Obstructive sleep apnea (OSA) is one of the most common sleep disorders in the general population. It is characterized by recurrent alterations in nocturnal oxygenation, which have wide-ranging consequences on health. Beyond its well-established links to cardiovascular, neurocognitive, and metabolic diseases, recent evidence suggests a possible association between OSA and cancer, particularly lung cancer, one of the leading causes of death worldwide. The advent of immunotherapy has significantly improved outcomes for lung cancer patients in both early and advanced stages. However, immunotherapy is frequently associated with endocrine toxicities, which may overlap or interact with the metabolic alterations observed in OSA. This perspective aims to emphasize the clinical relevance of diagnosing and treating OSA in lung cancer patients undergoing immunotherapy, as proper management could help optimize both therapeutic efficacy and overall health.

Background and aim Exacerbations are critical events in the natural history of bronchiectasis. While an international definition has been proposed for clinical trials by an EMBARC/BRR task force, the clinical presentation of exacerbations varies considerably among patients. The aim of our study was to assess the clinical heterogeneity of signs and symptoms of bronchiectasis exacerbations in a real-world setting. Methods This was a multicentre cross-sectional study involving nine bronchiectasis centres in Italy. Consecutive adults with bronchiectasis reported symptoms during stable-state and during typical exacerbations over the past 2 years. Symptom frequency, their impact on daily life, and concordance with the 2017 EMBARC/BRR definition were assessed overall and by comorbidity/infection subgroups. Results We enrolled 367 patients (79% female; median age 65 years). During exacerbations, cough (87%), increased sputum volume (81%), and purulence (77%) predominated and clustered with fatigue (72%) and exertional dyspnoea (64%). Patients ranked cough and sputum changes as highest impact. Overall, 85% of typical exacerbations met EMBARC/BRR criteria; exacerbation events that were not concordant with EMBARC/BRR criteria were more frequent in patients with NTM-PD (p=0.004). Patients with asthma/COPD as comorbidity reported more dyspnoea and wheezing, patients with chronic P. aeruginosa infection more frequently reported haemoptysis and nocturnal dyspnoea. Conclusions Exacerbations present with distinct symptom patterns across subgroups, and about one in seven typical patient reported events do not meet consensus criteria, underscoring the need for more sensitive patient-centred definitions.

Metastatic dissemination in lung cancer (LC) and other solid tumors is influenced not only by tumor-intrinsic biology and immune–inflammatory responses, but also by the physical properties of the vascular system through which circulating tumor cells (CTCs) migrate. Peripheral arterial disease (PAD), particularly when manifesting as aneurysmal dilation, is frequent among long-term smokers and is associated with chronic vascular inflammation and altered hemodynamics. We hypothesized that PAD-related vascular remodeling and rheological alterations may influence tumor metastatic capacity. Through a retrospective analysis of 976 patients diagnosed with both cancer and arteriopathy between 2018 and 2024, a cohort of 120 individuals with concomitant aneurysmal and neoplastic disease was identified. Demographic, biochemical, and pathological variables were examined, and metastatic burden at diagnosis was compared with that of an unselected LC population from the same institution and with literature-reported data. We focused on non-small cell lung cancer (NSCLC) as a well-characterized biological model and developed a phenomenological biophysical framework linking inflammation-driven changes in blood viscosity to metastatic competence. A Monte Carlo simulation approach was used to estimate metastasis probability under control and PAD-like rheological conditions. Despite marked male predominance and high smoking exposure, the study cohort exhibited an unexpectedly low metastatic burden, with 13.3% of patients presenting metastatic disease at diagnosis and only 7.6% showing extrathoracic dissemination, compared with an expected rate of approximately 30%. Partition analysis identified arteriopathy as the strongest predictor associated with reduced metastatic dissemination. The rheological model indicated that once inflammation exceeds a critical threshold, increased blood viscosity and disturbed flow patterns may act as a mechanical filter impairing CTC extravasation. Monte Carlo simulations supported this threshold-dependent mechanism, showing an approximately 50% reduction in predicted metastatic rates in PAD-like conditions compared with controls. Collectively, these findings suggest that chronic PAD and aneurysmal vasculopathy may reshape the circulatory microenvironment, with NSCLC providing a mechanistically interpretable framework for a transition from a metastasis-permissive to a metastasis-restrictive rheological regime.

Metastatic dissemination in lung cancer (LC) and other solid tumors is influenced not only by tumor-intrinsic biology and immune–inflammatory responses, but also by the physical properties of the vascular system through which circulating tumor cells (CTCs) migrate. Peripheral arterial disease (PAD), particularly when associated with aneurysmal dilation, is frequent among long-term smokers and is characterized by chronic vascular inflammation and altered hemodynamics. We hypothesized that PAD-related vascular remodeling and rheological alterations may influence tumor metastatic capacity. Through a retrospective analysis of 976 patients diagnosed with both cancer and arteriopathy between 2018 and 2024, a cohort of 120 individuals with concomitant aneurysmal and neoplastic disease was identified, with non-small cell lung cancer (NSCLC) considered the primary biologically interpretable model. Metastatic burden at diagnosis was compared with that of an unselected LC population from the same institution and with literature-reported data. Within this framework, a phenomenological biophysical model was developed linking inflammation-driven changes in blood viscosity to metastatic competence, and a Monte Carlo approach was used to estimate metastasis probability under control and PAD-like conditions. Despite marked male predominance and high smoking exposure, the study cohort exhibited an unexpectedly low metastatic burden, with 13.3% of patients presenting metastatic disease at diagnosis and only 7.6% showing extrathoracic dissemination, compared with an expected rate of approximately 30%. Multivariable analysis and partition modeling identified arteriopathy as the dominant factor associated with reduced metastatic dissemination, whereas conventional tumor and inflammatory biomarkers showed limited explanatory value. The rheological model indicated that once inflammation exceeds a critical threshold, increased blood viscosity and disturbed flow patterns may act as a mechanical filter impairing CTC extravasation. Monte Carlo simulations supported this threshold-dependent mechanism, showing an approximately 50% reduction in predicted metastatic rates in PAD-like conditions compared with controls. Collectively, these findings suggest that chronic PAD and aneurysmal vasculopathy may reshape the circulatory microenvironment, with NSCLC providing a mechanistically interpretable framework for a transition from a metastasis-permissive to a metastasis-restrictive rheological regime.

NTM pulmonary disease (NTM-PD) is frequently associated with low body mass index and weight loss, yet comprehensive nutritional evaluation at diagnosis remains limited. We conducted a multicenter observational study across eight Italian referral centers to assess nutritional status and physical performance in newly diagnosed NTM-PD patients. Assessments included anthropometry, nutritional and physical activity questionnaires, bioelectrical impedance analysis, handgrip strength, gait speed, and pulmonary function tests in order to identify nutritional phenotypes and sarcopenia according to EWGSOP2 definition. 69 patients (77

Chronic obstructive pulmonary disease (COPD) is often associated with cardiovascular disease and the both conditions share common risk factors (smoke), associated pathophysiological mechanisms (pulmonary hyperinflation and vasoconstriction, systemic inflammation and sympathetic activation) and drug use (beta agonists and/or antagonists, steroids, amiodarone). Moreover, COPD is known to be linked to peripheral arterial disease (PAD), mainly represented by aneurysmal dilations. Overall, this chronic immune-inflammatory context might be related to the growth and expansion of malignant clones with specific and well-known biologic traits. Recent improvement in the knowledge of molecular basis of COPD, heart diseases and PAD have pointed out a strong, complex and fascinating relationship linking these conditions, not simply definable as comorbidities. From these premises, we here aim at discussing on the novel and emerging integrated therapeutic perspectives, in some instances exploited from immune-oncology, which strongly deserve a multidisciplinary clinical management.

Non-cystic fibrosis bronchiectasis (NCFB) is a heterogeneous chronic airway disease characterized by irreversible bronchial dilatation, impaired mucociliary clearance, and recurrent infection. Historically, research and clinical practice have focused mainly on bacteria, particularly Pseudomonas aeruginosa, as major drivers of exacerbations and disease progression, whereas the contribution of fungi has received far less attention. Over the last decade, evidence from mycobiome studies, large registries, and prospective cohorts has increasingly identified Aspergillus spp. as clinically relevant contributors in a substantial subset of patients with bronchiectasis. Data from the European Bronchiectasis Registry (EMBARC) indicate that approximately one quarter of patients exhibit Aspergillus-related immunological signals, including allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization, and elevated Aspergillus-specific IgG, and that these phenotypes are associated with more severe disease and worse clinical outcomes. Mechanistic studies further suggest that Aspergillus-related disease in bronchiectasis is underpinned by distinct molecular and immunological programs involving epithelial dysfunction, impaired mucociliary clearance, innate fungal sensing, inflammasome-related signaling, and divergent type-2 versus non-type-2 inflammatory responses. In parallel, mycobiome and multi-biome studies indicate that Aspergillus should be interpreted within a broader airway interactome shaped by cross-kingdom relationships with bacterial pathogens and by host immune tone. In this review, we synthesize current evidence on the epidemiology, molecular pathobiology, inflammatory endotypes, biomarker profiles, clinical-radiologic spectrum, and therapeutic implications of Aspergillus in bronchiectasis. Current evidence suggests that Aspergillus-related findings in bronchiectasis should be interpreted within a structured clinical, radiological, microbiological, and immunological framework rather than considered solely as isolated culture results. However, most data remain observational or extrapolated from related airway diseases, and bronchiectasis-specific interventional evidence is limited. A cautious biomarker-informed approach may help standardize phenotyping, identify patients requiring closer follow-up, and define priorities for future prospective trials.

Metastatic dissemination defines a complex phenomenon driven by genetic forces and, importantly, determined by interaction between cancer cells and the surrounding stroma. Although the biologic and immune reactions which characterize the process have been widely and extensively evaluated, fewer data are available regarding the mechanical and physical forces to which circulating neoplastic clones are exposed. It should be hypothesized that this interaction can be modified in case of concomitant pathologic conditions, such as chronic vasculopathy, which frequently occurs in lung cancer patients. We here aim at analyzing and discussing the complex interplay between lung malignant transformation and arteriopathy, mainly focusing on the immune–inflammatory systemic reaction. Notably—in most instances—smoking-related fixed airflow obstruction, including but not limited to COPD, frequently coexists and contributes to both tumor progression and vascular complications. Attention is paid mainly to the analysis of the role of immune checkpoint inhibitors and their interaction with triple bronchodilation and antiaggregants. Understanding the biomechanical and molecular dynamics of lung cancer progression in altered vascular territories has several translational implications in defining risk stratification and in surgical planning and therapeutic targeting. Moreover, computational modeling of the physical forces which regulate the transit and extravasation of metastatic clones in altered contexts could be of help in deciphering the whole process and in determining more effective blockade strategies.

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: 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.

Cancer progression is a multistep process driving by oncogenic forces and promoted by the close interaction between neoplastic cells and the surrounding microenviroment as well as the pre-metastatic niche. In this perspective the context of chronic arteriopathy represents a specific setting which can be associated with the arousal of lung cancer being and most often the both diseases share smoke as common risk factor. Within respect to the arterial disease we focused on the role of aneurysma dilations and on its impact on blood dynamics in cancer. Through a physical approach we defined a mathematical model which identifies altered viscosity as the physical variable linking cancer to aneurysm-related rheology. To further validate this theroretic approach an extensive screening of 976 patients carried diagnosis of cancer and arteriopaty from 2018 to 2024 was performed. From them a population of 120 cancer patients with concomitant aneurysmal disease was selected. The study cohort was subdivided based on primary site of origin into 3 groups: lung cancer (39 cases), other solid organ cancer (66 cases) and hematologic neoplasms (15 cases). Exaustive demographic, clinical and biologic data were available for each case. A close male gender-specificity was documented (83.3% of cases) as well as significant exposure to cigarette smoke. Quite surprisingly a reduced metastatic potential was reported in in all cancer types.

AimSevere pneumonia management in the hospital setting often relies heavily on established clinical practice and physician experience. This approach has the purpose of enabling early identification of risk factors most strongly associated with severe pneumonia at the time of hospital admission.MethodsThis retrospective study analyzed inpatients with pneumonia treated in a Respiratory disease unit, stratifying them into two groups—severe and non-severe pneumonia — according to the 2007 IDSA/ATS criteria, identifying differences in demographic profiles, clinical features, treatment strategies, and prognostic outcomes.ResultsOut of a cohort of 302 patients, 26 (8.6%) met the criteria for severe pneumonia. A statistically significant difference was observed in the Pneumonia Severity Index (PSI > 90), recorded in 61.53% of patients with severe pneumonia compared to 41.31% in non-severe cases. The Charlson Comorbidity Index (CCI ≥ 4), indicative of lower 10-year survival due to comorbidities, was significantly more frequent in the severe group (84.61% vs. 61.23%). Microbiological analysis of bronchoalveolar lavage (BAL) showed a positivity rate of 75% in the severe group versus 35.48% in the non-severe group (p < 0.05). Significant differences were also found in the use of respiratory support: high-flow nasal cannula (HFNC) was used in 69.23% of severe cases versus 32.97% in non-severe cases, while CPAP was administered in 23.07% versus 5.43%, respectively. Finally, antibiotic therapy was significantly longer in the severe group, with a mean duration of 14.69 days compared to 11.77 days in non-severe patients, involving both intravenous and oral regimens as part of initial or sequential treatment.ConclusionTimely recognition of these factors is essential to ensure optimal patient care, facilitate close monitoring of critically ill individuals, allow for prompt therapeutic escalation, and support ICU admission when needed. This analysis highlights the need for a critical reassessment of existing guidelines and underscores the value of integrating them with real-world clinical experience.

Background: Bronchiectasis is a chronic respiratory condition characterized by permanent bronchial dilation, recurrent infections, and progressive lung damage. A subset of patients, known as frequent exacerbators, experience multiple exacerbations annually, leading to accelerated lung function decline, hospitalizations, and reduced quality of life. The aim of this study is to identify distinct phenotypes and treatable traits in bronchiectasis frequent exacerbators, since it could be crucial for optimizing patient management. Research question: Could clinically distinct phenotypes and treatable traits be identified among frequent exacerbators with bronchiectasis to guide personalized management strategies? Methods: We analysed a cohort of 56 bronchiectasis frequent exacerbator patients using 21 clinically relevant variables, including pulmonary function tests, radiological patterns, and microbiological data. Hierarchical clustering and k-means algorithms were applied to identify subgroups. Key outcomes included cluster-specific characteristics, treatable traits, and their implications for management. Results: Four distinct clusters were identified: 1. Mild, idiopathic bronchiectasis (Cluster 1): Predominantly mild disease (FACED), idiopathic etiology (93.3%), and cylindrical bronchiectasis with moderate obstruction (60%). 2. Rheumatological and NTM-associated bronchiectasis (Cluster 2): Patients with systemic inflammatory diseases (50%) and NTMever (50%) but minimal infections by Pseudomonas aeruginosa. 3. Mild, post-infective bronchiectasis (Cluster 3): Exclusively mild disease, mixed idiopathic and post-infective etiologies, and preserved lung function. 4. Severe, chronic infection phenotype (Cluster 4): Severe disease with high colonization rates of Pseudomonas aeruginosa (71.4%), advanced structural damage (57.1% varicose, 50% cystic bronchiectasis), and frequent exacerbations. Interpretation: This analysis highlights the heterogeneity of bronchiectasis and its frequent exacerbator phenotype. The treatable traits framework underscores the importance of aggressive infection control and management of airway inflammation in severe cases, while milder clusters may benefit from preventive strategies. These findings support the integration of precision medicine in bronchiectasis care, focusing on phenotype-specific interventions to improve outcomes.

Bronchiectasis is a chronic and heterogeneous respiratory condition, which is characterized by irreversible abnormal dilatation of the bronchial tree, chronic cough, copious sputum production, and increased risk of acute exacerbations that contribute to the development of chronic respiratory failure, poor exercise tolerance and, consequently, poor quality of life (QoL). A large amount of published data explore regarding the diagnostic approach, the clinical management, and the development of novel therapeutic strategies. Moreover, it is well-known that the exercise-training rehabilitation can be helpful in reducing disease deterioration and relieve symptoms. However, the effect of exercise in patients with non-cystic fibrosis-related bronchiectasis (NCFB) is scarce, and no athletic programs have been fully developed. Thus, the aim of the present study is to investigate the results obtained by administering a specific athletic/physical protocol to these patients. Among all patients affected by NCFB and followed in our Institution, those with the highest scores of performance status will be addressed to the Interdipartimental Centre in Motor and Sport Activities, Sport Medicine Centre, University of Pavia for a work protocol based on mesocycles of 3 times/week for 6 months. A patient-tailored active training regimen will be set up considering major complaints—endurance training for patients with dyspnea, strength training for patients with cough and difficult sputum expectoration, and a balanced aerobic and anaerobic training for patients with asthenia. To the best of our knowledge, the ATHOS study is the first perspective clinical trial, encompassing athletic programs for non-CF bronchiectasis patients, and rationale and in itinere, partial results will be presented, analyzed, and discussed in comparison to standard disease management.