Background: The methacholine challenge test is commonly used to evaluate bronchial responsiveness in diagnosis and follow-up of asthmatic patients. Objective: To investigate late effects of methacholine challenge on induced sputum. Methods: Ten non-smoker patients with mild or moderate stable asthma were recruited. At 12:00 p.m., patients were randomly assigned to inhale either methacholine (challenge) or physiologic saline. At 6:00 p.m., sputum induction was performed. On the second visit, one week apart, patients completed their participation in the study by undergoing another inhalation and sputum induction. Results: After methacholine, 8.6 ± 9 g of sputum were expectorated with 8.6 ± 6 million cells, 78 ± 10% were viable, and 6.8 ± 7% eosinophils. These data were not different from results obtained after saline: sputum amount = 7.6 ± 6 g, total cell count = 12.4 ± 12 million, viability = 82 ± 10%, and eosinophils = 6.6 ± 9%. Expiratory flow (PF) peak fall during sputum induction was not different: 21.4 ± 12% after methacholine and 18.4 ± 15% after saline. The PF fall observed during induction correlated with the amount of expectorated sputum (p = 0.018) and eosinophil relative number (p = 0.003). No other significant correlation between lung function measurements and sputum characteristics was found. Conclusion: A methacholine challenge carried out six hours before sputum induction does not significantly alter the cellular constituents or amount of sputum.

Keywords: Asthma. Methacholine chloride. Bronchial provocation tests.

Objective: To determine the proportion of asthma patients with a poor perception of dyspnea, correlating the level of that perception with the severity of acute bronchoconstriction, bronchial hyperresponsiveness, use of maintenance medication, and asthma control. Methods: Uncontrolled clinical trial involving asthma patients treated at the Pulmonology Outpatient Clinic of the São Lucas Hospital, in Porto Alegre, Brazil. Methacholine challenge testing was performed using a five-breath dosimeter protocol. The perception of dyspnea after each breath was determined using the Borg scale. Data concerning asthma control, medication in use, and use of rescue short-acting bronchodilators were recorded. Results: Of the 65 patients included in the study, 53 completed the evaluation. Of those, 32 (60.5%) showed adequate perception of dyspnea after the methacholine challenge test, whereas 21 (39.5%) did not perceive any changes in the degree of dyspnea even after a 20% fall in FEV1. There were no significant differences between the two groups regarding baseline FEV1, percentage fall in FEV1, and the dose of methacholine causing a 20% fall in FEV1. The perception of dyspnea was not significantly associated with age (p = 0.247); gender (p = 0.329); use of maintenance medication (p = 0.152); asthma control (p = 0.562), bronchial hyperresponsiveness (p = 0.082); or severity of acute bronchoconstriction (p = 0.749). Conclusions: A significant proportion of asthma patients have a poor perception of dyspnea. The factors related to the inability of these patients to identify changes in pulmonary function have not yet been well defined. In order to reduce asthma-related morbidity and mortality, it is essential that this group of patients be identified and counseled.

Keywords: Asthma; Dyspnea; Airway obstruction.

Background: Airway inflammation, acknowledged as an important feature of asthma, can be assessed by the examination of induced sputum. Objective: To determine the pattern of inflammatory cells in induced sputum from stable steroid-naïve asthmatics, in Florianópolis, Santa Catarina. Method: The induced sputum from 34 asthmatics using exclusively inhaled bronchodilators on demand was examined. The patients' clinical characteristics were obtained at visit 1, and sputum was induced at visit 2. Differential cell count was performed on Giemsa-stained cytospins. Sputum was considered to be eosinophilic if there were ³ 3% eosinophils, and neutrophilic if there were ³ 65% neutrophils. Results: Results are expressed by median and interquartile range. The total cell count was 3.4 (3.7) x 106 cells/ml, and cell viability was 80.0 (16.4) %. The proportion of neutrophils was 14.4 (22.1) %, of eosinophils 6.4 (17.2) %, of macrophages 60.3 (37.5) %, and of lymphocytes 1.1 (1.2) %. Eosinophilic sputum was observed in 24 subjects (70.6%); none of them had neutrophilic sputum. There were no significant differences between the eosinophilic and non-eosinophilic groups concerning the measured clinical outcomes, total cell count and proportions of cells in the sputum, except for the proportion of eosinophils (14.4 [19.3] vs 0.4 [1.1], p < 0.001). Conclusions: In our environment, steroid-naïve asthmatics present a higher proportion of sputum eosinophils, as compared to the established reference values. The clinical and physiological parameters analyzed were unable to predict the presence of eosinophilic inflammation of the airways.

Keywords: Asthma. Inflammation. Sputum. Eosinophils. Neutrophils.

Objective: To evaluate whether methylene blue (MB) could minimize the effects of ischemia-reperfusion injury in the nonischemic lung on a lung transplantation rodent model. Methods: Forty female Sprague-Dawley rats were divided into 20 donors and 20 recipients. The 20 recipient rats were divided into two groups (n = 10) according to the treatment (0.9% saline vs. 1% MB solutions). All animals underwent unilateral lung transplantation. Recipients received 2 mL of saline or MB intraperitoneally prior to transplantation. After 2 h of reperfusion, the animals were euthanized and histopathological and immunohistochemical analyses were performed in the nonischemic lung. Results: There was a significant decrease in inflammation-neutrophil count and intercellular adhesion molecule-1 (ICAM-1) expression in lung parenchyma were higher in the saline group in comparison with the MB group-and in apoptosis-caspase-3 expression was higher in the saline group and Bcl-2 expression was higher in MB group. Conclusions: MB is an effective drug for the protection of nonischemic lungs against inflammation and apoptosis following unilateral lung transplantation in rats.

Keywords: Reperfusion injury; Methylene blue; Lung transplantation; Apoptosis; Inflammation.

Objective: To determine the occurrence of exercise-induced bronchoconstriction and analyze cardiorespiratory response during maximal exercise in asthmatic patients. Patients and methods: Fourteen subjects with asthma (FEV1 of 86.3% predicted), as defined by the American Thoracic Society criteria were submitted to a maximal exercise test. Volume-flow curves were performed prior to progressive maximal exercise and seven and 15 minutes after it. Six patients (43%) showed a decline in FEV1 equal or greater than 15% after exercise (group I). The remaining patients constituted group II. Group I showed a FEV1 fall of 40.9% and 26.7%, seven and 15 minutes after exercise, respectively. In group II, there was a decrease of 2.6%, after 7 min and an increase of 1.2% after 15 min. At peak exercise, both groups reached heart rate above 91% of reference values; peak work was 82.7% and 62.5%, VO2max (mL/kg/min) 93.5% and 58,9% and VEmax 91.5% and 63.8%, respectively, in groups I and II. These differences were statistically significant. The correlation between the FEV1 fall rate (7 min post-exercise) and VEmax (% predicted) has showed a coefficient r = 0.8989 in group I and r = 0.3629 in group II. There was no correlation between delta VEF1 and VO2max (% predicted) in both groups. These findings showed that, in exercise-induced asthma patients, the occurrence of bronchoconstriction correlated with the level of maximal ventilation, but not with physical fitness.

Keywords: Exercise induced asthma. Bronchoconstriction. Tidal volume. Respiratory function tests.

Objective: The shortage of viable lungs is still a major obstacle for transplantation. Trauma victims who represent potential lung donors commonly present hypovolemic shock leading to pulmonary inflammation and deterioration and rejection after transplantation. Seeking to improve lung graft, new approaches to donor treatment have been tested. This study focuses on treatment with mesenchymal stem cells (MSCs) or soluble factors produced by MSCs (FS-MSC) using a rat model for lung donors after hemorrhagic shock. Methods: Forty-eight rats were divided into four groups: Sham (n=12), animals without induction of hypovolemic shock; Shock (n=12), animals submitted to hypovolemic shock (mean arterial pressure 40 mmHg); MSC (n=12), animals submitted to hypovolemic shock and treated with MSCs, and FS (n=12), animals submitted to hypovolemic shock and treated with FS-MSC. The animals were subjected to a 50-minute hypovolemic shock (40 mmHg) procedure. The treated animals were monitored for 115 minutes. We performed histopathology of lung tissue and quantification of inflammatory markers (TNF-a, IL-1ß, IL-6, IL-10, iCAM and vCAM) in lung tissue and peripheral blood leukocytes (PBLs). Results: Hemorrhagic shock resulted in higher PBLs and neutrophil infiltrate in the lungs. FS animals had lower neutrophil density comparing with Shock and MSC animals (p<0.001). No differences in the cytokine levels in lung tissue were observed between the groups. Conclusions: The lungs of rats submitted to hemorrhagic shock and treated with FS-MSC showed reduced inflammation indicated in a decrease in lung neutrophil infiltrate.

Keywords: Lung transplantation; Tissue donors; Hypovolemic shock; Mesenchymal cells; Inflammation.

The growth of children with asthma has attracted great interest because it is a chronic respiratory illness whose prevalence in childhood has increased during the last decades. The relationship between asthma and growth has been studied for a long time, but the great variability of diagnosis, therapy, and different methods of investigation make it difficult to disentangle the factors that are responsible for the growth retardation detected by some authors. As a result of different observations, there remain many doubts about the impact of asthma on child and adolescent growth. The aim of this paper is to provide a general view on the issue.

Pulmonary thromboembolism and exacerbation of chronic obstructive pulmonary disease are common conditions. Chronic obstructive pulmonary disease is a clinical risk factor for pulmonary thromboembolism. The presentation of acute pulmonary thromboembolism and acute exacerbation of chronic obstructive pulmonary disease often mimic each other so closely that they cannot be distinguished clinically. The structural abnormalities of the lungs in chronic obstructive pulmonary disease make also difficult to interpret the results of noninvasive tests like ventilation-perfusion lung scans. Therefore, diagnosing acute pulmonary thromboembolism in patients with underlying chronic obstructive pulmonary disease is a challenging task. In order to update knowledge of the subject and offer suggestions regarding conduct, we evaluated various studies addressing this theme, including case reports and case series. In addition, we reviewed diagnostic approaches to acute pulmonary thromboembolism, and we reflect upon that topic. The clinical probability of pulmonary thromboembolism concomitant to chronic obstructive pulmonary disease is typically intermediate, as is positivity on the ventilation-perfusion lung scan. Diagnostic algorithms should take that into consideration.

Keywords: Pulmonary disease, chronic obstructive/complications; Pulmonary embolism/diagnosis; Pulmonary embolism/epidemiology; Ventilation-perfusion ratio

Summary: b-agonists are considered the agents of first choice for the treatment of asthmatic symptoms and are usually available for aerosol administration. Its propellants damage the ozone layer and are often not used properly by the patients. Turbuhaler seems a better alternative since it does not present these inconveniences. In Brazil, it has been recently introduced. Purpose: Compare salbutamol aerosol (SA) to terbutaline turbuhaler (TT) in relation to technical use, bronchodilation and adverse effects in outpatients with mild-obstruction asthma (PFR ³ 60 and < 80% predicted). Material and methods: Open, parallel randomized study performed in each arm of 20 patients (SA: 200 mg and TT: 500 mg). After 30 minutes, a second dose was given if PFR was not 15% or 30 L/min greater than the initial one; a second dose was also delivered if PFR was not greater than 80%. All patients were instructed on how to use both devices. Results: Clinical improvement and increase in PFR were similar in both groups (SA 69.5 vs. TT 58.1 L/min, p > 0.05). A second dose was given to 13 patients (SA 6 and TT 7) with similar results. Errors in the usage were observed in all 20 patients of group SA vs. 11 patients in group TT (p < 0.05). Adverse effects were more frequent with TT - 9 patients - due to its unpleasant taste. Fifteen patients of group TT and with previous experience with SA considered turbuhaler easier. Conclusions: 1) administration by the patient is easier with turbuhaler than with SA; 2) bronchodilation is not different with SA 200 mg and TT 500 mg; 3) unpleasant taste was noted only in group TT (50% of the patients).

Keywords: Asthma. Salbutamol aerosol. Terbutaline Turbuhaler.

Objetivo: Medir a resistência de vias aéreas utilizando a técnica de resistência do interruptor (Rint) em pacientes com fibrose cística (FC) e correlacioná-la com parâmetros espirométricos, assim como avaliar a acurácia de Rint para determinar a resposta das vias aéreas a um broncodilatador. Métodos: Estudo transversal com 38 crianças e adolescentes com FC acompanhados no Ambulatório de FC do Hospital São Lucas, em Porto Alegre (RS). Após a determinação de Rint, os pacientes foram submetidos à espirometria. Para a avaliação da resposta ao broncodilatador, as medições foram repetidas após o uso de salbutamol inalatório. Resultados: Houve uma forte correlação entre o inverso de Rint e VEF1 (r = 0,8; p < 0,001) e moderadas correlações entre o inverso de Rint e FEF25-75% (r = 0,74; p < 0,001) e entre o inverso de Rint e índice de massa corpórea (r = 0,62; p < 0,001). A curva ROC foi utilizada na comparação da resposta ao broncodilatador determinada por Rint com aquela determinada por valores espirométricos. Para um ponto de corte de −28% para Rint, a área sob a curva foi de 0,75, com uma sensibilidade de 66% e uma especificidade de 82%. Conclusões: Nossos achados indicam que Rint apresenta uma boa correlação com parâmetros espirométricos, embora a técnica Rint não tenha sido suficientemente acurada para substituir a espirometria na avaliação da resposta ao broncodilatador.

Keywords: Testes de função respiratória; Fibrose cística; Espirometria; Resistência das vias respiratórias.

Objective: To compare two methods of respiratory inductive plethysmography (RIP) calibration in three different positions. Methods: We evaluated 28 healthy subjects (18 women and 10 men), with a mean age of 25.4 ± 3.9 years. For all of the subjects, isovolume maneuver calibration (ISOCAL) and qualitative diagnostic calibration (QDC) were used in the orthostatic, sitting, and supine positions. In order to evaluate the concordance between the two calibration methods, we used ANOVA and Bland-Altman plots. Results: The values of the constant of proportionality (K) were significantly different between ISOCAL and QDC in the three positions evaluated: 1.6 ± 0.5 vs. 2.0 ± 1.2, in the supine position, 2.5 ± 0.8 vs. 0.6 ± 0.3 in the sitting position, and 2.0 ± 0.8 vs. 0.6 ± 0.3 in the orthostatic position (p < 0.05 for all). Conclusions: Our results suggest that QDC is an inaccurate method for the calibration of RIP. The K values obtained with ISOCAL reveal that RIP should be calibrated for each position evaluated.

Keywords: Plethysmography; Respiratory mechanics; Posture; Calibration.

Objective: Many patients with proportional reductions in FVC and FEV1 on spirometry show no reduction in TLC. The aim of this study was to evaluate the role that measuring lung volumes and airway resistance plays in the correct classification of patients with a possible restrictive pattern on spirometry. Methods: This was a prospective study involving adults with reduced FVC and FEV1, as well as an FEV1/FV(C) ratio within the predicted range. Restrictive lung disease (RLD) was characterized by TLC below the 5th percentile, as determined by plethysmography. Obstructive lung disease (OLD) was characterized by high specific airway resistance, significant changes in post-bronchodilator FEV1, or an FEF25-75% < 50% of predicted, together with a high RV/TLC ratio. Nonspecific lung disease (NLD) was characterized by TLC within the predicted range and no obstruction. Combined lung disease (CLD) was characterized by reduced TLC and findings indicative of airflow obstruction. Clinical diagnoses were based on clinical suspicion, a respiratory questionnaire, and the review of tests of interest. Results: We included 300 patients in the study, of whom 108 (36%) were diagnosed with RLD. In addition, 120 (40%) and 72 (24%) were diagnosed with OLD/CLD and NLD, respectively. Among the latter, 24 (33%) were clinically diagnosed with OLD. In this sample, 151 patients (50.3%) were obese, and obesity was associated with all patterns of lung disease. Conclusions: Measuring lung volumes and airway resistance is often necessary in order to provide an appropriate characterization of the pattern of lung disease in patients presenting with a spirometry pattern suggestive of restriction. Airflow obstruction is common in such cases.

Keywords: Spirometry; Airway resistance; Lung volume measurements.

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 evaluate the electromyographic activity (EA) of sternocleidomastoid (SCM) and scalene muscles during and after the use of expiratory positive airway pressure (EPAP) in patients with COPD. Methods: This was a clinical single-blind trial involving 13 healthy subjects as controls and 12 patients with stable COPD. At baseline, we determined EA during spontaneous respiration, lung function parameters, and respiratory muscle strength. Subsequently, EPAP at 15 cmH2O was applied by means of a face mask for 25 min, during which the EA of the SCM and scalene muscles was recorded every 5 min. A final record was obtained 10 min after the mask removal. Results: We found that the behavior of the EA of SCM and scalene muscles was comparable between the controls and the COPD patients (p = 0.716 and p = 0.789, respectively). However, during the use of EPAP, both muscles showed a trend toward an increase in the EA. In addition, there was a significant decrease in the EA of the SCM between the baseline and final measurements (p = 0.034). Conclusions: The use of EPAP promoted a significant reduction in the EA of the SCM in the controls and in the patients with stable COPD. However, this did not occur regarding the EA of the scalene muscle.

Keywords: Electromyography; Respiratory muscles; Pulmonary disease, chronic obstructive; Positive-pressure respiration.

Background: Nasal and pharyngeal symptoms are common in patients with obstructive sleep apnoea (OSA) treated with nasal continuous positive airway pressure (CPAP). However, these symptoms are common in OSA patients even before the treatment. Objectives: Determine the impact of nasal CPAP on nasal and pharyngeal symptoms in OSA patients. Method: Thirty-five adult patients (28 males), age 54±10 years old, with OSA diagnosed by polissonography. All patients answered to a questionnaire about the presence and quantification of sneezing, rhinorrhea, nasal pruritus, obstruction and bleeding, nasal and pharyngeal dryness. The questionnaire was answered before and after at least three months of CPAP therapy. Results: The apnea-hypopnea index was 50±25 events per hour. Twenty six patients (74%) presented at least one naso-pharingeal symptom before treatment. Nasal obstruction was the most common symptom, being referred by 18 patients (51%). Among the patients that were initially assymptomatic (n=9), 78% developed adverse nasal reactions to CPAP. In contrast, among the patients that presented nasal symptoms before treatment, there was a significant reduction in nasal obstruction, nasal and throat dryness scores as well as nasal bleeding after CPAP therapy. Conclusions: Nasal na pharyngeal symptoms are frequent in OSAS patients. CPAP therapy may originate nasal symptoms in patients previously assymptomatic, as well as reduce the intensity of these symptoms in patients that are previously symptomatic.

Keywords: Obstructive sleep apnea syndrome. Nasal obstruction. Continuous positive airway pressure, compliance.

Objective: To identify microorganisms in sputum samples of patients with stable non-cystic fibrosis bronchiectasis and to determine risk factors related to the isolation of Pseudomonas aeruginosa (PA) in those patients. Methods: Consecutive patients were recruited from a tertiary hospital outpatient clinic in the city of Fortaleza, Brazil. The patients were submitted to spirometry, six-minute walk test, HRCT, and sputum collection. Data on serum fibrinogen levels, disease severity, sputum color, and history of azithromycin treatment were collected. Results: The study included 112 patients, and females predominated (68%). The mean age was 51.6 ± 17.4 years. Most patients presented with mild-to-moderate disease (83%). The mean six-minute walk distance was 468.8 ± 87.9 m. Mean FEV1 and FVC, in % of predicted values, were 60.4 ± 21.8% and 69.9 ± 18.5%, respectively. The mean serum fibrinogen level was 396.1 ± 76.3 mg/dL. PA was isolated in 47 patients, other potentially pathogenic microorganisms (PPMs) were isolated in 31 patients, and non-PPMs were isolated in 34 patients. Purulent sputum was identified in 77 patients (68%). The patients with PA, when compared with those without it, presented with more severe disease, higher serum fibrinogen levels, and lower FVC%. In addition, purulent sputum and long-term azithromycin treatment were more common in those with PA. The multivariate regression analysis showed that the independent factors associated with PA were serum fibrinogen level > 400 mg/dL (OR = 3.0; 95% CI: 1.1-7.7) and purulent sputum (OR = 4.3; 95% CI: 1.6-11.3). Conclusions: In our sample, the prevalence of PA in sputum was 42%. Sputum color and inflammatory markers were able to predict the isolation of PA, emphasizing the importance of routine sputum monitoring.

Keywords: Bronchiectasis; Pseudomonas aeruginosa; Sputum/microbiology.

Objective: Obstructive sleep apnea syndrome (OSAS) has a high prevalence and carries significant cardiovascular risks. It is important to study new therapeutic approaches to this disease. Positional therapy might be beneficial in reducing the apnea-hypopnea index (AHI). Imaging methods have been employed in order to facilitate the evaluation of the airways of OSAS patients and can be used in order to determine the effectiveness of certain treatments. This study was aimed at determining the influence that upper airway volume, as measured by cervical CT, has in patients diagnosed with OSAS. Methods: This was a quantitative, observational, cross-sectional study. We evaluated 10 patients who had been diagnosed with OSAS by polysomnography and on the basis of the clinical evaluation. All of the patients underwent conventional cervical CT in the supine position. Scans were obtained with the head of the patient in two positions (neutral and at a 44° upward inclination), and the upper airway volume was compared between the two. Results: The mean age, BMI, and neck circumference were 48.9 ± 14.4 years, 30.5 ± 3.5 kg/m2, and 40.3 ± 3.4 cm, respectively. The mean AHI was 13.7 ± 10.6 events/h (range, 6.0-41.6 events/h). The OSAS was classified as mild, moderate, and severe in 70%, 20%, and 10% of the patients, respectively. The mean upper airway volume was 7.9 cm3 greater when the head was at a 44° upward inclination than when it was in the neutral position, and that difference (17.5 ± 11.0%) was statistically significant (p = 0.002). Conclusions: Elevating the head appears to result in a significant increase in the caliber of the upper airways in OSAS patients.

Keywords: Sleep apnea, obstructive/prevention and control; Sleep apnea, obstructive/therapy; Tomography.