology, mitophagy, metabolism, and metabolites). We review our current knowledge of healthy lung aging, discuss which pathomechanisms in chronic lung disease are characterized by senescence, and summarize current target therapeutics and their impact on lung disease. Within this exponentially growing field, we propose emerging concepts and current gaps in knowledge that need to be addressed to develop better opportunities for therapeutic strategies and future investigations.

To investigate the effects of Shenling Baizhu Powder (SLBZP) on non-tuberculous mycobacteria (NTM)-induced lung disease in mice. An NTM lung disease mouse model was established by Mycobacterium kansasii infection. C57BL/6J female mice were randomly divided into 5 groups by a random number table (n=6): negative control, NTM, SLBZP-L (2.34 g/kg), SLBZP-H (4.68 g/kg), and rifampicin (20 mg/kg). M. kansasii load in the lungs, liver, and spleen was quantified. Lung histology was performed using hematoxylin and eosin staining. Gene and cytokine expressions related to CD4+ T and natural killer (NK) cells were detected by enzyme linked immunosorbent assay, flow cytometry, real-time quantitative reverse transcription PCR, and Western blot, respectively. SLBZP-L and SLBZP-H treatments inhibited M. kansasii growth and reduced the histological damage and granuloma lesion areas in lungs of mice (P<0.01). SLBZP-H increased interleukin (IL)-17A and interferon-gamma (IFN-γ) levels, along with the proportion of CD4+ T cells, NK cells, and IFN-γ+ NK cells, while decreased IL-10 (P<0.01). Furthermore, SLBZP-H inhibited mRNA levels of tumor necrosis factor, IL-6, IL-1β, C-C motif chemokine ligand 2, C-X-C motif chemokine ligand (CXCL) 2, GATA binding protein 3 and T-bet, and increased mRNA level of retinoic acid receptor-related orphan receptor γ (P<0.05 or P<0.01). SLBZP-L and SLBZP-H also reduced the protein expressions of CXCL13 and C-X-C chemokine receptor type 5 (P<0.05 or P<0.01). SLBZP alleviated NTM-induced lung damage and enhanced NK cell immune response, which might be linked to CD4+ T cell immunity.

Antioxidants in lung disease: Failures and pathways for success.

Alveolar macrophages (AMs) are pivotal immune sentinels, essential for maintaining tissue homeostasis and mediating immune responses to inhaled particles and pathogens. They demonstrate remarkable plasticity by transitioning from proinflammatory (M1) and anti-inflammatory/reparative (M2) phenotypes in response to local signals. Upon exposure to environmental agents, such as particulate matter, atypical respiratory pathogens, opportunistic Gram-negative bacteria, or respiratory viruses, they undergo dynamic activation that profoundly influences their functional repertoire. Acute or chronic environmental/biological insults disrupt normal AM activities such as phagocytosis, efferocytosis, and cytokine production, inciting oxidative stress, inflammasome activation, and in some cases forms of programmed cell death such as pyroptosis. Although these responses are indispensable for eliminating noxious particles and pathogens, such as Mycoplasma pneumoniae or Klebsiella pneumoniae, influenza A, or SARS-CoV-2, they can also derail the resolution phase by perpetuating inflammation, driving tissue remodeling and fibrosis, and thereby fueling chronic lung disorders such as chronic obstructive pulmonary disease (COPD), pneumoconiosis, and post-COVID interstitial lung disease. Moreover, environmental and microbial exposures modify AMs by altering receptor repertoires, intracellular phenotype by signaling cascades, and cross talk with epithelial and mesenchymal cells that collectively determine the disease trajectory. Elucidating how diverse environmental agents, together with pathogens such as M. pneumoniae, K. pneumoniae, influenza A, and SARS-CoV-2, shape AM biology is therefore pivotal for understanding the pathogenesis of COPD, pneumoconiosis, progressive fibrotic lung disease, and COVID-19-related pulmonary sequelae. This review brings together the current insights into exposure-driven modulation of AM functions, highlighting recent advances and identifying knowledge gaps relevant for therapeutic targeting of exposure-induced and pathogen-mediated lung pathology.

When MicroRNAs meet hypoxic pulmonary hypertension.

Macrophage polarization as a therapeutic target in lung diseases: From pathogenesis to precision intervention.

Lung transplant remains the ultimate life-saving therapy for people with progressive end-stage lung disease. It is important to highlight the evolution of the field in the United States, as its development has had varying impacts on the different lung transplant candidate groups. This review seeks to synthesize current evidence on the evolution of transplantation across various patient groups, reflecting advances in medical therapies, the implementation of the new composite allocation score (CAS) and trends in lung transplant candidate groups over the years. The proportion of waitlisted candidate with chronic obstructive pulmonary disease (COPD, group A) and cystic fibrosis (group C) has declined, reflecting the impact of novel therapeutics and advanced procedural interventions. In contrast, restrictive lung disease patients (group D) now account for most lung transplant recipients, which is likely reflective of our increased use of extracorporeal membrane oxygen (ECMO) for bridging and transplant centers expanded eligibility. Pulmonary hypertension patients (group B) continue to face high waitlist mortality despite the change to the new allocation scoring system. Advancements in medical therapies and the new composite allocation scoring system has altered both the timing and outcomes for various transplant candidate groups. It is important that we continue to study these findings to optimize patient outcomes and organ allocation.

As multimodal information becomes central to complex task understanding, efficiently integrating heterogeneous data remains a challenge. This paper proposes a knowledge-driven hybrid fusion framework that enhances model classification performance by integrating the modeling of images and text. We designed an adaptive gating network to dynamically balance the contributions of visual and textual modalities, enabling flexible and robust knowledge integration across diverse clinical scenarios. The framework incorporates a hybrid fusion strategy, early fusion captures fine-grained semantic associations across modalities, while late fusion preserves modality-specific representations, enhancing model consistency and discriminative capabilities under multi-task optimization. Experimental results on multiple multimodal medical datasets validate the effectiveness and generalizability of the proposed hybrid fusion framework in clinical scenarios. The framework’s near-clinical accuracy in lung disease and cancer classification highlights its potential for clinical decision support. • We propose a local interaction attention mechanism that aligns semantic cues from clinical text with corresponding regions in chest X-ray images, enabling fine-grained diagnostic knowledge modeling. • We design an adaptive gating network that dynamically balances the contributions of textual and visual modalities, allowing flexible knowledge fusion and improving decision-support robustness under varying clinical scenarios. • This is an early research that constructs a hybrid fusion architecture employs early fusion for cross-modal semantic interaction and combines late fusion to preserve modality-specific knowledge. By incorporating a contrastive learning mechanism, enabling the model to simultaneously optimize classification tasks and contrastive tasks within a multi-task learning framework. This approach achieves more accurate, reliable, and comprehensive decision support.

Objectives. To examine telehealth use and modality choice among US older adults (≥ 65 years) and identify factors associated with adoption and modality preference in the postpandemic era. Methods. Using data from 2723 device-owning older adults in the 2024 Health Information National Trends Survey (HINTS 7; nationally representative, March-September 2024), multivariable logistic and multinomial logit models examined associations between telehealth use, modality, and covariates, including socioeconomic factors, health conditions, digital literacy, and prior health information technology use. Results. Overall, 31.4% of older adults used telehealth in 2024 (video: 12.38%; phone-only: 12.41%). Higher odds of use were associated with Hispanic ethnicity (adjusted odds ratio [AOR] = 1.92; 95% confidence interval [CI] = 1.07, 3.81), lung disease (AOR = 2.32; 95% CI = 1.22, 4.42), depression (AOR = 1.89; 95% CI = 1.01, 3.54), and frequent provider visits; lower odds were associated with nonmetropolitan adjacent residence (AOR = 0.36; 95% CI = 0.17, 0.76) and health insurance coverage (AOR = 0.13; 95% CI = 0.03, 0.62). In addition to these factors, video use was uniquely associated with higher income, ability to use apps without assistance, and prior health IT use. Nonusers most commonly cited preference for in-person care (45.7%) or not being offered telehealth (13.4%). Conclusions. Telehealth use has stabilized but remains low among US older adults, with persistent geographic and socioeconomic disparities in modality choice. Policies ensuring audio-only parity and targeted digital literacy interventions are essential to promote equitable telehealth access as telehealth becomes integrated into postpandemic care. (Am J Public Health. 2026;116(S3): S218-S228. https://doi.org/10.2105/AJPH.2026.308575).

Early treatment for progressive pulmonary fibrosis (PPF) improves outcomes. However, diagnosis of fibrotic-interstitial lung diseases (fibrotic ILDs) and detection of potentially emergent PPF are delayed by 9-12months on average. New ILD diagnostic and PPF monitoring strategies are being investigated toenable early treatment and improve patient outcomes. A time-to-event cost-effectiveness model for reducing delays in ILD diagnosis and PPF detection was developed. Model inputs were obtained from ILD expert clinicians, the literature, and statistical progression equations derived from the INBUILD trial. The study investigated discounted health economic outcomes of early diagnosis of ILD and detection of PPF in eight European countries (Belgium, Denmark, Finland, Greece, Norway, The Netherlands, Portugal, and Sweden). The study highlights substantial benefits from reducing the time to diagnose fibrotic ILD and identifying PPF across various ILD subtypes. Clinical advantages arise from any reduction in diagnostic delays, primarily by delaying the onset of PPF and facilitating earlier nintedanib treatment. The model indicates that earlier diagnosis results in quality-adjusted life-year (QALY) gains across all countries, with improvements ranging from 0.061 to 0.084 in the base case. Furthermore, all tested scenarios confirm the cost-effectiveness of early diagnosis of fibrotic ILD and of PPF detection across all studied countries. Early diagnosis of ILD and detection of PPF yield cost-effective clinical benefits, supporting the adoption of approaches to speed up ILD diagnosis and PPF detection. ClinicalTrials.gov identifier, NCT02999178.

This mini-review, inspired by the 20th Anniversary Stem Cells, Cell Therapies and Bioengineering in Lung Biology and Diseases conference, summarizes two decades of advances in human-specific lung disease modeling. We discuss endogenous stem cell-based platforms for both distal alveolar and proximal airway epithelia, including primary alveolar type II cells, bronchial and nasal epithelial cultures established as organoids, air-liquid interface cultures, and ex vivo preparations. Advances in iPSC-derived basal and alveolar epithelial cells, humanized graft models, and high-throughput therapeutic screening are highlighted. Collectively, these in vitro and in vivo models are transforming the study of lung development, injury, and repair, while accelerating drug discovery and regenerative medicine strategies. Finally, we emphasize the critical need for integrating immune components into organotypic cultures and for establishing rigorous validation and benchmarking standards to maximize translational relevance.

Almost all patients with mucopolysaccharidosis (MPS) develop respiratory dysfunction of varying severity during disease progression. While respiratory disease in MPS has traditionally been attributed to upper airway obstruction caused by glycosaminoglycan (GAG) accumulation in the trachea and bronchi, involvement of the intrapulmonary conducting airways and lung parenchyma remains poorly defined. Here, we characterised lung disease in a mouse model of MPS I using a combination of non-invasive X-ray Velocimetry (XV) functional lung imaging and gold-standard flexiVent respiratory mechanics testing, complemented by lung volume measurements and histological analysis. XV provides regional ventilation information across the entire lung during tidal breathing. MPS I mice demonstrated reduced mean specific ventilation (the average regional expansion of lung tissue across the respiratory cycle), driven predominantly by reduced ventilation in the inner (mediastinal-adjacent) lung regions, with evidence of spatially heterogeneous ventilation distribution. Lung mechanics testing showed increased conducting airway resistance, increased respiratory system compliance and reduced tissue elastance, consistent with impaired elastic recoil and expiratory flow limitation. Lung volume analysis revealed reduced opening pressure following degassing together with increased residual volume, functional residual capacity and vital capacity. Histological analysis demonstrated heterogeneous parenchymal architecture with regions of enlarged airspaces. Together, these findings demonstrate that respiratory dysfunction in MPS I is not limited to upper airway obstruction but also involves intrinsic abnormalities of the intrapulmonary conducting airways and lung parenchyma. This intrinsic pulmonary pathology likely contributes to obstructive lung disease and may underlie the susceptibility to respiratory failure observed in patients with MPS I.

Few studies have described long-term respiratory sequelae of adolescent (people aged 10-19years) tuberculosis (TB) survivors. We hypothesized that compared with healthy adolescents with no history of TB, survivors of adolescent pulmonary TB have greater respiratory impairment (reduced lung function) and disability (symptoms and activity limitations). In this prospective cohort study in Lima, Peru, we used spirometry, oscillometry, and the St George's Respiratory Questionnaire (SGRQ) to evaluate, on 2 separate occasions, the lung health of adolescents successfully treated for pulmonary TB and matched healthy controls. TB survivors with abnormal lung function underwent chest computed tomography (CT). Using mixed-effects regression with an interaction term for time since treatment completion and random effects for individual and matched pairs, we modeled changes in lung function and disability over 24months from treatment completion, comparing findings between TB survivors and controls. Compared with 101 controls (median age 17years, 56% male), 101 TB survivors (median age 18years, 56% male) had less favorable forced expiratory volume in 1 second, forced vital capacity, total airway resistance (R5), small airway resistance (R5-20), and reactance area (AX). Over the study period, AX, R5, and R5-20 improved for TB survivors but remained worse than controls. TB survivors had persistently greater respiratory disability (measured by SGRQ). Chest CTs of TB survivors demonstrated architectural distortion, reticular patterns, nodules, and bronchiectasis. Adolescent TB survivors experience persistent, symptomatic chronic lung disease despite bacteriological cure. Our findings highlight the need for respiratory assessments beyond treatment completion.