OBJECTIVE:Idiopathic pulmonary fibrosis (IPF) and systemic autoimmune rheumatic disease (SARD)-associated interstitial lung disease (ILD) are lung disorders with distinct clinical trajectories. This study aimed to compare survival and pulmonary function trends between IPF and SARD-ILD. METHODS:We retrospectively analyzed 410 patients with ILD (154 IPF, 256 SARD-ILD) from 6 Italian centers. SARD-ILD subtypes included antisynthetase syndrome (ASyS; n = 58), dermatomyositis (DM; n = 55), systemic sclerosis (SSc; n = 106), and Sjögren disease (SjD, n = 37). Outcomes included 5-year survival and pulmonary function test (PFT) changes. RESULTS:Five-year survival was lower in patients with IPF (mean 33.6 months) than in those with SARD-ILD (mean 56.0 months; P < 0.001). SARD subtypes showed comparable survival: 58.2 months in patients with ASyS, 52.9 months in DM, 55.2 months in SSc, and 58.6 months in SjD. Patients with ASyS and DM demonstrated significant functional improvement, with forced vital capacity (FVC) increasing from 71% to 81% in ASyS (+14.1% relative) and from 69% to 78% in DM (+13%). IPF FVC declined from 78% to 72% (-7.7%). Usual interstitial pneumonia pattern was universal in IPF but seen in < 20% of patients with SARD-ILD. ILD pattern did not significantly influence functional trajectory in patients with SARD-ILD; instead, diagnosis was the primary determinant (multivariable ANOVA P < 0.001). Multivariable analysis confirmed SARD-ILD as a favorable prognostic factor (adjusted hazard ratio [aHR] 0.21), with age (aHR 1.06) and male sex (aHR 1.98) linked to poorer outcomes. CONCLUSION:SARD-ILD is associated with higher survival than IPF. Functional trajectories improved in patients with ASyS and DM, in contrast to the decline observed in those with IPF. Prognosis is more strongly influenced by the underlying diagnosis, supporting a diagnosis-centered approach to disease management.

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: Breath-hold training (BHT) has emerged as a novel strategy to enhance metabolic efficiency and autonomic resilience in national-level athletes. This signal-generating single-case study examined physiological and neuroendocrine adaptations to an eight-week BHT program in a nationally ranked competitive swimmer. Methods: A national-level 23-year-old female freestyle sprinter (50 m best time = 26.59 s; 100 m = 60.40 s) completed three weekly BHT sessions integrated into her regular training. Pre- and post-intervention assessments included an incremental Mader cycling test with measurements of blood lactate ([La−]), heart rate (HR), salivary cortisol (sCort), and salivary alpha-amylase (sAA). Blood chemistry and pulmonary function, including diffusing capacity of the lung for carbon monoxide (DLCO), were also evaluated. Results: Post intervention, the athlete demonstrated reduced [La−] and HR at all workloads, a 20 W increase in power at 4 mmol·L−1 [La−], and an elevated final workload achieved during the Mader test. Salivary stress biomarkers showed blunted responses with significant reductions in area under the curve and large effect sizes. These changes were observed under standardized pre-analytical conditions and individualized training adjustments. Conclusions: This study highlights coordinated improvements in metabolic, cardiovascular, and stress regulation mechanisms following BHT in a swimmer with verified national-level performance benchmarks. BHT, when applied in sport-specific contexts, may serve as an effective adjunct to high-performance training.

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by alveolar-capillary membrane remodeling and impaired gas diffusion. The diffusing capacity of the lung for nitric oxide (DLNO) has been proposed as a physiological parameter reflecting membrane diffusing capacity and pulmonary vascular involvement, potentially providing complementary information to diffusing capacity of the lung for carbon monoxide (DLCO). This study aimed to evaluate the role of DLNO in the functional assessment of patients with IPF and its correlation with clinical and echocardiographic outcomes. Materials and Methods: This observational, retrospective study included 35 consecutive IPF patients receiving antifibrotic therapy between February and December 2023. All participants underwent plethysmography, combined single-breath DLNO and DLCO testing, six-minute walk test (6MWT), mMRC dyspnea scale assessment, and echocardiography for the estimation of a higher probability of pulmonary hypertension (PH). Results: DLNO was significantly lower in males compared to females (49.3 ± 16.7% vs. 74.6 ± 16.1%, p < 0.001), with a reduced DLNO/DLCO ratio in men. DLNO correlated with oxygen therapy requirement (p = 0.010) and lower oxygen saturation during the 6MWT (p = 0.021). Patients with higher echocardiographic probability of PH showed markedly reduced DLNO values (17.6 ± 7.6%, p = 0.016) and higher FVC/DLNO ratios (2.31 ± 0.85 vs. 1.65 ± 0.64, p = 0.023), together with lower DLCO levels (p = 0.037). Conclusions: DLNO may complement DLCO in the evaluation of gas exchange and alveolar-capillary dysfunction in IPF. Although preliminary, these findings support the potential clinical utility of DLNO as an adjunct parameter in the functional characterization of IPF. Further multicenter studies are warranted to confirm these results.

INTRODUCTION:Sex influences asthma phenotypes and treatment outcomes. However, real-world data on sex-related differences in severe asthma patients treated with biologics are limited. The objective of this study was to assess sex differences in baseline characteristics and treatment outcomes in a cohort of severe eosinophilic asthma (SEA) patients treated with biologics. METHODS:We retrospectively analyzed 370 SEA patients (235 females, 135 males) treated with mepolizumab, benralizumab, or dupilumab. Clinical remission was defined as no OCS use plus at least two of: no exacerbations, ACT ≥20, or FEV1 >80%. Logistic regression was used to identify sex-specific predictors of remission at 24 months. RESULTS:Severe type 2 asthma showed a prevalence in females (female-to-male ratio of 1.7:1). Baseline characteristics revealed higher prevalence of obesity (p = 0.015) and osteoporosis (p = 0.006) in females, and greater tobacco exposure (p = 0.05), FeNO (p = 0.03), and nasal polyposis (p = 0.0002) in males. Males had greater reduction in FeNO (p ≤ 0.05) and more male patients stopped exacerbations at 24 months (p < 0.0001), while females showed greater FEF25-75% (p ≤ 0.05) improvement and larger IgE drops (p < 0.0001). Remission rates were similar across sexes at both 12 months (64.3% versus 74.1%; p = 0.06) and 24 months (71.5% versus 77.0%; p = 0.27). In females, remission was associated with eosinophils >300/μL (OR: 2.68; 95% CI: 1.41-5.07; p = 0.003), FeNO >50 ppb (OR: 21.05; 95% CI: 10.24-43.34; p < 0.0001), and nasal polyposis (OR: 2.74; 95% CI: 1.46-5.13; p = 0.001); obesity (OR: 0.20; 95% CI: 0.11-0.37; p < 0.0001), smoking (OR: 0.38; 95% CI: 0.21-0.70; p = 0.002), anxiety (OR: 0.47; 95% CI: 0.23-0.94; p = 0.04), and reflux (OR: 0.47; 95% CI: 0.27-0.84; p = 0.01) were negative predictors. In males, OCS dependency (OR: 0.35; 95% CI: 0.13-0.94; p = 0.03) and FEV1 <80% (OR: 0.18; 95% CI: 0.05-0.63; p = 0.004) were negative predictors. CONCLUSION:Biologics were equally effective in inducing clinical remission across sexes, but different predictors influenced outcomes. Sex-aware strategies may support personalized asthma care.

Patient awareness extends beyond factual knowledge, encompassing emotional and cognitive engagement with the disease. As in other chronic diseases, it plays a critical role in asthma management. A comprehensive, validated tool for assessing this multifaceted construct in patients with asthma has been lacking. This study aimed to develop and validate the Asthma Awareness Questionnaire (AAQ) within the framework of the Mild/Moderate Asthma Network of Italy (MANI) study, a real-world, prospective, longitudinal cohort study involving adults diagnosed with mild-to-moderate asthma according to Global Initiative for Asthma (GINA) 2020 criteria. The questionnaire was developed through a Delphi process involving clinicians and patients. Psychometric properties (scale dimensions, internal validity, construct validity, and reliability) were explored, as well as the total and domain level of awareness. Starting from an initial list of 39 items, the Delphi process led to a provisional 22-item version. A total of 149 participants completed the AAQ at baseline and 6-month follow-up visit. Exploratory and confirmatory factor analyses supported a three-factor structure—agency, knowledge, and acceptance—with the exclusion of four items. Internal consistency (Cronbach’s α = 0.78), construct validity (assessed through correlations with established patient-reported outcome measures), and test–retest reliability (ICC = 0.723) were assessed. Awareness levels were suboptimal overall (mean total score ≈ 60/100), with knowledge scores nearing the 80/100 threshold, while agency and acceptance lagged. The AAQ is a psychometrically sound instrument that captures the multidimensional nature of asthma awareness. Its use may guide future interventions aimed at improving patient self-management. Further validation in broader clinical settings is warranted. ClinicalTrials.gov identifier, NCT12345678.

A substantial proportion of patients with asthma remain uncontrolled despite high-dose ICS/LABA therapy, often due to persistent small-airway dysfunction and heightened cholinergic activation. Acetylcholine (ACh) produced by neuronal and non-neuronal airway cells amplifies inflammation, bronchoconstriction, and remodelling. Exhaled breath condensate (EBC) provides a non-invasive means to sample the distal airways, but ACh has never been quantified in EBC in asthma. Extrafine single-inhaler triple therapy (SITT) may modulate cholinergic activity through muscarinic blockade and improved small-airway deposition. To determine whether ACh concentration in EBC (ACh-EBC) distinguishes patients with not-well-controlled asthma on high-dose ICS/LABA from those achieving good control under extrafine SITT, and to evaluate its relationship with functional and inflammatory markers. In this cross-sectional observational study, 22 adults with asthma managed at the University Hospital of Bari were stratified by asthma control and treatment: uncontrolled asthma on high-dose ICS/LABA (n = 15) and controlled asthma on extrafine SITT (n = 7), alongside healthy controls (n = 7). ACh-EBC was quantified using a competitive high-sensitivity ELISA (A3574). Secondary assessments included FeNO50/FeNO350, spirometry, plethysmography, and impulse oscillometry (IOS). Group comparisons, ROC analysis, and discriminant analysis were performed. ACh-EBC exhibited a clear gradient: highest in uncontrolled ICS/LABA patients (3.23 pg), intermediate in SITT-controlled patients (2.97 pg), and lowest in healthy controls (2.75 pg; p = 0.001). Fres was significantly higher in uncontrolled asthma (18.80 vs. 13.50 Hz; p = 0.037), while FeNO50 was also elevated (p = 0.037). ROC analysis showed strong discriminatory accuracy for ACh-EBC (AUC 0.867; p = 0.007), with an optimal threshold of 3.000 pg. A multivariable discriminant model combining oscillometric and biochemical markers achieved 77.3% cross-validated accuracy. ACh-EBC is a promising non-invasive biomarker reflecting cholinergic activation and small-airway dysfunction in asthma. Elevated ACh-EBC identifies patients remaining uncontrolled on ICS/LABA, whereas lower levels in those receiving extrafine SITT mirror improved control and reduced cholinergic signalling. Integration of ACh-EBC with FeNO and IOS indices may support precision-medicine approaches aimed at identifying cholinergic-driven asthma and optimizing escalation to triple therapy.

IntroductionAsthma is often treated with oral corticosteroids (OCS), despite their association with significant adverse effects. While guidelines recommend minimizing OCS use through alternative therapies and patient-centered approaches, discrepancies between recommendations and real-world practices persist. This study evaluates OCS usage patterns and barriers to adherence to asthma treatment guidelines in Italy, using surveys conducted with healthcare professionals (HCPs) and patients.MethodsTwo cross-sectional surveys were administered between January and March 2024 to HCPs and asthma patients. The surveys assessed OCS prescription practices, treatment adherence, patient involvement, adverse event management, and perceptions of OCS use. Descriptive analysis was performed to identify patterns and highlight gaps in current practices.ResultsThe surveys revealed considerable variability in OCS prescribing practices, treatment duration and daily dosages. Over 80% of patients reported using OCS and 18% of HCPs believed that the maximum daily doses of OCS are higher than the guideline-recommended doses. Patients did not feel fully involved in treatment decisions, with over 40% of patients reporting unsatisfactory communication about treatment alternatives or adverse effects. Barriers to optimal care included inadequate access to specialists, inconsistent monitoring protocols, and a lack of multidisciplinary approaches. Both HCPs and patients highlighted the need for clearer definitions of OCS dependency and enhanced tools for tracking treatment adherence.DiscussionThe findings underscore the urgent need for systemic reforms to align clinical practice with guidelines. These include establishing pragmatic definitions for OCS dependency, promoting multidisciplinary care, and leveraging technology for monitoring. Addressing psychosocial factors and empowering patients through education and shared decision-making are also critical.

Although 90% of asthmatic patients suffer from mild and moderate disease, little is known about the burden on health status and quality of life, the long-term trajectory of disease severity, and the socio-economic impact. The Mild Moderated Asthma Network of Italy (MANI) is a real-world, cross-sectional, prospective, observational cohort study designed to explore these issues. Here we aimed to provide an identikit of asthmatic patients receiving treatment according to GINA steps 1–4, and enrolled in the centers of excellence participating in the MANI. Among 679 analyzed patients, 63% were female, and the mean age was 50 ± 16 years. Asthma was mild in 15.8% of patients (GINA steps 1–2) and moderate in 84.2% (GINA steps 3–4). The mean age of asthma diagnosis was 34.3 ± 17.7 years, 50% of patients were suffering from allergic rhinitis, and 13% from nasal polyposis. Mean FEV1% was 91.4 ± 19.4%, predicted with a FEV1/FVC ratio of 74.7 ± 11.9. The mean asthma control test value was 21.2 ± 3.73, and AQLQ score was 5.74 ± 1.07. Among the included patients, 17.2% had at least one asthma exacerbation in the previous year, with 14.2% requiring systemic steroids; 6.2% were referred to an emergency room in the year prior to enrollment; 2.2% required an asthma-related hospitalization; and 0.6% had been admitted to an Intensive Care Unit (ICU). Unscheduled visits were necessary for 3.8% of patients, 6.5% reported ≥5 lost work days due to asthma, and 11.5% declared ≥10 lost days of spare time. About 70% of patients were receiving treatment according to GINA Track 1. Uncontrolled cases constituted 16.7% of patients treated according to GINA steps 1–2, and 26.3% of patients treated according to GINA steps 3-4 were uncontrolled. Compared to patients with mild asthma, those with moderate asthma had more impaired lung function (FEV1% 88.5 ± 18.4 vs 94.4 ± 17.9, p = 0.05; FEV1/FVC 73.0 ± 9.76 vs 79.6 ± 9.56, p > 0.001), exhibited greater need for systemic corticosteroids for treating exacerbations (13.8% vs 2.3%, p = 0.032), and showed greater adherence to therapy (TAI score 50.0 ± 5.66 vs 45.7 ± 8.42, p < 0.001). Overall, mild/moderate asthma exhibited a substantial clinical and care impact. Patients treated with GINA steps 3–4 constituted the vast majority of patients attending specialist centers. A quarter of these patients were uncontrolled, and therefore need re-evaluation or treatment upgrade. Expanding recruitment of the MANI study will allow further phenotyping of these patients.

Background: Pulmonary hypertension (PH) is a condition characterized by increased pressure in the pulmonary arteries with poor prognosis and, therefore, an optimal management is necessary. The study’s aim was to search for PH phenotypes and develop a predictive model of five-year mortality using machine learning (ML) algorithms. Methods: This multicenter study was conducted on 122 PH patients. Clinical and demographic data were collected and then used to identify phenotypes through clustering. Subsequently, a predictive model was performed by different ML algorithms. Results: Three PH clusters were identified: Cluster 1 (mean age 68.57 ± 10.54) includes 57% females, 69% from non-respiratory PH groups, and better cardiac (NYHA class 2.61 ± 0.84) and respiratory function (FEV1% 78.78 ± 21.54); Cluster 2 includes 50% females, mean age of 71.36 ± 8.32 years, 44% from PH group 3, worse respiratory function (FEV 1% 68.12 ± 10.20); intermediate cardiac function (NYHA class 3.18 ± 0.49) and significantly higher mortality (75%); Cluster 3 represents the youngest cluster (mean age 61.11 ± 13.50) with 65% males, 81% from non-respiratory PH groups, intermediate respiratory function (FEV1% 70.51 ± 17.91) and worse cardiac performance (NYHA class 3.22 ± 0.58). After testing ML models, logistic regression showed the best predictive performance (AUC = 0.835 and accuracy = 0.744) and identified three mortality-risk factors: age, NYHA class, and number of medications taken. Conclusions: The results suggest that the integration of ML into clinical practice can improve risk stratification to optimize treatment strategies and improve outcomes for PH patients.

Background: Obstructive sleep apnea (OSA) is a heterogeneous disorder associated with substantial cardiometabolic and neurocognitive morbidity. Although the apnea-hypopnea index (AHI) remains the conventional measure of OSA severity, it only partially reflects the underlying pathophysiological complexity. Growing evidence indicates that nocturnal hypoxemia may be a more powerful marker of adverse outcomes than event frequency alone. Therefore, this study aimed to identify distinct OSA phenotypes based on oximetry-derived features and to assess whether these profiles offer additional clinical insight beyond traditional AHI-based classification. Methods: This multicenter retrospective study, part of the Living with OSA and CPAP: The Apulia Region Experience project, included 1386 adults diagnosed with OSA across 15 sleep centers in Southern Italy. Standardized clinical, anthropometric, and polysomnographic (PSG) data were collected. Hierarchical clustering analysis was performed based on PSG oximetry-derived variables. Resulting clusters were compared across demographic, clinical, hypoxemic, and therapeutic features. Results: Three reproducible clusters emerged. Cluster 1 (mild-non-obese) included younger, leaner patients with lower AHI (22.9 ± 10.5 events·h-1), minimal desaturation (T90 5.6 ± 7.6%), and limited comorbidities. Cluster 2 (severe-obese-hypoxemic) represented the most critical phenotype, characterized by marked obesity (BMI 39.2 ± 8.2 kg·m-2), severe OSA (AHI 74.9 ± 17.9 events·h-1), profound nocturnal hypoxemia (T90 51.5 ± 28.2%), and a high prevalence of metabolic disorders (76%), requiring higher CPAP pressures and frequent oxygen supplementation. Cluster 3 (older-comorbid) comprised older males (63.7 ± 11.8 years) with moderate-to-severe OSA (AHI 44.8 ± 15.2 events·h-1) and multiple cardiometabolic comorbidities. Conclusions: Oximetry-derived variables identify distinct and clinically meaningful OSA phenotypes that extend beyond traditional AHI-based classification. Recognizing hypoxemia-driven subtypes could improve risk stratification and enable more personalized management strategies in clinical practice.

INTRODUCTION The use of corticosteroids in respiratory infections remains a topic of clinical debate, particularly regarding indications, frequency, and alignment with patient phenotypes. We aimed to analyze prescribing patterns, decision-making processes, and perceived efficacy of corticosteroids across a diverse group of physicians. METHODS Within a cross-sectional survey, we analyzed responses from 203 physicians across various medical specializations, with a majority representing pulmonology (73.89%). The survey was conducted in Italy between March and June 2024 using an anonymous, structured online questionnaire. Eligible participants were practicing physicians with at least one year of experience in managing respiratory infections; trainees and non-clinical professionals were excluded. An anonymous, structured questionnaire explored prescribing rationales, frequencies, inflammatory phenotype considerations, and biomarker utilization. Data were analyzed using descriptive statistics and chi-squared tests, with statistical significance set at p<0.05. RESULTS Key findings revealed that inflammation reduction (60.59%) was the predominant reason for corticosteroid use, with eosinophilic inflammation guiding prescriptions in 39.90% of cases. Inhaled corticosteroids were generally preferred over oral formulations (60.10%). Despite a reliance on clinical judgment (44.33%), biomarker-driven approaches remain underutilized. Statistically significant differences were observed in phenotype-based prescribing and biomarker monitoring, indicating variability in decision-making. CONCLUSIONS These findings underscore the need for standardized guidelines and personalized therapeutic strategies. The observed gaps in biomarker utilization and inflammatory phenotyping highlight areas for improvement. Future research should focus on integrating standardized diagnostic approaches to enhance treatment precision and optimizing patient outcomes.

Background: The current availability of monoclonal antibodies against key mediators of type-2 (T2) inflammation has led to a redefinition of the ultimate objectives of severe asthma treatment to a more composite concept of disease remission. Objectives: The aim of this real-life study was to estimate the percentage of patients who achieved clinical remission over 4 years of treatment with benralizumab, and to identify baseline predictors for the achievement of such a composite outcome in the long term. Methods: Data from a 4-year follow-up of 23 patients who were prescribed benralizumab as an add-on therapy because of uncontrolled severe eosinophilic asthma were retrospectively analyzed and compared. Clinical remission was considered to be “complete” if oral corticosteroid (OCS) use was not required, there were no exacerbations, an asthma control test (ACT) score ≥ 20 was achieved and a pre-bronchodilation percent predicted a forced expiratory volume in 1 s (FEV1%) ≥ 80%. Clinical remission was considered to be “partial” if OCS use was not required, plus at least two of the other three aforementioned criteria. Results: The overall percentage of patients who achieved clinical remission was 86.9% after 12 months, and 91.3% after 24 and 48 months of treatment. The rate of complete remission over partial remission increased over time. After 12 months of treatment, 65% of patients fulfilled the criteria for complete remission and 35.0% for partial remission. After 48 months of treatment, 71.4% of patients were in a status of complete remission and 28.6% in a status of partial remission. A long-term composite outcome of complete clinical remission was more likely to be achieved by severe eosinophilic asthma patients with comorbid nasal polyposis, bronchiectasis and osteoporosis, and with OCS dependency, a predicted pre-bronchodilation FEV1% ≥ 80% and a predicted FEF25–75% < 65% at baseline. Conclusions: Our real-life experience suggests that treatment with benralizumab may allow the achievement and long-term maintenance of clinical remission in a high percentage of severe eosinophilic asthma patients, up to 4 years of follow-up.

BACKGROUND:Asthma with low levels of type 2 (T2) biomarkers is poorly understood. OBJECTIVE:To characterize severe asthma phenotypes and compare changes in asthma outcomes from pre- to postbiologic treatment along a gradient of T2 involvement. METHODS:This was a registry-based cohort study including data from 24 countries. Biomarker distribution (blood eosinophil count, fractional exhaled nitric oxide, and IgE) was quantified before biologic initiation. Clusters were identified using a 5-component Gaussian finite mixture model and phenotypically characterized. Changes in asthma and health care utilization outcomes between 1-year pre- and postbiologic initiation were compared between clusters and by biologic class. RESULTS:Among 3675 patients, 5 biomarker clusters were identified along a gradient of T2 involvement: cluster A with the lowest T2 involvement (16.4%), cluster B (20.4%), cluster C (22.9%), cluster D (30.3%), and cluster E with the highest T2 involvement (10.0%). In multivariable analysis, biologic use was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. For example, patients in cluster C had a significantly greater increase in forced expiratory volume in 1 second compared with cluster A (difference 0.16 L [95% confidence interval: 0.08, 0.25]; P < .001). The odds of uncontrolled asthma were approximately 0.6 for all clusters compared with cluster A. Overall, exacerbation rates were lower, and greater improvements in lung function and asthma control were noted for anti-IL-5/5 receptor (R) (but not anti-IgE or anti-IL-4Rα) for all clusters compared with cluster A. CONCLUSION:T2-targeting biologics have utility in the management of asthma with low T2 involvement, but more effective therapies are needed. Further research is warranted to identify specific pathogenic pathways at the lower end of the T2 spectrum that can be effectively targeted by biologics.