The relationship between structure and function in asthma has been extensively studied. All the compartments of the airway have been shown to have some structural alterations contributing to functional defects. The structural alterations are thought to be a consequence of the chronic inflammation present in asthmatic airways, leading ultimately to remodeling. The decline of the ventilatory function over time in some asthmatic patients may be a consequence of airway remodeling. In this review, the authors describe the phenomena leading to airway remodeling and discuss the role of inflammatory mediators involved in this process. The structural alterations of the asthmatic airways are presented and the possible correlated functional defects are discussed.

Keywords: bronchii; pathology; asthma.

Currently available treatments for asthma provide satisfactory control of the disease in most cases. However, a significant number of patients do not respond to such treatments (i.e., do not achieve effective symptom relief). One novel approach to treating asthma is bronchial thermoplasty, in which the airway smooth muscle is specifically and directly treated. This procedure delivers radiofrequency energy to the airways in order to reduce smooth muscle-mediated bronchoconstriction. In this article, we present the thermoplasty technique, summarizing the results of the major randomized clinical trials of the procedure, as well as discussing its mechanisms of action and potential adverse effects. We also propose strategies for the future clinical use of this new treatment.

Keywords: Asthma/prevention & control; Asthma/therapy; Bronchoscopy.

Bronchial asthma is an inflammatory chronic disease of the respiratory tract whose prevalence is increasing worldwide. Since there is no curative treatment available, the principal objective of every approach is to control the disease and to improve the quality of life of patients. Over the last few decades, intervention programs supplementing conventional medical treatments have been tested and implemented. The majority of such programs consist of educational interventions or include some type of educational component. In this study, we attempted to determine the characteristics and the impact of educational interventions on asthma by means of the following: a) an updated review of the various educational interventions developed and implemented for asthma patients; b) the identification of aspects that are common to all of these interventions; and c) the analysis of the findings in the literature regarding the impact that these interventions have on the health and quality of life of patients. We conclude that educational interventions are effective in improving the health and quality of life of asthma patients, as well as in reducing the use and costs of health resources. These findings indicate the importance of including an educational component as part of an integrated approach to this population. Likewise, the inherent complexity of the educational process highlights the importance of a complementary joint effort including various health professionals.

Keywords: Asthma/prevention and control; Health education; Therapeutics.

Bronchial thermoplasty is a new bronchoscopic procedure that delivers radiofrequency energy to the airway and potentially reduces the smooth muscle-mediated bronchoconstriction. We report the case of a 48-year-old man with persistent moderate asthma submitted to bronchial thermoplasty. The treatment increased the forced expiratory volume in one second, increased the number of symptom-free days, reduced the use of relief medications, and improved the Juniper Asthma Quality of Life Scale score. In this patient, bronchial thermoplasty was well tolerated and safe. This was the first bronchial thermoplasty performed in Latin America. At 12 months after the procedure, the results were encouraging in terms of its potential benefits in patients with difficult-to-control asthma.

Keywords: Asthma/treatment; Respiratory function tests; Case reports [publication type].

Acute respiratory distress syndrome (ARDS) is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibroproliferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient's prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

Keywords: Respiratory distress syndrome. Pulmonary alveoli/lesions. Extracellular matrix. Cytokines/ultrastructure.

Objective: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. Methods: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. Results: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = −0.90; p = 0.04). Conclusions: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.

Keywords: Sarcoidosis; Granulomatous disease, chronic; Extracellular matrix; Immunophenotyping; Respiratory function tests.

Objective: To evaluate the asthma prevalence in the Federal District of Brazil, using the questionnaire developed for the International Study of Asthma and Allergies in Childhood to look for correlations with socioeconomic levels. Methods: A total of 6437 children (3183 from six to seven years old and 3254 from thirteen to fourteen years old), attending public or private schools, were evaluated. The data were analyzed by gender and socioeconomic status (chi-square test). Results: The prevalence of asthma in the Federal District was 12.1% among the six- and seven-year-olds and 13.8% among the thirteen- and fourteen-year-olds (p < 0.04). In the six-to-seven age bracket, asthma prevalence was significantly greater, and asthma-related symptoms were more frequent, among males (p < 0.001). In contrast, asthma-related symptoms were more frequent among females in the thirteen-to-fourteen age bracket (p < 0.05). Children belonging to the lowest socioeconomic class, as determined by the responses given on the questionnaire completed by the parents, presented the highest prevalence of asthma, regardless of age bracket (p < 0.001). Among such children, asthma-related symptoms were also more frequent (p < 0.05). In the thirteen-to-fourteen age bracket, the prevalence of asthma was greater among those belonging to the highest socioeconomic class (p = 0.001). Conclusions: Overall, economically disadvantaged children more frequently presented asthma-related symptoms and experienced asthma attacks that were of greater severity. In addition, the prevalence of suspected asthma was higher than that of diagnosed asthma in this group, suggesting that asthma is underdiagnosed in children belonging to the lowest socioeconomic class.

Keywords: Asthma/epidemiology; Asthma/diagnosis; Socioeconomic factors; School health; Questionnaires

Objective: Various studies of emphysema involve long-term exposure of animals to cigarette smoke, focusing on the cell type involved in the protease/antiprotease imbalance and on extracellular matrix degradation. In emphysema, increased expression of metalloproteinases is associated with cytokines, and evidence suggests that the matrix metalloproteinase-12 (MMP-12) plays an important role. Our objective was to investigate tissue inhibitor of metalloproteinase-2 (TIMP-2), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) detection by immunohistochemical methods in mouse lung. Methods: Male C57BL/6 mice were exposed 3 times a day to the smoke of 3 cigarettes over a period of 10, 20, 30 or 60 days in an inhalation chamber (groups CS10, CS20, CS30 and CS60, respectively). Controls were exposed to the same conditions in room air. Results: A progressive increase in the number of alveolar macrophages was observed in the bronchoalveolar lavage fluid of the exposed mice. The mean linear intercept, an indicator of alveolar destruction, was greater in all exposed groups when compared to control group. In the CS10, CS20 and CS30 mice, the immunohistochemical index (II) for MMP-12 increased in parallel with a decrease in II for TIMP-2 in the CS10, CS20 and CS30 mice. The II for the cytokines TNF-α and IL-6 was greater in all exposed groups than in the control group. Emphysema, with changes in volume density of collagen and elastic fibers, was observed in the CS60 group. Conclusions: These findings suggest that cigarette smoke induces emphysema with major participation of TNF-α and IL-6 without participation of neutrophils.

Keywords: Macrophages, alveolar; Emphysema; Tissue inhibitor of metalloproteinase-2; Interleukin-6.

Background: Structural alterations to the pulmonary circulation characterize the vascular remodeling process and are likely correlated with local variations in flow and ischemia. Objective: To define the histological alterations to the pulmonary circulation seen after experimentally-induced ischemia of the pulmonary artery and to correlate those alterations with known patterns of blood redistribution and vascular remodeling. Method: Wistar rats (n = 48) were randomized into two groups with ligation of the pulmonary artery and without (controls) and were sacrificed on post-ischemia days 1, 7, 30 and 60. Lungs were removed and inspected for signs of parenchymal injury. External diameters, as well as wall thicknesses in the pulmonary, alveolar and bronchial end arterioles, were measured. Internal diameter and wall thickness percentage were calculated. Results: Infarction, necrosis and hemorrhage occurred only in ischemic lungs. In nonischemic lungs, there was a sustained increase in the internal and external arteriolar diameters, with an initial reduction in wall thickness on day 1, and day-60 values were similar to those seen in controls. In ischemic lungs, there was a transitory reduction in the internal and external diameters of the pulmonary and bronchial end arterioles, together with an initial, equally transitory, increase in their wall thickness. The alveolar arterioles presented sustained and progressive increases in external diameter and wall thickness, with concomitant reductions in internal diameter. Conclusion: This model mimics distal arterial disease in patients with chronic pulmonary thromboembolism. The vascular response in nonischemic lungs was consistent with a pattern of flow remodeling, whereas that seen in ischemic lungs was more consistent with flow and ischemia. In the pulmonary and bronchial end arterioles, the response was transitory, in contrast to the sustained and progressive response seen in the alveolar arterioles, which was probably caused by delayed local flow.

Keywords: Key-words: Pulmonary embolism. Pulmonary circulation. Vascular remodelling. Pulmonary artery.

Objective: To identify this vagal reflex using bronchial provocation tests in patients with gastroesophageal reflux disease. Methods: The study group was composed of 10 patients presenting endoscopic evidence of hiatal hernia or gastroesophageal reflux disease, and the control group consisted of 11 patients presenting no evidence of either condition. All subjects were submitted to bronchial provocation with carbachol. Results: The provocation test was positive in 5 (50%) of the study group patients and 3 (27%) of the control group patients (p = 0.64). Conclusion: The hypothesis that the airways of patients with gastroesophageal reflux disease (and no history of asthma-like respiratory symptoms) might be more responsive than those of individuals without the disease remains unproven.

Keywords: Asthma/complications; Gastroesophageal reflux/complications; Hernia hiatal; Peak expiratory flow rate; Bronchial hyperreactivity; Forced expiratory volume; Carbachol/diagnostic use

Objective: To assess airway hyperresponsiveness to 4.5% hypertonic saline solution in comparison to that obtained through challenge with other bronchoconstriction agents and in relation to patient allergic sensitization. Methods: A cross-sectional, experimental study was conducted, initially involving 85 subjects. After exclusions, the final sample consisted of 62 patients, divided into two groups: a study group of those with asthma (n = 45) and a control group of those with no asthma or allergies (n = 17). Hypertonic saline was nebulized using an ultrasonic nebulizer and administered successively for 0.5, 1, 2, 4 and 8 minutes until a drop in forced expiratory volume in one second of = 15% was achieved in relation to the baseline value. The level of specific immunoglobulin E to Dermatophagoides pteronyssinus level was determined by ImmunoCAP assay and was considered positive when > 0.35 kU/L. Results: In the 36 asthma group subjects presenting a response, the mean drop in forced expiratory volume in one second after hypertonic saline nebulization was 27.4%. None of control group subjects (immunoglobulin E < 0.35 kU/L) presented a positive response to hypertonic saline. The mean forced expiratory volume in one second for control group subjects was 9%. The results of a bronchial provocation test were negative in 9 of the asthma group subjects. The frequency of bronchial provocation test positivity was higher in the subjects presenting elevated levels of specific immunoglobulin E, indicating that there is a relationship between bronchial hyperresponsiveness and the level of specific immunoglobulin E. The sensitivity and specificity of the test were 80% and 92%, respectively. Conclusion: Bronchial provocation with hypertonic saline presents satisfactory sensitivity and specificity. Therefore, in addition to being a low cost procedure that requires very little equipment, it is a useful means of assessing hyperresponsiveness in children and adolescents.

Keywords: Bronchial provocation tests; Bronchial hyperreactivity; Saline solution, hypertonic; Administration, inhalation;

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: To evaluate the effects of azathioprine on the mucociliary system in a model of bronchial section and anastomosis in rats. Methods: Thirty-six male Wistar-Furth rats were submitted to left bronchial section and anastomosis and divided into two groups to receive either saline solution or azathioprine. After 7, 15 and 30 days of treatment, six animals from each group were killed, after which in situ mucociliary transport velocity, in vitro mucus transportability, and contact angle of mucus in the right (intact) and left (sectioned) bronchi were measured. Results: In situ mucociliary transport velocity was significantly lower in the sectioned bronchi than in the intact bronchi (p < 0.001). In situ mucociliary transport velocity was lower in the intact bronchi of the animals treated with azathioprine for 7 days (p < 0.05), and those bronchi presented full recovery after 30 days of treatment. The contact angle was higher in the mucus samples collected from the sectioned bronchi of the animals treated with saline solution for 30 days (p < 0.001), which is in accordance with the decreased in vitro mucus transportability observed in the same animals (p < 0.001). Conclusions: We conclude that, in the sectioned bronchi of rats, treatment with azathioprine causes only transitory impairment of mucociliary transport, whereas administration of saline solution impairs mucociliary transport for up to 30 days. In addition, azathioprine protects against alterations in mucus surface properties.

Keywords: Mucociliary clearance; Anastomosis, surgical; Immunosuppression; Lung.

Background: The relationship between asthma and gastroesophageal reflux is, as yet, not completely understood. Among the mechanisms thought to be responsible for gastroesophageal reflux-related worsening of asthma symptoms are the vagovagal reflex and microaspiration. Objective: To assess forced expiratory volume in one second after acid infusion. Method: This study investigated the effect of acid infusion in 13 volunteers with moderate asthma and gastroesophageal reflux. Spirometry was performed before and after insertion of an 8F nasogastric tube and a pH meter. After 15 minutes of saline solution infusion into the midpoint between the upper esophageal sphincter and lower esophageal sphincter, and again after 15 minutes of esophageal acidification (with hydrochloric acid) of the same area, forced expiratory volume in one second was reassessed. Acidification was repeated every 5 minutes until forced expiratory volume in one second values stabilized (variation: < 5%). Results: Mean forced expiratory volume in one second values remained stable during the tube insertion, saline infusion, initial hydrochloric acid infusion and subsequent hydrochloric acid infusion procedures (p = 0.72). Lower forced expiratory volume in one second values were seen resulting from the tube insertion in two patients (drops of 11% and 22%, respectively), after saline infusion in another two (drops of 13% and 14%) and after acid infusion in 1 (a drop of 22%). Conclusion: Esophageal acidification over short periods does not lead to spirometric alterations in a group of asthmatics with gastroesophageal reflux. However, in some cases, simple esophageal procedures or infusions result in bronchospasm.

Keywords: Key words: Asthma. Gastroesophageal reflux. Respiratory function tests. Endoscopy/methods.

Objective: To determine the proportion of asthma patients with poor perception of asthma control and to evaluate the characteristics of this subgroup. Methods: A cross-sectional study in which consecutive outpatients (over the age of 12) with mild, moderate, or severe asthma were selected. The patients underwent clinical examination, and pulmonary function tests, as well as being assessed for depression and perception of asthma control. The degree of concordance between patients and physicians regarding the perception of asthma control was determined. Patients with good perception of asthma control were compared, in terms of characteristics, with those presenting poor perception. Results: The degree of concordance between patients and physicians regarding the perception of asthma control was low (kappa index = 0.5). Of the 289 patients included, 66 (23%) presented poor perception of asthma control. The preliminary univariate analysis revealed that the patients with poor perception of asthma control were older, had a lower income, and presented a lower degree of asthma severity. Those factors did not change in the multivariate analysis. There were no differences between the groups in terms of gender, frequency of having literate patients, duration of asthma symptoms, having been diagnosed with rhinitis, frequency of depression, pulmonary function, or treatment compliance. Conclusions: The incidence of poor perception of asthma control in asthma patients is high, especially in elderly patients with lower income and a lower degree of asthma severity.

Keywords: Asthma; Signs and symptoms; Asthma/therapy.