Objectives: Here, we investigated the effects of hyperventilation on acute lung injury (ALI) in spontaneously breathing rats. Methods: Wistar rats were randomized to receive either intraperitoneal lipopolysaccharides (LPS) or saline, and intravenous infusion of NH4Cl (to induce metabolic acidosis and hyperventilation) or saline. Four groups were established: control-control (C-C), control-hyperventilation (C-HV), LPS-control (LPS-C), and LPS-hyperventilation (LPS-HV). Venous blood gases were collected before and after NH4Cl infusion and analyzed to confirm the presence of metabolic acidosis and hyperventilation. After euthanasia, lung injury was assessed using the ALI score, morphometric quantification of perivascular edema, neutrophil counts in the bronchoalveolar lavage, and mRNA expression of biological markers in the lung tissue. Results: Hyperventilation induced inflammatory lung injury in previously healthy lungs and exacerbated injuries previously induced by LPS (ALI score: C-C=0.14 [IQR 0.12; 0.14]; C-HV=0.36 [IQR 0.31; 0.37]; LPS-C=0.51 [IQR 0.50; 0.54]; LPS-HV=0.58 [IQR 0.56; 0.62]; p<0.01). Perivascular edema, neutrophil counts in bronchoalveolar lavage, and amphiregulin mRNA expression were higher in the LPS-HV group compared to the control group. Conclusions: Hyperventilation increased inflammatory injury in rats with ALI during spontaneous ventilation. These results suggest that the impact of vigorous spontaneous breathing efforts on worsening inflammatory lung injury warrants further investigation.

Keywords: acute lung injury, acute respiratory distress syndrome, spontaneous breathing, hyperventilation, lung injury.

Objective: Silicosis is a pneumoconiosis characterized by fibrosis of the lung parenchyma caused by the inhalation of silica particles. Silica dust inhalation is associated with inflammation and induction of oxidative stress in the lungs. This oxidative stress affects telomeres, which are short tandem DNA repeats that cap the end of linear chromosomes. We aimed to determine whether telomere length (TL) correlates with silicosis or severity of silicosis in silica-exposed workers in Brazil. Methods: We included 200 men in southeastern Brazil: 100 with silicosis and 100 who had not been exposed to silica. We extracted DNA from buccal cells and assessed TL by multiplex quantitative polymerase chain reaction. Results: The median TL was significantly shorter in the patients with silicosis than in the unexposed controls (p < 0.0001), although it did not differ between the patients with simple silicosis and those with complicated silicosis (p = 0.961). We also found that, in patients with silicosis, TL was influenced by smoking (p = 0.034) and by a history of personal protective equipment use in the workplace (p = 0.002). Conclusions: Silica exposure appears to have an impact on TL, which was found to be shorter in patients with silicosis than in unexposed controls. Further studies are needed in order to confirm the impact that oxidative stress caused by silica inhalation has on telomeres.

Keywords: Silicosis; Oxidative stress; Inflammation; Telomere.

Objective: A significant number of patients with chronic thromboembolic pulmonary hypertension (CTEPH) are not eligible for pulmonary endarterectomy and may be treated with balloon pulmonary angioplasty (BPA). Although BPA programs have recently been developed in Brazil, no results have yet been published. The objective of this study was to assess the clinical and hemodynamic progression of the first patients treated with BPA at our center. Methods: This was an observational study of 23 patients with CTEPH enrolled in the BPA program of a specialized center in Brazil between 2015 and 2020. Results: After a mean of 5.6 ± 1.3 sessions and 11 ± 2.8 treated segments/patient (at a mean of 6.7 ± 2.9 months post-BPA), there was a 26% decrease in mean pulmonary artery pressure (51 ± 11 vs. 38 ± 11 mmHg; p < 0.0001), a 43% decrease in pulmonary vascular resistance (10 ± 3.7 vs. 5.7 ± 3.3 WU; p < 0.0001), and a 22.5% increase in the cardiac index (2.38 ± 0.6 vs. 2.95 ± 0.6 L/min/m2; p < 0.0001). There was an increase in the six-minute walk distance and an improvement in functional class. Acute lung injury with clinical manifestations was observed after 7% of the BPA sessions. None of the patients required intubation. During a mean outpatient follow-up period of 38 ± 22 months, two patients were referred for additional BPA sessions due to clinical worsening and new hospitalizations. Two deaths were recorded (due to CTEPH progression and gastrointestinal bleeding, respectively). Conclusions: Among this first group of patients treated with BPA in Brazil, there was significant short- and long-term clinical improvement, together with a low frequency of complications.

Keywords: Hypertension, pulmonary; Pulmonary embolism; Angioplasty, balloon.

Objective: Surgical resection remains the gold standard treatment for bronchiectasis in patients who present with hemoptysis or suppuration, as well as in those who do not respond to clinical treatment. We sought to investigate the efficacy of sublobar resection (segmentectomy) and compare it with that of lobar resection (lobectomy) in patients with non-cystic fibrosis bronchiectasis. Methods: Patients undergoing lobectomy or segmentectomy between 2019 and 2023 were included in the study. We analyzed intraoperative complications and postoperative outcomes, including length of hospital stay, length of ICU stay, and disease recurrence. Results: There was no significant difference between the lobectomy and segmentectomy groups regarding the occurrence of intraoperative complications such as bleeding > 1000 ml, cardiogenic shock, and ventilatory instability (p > 0.999). However, the frequency of complications was significantly lower in the segmentectomy group than in the lobectomy group (p = 0.016). Hospital stays were longer in the lobectomy group than in the segmentectomy group (16 days vs. 5 days; p = 0.027), as were ICU stays (7 days vs. 1 day; p = 0.006). There was no significant difference between the lobectomy and segmentectomy groups regarding the recurrence rate (p = 0.541). Conclusions: Early identification of bronchiectasis patients who are candidates for surgical resection is essential because those who are identified as such early on are candidates for parenchyma-sparing resections, which are similar to lobar resections in terms of disease control and lead to shorter hospital stays and better postoperative outcomes.

Keywords: Bronchiectasis; Thoracic surgery; Disease-free survival.

Objective: The PACIFIC trial established standard therapy for patients with unresectable stage III NSCLC who did not progress after platinum-based concurrent chemoradiation therapy. However, real-world data, particularly from Latin America, remain limited. The LACOG 0120 study aimed to evaluate the efficacy and safety of consolidation therapy with durvalumab in a real-world setting in Brazil. Methods: Patients with unresectable stage III NSCLC who received chemoradiotherapy followed by durvalumab consolidation therapy through an expanded access program were evaluated. The primary objective was to assess progression-free survival (PFS). Secondary endpoints included overall survival (OS), treatment compliance, and safety, with a focus on the incidence and severity of immune-mediated adverse events (NCT04948411). Results: Thirty-one patients from seven centers were evaluated. Median follow-up was 50.3 months (95% CI: 48.6–54.4). Median PFS was 9.9 months (95% CI: 7.3–52.4), with a 36 month-PFS of 34.5% (95% CI: 17.7–52.1). Median OS was 34.9 months (95% CI: 26.0–NR), and the 36 month-OS was 46.3% (95% CI: 25.7–64.6). Durvalumab was administered for a median of 17 cycles (10 to 24), with 45.2% of patients completing the planned therapy. The main reason for discontinuation was disease progression. Treatment-related adverse events of any grade occurred in 12 patients (38.7%), with grade 3 events reported in two (6.5%). Pneumonitis was observed in 4 patients (12.9%) – grade 3 in 1 patient. Conclusions: PFS was lower in this analysis compared to the PACIFIC trial; however, OS was similar, indicating comparable efficacy in a real-world setting among Brazilian patients with unresectable stage III NSCLC. No new safety concerns were identified.

Objective: To evaluate the perspectives of tuberculosis experts from different countries regarding national screening procedures. Methods: This was a qualitative descriptive study. Data were collected by using electronic, anonymized surveys with experts in tuberculosis in seven different countries within two World Health Organization regions (Europe and Africa). Thematic analysis was employed. Results: The survey results indicate that there are varied perceptions of and experiences with national guidelines on screening for and treatment of tuberculosis (especially in the population tested), the appropriate timing of screening, types of tests, best practices, barriers, and limitations of the screening. The participants highlighted the importance of integrating health care services into the community to achieve people-centered health care. The study also sheds light on the importance of involving trained nurses and social workers in the screening process and of networks to ensure continuity of care. Conclusions: The overall perceptions of the respondents underscore the importance of standardized screening guidelines. The ongoing collaboration between public health services, the private sector, and the community is essential to reduce tuberculosis transmission, as well as to provide substantial public health and economic benefits.

Keywords: Europe; Communicable diseases; Transients and migrants; Public health; Tuberculosis.

Objective: The demanding nature and psychosocial burdens of directly observed treatment (DOT) have opened a path to alternative strategies such as video-observed therapy (VOT), which offers comparable treatment outcomes and patient satisfaction while potentially saving time and reducing costs. The objective of this study was to evaluate the perceptions and experiences of patients and health care professionals regarding DOT and other treatment strategies implemented in Portugal. Methods: Patients with a confirmed diagnosis of tuberculosis, treated at the Vila Nova de Gaia Outpatient Tuberculosis Centre in the last two years, were asked to complete a brief questionnaire, as were health care professionals working in the northern region of Portugal. Differences were analysed with chi-square tests, complemented by thematic analysis. Results: A total of 62 individuals completed the questionnaire: 29 health care professionals and 33 patients. There were significant differences between the two groups in their views regarding the impact of DOT on treatment outcomes, with health care professionals perceiving a higher degree of negative effects and patients expressing greater satisfaction. Long travel distances, transportation issues and high costs were some of the challenges mentioned by the patients. Significant differences were also found regarding the role DOT plays in ensuring treatment adherence, with patients emphasising personal responsibility and its importance in preventing loss to follow-up and strengthening relationships with health care professionals. Dose dispensing was favoured for its convenience in specific situations, and VOT was generally preferred to reduce constant travelling. Both parties raised some concerns. Conclusions: Existing discrepancies suggest a misalignment between patient experiences and health care provider perceptions, underscoring the need for enhanced communication and a more nuanced understanding of patient perspectives when designing and implementing different tuberculosis treatment adherence strategies.

Keywords: Treatment adherence and compliance; Directly observed therapy; Patient satisfaction; Tuberculosis.

Objective: To evaluate the available evidence comparing the use of the bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) regimen for 6 months with that of standard-of-care regimens for patients with multidrug-resistant or rifampin-resistant tuberculosis (MDR/RR-TB). Methods: This was a systematic review of clinical trials comparing the use of the BPaLM regimen with the standard of care in patients with MDR/RR-TB. The main outcome measure was an unfavorable endpoint (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, and recurrence), and secondary outcome measures included adverse events and serious adverse events. We searched the MEDLINE, EMBASE, Google Scholar, LILACS, and ClinicalTrials.gov databases, from their inception to January 31, 2024, with no limitation as to language or year of publication. The risk of bias was assessed by using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation approach. Results: A total of 3,668 studies were retrieved; only one (a randomized clinical trial) met the inclusion criteria and was included. In patients with MDR/RR-TB, treatment with the BPaLM regimen, when compared with the standard of care, reduced the risk of an unfavorable outcome (composite, number needed to treat [NNT] = 7); early treatment discontinuation (NNT = 8); adverse events and discontinuation (NNT = 12); and serious adverse events (NNT = 5). Conclusions: This systematic review of the use of BPaLM in patients with MDR/RR-TB, although it included only one study, showed that BPaLM is more effective than is the standard of care and has a better safety profile. That has major implications for guidelines on the treatment of MDR/RR-TB.

Keywords: Tuberculosis, multidrug-resistant; Antitubercular agents; Diarylquinolines; Linezolid; Moxifloxacin; Nitroimidazoles.