Objective: Fungal pulmonary infections are a significant complication in lung cancer, adversely affecting prognosis and treatment outcomes. This meta-analysis aimed to estimate the prevalence of chronic pulmonary aspergillosis (CPA) and Pneumocystis jirovecii pneumonia (PJP) in lung cancer patients and to identify associated clinical predictors. Methods: A systematic search of EBSCOhost, Embase, PubMed/MEDLINE, Scopus, and Web of Science retrieved 2,823 records, of which 7 studies were eligible (PROSPERO: CRD42024551104). Meta-analyses of proportions and dichotomous and continuous variables were performed using R (meta package) via Jamovi and RevMan 5, with statistical significance set at p<0.05. Results: Among 15,901 lung cancer patients, 177 had CPA and 135 had PJP. The pooled prevalence was 1% for CPA and 23% for PJP. CPA was significantly associated with male sex, smoking, COPD, interstitial lung disease, tuberculosis, and squamous cell carcinoma, and negatively associated with adenocarcinoma. CPA patients also had significantly lower BMI. Bilobectomy, radiotherapy, and concurrent chemoradiotherapy were additional risk factors for CPA. High-dose corticosteroid use (=20 mg/day) was significantly associated with PJP. Conclusion: CPA occurs in a clinically distinct subset of lung cancer patients with identifiable risk factors, while PJP appears to be strongly linked to immunosuppressive therapy. Improved screening strategies are warranted to mitigate the burden of these infections in vulnerable lung cancer populations.

Keywords: lung cancer; fungal infection; pulmonary infection; aspergillosis; Pneumocystis jirovecii; pneumonia.

Various wheezing phenotypes can be identified based on differences in natural histories, risk factors and responses to treatment. In epidemiologic studies, atopic asthma or virus-induced wheezing can be discriminated by the presence or the absence of sensitization to allergens. Children with asthma have been shown to present lower levels of lung function. Patients with viral respiratory infections evolve from normal lung function to enhanced airway reactivity. The objective of this study was to identify genes and polymorphisms associated with different wheezing phenotypes. Using data obtained from the Genetic Association Database, we systematically reviewed studies on genes and polymorphisms that have been associated with virus-induced wheezing or atopic asthma. The research was carried out in February of 2009. Genes associated with the studied outcomes in more than three studies were included in the analysis. We found that different genes and loci have been associated with virus-induced wheezing or atopic asthma. Virus-induced wheezing has frequently been associated with IL-8 polymorphisms, whereas atopic asthma and atopy have frequently been associated with Th2 cytokine gene (CD14 and IL-13) polymorphisms on chromosome 5. This review provides evidence that different wheezing disorders in childhood can be differently affected by genetic variations, considering their role on airway inflammation and atopy. Future studies of genetic associations should consider the different wheezing phenotypes in infancy. In addition, stratified analyses for atopy can be useful for elucidating the mechanisms of the disease.

Keywords: Genetics; Polymorphism, genetic; Asthma; Interleukins; Respiratory syncytial viruses.

Objective: To describe the mortality trends for lung cancer, cancer of the trachea, and bronchial cancer in relation to gender and age brackets in Brazil. Methods: Data related to mortality between 1980 and 2003 were collected from the Brazilian Mortality Database. A trend analysis of mortality was carried out, nationwide and in selected states, using the LOWESS technique for rate smoothing and model adjustments. Results: In Brazil, the standardized mortality rate for lung cancer, cancer of the trachea, and bronchial cancer increased from 7.21/100,000 inhabitants in 1980 to 9.36/100,000 inhabitants in 2003. Specific mortality rates decreased in males in the 30-49 and 50-59 age brackets. In the 60-69 age bracket, the rates for males increased from 1980 to 1995 and declined thereafter. There was a trend toward higher mortality rates in males over 70, as well as in females over 30, throughout the period evaluated. Conclusions: The decrease in the mortality rates in younger males might have resulted from recent national interventions aimed at reducing the prevalence of smoking and reducing exposure in younger cohorts. High mortality rates in older populations remained constant due to prior tobacco use. Increased mortality rates in females are a worldwide trend and are attributable to the recent increase in smoking prevalence in females.

Keywords: Lung neoplasms/epidemiology; Mortality/trends; Brazil.

Objective: Lung cancer (LC) is one of the leading causes of death worldwide. Accurate mediastinal staging is mandatory in order to assess prognosis and to select patients for surgical treatment. EBUS-TBNA is a minimally invasive procedure that allows sampling of mediastinal lymph nodes (LNs). Some studies have suggested that EBUS-TBNA is preferable to surgical mediastinoscopy for mediastinal staging of LC. The objective of this systematic review and meta-analysis was to compare EBUS-TBNA and mediastinoscopy in terms of their effectiveness for mediastinal LN staging in potentially operable non-small cell lung cancer (NSCLC). Methods: This was a systematic review and meta-analysis, in which we searched various databases. We included studies comparing the accuracy of EBUS-TBNA with that of mediastinoscopy for mediastinal LN staging in patients with NSCLC. In the meta-analysis, we calculated sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios. We also analyzed the risk difference for the reported complications associated with each procedure. Results: The search identified 4,201 articles, 5 of which (with a combined total of 532 patients) were selected for inclusion in the meta-analysis. There were no statistically significant differences between EBUS-TBNA and mediastinoscopy in terms of the sensitivity (81% vs. 75%), specificity (100% for both), positive likelihood ratio (101.03 vs. 95.70), or negative likelihood ratio (0.21 vs. 0.23). The area under the summary ROC curve was 0.9881 and 0.9895 for EBUS-TBNA and mediastinoscopy, respectively. Although the number of complications was higher for mediastinoscopy, the difference was not significant (risk difference: −0.03; 95% CI: −0.07 to 0.01; I2 = 76%). Conclusions: EBUS-TBNA and mediastinoscopy produced similar results for mediastinal staging of NSCLC. EBUS-TBNA can be the procedure of first choice for LN staging in patients with NSCLC.

Keywords: Lung neoplasms/diagnosis; Neoplasm staging; Mediastinal neoplasms/diagnosis; Endoscopic ultrasound-guided fine needle aspiration; Mediastinoscopy.

Objective: Mobile health (mHealth) applications are scarce for children and adolescents with chronic pulmonary diseases (CPDs). This study aimed to map and describe the contents of the mHealth apps available for use in children and adolescents with CPDs. Methods: We performed a systematic mapping review of published scientific literature in PubMed, Scopus, and Cochrane Library by February of 2023, using relevant keywords. Inclusion criteria were as follows: children aged < 18 years with CPDs; and studies published in English on mHealth apps. Results: A total number of 353 studies were found, 9 of which met the inclusion criteria. These studies described seven mHealth apps for Android and iOS, designed either for asthma (n = 5) or for cystic fibrosis (n = 2). Five content areas were identified: education/information; pharmacological treatment; emergency; support; and non-pharmacological treatment. The studies (4, 2, and 3, respectively) showed consistent findings using qualitative, quantitative, and mixed methodologies. Conclusions: This mapping review provided a guided selection of the most appropriate mHealth apps for use in children and adolescents with CPDs based on the needs of each target population. However, these mHealth apps have limited capabilities to reinforce disease self-management and provide information related to treatment compliance.

Keywords: Lung diseases; Child, Adolescent; Treatment adherence and compliance; Telemedicine; Self-management.

Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

Keywords: Molecular targeted therapy; Receptor, epidermal growth factor; Lung neoplasms/drug therapy; Mutation; Oncogenes.

Objective: To determine morbidity and mortality rates by risk category in accordance with the American College of Chest Physicians guidelines, to determine what role pulmonary function tests play in this categorization process, and to identify risk factors for perioperative complications (PCs). Methods: This was a historical cohort study based on preoperative and postoperative data collected for cases of lung cancer diagnosed or suspected between 2001 and 2010. Results: Of the 239 patients evaluated, only 13 (5.4%) were classified as being at high risk of PCs. Predicted postoperative FEV1 (FEV1ppo) was sufficient to define the risk level in 156 patients (65.3%); however, cardiopulmonary exercise testing (CPET) was necessary for identifying those at high risk. Lung resection was performed in 145 patients. Overall morbidity and mortality rates were similar to those reported in other studies. However, morbidity and mortality rates for patients at an acceptable risk of PCs were 31.6% and 4.3%, respectively, whereas those for patients at high risk were 83.3% and 33.3%. Advanced age, COPD, lobe resection, and lower FEV1ppo were correlated with PCs. Conclusions: Although spirometry was sufficient for risk assessment in the majority of the population studied, CPET played a key role in the identification of high-risk patients, among whom the mortality rate was seven times higher than was that observed for those at an acceptable risk of PCs. The risk factors related to PCs coincided with those reported in previous studies.

Keywords: Algorithms; Lung neoplasms; Postoperative complications.

Pulmonary complications are the most common cause of morbidity and mortality in immunocompromised patients, who lack of the basic mechanisms of cellular defense. Regardless of the cause of the immunodeficiency, the most common complications are infections (bacterial, viral or fungal). Among the fungal infections, aspergillosis is the most common (incidence, 1-9%; mortality, 55-92%) following organ transplant. Although pulmonary involvement is the most common form of aspergillosis, central nervous system involvement and sinusitis are not uncommon. On CT scans, the halo sign represents an area of low attenuation around the nodule, revealing edema or hemorrhage. The gold standard for the diagnosis is the culture identification of the fungus in sputum, BAL fluid or biopsy samples. Failing this identification, the detection of galactomannan, which is one of the fungal wall components, has shown sensitivity and specificity of 89% and 98%, respectively. Amphotericin B, liposomal amphotericin B, caspofungin and, especially, voriconazole are effective against the fungus. Although Pneumocystis jirovecii pneumonia can be fatal, the incidence of this disease has decreased due to the prophylactic use of trimethoprim-sulfamethoxazole. In immunocompromised patients presenting with dyspnea and hypoxemia, screening for fungi is indicated. A 14- to 21-day course of trimethoprim-sulfamethoxazole in combination with corticosteroids is usually efficacious. Another rare fungal infection is disseminated candidiasis, which is caused by Candida spp.

Keywords: Pneumonia; Immunosuppression; Lung diseases, fungal.

Objective: To evaluate the effect size of oral corticosteroid treatment on eosinophilic bronchitis in asthma, through systematic review and meta-analysis. Methods: We systematically reviewed articles in the Medline, Cochrane Controlled Trials Register, EMBASE, and LILACS databases. We selected studies meeting the following criteria: comparing at least two groups or time points (prednisone vs. control, prednisone vs. another drug, or pre- vs. post-treatment with prednisone); and evaluating parameters before and after prednisone use, including values for sputum eosinophils, sputum eosinophil cationic protein (ECP), and sputum IL-5-with or without values for post-bronchodilator FEV1-with corresponding 95% CIs or with sufficient data for calculation. The independent variables were the use, dose, and duration of prednisone treatment. The outcomes evaluated were sputum eosinophils, IL-5, and ECP, as well as post-bronchodilator FEV1. Results: The pooled analysis of the pre- vs. post-treatment data revealed a significant mean reduction in sputum eosinophils (8.18%; 95% CI: 7.69-8.67; p < 0.001), sputum IL-5 (83.64 pg/mL; 95% CI: 52.45-114.83; p < 0.001), and sputum ECP (267.60 µg/L; 95% CI: 244.57-290.63; p < 0.0001), as well as a significant mean increase in post-bronchodilator FEV1 (8.09%; 95% CI: 5.35-10.83; p < 0.001). Conclusions:In patients with moderate-to-severe eosinophilic bronchitis, treatment with prednisone caused a significant reduction in sputum eosinophil counts, as well as in the sputum levels of IL-5 and ECP. This reduction in the inflammatory response was accompanied by a significant increase in post-bronchodilator FEV1.

Keywords: Meta-analysis; Bronchitis; Asthma; Pulmonary eosinophilia; Evidence-based medicine; Prednisone.

Objective: Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the use of remdesivir for the treatment of patients hospitalized with moderate to severe COVID-19. Methods: This was a systematic review and meta-analysis including phase 3 randomized clinical trials (RCTs) and observational cohort studies selected from various databases, comparing patients hospitalized with moderate to severe COVID-19 receiving remdesivir and controls. Results: A total of 207 studies were retrieved, 9 of which met the eligibility criteria and were included in the study. The meta-analysis using RCTs alone showed no statistically significant differences regarding mortality or use of mechanical ventilation/extracorporeal membrane oxygenation between remdesivir and control groups, and the quality of evidence was moderate and low, respectively. The use of remdesivir increased the recovery rate by 6% (95% CI, 3-9); p = 0.004) and the clinical improvement rate by 7% (95% CI, 1-14); p = 0.02). Additionally, no significant differences in mortality were found between remdesivir and control groups when the meta-analysis used observational cohort studies alone (risk difference = -0.01 (95% CI, -0.02 to 0.01; p = 0.32), the quality of evidence being moderate, and the risk of adverse events was 4% ([95% CI, -0.08 to 0.01]; p = 0.09). Conclusions: The use of remdesivir for the treatment of patients with moderate to severe COVID-19 had no significant impact on clinically important outcomes.

Keywords: Antiviral agents; COVID-19; SARS-CoV-2.

Objective: To answer questions related to the use of anticoagulants in the treatment of COVID-19 patients. Methods: This was a systematic review and meta-analysis of phase 3 randomized controlled trials comparing the use of anticoagulants in non-hospitalized and hospitalized COVID-19 patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to January 22, 2022. The risk of bias was assessed by the Cochrane risk-of-bias tool, and the quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation system. Results: A total of 401 studies were initially selected. Of those, 9 met the inclusion criteria and were therefore analyzed (a total of 6,004 patients being analyzed). In non-hospitalized COVID-19 patients, no significant difference was found between post-discharge prophylactic anticoagulation and no intervention regarding venous thromboembolism or bleeding at 30 days. In hospitalized COVID-19 patients, full anticoagulation resulted in a slight reduction in thrombotic events at 30 days (risk difference, -0.03; 95% CI, -0.06 to -0.00; p = 0.04; I2 = 78%), the quality of evidence being moderate. However, no significant difference was found between full anticoagulation and no intervention regarding the risk of major bleeding, the quality of evidence being very low. No significant difference was found between intermediate- and standard-dose prophylactic anticoagulation (risk difference, -0.01; 95% CI, -0.07 to 0.06; p = 0.81; I2 = 0%), the quality of evidence being very low. Conclusions: Therapeutic anticoagulation appears to have no effect on mortality in COVID-19 patients, resulting in a slight reduction in venous thromboembolism in hospitalized patients.

Keywords: Anticoagulants; COVID-19; SARS-CoV-2.

This article reviews the effects of aging, tobacco-smoking, chronic bronchitis and emphysema, heart failure, oropharyngeal colonization, aspiration (micro and macro), alcoholism, hepatic cirrhosis, nutritional deficiency, immunosuppression, and environmental factors on the risk of community-acquired pneumonia and its severity. In the second part, the authors review the prophylactic action of anti-influenza and anti-pneumococcus vaccines as well as the role of prevention and treatment of antiviral agents in community-acquired pneumonia.

Keywords: Pneumococcal pneumonia. Influenza. Influenza vaccine. Viral vaccines. Risk factors.

The objective of this systematic review was to select articles including chest X-ray or chest CT findings in patients who developed pulmonary tuberculosis following solid organ transplantation (lung, kidney, or liver). The following search terms were used: "tuberculosis"; "transplants"; "transplantation"; "mycobacterium"; and "lung". The databases used in this review were PubMed and the Brazilian Biblioteca Virtual em Saúde (Virtual Health Library). We selected articles in English, Portuguese, or Spanish, regardless of the year of publication, that met the selection criteria in their title, abstract, or body of text. Articles with no data on chest CT or chest X-ray findings were excluded, as were those not related to solid organ transplantation or pulmonary tuberculosis. We selected 29 articles involving a collective total of 219 patients. The largest samples were in studies conducted in Brazil and South Korea (78 and 35 patients, respectively). The imaging findings were subdivided into five common patterns. The imaging findings varied depending on the transplanted organ in these patients. In liver and lung transplant recipients, the most common pattern was the classic one for pulmonary tuberculosis (cavitation and "tree-in-bud" nodules), which is similar to the findings for pulmonary tuberculosis in the general population. The proportion of cases showing a miliary pattern and lymph node enlargement, which is most similar to the pattern seen in patients coinfected with tuberculosis and HIV, was highest among the kidney transplant recipients. Further studies evaluating clinical data, such as immunosuppression regimens, are needed in order to improve understanding of the distribution of these imaging patterns in this population.

Keywords: Tomography, X-ray computed; Radiography; Tuberculosis, pulmonary; Lung/transplantation; Kidney/transplantation; Liver/transplantation.

Objective: To evaluate the effects of high-intensity interval training (HIIT), in comparison with those of continuous exercise, on functional capacity and cardiovascular variables in patients with COPD, through a systematic review and meta-analysis of randomized controlled trials. Methods: We searched PubMed, the Physiotherapy Evidence Database, the Cochrane Central Register of Controlled Trials, and EMBASE, as well as performing hand searches, for articles published up through January of 2017. We included studies comparing exercise regimens of different intensities, in terms of their effects on functional capacity and cardiovascular variables in patients with COPD. Results: Of the 78 articles identified, 6 were included in the systematic review and meta-analysis. Maximal oxygen consumption (VO2max) did not differ significantly between HIIT and control interventions. That was true for relative VO2max (0.03 mL/kg/min; 95% CI: −3.05 to 3.10) and absolute VO2max (0.03 L/min, 95% CI: −0.02 to 0.08). Conclusions: The effects of HIIT appear to be comparable to those of continuous exercise in relation to functional and cardiovascular responses. However, our findings should be interpreted with caution because the studies evaluated present a high risk of bias, which could have a direct influence on the results.

Keywords: Pulmonary disease, chronic obstructive; Exercise; Oxygen consumption.

Objective: To evaluate the efficacy of wearing a mask to prevent COVID-19 infection. Methods: This was a systematic review and meta-analysis of cohort and case-control studies, considering the best level of evidence available. Electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov) were searched to identify studies that evaluated the effectiveness of wearing masks compared with that of not wearing them during the COVID-19 pandemic. Risk of bias and quality of evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation. Results: Of the 1,028 studies identified, 9 met the inclusion criteria (2 cohort studies and 7 case-control studies) and were included in the analysis. The meta-analysis using cohort studies alone showed statistically significant differences, wearing a cloth mask decreased by 21% [RD = -0.21 (95% CI, -0.34 to -0.07); I2 = 0%; p = 0,002] the risk of COVID-19 infection, but the quality of evidence was low. Regarding case-control studies, wearing a surgical mask reduced the chance of COVID-19 infection [OR = 0.51 (95% CI, 0.37-0.70); I2 = 47%; p = 0.0001], as did wearing an N95 respirator mask [OR = 0.31 (95% CI, 0.20-0.49); I2 = 0%; p = 0.00001], both with low quality of evidence. Conclusions: In this systematic review with meta-analysis, we showed the effectiveness of wearing masks in the prevention of SARS-CoV-2 infection regardless of the type of mask (disposable surgical mask, common masks, including cloth masks, or N95 respirators), although the studies evaluated presented with low quality of evidence and important biases.

Keywords: Antiviral agents; COVID-19; SARS-CoV-2; Masks.

Objective: To investigate the efficacy of upper limb exercise training (ULExT) in improving the performance of activities of daily living (ADL) that involve the upper limbs (UL) in patients with COPD. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review. PubMed and EBSCOhost databases were searched to identify randomized controlled trials involving adults with COPD who underwent ULExT, compared with those who underwent other types of exercise or no exercise, in order to assess the performance of ADL that involve the UL. The methodological quality of the selected studies was assessed using the Physiotherapy Evidence Database scale. Results: Five studies, with a total sample of 173 subjects, met the inclusion criteria. The results of the selected studies showed that ULExT is safe and can significantly improve the performance of ADL that involve the UL in patients with COPD. However, there were inconsistencies in the results, especially regarding the perception of symptoms during ADL. The small number of studies included and their methodological quality do not allow for firm conclusions. Conclusions: The findings of this review revealed that ULExT is a safe therapeutic approach and can improve the performance of ADL that involve the UL in patients with COPD, but the results are unclear. Further investigation through well-designed randomized trials is warranted to determine the effectiveness of ULExT in improving the performance of ADL that involve the UL in patients with COPD.

Keywords: Upper extremity; Pulmonary disease, chronic obstructive; Activities of daily living, Exercise therapy.

Nitric oxide (NO) is an endogenous vasoactive compound that contributes to pulmonary vascular homeostasis and is produced by three nitric oxide synthase (NOS) isoforms-neuronal NOS (nNOS); inducible NOS (iNOS); and endothelial NOS (eNOS)-all three of which are present in the lung. Studies using pharmacological inhibitors or knockout mice have shown that eNOS-derived NO plays an important role in modulating pulmonary vascular tone and attenuating pulmonary hypertension. However, studies focusing on the role of iNOS have shown that this isoform contributes to the pathophysiology of acute lung injury and acute respiratory distress syndrome. This review aimed at outlining the role played by NO in the control of pulmonary circulation, both under physiological and pathophysiological conditions. In addition, we review the evidence that the L-arginine-NO-cyclic guanosine monophosphate pathway is a major pharmacological target in the treatment of pulmonary vascular diseases.

Keywords: Nitric oxide; Arginine; Nitric oxide synthase; Cyclic GMP; Pulmonary circulation.