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.

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.

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 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.

Although cystic fibrosis (CF) is an irreversible genetic disease, advances in treatment have increased the life expectancy of CF patients. Upper airway involvement, which is mainly due to pathological changes in the paranasal sinuses, is prevalent in CF patients, although many are only mildly symptomatic (with few symptoms). The objective of this literature review was to discuss the pathophysiology and current therapeutic management of chronic rhinosinusitis (CRS) in CF patients. The review was based on current evidence, which was classified in accordance with the Oxford Centre for Evidence-Based Medicine criteria. When symptomatic, CRS with nasal polyps can affect quality of life and can lead to pulmonary exacerbations, given that the paranasal sinuses can be colonized with pathogenic bacteria, especially Pseudomonas aeruginosa. Infection with P. aeruginosa plays a crucial role in morbidity and mortality after lung transplantation in CF patients. Although clinical treatment of the upper airways is recommended as initial management, this recommendation is often extrapolated from studies of CRS in the general population. When sinonasal disease is refractory to noninvasive therapy, surgery is indicated. Further studies are needed in order to gain a better understanding of upper airway involvement and improve the management of CRS in CF patients, with the objective of preserving lung function and avoiding unnecessary invasive procedures.

Keywords: Nose diseases; Cystic fibrosis; Nasal polyps; Paranasal sinuses; Sinusitis.

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.

Over the last five years, knowledge in the field of pulmonary hypertension has grown consistently and significantly. On the basis of various clinical studies showing the usefulness of new diagnostic tools, as well as the efficacy of new medications and drug combinations, new diagnostic and treatment algorithms have been developed. Likewise, in order to simplify the clinical management of patients, the classification of pulmonary hypertension has been changed in an attempt to group the various forms of pulmonary hypertension in which the diagnostic and therapeutic approaches are similar. The objective of this review was to discuss these modifications, based on the 2005 Brazilian guidelines for the management of pulmonary hypertension, emphasizing what has been added to the international guidelines.

Keywords: Hypertension, pulmonary/diagnosis; Hypertension, pulmonary/therapy; Clinical protocols.

We summarize here data regarding the spectrum of action, the pharmacological aspects, the toxicological aspects and the clinical efficacy of liposomal amphotericin B, amphotericin B in colloidal dispersion, amphotericin B lipid complex, voriconazole and caspofungin. We discuss the use of these more recently introduced antifungal agents in terms of their safety, efficiency and cost. We also offer suggestions for the clinical use of these drugs in pulmonary and systemic infections, with an emphasis on the lower toxicity of the lipid formulations of amphotericin B in comparison with conventional medications. In addition, we explore the possibility of using voriconazole as the primary treatment for invasive infections such as aspergillosis, as well as those caused by Scedosporium spp. and Fusarium spp., together with that of using caspofungin to treat disseminated candidiasis and invasive aspergillosis.

Keywords: Aspergillosis; Lung diseases, fungal/drug therapy; Amphotericin b/administration & dosage;

Worldwide, COPD is a major cause of morbidity and mortality. The clinical and functional manifestations of COPD result from lung injury occurring through various mechanisms, including oxidative stress, inflammation, protease-antiprotease imbalance and apoptosis. Oxidative stress is central to the pathogenesis of COPD, since it can directly damage lung structures and exacerbate the other mechanisms involved. The cellular and molecular events involved in such lung injury are believed to occur long before the clinical and functional expression of COPD. Although the use of bronchodilators is currently the principal treatment for COPD, bronchodilators have little or no effect on disease progression. A better understanding of the pathogenesis of COPD, together with renewed efforts in basic and clinical research, will allow the diagnosis of COPD at a pre-clinical stage and provide more appropriate monitoring of disease activity, as well as leading to the development of novel therapeutic agents that will effectively prevent the progression of the disease.

Keywords: Pulmonary disease, chronic obstructive; Oxidative stress; Oxidants; Antioxidants; Inflammation.

Objective: To evaluate the quality of diagnosis and the epidemiological profile of patients with pleural tuberculosis in the state of Roraima, Brazil, in order to provide technical support for the development and implementation of public policies to combat the disease. Methods: This was a cross-sectional study designed to determine the prevalence of pleural forms of tuberculosis in Roraima between 2005 and 2013 and to evaluate the diagnostic criteria used, as well as their determinants. This study was based on secondary data from the Brazilian Case Registry Database, including all reported cases of pleural tuberculosis in the state during the study period. Diagnoses based on bacteriological or histopathological confirmation were defined as high-quality diagnoses. Results: Among the 1,395 cases of tuberculosis reported during the study period, 116 (8.3%) were cases of pleural tuberculosis, accounting for 38.9% of all cases of extrapulmonary tuberculosis in the sample. The incidence rate of pleural tuberculosis did not follow the downward trend observed for the pulmonary form of the disease during the same period. The prevalence of cases with a high-quality diagnosis was 28.5% (95% CI: 20.4-37.6%). In a univariate analysis, none of the demographic or clinical characteristics collected from the database were found to have a significant impact on the outcome (as explanatory variables). Conclusions: The quality of the diagnoses in our study sample was considered unsatisfactory. Limited access to specific diagnostic methods might have contributed to these results.

Keywords: Tuberculosis/diagnosis; Tuberculosis/epidemiology; Tuberculosis, pleural.

Smoking is the leading cause of respiratory disease (RD). The harmful effects of smoking on the respiratory system begin in utero and influence immune responses throughout childhood and adult life. In comparison with "healthy" smokers, smokers with RD have peculiarities that can impede smoking cessation, such as a higher level of nicotine dependence; nicotine withdrawal; higher levels of exhaled carbon monoxide; low motivation and low self-efficacy; greater concern about weight gain; and a high prevalence of anxiety and depression. In addition, they require more intensive, prolonged treatment. It is always necessary to educate such individuals about the fact that quitting smoking is the only measure that will reduce the progression of RD and improve their quality of life, regardless of the duration and severity of the disease. Physicians should always offer smoking cessation treatment. Outpatient or inpatient smoking cessation treatment should be multidisciplinary, based on behavioral interventions and pharmacotherapy. It will thus be more effective and cost-effective, doubling the chances of success.

Keywords: Respiratory tract diseases/therapy; Respiratory tract diseases/drug therapy; Tobacco use disorder/epidemiology; Smoking cessation; Counseling; Lung neoplasms.

Objective: Pulmonary nontuberculous mycobacterial infections are caused by nontuberculous mycobacteria (NTM), the microbiological diagnosis of which involves the isolation and identification of the same species in at least two sputum samples, one BAL fluid sample, or one lung biopsy sample. The objective of the present study was to determine the frequency at which the various NTM species are identified among selected individuals and in potential cases of pulmonary nontuberculous mycobacterial infection. Methods: This was a retrospective analysis of the data on species isolated from respiratory specimens collected from 2,843 individuals between 2011 and 2014. Potential NTM infection cases were identified on the basis of the international microbiological criteria adopted in the state of São Paulo. Results: A total of 50 species were identified using the molecular method PCR-restriction enzyme analysis. Samples collected from 1,014 individuals were analyzed in relation to the microbiological criteria, and 448 (44.18%) had a presumptive diagnosis of pulmonary nontuberculous mycobacterial infection, the species identified most frequently being, in descending order, Mycobacterium kansasii, M. abscessus, M. intracellulare, M. avium, and M. szulgai. Conclusions: Although various NTM species were identified among the individuals studied, those presumptively identified most frequently on the basis of the microbiological criteria adopted in the state of São Paulo were the ones that are most commonly associated with pulmonary nontuberculous mycobacterial infection worldwide or in specific geographic regions.

Keywords: Nontuberculous mycobacteria/classification; Mycobacterium infections, nontuberculous/diagnosis; Lung.