Azathioprine (AZA) is a widely prescribed immunosuppressive agent in the long-term management of autoimmune hepatitis (AIH), valued for its steroid-sparing properties and efficacy in maintaining disease remission. While its common adverse effects - such as myelosuppression, hepatotoxicity, and gastrointestinal intolerance - are well-recognized and routinely monitored, hypersensitivity pneumonitis (HP) remains an exceptionally rare but potentially life-threatening complication. Herein, we describe a 21-year-old female patient with AIH diagnosed at age 18. Who developed possible AZA-induced HP during the 3[rd] year of continuous therapy. We discuss the potential immunopathogenic mechanisms, review the limited literature on AZA-related pulmonary toxicity, and emphasize the importance of early recognition to prevent irreversible lung injury and optimize patient outcomes.

The patient was a man in his 20s with a history of childhood asthma who presented with fever and dyspnea. Chest CT revealed diffuse bilateral centrilobular ground-glass opacities, and a history of environmental exposure suggested acute hypersensitivity pneumonitis (HP). However, bronchoalveolar lavage revealed marked eosinophilia (75%), and a transbronchial lung biopsy demonstrated small vessel vasculitis with eosinophilic infiltration. Combined with negative anti-neutrophil cytoplasmic antibodies (ANCA), ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) was diagnosed in this patient. Prednisolone (30 mg/day) resulted in rapid improvement, and remission was maintained for 6 months. This case shows that EGPA can mimic acute HP, underscoring the diagnostic value of bronchoscopy and histopathology when eosinophilic inflammation is present.

Hypersensitivity pneumonitis (HP) is a complex immune-mediated interstitial lung disease triggered by repeated or persistent inhalation of a variety of inhaled antigens in genetically predisposed individuals. The disease encompasses a wide clinical spectrum and may present as predominantly inflammatory or fibrotic forms, the latter associated with irreversible architectural distortion and progressive loss of pulmonary function. Although mechanisms involving dysregulated T-cell activation, aberrant antigen processing and maladaptive tissue-repair pathways are recognised as central contributors to HP pathogenesis, the precise mechanisms and the sequence of immunologic events that occur during inflammation and mainly those that drive the transition from inflammation to fibrosis remains unclear. Animal models, particularly murine systems, have helped in dissecting these mechanisms, yet they continue to fall short in fully recapitulating the heterogeneity and chronicity observed in human HP. In this review, we provide an in-depth and critical examination of existing wild-type and genetically modified mouse models used to investigate HP, with emphasis on antigen sources, exposure paradigms and the strengths and limitations of each approach. We synthesise current insights into how specific genes, signalling pathways and immune cell subsets, including T-helper cell polarisation, regulatory T-cell function, dendritic cell activation and immune complexes contribute to disease initiation, amplification and progression.

Trichosporon spp. have emerged as important agents of disseminated infections in immunocompromised patients, where they can express multiple virulence factors and exhibit reduced susceptibility to commonly used antifungal drugs. In this context, natural products have attracted increasing interest as alternative therapeutic agents. This study evaluated the antifungal and antibiofilm activity of a standardized green propolis ethanolic extract against ten clinical isolates of Trichosporon asahii, alone and in combination with conventional antifungals.Minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) were determined using the broth microdilution method. Interactions with amphotericin B and fluconazole were assessed by the checkerboard assay. Biofilm inhibition and eradication were quantified and analyzed by scanning electron microscopy (SEM). Cytotoxicity was evaluated in murine fibroblasts.The extract exhibited significant antifungal activity against planktonic cells, with MIC and MFC values ranging from 276.25 to 1105 mg/L. Although no synergistic interactions were observed with amphotericin B or fluconazole, the combination with propolis reduced the MICs of these antifungals for some isolates. The extract also showed strong antibiofilm activity, reducing biofilm biomass by up to 100% in inhibition assays and up to 99% in eradication assays. SEM analyses confirmed a marked reduction in biofilm density and structural complexity following treatment. Cytotoxic effects were observed at concentrations ranging from 69.06 to 276.25 mg/L, whereas higher concentrations unexpectedly increased fibroblast viability. These findings demonstrate the antifungal and antibiofilm potential of standardized green propolis against T. asahii, highlighting its promise as a source of bioactive compounds for the development of alternative strategies to control difficult-to-treat trichosporonosis.

Aspergillus fumigatus is a clinically important airborne fungal pathogen capable of causing a broad spectrum of respiratory disorders. Persistent exposure or airway colonization can provoke severe allergic diseases, particularly in patients with asthma or cystic fibrosis, whereas impaired immunity or pre-existing structural lung damage may allow the development of chronic or life-threatening invasive pulmonary aspergillosis. Accordingly, the aim of this review was to synthesize current evidence on the role of A. fumigatus in the development of allergic and non-allergic diseases, with particular emphasis on its pathogenic mechanisms, clinical manifestations, diagnostic approaches, treatment strategies, and preventive measures. A systematic search was conducted in PubMed, ResearchGate, Scopus, Web of Science, and Google Scholar, and data on disease course, diagnosis, and management were synthesized. A. fumigatus is a widespread fungus whose spores are abundant in the air and pose a particular risk to immunocompromised individuals. Its virulence factors include thermotolerance, toxin and allergen production, and resistance to oxidative stress. The fungus causes allergic diseases, such as allergic bronchopulmonary aspergillosis, hypersensitive pneumonitis, and severe asthma with fungal sensitivity, as well as non-allergic diseases, including invasive and chronic pulmonary aspergillosis. Infection primarily affects the respiratory system, presenting with cough, weakness, catarrhal symptoms, and haemoptysis. Disseminated infection can involve the brain (cerebral aspergillosis), eyes (endophthalmitis), bones (osteomyelitis), and skin (dermatitis). Diagnosis involves histological tissue examination for fungal hyphae, detection of fungal antigens in blood or respiratory samples, measurement of specific immunoglobulin E, skin tests, and imaging studies. Antifungal and antiallergic drugs are the mainstay of treatment; in case of complications, surgical treatment is performed. To prevent aspergillosis, it is necessary to identify and inform risk groups; control air humidity; and wear masks in places of high risk of infection. A. fumigatus is a dangerous mycosis that causes severe allergic and non-allergic diseases, mainly in people with weakened immune systems.

Background Hypersensitivity pneumonitis (HP) is characterized by a complex immunological reaction of the lung that may lead to chronic interstitial lung disease (ILD). Pulmonary hypertension (PH) may aggravate the clinical picture. We aimed to assess the prevalence of PH in two independent cohorts including patients with moderate and severe HP. Patients and Methods We retrospectively analyzed the data of HP patients with severe ILD undergoing lung transplantation (cohort-1) and invited HP patients with mild disease participating at pulmonary rehabilitation for a prospective screening for PH (cohort-2). The presence of PH was assessed by both echocardiography and right heart catheterization (RHC). Results In cohort 1 (n = 55, median age 57 [95% CI 52-60] years, 59% male, forced vital capacity [FVC] 37 [35-45] % predicted), echocardiographic systolic pulmonary arterial pressure (sPAP) was available in 31 patients and showed elevated values (53 [45-63] mmHg). Sixteen patients (29%) had a high probability of pulmonary hypertension (PH; sPAP > 50 mmHg). Based on clinical assessment, a non-invasive evaluation using echocardiography was performed in accordance with current guideline recommendations, followed by invasive assessment with right heart catheterization (RHC) in selected patients. RHC was performed in 21 patients, revealing a mean pulmonary arterial pressure (mPAP) of 28 (24-33) mmHg and a pulmonary vascular resistance (PVR) of 2.8 (2.2-3.4) Wood units; PH was confirmed in 15 patients (71% of those undergoing RHC, 27% of the total cohort). In cohort 2 (n = 96, median age 62 [60-65] years, 66% male, FVC 98 [95-104] % predicted), echocardiographic screening was available in 88 patients and showed upper-normal sPAP values (29 [28-31] mmHg). One patient (1%) had a high probability of PH. Following clinical assessment and guideline-recommended non-invasive screening, RHC was performed in 13 patients with suspected PH. Hemodynamic measurements showed an mPAP of 19 (16-21) mmHg and a PVR of 1.9 (1.7-2.8) Wood units; PH was confirmed in 5 patients (38% of those undergoing RHC, 5% of the total cohort). All five patients had a plausible alternative explanation for their PH. Conclusion PH is a frequent complication in patients with HP and severe ILD. In HP patients with mild disease, PH is uncommon and alternative causes should be considered.

Lung cancer is significantly more common in patients with idiopathic pulmonary fibrosis (IPF) than the general population. Whether this risk extends to other fibrotic interstitial lung diseases (ILDs) including hypersensitivity pneumonitis (HP) and connective-tissue disease ILD (CTD-ILD), remains uncertain. We aimed to characterise lung cancer prevalence and incidence across ILDs.