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.

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.

[Value of lamellar body quantification in leukocytes in amiodarone toxicity]. / Valor da quantificação dos corpos lamelares em leucócitos na toxicidade por amiodarona.

Amiodarone is an amphiphilic drug that penetrates easily through the plasmatic membrane and can induce the production of lysosome lamellar bodies in virtually all cells of the organism, independently of toxic effects. This study determines the value of searching for lamellar bodies in peripheric leucocytes as a method of prevention of pulmonary toxic effects in long term amiodarone treated patients. The rate of leucocytes with lamellar bodies was determined in three groups of patients. The group I was composed of 8 patients with amiodarone induced pneumonia who were taking the drug for an average of 16.88 months (average of 386.60 mg a day). The group II was composed of 19 patients not presenting any toxic effects, and who were taking amiodarone for an average of 38.32 months (average of 260.62 mg a day). The group III consisted by 8 healthy volunteers. The leucocyte layer was sampled from centrifuged peripheric blood and examined by transmission electron microscopy. The average percentage of leucocytes with lamellar bodies was 1.82 in group I, 1.65 in group II and 3.47 in group III. The lamellar inclusions were seen in all groups. There were no significant qualitative or quantitative differences between the groups. The inclusions couldn't be differentiated from other previously described non amiodarone lamellar bodies, such as artifacts and those produced by cellular degeneration. Although lamellar bodies can be observed in leucocytes of patients taking amiodarone, the determination of the rate of affected leucocytes is of no help for predicting amiodarone pulmonary toxicity.

[Effects of adrenergic beta 2 agonists by oral route on theophylline blood levels]. / Efeitos dos agonistas beta-2-adrenérgicos por via oral, sobre os níveis séricos de teofilina.

Several drugs interfere with theophylline pharmacokinetics, inducing changes on it's serum levels. With the purpose of determining a possible influence of oral administered beta-2-adrenergics agents on theophylline serum levels ten patients with bronchial obstruction, whose ages ranged from 51 to 69 (average 59.90 +/- 6.67) years, were analysed. After a period of 24 hours without any medication, the patients received 600 mg of oral slow release theophylline per day, for 7 days, followed by 7 days of the same dose of theophylline combined with 16 mg of oral salbutamol. Blood samples were drawn after the 24 hours without medication and at the 4th hour after the morning dose of theophylline, at the end of each week. The serum levels were, respectively, 2.08 +/- 1.20 micrograms/ml, 15.18 +/- 6.87 micrograms/ml and 11.45 +/- 5.15 micrograms/ml. The levels of the phase (theophylline alone) were significantly higher than those obtained after the concurrent use of theophylline and salbutamol. It can be concluded that this association interferes on theophylline pharmacokinetics. We suggest that in patients taking these drugs the serum levels of theophylline shall be measured to permit an eventual correction of the dose of theophylline being administered.

[Influence of the combination of theophylline and beta 2 agonists by oral route on pulmonary function of patients with chronic obstructive lung disease]. / Influência da associação teofilina e beta-2-agonista por via oral, na função pulmonar de pacientes portadores de doença pulmonar obstrutiva crônica.

The role of the concurrent use of theophylline and beta-adrenergic agents for relief of bronchial obstruction is controversial. For this reason, we studied the lung function of 9 patients with chronic obstructive pulmonary disease, whose ages ranged from 51 to 69 (average 60.6 +/- 6.6) years, after the oral administration of theophylline and theophylline plus salbutamol. After withdrawal of all bronchodilators for 24 hours, the basal values of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were obtained. Oral slow release theophylline (600 mg/day) was then administered for 7 days, followed by 7 days of the concurrent use of the same dose of theophylline plus salbutamol (16 mg/day). Spirometry was reevaluated at the end of each week. Pretreatment FVC ranged from 0.85 to 2.57 (average 1.78 +/- 0.64) liters, FEV1 from 0.70 to 1.64 (average 1.15 +/- 0.30) liters and theophylline serum levels from 0.1 to 3.1 (average 1.81 +/- 1.01) micrograms/ml. At the end of the first week, FVC was 1.38 to 3.26 (average 2.03 +/- 0.65) liters, FEV1 0.85 to 1.73 (average, 1.40 +/- 0.29) liters and theophylline serum levels 8.1 to 21.0 (average 13.40 +/- 4.18) micrograms/ml. With the concurrent use of theophylline and salbutamol FVC ranged from 1.24 to 2.57 (average 1.90 +/- 0.50) liters and FEV1 from 0.96 to 1.90 (average 1.46 +/- 0.33) liters, values not statistically different from theophylline alone.

[Pneumoconiosis in abrasive industry workers]. / Pneumoconiose em trabalhadores de indústria de abrasivos.

Occupational lung disease is uncommon in workers of abrasive industries. Twenty-two workers of these industries presenting radiological lung lesions were analysed. All were males with ages ranging from 29 to 59 years. Nineteen worked in the production of silicon carbide, three in the production of aluminum dioxide and one in both for a period of 8 to 27 years. In 20 patients the predominant radiological changes (ILO-80) were small opacities. Association of small and large opacities was observed in one case and isolated large opacities in another one. The small opacities were predominantly round and diffuse. The large opacities in both patients were classified as being of category B. It is concluded that the workers in abrasive industries are at a higher risk of developing occupational lung disease produced by silicon carbide.

Valor da quantificacao dos corpos lamelares em leucocitos na toxicidade por amiodarona / Value of lamellar bodies quantification in leukocytes in toxicity by amiodarone

Amiodarona e uma droga anfifilica que facilmente atravessa a membrana plasmatica, podendo induzir producao de corpos lamerares nos lisossomas de praticamente todas as celulas do organismo, independente de efeitos toxicos. Este estudo determina o valor da pesquisa destes corpos lamelares em leucocitos de sangue periferico como metodo de prevencao da toxicidade pulmonar em pacientes tratados cronicamente com amiodarona. A porcentagem de leucocitos com corpos lamelares foi determinada em tres grupos. O grupo I foi formado por oito pacientes com pneumonite por amiodarona que tomavam a droga por media de 16,88 meses (media de 386,60 mg ao dia). O grupo II por 19 pacientes sem nenhum efeito toxico da droga, e os que tomavam em media por 38,32 meses (media de 260,62 mg ao dia). O grupo III foi composto por oito individuos higidos que nao tomavam nenhuma medicacao. A camada de leucocitos obtida por centrifugacao de sangue periferico foi examinada por microscopia eletronica. A porcentagem de leucocitos com corpos lamelares foi determinada em todos os pacientes dos tres grupos. A media de leucocitos com corpos lamelares foi 1,82 por cento no grupo I, 1,65 por cento no grupo II e 3,47 por cento no grupo III. As inclusoes lamelares foram evidenciadas nos tres grupos...

Influencia da associacao teofilina e beta-2-agonista por via oral, na funcao pulmonar de pacientes portadores de doenca pulmonar obstrutiva cronica / Influence of the combination of theophylline and beta 2 agonists by oral route on pulmonary function of patients with chronic obstructive lung disease

A eficacia da associacao de teofilina e agentes beta-adrenergicos na terapeutica da obstrucao bronquica e tema controverso na literatura. Com este objetivo, foram estudados nove pacientes portadores de DPOC, com idades entre 51 e 69 (media de 60,6 ñ 6,6) anos, nos quais foi comparada a funcao pulmonar com o uso de teofilina isolada ou combinada ao salbutamol, por via oral. Apos a suspensao de qualquer medicacao broncodilatadora por 24 horas foram determinados os valores basais da capacidade vital forcada (CVF) e do volume expiratorio forcado no primeiro segundo "(VEF IND. 1)". Teofilina de acao prolongada (600mg/dia) foi, entao, administrada por via oral por sete dias, seguidos de sete dias de ingestao oral na mesma dose de teofilina associada a 16mg/dia de salbutamol. Os parametros espirometricos foram analisados ao final de cada semana. A CVF basal foi de 0,85 e 2,57 (media 1,78 ñ 0,64) litros, o "VEF IND. 1" 0,70 a 164 (medida 1,15 ñ 0,30) litros e a teofinemia 0,1 a 3,1 (media 1,81 ñ 1,01) ug/ml. Ao final da primeira semana, a CVF foi de 1,38 a 3,26 (media 2,03 ñ 0,65) litros, o "VEF IND. 1" 0,85 a 1,73 (media 1,40 ñ 0,29) litros e os niveis sericos de teofilina 8,1 a 21,0 (media 13,40 ñ 4,18) ug/ml. Com a associacao teofilina e salbutamol a CVF encontra-se entre 1,24 e 2,57 (media 1,90 ñ 0,50) litros e o "VEF IND. 1" entre 0,96 e 1,90 ...

Efeitos dos agonistas beta-2-adrenergicos por via oral, sobre os niveis sericos de teofilina / Effects of adrenergic beta 2 agonists by oral route on theophylline blood levels

Diversas drogas interferem com a farmacocinetica da teofilina, acarretando variacoes de seus niveis sericos. Com o objetivo de caracterizar possiveis influencias dos beta-2-adrenergicos por via oral, na teofilinemia de pacientes em uso desta droga, analisamos dez portadores de obstrucao bronquica, com idades entre 51 a 69 (media de 59,90 ñ 6,67) anos. O estudo consistiu na analise da concentracao serica de teofilina 24 horas apos a suspensao de toda medicacao, depois de um periodo de administracao diaria isolada de 600 mg de teofilina de acao prolongada, e apos sete dias de associacao da mesma dose de teofilina com 16 mg diarios de salbutamol por via oral. As amostras sanguineas foram colhidas 4 horas apos a ingestao da dose matinal de teofilina. Os resultados obtidos foram respectivamente 2,08 ñ 1,20 ug/ml, 15,18 ñ 6,87 ug/ml e 11,45 ñ 5,15 ug/ml. Os valores da fase (teofilina isolada) foram significativamente maiores aos obtidos apos a combinacao de teofilina e salbutamol. Estes resultados permitem concluir que esta associacao por via oral interfere na farmacocinetica da teofilina. Sugerimos que nos individuos em uso destas drogas, os niveis de teofilina sejam monitorizados, para eventual correcao da dose administrada.

Pneumoconiose em trabalhadores de industria de abrasivos / Pneumoconiosis in workers of abrasive industry

O desenvolvimento de pneumopatia profissional em operarios de industrias de material abrasivo e incomun, sendo ate recentemente considerada a silica como causadora da pneumoconiose. Analisamos 22 operarios destas industrias em que se detectaram alteracoes radiograficas de torax. Todos eram do sexo masculino, com idades variando de 29 a 59 anos. Dezenove trabalhavam na producao de carbeto de silicio, tres na producao de oxido de aluminio e um em ambos, tendo ficado expostos por um periodo de 8 a 27 anos. As alteracoes radiologicas (ILO-80) predominantes foram pequenas opacidades em 20 pacientes. Associacao de grandes e pequenas opacidades foram observadas em um caso e grandes opacidades isoladamente em um. As pequenas opacidades foram predominantemente difusas e arredondadas. Nos dois doentes com grandes opacidades, estas se enquadravam como categoria B. Conclui-se que operarios em industrias de abrasivos encontram-se sob risco de desenvolvimento de pneumopatia profissional mais provavelmente desencadeada pela inalacao de carbeto de silicio.

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 + or - 0.3 L; PaO2 = 65.7 + or - 9.0 mmHg) we 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 an 17.7 µg/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