Repeated dosis of inhaled β2-agonists have been used in the treatment of acute asthma. The effect of added ipratropium bromide (IB) to β2-agonist is controversial in adults. Objective: To evaluate if addition of IB to fenoterol, in repeated doses, induces a greater bronchodilation, a greater reversion of the attack, and discharge from emergency unit in adults with acute severe asthma. Setting: Pneumology Emergency Department, Unifesp-Hospital São Paulo, in the period from July 1995 to February 1997. Type of study: Open, randomized and parallel study. Discharge from the hospital: FEV1 and PEF ≥ 60% of the predicted value. Methods: 120 patients with FEV1 and PEF ≤ 50% of the predicted value were divided into two groups (N = 60): fenoterol (F) and ipratropium bromide + fenoterol (IBF). Each group received inhalation treatment through a metered-dose inhaler (MDI) attached to a holding chamber, administered at 30-minute interval, for a total of three treatments. In the group F four puffs of fenoterol (400 μg) were administered, and in the IBF group, 160 μg of BI and 400 μg of fenoterol (four puffs). Results: The patients did not differ from basal PEF (F = 36 ± 7% vs IBF = 35 ± 9% predicted) and basal FEV1 (F = 33 ± 9% vs IBF = 32 ± 9% predicted). Thirty-two patients of group F and 33 of group IBF were discharged from hospital after the inhalation treatment. The final FEV1 and PEF after inhalation treatments were F = 60 ± 13% vs IBF = 61 ± 11% e F = 74 ± 18% vs IBF = 77 ± 13% (NS). Conclusion: The addition of ipratropium bromide to fenoterol results in insignificant functional effect and without clinical impact in the treatment of acute asthma in adults.

Keywords: Fenoterol. Ipratropium. Status asthmaticus. Respiratory therapy.

Asthma is a disease with high prevalence in our country and around the world. Although new therapeutic approaches have been recently developed, there appears to be a worldwide increase in morbidity and mortality from asthma. In many institutions, asthma exacerbation is still a common medical emergency. Clinical evidence demonstrates that the first hour of management of acute asthma in the emergency room entails crucial decisions that could be determinant in the clinical outcome. In this non-systematic review, the authors focus on the first hour assessment and treatment of patients with acute asthma and outline an appropriate strategy for their management. Diagnosis, severity assessment, pharmacological treatment, complications, and the decision regarding the place where additional treatment will take place will be considered. It is reasonable to expect that these recommendations will help physicians make appropriate decisions about the first hour care of acute asthma in the emergency room.

Keywords: Asthma. Emergency medicine. Emergency treatment. Clinical procedures. Emergency medical services.

Introduction: The diagnosis of diffuse lung disease is still a challenge for the pediatric intensive care physician. Routine clinical examinations and laboratory tests are frequently negative. The objective of this study was to evaluate the diagnostic potential, the impact on therapy and the rate of complications of open lung biopsy in children with undiagnosed diffuse lung disease, respiratory failure and inappropriate response to initial therapy. Methods: From January 1987 to January 1997, 29 children with diffuse pulmonary disease of unknown etiology, respiratory failure (PaO2 /FiO2 < 300) and no response to previous treatments were considered for open lung biopsy. Newborns, children with known chronic pulmonary disease and children with untreatable shock or coagulopathy were excluded. All biopsies were performed by a thoracic surgeon by a microthoracotomy in the lung shown to be the most affected by X-ray examination. Tissue samples were analyzed in terms of cultures, light microscopy, electron microscopy and immunofluorescence microscopy, according to the pathologist's decision. Results: All biopsies (100%) resulted in at least one histological diagnosis and in 20 patients (68.9%) it was obtained a specific diagnosis. The most frequent histological patterns found were: non-specific interstitial pneumonitis with variable degrees of fibrosis in 18 cases; bronchiolitis in eight cases and pulmonary hypertension in three cases. Regarding the most frequent specific diagnosis, six children were found with cytomegalovirus infection, three with Pneumocystis carinii, three with adenovirus and three with respiratory syncytial virus infection. These data induced a change in therapy in 20 children (68.9%). The most frequent changes in therapy were the use of corticosteroids in 14 children and a review of the antibiotic regimen in six patients. Seven patients (24.1%) presented with complications that were easily resolved. There were 13 deaths, probably due to the critical conditions of these patients, all unrelated to the procedure. Conclusions: Open lung biopsy, though an invasive procedure, should be considered in the evaluation of selected children with undiagnosed diffuse lung disease, respiratory failure and with no satisfactory response to previous therapies.

Objective: To evaluate the efficacy and safety of a fixed-dose, single-capsule budesonide-formoterol combination, in comparison with budesonide alone, in patients with uncontrolled asthma. Methods: This was a randomized, double-blind, multicenter, phase III, parallel clinical trial, comparing the short-term efficacy and safety of the combination of budesonide (400 μg) and formoterol (12 μg), with those of budesonide alone (400 μg), both delivered via a dry powder inhaler, in 181 patients with uncontrolled asthma. The age of the patients ranged from 18 to 77 years. After a run-in period of 4 weeks, during which all of the patients received budesonide twice a day, they were randomized into one of the treatment groups. The treatment consisted of the administration of the medications twice a day for 12 weeks. The primary outcome measures were FEV1, FVC, and morning PEF. We performed an intention-to-treat analysis of the data. Results: In comparison with the budesonide-only group patients, those treated with the budesonide-formoterol combination showed a significant improvement in FEV1 (0.12 L vs. 0.02 L; p  =   0.0129) and morning PEF (30.2 L/min vs. 6.3 L/min; p  = 0.0004). These effects were accompanied by good tolerability and safety, as demonstrated by the low frequency of adverse events, only minor adverse events having occurred. Conclusions: The single-capsule combination of budesonide-formoterol appears to be efficacious and safe. Our results indicate that this formulation is a valid therapeutic option for obtaining and maintaining asthma control. (ClinicalTrials.gov Identifier: NCT01676987 [http://www.clinicaltrials.gov/])

Keywords: Asthma; Budesonide; Adrenergic beta-2 receptor agonists.

Background: There is a wide variability in clinical practice for treating acute asthma (AA) in the emergency room (ER) interfering in the quality of management. Objective: To evaluate the impact of a clinical protocol for care of acute asthma in the ER of the Hospital de Clínicas de Porto Alegre. Method: In this hospital a cross-sectional study was conducted before and after implementation of the protocol, of consecutive patients presenting with acute asthma in the adult ER (age ³ 12 years). The intention was to measure the effect of recommendations on the objective assessment of severity, utilization of diagnostic tools, proposed therapy, not recommended therapy and on the outcomes. Results: The pre-protocol group comprised 108 patients and the protocol group comprised 96 patients. There was a significant increase in the use of pulse oximetry (8% to 77%, p<0.001) and PEFR (5% to 21%, p<0.001). There was an increase in the utilization of radiology (33% to 66%, p<0.001) and in that of blood tests (11% to 25%, p=0.016). There was also an increase in the number of patients receiving the three recommended nebulizations in the first hour (22% to 36%, p=0.04). Although the overall use of corticosteroids did not change, there was a significant increase in the use of oral steroids (8% to 28%, p<0.001). There was no significant difference in the not recommended therapy, time of stay and outcomes. Conclusion: The acute asthma clinical protocol used in the ER was associated to a positive effect on the objective assessment of severity of asthma and on the use of the recommended therapy. No other significant influence on the treatment or on the outcome was perceived.

Keywords: Clinical protocols. Asthma. Emergency medicine.

Objective: To evaluate clinical and pulmonary function measurements taken in the first fifteen minutes of the assessment of acute asthma in the emergency room and used for prognostic purposes. Methods: A prospective cohort study involving consecutive patients with acute asthma. Only patients who were between the ages of 12 and 55 and presented peak expiratory flow rates < or = 50% of predicted were included. Evaluations were performed upon admission, then again at 15 minutes and 4 hours after the initiation of treatment. Treatment included albuterol and ipratropium delivered by metered-dose inhaler with a spacer, together with 100 mg of intravenous hydrocortisone. Favorable outcomes were defined as peak expiratory flow > or = 50% of predicted after 4 hours of treatment, and unfavorable outcomes were defined as peak expiratory flow < 50% after 4 hours of treatment. Results: Favorable outcomes were seen in 27 patients, and unfavorable outcomes were seen in 24 patients. In the multivariate analysis, peak expiratory flow as percentage of predicted was identified as the variable with the highest predictive value. A peak expiratory flow > or = 40% after 15 minutes of treatment showed significant power in predicting a favorable outcome (sensitivity = 0.74, specificity = 1.00, and positive predictive value = 1.00). A peak expiratory flow < 30% after 15 minutes of treatment was predictive of a poor outcome (sensitivity = 0.54, specificity = 0.93, and positive predictive value = 0.87). Conclusion: Our results suggest that measuring peak expiratory flow after 15 minutes of management in the emergency room is a useful tool for predicting outcomes in cases of acute asthma.

Keywords: Asthma; Acute disease; Respiratory mechanics; Prognosis; Emergency Service, Hospital; Cohort studies

Objectives: This study primarily aimed to investigate the clinical determinants of the Modified Incremental Step Test (MIST) in adults with non-cystic fibrosis bronchiectasis (NCFB). A secondary objective was to compare the cardiopulmonary responses after the MIST and Incremental Shuttle Walk Test (ISWT), two commonly adopted symptom-limited maximum field tests in chronic respiratory diseases. Methods: Forty-six patients with clinically stable bronchiectasis participated in this cross-sectional study. MIST and ISWT were performed to determine exercise capacity, while disease severity, fatigue, and quality of life were assessed using the Bronchiectasis Severity Index (BSI), the Fatigue Severity Scale (FSS), and St. George's Respiratory Questionnaire (SGRQ), respectively. Quadriceps muscle strength was evaluated using a hand-held dynamometer, walking speed with a wireless inertial sensing device, and the level of physical activity (steps/day) with a pedometer. Results: The BSI score, quadriceps muscle strength, daily step count, and the SGRQ total score explained 61.9% of the variance in the MIST (p < 0.001, R2 = 0.67, AR2 = 0.619). The BSI score (r = -0.412, p = 0.004), quadriceps muscle strength (r = 0.574, p = 0.001), daily step count (r = 0.523, p < 0.001), walking speed (r = 0.402, p = 0.006), FSS score (r = -0.551, p < 0.001), and SGRQ total score (r = -0.570, p < 0.001) correlated with the MIST. The patients achieved higher heart rates (HR), HR%, desaturation, dyspnea, and leg fatigue in the MIST compared to the ISWT (p < 0.05). Conclusions: Disease severity, quadriceps muscle strength, physical activity level, and quality of life were determinants of MIST. The advantages of the MIST, including higher cardiopulmonary response than ISWT and greater portability, which facilitates its use in various settings, make MIST the preferred choice for investigating symptom-limited exercise capacity in patients with NCFB.

Keywords: bronchiectasis, exercise capacity, step test, physical activity, walking speed, quality of life.

We compared the nitrate reductase assay with the proportion method, which is considered the gold standard, in 57 Mycobacterium tuberculosis strains isolated from patients treated at the Federal University of Minas Gerais Hospital das Clínicas, located in the city of Belo Horizonte, Brazil. For rifampin and isoniazid, the sensitivity, specificity, and accuracy of the nitrate reductase assay were all 100%, whereas they were 100%, 88.9%, and 66.7%, respectively, for streptomycin and 98.0%, 100%, and 98.2%, respectively, for ethambutol. The mean time to results was ten days. In the study sample, the nitrate reductase assay proved highly accurate and showed excellent concordance with the gold standard.

Keywords: Mycobacterium tuberculosis; Microbial sensitivity tests; Tuberculosis, multidrug-resistant; Nitrate reductase.

Objective: To use clinical and functional characteristics observed upon admission to an emergency room to identify factors predictive of the occurrence and course of acute asthma attacks in children. Methods: We prospectively studied 130 asthmatic children, from 1 to 13 years of age, who were treated for acute asthma attacks in an emergency room, evaluating status determined at admission and over the course of the crisis. Clinical scores were determined and arterial oxygen saturation by pulse oximetry was measured, as was peak expiratory flow. Results: The initial clinical score, arterial oxygen saturation by pulse oximetry and peak expiratory flow correlated with the number of inhalations performed, as well as with the need for corticosteroid treatment. Mean initial clinical score and mean arterial oxygen saturation by pulse oximetry of the hospitalized patients were statistically different from those of patients who were not hospitalized. Initial clinical score, arterial oxygen saturation and prior treatment for the same exacerbation were predictive of the need for hospitalization. Conclusion: The measurement of arterial oxygen saturation by pulse oximetry and the clinical score were useful in predicting the occurrence and course of acute asthma attacks in children. The measurement and interpretation of peak expiratory flow is difficult in children and, under these conditions, served no practical application.

Keywords: Asthma; Acute disease; Prospective studies; Predictive value of tests; Child

Background: It is questionable whether pressure-controlled ventilation (PCV) has advantages over volume-cycled ventilation (VCV). Objectives: To compare PCV to VCV with decelerating flow profile during assisted and controlled modes in an acute lung injury experimental model. Methods: Severe acute lung injury (PaO2/FIO2 < 100 mmHg) was induced by oleic acid IV infusion (0.05 mg/kg) in seven dogs. The animals were submitted to PCV and VCV in a randomized sequence. After 40 minutes in the assisted mode, ventilation was changed to the controlled mode after neuromuscular blockade. The tidal volume and the inspiratory time were kept constant throughout the experiment. Results: There were no differences in gas exchange (PaO2 and PaCO2), cardiac output or oxygen delivery (DO2) between VCV and PCV. The same was observed regarding maximum airway and plateau pressures, and also to the static compliance. Oxygen consumption (VO2) after neuromuscular blockade was 124 ± 48 in VCV versus 143 ± 50 ml/min in PCV, p = 0.42. In the assisted mode, there was a statistical trend of a higher VO2 in PCV (219 ± 72 versus 154 ± 67 ml/min in VCV, p = 0.06), that was associated with a statistical trend of a higher oxygen cost of breathing (OCB) during assisted PCV, although without statistical significance (31 ± 77 in VCV versus 75 ± 96 ml/min in PCV, p = 0.23), and also in a lower PvO2 (34 ± 7 in PCV versus 42 ± 6 ml/min in VCV, p = 0.02). These occurred despite a higher maximum inspiratory flow in the assisted mode in PCV (58 ± 9 versus 48 ± 4 L/min in VCV, p = 0.01). In both VCV and PCV the institution of controlled ventilation reduced cardiac debit and DO2 in as much as 20% relative to the assisted mode. Conclusions: The implementation of controlled ventilation improved the oxygen delivery/consumption relationship in this severe and with high OCB acute lung injury model. The PCV offered no additional benefits to VCV and it was associated with a higher OCB during the assisted mode.

Keywords: Artificial respiration. Pulmonary gas exchange. Tidal volume.

Objective: To evaluate the incidence of viral infection in patients with acute asthma treated in the emergency room. Methods: We conducted a cohort study of patients aged 12 and older presenting to the emergency room of the Hospital de Clínicas de Porto Alegre with acute asthma. Nasopharyngeal aspirate was collected, and antigens were detected through indirect immunofluorescence staining for respiratory syncytial virus, adenovirus and influenza, as well as for parainfluenza types 1, 2, 3 and 4. Data were collected regarding demographic characteristics, medical history, the attack that led to the current emergency room visit, and clinical outcomes. Results: From March to July of 2004, 49 patients were examined for viral infection of the respiratory tract. Respiratory viruses were identified in 6 patients (3 with adenovirus, 2 with influenza A, 1 with parainfluenza type 1). The mean age of the patients with viral infection of the respiratory tract was 61.7 ± 11.5 years, compared with 41.7 ± 20.9 years for the patients without such infection (p = 0.027). There were no other significant differences in clinical characteristics or outcomes. Conclusion: The incidence of viral infection of the respiratory tract in acute asthma patients 12 years and older treated in an emergency room was 12.2%, which confirms that viral infection is a significant precipitant of acute asthma for patients in this age bracket.

Keywords: Emergency Service, Hospital; Vírus diseases/prevention & control; Asthma; Respiratory tract infections; Influenza A virus, human

To evaluate the characteristics of users of inhalers and the frequency of inhaler use among adolescents and adults with self-reported physician-diagnosed asthma, bronchitis, or emphysema. Methods: A population-based study conducted in the city of Pelotas, Brazil, involving 3,670 subjects ≥ 10 years of age, evaluated with a questionnaire. Results: Approximately 10% of the sample reported at least one of the respiratory diseases studied. Among those individuals, 59% reported respiratory symptoms in the last year, and, of those, only half reported using inhalers. The use of inhalers differed significantly by socioeconomic status (39% and 61% for the lowest and the highest, respectively, p = 0.01). The frequency of inhaler use did not differ by gender or age. Among the individuals reporting emphysema and inhaler use, the use of the bronchodilator-corticosteroid combination was more common than was that of a bronchodilator alone. Only among the individuals reporting physician-diagnosed asthma and current symptoms was the proportion of inhaler users higher than 50%. Conclusions: In our sample, inhalers were underutilized, and the type of medication used by the individuals who reported emphysema does not seem to be in accordance with the consensus recommendations.

Keywords: Metered dose inhalers; Asthma; Pulmonary disease, chronic obstructive; Bronchitis; Emphysema; Dry powder inhalers.

Objective: Studies assessing the characteristics and management of patients hospitalized with asthma have been limited to a small number of facilities and have evaluated short time periods. The present study evaluated long-term changes among hospitalized asthma patients at a large number of facilities. Methods: This was a retrospective, hospital-based observational case series, designated the Study of Severe Asthma in Latin America and Spain, which was conducted in Spain and in eight Latin-American countries. We reviewed the hospital records of 3,038 patients (age range, 15-69 years) hospitalized with acute severe asthma at one of nineteen tertiary-care hospitals in 1994, 1999 and 2004. Results: Over time, the use of inhaled corticosteroids and long-acting β2 agonists increased significantly, whereas the use of theophylline as a controller medication decreased. The utilization of pulmonary function tests also increased. There was a significant reduction in the mean hospital stay (8.5 days, 7.4 days and 7.1 days in 1994, 1999 and 2004, respectively, p = 0.0001) and a significant increase in the mean of the lowest arterial pH at hospital admission. In contrast, there was a significant decrease in the proportion of cases in which PEF was determined in the emergency room (48.6% in 1994 vs. 43.5% in 2004, p = 0.0001). We found the quality of asthma management and care to be generally better in Spain than in Latin America. Conclusions: Although there have been certain improvements in the management of asthma between severe exacerbations and during hospitalization, asthma management remains suboptimal in Spain and, especially, in Latin America.

Keywords: Status asthmaticus; Asthma/therapy; Hospitalization.

Objective: To assess the diagnostic performance of the Xpert MTB/RIF assay, a rapid molecular test for tuberculosis, comparing it with that of AFB staining and culture, in BAL fluid (BALF) samples from patients with clinically suspected pulmonary tuberculosis (PTB) who are sputum smear-negative or produce sputum samples of insufficient quantity. Methods: This was a retrospective study of 140 cases of suspected PTB in patients who were smear-negative or produced insufficient sputum samples and were evaluated at a tertiary teaching hospital in the city of Rio de Janeiro, Brazil. All of the patients underwent fiberoptic bronchoscopy with BAL. The BALF specimens were evaluated by AFB staining, mycobacterial culture, and the Xpert MTB/RIF assay. Results: Among the 140 patients, results for all three microbiological examinations were available for 73 (52.1%), of whom 22 tested positive on culture, 17 tested positive on AFB staining, and 20 tested positive on the Xpert MTB/RIF assay. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for AFB staining were 68.1%, 96.1%, 88.2%, 87.5%, and 87.6%, respectively, compared with 81.8%, 96.1%, 90.0%, 92.4%, and 91.8%, respectively, for the Xpert MTB/RIF assay. The agreement between AFB staining and culture was 82.3% (kappa = 0.46; p < 0.0001), whereas that between the Xpert MTB/RIF assay and culture was 91.8% (kappa = 0.8; p < 0.0001). Conclusions: In BALF samples, the Xpert MTB/RIF assay performs better than do traditional methods, providing a reliable alternative to sputum analysis in suspected cases of PTB. However, the rate of discordant results merits careful consideration.

Keywords: Tuberculosis; Molecular diagnostic techniques; Bronchoscopy; Bronchoalveolar lavage fluid; Mycobacterium tuberculosis.

Abstract Objective: The incidence of tuberculosis worldwide has emphasized the need for better assays designed to diagnose the disease, principally the extrapulmonary form. The objective of the present study was to validate the performance of an automated method for the determination of adenosine deaminase (ADA) activity in pleural fluid (PF) and cerebrospinal fluid (CSF), comparing it with a conventional method (the modified Giusti method). Methods: In total, 134 samples were selected from among those tested in our laboratory: 94 PF samples and 40 CSF samples. The ADA activity was determined using the two methods. Inter- and intra-assay precision was determined, linear regression analysis was performed, simple concordance tests were conducted, and the means of the differences were calculated. Results: The correlation coefficients for PF and CSF samples were, respectively, 0.96 and 0.95. Inter-assay precision was determined using 21 replicates at 3 different activity levels: low, medium and high. The percentage coefficient of variation (%CV) was, respectively, 5.9, 8.1 and 5.8 for PF samples, compared with 21.9, 18.6 and 13.8 for CSF samples. Intra-assay precision in %CV was 1.3 and 11.7, respectively, for PF and CSF samples. The concordance between the methods in PF and CRF samples was, respectively, 96.8% and 100%, considering the reference values for the diagnosis of TB to be 40 U/L (conventional) and 30 U/L (automated) in PF samples, versus 9 U/L (for both methods) in CSF samples. Conclusions: The results validate the use of the automated method of determining ADA activity in PF and CSF samples as an alternative to the conventional method.

Keywords: Adenosine deaminase; Tuberculosis/diagnosis; Pleural effusion; Cerebrospinal fluid.

Objective: To determine the impact that open lung biopsy findings have on decisions regarding changes in the treatment strategies employed for critically ill patients presenting diffuse pulmonary infiltrates and suffering from refractory acute respiratory failure, as well as on their clinical improvement. Methods: This study involved 12 mechanically ventilated patients with acute respiratory failure who were subjected to open lung biopsy (by thoracotomy) after not presenting a clinical response to standard treatment. Results: The single most common cause of the acute respiratory failure was viral infection, which was identified in 5 patients (40%). The pre-operative evaluation of the cause of respiratory failure was modified in 11 patients (91.6%), and a specific diagnosis was made in 100% of the cases. Regardless of changes in treatment regimen, the mortality rate was 50%. Six patients (50%) survived to be discharged from the hospital. All of the discharged patients survived for at least one year after the open lung biopsy, for an overall one-year survival rate of 50% among the 12 patients studied. For the patients who died in the hospital, the time of survival after open lung biopsy was 14 + 10.8 days. Conclusion: We conclude that open lung biopsy is a useful tool in the management of acute respiratory failure when there is no clinical improvement after standard treatment, since it can lead to a specific diagnosis that requires distinct treatment, which probably lowers the mortality rate among such patients.

Keywords: Respiratory distress syndrome, adult; Lung/pathology; Biposy; Acute respiratory syndrome