Objective: To evaluate the prevalence of alpha-1 antitrypsin (AAT) variants through SERPINA1 genotyping in patients with non-cystic fibrosis bronchiectasis, and assess their clinical, functional and radiological characteristics. AAT deficiency is underdiagnosed, and an etiology to be considered when evaluating bronchiectasis. Methods: A cross-sectional study was conducted at an outpatient clinic focused on bronchiectasis in a tertiary hospital. Data from patients followed between 2005 and 2023 were collected. Genotyping for AAT was performed. Demographic, clinical, pulmonary function tests, serum AAT levels and chest CT data were analyzed. Results: A total of 136 patients were included, predominantly female (72.1%), with a median age of 56.6 years. The prevalence of SERPINA1 gene mutations was 25.7% (n=35). Among the detected variant genotypes were Pi*MS (15.4%), Pi*MZ (5,1%), Pi*SS (1,5%), Pi*ZZ (1,5%), Pi*MI (0,7%), Pi*SZ (0,7%) and Pi*ZMMalton (0,7%). When comparing patients with and without SERPINA1 mutations, significant differences were observed in AAT serum levels, emphysema type (panlobular) and distribution (diffuse and lower-lobe predominant). No other clinical, microbiological, functional or radiological differences were found, including emphysema presence or absence. Notably, 16 (45.7%) of individuals carrying SERPINA1 mutations exhibited normal serum AAT levels. Conclusions: AAT variants are not uncommon among patients with bronchiectasis. Presence of panlobular, diffuse or lower-lobe predominant emphysema should prompt AATD diagnostic consideration. However, the absence of emphysema does not exclude the diagnosis. Moreover, SERPINA1 variants may occur along with normal AAT serum levels. Clinicians should consider genotyping in patients with normal AAT levels, particularly when bronchiectasis remains unexplained.

Keywords: Alpha 1-antitrypsin deficiency; Bronchiectasis; Genotype; Mutation; Alleles

Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of < 113 mg/dL underwent genotyping. In case of conflicting results, SERPINA1 gene sequencing was performed. Results: Of the 926 COPD patients studied, 85 had DBS AAT levels ≤ 2.64 mg/dL, and 24 (2.6% of the study sample) had serum AAT levels of < 113 mg/dL. Genotype distribution in this subset of 24 patients was as follows: PI*MS, in 3 (12.5%); PI*MZ, in 13 (54.2%); PI*SZ, in 1 (4.2%); PI*SS, in 1 (4.2%); and PI*ZZ, in 6 (25.0%). In the sample as a whole, the overall prevalence of AATD was 2.8% and the prevalence of the PI*ZZ genotype (severe AATD) was 0.8% Conclusions: The prevalence of AATD in COPD patients in Brazil is similar to that found in most countries and reinforces the recommendation that AAT levels be measured in all COPD patients.

Keywords: alpha 1-antitrypsin deficiency/epidemiology; pulmonary disease, chronic obstructive/epidemiology; Alleles; alpha 1-antitrypsin.

Alpha-1 antitrypsin deficiency (AATD) is a relatively rare genetic disorder, inherited in an autosomal codominant manner, that results in reduced serum AAT concentrations, with a consequent reduction in antielastase activity in the lungs, as well as an increased risk of diseases such as pulmonary emphysema, liver cirrhosis, and necrotizing panniculitis. It results from different mutations in the SERPINA1 gene, leading to changes in the AAT glycoprotein, which can alter its concentration, conformation, and function. Unfortunately, underdiagnosis is quite common; it is possible that only 10% of cases are diagnosed. The most common deficiency is in the Z variant, and it is estimated that more than 3 million people worldwide have combinations of alleles associated with severe AATD. Serum AAT concentrations should be determined, and allelic variants should be identified by phenotyping or genotyping. Monitoring lung function, especially through spirometry, is essential, because it provides information on the progression of the disease. Although pulmonary densitometry appears to be the most sensitive measure of emphysema progression, it should not be used in routine clinical practice to monitor patients. In general, the treatment is similar to that indicated for patients with COPD not caused by AATD. Exogenous administration of purified human serum-derived AAT is the only specific treatment approved for AATD in nonsmoking patients with severe deficiency (serum AAT concentration of < 57 mg/dL or < 11 µM), with evidence of functional loss above the physiological level.

Keywords: alpha 1-antitrypsin; Emphysema; Pulmonary disease, chronic obstructive.

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder caused by a mutation in the SERPINA1 gene, which encodes the protease inhibitor alpha-1 antitrypsin (AAT). Severe AATD predisposes individuals to COPD and liver disease. Early diagnosis is essential for implementing preventive measures and limiting the disease burden. Although national and international guidelines for the diagnosis and management of AATD have been available for 20 years, more than 85% of cases go undiagnosed and therefore untreated. In Brazil, reasons for the underdiagnosis of AATD include a lack of awareness of the condition among physicians, a racially diverse population, serum AAT levels being assessed in a limited number of individuals, and lack of convenient diagnostic tools. The diagnosis of AATD is based on laboratory test results. The standard diagnostic approach involves the assessment of serum AAT levels, followed by phenotyping, genotyping, gene sequencing, or combinations of those, to detect the specific mutation. Over the past 10 years, new techniques have been developed, offering a rapid, minimally invasive, reliable alternative to traditional testing methods. One such test available in Brazil is the A1AT Genotyping Test, which simultaneously analyzes the 14 most prevalent AATD mutations, using DNA extracted from a buccal swab or dried blood spot. Such advances may contribute to overcoming the problem of underdiagnosis in Brazil and elsewhere, as well as being likely to increase the rate detection of AATD and therefore mitigate the harmful effects of delayed diagnosis.

Keywords: alpha 1-antitrypsin deficiency/diagnosis; alpha 1-antitrypsin deficiency/genetics; Genotyping techniques.

Objective: The clinical, functional, radiological and genotypic descriptions of patients with an alpha-1 antitrypsin (A1AT) gene mutation in a referral center for COPD in Brazil. Methods: A cross-sectional study of patients with an A1AT gene mutation compatible with deficiency. We evaluated the A1AT dosage and genotypic, demographic, clinical, tomographic, and functional characteristics of these patients. Results: Among the 43 patients suspected of A1AT deficiency (A1ATD), the disease was confirmed by genotyping in 27 of them. The A1AT median dosage was 45 mg/dL, and 4 patients (15%) had a normal dosage. Median age was 54, 63% of the patients were male, and the respiratory symptoms started at the age of 40. The median FEV1 was 1.37L (43% predicted). Tomographic emphysema was found in 77.8% of the individuals. The emphysema was panlobular in 76% of them and 48% had lower lobe predominance. The frequency of bronchiectasis was 52% and the frequency of bronchial thickening was 81.5%. The most common genotype was Pi*ZZ in 40.7% of participants. The other genotypes found were: Pi*SZ (18.5%), PiM1Z (14.8%), Pi*M1S (7.4%), Pi*M2Z (3.7%), Pi*M1I (3.7%), Pi*ZMnichinan (3.7%), Pi*M3Plowell (3.7%), and Pi*SF (3.7%). We did not find any significant difference in age, smoking load, FEV1, or the presence of bronchiectasis between the groups with a normal and a reduced A1AT dosage, neither for 1 nor 2-allele mutation for A1ATD. Conclusions: Our patients presented a high frequency of emphysema, bronchiectasis and bronchial thickening, and early-beginning respiratory symptoms. The most frequent genotype was Pi*ZZ. Heterozygous genotypes and normal levels of A1AT also manifested significant lung disease.

Keywords: Alpha-1 antitrypsin; Emphysema; Alleles.

Objective: To determine the prevalence of nutritional deficiency among patients with pulmonary tuberculosis. Methods: This was a cross-sectional study using data obtained from the Brazilian Case Registry Database and from the medical records of patients diagnosed with pulmonary tuberculosis (15-59 years of age) residing in one of the municipalities that make up the 16th Regional Health District of the state of Bahia. We calculated the incidence, lethality, and mortality rates, as well as the prevalence of nutritional deficiency, as evaluated by body mass index. Demographic, social, clinical, and epidemiological data were collected. Results: Of the 72 confirmed cases of tuberculosis, 59 (81.9%) were in males, and 21 (29.2%) of the patients were in the 40-49 year age bracket. The majority (85.3%) described themselves as Mulatto or Black; 55.2% reported using alcohol; and approximately 90% were treated as outpatients. In the district and age bracket studied, the incidence of pulmonary tuberculosis was 30.6/100,000 population. Among the 72 patients, data regarding nutritional status was available for 34. Of those, 50% and 25%, respectively, presented nutritional deficiency at the beginning and at the end of treatment. No statistically significant differences were found between normal-weight and malnourished patients regarding the characteristics studied. Conclusions: The prevalence of nutritional deficiency was high among our sample of patients with pulmonary tuberculosis. This underscores the importance of nutritional follow-up for the assessment of tuberculosis treatment in the decision-making process regarding therapeutic interventions.

Keywords: Malnutrition; Tuberculosis; Body mass index; Malnutrition/epidemiology.

Objective: To analyze and compare the transport properties of respiratory secretions, classified by selected parameters, in individuals with bronchiectasis unrelated to cystic fibrosis. Methods: We collected mucus samples from 35 individuals with bronchiectasis unrelated to cystic fibrosis. The samples were first classified by their surface properties (adhesive or nonadhesive), as well as by their aspect (mucoid or purulent). We then tested the samples regarding relative transport velocity (RTV), displacement in a simulated cough machine (SCM), and contact angle (CA). For the proposed comparisons, we used ANOVA models, with a level of significance set at 5%. Results: In comparison with nonadhesive samples, adhesive samples showed significantly less displacement in the SCM, as well as a significantly higher CA (6.52 ± 1.88 cm vs. 8.93 ± 2.81 cm and 27.08 ± 6.13° vs. 22.53 ± 5.92°, respectively; p < 0.05 for both). The same was true in the comparison between purulent and mucoid samples (7.57 ± 0.22 cm vs. 9.04 ± 2.48 cm and 25.61 ± 6.12° vs. 21.71 ± 5.89°; p < 0.05 for both). There were no significant differences in RTV among the groups of samples, although the values were low regardless of the surface properties (adhesive: 0.81 ± 0.20; nonadhesive: 0.68 ± 0.24) or the aspect (purulent: 0.74 ± 0.22; mucoid: 0.82 ± 0.22). Conclusions: The respiratory secretions of patients with bronchiectasis showed decreased mucociliary transport. Increased adhesiveness and purulence cause the worsening of transport properties, as demonstrated by the lesser displacement in the SCM and the higher CA.

Keywords: Bronchiectasis; Mucus; Mucociliary clearance; Adhesiveness.

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 the prevalence of vitamin D deficiency/insufficiency in children 0-18 years of age with recurrent wheezing and/or asthma residing in the microregion of Viçosa, Minas Gerais, Brazil, and treated at a referral center, and to determine its association with major risk factors for wheezing. Methods: A cross-sectional study was performed using a semi-structured questionnaire, which was administered by trained interviewers to the legal guardians of the study participants. Data were obtained regarding general characteristics of recurrent wheezing; general sociodemographic, environmental, and biologic factors; and atopy-related factors. The magnitude of the statistical association was assessed by calculating ORs and their corresponding 95% CIs by using multiple logistic regression. Results: We included 124 children in the study. The prevalence of vitamin D deficiency/insufficiency in the sample was 57.3%. Vitamin D deficiency/insufficiency was found to be associated with wheezing in the first year of life, personal history of atopic dermatitis, environmental pollution, and vitamin D supplementation until 2 years of age. Conclusions: The prevalence of vitamin D deficiency/insufficiency was high in our sample. Vitamin D concentrations were directly associated with vitamin D supplementation until 2 years of age and were inversely associated with wheezing events in the first year of life, personal history of atopic dermatitis, and environmental pollution.

Keywords: Vitamin D; Asthma; Respiratory sounds; Minors.

Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical implications. Alpha-1 antitrypsin is mainly produced in the liver and acts as an antiprotease. Its principal function is to inactivate neutrophil elastase, preventing tissue damage. The mutation most commonly associated with the clinical disease is the Z allele, which causes polymerization and accumulation within hepatocytes. The accumulation of and the consequent reduction in the serum levels of alpha-1 antitrypsin cause, respectively, liver and lung disease, the latter occurring mainly as early emphysema, predominantly in the lung bases. Diagnosis involves detection of low serum levels of alpha-1 antitrypsin as well as phenotypic confirmation. In addition to the standard treatment of chronic obstructive pulmonary disease, specific therapy consisting of infusion of purified alpha-1 antitrypsin is currently available. The clinical efficacy of this therapy, which appears to be safe, has yet to be definitively established, and its cost-effectiveness is also a controversial issue that is rarely addressed. Despite its importance, in Brazil, there are no epidemiological data on the prevalence of the disease or the frequency of occurrence of deficiency alleles. Underdiagnosis has also been a significant limitation to the study of the disease as well as to appropriate treatment of patients. It is hoped that the creation of the Alpha One International Registry will resolve these and other important issues.

Keywords: alpha 1-antitrypsin; Emphysema; Pulmonary disease, chronic obstructive.

Background: The relationship between myasthenia and the thymus is evident and the current treatment of this condition includes thymectomy. However, a revision of our experience with thymectomy has revealed the necessity of a more radical technique. Objective: To analyze, retrospectively, myasthenia gravis patients who underwent videothoracoscopic radical thymectomy, emphasizing the advantages and drawbacks of the methodology, pathological findings and results related to disease control. Material and methods: Twenty-one myasthenic patients (18 females and 3 males, aged 17 to 51 years), underwent videothoracoscopic bilateral thymectomy associated to transverse cervicotomy for removal of the thymus gland and surrounding tissues, and right and left pericardiac fat tissues. Those tissues were separately sent to pathology analysis. The mean time of follow-up was 39.2 months. Results: There were no intra-operative deaths. Two patients (9.5%) suffered vascular injury, and one patient (4.8%) presented a low level permanent dysphonia. Nineteen patients (90.4%) are doing well, with none or low dose medications. Pathology studies showed 10 hyperplastic thymuses, 6 with involution and 5 with normal aspect. Ectopic thymic tissue was found in six patients (28.6%). Conclusion: Videothoracoscopic radical thymectomy offered a good control of myasthenia gravis. Additionally, ectopic thymus tissue was removed from some patients.

Keywords: Thorax. Surgery, video-assisted. Myastenia gravis. Thymectomy.

Objective: To analyze and compare the mutations in two different regions of the katG gene, which is responsible for isoniazid (INH) resistance. Methods: We analyzed 97 multidrug-resistant Mycobacterium tuberculosis strains isolated in cultures of sputum samples obtained from the Professor Hélio Fraga Referral Center, in Brasília, Brazil. Another 6 INH-sensitive strains did not present mutations and were included as controls. We used PCR to amplify two regions of the katG gene (GenBank accession no. U06258)-region 1, (from codon 1 to codon 119) and region 2 (from codon 267 to codon 504)-which were then sequenced in order to identify mutations. Results: Seven strains were resistant to INH and did not contain mutations in either region. Thirty strains carried mutations in region 1, which was characterized by a high number of deletions, especially at codon 4 (24 strains). Region 2 carried 83 point mutations, especially at codon 315, and there was a serine-to-threonine (AGC-to-ACC) substitution in 73 of those cases. The analysis of region 2 allowed INH resistance to be diagnosed in 81.4% of the strains. Nine strains had mutations exclusively in region 1, which allowed the proportion of INH-resistant strains identified to be increased to 90.6%. Conclusions: The number of mutations at codon 315 was high, which is consistent with cases described in Brazil and in other countries, and the analysis of region 1 resulted in a 9.2% increase in the rate at which mutations were identified.

Keywords: Isoniazid; Mutation; Tuberculosis; Drug resistance, multiple.

Background: Lobectomy is still considered the most effective method of controlling primary lung tumors. Method: During the period from 1995 to 2000, 733 cases of non-small cell bronchial carcinoma. After clinical evaluation and surgical staging, 191 patients were submitted to surgical resection. Of those 191 surgeries, 63 were for locally advanced tumors and 128 (69 segmentectomies and 59 lobectomies) for primary tumors. Post-operative FEV1 of at least 800 ml was used as a measure of surgical success. Extended segmentectomies, in which the resection passes the intersegmental line, including the parenchyma of the adjoining segment, were used. Results: Among the 128 patients with primary tumors, there were 3 deaths and 10 patients fell out of contact. Therefore, 62 segmentectomies and 53 lobectomies were evaluated. There were 72 adenocarcinomas and 43 epidermoid carcinomas. The 5-year survival of lobectomy patients was 80% (T1N0), 72.7% (T2N0), 50% (T1N1) and 31.8% (T2N1), whereas that of segmentectomy patients was 80% (T1N0), 66.6% (T2N0), 41.1% (T1N1) and 30% (T2N1) (p > 0.05). Tumor size and enlarged interlobar lymph nodes were prognostically significant (p < 0.001), although method of resection influenced neither survival nor local or remote recurrence (p > 0.05). Conclusion: Extended segmentectomy represents an alternative treatment for primary tumors in patients with limited lung reserve.

Keywords: Lung Neoplasms, surgery. Pulmonary Surgical Procedures. Carcinoma, Non-Small-Cell Lung.

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.

Tracheal diverticulum, defined as a benign outpouching of the tracheal wall, is rarely diagnosed in clinical practice. It can be congenital or acquired in origin, and most cases are asymptomatic, typically being diagnosed postmortem. We report a case of a 69-year-old woman who was hospitalized after presenting with fever, fatigue, pleuritic chest pain, and a right neck mass complicated by dysphagia. Her medical history was significant: pulmonary emphysema (alpha-1 antitrypsin deficiency); bronchiectasis; and thyroidectomy. On physical examination, she presented diminished breath sounds and muffled heart sounds, with a systolic murmur. Laboratory tests revealed elevated inflammatory markers, a CT scan showed an air-filled, multilocular mass in the right tracheal wall, and magnetic resonance imaging confirmed the CT findings. Fiberoptic bronchoscopy failed to reveal any abnormalities. Nevertheless, the patient was diagnosed with tracheal diverticulum. The treatment approach was conservative, consisting mainly of antibiotics. After showing clinical improvement, the patient was discharged.

Keywords: Tracheal diseases; Pulmonary emphysema; Diverticulum; alpha 1-antitrypsin deficiency.