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 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.

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.

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.

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.

Objectives: To describe a group of patients with thymoma who were submitted to surgica treatment associated or not with therapy, and evaluate their prognosis. Methods: Of the 104 patients with thymic tumors who were operated at Hospital das Clínicas - São Paulo University Medical School between 1965 and 1998, (66.3%) were males. Mean age at diagnosis, was 47.9% ± 16.3 years (ranging from 13 to 76 years). Results: Of the 104 patients, 89 (85.6%) underwent complete thymoma resection, 6 (5.8%) underwent partial resection and, in 9 (8.6%) of them, biopsy was performed. Anatomopathologic diagnosis (thymoma vs malignant thymoma) and the type of surgery (biopsy vs complete resection vs partial resection) were significant predictors of survival mean time (p < 0.02). Conclusions: Complete resection is the treatment of choice for thymomas. These tumors, when not invasive and completely resected, have good immediate and late prognosis.

Keywords: Thymoma.

This study was a review of the literature on the epidemiological, clinical, diagnostic and therapeutic aspects of allergic rhinitis. Bibliographic searches were based on the information contained within the Medline, Latin American and Caribbean Health Sciences Literature and HighWire databases, covering the last thirty years and using the following search terms: 'allergic rhinitis', 'epidemiology', 'diagnosis' and 'treatment'. Sixty articles were selected. This study describes the increase in the prevalence of allergic rhinitis, its relationship with asthma, the diagnostic criteria and the treatment. The classification of allergic rhinitis and strategies for its treatment are presented. Therapeutic modalities presented and discussed include the administration of antihistamines, corticosteroids, immunotherapy, anti-leukotrienes, sodium cromoglycate and anti-IgE antibodies, as well as minimizing exposure to inhaled allergens. Finally, the importance of the management of allergic rhinitis in public health is emphasized.

Keywords: Rhinitis/therapy; Hypersensitivity; Epidemiology; Diagnosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease without a clear recognizable cause. IPF has been at the forefront of new diagnostic algorithms and treatment developments that led to a shift in patients' care in the past decade, indeed influencing the management of fibrotic interstitial lung diseases other than IPF itself. Clinical presentation, pathophysiology, and diagnostic criteria are briefly addressed in this review article. Additionally, evidence regarding the use of antifibrotics beyond the settings of clinical trials, impact of comorbidities, and therapeutic approaches other than pharmacological treatments are discussed in further detail.

Keywords: Idiopathic pulmonary fibrosis/diagnosis; Idiopathic pulmonary fibrosis/physiopathology; Idiopathic pulmonary fibrosis/therapy; Idiopathic pulmonary fibrosis/rehabilitation.

Objectives: Thoracoscopic management of mediastinal tumors is still subject to analysis. Seventy-three patients were submitted to thoracoscopy for the treatment of mediastinal masses and were analyzed retrospectively, in order to evaluate the effectiveness and complications of the procedure. Methods: Between 1983 and 1999, 21 conventional thoracoscopies and 52 video-assisted thoracic surgeries were performed (33 for diagnostic purposes and 40 for therapy). Patient ages ranged from two to 81 years (mean 43.8) with a slight predominance of females over males (41 versus 32). All underwent general anesthesia using simple (22) or double lumen (51) intubation. Results: The histological type of tumor was identified in all patients. For therapeutic purposes, conversion to thoracotomy was necessary in nine patients. The reasons were tumor size and invasion of nearby structures, difficulty to continue dissection, to perform an upper lobectomy, and to suture the iatrogenic diaphragm lesion. Four patients died during the first 30 postoperative days as a consequence of their primary pathology. Conclusions: Thoracoscopy was confirmed to be an effective diagnostic and therapeutic alternative for the treatment of mediastinal disorders.

Keywords: Thoracoscopy, thoracic surgery, mediastinal neoplasms, mediastinal cysts.

With the objective of establishing guidelines for the prevention, diagnosis and treatment of compensatory hyperhidrosis, consensus meetings were held. Attendees included a general surgeon and thoracic surgeons affiliated with the Brazilian Society of Thoracic Surgery. The topics addressed were those that would ostensibly broaden multidisciplinary knowledge. Based on recent guidelines for the prevention, diagnosis and (clinical and surgical) treatment of compensatory hyperhidrosis, as well as on a review of the medical literature, the participants prepared a preliminary text, whose recommendations were revised and subsequently approved by all of the participants. The consensus text was posted on the Internet, becoming the object of further corrections and revisions prior to taking on its present form.

Keywords: Hyperhidrosis/therapy; Hyperhidrosis/surgery; Sympathectomy/methods; Postoperative complications; Thoracic surgery, video‑assisted.

Background: Lung cancer is the leading cause of cancer-related death worldwide. Objective: To determine the time spent diagnosing, staging and surgically treating lung cancer in a university hospital. Method: Between January 1990 and December 1998, 69 (53 male, 16 female) patients were diagnosed with lung cancer and underwent surgery. The hospital records of these patients were reviewed to evaluate clinical and histological data, dates of outpatient visits, hospital admission, tests and procedures, as well as to determine if the patients were examined as inpatients or as outpatients. Results: The 15 patients investigated as outpatients were designated as group I, the 28 examined as both inpatients and outpatients as group II, and the 26 investigated as inpatients as group III. Age ranged from 43 to 79 years (mean ± SD; 61 ± 10). Of the 69 patients, 43 were smokers and 23 were ex-smokers. The mean time from onset of symptoms to the first outpatient visit was 110 days and 33 days from the first outpatient visit until diagnosis. There was a lapse of 25 days between diagnosis and surgery. The mean total elapsed time between the first outpatient visit and surgery was 58 days. The mean total time was 72 days for group I, 72 days for group II, and 35 days for group III (p < 0.01). There was no significant difference regarding total time in relation to the different stages of the disease (p = 0.16). Conclusions: The results show that patients waited too long before seeking medical assistance and that medical treatment of lung cancer was further delayed when patients were examined in an outpatient setting.

Keywords: Lung neoplasm/surgery. Disease progression.

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.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by dysfunction of the CFTR gene. It is a multisystem disease that most often affects White individuals. In recent decades, various advances in the diagnosis and treatment of CF have drastically changed the scenario, resulting in a significant increase in survival and quality of life. In Brazil, the current neonatal screening program for CF has broad coverage, and most of the Brazilian states have referral centers for the follow-up of individuals with the disease. Previously, CF was limited to the pediatric age group. However, an increase in the number of adult CF patients has been observed, because of the greater number of individuals being diagnosed with atypical forms (with milder phenotypic expression) and because of the increase in life expectancy provided by the new treatments. However, there is still great heterogeneity among the different regions of Brazil in terms of the access of CF patients to diagnostic and therapeutic methods. The objective of these guidelines was to aggregate the main scientific evidence to guide the management of these patients. A group of 18 CF specialists devised 82 relevant clinical questions, divided into five categories: characteristics of a referral center; diagnosis; treatment of respiratory disease; gastrointestinal and nutritional treatment; and other aspects. Various professionals working in the area of CF in Brazil were invited to answer the questions devised by the coordinators. We used the PubMed database to search the available literature based on keywords, in order to find the best answers to these questions.

Keywords: Cystic fibrosis/diagnosis; Cystic fibrosis/therapy; Cystic fibrosis/complications; Practice guideline.

The authors report the case of a 7-year-old girl, with a history of recurrent respiratory infections since five months of age. Immunological evaluation at four years of age revealed a normal level of total serum immunoglobulins, but a deficient humoral response to Streptococcus pneumoniae. Although having all normal IgG subclasses, the patient had inadequate antibody levels to all serotypes tested (1, 3, 5, 6, 9, and 14). Concurrent radiological evaluation showed diffuse atelectasis and bronchiectasis. Patient was started on IVIG, and subsequent chest CT scan revealed resolution of the above-mentioned lesions. To prevent irreversible damage to lung parenchyma, due to recurrent lower respiratory infections, it is important to identify immunocompromised individuals and treat them accordingly.

Keywords: Immunologic deficiency syndromes. Streptococcus pneumoniae.

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.

The epidemiological relevance of tuberculosis is directly related to the socioeconomic profile of a given country. Vulnerability to tuberculosis is influenced by biological factors (e.g., malnutrition, HIV infection, and age) and social factors (e.g., unhealthy housing, high population density, inappropriate working conditions, and lack of access to health services). In many cases, multiple vulnerabilities occur in conjunction. We propose here a reflection on tuberculosis from the point of view of the social determinants of health, as well as the costs associated with its diagnosis and treatment in Brazil, based not only on data in the international literature but also on evidence related to the national context. Given the magnitude of tuberculosis as a socially mediated disease, there is an evident need for greater involvement of health professionals and of the scientific community to implement relevant operational and research measures to understand the social conditions influencing the health-illness continuum for tuberculosis patients. Although the recent economic crisis in Brazil has contributed to increased mortality from all causes, including tuberculosis, health and social protection expenditures have mitigated detrimental health effects. The evidence presented here underscores the importance of public social protection policies for minimizing the effects of tuberculosis indicators, with the aim of eliminating tuberculosis in Brazil.

Keywords: Tuberculosis; Social determinants of health; Cost of illness; Costs and cost analysis.