Search Results (97)

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease characterized by immune-mediated inflammation and variable degrees of fibrosis. Aims: To evaluate the clinical, radiological, and hematological features of patients diagnosed with HP. Study Design: Retrospective cross-sectional study. Methods: We included 100 patients diagnosed and followed for HP between 2020 and 2024. Demographic characteristics, pulmonary function test results, diffusing capacity, six-minute walk test findings, antigen exposure history, and high-resolution computed tomography (HRCT) patterns were retrospectively analyzed. Results: The mean age was 63 ± 14 years, with equal sex distribution. Sixty-five percent of patients had identifiable antigen exposure, predominantly related to birds or bird products (86.4%). Surgical lung biopsy confirmed the diagnosis in 29% of cases. The most common HRCT findings were reticulation (87%), ground-glass opacities (84.7%), and centrilobular nodules (75%); fibrotic features were present in 48% of patients. Glucocorticoids were the main treatment (77%), and antifibrotic therapy was used in 20% of cases. Neutrophil count showed a modest positive correlation with honeycombing (r = 0.27, p = 0.025). Basophil count demonstrated a mild association with bird-related antigen exposure (r = 0.26, p = 0.035). Conclusions: Peripheral neutrophil and basophil counts showed weak but statistically significant associations with fibrotic HRCT features and exposure patterns. These exploratory findings suggest that routinely available hematologic parameters may provide supportive information alongside radiologic and clinical data. Prospective studies are needed to validate their diagnostic and prognostic relevance in HP. Full article

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by repeated exposure to inhaled antigens in susceptible subjects. High-resolution computed tomography (HRCT) of the lungs is the leading diagnostic method for ILDs, but in some cases HRCT findings are not sufficient to distinguish HP and other ILDs, particularly, fibrotic HP (fHP) and usual interstitial pneumonia (UIP). Objective: The aim of this study was to develop HRCT criteria to diagnose fHP in patients with a UIP-like pattern. Methods: In this retrospective study, we analyzed HRCT scans of patients with fHP and a UIP-like pattern who underwent lung biopsy, and patients with idiopathic pulmonary fibrosis (IPF) and a UIP pattern in HRCT. Results: We included 51 patients with confirmed fHP and 24 patients with IPF/UIP in the analysis. IPF/UIP patients were older, were prevalently males, and did not have any systemic autoimmune diseases or risk factors for other ILDs. fHP patients were younger, with an equal number of males and females, and were more likely to be exposed to environmental antigens. HRCT abnormalities in the fHP group predominated in the lower lung areas or were diffuse in axial scans, whereas IPF/UIP patients mostly demonstrated a diffuse craniocaudal distribution and subpleural axial predominance. Centrilobular nodules and mosaic attenuation were present significantly more often in the fHP group; honeycombing, traction bronchiectasis, and emphysema prevailed in IPF/UIP patients. In the logistic regression analysis, patients with fHP and IPF/UIP differed in the presence of centrilobular nodules, honeycombing, and in both craniocaudal and axial distributions of HRCT abnormalities. In the ROC analysis, the combination of centrilobular nodules, honeycombing, and diffuse axial and craniocaudal distributions can predict the diagnosis of fHP (AUC, 0.953 ± 0.022; 95%CI, 0.910–0.995; p < 0.001). Mosaic attenuation and reticulation did not change the probability of fHP. Conclusions: The most significant HRCT features of fHP compared to the UIP pattern were centrilobular nodules, honeycombing, and a diffuse axial and craniocaudal distribution of abnormal findings. Reticulation, mosaic attenuation, and GGO do not increase the probability of fHP. Full article

Although vitamin D3 (VD3) deficiency has been recognized as a harmful agent in several respiratory diseases, the present study is the first one to investigate its influence on the development of hypersensitivity pneumonitis (HP). This research was conducted in a murine model of HP, wherein pulmonary fibrosis was induced by antigen of Pantoea agglomerans. VD3 deficiency was provoked by diet with 10-times less cholecalciferol than feed given to VD3-sufficient mice. Before and after 14 and 28 days of nebulization, lung function was evaluated. Moreover, at indicated time points, lungs were collected and subjected to histological assessment, flow cytometry, gene expression assays, and ELISA. The performed research showed a higher sensitivity of VD3-deficient mice to fibrosis response to P. agglomerans antigen, which was strongly associated with enhanced epithelial-to-mesenchymal transition, the signs of which were over-expression of EMT-transcription factors (Snail2, Zeb1, Zeb2) and mesenchymal cell markers (Cdh2/N-cadherin, Acta2/SMA, Fn1/Fibronectin, Vim/Vimentin). Indicated negative changes in VD3-deficient mice with developed HP were supported by deepening calcitriol deficiency and worsening respiratory functions, including the frequency of breathing, minute volume, total cycle times, expiratory and inspiratory time. Moreover, typical for VD3-deficient mice with HP, there was also an increased influx of immune cells into the lungs (especially neutrophils, macrophages, dendritic cells and lymphocytes Tc), a disturbed cytokine profile with over-production of growth factors favoring fibrosis (FGF2 and TGFβ), and lowered synthesis of several cytokines (IL1β, IL6, IL12, IL4 IL10, IL13). The present study reveals that VD3 deficiency promotes the development of pulmonary fibrosis in the murine model of HP. Full article

Sarcoidosis is a chronic, idiopathic, multisystemic inflammatory disease characterized by non-caseating granulomas, most commonly affecting the lungs and mediastinal lymph nodes. Radiological imaging plays a fundamental role in the diagnosis, assessment of disease extent, and differentiation from other pulmonary conditions. This narrative review offers a comprehensive overview of the imaging features of pulmonary sarcoidosis, focusing on both typical patterns—such as bilateral hilar lymphadenopathy, perilymphatic nodules, and upper lobe-predominant infiltrates—and atypical manifestations—including alveolar opacities, miliary nodules, fibrocystic changes, and lower lobe involvement. Emphasis is placed on the utility of high-resolution computed tomography (HRCT) in detecting early parenchymal changes and complications such as fibrosis, bronchiectasis, and pulmonary hypertension. Differential diagnosis, including tuberculosis, silicosis, metastatic disease, organizing pneumonia, and hypersensitivity pneumonitis, are discussed to aid interpretation. Recognizing the spectrum of radiological presentations is essential for distinguishing sarcoidosis from other interstitial and granulomatous lung diseases. Radiologists play a pivotal role in the multidisciplinary diagnostic process, contributing to timely diagnosis, risk stratification, and optimized patient management. Full article

Background: Some hypersensitivity pneumonitis (HP) patients exhibit autoimmune features (HPAF). This study compared outcomes of HPAF and HP without autoimmune features, focusing on progressive pulmonary fibrosis (PPF) and response to immunosuppression. Methods: A retrospective cohort study included HP patients from a single center. HPAF was defined as HP overlapping with autoimmune disease or presenting autoimmune markers/symptoms not fulfilling connective tissue disease criteria. A control HP group without autoimmune features was randomly selected. Demographics, autoimmune profiles, and outcomes over two years were analyzed. Results: 103 patients were included (52 HPAF; 51 HP). In HPAF, the most common autoimmune diseases were rheumatoid arthritis (9.6%), while 57.7% had isolated autoimmune serology. Groups showed no baseline differences in demographics, exposures, smoking, or lung function. Fibrotic disease on high-resolution CT at diagnosis was less frequent in HPAF (71.2% vs. 88.2%; p = 0.031). At two-year follow-up, survival, transplantation, and PPF prevalence were similar. HPAF patients received immunosuppression less often (69.2% vs. 86.3%; p = 0.038). Among patients under immunosuppression, PPF was significantly lower in HPAF group (8.6% vs. 29.5%; p = 0.021). Conclusions: Within two years post-diagnosis, HPAF and HP had comparable overall outcomes. However, under immunosuppression, HPAF patients had significantly lower odds of developing PPF (adjusted OR 0.08; 95% CI 0.008–0.816; p = 0.033) compared to HP patients, suggesting a more favorable treatment response. Full article

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) characterized by inflammation of the lung parenchyma, alveoli and bronchioles induced by inhalation of organic compounds. Bird-related-HP (BRHP) is the most common type of HP, occurring in susceptible people in regular contact with birds, although a genetic susceptibility is unclear. This study investigates the impact of environmental volatile organic compounds (VOCs) on the development of HP and other pulmonary diseases, and their relationship with pulmonary inflammatory cell composition and patient outcomes. Methods: Geospatial environmental levels of VOCs (benzene, toluene, ethylbenzene, m,p-xylene and o-xylene) in patients’ homes were related to bronchoalveolar lavage (BAL) leukocyte profiles analyzed by flow cytometry of 1515 patients with different lung diseases in the region of Murcia (southeastern Spain). Results: Ethylbenzene levels over the threshold limit of 10 µg/m³ (EB10) were associated with HP (23.9% vs. 15.2%, p < 0.05). A strong association with HP was observed in patients in contact with birds living in areas with EB10 (63.0% vs. 27.4%, p < 0.001). Linear regression analysis showed that age (B = −0.058, p < 0.012), smoking (B = −0.125, p < 0.001), bird contact (B = 0.275, p < 0.001) and EB10 (B = 0.109, p < 0.001) were independent variables associated with HP. In HP patients, BAL CD4/CD8-ratio > 1.5 was associated with shorter overall survival (8.9 years vs. not-reached, p < 0.011), probably due to lower CD8+ T-lymphocyte counts observed in HP fibrotic patients (11.65 ± 2.8% vs. 23.6 ± 2.9%, p = 0.008) and in those who died during follow-up (10.0 ± 1.9% vs. 23.8 ± 2.7%, p = 0.012), suggesting a protective role for CD8+ T cells. Conclusions: High environmental ethylbenzene is strongly associated with BRHP. CD8+ T-lymphocytes could have a protective role in HP, preventing fibrosis and increasing overall survival. Full article

Autoimmune pulmonary alveolar proteinosis (aPAP) is characterized by the accumulation of phospholipids and surfactant proteins in the peripheral air spaces due to alveolar macrophage dysfunction caused by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (GMAb). Hypersensitivity pneumonitis (HP) is a granulomatous lung disease associated with GM-CSF. In this report, we evaluated serial changes in serum GMAb levels in a 67-year-old male current smoker with HP and aPAP and examined their correlation with HP disease activity. GMAb levels increased at HP onset and decreased after HP remission with oral prednisolone therapy. After the first remission, the patient experienced three relapses and remissions. Although GMAb levels were not evaluated for all HP relapses and remissions, GMAb levels increased at one relapse but decreased at two remissions induced by the oral prednisolone therapy. Pulmonary fibrosis progressed, and the patient died of pneumonia. GMAb was at its almost normal levels at 8 months before the onset of pneumonia. We hypothesized that GMAbs may have been induced to improve HP through neutralizing GM-CSF. Although the hypothesis needs to be confirmed in additional patients, serial measurement of GMAb may be useful for a better understanding of the pathophysiology and deciding the appropriate treatment for HP with aPAP. Full article

Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases. Full article

Background and Objectives: Immune checkpoint inhibitors (ICIs) have emerged as groundbreaking agents in cancer therapy; however, their immune-related adverse effects, especially pulmonary toxicity, significantly limit their use. This study aimed to determine the incidence and risk factors associated with ICI-induced pulmonary toxicity. Materials and Methods: We conducted a prospective observational study involving 126 patients aged ≥18 years with malignancies treated with ICIs between April 2022 and April 2024. Patients were followed every six months over a two-year period. Clinical, laboratory, and radiological data were collected to assess pulmonary toxicity. Results: The mean age of our patients was 62.93 ± 12.94 years, and 81% were male. The ICI-related pulmonary toxicity rate was 16.7%, and the all-cause mortality rate was 68.3%. In the analysis, the conditions associated with pulmonary toxicity were the type of malignancy, the presence of lung cancer, COPD, long-term ICI use, dyspnea, cough and sputum, the pre-ICI lung nodule mass, and high blood monocyte levels. Our regression analysis results for the determination of risk factors showed a 7.70-fold increase in the presence of cough symptoms, a 4.57-fold increase in the presence of COPD, a 0.998-fold increase for every 1 unit decrease in lymphocyte count, and an 11.75-fold increase in risk for a monocyte count of 130 or less. Conclusions: Our study’s findings suggest that patients with identifiable risk factors for pulmonary toxicity should undergo closer monitoring and early diagnostic evaluation during ICI therapy to reduce morbidity and mortality. Full article

Background/Objectives: Hypersensitivity pneumonitis (HP), a subtype of interstitial lung disease (ILD), is often misdiagnosed as idiopathic pulmonary fibrosis (IPF), particularly when the causative antigen cannot be identified. Typically resulting from chronic exposure to inhaled organic particles smaller than 5 microns, HP presents a diagnostic challenge. This report outlines a case of fibrotic HP initially misclassified as asthma. No triggering antigen was identified despite extensive investigation. The disease progressed despite corticosteroid, immunosuppressive, and antifibrotic therapy, ultimately leading to an advanced fibrotic stage and requiring lung transplantation. This clinical course is rare and infrequently reported, particularly in cases requiring lung transplantation without an identifiable causative antigen. Such progression is uncommon and underreported, especially in patients initially misclassified as having asthma. Methods: Medical records of 24 patients diagnosed with HP were reviewed. Only one case demonstrated progression to fibrotic HP; this case was selected for detailed analysis. Results: Clinical and functional deterioration occurred despite standard therapy. Given the advanced stage of fibrosis and treatment resistance, lung transplantation was deemed the next appropriate therapeutic option. Conclusions: HP remains underdiagnosed due to difficulties in identifying the causative antigen and overlapping features with other ILDs. Early and accurate differentiation from IPF is essential, particularly in progressive fibrotic forms unresponsive to conventional therapies. Full article

Nitrofurantoin, a commonly prescribed antibiotic for urinary tract infections, has been associated with rare but potentially serious pulmonary toxicity, which can present in acute, subacute, or chronic forms. Acute toxicity typically manifests in the form of hypersensitivity pneumonitis, which is characterized by fever, dyspnea, and eosinophilia, often resolving rapidly after drug discontinuation. However, chronic toxicity can lead to interstitial lung disease with progressive fibrosis, causing significant and sometimes irreversible pulmonary impairment. The pathophysiology of nitrofurantoin-induced lung injury is thought to involve oxidative stress, immune-mediated mechanisms, and direct cytotoxic effects; however, the exact pathways remain incompletely understood. Clinical diagnosis is challenging due to nonspecific symptoms that often resemble other respiratory conditions, leading to delays in recognition and treatment. Radiographic findings vary, with acute cases showing diffuse ground-glass opacities, while chronic cases may demonstrate reticular interstitial changes and fibrosis. The discontinuation of nitrofurantoin is the primary intervention, but corticosteroids may be beneficial, particularly in chronic cases with persistent inflammation or fibrosis, though their efficacy remains uncertain. Given the risk of long-term respiratory complications, heightened awareness among healthcare providers is essential for early diagnosis and intervention. Future research is needed to better define risk factors, improve diagnostic criteria, and explore alternative treatment strategies that mitigate the potential for pulmonary toxicity while maintaining effective antimicrobial therapy. This review explores the pathophysiology, clinical presentation, diagnostic challenges, and management strategies for nitrofurantoin-induced pulmonary toxicity. Full article

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

Several studies have reported the incidence of fungi and mycotoxins in coffee beans; however, there are few reports related to occupational exposure to these agents at coffee dry milling industries. The aim of this review was to identify and to analyze studies assessing occupational exposure to fungi and mycotoxins in coffee industries. Therefore, a systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and focusing on the assessment of occupational exposure to fungi and mycotoxins in the coffee industry. In these papers, different environmental matrices were considered in evaluating occupational exposure, but the most used matrix was airborne dust (four of the five studies). Airborne fungi were sampled using active (four of the five studies) and passive sampling. Only the most recent of the studies (2022) identified microorganisms by their genera and species, and only two groups of mycotoxins were analyzed in the studies considered, namely, Ochratoxin A and Aflatoxins. None of the studies reported data on both fungi and mycotoxins. The fungal genera identified in these occupational environments included Cladosporium, Paecilomyces, Aspergillus, Penicillium, and other genera. Among the mycotoxins, only aflatoxins and ochratoxin A were investigated. Occupational exposure to these biological agents may lead to several health effects. Fungal spores and fragments can cause respiratory diseases such as asthma, allergic rhinitis, bronchitis, and hypersensitivity pneumonitis. Additionally, the mycotoxins studied—particularly Aflatoxins and Ochratoxin A—are associated with serious toxicological effects. Coexposure to both fungi and mycotoxins may enhance health risks and should be carefully considered in occupational risk assessments. Considering the possible effects related to exposure to fungi and mycotoxins and the number of workers involved in this type of industry in the world, more studies should be developed. This is the first review to systematically consolidate data on occupational exposure to both fungi and mycotoxins specifically within the coffee industry, highlighting existing knowledge gaps and the need for targeted risk assessments in coffee-producing settings. Full article

Background: Hypersensitivity pneumonitis (HP) represents a chronic lung disease with an unpredictable clinical course. There is a pressing need for clinically applicable prognostic biomarkers in patients with HP. Methods: This was an observational, retrospective study. We investigated the prognostic potential of complete blood count parameters in treatment-naïve patients diagnosed with HP between 15 December 2010 and 1 October 2023. Receiver operating characteristic (ROC) curve analysis identified the optimal cut-off thresholds for each parameter in terms of mortality prediction. Results: We included 129 patients diagnosed with HP [median age: 68.0 years (95% CI: 65.0 to 69.0), fibrotic HP: n = 85, 65.9%]. Patients with HP and an eosinophil count > 160 cells/μL [ROC curve, area under curve (AUC): 0.61] exhibited increased mortality risk compared to patients with HP and an eosinophil count ≤ 160 cells/μL [Kaplan–Meier, HR: 2.95 (95% CI: 1.36 to 6.42), p = 0.006]. Patients with HP and a monocyte count > 350 cells/μL (ROC curve, AUC: 0.52) had worse survival compared to patients with HP and a monocyte count lower than this threshold [Kaplan–Meier, HR: 2.48 (95% CI: 1.03 to 5.09), p = 0.04]. Patients with HP and an eosinophil–lymphocyte ratio (ELR) > 0.09 (ROC curve, AUC: 0.64) had a higher risk of mortality compared to patients with HP and ELR ≤ 0.09 [Kaplan–Meier, HR: 2.75 (95% CI: 1.3 to 5.78), p = 0.008]. Conclusions: This study demonstrated that eosinophil count, monocyte count, and ELR could be prognostic biomarkers in patients with HP. Further studies aiming to validate the prognostic potential of complete blood count parameters in patients with HP are greatly anticipated. Full article