Marcel Topilsky

A clinical and immunologic study of colchicine in asthma.

A double-blind, randomized, crossover chronic study was done to determine the efficacy of colchicine in 10 atopic patients with asthma. A constant dose of sustained-release theophylline and albuterol by inhalation, as needed, was administered. Compared to placebo, colchicine, 0.5 mg twice daily, significantly reduced the mean (+/- SEM) daily clinical score from 2.18 +/- 0.34 to 1.64 +/- 0.32 (p less than 0.05), and the daily number of inhalations of albuterol from 5.89 +/- 1.48 to 4.01 +/- 1.26 (p less than 0.02). Colchicine significantly (p less than 0.05) increased the concanavalin A-induced suppressor cell function from 16.2 +/- 4.6% to 39.0 +/- 10.7%, which was similar to healthy volunteers (41.1 +/- 3.5%). Furthermore, colchicine significantly (p less than 0.05) decreased serum IgE from 248 +/- 63 to 188 +/- 46 IU/ml. Colchicine had no significant effect on pulmonary function tests, the early phase reaction of antigen-induced bronchial inhalation challenge, and immediate skin test responses. Thus, colchicine has immunomodulatory effects that may perhaps have a mild benefit in the treatment of asthma.

The effect of food and exercise on the skin response to compound 48/80 in patients with food-associated exercise-induced urticaria-angioedema.

Food-associated, exercise-induced urticaria-angioedema is increasingly being recognized. We studied five atopic individuals in whom ingestion of food was followed by exercise-induced urticaria-angioedema. The combined effect of food and exercise on skin wheal response to compound 48/80 and histamine was studied. Symptoms could be reproduced in only four of the patients who performed strenuous exercise after ingestion of food to which they were skin sensitive. When symptoms appeared, that is, after a combination of food and exercise challenge, there was a marked increase in the wheal response to compound 48/80 (greater than 200%) and not to histamine. Food or exercise challenge alone did not induce any significant change in the skin reactivity to compound 48/80 or to histamine. It was concluded that mast cell releasability could be increased when the patient was subjected to combined factors.

Mite asthma in childhood: A study of the relationship between exposure to house dust mites and disease activity

BACKGROUND Children with asthma are commonly sensitized to the house dust mite. METHODS We took monthly measurements from July to December of the amount of mites in the mattresses of asthmatic children and correlated them with symptom score, pulmonary function, and airway hyperreactivity to methacholine. RESULTS In spite of the high number of Dermatophagoides pteronyssinus throughout this period, symptom and treatment scores, as well as PC20 to methacholine, worsened during the months of September and October. CONCLUSIONS It is concluded that when asthmatic children allergic to mites are exposed to high levels of mite allergen, the number of mites in the mattress dust no longer correlate with increased symptoms, and that other factors are more likely to be associated with exacerbation.

Sarcoidosis: an organized pattern of reaction from immunology to therapy

Advances in our understanding of sarcoidosis and other granulomatous disorders were discussed at a recent meeting. In particular, the role of cytokines and cell interactions, and the expression of specific T-cell receptor molecules, were considered in relation to the regulation of the pathogenesis of these diseases in humans.

Small airway responsiveness to exercise as an objective measure of exercise-induced asthma in children

Exercise has been proposed as a useful challenge test for measuring bronchial hyper-responsiveness. The accepted diagnosis of exercise-induced asthma (EIA) is an end FEV1- change index of at least 10-20% post standard exercise. This preliminary study aimed to demonstrate the importance of the contribution of the small airways to the obstruction postexercise. Ninety-one asthmatic children aged 6-17 years, of whom 70 had clinical presentation of EIA, participated in this study. They were subdivided into three groups according to the percentage fall index of FEV1 post an exercise challenge. Thirty-nine children showed a reduction of 35 ± 12% in FEV1, and a reduction of 50%, 55%, and 54% in FEF25%, FEF50%, and FEF75%, respectively. Thirty-one had a reduction of 12 ± 5% in FEV1, and a reduction of 21%, 29%, and 33% in FEF25%, FEF50%, and FEF75%, respectively. Twenty-one asthmatic children without clinical EIA demonstrated a percentage fall index in FEV1 (2 ± 2%) and a mean percentage fall in FEF25%, FEF50%, an...

Differential Proliferative Characteristics of Alveolar Fibroblastsin Interstitial Lung Diseases: Regulative Role of IL-1 and PGE2

Fibroblasts (Fb) from patients with sarcoidosis (SA) and hypersensitivity pneumonitis (HP) exhibited a lower proliferative capacity compared with Fb obtained from control (CO) and diffuse interstitial fibrosis patients (DIF). Proliferation of Fb from SA or lip patients was suppressed by autologous LPS-stimulated alveolar macrophages (AM) supernatants but not by those from CO patients. Similarly, alveolar macrophages (AM) derived supernatant, obtained from CO, did not suppress the proliferation of SA and HP Fb. AM from SA and HP patients secreted higher amounts of IL-1α and β compared with controls and compared with Fb from SA and HP patients. Steady levels of IL-1α and βmRNA were expressed in unstimulated and stimulated cultures. Fb from SA and HP patients could be stimulated by LPS to secrete significantly higher levels of PGE2 than those detected in supernatants from LPS stimulated Fb of DIF patients. Only the proliferation of Fb from SA and HP patients was sensitive to amounts of IL-1 equivalent to those detected in the lung of these diseases. As SA and HP are two diseases where irreversible deterioration occurs in only 20% of the patients, we hypothesize that mediators in the lung may modulate Fb proliferation. IL-1 of AM origin and PGE2 of Fb origin secreted at high levels, may be candidates for this suppression because it was abrogated by anti IL-1β and indomethacin.

Short- and long-term follow-up after coronary bypass grafting for single-vessel coronary artery disease.

Short-term outcome and 10-year clinical outcome were reviewed in 114 consecutive patients after coronary artery bypass grafting (CABG) for single-vessel coronary artery disease (CAD). Gated equilibrium radionuclide cineangiography was performed soon after CABG in all cases, and revealed very good early graft patency rates. There was no perioperative mortality, and very low morbidity. During follow-up there were seven late deaths, two from cardiac disease and five from non-cardiac causes. Cumulative survival at 10 years was 93%. Cumulative freedom from additional cardiac invasive procedures was 96%, 93% and 80% at 1, 5, and 10 years, respectively, and cumulative freedom from angina was 93%, 80% and 73%. Conventional single-vessel CABG thus can be safely performed, with minimal postoperative morbidity and no mortality, providing good long-term relief of angina and circumventing need for additional invasive procedures.