Resumo em Inglês:

ABSTRACT Objective: To compare the survival rates for two cohorts of COPD patients living in Mexico City and studied 20 years apart at the same referral center, with demographic characteristics, lung function, hypoxemia, type of exposure associated with COPD, and socioeconomic status being analyzed. Methods: Two cohorts of COPD patients were studied and followed at a single referral center for respiratory diseases in Mexico City, at an altitude of 2,240 m above sea level. The first cohort was studied between 1996 and 2003, and the second was studied between 2016 and 2023. Participants were followed for seven years, and a multivariate Cox model was used in order to analyze survival. Results: The first cohort included 434 patients, and the second comprised 416 patients, with a total of 850 patients being analyzed. Of those, 68% had COPD from tobacco smoking and 32% had COPD from biomass smoke exposure. In the multivariate Cox model adjusted for age, sex, smoking status, exposure to biomass smoke, BMI < 21 kg/m2, hypoxemia, six-minute walk distance, and lung function as assessed by spirometry, the 2016-2023 cohort showed a significant reduction in the seven-year mortality rate (hazard ratio = 0.59; 95% CI, 0.44-0.81; p = 0.001) when compared with the 1996-2003 cohort. Conclusions: Survival of COPD patients has improved over the past 20 years after accounting for several mortality predictors.

Resumo em Inglês:

ABSTRACT Objective: To analyze endogenous metabolites in exhaled breath condensate before and after eucapnic voluntary hyperventilation (EVH) in adolescents with asthma with and without exercise-induced bronchoconstriction (EIB). Methods: This was an exploratory study including 44 adolescents with asthma in the 10- to 20-year age bracket. They were divided into two groups: the group of patients with EIB (n = 25) and that of those without (n = 19). EIB was defined as a ≥ 10% reduction in FEV1 after a six-minute EVH challenge using 5% carbon dioxide. Ventilation was maintained at 21 times the baseline FEV1. Exhaled breath condensate was collected before EVH and 15-30 min after EVH by using a validated device. Samples were analyzed by proton nuclear magnetic resonance focusing on the region of d1.60-2.00 parts per million. Data were preprocessed by using sum normalization and autoscaling for orthogonal partial least squares discriminant analysis. Results: All participants completed the protocol without adverse events. The mean reduction in FEV1 was significantly greater in the group of patients with EIB than in that of those without (−25.13% vs. −4.37%; mean difference, −20.76%; 95% CI, −26.45 to −15.07). In the EIB group, responses were classified as mild (n = 15), moderate (n = 9), or severe (n = 1). Post-EVH orthogonal partial least squares discriminant analysis showed significant separation between pre- and post-EVH metabolic profiles in the group of patients with EIB (p < 0.001) but not in that of those without (p = 0.195). The discriminative response in patients with EIB was associated with a marked increase in acetate signal intensity at 1.76 parts per million. Conclusions: Adolescents with EIB show a distinct metabolic fingerprint that is significantly associated with ventilatory stress. Acetate emerged as a key metabolic differentiator, suggesting a specific biochemical pathway associated with the exercise response and supporting its potential role in precision phenotyping of EIB.

Resumo em Inglês:

ABSTRACT Objective: Severe eosinophilic asthma (SEA) is often associated with chronic rhinosinusitis with nasal polyps (CRSwNP) characterized by type 2-driven eosinophilic inflammation. We sought to investigate the effect of mepolizumab on relevant clinical, functional, and inflammatory endpoints in naïve SEA patients with or without nasal polyps evaluated through induced sputum and followed for 12 months. Methods: We conducted an exploratory observational real-world cohort study including biologic-naïve SEA patients who initiated treatment with mepolizumab at an asthma referral center in Tradate, Italy. Clinical, functional, and inflammatory parameters were assessed at baseline and after 12 months. Induced sputum was used to evaluate airway inflammation. Patients were stratified by presence or absence of CRSwNP. Results: Forty patients were included, 27/40 (67.5%) had CRSwNP. After 12 months, significant reductions were observed in annual exacerbations (median, 2.0 vs. 0.0; adjusted p value [p-adj] < 0.001), maintenance oral corticosteroid use (5.0 vs. 0.0 mg; p-adj = 0.004), blood eosinophil count (543 vs. 55 cells/µL; p-adj < 0.001), and sputum eosinophil % (39.0% vs. 1.3%; p = 0.004). Asthma control and FEV1 improved significantly. In patients with CRSwNP, sinonasal symptoms markedly improved (p-adj = 0.004). No post-treatment differences in airway eosinophilia were detected between the groups. Overall, 77.5% achieved clinical remission in accordance with Severe Asthma Network Italy Delphi consensus criteria. Conclusions: Mepolizumab provided substantial clinical, functional, and anti-inflammatory benefits in SEA, regardless of CRSwNP status. Despite higher baseline eosinophilia, patients with CRSwNP showed no clear differences in outcomes when compared with those without CRSwNP, supporting the concept of united airway disease. These findings highlight the value of induced sputum as a noninvasive tool and support integrated, comorbidity-driven approaches in severe asthma management.

Resumo em Inglês:

ABSTRACT Objective: To describe the development and validation process of a questionnaire to assess the knowledge, attitudes, and practices of ICU health care professionals regarding patient-ventilator asynchrony. Methods: This was a knowledge, attitudes, and practices questionnaire development study. Item generation was guided by a literature-based conceptual framework, followed by expert review to establish face and content validity. The instrument was refined through specialists in mechanical ventilation and questionnaire design. The tenth version was piloted in Portuguese among ICU health care professionals, including a 30-day test-retest assessment. Results: The final version of the questionnaire comprised 24 items (knowledge, 14 items; attitudes, 4; and practices, 6). Of the 83 ICU health care professionals who consented to participate, 49 completed at least 80% of the questionnaire twice and were included in the analysis. The knowledge section showed acceptable internal consistency (Cronbach’s alpha = 0.73) and moderate test-retest reliability (intraclass correlation coefficient = 0.48; 95% CI, 0.24-0.67). Median knowledge scores were 71 [57-79] at test and 64 [50-79] at retest, out of 100 (p = 0.052). Attitude scores also showed good test-retest reliability (intraclass correlation coefficient = 0.68; 95% CI, 0.50-0.81) and a moderate correlation (r = 0.60; p < 0.001), with median scores of 75 (out of 100) in both rounds. Practice item responses were generally consistent between test and retest. Conclusions: We developed a questionnaire to assess knowledge, attitudes, and practices related to patient-ventilator asynchrony among ICU health care professionals, with evidence of face and content validity, internal consistency, and test-retest reliability.

Resumo em Inglês:

ABSTRACT Objective: In cases in which tuberculosis is not diagnosed microbiologically through sputum samples, bronchoscopy has been the conventional method to increase diagnostic rates. Few studies have evaluated the performance of the Xpert MTB/RIF Ultra assay on BAL fluid samples. We therefore sought to evaluate the performance of Xpert MTB/RIF Ultra on BAL fluid samples for pulmonary tuberculosis diagnosis in a Brazilian city with a high incidence of tuberculosis. Methods: This was a cross-sectional study performed at a tertiary care university hospital in southern Brazil. Patients > 18 years of age with respiratory symptoms suggestive of pulmonary tuberculosis were invited to participate. Test results were collected, including smear microscopy, mycobacterial culture, and Xpert MTB/RIF Ultra on BAL fluid samples. Results: During the study period, 161 patients met the inclusion criteria and were therefore included in the analysis. With culture being considered the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of Xpert MTB/RIF Ultra on BAL fluid samples were 97.3% (95% CI, 90.6-99.7), 94.3% (95% CI, 87.1-98.1), 93.5% (95% CI, 86.0-97.1), and 97.6% (95% CI, 91.3-99.4), respectively. Conclusions: The Xpert MTB/RIF Ultra assay showed high sensitivity and specificity on BAL fluid samples from individuals with presumptive pulmonary tuberculosis. This demonstrates that the test is a useful tool for pulmonary tuberculosis diagnosis under programmatic conditions.

Resumo em Inglês:

ABSTRACT The prevalence of obesity and obstructive sleep apnea (OSA) has increased alarmingly over recent decades and is projected to continue to rise. These chronic disorders interact bidirectionally and increase cardiovascular and metabolic risks. OSA is a complex and heterogenous disease in which weight management plays a key role in achieving long-lasting therapeutic success. Multiple mechanisms are associated with the link between obesity and OSA, including enlargement of upper airway soft tissue, pharyngeal lengthening, reduced lung volume, and leptin impairment. In this review, we describe the mechanisms linking obesity and OSA, and examine the impact of CPAP therapy on body weight. We also review current obesity treatment strategies and their effects on reducing OSA severity, comparing the efficacy of lifestyle modifications, surgical approaches, and pharmacological treatments in promoting weight loss. Finally, we explore the potential of recent advances in pharmacological obesity treatments as therapeutic options for OSA, as well as the promise of combination therapy for achieving better short- and long-term weight reduction.

Resumo em Inglês:

ABSTRACT Objective: In a previous review, we summarized the safety of linezolid-containing regimens to treat rifampin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB), underscoring the persistent need for shorter and safer regimens. The objective of the present study was to explore the safety and tolerability directly attributable to linezolid in regimens designed to treat RR/MDR-TB in studies published between 2009 and 2025. Methods: We searched PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for studies reporting on the safety and tolerability of linezolid since it was introduced as a repurposed drug in the treatment of tuberculosis. Results: A total of 22 studies (including 26 arms) were identified, with a total of 3,014 patients. There was significant variation in geographic distribution, sample size (range, 8-655), linezolid dose (range, 300-1,200 mg), duration, and other core variables. The pooled rate of favorable outcomes among cohort studies (cure or treatment completion) was = 80.1%. Hematologic disorders (including anemia, thrombocytopenia, and leukopenia, in 33.1%) and peripheral neuropathy (in 33.9%) were the most common adverse events (AEs), followed by psychiatric and neurological disorders (in 12.3%), myalgia (in 7.0%), optic neuropathy (in 7.8%), gastrointestinal events (in 1.9%), ototoxicity (in 2.9%), and rash (in 1.0%). Serious AEs were rarely reported. Conclusions: Although the recommended linezolid-containing regimens are considered safe, linezolid still causes frequent and severe AEs. A new drug with similar characteristics but lower toxicity will significantly improve the safety of antituberculosis regimens, with improved adherence and treatment outcomes.