Abstract in English:

ABSTRACT Objectives: The advent of massively parallel next-generation sequencing (MP-NGS) offers potential advantages over sequential molecular profiling (SMP) in the management of non-small cell lung cancer (NSCLC). This study compares the two methodologies using samples obtained through endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), focusing on actionable mutation detection, turnaround time (TAT), and clinical outcomes. Methods: A retrospective analysis was conducted on NSCLC patients who underwent EBUS-TBNA and molecular characterization between January 2020 and December 2023. SMP and MP-NGS were compared in terms of actionable mutation detection rates, TAT, and impact on overall survival (OS). Results: Among 106 patients, MP-NGS demonstrated a significantly higher detection rate of actionable mutations compared to SMP (40.9% vs. 22.2%, p=0.042). The median TAT was slightly shorter with SMP than with externally outsourced MP-NGS (17 days vs. 23 days, p=0.076). Patients diagnosed via MP-NGS were more frequently allocated to targeted therapies (44.26% vs. 22.2%, p=0.038), which may have positively influenced overall survival (672 days vs. 138 days, p=0.053). Conclusion: MP-NGS provided superior diagnostic and clinical advantages over SMP in NSCLC, supporting its adoption as a standard diagnostic approach to enhance personalized therapy and improve patient outcomes.

Abstract in English:

ABSTRACT Objective: Given that b2 agonists constitute the primary treatment for asthma and that treatment response varies as a result of polymorphisms in the ADRB2 gene, we sought to investigate the associations between ADRB2 gene variants and bronchodilator response (BDR) in asthma patients. Methods: A genetic database comprising 813 individuals was analyzed for variants in the ADRB2 gene. A longitudinal analysis of severe asthma patients was performed to evaluate changes in BDR over time. Results: The rs1042713, rs1042714, and rs1042717 variants were associated with age-related changes in BDR in patients with severe asthma. The G allele (rs1042714) and the A allele (rs1042717) were associated with uncontrolled asthma, with carriers of the G46/G79/A252 alleles showing a higher risk of difficult-to-control asthma. Notably, no association was found between these variants and ADRB2 expression levels. Conclusions: Our findings suggest that a genetic panel including ADRB2 variants, as well as age-related differences in BDR, is a useful complementary tool in asthma management.

Abstract in English:

ABSTRACT Objective: To establish reference values and prediction equations for the strength index (S-Index), in order to meet the growing demand for clinical application and diagnostic understanding of maximal dynamic inspiratory pressure. Methods: This was a prospective study of 120 healthy subjects between 18 and 80 years of age. The S-Index, measured from RV to TLC after at least eight reproducible maximal maneuvers with a < 10% difference, was obtained. The MIP was also measured, and differences between S-Index and MIP values were analyzed. A multiple linear regression model estimating the S-Index value was based on clinically significant independent variables. For model cross-validation and diagnostic accuracy, we used a separate sample of COVID-19 survivors to compare the observed and predicted S-Index values. Results: The S-Index strongly correlated with the FEV1 and FVC. However, sex, age, weight, and height retained their significance in all final models, collectively explaining 62% of the variation in the observed values. The performance of the prediction equation was satisfactory in suggesting differences between COVID-19 survivors with an MIP < 80 cmH2O and those with an MIP ≥ 80 cmH2O. For both sexes, the S-Index exhibited the potential for ruling out, rather than confirming, inspiratory muscle weakness. If below the lower limit of normal, further evaluation is important, especially in men. Conclusions: To our knowledge, this is the first set of reference equations for the S-Index based on a healthy adult population across various age groups in Brazil. Its potential as an adjunct index in evaluating inspiratory muscle strength was also explored for the first time.

Abstract in English:

ABSTRACT Objective: To evaluate clinical, functional, and CT characteristics, as well as disease progression, in patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) treated at a referral center in Brazil. Methods: This was a retrospective cohort study analyzing demographic characteristics, clinical variables, pulmonary function test results, HRCT findings, serological profiles, treatments, and outcomes. Results: Seventy-nine IIM-ILD patients were included in the present study. The mean follow-up period was 8.7 ± 4.7 years. The most common diagnosis was antisynthetase syndrome, observed in 51 (64.5%) of the 79 patients. The most common symptoms were dyspnea (in 94.9%), arthralgia (in 82.2%), and muscle weakness (in 75.9%). Mean baseline FVC was 2.19 ± 0.75 L, corresponding to 62.5% of the predicted value. During follow-up, FVC showed significant improvement. The most common CT patterns were indeterminate (in 44.4%) and nonspecific interstitial pneumonia (in 35.4%). Treatment most frequently included prednisone (in 98.7%), azathioprine (in 92.3%), or methotrexate (in 57.7%). Overall survival was 84.8%. Mortality was higher among patients who developed pulmonary hypertension and those who required intravenous methylprednisolone pulse therapy. Conclusions: Most patients with IIM-ILD progress well with immunosuppressive therapy. Pulmonary hypertension and the need for methylprednisolone pulse therapy appear to be associated with higher mortality.

Abstract in English:

ABSTRACT Objective: In July of 2021, the Brazilian National Ministry of Health integrated three months of once-weekly isoniazid plus rifapentine (3HP) into the National Guidelines for Tuberculosis Control as a first-line tuberculosis preventive therapy (TPT) option for people living with HIV (PLHIV) and tuberculosis household contacts (HHCs). As part of the Unitaid-sponsored Increasing Market and Public Health Outcomes through Scaling up Affordable Access Models of Short Course Preventive Therapy for TB project to implement short-course TPT, we evaluated 3HP uptake, completion, and tolerability among PLHIV and pediatric HHCs in Brazil. Methods: We conducted a multicenter single-arm pragmatic project to roll out 3HP for PLHIV and HHCs in the 2- to 14-year age bracket in the cities of Rio de Janeiro and Manaus, Brazil. Participants were identified, treated, and monitored in accordance with Brazilian national tuberculosis guidelines. De-identified patient-level data on treatment initiation, adverse events, and completion were collected and analyzed. Results: From October of 2021 to March of 2023, 380 PLHIV (77.6% of whom were male; median age, 40 years [IQR, 31-51]) and 74 HHCs (54.1% of whom were male; median age, 8.6 years [IQR, 5.1-11.8]) were enrolled in the study. Treatment completion rates were 83.7% among PLHIV and 82.4% among HHCs. Completion rates were higher in Rio de Janeiro than in Manaus (PLHIV: 86.0% vs. 79.6%; HHCs: 85.2% vs. 80.9%), although completion of 10 doses was similar (PLHIV: 86.4% vs. 86.1%). Adverse event-related discontinuation was low (PLHIV: 2.4%; HHCs: 2.7%). One person living with HIV developed active tuberculosis during treatment. At six months of follow-up, 99.6% of the PLHIV remained free of tuberculosis. Conclusions: The 3HP regimen was successfully introduced, had high treatment completion rates, and was well tolerated. Widespread use of 3HP for TPT may accelerate tuberculosis elimination in Brazil.

Abstract in English:

ABSTRACT Objective: To evaluate tuberculosis diagnosis with the use of the lateral flow urine lipoarabinomannan assay (LF-LAM) in addition to the Xpert® MTB/RIF Ultra assay on sputum in HIV-positive inpatients and outpatients. Methods: This was a prospective cross-sectional study including HIV-positive patients ≥ 18 years of age with an indication for LF-LAM in accordance with Brazilian National Ministry of Health criteria. Results: A total of 140 patients were included in the study. LF-LAM was positive in 23 (16.4%). An additional 12 (8.6%) were diagnosed with the aid of LF-LAM, this increase in tuberculosis detection being statistically significant. LF-LAM-positive patients were younger and had lower CD4 counts in comparison with LF-LAM-negative patients. Smoking was more common among LF-LAM-negative patients than among LF-LAM-positive patients. Conclusions: The use of LF-LAM significantly increases the detection of tuberculosis in HIV-positive patients, mostly in those who are hospitalized. These findings highlight the utility of LF-LAM, especially in regions with high tuberculosis and HIV infection incidence.

Abstract in English:

ABSTRACT Objective: Personal experiences, perceptions, and views of patients are crucial in understanding the subjective impacts of diseases. The complexity and duration of tuberculosis treatment impose significant physical, emotional, social, and economic burdens, highlighting the need for person-centered, integrated care strategies that address stigma, fatigue, and accessibility to support well-being. Patient-reported outcomes (PROs) are essential for capturing patient perspectives and improving health care strategies. In this study we explored the multifaceted experiences of patients with tuberculosis, seeking to understand their values and priorities during treatment. Methods: Semistructured interviews with adult tuberculosis patients were conducted at a referral center for tuberculosis diagnosis and management in northern Portugal. After verbatim transcription and anonymization, thematic analysis was performed. Results: Seventeen interviews were conducted. Most (58.8%) of the study participants were male, and most had pulmonary tuberculosis. Our thematic analysis identified five PROs: treatment experiences; health-related quality of life; functional status; symptoms and symptom burden; and health behaviors. People with tuberculosis acknowledged the impact of multiple factors on their overall health, particularly the psychological and physical burdens of tuberculosis and its treatment. Several areas for improvement and opportunities for enhanced support were identified, particularly in communication, emotional support, and management of treatment burden. Conclusions: Our findings highlight the need for tailored PRO measures (PROMs) addressing treatment burden, psychosocial distress, and functional limitations in tuberculosis care. Enhancing communication, psychological support, and multidisciplinary approaches in tuberculosis management could improve patient outcomes and overall well-being. Addressing tuberculosis-related stigma and providing targeted interventions may contribute to a more people-centered approach to care.

Abstract in English:

ABSTRACT Electronic nicotine delivery systems, electronic cigarettes, or vapes have been extensively marketed as a safer alternative to combustible cigarettes and as aids for smoking cessation. However, electronic cigarettes often deliver more potent forms of nicotine, such as nicotine salts and synthetic nicotine, which are masked by appealing aromas and flavors, thereby attracting nonsmoking children and adolescents. On the other hand, adults dependent on freebase nicotine (found in conventional cigarettes) often become addicted to these new forms of nicotine in electronic cigarettes. Dual use is common and poses significant health risks, potentially exceeding those of using either product alone. Dual users experience increased odds of COPD, lung cancer, cardiovascular disease, and stroke. Electronic cigarettes represent a new challenge for global public health and health professionals. There are currently no specific guidelines for vaping cessation treatment. This study sought to provide health professionals with a comprehensive vaping cessation approach, including effective strategies such as behavioral support, nicotine replacement therapy, and the use of nicotine-free medications.