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ABSTRACT Objective: There has been limited research comparing the inflammatory characteristics of moderate and severe asthma in Brazil. To describe and compare the phenotypes of moderate asthma (MA) and severe asthma (SA) in Brazilian patients. Methods: In this cross-sectional study, we defined SA per the 2014 European Respiratory Society/American Thoracic Society criteria and MA per the 2018 GINA criteria. No participants had other lung diseases, recent respiratory infection, or a recent exacerbation. Asthma was characterized and phenotyped by using validated tests. Results: Compared to MA (n = 55), SA (n = 51) had more hospital (p < 0.001) and ICU admissions (p = 0.01), worse fixed airflow limitation (FEV1/FVC post-BD = 0.61; p < 0.001), poorer asthma control (p = 0.001), and reduced quality of life. However, this was not associated with higher activity of inflammation as measured by IS and Beos counts, which were similar. In addition, of the 19 patients with MA who reported ≥ 1 exacerbation in the last year, 12 (63.1%) had residual eosinophilia in induced sputum, compared with 22 (62.8%) of the 35 such patients with SA. The correlation between IS eosinophils and Beos was strong (rs = 0.75, R2 = 0.35; p < 0.001), though agreement was moderate. T2 phenotypes were predominant (76% in both groups). However, in the MA group, the prevalence of eosinophilic allergic asthma was higher than that of nonallergic asthma (56% vs. 20%; p < 0.001). In the SA group, those phenotypes had a similar prevalence (41% and 35%, respectively). Conclusions: Our analysis indicates that most subjects with SA or MA have the T2-high asthma phenotype, primarily allergic eosinophilic, in MA. Significant residual eosinophilic airway inflammation and recurrent exacerbations in some patients with MA suggest the need for further research on the optimal timing for

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ABSTRACT Objective: Obstructive sleep apnea (OSA) of varying severity significantly impacts mental health and quality of life. Recent studies have identified different OSA phenotypes, emphasizing symptom-based patient profiles. We sought to determine the association between symptom-based OSA phenotypes and depression. Methods: This was an observational study including 1,083 patients (883 men and 200 women) who were part of a previous cohort study and who had been diagnosed with OSA on the basis of an apnea-hypopnea index ≥ 5 events/h on a home sleep apnea test. Sleep-related symptoms were assessed by the Epworth Sleepiness Scale (ESS) and self-reported sleep patterns. Objective respiratory parameters derived through polysomnography were used in order to characterize OSA severity. Depressive symptoms were evaluated with the Beck Depression Inventory (BDI). Cluster analysis defined three groups: nonsleepy patients; patients with disturbed sleep; and patients with excessive daytime sleepiness. Linear regression models were adjusted for age, sex, BMI, respiratory disturbance index, and total sleep time. A sensitivity analysis correlated ESS scores and total sleep time with BDI scores by means of Spearman correlation. Results: The median respiratory disturbance index was 21.6 events/h (IQR, 12.4-38.1), and the median ESS score was 8.0 (IQR, 5.0-12). A total of 431 patients (39.8%) were nonsleepy, 485 (44.7%) had disturbed sleep, and 167 (14.4%) presented with excessive daytime sleepiness, with a median BDI score of 12 (IQR, 6.0-53.1). Linear regression revealed higher depressive symptoms in patients with disturbed sleep and in those with excessive daytime sleepiness. Conclusions: Patients with excessive daytime sleepiness and OSA have a higher risk of poor mental health. This underscores the need to address physiological and psychological aspects of OSA for improved patient well-being.

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ABSTRACT Objective . Spirometry is the gold standard among pulmonary function tests, with acceptability criteria established to ensure reliable results. However, variability in the interpretation of spirometry by trained reviewers remains unexplored. This study assessed agreement among trained reviewers regarding spirometric acceptability and its components, including the number of acceptable maneuvers, predominant defect, and repeatability. Methods . Spirometries from 3,982 adults (≥40 years) participating in an epidemiological study across six cities in Argentina were independently reviewed by junior reviewers (JRs) and adjudicated by senior reviewers (SRs), following the 2005 ATS/ERS guidelines. Agreement was analyzed using Cohen’s kappa, McNemar’s test, and proportion comparisons. Results . A total of 7,964 pre- and post-bronchodilator spirometries were analyzed. Agreement on overall acceptability between JRs was 76% and 84% in two independent reviewer teams (RvTa and RvTb, respectively). Agreement on specific defects was highest for numerical criteria, such as insufficient expiratory time (k=0.61) and excessive back-extrapolated volume (BEV; k=0.52), but lower for subjective criteria, including weak effort (k=0.19) and cough in the first second (k=0.36). No agreement was observed for glottic closure (k=0). SR adjudication increased the proportion of acceptable tests from 54% to 65%. Conclusions: Reviewer variability significantly affects spirometric acceptability, with numerical criteria achieving higher agreement than subjective assessments. These discrepancies have implications for large-scale studies, data quality, and automated algorithm development. Cross-checking reviews is recommended to enhance reliability. Further standardization of acceptability criteria is warranted.

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ABSTRACT Objective: To describe the spatial distribution of spirometry tests recorded in the Brazilian Sistema Único de Saúde (SUS, Unified Health Care System) in 2023 and 2024. Methods: This was a population-based observational study analyzing all spirometry records in the SUS Outpatient Database for the 2023-2024 period across all 5,570 Brazilian municipalities. Rates of spirometry per 100,000 population were calculated by using population projections from the Brazilian Institute of Geography and Statistics, considering only individuals ≥ five years of age, and subtracting those with private health insurance-as per data from the National Regulatory Agency for Private Health Insurance and Plans. Results: A total of 718,464 spirometry tests were recorded in the SUS during the study period (341,654 in 2023 and 376,810 in 2024). The tests were performed in only 398 municipalities (7.1% of the total number of Brazilian municipalities). It is estimated that approximately 83.5 million individuals, representing 61% of the SUS-dependent population, live in municipalities without any records of spirometry. The median distance to the nearest municipality with spirometry was 50 km, being as high as 902 km in remote areas of the Amazon region. The southeastern region had the highest proportion of municipalities providing the test (11.6%), and the northern region had the lowest (2.7%). Among the state capitals, there was marked heterogeneity in test rates, with Vitória at the top (with 2,406 tests per 100,000 population) and Macapá recording no tests. Conclusions: Access to spirometry in the SUS is highly unequal, with severe geographic and population-based disparities. A significant proportion of the population lacks local availability, often requiring long travel distances to have access to spirometry.

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ABSTRACT Objective: Pembrolizumab monotherapy is an established first-line treatment option in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) expressing programmed death ligand 1 (PD-L1) with a tumour proportion score (TPS) ≥ 50%. However, real-life data are scarce. The aim of this study was to evaluate the effectiveness and safety of pembrolizumab in such patients and to identify predictive factors for progression-free survival (PFS) and overall survival (OS). Methods: This was a retrospective observational study of patients with advanced/metastatic NSCLC, expressing PD-L1 with a TPS ≥ 50%, treated with first-line pembrolizumab monotherapy at a Portuguese centre between January of 2017 and December of 2023. We assessed PFS, OS and safety. Results: Of the 101 patients included, 67.3% were men, 92.1% were White, 89.1% had a performance status 0-1, 76.2% had a non-squamous histology and 90.1% had metastatic disease. The median age was 65 years. The median PFS and OS were 11.0 months (95% CI: 7.03-14.97) and 15.0 months (95% CI: 10.81-19.19), respectively. Immune-mediated adverse events occurred in 31.7% of the cases. Multivariate analysis identified squamous histology as a negative predictive factor for PFS (HR = 2.60; 95% CI: 1.48-4.50; p = 0.001) and OS (HR = 2.28; 95% CI: 1.30-3.97; p = 0.004) and showed brain metastases to be associated with shorter OS (HR = 1.98; 95% CI: 0.90-4.36; p = 0.026). Conclusions: This study supports the effectiveness and safety of first-line pembrolizumab monotherapy in patients with advanced/metastatic NSCLC expressing PD-L1 with a TPS ≥ 50%, highlighting the disparity of outcomes according to histology.

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ABSTRACT Objective: Chronic cough (CC)-i.e., cough lasting for ≥ 8 weeks- is a common and burdensome symptom in asthma patients; however, its pathophysiological mechanisms and clinical relevance remain unclear. We sought to investigate clinical, functional, and inflammatory differences between asthma patients with chronic cough (ACC) and those without. (ANCC) Methods: We included 344 patients with moderate-to-severe asthma evaluated at a referral center from 2017 to 2024. Clinical data, lung function, inflammatory biomarkers, and health resource utilization were compared between ACC and ANCC. Further analyses stratifying patients by sputum eosinophil percentage (≥ 3% vs. < 3%) and CC were also performed. Multivariate logistic regression was used to identify factors independently associated with chronic cough. Results: ACC (n = 124; 36%) had significantly worse asthma control (ACQ: p = 0.001), as well as higher number of exacerbations (p = 0.011), health care utilization, (p < 0.0001) and treatment dose of inhaled corticosteroids, (p = 0.004) when compared with ANCC. Despite similar lung function and inflammatory biomarkers, dyspnea, nocturnal symptoms, Cumulative Illness Rating Scale scores, and health care use were independently associated with CC. Further stratifications by sputum eosinophil percentage and CC revealed that ACC experienced a greater disease burden, regardless of whether sputum eosinophil percentage was ≥ 3% or < 3%. Conclusions: CC identifies a subgroup of asthma patients with poorer disease control, increased health care needs, and distinct clinical profiles, independently of airway inflammation. Routine recognition of cough as a symptom in asthma assessment may guide referral and personalized management.

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ABSTRACT Objective: Diagnosis of interstitial lung diseases (ILDs) relies on multidisciplinary discussion. However, when uncertainty persists, histopathological evaluation is required. Surgical lung biopsy (SLB) offers high diagnostic yield but carries relevant morbidity and non-negligible mortality. Although transbronchial lung cryobiopsy (TBLC) has emerged as a less invasive alternative, its economic impact on middle-income countries remains underexplored. This study sought to evaluate the cost-effectiveness of TBLC in comparison with that of SLB for the diagnosis of ILDs from the perspective of the Brazilian public health care system. Methods: A decision tree model compared three strategies in a hypothetical cohort of 100 patients: standalone TBLC, standalone SLB, and a step-up strategy starting with TBLC and reserving SLB for inconclusive cases. Model probabilities were obtained from an umbrella review and Brazilian public health care system data. Direct medical costs were estimated by microcosting. Sensitivity analyses assessed model robustness. Results: Mean costs (in Brazilian reals [BRL]) were BRL 5,623.34 for TBLC and BRL 22,855.94 for SLB (including hospitalization). The step-up strategy was the most cost-effective, yielding higher effectiveness than standalone SLB and saving approximately BRL 1.3 million per 100 patients. The step-up approach remained dominant in sensitivity analyses. Conclusions: In the Brazilian public health care system, a step-up diagnostic pathway using TBLC first and SLB only if necessary maximizes diagnostic yield while reducing costs, hospitalizations, and mortality. These findings support TBLC as the initial procedure of choice for ILD evaluation and reinforce alignment with international evidence. They may guide policy and resource allocation in Brazil and other countries with similar health care systems.

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ABSTRACT Objective: Critically ill patients with respiratory disease often experience impaired airway clearance, which contributes to adverse clinical outcomes. N-acetylcysteine (NAC) has mucolytic and antioxidant properties, and may have therapeutic potential in this setting. This study evaluated the impact of NAC on clinical outcomes in ICU patients with underlying respiratory disease. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from January of 2000 to July of 2025 in order to identify randomized controlled trials evaluating NAC in ICU patients with respiratory conditions. Primary outcomes included hospital mortality, duration of mechanical ventilation, ICU length of stay (LOS), and hospital LOS. Data were synthesized using fixed- or random-effects models based on heterogeneity. Subgroup analyses were performed based on the route of NAC administration. Results: Five randomized controlled trials comprising 340 patients were included. Hospital mortality was 44.76% in the NAC group and 47.61% in the control group (OR = 0.87; 95% CI: 0.49-1.53). No significant differences were observed in ventilation duration (mean difference [MD] = 0.79 days; 95% CI: −2.87 to 4.44) or ICU LOS (MD = 0.21 days; 95% CI: −3.75 to 4.17). However, NAC was associated with a shorter hospital stay (MD = −3.84 days; 95% CI: −7.44 to −0.24). Subgroup analysis suggested variability in mortality outcomes based on administration route. Conclusions: NAC may reduce hospital LOS in critically ill patients with respiratory disease, although its effects on mortality and ventilation duration remain inconclusive. These findings may inform future research, particularly in patients with post-infectious lung damage such as that seen in COVID-19 or tuberculosis.