Specific molecular and inflammatory endotypes have been identified for chronic respiratory disorders, including asthma and COPD (chronic obstructive pulmonary disease). These endotypes correspond with clinical aspects of disease, enabling targeted medicines to address certain pathophysiologic pathways, often referred to as “precision medicine”. With respect to bronchiectasis, many comorbidities and underlying causes have been identified. Inflammatory endotypes have also been widely studied and reported. Additionally, several genes have been shown to affect disease progression. However, the lack of a clear classification has also hampered our understanding of the disease’s natural course. The aim of this review is, thus, to summarize the current knowledge on biomarkers and actionable targets of this complex pathologic condition and to point out unmet needs, which are required in the design of effective diagnostic and therapeutic trials.

Pleural mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. Here, we review all these aspects to underline the progress being made in its investigation and to emphasize how much work remains to be carried out to improve prognosis and treatment.

Background: Patients with fibrotic interstitial lung disease (ILD) are at increased risk of lung cancer, yet the impact of antifibrotic therapy on oncologic outcomes remains unclear. Objective: This study aimed to explore associations between antifibrotic therapy and overall survival (OS) and acute exacerbations of ILD (AE-ILD) in patients with fibrotic ILD who develop lung cancer. Methods: We retrospectively analyzed 61 patients from multiple Italian centers: 35 received antifibrotic therapy (pirfenidone or nintedanib) and 26 did not. Outcomes included OS from cancer diagnosis and post-treatment AE-ILD. Results: Mean OS was 17.9 months in the antifibrotic group and 33.2 months in the non-antifibrotic group; no adjusted survival analyses were possible due to missing censoring data, and these descriptive values should not be overinterpreted. AE-ILD occurred in 11.4% of antifibrotic-treated patients and 11.5% of those without antifibrotics. PD-L1 expression was detected in 24.1% vs. 21.8% of tumors in the two groups, and autoantibody positivity was observed in 22.8% vs. 30.7%, respectively, reflecting differences in ILD subtypes. Conclusions: In this heterogeneous real-world cohort, antifibrotic therapy was not associated with increased AE-ILD risk, and descriptive OS comparisons showed no clear survival advantage. These exploratory findings warrant confirmation in larger, prospective studies.

Background: Exophiala dermatitidis is a dematiaceous, thermotolerant, yeast-like fungus increasingly recognized as an opportunistic pathogen in chronic airway diseases. While commonly associated with cystic fibrosis, its clinical significance in non-cystic fibrosis bronchiectasis (NCFB) remains unclear. Case Presentation: We report the case of a 66-year-old immunocompetent woman with a history of breast cancer in remission and NCFB, who presented with chronic cough and dyspnea. Chest CT revealed bilateral bronchiectasis with new pseudonodular opacities. Bronchoalveolar lavage cultures identified E. dermatitidis, along with Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus. Given clinical stability and the absence of systemic signs, initial therapy included oral voriconazole, levofloxacin, doxycycline, and inhaled amikacin. Despite persistent fungal isolation on repeat bronchoscopy, the patient remained asymptomatic with stable radiologic and functional findings. Antifungal therapy was discontinued, and the patient continued under close monitoring. The patient exhibited clinical and radiological stability despite repeated fungal isolation, reinforcing the hypothesis of persistent colonization rather than active infection. Discussion: This case underscores the diagnostic challenges in distinguishing fungal colonization from true infection in structurally abnormal lungs. In NCFB, disrupted mucociliary clearance and microbial dysbiosis may facilitate fungal persistence, even in the absence of overt immunosuppression. The detection of E. dermatitidis should prompt a comprehensive evaluation, integrating clinical, radiologic, and microbiologic data to guide management. Voriconazole is currently the antifungal agent of choice, though therapeutic thresholds and duration remain undefined. Conclusions: This report highlights the potential role of E. dermatitidis as an under-recognized respiratory pathogen in NCFB and the importance of a multidisciplinary, individualized approach to diagnosis and treatment. This case underscores the need for further research on fungal colonization in NCFB and the development of evidence-based treatment guidelines. Further studies are needed to clarify the pathogenic significance, optimal management, and long-term outcomes of E. dermatitidis in non-CF chronic lung diseases.

Background: Scedosporium apiospermum is a filamentous fungus increasingly recognized as an opportunistic pathogen in immunocompromised hosts, though rare infections in immunocompetent individuals with structural lung disease have been reported. Its diagnosis and management remain challenging due to non-specific clinical presentation and intrinsic resistance to multiple antifungal agents. Case Presentation: We report the case of a 66-year-old immunocompetent woman with idiopathic bilateral non-cystic fibrosis bronchiectasis, who presented with subacute cough and increased sputum production. Chest high-resolution CT revealed new subsolid and ground-glass infiltrates superimposed on stable bronchiectatic changes. Bronchoalveolar lavage (BAL) cultures isolated S. apiospermum as the sole pathogen. The patient was treated with oral voriconazole (200 mg BID) for 4 weeks, followed by a 4-week course of aerosolized amphotericin B. Clinical and radiological improvement was observed, and no relapse occurred during follow-up. Discussion: This case highlights the potential for S. apiospermum to cause clinically relevant pulmonary infection in structurally abnormal but immunocompetent lungs. Non-CF bronchiectasis may facilitate fungal colonization due to impaired mucociliary clearance and chronic mucus retention. Combined antifungal therapy involving systemic voriconazole and inhaled amphotericin B (though not yet standardized) was employed based on clinical rationale and the available literature, resulting in favorable outcomes. Conclusions:S. apiospermum pulmonary infection, although rare in immunocompetent hosts with bronchiectasis, should be considered in cases of new or persistent infiltrates. Early recognition and individualized antifungal strategies, including the potential role of inhaled agents, may improve clinical outcomes. This case reinforces the importance of multidisciplinary collaboration in the management of complex fungal infections in chronic airway disease.

Background: Tracheobronchial stenosis is a significant complication in granulomatosis with polyangiitis (GPA), a systemic vasculitis that primarily affects the upper respiratory tract, kidneys, and lungs. The involvement of the tracheobronchial tree in GPA leads to airway narrowing, which can result in severe respiratory symptoms and increased morbidity, often requiring prompt diagnosis and management to prevent life-threatening airway obstruction. Method: We present the case of a 28-year-old male with mild exertional dyspnea, stridor, and retropharyngeal sputum. Clinical investigations revealed subglottic and bronchial concentric stenosis with granulomatous inflammation. A diagnosis of granulomatosis with polyangiitis (GPA) with isolated tracheobronchial stenosis (TBS) was confirmed. Results: Given the severity of airway obstruction, multidisciplinary management was initiated, combining rigid bronchoscopy with systemic immunosuppressive therapy. Post-intervention follow-up demonstrated significant airway improvement and maintained remission after two years. Conclusions: This case highlights TBS as a potentially debilitating GPA manifestation requiring a combination of systemic and endoscopic therapies. Further studies are needed to optimize therapeutic approaches and improve outcomes in GPA-associated TBS.