Changes after 12 years of follow-up severe asthma patients cohort: higher obstruction and comorbidities, but significant better quality of life.

BACKGROUND: The Brazilian Cohort of Asthma São Paulo (BRASASP) had a well-characterized severe asthmatic in Brazil, with 12 years of follow-up under standard treatment. METHODS: Sequential assessment of patients with uncontrolled asthma from BRASASP cohort was carried out with 12 years of follow-up, performing exams and comparing with previous measurements. RESULTS: 50 from the 60 initial patients were reevaluated. Twelve years later, FEV1 and the FEV1/FVC ratio have significantly decreased, with a rate of loss of lung function of 11.8 and 14%, respectively, and worsening in small airway parameters such as RV/TLC. BMI, The Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores haven't changed. However, exacerbations decreased by 56%. Mean daily inhaled corticosteroid use was similar over time, but daily oral corticosteroid use decreased, in addition to a significant reduction in induced sputum eosinophilic and neutrophilic profile and serum IgE. Rhinitis, sinusitis, and GERD were the main comorbidities. In quality of life according to respiratory questionnaire SGRQ, total score showed a huge improvement (62% of patients). CONCLUSIONS: There was significant decrease in FEV1 and FEV1/FVC. Data of pulmonary functional small airway characteristics show globally affected airways. Although higher doses of medications, patients were still uncontrolled, but with reduction of exacerbations, daily use of oral corticosteroid, less eosinophils and neutrophils in induced sputum and lower levels of IgE. Improvement in quality of life in 62% of patients.

Airway pathology in severe asthma is related to airflow obstruction but not symptom control.

BACKGROUND: Patients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment. METHODS: Fifty severe asthmatics received prednisone 40 mg/d for 2 weeks and maintenance therapy with budesonide/formoterol 400/12 µg twice daily + budesonide/formoterol 200/6 µg as needed for 12 weeks. Endobronchial biopsies were performed at the end of 12 weeks. We performed extensive immunopathological analyses of airway tissue inflammation and remodeling features in patients stratified by asthma symptom control and by airflow obstruction. RESULTS: Airway tissue inflammation and remodeling were not associated with symptom control. Asthmatics with persistent airflow obstruction had greater airway smooth muscle (Asm) area with decreased periostin and transforming growth factor beta-positive cells within Asm bundles, in addition to lower numbers of chymase-positive mast cells in the submucosa compared to patients with nonpersistent obstruction. CONCLUSIONS: Symptom control in severe asthmatics was not associated with airway tissue inflammation and remodeling, although persistent airflow obstruction in these patients was associated with bronchial inflammation and airway structural changes.

Influence of diaphragmatic mobility on exercise tolerance and dyspnea in patients with COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) present increased airway resistance, air trapping, pulmonary hyperinflation, and diaphragm muscle alterations, all of which affect pulmonary mechanics. PURPOSE: To evaluate the influence diaphragmatic mobility has on exercise tolerance and dyspnea in patients with COPD. MATERIALS AND METHODS: Fifty-four COPD patients with lung hyperinflation were evaluated to assess pulmonary function, diaphragm mobility, exercise tolerance, and dyspnea (score). Twenty healthy (age- and body mass index-matched) subjects were evaluated as controls. RESULTS: The COPD patients presented lower diaphragmatic mobility than did the controls (36.27+/-10.96 mm vs. 46.33+/-9.46 mm). Diaphragmatic mobility presented a linear correlation with distance covered on the 6-min walk test (6MWT) (r=0.38; p=0.005) and a negative correlation with dyspnea (r=-0.36; p=0.007). Patients were then divided into two subgroups based on the degree of diaphragmatic mobility: G1 (or=34 mm). Those in G1 presented poorer 6MWT performance and greater dyspnea upon exertion than did those in G2 (distance covered on the 6MWT: 454.76+/-100.67 m vs. 521.63+/-70.82 m; dyspnea score: 5.22+/-3.06 vs. 3.48+/-2.77). The G1 patients also presented greater residual volume (in liters) and lower maximal voluntary ventilation (in % of predicted values) than did the G2 patients (266.20+/-55.30 vs. 209.74+/-48.49 and 39.00+/-14.94 vs. 58.11+/-20.96). CONCLUSION: Diaphragmatic mobility influences dyspnea and exercise tolerance in patients with COPD.

Respiratory pattern, thoracoabdominal motion and ventilation in chronic airway obstruction.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) present abnormal respiratory mechanics, but its relation to ventilation variables at rest is not fully understood. METHODS: We evaluated breathing pattern, thoracoabdominal motion, and ventilation in moderate and severe COPD patients by means of respiratory inductive plethysmograph and analysis of respiratory metabolism in semirecumbent position at rest. Diaphragmatic movement was measured using radiographs. RESULTS: COPD patients showed an increase in mean inspiratory flow, minute ventilation, dead space ventilation, oxygen and carbon dioxide ventilatory equivalents and reduction of respiratory times and pulse oxymetry. These findings were more pronounced in severe COPD. Changes in ventilatory efficiency were correlated with decreased respiratory times, reduced diaphragmatic movement, and lower oxygen uptake. CONCLUSIONS: Rapid shallow breathing and reduced diaphragmatic movement have led to ventilatory inefficiency without changes in thoracoabdominal motion.

High-resolution CT scan in the evaluation of exercise-induced interstitial pulmonary edema in cardiac patients.

OBJECTIVE: To evaluate the onset of exercise-induced interstitial pulmonary edema in cardiac patients by high-resolution CT (HRCT). DESIGN: Prospective, normal controlled. PARTICIPANTS: Thirty subjects divided into three groups: group 1--10 outpatients with chronic congestive heart failure (CCHF), New York Heart Association (NYHA) class I; group 2--10 outpatients with CCHF, NYHA class II/III; and group 3 (control)--10 normal subjects. METHOD: HRCT scans were obtained at rest and 4, 8, 12, 16, and 20 min after progressive treadmill exercise test. RESULTS: The following HRCT findings consistent with interstitial edema were significantly different (p<0.05) in group 2 when compared with groups 1 and 3: artery/bronchus ratio > 1 in the upper lobes, peripheral increase in the vascular markings, interlobular septal thickening, and peribronchial "cuffing." These differences were maximal at 12 min after exercise and returned to normal values after 20 min. CONCLUSION: Interstitial pulmonary edema was present immediately after exercise in CCHF patients. It may be important in the genesis of dyspnea of these patients.

Relationship between pleural changes after myocardial revascularization and pulmonary mechanics.

It is known that coronary artery bypass grafting (CABG) results in impairment of postoperative pulmonary function. There is also a high incidence of pleural changes (pleural effusion or pleural thickening) after CABG. We hypothesized that those patients with pleural changes in the postoperative period would have a greater decrease in pulmonary function test (PFTs) results. The present study reports the results of 110 male patients who underwent CABG. The chest films and the PFT results obtained preoperatively and on the sixth postoperative day were reviewed. The relationship between pleural changes and PFTs was analyzed in patients who received saphenous vein graft alone (SVG group: 50 patients) or in combination with internal mammary artery grafting (IMA group: 60 patients). In the IMA group, the patients who had pleural changes had significantly greater decreases in their pulmonary function than did the patients without pleural changes. The decrease in the FVC, TLC and FEV1 in the patients with pleural effusions (37.6, 27.8 and 36.8 percent) was similar to that in patients with pleural thickening (34.6, 28.3 and 35.0 percent) and both were significantly greater (p < 0.05) than the changes in the patients with a normal radiograph (26.1, 17.6 and 26.9 percent). In the SVG group, the presence of pleural changes was not significantly related to the decrement in pulmonary function. The values of RV, FRC, Cst, and blood gases were not affected in the SVG or IMA group by the presence of pleural changes. We conclude that the presence of pleural changes on the chest radiograph is associated with a larger decrement of pulmonary function after CABG in the IMA group. This larger decrease probably reflects added thoracic trauma and is not due to the presence of pleural changes per se.

Effect of inhaled furosemide on the bronchial response to lysine-aspirin inhalation in asthmatic subjects.

It has been demonstrated recently that inhaled furosemide inhibits bronchoconstriction induced by cold air, physical exercise, various antigens, and metabisulfite. The goal of the present study was to determine if the inhalation of furosemide would inhibit the bronchoconstriction resulting from the inhalation of lysine-aspirin in aspirin-sensitive asthmatics. Six female subjects with known hypersensitivity to aspirin participated in this crossover study comparing 20 mg of inhaled furosemide and placebo. The volunteers inhaled increasing concentrations of lysine-aspirin after the inhalation of furosemide or placebo. The geometric mean provocative dose causing a 20 percent decrease in the FEV1 (PD20) after the inhalation of placebo was 30.4 mg/ml and the PD20 was equal or below 90 mg/ml in all patients. In contrast, the FEV1 did not decrease by 20 percent in any of the patients pretreated with furosemide when the inhaled concentration was increased to 360 mg/ml. From this study, we conclude that the administration of furosemide blocks the bronchospasm induced by the inhalation of lysine-aspirin in aspirin-sensitive asthmatics.

Scimitar sign with normal pulmonary venous drainage and systemic arterial supply. Scimitar syndrome or bronchopulmonary sequestration?

The classic definition of the scimitar syndrome is a triad of hypoplasia of the right lung with anomalous venous drainage and a systemic arterial supply of a variable degree. We report a case in which a scimitar-shaped anomalous vein was observed on the plain chest radiograph, but subsequently a pulmonary angiogram showed that it drained normally into the left atrium.

Relationship between pleural effusion and pericardial involvement after myocardial revascularization.

The explanation for the high incidence of pleural effusion after cardiac surgery is unclear. There is a high incidence of left pleural effusion with inflammatory pericardial disease. We hypothesized that after coronary artery bypass grafting (CABG) there would be a higher incidence of pleural effusions in patients with pericardial involvement. We prospectively studied 47 patients undergoing elective CABG; 17 had only saphenous vein grafts (SVG group) and 30 received at least one internal mammary artery graft (IMA group) in addition to SVG. Patients had a chest radiograph, chest ultrasound, and an echocardiogram on the 7th, 14th, and 30th postoperative days. Seven days after the surgery, 42 to 47 patients (89.4 percent) had a pleural effusion and 36 (76.6 76.6 percent) pericardial involvement. No relationship was found between the presence of a pleural effusion and a pericardial effusion (p > 0.05). On the 14th postoperative day, 36 patients (76.6 percent) had a pleural effusion while 33 patients (70.2 percent) had a pericardial effusion. There was a significant relationship between the presence of a pleural effusion and a pericardial effusion (p < 0.05). On the 30th postoperative day, 27 patients (57.4 percent) had a pleural effusion and 25 (53.2 percent) had a pericardial effusion. Again, there was a significant relationship between a pleural effusion and a pericardial effusion (p < 0.05). Finally, there was no relationship between the ejection fraction and the presence of pleural effusion at any time (p > 0.05). From this study, we conclude that there is a high prevalence of both pleural and pericardial effusion postoperatively in patients undergoing CABG. Both types of effusions tend to be asymptomatic, gradually disappear, and are more common in the IMA group. Patients who have a persistent pericardial effusion are more likely to have a persistent pleural effusion.

The relationship between pleural fluid findings and the development of pleural thickening in patients with pleural tuberculosis.

The objective of the study was to determine if residual pleural thickening after treatment for pleural tuberculosis could be predicted from the pleural fluid findings at the time of the initial thoracentesis. Forty-four patients initially diagnosed as having pleural tuberculosis between January 1986 and January 1988 were separated into two groups: the 23 patients in group 1 had residual pleural disease, while the 21 patients in group 2 had no residual pleural disease after treatment for their pleural tuberculosis was completed. The clinical characteristics of the two different groups did not differ significantly, but the patients in group 1 tended to be a little sicker in that the duration of their symptoms was longer, their hemoglobin values were lower, and weight loss and cough were more frequent. There were no significant differences in the pleural fluid findings in the two different groups. The mean pleural fluid protein level was 5.40 +/- 0.58 g/dl for group 1 and 5.17 +/- 0.80 g/dl for group 2, while the mean pleural fluid glucose level was 78.6 +/- 19.5 mg/dl for group 1 and 79.5 +/- 20.1 mg/dl for group 2. The mean pleural fluid lactate dehydrogenase (LDH) level in group 1 was 593 +/- 498 IU/L, while the mean level for group 2 was 491 +/- 198 IU/L. The presence of residual pleural thickening was not related to the chemotherapeutic regimen or the performance of a therapeutic thoracentesis. From this study we conclude that approximately 50 percent of patients with pleural tuberculosis will have residual pleural thickening when their therapy is completed, but that one cannot predict which patients will have residual pleural thickening from either their clinical characteristics or their pleural fluid findings.

Influence of atelectasis on pulmonary function after coronary artery bypass grafting.

The purpose of this study was to determine the influence of atelectasis on pulmonary function 6 days following coronary artery bypass grafting (CABG). After 6 days, 30 patients had normal chest radiographs, 38 had atelectasis, and 57 had pleural changes. In 11 patients, atelectasis only was observed in the radiograph, and in 27 it was in combination with pleural changes. The decrease in FVC and FEV1 in the patients with atelectasis was 33.4 and 33.5 percent in the SVG group and 34.8 and 34.3 percent in the IMA group, while in those patients with a normal radiograph, the decrements were 26.3 and 26.9 percent in SVG group and 26.1 and 26.9 percent in IMA group, respectively. Thus, patients with atelectasis on the 6th postoperative day have a larger decrement in pulmonary function post CABG than the patients with normal chest radiograph and this reduction reflects a higher degree of thoracic trauma.

Arterial blood gases after coronary artery bypass surgery.

Coronary artery bypass graft (CABG) surgery adversely affects arterial blood gas (ABG) determinations. The purposes of this study were to assess serial changes in ABGs following bypass surgery and identify factors that may influence these changes. Room air ABGs were obtained preoperatively and on days 1, 2, 4, 6, and 8 postoperatively on 125 patients undergoing bypass surgery. Fifty-five patients (saphenous vein grafting [SVG] group) had only SVG grafting while 70 (internal mammary artery [IMA] group) received one (60 patients) or two (10 patients) IMA grafts in addition to the SVG grafts and were subjected to pleurotomy. The mean preoperative values (+/- SD) were as follows: PaO2, 75.1 +/- 7.7 mm Hg, P(A-a)O2, 20.9 +/- 7.5 mm Hg; PaCO2, 33.6 +/- 4.1 mm Hg; pH, 7.43 +/- 0.04; hemoglobin, 14.8 +/- 1.4 g/dl; and hematocrit, 44.2 +/- 3.9 percent. There was a large decrease in the PaO2 postoperatively. The nadir for the PaO2 (55.7 +/- 6.6 mm Hg) occurred on the second postoperative day. Eight days postoperatively, there were still significant abnormalities; the PaO2 was 65.7 +/- 7.3 mm Hg, the P(A-a)O2 was 33.2 +/- 8.8 mm Hg; the hemoglobin was 10.5 +/- 1.4 g/dl; and the hematocrit was 31.7 +/- 4.0 percent. The decrease in the PaO2 was particularly noteworthy given the large decrease in the hemoglobin and hematocrit. The changes in the PaO2 were not significantly correlated with the age, number of grafts, pump time, length of anesthesia, or endotracheal intubation or smoking history. Immediately postoperatively, changes were similar in both groups (p > 0.05); on the second postoperative day, the PaO2 had decreased 26.9 percent in the SVG group and 25.5 percent in the IMA group. However, the postoperative abnormalities resolved more slowly in the IMA group (p < 0.05). These observations suggest that the additional trauma to the lungs and chest wall in the IMA group (pleurotomy, the placing of pleural drains, etc) will result in a longer recovery time in the IMA group than in SVG group.

Postoperative pleural changes after coronary revascularization. Comparison between saphenous vein and internal mammary artery grafting.

Coronary artery bypass grafting (CABG) is commonly performed with a saphenous vein graft (SVG) and/or an internal mammary artery graft (IMA). We hypothesized that there would be a higher incidence of pleural changes after CABG in patients who underwent IMA grafting because pleurotomy is usually performed. In the present study, the pre and the 6th postoperative day chest roentgenograms of 122 patients who received CABG were reviewed. The incidence of effusion in the patients who received only SVG was 43 percent (23/54) and did not differ significantly (p greater than 0.05) from the incidence in the patients who also had IMA 41 percent (28/68). Almost all of the patients (43/51) had unilateral left-sided pleural effusions. Most of the effusions were small and did not require treatment. The incidence of effusion was not higher in patients with enlargement of their cardiac silhouette or atelectasis and was not related to the presence of chest tubes. The incidence of pleural thickening was higher in the IMA group (49 percent) than in the SVG group (31 percent) but the difference did not achieve statistical significance (p greater than 0.05). We conclude that there is a high (approximately 40 percent) incidence of small effusions and thickening after CABG. The incidence of pleural effusion and pleural thickening do not appear to be influenced by the type of surgery (IMA vs SVG). We speculate that the effusions are due to pericardial inflammation.

Pulmonary function after coronary artery bypass surgery.

Coronary artery bypass graft surgery (CABG) adversely affects pulmonary function tests (PFTs). Although several previous studies have addressed these changes, none has measured the forced vital capacity (FVC) on a daily basis. The purpose of the present study was to assess serial changes in the FVC following CABG and to identify factors that may influence these changes. The FVC was obtained pre- and daily postoperatively (1-10 days) in 120 patients. Fifty-one patients received saphenous vein grafts (SVG group) while 69 received at least one internal mammary artery graft in addition to SVG (IMA group). On the first postoperative day, the FVC decreased to 33% of the pre-operative value in the SVG group and to 29% in the IMA group. The spirometry gradually improved, but after 10 days, the FVC remained reduced (SVG, 70%; IMA, 60%). Although the decreases in FVC tended to be greater in the IMA group, there was no significant difference in the two groups (P = 0.27). The changes in FVC were not significantly related to age (P = 0.48), smoking history (P = 0.65), anesthesia (P = 0.38) or pump time (0.09). From this study, it is concluded that after CABG, there is a significant worsening of the pulmonary function. The nadir of FVC occurs immediately after surgery and improves gradually thereafter. However, on the tenth postoperative day, the FVC still remains more than 30% below pre-operative values. Since there is only a slight tendency for patients undergoing IMA grafting to have larger decreases in their pulmonary function, patients with ventilatory impairment should not be excluded from IMA grafting.

Gallium-67 lung imaging and pulmonary clearance of 99mTc-DTPA aerosol in patients with amiodarone pneumonitis.

The aim of this study was to compare gallium-67 citrate lung imaging with the pulmonary clearance of 99mTc-DTPA (technetium 99m diethylenetriaminepentaacetic acid) in 9 patients with amiodarone pneumonitis (8 males and 1 female, aged 58 to 76 years). The diagnosis of amiodarone pneumonitis was based on clinical and radiological grounds in all patients, and histological changes in seven. The mean values for the effective half-life of the pulmonary clearance of 99mTc-DTPA aerosol were below the normal range in all 9 patients, and lower than the values obtained previously for patients on a long-term amiodarone regimen without side effects. Positive gallium-67 accumulation was demonstrated in 7 of the 9 patients. Two patients had negative gallium-67 imaging and increased alveolar-capillary 99mTc-DTPA clearance; with corticosteroid therapy and discontinuation of amiodarone, their radiological changes and clearance became normal within 120 days. In conclusion, when compared to gallium-67 lung imaging, the 99mTc-DTPA aerosol clearance is more advantageous because it is a much faster test than the gallium scan. This is essential for those patients suspected of amiodarone pneumonitis who need specific therapy as soon as possible. Moreover, the 99mTc-DTPA aerosol clearance test appears to be a more useful diagnostic tool because it is positive even in those patients who have normal gallium-67 lung imaging.

Theophylline-ranitidine interaction in elderly COPD patients.

Most controlled studies in humans indicate that ranitidine does not alter theophylline metabolism, even at high doses. However, there have been several case reports published recently which demonstrate the development of theophylline toxicity mostly in older patients receiving stable oral doses of this drug when ranitidine was administered simultaneously. We studied eleven elderly (mean age, 69.0 +/- 6.2 years) patients with chronic obstructive pulmonary disease (COPD). During one week the patients took slow-release theophylline, 200 mg every 12 h, followed by one week intake of the same dose of theophylline plus ranitidine tablets, 150 mg every 12 h. At the end of each period, blood samples were obtained 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12 h after the morning dose for the determination of serum theophylline levels. The peak theophylline concentration (Tmax) was achieved after 4.1 +/- 0.9 h while the patients were taking theophylline, and after 2.9 +/- 1.4 h with the combined regimen. This difference was statistically significant (P < 0.01). In only 3/11 subjects did Tmax remain unchanged during both phases of the study. The mean theophylline clearance rates while the patients were receiving theophylline alone (39.58 +/- 19.89 ml/min) and when they were receiving both medications (34.42 +/- 10.55 ml/min) were similar. The mean serum levels while the patients were receiving theophylline alone were slightly higher but not statistically different. These results suggest that the reported increases in serum theophylline levels in older patients receiving theophylline and ranitidine cannot be ascribed to slower theophylline metabolism in the geriatric patients with COPD who is also given ranitidine.

Arrhythmogenic effects of combined orally administered theophylline and albuterol in patients with chronic obstructive pulmonary disease.

1. Studies in asthmatic subjects have reported conflicting results about the arrhythmogenic effects of beta agonist and theophylline. The purpose of the present study was to evaluate the effects of the combination of these drugs in patients with chronic obstructive pulmonary disease (COPD). 2. Twelve COPD patients (FEV1 = 1.2 +/- 0.3 L; PaO2 = 65.7 +/- 9.0 mmHg) were evaluated by 24-h Holter monitoring on three different days. The first evaluation was done after the patient had been without any treatment for at least 24 h, the second after sustained-release theophylline for one week and the third after oral beta agonist (albuterol) and theophylline for one week. 3. Mean serum level of theophylline was 1.9, 15.6 and 11.7 micrograms/ml, and mean heart rate was 78.3, 82.0 and 84.5 beats/min for the first, second and third period, respectively. Four patients showed more than 10 premature atrial contractions/h in the baseline Holter, and this rate did not increase after either treatment. Three patients had more than 10 premature ventricular contractions/h (PVC) at baseline, with no increase while receiving theophylline or the combination of theophylline and albuterol. However, one patient did have worsening of the arrhythmia while taking both drugs. There were 5 single PVCs/h at baseline and 150 single and 9 coupled PVCs/h plus 1 episode of non-sustained ventricular tachycardia during combined therapy. 4. We conclude that the combination of theophylline and a beta agonist (albuterol) may increase the premature ventricular contraction rate and the complexity of ectopic activity in COPD patients.

Comparison of knowledge on asthma: doctors completing internal medicine residency and doctors completing medical school.

CONTEXT: Asthma has been reported as a disease of increasing prevalence. OBJECTIVE: To assess the level of information and knowledge about asthma by means of a questionnaire among recent graduate physicians applying for medical residency at the Clinical Hospital of the University of São Paulo Medical School, Brazil. DESIGN: 14 multiple-choice questions for asthma diagnosis and management. SETTING: University of São Paulo Medical School (FMUSP). PARTICIPANTS: Recent graduate physicians applying for the medical residency program at FMUSP in 1999 (n = 448) and physicians that had completed 2 year of internal medicine residency (n = 92). MAIN MEASUREMENTS: We applied a questionnaire with 14 multiple-choice questions about the management of asthma based upon the Expert Panel Report 2 - Guidelines for the Diagnosis and Management of Asthma, NIH/NHLBI, 1997 (EPR-2). RESULTS: The medical residency program in Internal Medicine improved treatment skills (the ability to propose adequate therapy) when compared to medical education (a score of 57.2% versus 46.9%, P < 0.001) but not diagnosis knowledge (understanding of asthma symptoms related to medicine intake) (33.5% versus 33.3%, P = 0.94). Treatment skills were higher among physicians who received their Medical Degree (MD) from public-sponsored medical schools in comparison with those from private schools [49.7 (SE 1.17)] versus [41.8 (SE 1.63)], P < 0.001. CONCLUSION: Medical schools might consider reevaluating their programs regarding asthma in order to improve medical assistance, especially when considering the general results for residents, as they were supposed to have achieved performance after completing this in-service training.

[Pneumonitis induced by amiodarone]. / Pneumonite por amiodarona.

Fifteen patients, eleven males and four females, with amiodarone induced pulmonary disease were studied. Their ages ranged between 52 and 79 (mean = 64.0) years. 66% of the patients were taking a daily dose of 200 mg of amiodarone. The time elapsed between the initial dose and the diagnosis of the pneumonitis varied from 2 to 84 (mean = 23.3) months. Premature ventricular beats and recurrent episodes of paroxistic supra ventricular tachycardia were the most common indications for the use of the drug. The most frequent clinical complaints were progressive dyspnea and cough. Weight loss was observed in five patients, fever in six and chest pain in two. The most habitual thoracic physical sign was diffuse crepitation. Chest roentgenograms disclosed bilateral interstitial infiltrates in all patients, associated to pleural effusions in two. An increased diffuse uptake of 67 gallium citrate was observed in the nine patients to whom it was done. Lung function tests showed a pattern of restrictive ventilatory respiratory insufficiency and hypoxemia. Lung tissue specimens were obtained in ten patients, bronchoalveolar lavage in one and pleural fluid in one. The material was examined by light and electron microscopy. Amiodarone was discontinued in all patients and corticosteroids were introduced in thirteen. Five patients (33.3%) died, eight improved and two remained with radiographic scars.

Fluticasone/formoterol dry powder versus budesonide/formoterol in adults and adolescents with uncontrolled or partly controlled asthma.

UNLABELLED: This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 µg b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmacêutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 µg b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF). The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV(1)) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events. In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV(1) and asthma control when compared to a combination of budesonide plus formoterol. ( CLINICAL TRIAL NUMBER: ISRCTN60408425).