Clinical Severity Of Asthma Research Articles

Reduction of budesonide after a year of increased use: A randomized controlled trial to evaluate whether improvements in airway responsiveness and clinical asthma are maintained

We have demonstrated recently that 1 year of regular inhaled budesonide use can produce substantial improvements in airway responsiveness accompanied by significant improvements in clinical asthma severity. The present study was designed to evaluate whether these improvements are maintained when the dose of budesonide is reduced. At the end of the original study, 28 subjects with asthma, who had been in the active-treatment arm of the study were randomized either to continue taking the dose of budesonide taken in the original study or to have the dose reduced. Airway responsiveness to methacholine, bronchodilator requirements, symptoms, and spirometry were assessed after 6 weeks and 3 months. During the 3 months, no subject experienced an asthma exacerbation, and there was no evidence of change in airway responsiveness in subjects who had their steroids reduced (provocative concentration causing a 20% drop in FEV 1: initial, 2.03 mg/ml; final, 1.91 mg/ml), and this change was not different from change in subjects maintained with a higher dose (initial, 3.02 mg/ml; final, 3.12 mg/ml) ( p = 0.39). Similarly, there was no evidence of any change in bronchodilator requirements ( p = 0.89). However, after 3 months of reduced steroid use, there was a small decline in spirometry (FEV 1 percent predicted: initial, 84.4%; final, 81.5%), and this change was significantly different from change in subjects in whom steroids were not reduced (initial, 90.2%; final, 90.2%) ( p = 0.002). At 3 months, symptoms (predominantly sputum production) were also beginning to redevelop in the reduced budesonide group ( p = 0.056). The results suggest that, when inhaled steroids are reduced after prolonged treatment, improvements in airway responsiveness can be maintained for at least 3 months and that a deterioration in spirometry and symptoms may precede an increase in responsiveness.

Long-term effects of budesonide on airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthmatics

Budesonide 400 micrograms daily, in nonsteroid-dependent asthma, can produce improvements in airway responsiveness and clinical asthma severity, with some patients returning to normal responsiveness and becoming asymptomatic. This study examined whether similar improvements occur when asthmatics, who are dependent upon inhaled steroids, take either a regular maintenance dose of inhaled steroid or twice that amount for a year. Thirty two asthmatics were each stabilized on the minimum amount of inhaled steroid that would keep symptoms non-troublesome. In a double-blind, randomized manner, half were assigned to remain on a maintenance dose (MD) and the rest received twice that dose (MDx2) for one year. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, inhaled bronchodilator use and number of asthma exacerbations. There was a significant improvement in airway responsiveness and clinical asthma severity in both treatment groups. Those on MDx2 showed the greatest improvement but the difference between the two groups did not reach significance. This study provides strong evidence that prolonged use of inhaled steroids is associated with improvement in airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthma with a suggestion that the improvements are dose related.

Eosinophilic Inflammation in Asthma

The importance of eosinophils in the pathogenesis of bronchial asthma is not established. In an attempt to evaluate the role of eosinophilic inflammation in asthma, we compared 10 normal subjects with 43 patients with chronic asthma, 19 of whom had severe disease as assessed by a clinical scoring method described by Aas and by pulmonary-function tests. Eosinophils were counted in peripheral blood and bronchoalveolar-lavage fluid, and in biopsy specimens obtained from the patients and post mortem from 8 subjects without asthma, but not from the 10 normal controls. Eosinophil cationic protein was titrated by radioimmunoassay in the bronchoalveolar-lavage fluid from all subjects and studied by immunohistochemistry in the biopsy specimens. There was a significant increase in the number of peripheral-blood eosinophils in the patients that was correlated with the clinical severity of asthma (P less than 0.001) and pulmonary function (P less than 0.03). Levels of eosinophils and eosinophil cationic protein were increased in the bronchoalveolar-lavage fluid from the patients and were also correlated with the severity of asthma (P less than 0.001 and P less than 0.002, respectively). Hematoxylin-eosin staining of bronchial-biopsy specimens showed that intraepithelial eosinophils were present only in patients with asthma. Immunohistochemical analysis of eosinophil cationic protein revealed that normal subjects had only a few nondegranulated eosinophils deep in the submucosa, whereas all the patients had degranulated eosinophils beneath the basement membrane and among epithelial cells. In some patients there was a relation between the presence of degranulated eosinophils and epithelial damage. Eosinophilic inflammation of the airways is correlated with the severity of asthma. These cells are likely to play a part in the epithelial damage seen in this disease.

Effect of Long-term Treatment with an Inhaled Corticosteroid (Budesonide) on Airway Hyperresponsiveness and Clinical Asthma in Nonsteroid-dependent Asthmatics

Several short-term studies have shown that inhaled steroids can reduce airway hyper-responsiveness in asthma. To evaluate whether prolonged treatment can bring about full recovery, this double-blind, randomized, controlled trial examined the effect of budesonide, 400 micrograms daily for 1 yr, on airway hyperresponsiveness. The time course and characteristics of improvements and associated changes in clinical asthma severity were also evaluated. Thirty-two stable adult asthmatics, requiring bronchodilators alone, were selected. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, daily bronchodilator use, and number of asthma exacerbations. Patients receiving budesonide showed a fourfold mean improvement in airway responsiveness compared with those receiving placebo (p less than 0.0005), whose responsiveness remained very stable. Fifteen of the 16 budesonide subjects improved and 5 returned to the normal range. Largest improvements occurred during the first 3 months but, in some, were still progressing slowly at 1 yr. Improvements in responsiveness were accompanied by significant improvements in asthma symptoms, bronchodilator use, and number of asthma exacerbations. The results show that regular, prolonged use of inhaled steroid can produce marked improvements in airway hyperresponsiveness, sometimes with full resolution, and these improvements are accompanied by clinically significant improvements in clinical asthma.

Improvement in airway responsiveness and asthma severity during pregnancy. A prospective study.

In the myometrium and gut, smooth muscle becomes less contractile during pregnancy, probably because of the effect of progesterone and estrogen. It is not known whether these hormones cause similar changes in airway smooth muscle, and therefore, this study examined airway responsiveness during the large hormonal changes of pregnancy and evaluated whether changes in responsiveness are associated with changes in (1) progesterone and estrogen and (2) the clinical severity of asthma. Twenty nonpregnant asthmatic women were assessed every 3 months until conception. In the 16 who conceived, assessments were repeated once during the second and third trimesters and 1 month after delivery. Data collected preconception and from those who did not conceive within 1 yr were used for control subjects. There was a 2-fold improvement in airway responsiveness during pregnancy from a preconception mean PC20 0.35 to 0.72 mg/ml during the second trimester and 0.58 mg/ml during the third (p = 0.03). Post-delivery responsiveness (0.48 mg/ml) was not significantly different from preconception. The improvements during pregnancy were greater than the 3 monthly fluctuations when not pregnant (p = 0.04) and were greatest in those who were most hyperresponsive initially (p = 0.01). There was an associated improvement in clinical asthma severity as indicated by a reduction in minimum medication requirements (p = 0.03) and this was not at the expense of good symptoms control; both symptoms and spirometry remained unchanged during pregnancy. Changes in responsiveness were not closely related to progesterone or estriol, suggesting that other nonhormonal factors may also contribute to the improvement during pregnancy and that the control of asthmatic airway smooth muscle may not be exactly the same as that of the myometrium and gut.

Clinical Significance of Nonspecific Bronchial Hyperresponsiveness in Asthma

Measurement of nonspecific bronchial hyperresponsiveness remains largely a research tool in asthma, and its usefulness in the assessment and management of asthma is poorly defined. We studied the relationship of bronchial hyperresponsiveness to the clinical severity of asthma in 54 asthmatic subjects. In order to find out whether measurement of bronchial hyperresponsiveness could be used to predict future symptomatic status and requirements for drugs, ten patients were followed for three months. We found that there was no correlation between the clinical severity of asthma and the degree of bronchial hyperresponsiveness and, also, that the latter could not be used as a prognostic indicator of future symptomatic status and drug requirements. Measurement of nonspecific bronchial hyperresponsiveness, therefore, adds little to the assessment and management of asthma.

Factors predisposing to exercise-induced late asthmatic responses

Seventeen children developed reproducible early and late asthmatic responses (dual reactions) after cycle ergometer exercise. There was a significant correlation between the magnitude of their early and late reactions, emphasizing the direct relationship of these events. No ;significant differences were observed in the clinical severity of asthma, diurnal variations in FEV 1 and extent of the early reaction after exercise between children with dual responses and 19 children with single reactions. These findings suggest that the occurrence of late reactions after exercise is not determined by differences in severity of disease or baseline airway reactivity in the asthmatic subjects. This view is supported by the finding that there was no significant difference in the dose of acetylcholine necessary to elicit a 20% decrease in FEV, between eight children with dual response and seven children with single early response after exercise. The rate of spontaneous recovery from early reactions was slower in children with dual responses, suggesting that this variable may predict development of late-phase reactions in exercise-induced asthma.

Cold air challenge of airway hyperreactivity in children: practical application and theoretical aspects.

In 23 children with asthma and 18 healthy controls, cold air challenge ( CACh ) was done twice during the same half day, and in the asthmatics a third time together with a histamine challenge (HCh) 2 wk later. Pulmonary functions were tested before and after each challenge. No overlapping of individual responses to CACh in seven forced expiratory flow tests proved the power of discrimination of this technique in children. The limits of "normal" reactions ranged from minus 9% for larger airway-related to 26% for smaller airway-related flows. Short-term reproducibility of induced changes, in percentage of baseline, was excellent (r = 0.815-0.954); in percentage of predicted postchallenge abnormality it was even better (r = 0.926-0.975). The response in small airway-related flow rates (-43.1 +/- 12.8 to -51.9 +/- 16.8% of baseline) was much larger than in others (-27.6 +/- 14.6 to -32.1 +/- 17.3% of baseline). This, the different baseline-to-response correlations in various measurements, and the divergent dose response to colder versus less cold air in large (60.7 +/- 21.9 versus 65.4 +/- 21.5% predicted, postchallenge values) and small airway-related tests (28.9 +/- 18.7 versus 29.5 +/- 15.1% predicted, postchallenge values) in asthmatic children suggest a predetermined, small airway-related limitation of individual reactivity, which is independent of the baseline situation. All asthmatics responded positively to HCh but quantitative results of the two methods did not correlate. Responses to CACh also better characterized the clinical severity of asthma than those of HCh.(ABSTRACT TRUNCATED AT 250 WORDS)

GROWING OUT OF ASTHMA: CLINICAL AND IMMUNOLOGICAL CHANGES OVER 5 YEARS

Asthmatic children with bronchial reactivity to a seasonal allergen, rye-grass pollen, and/or a perennial allergen, Dermatophagoides pteronyssinus, were studied over 5 years. Changes in their clinical symptoms and drug usage were correlated with changes in levels of serum IgG and IgE antibodies to the rye and mite allergens. The overall clinical severity of the children's asthma declined significantly during the study period and was accompanied by a significant fall in IgG and IgE anti-mite antibodies. The asthma of those children with bronchial reactivity to rye-grass pollen continued to be exacerbated in the pollen season of year 5, and both IgG and IgE anti-rye antibodies continued to rise and fall in relation to the season. These observations suggest that long-term perennial allergen exposure favours the induction of clinical and immunological hyporesponsiveness, whereas intermittent seasonal allergen exposure is associated with persistent clinical and immunological hypersensitivity.