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Hypersensitivity pneumonitis (HP) is an immune‐mediated interstitial lung disease (ILD) relating to specific occupational, environmental or medication exposures. Disease behaviour is influenced by the nature of exposure and the host response, with varying degrees of lung inflammation and fibrosis seen within individuals. The differentiation of HP from other ILDs is important due to distinct causes, pathophysiology, prognosis and management implications. This Thoracic Society of Australia and New Zealand (TSANZ) position statement aims to provide an up‐to‐date summary of the evidence for clinicians relating to the diagnosis and management of HP in adults, in the Australian and New Zealand context. This document highlights recent relevant findings and gaps in the literature for which further research is required. [ABSTRACT FROM AUTHOR]

Hypersensitivity pneumonitis (HP) caused by avian antigens is one of the most prevalent forms of HP, with pigeon antigens being the most common culprits. While the health effects on pigeon breeders are well documented, there is limited information on the impact that pigeon breeding has on the health of family members and individuals living near breeding pigeons. This case study describes the condition of a 56-year-old housewife who was referred to an academic hospital's respiratory outpatient department with a principal complaint of six years of progressively worsening dyspnoea and intermittent dry cough. Comprehensive evaluations included a physical examination, chest X-rays (CXR), highresolution computed tomography (HRCT) and lung-function testing. Her blood was analysed for specific immunoglobulin G (sIgG) to avian antigens due to the patient's husband breeding birds at their residence for racing. The clinical work-up suggested an HP diagnosis supported by the laboratory analysis of elevated sIgG antibodies to pigeon mix Ge 91 (pigeon serum proteins, feathers and droppings) and Ge 93 (pigeon serum proteins). These results enabled a confirmatory diagnosis of HP to secondary pigeon exposure. The findings underscore the importance of incorporating sIgG testing to support an HP diagnosis, which is critical to effective disease and exposure management. This case emphasises the necessity of establishing national reference ranges for IgG against common antigens to improve the utility of sIgG antigen testing in the HP diagnostic framework. In addition, it highlights the importance of monitoring exposures in rapidly growing cottage industries in South Africa to reduce the risk of exposure to people, animals and the environment. [ABSTRACT FROM AUTHOR]

Background: Few data are available on acute exacerbation (AE) in patients with progressive pulmonary fibrosis (PPF) besides idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the AE incidence and outcomes among patients with PPF. Methods: Clinical data of patients with PPF (n = 133) were retrospectively collected at a single center. PPF was defined based on the criteria used in the INBUILD trial. AE was defined as a worsening of dyspnea typically within 30 days with new bilateral lung infiltration and no evidence of cardiac failure or fluid overload. Results: Among patients with PPF, the mean age was 60.6 years old, 57.1% were females, and the most common etiology was connective tissue disease-related ILDs (63%). During the follow-up (median: 38.0 months) after PPF diagnosis, 42 patients (31.6%) experienced AE. The 1-, 3-, and 5-year AE incidences were 12.5%, 30.3%, and 38.0%, respectively. Older age, rheumatoid arthritis associated ILD, fibrotic hypersensitivity pneumonitis, and lower lung diffusing capacity for carbon monoxide were AE risk factors. Patients with AE demonstrated worse survival (median survival: 30 months vs. not reached; p < 0.001) after PPF diagnosis than those without. AE was independently associated with mortality in patients with PPF (hazard ratio [HR], 2.194; 95% confidence interval [CI], 1.285—3.747; p = 0.004) in the multivariable Cox analysis, along with older age, lower lung diffusing capacity for carbon monoxide, and the usual interstitial pneumonia-like pattern on high-resolution computed tomography. Conclusions: Our results suggest AE is not uncommon and significantly impacts on survival in patients with PPF. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of hypersensitivity pneumonitis involves removal of the antigen and may include the use of immunosuppression or antifibrotic therapy. It remains unclear whether antifibrotic or immunosuppressive therapy is more beneficial in fibrotic hypersensitivity pneumonitis or if clinical markers can predict a patient's response to therapy. Methods: We evaluated a retrospective cohort in order to determine if certain clinical characteristics can predict physiologic improvement with immunosuppressive treatment in patients with chronic hypersensitivity pneumonitis. Patients with a diagnosis of hypersensitivity pneumonitis with a moderate, high, or definite confidence according to the American Thoracic Society criteria were included in the study. Results: Overall immunosuppression did not lead to improvement in % predicted forced vital capacity (FVC%) and % predicted diffusion capacity (DLCO%). Patients with fibrotic hypersensitivity pneumonitis and those with familial interstitial lung disease demonstrated a decline in FVC% predicted as well as DLCO% predicted over one year and the use of immunosuppression does not modify that risk. In contrast, patients with extensive ground glass demonstrated improvement in DLCO% predicted but not FVC% predicted over one year with or without the use of immunosuppression. Conclusion: Our study demonstrates that certain radiographic variables trend toward a significant impact on FVC% predicted as well as DLCO% predicted and suggests that antifibrotic therapy may be a better initial choice of therapy in patients with fibrotic hypersensitivity pneumonitis as decline occurred with or without the use of immunosuppression. [ABSTRACT FROM AUTHOR]

Introduction: Hypersensitivity pneumonitis (HP) is an extrinsic allergic alveolitis characterized by inflammation of the interstitium, bronchioles, and alveoli of the lung that leads to granuloma formation. We previously found that activation of protein kinase D1 (PKD1) in the lungs following exposures to Saccharopolyspora rectivirgula contributes to the acute pulmonary inflammation, IL-17A expression in the lungs, and development of HP. In the present study, we investigated whether PKD1 in myeloid-lineage cells affects the pathogenic course of the S. rectivirgula -induced HP. Methods: Mice were exposed intranasally to S. rectivirgula once or 3 times/week for 3 weeks. The protein and mRNA expression levels of cytokines/chemokines were detected by enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. Flow cytometry was used to detect the different types of immune cells and the levels of surface proteins. Lung tissue sections were stained with hematoxylin and eosin, digital images were captured, and immune cells influx into the interstitial lung tissue were detected. Results: Compared to control PKD1-sufficient mice, mice with PKD1 deficiency in myeloid-lineage cells (PKD1mKO) showed significantly suppressed expression of TNFα, IFNγ, IL-6, CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10 and neutrophilic alveolitis after single intranasal exposure to S. rectivirgula. Substantially reduced levels of alveolitis and granuloma formation were observed in the PKD1mKO mice repeatedly exposed to S. rectivirgula for 3 weeks. In addition, expression levels of the Th1/Th17 polarizing cytokines and chemokines such as IFNγ, IL-17A, CXCL9, CXCL10, CXCL11, and CCL20 in lungs were significantly reduced in the PKD1mKO mice repeatedly exposed to S. rectivirgula. Moreover, accumulation of CXCR3+CCR6+ nonconventional Th1 in the lungs were significantly reduced in PKD1mKO mice repeatedly exposed to S. rectivirgula. Discussion: Our results demonstrate that PKD1 in myeloid-lineage cells plays an essential role in the development and progress of HP caused by repeated exposure to S. rectivirgula by contributing Th1/Th17 polarizing proinflammatory responses, alveolitis, and accumulation of pathogenic nonconventional Th1 cells in the lungs. [ABSTRACT FROM AUTHOR]

Rationale: Fibrotic hypersensitivity pneumonitis (FHP) is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in FHP in single-cell resolution. Methods: Single-cell 5′ RNA sequencing was conducted on peripheral blood mononuclear cells and BAL cells obtained from 45 patients with FHP, 63 patients with idiopathic pulmonary fibrosis (IPF), 4 patients with nonfibrotic hypersensitivity pneumonitis, and 36 healthy control subjects in the United States and Mexico. Analyses included differential gene expression (Seurat), TF (transcription factor) activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3 and Velocyto-scVelo-CellRank). Measurements and Main Results: Overall, 501,534 peripheral blood mononuclear cells from 110 patients and control subjects and 88,336 BAL cells from 19 patients were profiled. Compared with control samples, FHP has elevated classical monocytes (adjusted-P = 2.5 × 10−3) and is enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-P < 2.2 × 10−16). Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis. Compared with both control subjects and IPF, cells from patients with FHP are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit TF activities indicative of TGFβ and TNFα and NFκB pathways. These results are publicly available at . Conclusions: Single-cell transcriptomics of patients with FHP uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells—reflecting this disease's unique inflammatory T cell–driven nature—as well as increased S100Ahi and CCL3hi/CCL4hi classical monocytes also observed in IPF. Both cell populations may guide the development of new biomarkers and therapeutic interventions. [ABSTRACT FROM AUTHOR]

This study examines the radiological and clinical evolution of a case involving mixed idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis, utilizing conventional CT imaging and artificial intelligence tool. Through a series of exams and clinical assessments, the patient was followed for over 3 years, highlighting the challenge in differentiating these interstitial pathologies and the importance of a multidisciplinary approach. The radiological progression towards pulmonary fibrosis was correlated with clinical symptoms, emphasizing the significance of early diagnosis and regular follow‐up. The combined use of advanced technologies offers a more comprehensive framework in managing complex lung diseases, enhancing the quality of care and understanding of interstitial pathologies. [ABSTRACT FROM AUTHOR]

The article discusses the development of an integrated care pathway for occupational pulmonary diseases, emphasizing the importance of early detection and collaboration between health care providers and occupational health professionals. The pathway consists of five steps, including medical consultation, occupational history assessment, diagnostic work-up, counseling, and follow-up. The ultimate goal is to ensure optimal prevention and care for work-related pulmonary diseases through collaboration among specialists and the registration of patient data in a national database. This Dutch model could serve as practical guidance for other countries aiming to optimize care for occupational pulmonary diseases. [Extracted from the article]

Fibrosing interstitial lung diseases (ILDs) encompass a diverse range of scarring disorders that lead to progressive lung failure. Previous gene expression profiling studies focused on idiopathic pulmonary fibrosis (IPF) and bulk tissue samples. We employed digital spatial profiling to gain new insights into the spatial resolution of gene expression across distinct lung microenvironments (LMEs) in IPF, chronic hypersensitivity pneumonitis (CHP) and non-specific interstitial pneumonia (NSIP). We identified differentially expressed genes between LMEs within each condition, and across histologically similar regions between conditions. Uninvolved regions in IPF and CHP were distinct from normal controls, and displayed potential therapeutic targets. Hallmark LMEs of each condition retained distinct gene signatures, but these could not be reproduced in matched lung tissue samples. Based on these profiles and unsupervised clustering, we grouped previously unclassified ILD cases into NSIP or CHP. Overall, our work uniquely dissects gene expression profiles between LMEs within and across different types of fibrosing ILDs. [ABSTRACT FROM AUTHOR]

Occupational lung diseases result from worker exposure in occupational settings to unhealthy environments and agents, such as silica dust, antigens, coal dust, washed coal/mixed dust, asbestos, and beryllium. Most of these conditions have long latency periods, with disease manifesting years after exposure. Approximately 1 million workers in the U.S. report occupational exposure-related illnesses, including respiratory diseases. We evaluated major occupational lung diseases via an extensive literature review and present here advances in diagnosing major occupational lung diseases, preventive strategies, and regulatory considerations for maintaining a healthy workforce. We include the widely studied occupational lung diseases asbestosis, coal workers' pneumoconiosis and all other pneumoconioses, silicosis, byssinosis, malignant mesothelioma, hypersensitivity pneumonitis, and work-related asthma. The chemistry and physical properties of exposed materials play a role in the severity and pathogenesis of most occupational lung diseases. Knowledge of clinical signs and symptoms of these diseases, exposure history, and consensus diagnostic tools and criteria are crucial for accurate diagnosis, early detection, management, and improved outcomes. Further, regulatory agencies and other interested parties need to develop new and improved surveillance strategies, exposure limits, and technological and industrial safety measures, as well as implement regulations to guide industries and provide recommendations to protect all workers and reduce disease burden. [ABSTRACT FROM AUTHOR]

In this meta-analysis, we aimed to evaluate the prevalence of occupational hypersensitivity pneumonitis (OHP) among different occupations globally. Our search was conducted on MEDLINE via PubMed, Scopus, Web of Science, and Cochrane CENTRAL from inception to September 2023. Eligible studies were observational in nature and focused on several specific occupations. A total of 46 articles were included (n = 2,826,420 participants). The overall prevalence of OHP was found to be 4.2% (95% CI: 2.1% to 8.0%), but this varied significantly based on occupation and geographic location. Printers had the highest OHP prevalence at 57.14%, followed by tobacco workers (26.32%), and water-related workers (24.10%). South America showed the highest prevalence of 16.71%, compared to Asia (15.19%), and North America (8.52%). Significant variations in OHP prevalence by occupation and region were found, with the highest rates in printers and tobacco workers. Age and smoking were identified as contributing factors to the prevalence variability. [ABSTRACT FROM AUTHOR]

Patients with interstitial lung diseases (ILDs) associate a large variety of comorbidities that have a significant impact on their clinical outcomes and survival. Among these comorbidities is neurological impairment. This review highlights what is known about the cognitive function, central nervous system (CNS), depression, and anxiety in patients with specific forms of fibrosing ILDs, such as idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis, connective tissue diseases, etc. The most common pathogenic mechanisms for neurocognitive dysfunction as well as the screening methods and tools for their identification are also described in this review. [ABSTRACT FROM AUTHOR]

Background: Multidisciplinary discussion (MDD), in which physicians, radiologists, and pathologists communicate and diagnose together, has been reported to improve diagnostic accuracy compared to diagnoses made solely by physicians. However, even among experts, diagnostic concordance of MDD is not always good, and some patients may not receive a specific diagnosis due to insufficient findings. A provisional diagnosis based on the ontology with a diagnostic confidence level has recently been proposed. Additionally, we developed an artificial intelligence model to differentiate idiopathic pulmonary fibrosis (IPF) from other chronic interstitial lung diseases (ILD)s, which needs validation in a broader population. Methods: This prospective nationwide ILD registry has recruited patients with newly diagnosed ILD at the referral respiratory hospitals in Japan and provides rapid MDD diagnoses and treatment recommendations through a central online MDD platform with a 3-year follow-up period. A modified diagnostic ontology is used. If no diagnosis reaches more than 50% certainty, the diagnosis is unclassifiable ILD. If multiple diseases are expected, the diagnosis with a high probability takes precedence. If the confidence levels for the top two possible diagnoses are equal, the diagnosis can be unclassifiable. The registry uses tentative diagnostic criteria for nonspecific interstitial pneumonia with organising pneumonia and smoking-related ILD not otherwise specified as possible new entities. Central MDD diagnosticians review the clinical data, test results, radiology images, and pathological specimens on a dedicated website and conduct MDD diagnoses using online meetings with a cloud-based reporting system. This study aims to (1) provide MDD diagnoses with treatment recommendations; (2) determine the overall ILD rates in Japan; (3) clarify the reasons for unclassifiable ILDs; (4) evaluate possible new disease entities; (5) identify progressive phenotypes and create a clinical prediction model; (6) measure the agreement rate between institutional and central diagnoses in ILD referral and non-referral centres; (7) identify key factors for each specific ILD diagnosis; and (8) create a new disease classification system based on treatment strategies, including the use of antifibrotic drugs. Discussion: This study will provide ILD frequencies, including new entities, using central MDD on dedicated online systems, and develop a machine learning model for ILD diagnosis and prognosis prediction. Trial registration: UMIN-CTR Clinical Trial Registry (UMIN000040678). [ABSTRACT FROM AUTHOR]

Fibrosing interstitial lung diseases (FILDs) other than idiopathic pulmonary fibrosis (IPF) can develop into progressive pulmonary fibrosis (PPF) despite initial management. A substantial proportion of patients with non-IPF interstitial lung diseases (ILDs) progress to PPF, including connective tissue disease-associated ILD (such as rheumatoid arthritis-associated ILD, systemic sclerosis-associated ILD, and idiopathic inflammatory myositis-associated ILD), fibrosing hypersensitivity pneumonitis, and fibrosing occupational ILD. The concept of PPF emerged only recently and several studies have confirmed the impact of PPF on mortality. In addition to poor prognosis among patients with PPF, there remains a lack of consensus in the diagnosis and treatment of PPF across different types of ILDs. There is a need to raise awareness of PPF in FILDs and to explore measures to improve PPF diagnosis and treatment, which in turn could potentially reduce the progression from FILD to PPF. This review discusses the disease burden of PPF and recent advances in the management of PPF among patients with ILDs, including antifibrotic medications that have emerged as promising treatment options. Additionally, this review highlights the perspectives of expert Chinese physicians with regard to their experience in managing PPF in clinical practice. [ABSTRACT FROM AUTHOR]

Despite numerous scientific reports on the negative impact of vitamin D3 deficiency on many respiratory diseases, little is known about the influence of this phenomenon on the development and progression of hypersensitivity pneumonitis (HP). The presented study is an attempt to shed light on this occurrence. The research was performed on mouse strain C57BL/6J exposed to the antigen of Pantoea agglomerans (etiological factor of HP). To induce vitamin D3 deficiency, mice received a diet with a 10 times lower amount of cholecalciferol than the main control group. VD3-deficient mice inhaled 25(OH)-VD3 or 1,25(OH)2-VD3 used separately or with SE-PA. At the beginning of the experiment and after 14 and 28 days of inhalation, respiratory function was examined using whole-body plethysmography. Moreover, at indicated time points, mice were sacrificed and samples collected for histological examination, flow cytometry, and ELISA. The performed study revealed that inhalations with 25(OH)-VD3 and 1,25(OH)2-VD3 effectively eliminated most of the negative changes in the respiratory system caused by vitamin D3 deficiency by restoring the physiological concentration of 1,25(OH)2-VD3 in the body. VD3-deficient mice which inhaled P. agglomerans antigen and vitamin D3 metabolites also demonstrated the ability of the tested compounds to eliminate, or at least weaken, the negative effects of the HP causative factor and desired effect, including improvement of respiratory functions and attenuation of inflammation and signs of fibrosis. The obtained results suggested that the beneficial influence of inhaled vitamin D3 metabolites on HP development was associated with the restoration of the physiological concentration of 1,25(OH)2-VD3 in the pulmonary compartments in VD3-deficient mice. [ABSTRACT FROM AUTHOR]

Background and Objectives: Intravenous amikacin, recommended for severe or recurrent M. avium complex (MAC) infections and as initial treatment for M. abscessus lung disease, is often limited by serious adverse effects such as renal and auditory toxicities. Inhaled Amikacin Liposome Inhalation Suspension (ALIS) enhances pulmonary drug deposition while minimizing systemic adverse effects, and it has recently been introduced as an add-on therapy for refractory MAC infections or when other standard treatments are inadequate. This study aims to retrospectively describe the outcomes of Greek patients with difficult-to-treat non-tuberculous mycobacterial (NTM) lung disease following the addition of ALIS to guideline-based therapy. Materials and Methods: Seventeen consecutive patients (median age: 66 years) treated with ALIS as an add-on therapy to a standard regimen at "Sotiria" General Hospital of Chest Diseases (Athens, Greece) from 2020 to 2023 were enrolled in this study. These patients had recurrent or refractory NTM lung disease and/or limited treatment options due to prior treatment-related adverse effects. Clinical, radiological, and microbiological data on treatment response and overall outcomes after ALIS initiation were recorded for each patient. Results: By the end of 2023, 14 out of 17 patients had either successfully completed or were continuing their ALIS therapy. At 6 months, 85.7% (12/14) showed clinical, microbiological, and radiological improvement. However, 25% (3/12) of treated patients, primarily those with monomicrobial or combined M. abscessus lung disease, experienced disease relapse after therapy completion. The most frequent adverse effects related to ALIS were mild and localized to the respiratory tract, with only one patient discontinuing therapy due to hypersensitivity pneumonitis. Conclusions: Adding ALIS to standard regimens was effective and safe in a small group of Greek patients with refractory or recurrent NTM lung disease, particularly those who had discontinued intravenous aminoglycosides due to significant adverse effects, with notable responses observed in MAC lung disease. Further research is needed to validate these findings in clinical practice and to investigate ALIS's role in NTM lung disease caused by other species. [ABSTRACT FROM AUTHOR]

Abstract Background Multidisciplinary discussion (MDD), in which physicians, radiologists, and pathologists communicate and diagnose together, has been reported to improve diagnostic accuracy compared to diagnoses made solely by physicians. However, even among experts, diagnostic concordance of MDD is not always good, and some patients may not receive a specific diagnosis due to insufficient findings. A provisional diagnosis based on the ontology with a diagnostic confidence level has recently been proposed. Additionally, we developed an artificial intelligence model to differentiate idiopathic pulmonary fibrosis (IPF) from other chronic interstitial lung diseases (ILD)s, which needs validation in a broader population. Methods This prospective nationwide ILD registry has recruited patients with newly diagnosed ILD at the referral respiratory hospitals in Japan and provides rapid MDD diagnoses and treatment recommendations through a central online MDD platform with a 3-year follow-up period. A modified diagnostic ontology is used. If no diagnosis reaches more than 50% certainty, the diagnosis is unclassifiable ILD. If multiple diseases are expected, the diagnosis with a high probability takes precedence. If the confidence levels for the top two possible diagnoses are equal, the diagnosis can be unclassifiable. The registry uses tentative diagnostic criteria for nonspecific interstitial pneumonia with organising pneumonia and smoking-related ILD not otherwise specified as possible new entities. Central MDD diagnosticians review the clinical data, test results, radiology images, and pathological specimens on a dedicated website and conduct MDD diagnoses using online meetings with a cloud-based reporting system. This study aims to (1) provide MDD diagnoses with treatment recommendations; (2) determine the overall ILD rates in Japan; (3) clarify the reasons for unclassifiable ILDs; (4) evaluate possible new disease entities; (5) identify progressive phenotypes and create a clinical prediction model; (6) measure the agreement rate between institutional and central diagnoses in ILD referral and non-referral centres; (7) identify key factors for each specific ILD diagnosis; and (8) create a new disease classification system based on treatment strategies, including the use of antifibrotic drugs. Discussion This study will provide ILD frequencies, including new entities, using central MDD on dedicated online systems, and develop a machine learning model for ILD diagnosis and prognosis prediction. Trial registration UMIN-CTR Clinical Trial Registry (UMIN000040678).

Abstract Hypersensitivity pneumonitis (HP) is an immune-mediated inflammatory interstitial lung disease that may evolve to pulmonary fibrosis, a progressive disorder with a poor prognosis characterized by fibroblast activation and extracellular matrix accumulation. In HP lung fibroblasts, the gene expression of proteins involved in the interaction with the immune response, their isoforms, and how they influence their phenotype have yet to be elucidated. We analyzed the expression and splicing variants of 16 target genes involved in the interaction between HP fibroblasts and immune signaling and evaluated possible correlations with clinical data. The comparison of HP and control fibroblasts revealed distinct gene expression patterns. HP lung fibroblasts displayed an increased expression of IFI27 and PDFGRA and a downregulation of IL17RC and TGFBR3. IFI27 immunoreactive protein was markedly increased in HP lung tissues and normal fibroblasts treated with TGF-β. Furthermore, IFI27 overexpression in normal fibroblasts increased α-SMA and decreased cell number over time. The isoform analysis showed similar expression patterns for most genes, except for the AGER receptor with increased soluble variants relative to full-length AGER in HP fibroblasts. These findings indicate important differences in the expression of genes related to the immune response by HP fibroblasts, highlighting their unique characteristics and providing further insight into a possible profibrotic role of IFI27 in the disease.

Background: To assess the characteristics of patients enrolled in the ILD-PRO Registry. Methods: The ILD-PRO Registry is a multicentre US registry of patients with progressive pulmonary fibrosis. This registry is enrolling patients with an interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis who have reticular abnormality and traction bronchiectasis on HRCT, and who meet criteria for ILD progression within the prior 24 months. Patient characteristics were analysed based on the number of patients with available data. Results: Of the first 491 patients enrolled, the majority were white (75.4%) and female (60.6%); 47.4% had a history of smoking. Reported ILDs were autoimmune disease-associated ILDs (47.2%), hypersensitivity pneumonitis (17.5%), idiopathic non-specific interstitial pneumonia (9.1%), interstitial pneumonia with autoimmune features (8.9%), unclassifiable ILD (7.6%), other ILDs (9.7%). At enrolment, median (Q1, Q3) FVC % predicted was 62.2 (49.4, 72.4) and DLco % predicted was 39.2 (30.2, 49.2). Median (Q1, Q3) total score on the St. George's Respiratory Questionnaire was 50.8 (35.9, 64.7). The most common comorbidities were gastroesophageal reflux disease (61.1%) and sleep apnoea (29.6%). Overall, 64.5% of patients were receiving immunosuppressive or cytotoxic therapy, 61.1% proton-pump inhibitors, 53.2% oral steroids, 19.8% nintedanib and 3.6% pirfenidone. Conclusions: Patients enrolled into the ILD-PRO Registry have a variety of ILD diagnoses, marked impairment in lung function and health-related quality of life, and high medication use. Longitudinal data from this registry will further our knowledge of the course of progressive pulmonary fibrosis. Trial Registration: ClinicalTrials.gov, NCT01915511; registered August 5, 2013. [ABSTRACT FROM AUTHOR]

Rationale: Little is known about hospitalization in other types of interstitial lung disease (ILD) besides idiopathic pulmonary fibrosis (IPF). Objectives: To determine the frequency of hospitalizations in various types of ILD and elucidate the association of hospitalization with outcomes. Methods: An analysis of the Pulmonary Fibrosis Foundation Patient Registry data was performed. Inpatient hospitalization rates and survival posthospitalization were compared for various types of ILD. Measurements and Main Results: Hospitalization rates were similar across ILD types: 40.6% of participants with IPF, 42.8% of participants with connective tissue disease–related ILD (CTD-ILD), 44.9% of participants with non-IPF idiopathic interstitial pneumonia (IIP), 46.5% of participants with chronic hypersensitivity pneumonitis (CHP), and 53.3% of participants with "other" ILD. All-cause hospitalization was not associated with decreased transplant-free survival (adjusted hazard ratio [AHR], 1.20; 95% confidence interval [CI] = 0.98, 1.46; P = 0.0759) after adjusting for comorbidities and severity of illness; however, respiratory-related hospitalization was (AHR, 1.53; 95% CI = 1.23, 1.90; P = 0.0001). Participants with CTD-ILD (HR, 0.43; 95% CI = 0.25, 0.75; P = 0.0031) and non-IPF IIP (HR, 0.3; 95% CI = 0.15, 0.58; P = 0.005) had a lower risk of death posthospitalization compared with those with IPF, whereas those with chronic hypersensitivity pneumonitis (HR, 0.67; 95% CI = 0.37, 1.20; P = 0.1747) or other ILD (HR, 0.54; 95% CI = 0.19, 1.54; P = 0.25) had a risk comparable with that for IPF. Conclusions: Rates of hospitalization are similar across ILD subtypes. The risk of death or transplant after posthospitalization is lower in patients with CTD-ILD and non-IPF IIP, compared with patients with IPF. In a mixed population of participants with ILD, all-cause hospitalizations were not associated with decreased transplant-free survival; however respiratory-related hospitalizations were. [ABSTRACT FROM AUTHOR]

Background: PARP inhibitors (PARPi) are used in the treatment of ovarian, breast, pancreatic, and prostate cancers. Pneumonitis has been identified as a potential side effect, with a higher meta-analysis-assessed risk for olaparib versus other PARPi. Olaparib-induced interstitial lung disease (O-ILD) was first described within the Japanese population, with few information available for Caucasian patients. Methods: We performed a retrospective study by pooling data from the French and Belgian pharmacovigilance databases from 2018 to 2022. Patients with O-ILD were included following a central review by: 1) pharmacologists using the French drug causality assessment method; 2) senior pneumologists or radiologists, using the Fleischner Society's recommendations. Results: Five patients were identified and analysed. All were females, with ovarian or breast cancer. Median age at O-ILD diagnosis was 71 (38–72) years old, with no smoking history. Median delay between treatment initiation and symptom occurrence was 12 (6–33) weeks. Pneumonitis severity assessed using the Common Terminology Criteria for Adverse Events V5 was Grade 3 (n = 4) or 2 (n = 1). CT-scan review (n = 3) described hypersensitivity pneumonitis reaction as a common pattern. Bronchioalveolar lavage (n = 4) revealed lymphocytic alveolitis. Treatments relied on olaparib discontinuation (n = 5) and glucocorticoid intake (n = 4), with no fatal issue. Safe re-challenge with PARPi occurred in two patients. Forty additional O-ILD cases were identified in the WHO VigiBase database, including one fatal case. Conclusions: PARPi-ILD is a rare but potentially life-threatening disease, presenting as a hypersensitivity pneumonitis pattern within 3 months of PARPi initiation. Treatment primarily relies on medication discontinuation. Re-challenging with another PARPi could be considered. Clinical trial number: CEPRO #2023–010. [ABSTRACT FROM AUTHOR]

Introduction: Hypersensitivity pneumonitis (HP) is an interstitial inflammatory lung disease that develops as a result of exposition to various, mostly organic antigens. In some patients, fibrotic HP is diagnosed. Factors predisposing to the development of fibrotic lung disease in HP patients are not well documented in the literature. The genetic susceptibility of the patient, type of inciting antigen, and type of exposure, as well as various demographic and clinical variables, may influence the fibrotic process. Aim: The aim of the present study was to investigate whether the type of inciting antigen increases the risk of fibrotic lung disease in HP patients. Methods: Clinical data of consecutive patients with HP diagnosed between 2019 and 2023 were retrospectively reviewed. The exposition to the inciting antigens was investigated by the standardized questionnaire. Recent HP classification into fibrotic (fHP) and non-fibrotic (non-fHP) types was applied. Results: Sixty-six patients diagnosed with HP were analyzed. All patients filled out the exposure questionnaire, and 62 (94%) reported at least one possible exposure. The most prevalent exposures reported were avian, water systems, feather duvets, and hay/straw. Exposure to avian antigens as well as to coal/biomass heating were significantly more prevalent among patients with fHP compared to those with non-fHP (70% vs. 40%, p = 0.03 and 27% vs. 5%, p = 0.04, respectively). Nevertheless, in the multivariate analysis, older age at diagnosis was the only factor influencing the development of fHP (OR 1.064, 95% CI 1.004 to 1.138, p = 0.04). Reported avian antigen exposure correlated well with positive precipitins to avian antigens, whereas no correlation was found between hay/straw exposure and positive antibodies to termophilic actinomycetes. Conclusions: Exposure to birds and coal heating was the most frequently present factor in subjects with fHP, but only older age at diagnosis remained a significant fHP predictor in the multifactor analysis. [ABSTRACT FROM AUTHOR]

This document is a letter published in the journal Clinical Rheumatology. It discusses the use of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). The letter presents the results of a survey conducted among rheumatologists regarding their practices and opinions on the use of these medications in RA-ILD. The survey found that many rheumatologists would perform pulmonary screening prior to initiating MTX or TNFi, but most would not repeat screening. The majority of respondents would avoid MTX in patients with a documented history of ILD or hypersensitivity pneumonitis (HP). The letter also mentions the release of new guidelines by the American College of Rheumatology (ACR) for the management of systemic autoimmune rheumatic disease-associated ILD, which may impact clinical practice. The authors acknowledge the limitations of the survey and suggest further exploration of these practice trends in light of the new guidelines. [Extracted from the article]

Objective: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that can develop in patients with connective tissue diseases. Establishing autoimmunity in ILD impacts prognosis and treatment. Patients with ILD are screened for autoimmunity by measuring antinuclear autoantibodies, rheumatoid factors, and other nonspecific tests. However, this approach may miss autoimmunity that manifests as autoantibodies to tissue antigens not previously defined in ILD. Methods: We use Phage Immunoprecipitation‐Sequencing (PhIP‐Seq) to conduct an autoantibody discovery screen of patients with ILD and controls. We screened for novel autoantigen candidates using PhIP‐Seq. We next developed a radio‐labeled binding assay and validated the leading candidate in 398 patients with ILD recruited from two academic medical centers and 138 blood bank individuals that formed our reference cohort. Results: PhIP‐Seq identified 17 novel autoreactive targets, and machine learning classifiers derived from these targets discriminated ILD serum from controls. Among the 17 candidates, we validated CDHR5 and found CDHR5 autoantibodies in patients with rheumatologic disorders and importantly, patients not previously diagnosed with autoimmunity. Using survival and transplant free–survival data available from one of the two centers, patients with CDHR5 autoantibodies showed worse survival compared with other patients with connective tissue disease ILD. Conclusion: We used PhIP‐Seq to define a novel CDHR5 autoantibody in a subset of select patients with ILD. Our data complement a recent study showing polymorphisms in the CDHR5‐IRF7 gene locus strongly associated with titer of anticentromere antibodies in systemic sclerosis, creating a growing body of evidence suggesting a link between CDHR5 and autoimmunity. [ABSTRACT FROM AUTHOR]

Background: Antigen removal is a cornerstone of treatment of hypersensitivity pneumonitis (HP), but its association with transplant-free survival remains unclear. Further, HP guidelines conflict as to whether antigen removal is a recommended diagnostic test in patients with suspected HP. Objective: The purpose of this study is to (1) evaluate the impact of antigen removal on transplant-free survival and (2) to describe the impact of antigen removal on pulmonary function testing and imaging in a retrospective cohort of patients with HP. Methods: We retrospectively identified HP patients evaluated between 2011 and 2020. Demographic, physiologic, radiographic, and pathologic data were recorded. Results: 212 patients were included in the cohort. Patients who identified and removed antigen had a better transplant-free survival than patients who did not identify antigen and patients who identified but did not remove antigen. Antigen removal was associated with improvement in FVC by 10% predicted in 16.9% of patients with fibrotic HP and 56.7% of patients with nonfibrotic HP. Discussion: Our results suggest that over 50% of nonfibrotic HP patients and 16.9% of fibrotic HP patients improve with exposure removal. In addition, antigen removal, rather than antigen identification, is associated with transplant-free survival in HP. [ABSTRACT FROM AUTHOR]

Simple Summary: This study analyzed over eighty thousand adverse event reports from the Food and Drug Administration's Adverse Event Reporting System to identify records of patients administered with immune checkpoint inhibitors as monotherapy for various malignancies. We analyzed whether co-occurring viral, bacterial, or fungal infections increased the risk of developing immune-related adverse events, such as pneumonitis, sarcoidosis, myocarditis, nephritis, colitis, hepatitis, and others, in cancer patients treated with those inhibitors and quantified the association. We have found a statistically significant, at the 95% confidence level, association between co-occurring infections and immune-related adverse events in cancer patients treated with immune checkpoint inhibitors. Therapeutic antibodies designed to target three immune checkpoint proteins have been applied in the treatment of various malignancies, including small and non-small cell lung cancers, melanoma, renal cell carcinoma, and others. These treatments combat cancers by reactivating cytotoxic T cells. Nevertheless, this mode of action was found to be associated with a broad range of immune-related adverse events (irAEs), including pneumonitis, sarcoidosis, myocarditis, nephritis, colitis, and hepatitis. Depending on their severity, these irAEs often necessitate the suspension or discontinuation of treatment and, in rare instances, may lead to fatalities. We analyzed over nineteen million reports and identified over eighty thousand adverse event reports from patients treated with immune checkpoint inhibitors submitted to the Food and Drug Administration's Adverse Event Reporting System MedWatch. Reports concerning pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab, atezolizumab, and ipilimumab revealed a statistically significant association between the irAEs and concurrent infectious diseases for five out of seven treatments. Furthermore, the association trend was preserved across all three types of checkpoint inhibitors and each of the five individual therapeutic agent cohorts, while the remaining two showed the same trend, but an increased confidence interval, due to an insufficient number of records. [ABSTRACT FROM AUTHOR]

Occupational lung disease remains one of the most common work-related illnesses and accounts for most deaths from occupational illness. Occupational lung diseases often have delayed manifestation over decades and nonspecific clinical presentations, making it challenging for clinicians to promptly identify the disease and implement preventive measures. Radiologists play a crucial role in identifying and diagnosing occupational lung diseases, allowing for removal of the exposure and early medical intervention. In this review, we share our clinical and radiologic approach to diagnosing occupational lung disease and its subtypes. A collection of sample cases of occupational lung diseases commonly encountered in the modern era at a large Canadian university hospital is included to facilitate understanding. This review will provide radiologists with valuable insights into recognizing and diagnosing occupational lung diseases. [ABSTRACT FROM AUTHOR]

Purpose: Treatment with immune-checkpoint inhibitors (ICIs) can be associated with a wide spectrum of immune-related adverse events (irAEs). Among irAEs, immune-mediated pneumonitis (im-PN) is a rare but potentially life-threatening side effect. TPrompt multidisciplinary diagnosis and effective management of im-PN may be essential to avoid severe complications and allowing resumation of therapy. Patients and Methods: We collected a case series of skin (melanoma, cutaneous squamous cell carcinoma-CSCC), lung, and mesothelioma cancer patients (pts), treated with ICI at the Center for Immuno-Oncology University Hospital of Siena, Italy, and diagnosed with im-PN. Clinical and radiologic data were thoroughly collected, as well as bronchoalveolar lavage (BAL) samples; im-PN was graded using CTCAE v. 5.0. Radiological patterns were reported according to the Fleischner Society classification. Results: From January 2014 to February 2023, 1004 patients with melanoma (522), CSCC (42), lung (342) or mesothelioma (98) were treated with ICI (619 monotherapy; 385 combination). Among treated patients, 24 (2%) developed an im-PN and 58% were symptomatic. Im-PN were classified as grades G1 (10) and G2 (14). Prompt steroid treatment led to complete resolution of im-PN in 21 patients, with a median time to resolution of 14 weeks (range: 0.4– 51). Twelve patients resumed ICI therapy once fully-recovered and 2 experienced a recurrence that completely resolved with steroids after resumption of treatment. Three radiologic patterns were identified: organizational pneumonia-like (67%), pulmonary eosinophilia (29%), and hypersensitivity pneumonitis (4%). Furthermore, BAL analysis performed in 8 (33%) patients showed an inflammatory lymphocytic infiltrate, predominantly consisting of foam cell-like macrophage infiltrates in 6 cases. Notably, transmission electron microscopy evaluation performed in 2 patients revealed a scenario suggestive of a drug-mediated toxicity. Conclusion: Im-PN is a rare but challenging side effect of ICI therapy, with variable time of onset and with heterogeneous clinical and radiological presentations. A multidisciplinary assessment is mandatory to optimize the clinical management of im-PN. [ABSTRACT FROM AUTHOR]

A Gram‐positive, aerobic, rod‐shaped mesophilic bacterium was isolated from birch wood, referred to as the AB strain. Allergological tests suggest that this strain may cause allergic alveolitis in sawmill workers. Employing a polyphasic taxonomic approach, the AB strain's 16S rRNA gene sequence showed high similarity to Microbacterium barkeri and M. oryzae, with 97.25% and 96.91%, respectively, a finding supported by rpoB and gyrB sequence analysis. Further genome sequence comparison with the closely related M. barkeri type strain indicated a digital DNA–DNA hybridization value of 25.5% and an average nucleotide identity of 82.52%. The AB strain's cell wall peptidoglycan contains ornithine, and its polar lipids comprise diphosphatidylglycerol, phosphatidylglycerol, and unidentified glycolipids. Its major fatty acids include anteiso C15:0, anteiso C17:0, and iso C16:0, while MK‐10 is its predominant respiratory quinone. Comprehensive analysis through 16S rRNA, whole‐genome sequencing, phenotyping, chemotaxonomy, and MALDI‐TOF MS profiling indicates that the AB strain represents a new species within the Microbacterium genus. It has been proposed to name this species Microbacterium betulae sp. nov., with ABT (PCM 3040T = CEST 30706T) designated as the type strain. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) comprises a group of respiratory diseases affecting the interstitium of the lungs, which occur when a lung injury triggers an abnormal healing response, and an inflammatory process leads to altered diffusion and restrictive respiratory dysfunction. The term "interstitial" may be misleading, as other components of the lungs are usually also involved (epithelium, airways, endothelium, and so on). Pediatric conditions (childhood interstitial lung disease, chILD) are different from adult forms, as growing and developing lungs are affected and more diverse and less prevalent diseases are seen in childhood. Diffuse parenchymal lung disease (DPLD) and diffuse lung disease (DLD) can be used interchangeably with ILD. Known etiologies of chILD include chronic infections, bronchopulmonary dysplasia, aspiration, genetic mutations leading to surfactant dysfunction, and hypersensitivity pneumonitis due to drugs or environmental exposures. Many forms are seen in disorders with pulmonary involvement (connective tissue disorders, storage diseases, malignancies, and so on), but several conditions have unknown origins (desquamative pneumonitis, pulmonary interstitial glycogenosis, neuroendocrine cell hyperplasia in infancy, and so on). Currently, there is no consensus on pediatric classification; however, age grouping is proposed as some specific forms are more prevalent in infancy (developmental and growth abnormalities, surfactant dysfunction mutations, etc.) and others are usually seen in older cohorts (disorders in normal or immunocompromised hosts, systemic diseases, etc.). Clinical manifestations vary from mild nonspecific symptoms (recurrent respiratory infections, exercise intolerance, failure to thrive, dry cough, etc.) to a severe clinical picture (respiratory distress) and presentation related to the child's age. The diagnostic approach relies on imaging techniques (CT), but further investigations including genetic tests, BAL, and lung biopsy (VATS) are needed in uncertain cases. Pharmacological treatment is mostly empiric and based on anti-inflammatory and immunomodulatory drugs. Lung transplantation for selected cases in a pediatric transplantation center could be an option; however, limited data and evidence are available regarding long-term survival. International collaboration is warranted to understand chILD entities better and improve the outcomes of these patients. [ABSTRACT FROM AUTHOR]

Background Occupational short-latency respiratory disease (SLRD; predominantly asthma, rhinitis, hypersensitivity pneumonitis, and occupational infections) prevalence is difficult to determine but certain occupations may be associated with increased susceptibility. Aims This study aimed to examine which occupations and industries are currently at high risk for SLRD and determine their respective suspected causal agents. Methods SLRD cases reported to the SWORD scheme between 1999 and 2019 were analysed to determine directly standardized rate ratios (SRR) by occupation against the average rate for all other occupations combined. Results 'Bakers and flour confectioners' and 'vehicle spray painters' showed significantly raised SRR for SLRD in general, mostly due to occupational rhinitis (234.4; 95% CI 200.5–274.0) and asthma (63.5; 95% CI 51.5–78.3), respectively. Laboratory technicians also showed significantly raised SRR for occupational rhinitis (18.7; 95% CI 15.1–23.1), primarily caused by laboratory animals and insects. Metal machining setters and setter-operators showed increased SRR for occupational hypersensitivity pneumonitis (42.0; 95% CI 29.3–60.3), largely due to cutting/soluble oils. The occupation mostly affected by infectious disease was welding trades (12.9; 95% CI 5.7–29.3), mainly attributable to microbial pathogenicity. Conclusions This study identified the occupational groups at increased risk of developing an SLRD based on data recorded over a recent two-decade period in the UK. Occupational asthma and rhinitis were identified as the prevailing conditions and hypersensitivity pneumonitis as a potentially rising respiratory problem in the metalworking industry. [ABSTRACT FROM AUTHOR]

Background: Although transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real‐world utility in the therapeutic decision‐making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents. Methods: We analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC‐based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing. Results: In our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed‐effects analysis showed that declines in the slopes of %FVC and %DLCO in patients with TBLC‐based UIP "Score ≥ 2" were significantly steeper than those of patients with "Score ≤ 1." During follow‐up of patients with Score ≥ 2 (n = 24), more than half of them (n = 17) received an antifibrotic agent, with most patients (n = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure. Conclusions: TBLC‐based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti‐inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians. [ABSTRACT FROM AUTHOR]

SUMMARY OF KEY POINTS: Air pollutants have various effects on human health in environmental and occupational settings.Air pollutants can be a risk factor for incidence, exacerbation/aggravation and death due to various lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), hypersensitivity pneumonitis or pneumonia (HP), pulmonary fibrosis such as pneumoconiosis and malignant respiratory diseases such as lung cancer and malignant pleural mesothelioma.Environmental and occupational respiratory diseases are crucial clinical and social issues worldwide, although the burden of respiratory disease due to environmental and occupational causes varies depending on country/region, demographic variables, geographical location, industrial structure and socioeconomic situation.The correct recognition of environmental and occupational lung diseases and taking appropriate measures are essential to their effective prevention. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to monitor prescription patterns, clinical outcomes, and adverse drug reactions (ADR) among patients of various interstitial lung diseases (ILDs). Materials and Methods: This prospective study was conducted in the Department of Pharmacology and Therapeutics in collaboration with the Department of Respiratory Medicine, King George’s Medical University, Lucknow, for a period of 12 months (October 2020–September 2021). A total of 77 patients were enrolled after satisfying the inclusion and exclusion criteria. The prescriptions were collected, and necessary details were noted on the case report form. After completion of the study, the data were analyzed for prescription patterns, clinical outcomes, and quality of life with the help of a validated questionnaire-King’s Brief ILD (KBILD) questionnaire. At the same time, ADRs, if any, were assessed using Hartwig’s Severity Assessment Scale and Naranjo Causality Assessment Scale. Results: The most common ILD was acute/chronic hypersensitivity pneumonitis (HP). Average number of drugs per encounter was 4.45. Crepitations were the most common clinical signs. Clubbing and rhonchi were reported maximum in idiopathic pulmonary fibrosis. It was found that psychological, breathlessness and activities, chest symptoms, and total KBILD reduced significantly after 3 months as compared to baseline with a statistically significant difference as P < 0.01. ADRs were found in 23.38% (18) of the subjects. Maximum ADR reported was gastritis (9.09%), followed by hepatitis (3.90%). Conclusion: The high proportion of patients clinically diagnosed with HP in our study highlights the importance of a detailed environmental exposure history in the diagnostic evaluation of patients with ILD to avoid inaccurate diagnoses. ADR-related hospital admissions are a significant problem in the health-care system. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) has traditionally been considered the archetype of progressive fibrotic interstitial lung diseases (f-ILDs), but several other f-ILDs can also manifest a progressive phenotype. Integrating genomic signatures into clinical practice for f-ILD patients may help to identify patients predisposed to a progressive phenotype. In addition to the risk of progressive pulmonary fibrosis, there is a growing body of literature examining how pharmacogenomics influences treatment response, particularly regarding the efficacy and safety profiles of antifibrotic and immunomodulatory agents. In this narrative review, we discuss current studies in IPF and other forms of pulmonary fibrosis, including systemic autoimmune disorders associated ILDs, sarcoidosis and hypersensitivity pneumonitis. We also provide insights into the future direction of research in this complex field. [ABSTRACT FROM AUTHOR]

IntroductionHypersensitivity pneumonitis (HP) is an extrinsic allergic alveolitis characterized by inflammation of the interstitium, bronchioles, and alveoli of the lung that leads to granuloma formation. We previously found that activation of protein kinase D1 (PKD1) in the lungs following exposures to Saccharopolyspora rectivirgula contributes to the acute pulmonary inflammation, IL-17A expression in the lungs, and development of HP. In the present study, we investigated whether PKD1 in myeloid-lineage cells affects the pathogenic course of the S. rectivirgula-induced HP.MethodsMice were exposed intranasally to S. rectivirgula once or 3 times/week for 3 weeks. The protein and mRNA expression levels of cytokines/chemokines were detected by enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. Flow cytometry was used to detect the different types of immune cells and the levels of surface proteins. Lung tissue sections were stained with hematoxylin and eosin, digital images were captured, and immune cells influx into the interstitial lung tissue were detected.ResultsCompared to control PKD1-sufficient mice, mice with PKD1 deficiency in myeloid-lineage cells (PKD1mKO) showed significantly suppressed expression of TNFα, IFNγ, IL-6, CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10 and neutrophilic alveolitis after single intranasal exposure to S. rectivirgula. Substantially reduced levels of alveolitis and granuloma formation were observed in the PKD1mKO mice repeatedly exposed to S. rectivirgula for 3 weeks. In addition, expression levels of the Th1/Th17 polarizing cytokines and chemokines such as IFNγ, IL-17A, CXCL9, CXCL10, CXCL11, and CCL20 in lungs were significantly reduced in the PKD1mKO mice repeatedly exposed to S. rectivirgula. Moreover, accumulation of CXCR3+CCR6+ nonconventional Th1 in the lungs were significantly reduced in PKD1mKO mice repeatedly exposed to S. rectivirgula.DiscussionOur results demonstrate that PKD1 in myeloid-lineage cells plays an essential role in the development and progress of HP caused by repeated exposure to S. rectivirgula by contributing Th1/Th17 polarizing proinflammatory responses, alveolitis, and accumulation of pathogenic nonconventional Th1 cells in the lungs.

The article discusses hypersensitivity pneumonitis (HP), an inflammatory lung disease caused by exposure to antigens. The Thoracic Society of Australia and New Zealand's position statement highlights the importance of early diagnosis and treatment of HP, emphasizing the need for a high index of clinical suspicion. Challenges in diagnosis include identifying antigens, while treatment focuses on antigen elimination and immunosuppressive therapy. Multidisciplinary discussions are recommended for accurate diagnosis and treatment decisions. Further research is needed to optimize diagnostic and treatment strategies for HP. [Extracted from the article]

The article discusses a study that explores immune dysregulation in fibrotic hypersensitivity pneumonitis (FHP) and its differences from idiopathic pulmonary fibrosis (IPF), focusing on the role of immune subpopulations. Topics include immune cell analysis in FHP, the role of cytotoxic T cells, and potential therapeutic strategies based on precision medicine and pharmacogenomics.

This article discusses a case of a 62-year-old man with a history of systemic sclerosis-systemic lupus erythematosus overlap syndrome who presented with progressive shortness of breath. The chest computed tomography (CT) showed lower lobe fibrosis with honeycombing, which is typical of usual interstitial pneumonitis (UIP). The article also explores different imaging patterns of fibrosis and their association with connective tissue disease-interstitial lung disease (CTD-ILD). It emphasizes the importance of accurate diagnosis and management based on specific imaging signs. The article concludes by discussing the need for multidisciplinary assessment to reach a diagnosis and provide appropriate care. [Extracted from the article]

Hypersensitivity pneumonitis (HP) represents the third common interstitial lung disease caused by an exaggerated immune response following the inhalation of organic and/or chemical environmental antigens. The aim of this study was to determine the cut-off values of specific IgG antibodies (named precipitins) and their association with clinical data in the diagnosis of HP. In this 10-year retrospective study, the IgG concentrations against six antigens, Penicillium chrysogenum/notatum, Aspergillus fumigatus, Alternaria alternata, Aspergillus niger, Micropolyspora faeni, and pigeon droppings, were retrieved. The controlled group was made of 1516 healthy subjects without diagnosis of lung pathologies, while the case group consisted of 54 individuals affected by HP. Considering all six IgG antibodies together and the 97.5% percentiles determined in the control group, 30 of 54 subjects (56%) had one or more positive precipitins. In these patients, the major frequencies found were IgG antibodies against pigeon droppings, followed by Penicillium chrysogenum/notatum and Aspergillus niger. Although the sensitivity of serum precipitins depends on the population enrolled and the method used, the cut-off values determined in this study can be a valuable tool for clinicians in the diagnosis of HP, in eliminating the antigens responsible from the environment, and in establishing more specific IgG panels.

The reversed halo sign was initially reported as a representative computed tomography scan finding of cryptogenic organizing pneumonia. Since then, however, it has been reported in various diseases and is now considered a nonspecific finding. However, there are no cases of humidifier lung with the reversed halo sign. An 82-year-old Japanese male patient presented with moving difficulties 48 days after starting darolutamide treatment for prostate cancer. He was admitted to the hospital due to acute pneumonia, which presented as bilateral extensive nonsegmental ground-glass opacities in the peripheral regions and extensive areas of ground-glass opacity with a circumferential halo of consolidation, with the reversed halo sign on computed tomography scan. After darolutamide discontinuation with the concomitant administration of antibiotics, the patient's pneumonia improved, and he was discharged from the hospital. However, within a few days, he was again admitted to the hospital due to pneumonia. He was found to have been using an ultrasonic humidifier at home and was then diagnosed with humidifier lung based on the bronchoscopy and provocative testing findings. Hence, ultrasonic humidifier lung should be considered as a differential diagnosis in patients presenting with the reversed halo sign, and a detailed medical history must be taken.

Abstract Background A growing evidence on the role of vascular endothelial growth factor (VEGF) in the pathogenesis of interstitial lung diseases accumulated over the past decade; with the development of nintedanib for the treatment of fibrotic interstitial lung diseases, our aim was to quantify serum levels of VEGF in patients’ hypersensitivity pneumonitis (HP) and connective tissue disease-associated interstitial lung diseases (CTD-ILD) with an assessment of its relationship with functional status parameters and echocardiographic findings. Methods Spirometry, 6-min walking test, echocardiography, and serum VEGF levels were assessed in HP and CTD-ILD patients. Results The study included 31 HP patients, 30 CTD-ILD patients, and 29 control subjects. VEGF level was significantly higher in HP patients than in patients with CTD-ILD and control subjects. VEGF level showed positive correlation with 6-min walk distance and forced vital capacity percent predicted and inverse correlation with percent desaturation in 6-min walk test, dyspnea score, and echocardiographic findings in both groups. Conclusion Serum VEGF is higher in HP patients than in patients with CTD-ILD and control.

Abstract Background Hypersensitivity pneumonitis (HP) is a more frequently diagnosed picture of diffuse parenchymal lung disease. It is an inflammation of the lung tissue, provoked by immune mechanisms, which happens to prone individuals as a reaction to a wide range of antigens. There are different degrees of fibrosis and inflammation. A group of extracellular mediators both proinflammatory and profibrotic claimed to be involved in the pathogenesis of HP. Among these mediators, a significant role is played by transforming growth factor-beta (TGF-β). Aim Correlation between the severity of hypersensitivity pneumonitis and the serum level of TGF beta. Patients and methods Sixty subjects were included in the study who were classified into 30 patients newly diagnosed with hypersensitivity pneumonitis and 30 healthy subjects served as controls. All the participants were subjected to complete history taking, physical examination, spirometry, 6-min walk distance test, HRCT, and serum levels of TGF-β. Results The serum level of TGF beta is elevated in newly diagnosed HP cases (fibrotic and non-fibrotic) in relation to control participants showing statistical significance p value

Abstract Background Dyspnea impairs quality of life (QOL) in patients with fibrotic hypersensitivity pneumonitis (FHP). The Living with Pulmonary Fibrosis questionnaire (L-PF) assesses symptoms, their impacts and PF-related QOL in patients with any form of PF. Its scores have not undergone validation analyses in an FHP cohort. Methods We used data from the Pirfenidone in FHP trial to examine reliability, validity and responsiveness of the L-PF-35 Dyspnea domain score (Dyspnea) and to estimate its meaningful within-patient change (MWPC) threshold for worsening. Lack of suitable anchors precluded conducting analyses for other L-PF-35 scores. Results At baseline, Dyspnea’s internal consistency (Cronbach’s coefficient alpha) was 0.85; there were significant correlations with all four anchors (University of California San Diego Shortness of Breath Questionnaire scores r = 0.81, St. George’s Activity domain score r = 0.82, percent predicted forced vital capacity r = 0.37, and percent predicted diffusing capacity of the lung for carbon monoxide r = 0.37). Dyspnea was significantly different between anchor subgroups (e.g., lowest percent predicted forced vital capacity (FVC%) vs. highest, 33.5 ± 18.5 vs. 11.1 ± 9.8, p = 0.01). There were significant correlations between changes in Dyspnea and changes in anchor scores at all trial time points. Longitudinal models further confirmed responsiveness. The MWPC threshold estimate for worsening was 6.6 points (range 5–8). Conclusion The L-PF-35 Dyspnea domain appears to possess acceptable psychometric properties for assessing dyspnea in patients with FHP. Because instrument validation is never accomplished with one study, additional research is needed to build on the foundation these analyses provide. Trial registration The data for the analyses presented in this manuscript were generated in a trial registered on ClinicalTrials.gov; the identifier was NCT02958917.

Hypersensitivity pneumonitis (HP) is a complex interstitial pulmonary syndrome. This clinical entity is characterized by sensitization to a specific antigen. Early detection of this antigen is associated with an increased likelihood of a favorable outcome. Increased mortality in hypersensitivity pneumonitis is associated with the development of lung fibrosis. At the same time, clinical interventions do not significantly improve the prognosis of the disease due to a lack of understanding the mechanisms underlying the development of this type of fibrosis. Using reliable biomarkers that objectively reflect biological processes in lung fibrosis may improve clinical decisionmaking. Various biomarkers are now beginning to play a critical role in diagnosing and treating a variety of human diseases. Unfortunately, hypersensitivity pneumonitis is an exception to this general trend. There is still a great deal of research to be done in this area in the search for diagnostic biomarkers. The aim of this study was to identify biomarkers of lung fibrosis development in patients with hypersensitivity pneumonitis. We used mature serum microRNAs, which may regulate inflammation and fibrosis, as such diagnostic markers. Patients with a diagnosis of hypersensitivity pneumonitis (with and without lung fibrosis) as well as healthy individuals without chronic diseases (control group) were included into the study. Clinical and laboratory parameters were assessed in all patients. The miScript miRNA PCR Array Kit (QIAGEN) was used for gene expression profiling of mature serum miRNAs. The data obtained were verified using real-time PCR. Our research has identified a number of mature microRNAs that are likely to be involved in lung fibrosis and inflammation (miR-22, miR-150 and miR-106b). Following an extended study, including monitoring of disease progression over time, the applied diagnostic kit may be used in clinical practice to determine disease activity and development of fibrosis formation in lung tissue in patients with different variants of hypersensitivity pneumonitis.

Background: The management of intractable secondary pneumothorax poses a considerable challenge as it is often not indicated for surgery owing to the presence of underlying disease and poor general condition. While endobronchial occlusion has been employed as a non-surgical treatment for intractable secondary pneumothorax, its effectiveness is limited by the difficulty of locating the bronchus leading to the fistula using conventional techniques. This report details a case treated with endobronchial occlusion where the combined use of transbronchoscopic oxygen insufflation and a digital chest drainage system enabled location of the bronchus responsible for a prolonged air leak, leading to the successful treatment of intractable secondary pneumothorax. Case presentation: An 83-year-old male, previously diagnosed with chronic hypersensitivity pneumonitis and treated with long-term oxygen therapy and oral corticosteroid, was admitted due to a pneumothorax emergency. Owing to a prolonged air leak after thoracic drainage, the patient was deemed at risk of developing an intractable secondary pneumothorax. Due to his poor respiratory condition, endobronchial occlusion with silicone spigots was performed instead of surgery. The location of the bronchus leading to the fistula was unclear on CT imaging. When the bronchoscope was wedged into each subsegmental bronchus and low-flow oxygen was insufflated, a digital chest drainage system detected a significant increase of the air leak only in B5a and B5b, thus identifying the specific location of the bronchus leading to the fistula. With the occlusion of those bronchi using silicone spigots, the air leakage decreased from 200 mL/min to 20 mL/min, and the addition of an autologous blood patch enabled successful removal of the drainage tube. Conclusion: The combination of transbronchoscopic oxygen insufflation with a digital chest drainage system can enhance the therapeutic efficacy of endobronchial occlusion by addressing the problems encountered in conventional techniques, where the ability to identify the leaking bronchus is dependent on factors such as the amount of escaping air and the location of the fistula. [ABSTRACT FROM AUTHOR]

Patients with fibrotic hypersensitivity pneumonitis (fHP) are frequently treated with immunosuppression to slow lung function decline; however, the impact of this treatment has not been studied across different types of antigen exposure. In patients with fHP, do disease outcomes and response to treatment vary by antigen type? A multicenter interstitial lung disease database (Canadian Registry for Pulmonary Fibrosis) was used to identify patients with fHP. The causative antigen was categorized as avian, mold, unknown, or other. Treatment was defined as mycophenolate ≥ 1,000 mg/d or azathioprine ≥ 75 mg/d for ≥ 30 days. Statistical analysis included t tests, χ2 tests, and one-way analysis of variance. Unadjusted and adjusted competing risks and Cox proportional hazards models were used to assess survival. A total of 344 patients were identified with the following causative antigens: avian (n = 93; 27%), mold (n = 88; 26%), other (n = 15; 4%), and unknown (n = 148; 43%). Patient characteristics and lung function were similar among antigen groups with a mean FVC % predicted of 75 ± 20. The percent of patients treated with immunosuppression was similar between antigens with 58% of patients treated. There was no change in lung function or symptom scores with the initiation of immunosuppression in the full cohort. Immunosuppression was not associated with a change in survival for patients with avian or mold antigen (avian: hazard ratio, 0.41; 95% CI, 0.11-1.59; P =.20; mold: hazard ratio, 1.13; 95% CI, 0.26-4.97; P =.88). For patients with unknown causative antigen, survival was worse when treated with immunosuppression (hazard ratio, 2.65; 95% CI, 1.01-6.92; P =.047). Response to immunosuppression varies by antigen type in patients with fHP. Additional studies are needed to test the role of immunosuppression in fHP, and particularly in those with an unknown antigen. [ABSTRACT FROM AUTHOR]

Hypersensitivity pneumonitis (HP) represents the third common interstitial lung disease caused by an exaggerated immune response following the inhalation of organic and/or chemical environmental antigens. The aim of this study was to determine the cut-off values of specific IgG antibodies (named precipitins) and their association with clinical data in the diagnosis of HP. In this 10-year retrospective study, the IgG concentrations against six antigens, Penicillium chrysogenum/notatum, Aspergillus fumigatus, Alternaria alternata, Aspergillus niger, Micropolyspora faeni, and pigeon droppings, were retrieved. The controlled group was made of 1516 healthy subjects without diagnosis of lung pathologies, while the case group consisted of 54 individuals affected by HP. Considering all six IgG antibodies together and the 97.5% percentiles determined in the control group, 30 of 54 subjects (56%) had one or more positive precipitins. In these patients, the major frequencies found were IgG antibodies against pigeon droppings, followed by Penicillium chrysogenum/notatum and Aspergillus niger. Although the sensitivity of serum precipitins depends on the population enrolled and the method used, the cut-off values determined in this study can be a valuable tool for clinicians in the diagnosis of HP, in eliminating the antigens responsible from the environment, and in establishing more specific IgG panels. [ABSTRACT FROM AUTHOR]