Fluticasone propionate and bronchial hyperresponsiveness in childhood asthma.

Bronchial asthma is now agreed as being a chronic inflammatory disease of the airways. Inhaled steroids are widely accepted as a preventive medication in asthmatic patients of all ages and severity. However, the optimal use of inhaled steroids and the important issue of safety and efficacy still remain of concern, particularly in children. Recently, fluticasone propionate (FP) has been developed for use as an inhaled preparation for the treatment of asthma. Because of its high topical potency and increased lipophilicity, it is claimed that FP has an improved risk/benefit compared with other inhaled steroids. In order to evaluate the use of FP in children, we have studied the efficacy of high dose FP (500 microg/day) in asthmatic children. Thirteen children (9 boys and 4 girls), aged 7-17 years (10.8 +/- 2.6), were instructed to use a pressurized metered-dose inhaler connected to a Volumetric spacer. The standard methacholine bronchial challenge test was used as a principal outcome parameter. The PD20, a cumulative dose of methacholine inducing a 20% decrease in FEV1, was measured pre- and post-treatment with inhaled FP. After 4 weeks of FP, PD20 significantly increased from 21.6 +/- 14.3 inhalation unit to 106.6 +/- 78.5 inhalation unit (4.9 fold, p = 0.004) reflecting the improvement of airway reactivity. All subjects improved clinically. These results demonstrate that the anti-inflammatory action of FP 500 microg a day for four weeks can markedly reduce bronchial hyperresponsiveness, the basic physiologic abnormality in bronchial asthma.     

The effect of immunotherapy on nonspecific bronchial hyperresponsiveness in bronchial asthma and allergic rhinitis

Allergen injection therapy may improve nonallergic bronchial hyperresponsiveness, but results at the moment are less than convincing. The present study was conducted to evaluate the effect of immunotherapy on the degree of nonspecific bronchial hyperresponsiveness in patients with allergic bronchial asthma (BA) and/or allergic rhinitis (AR). Methacholine challenge bronchial provocation test, allergic skin test, serum IgE and peripheral blood eosinophil counts were performed before and after 12 months or more of immunotherapy. The improved group, as determined by a shift of at least two doubling concentrations of methacholine, was 75% of AR (n=16), 41.7% of BA (n=24) and 53.8% of BA+ AR (n=13). The geometric mean of the methacholine provocational concentration (PC20) changed from 3.40 to 14.36 mg/ml (P <0.05) in AR, from 0.73 to 1.04 mg/ml in BA (not significant), and from 1.43 to 5.07 mg/ml (P <0.05) in BA+ AR. In conclusion, nonspecific bronchial hyperresponsiveness was improved by immunotherapy in three quarters of the allergic rhinitis cases and in about a half of the allergic bronchial asthma patients, which suggests that immunotherapy might be helpful at preventing the development of bronchial hyperresponsiveness in allergic rhinitis patients, and that it does not improve bronchial hyperresponsiveness in about a half of allergic bronchial asthma patients.     

Effect of therapy on bronchial hyperresponsiveness in the long-term management of asthma

The aim of this study was to determine if prophylactic therapy leads to a reduction in the severity of bronchial hyperresponsiveness (BHR) in subjects with severe asthma. Measurements of bronchial responsiveness to histamine were made in two groups of subjects for periods up to 2 years. Thirteen subjects in the study group took regular medication and used a home monitor of airway function to determine the medication requirements needed to maintain optimal airway function. A control group of eleven subjects was managed with the same drugs but without daily monitoring and without any attempt to keep daily lung function at optimal levels. Subjects in the study group had a 10- to 100-fold decrease in the severity of BHR, which was independent of the improvement in baseline lung function. All but one subject in the study group became symptom free and six were able to maintain the improvement in BHR and symptoms on reduced medication. There was no change in the severity of BHR or in the baseline lung function in the control group. It is concluded that it is possible to reduce the severity of BHR in subjects with severe asthma by the use of pharmacological agents. This reduction in severity appears to require the long-term use of medications, including aerosol corticosteroids, with daily home monitoring to allow adjustment of the amount of treatment required.     

Comparison of the effects on bronchial hyperresponsiveness of antiallergic agents and beclomethasone dipropionate in long-term bronchial asthma

The effect of antiallergic agents (DSCG (disodium cromoglycate), ketotifen, and ibudilast) and beclomethasone dipropionate inhaler (BDI) on bronchial hyperresponsiveness to histamine inhalation was retrospectively assessed in 72 asthmatic patients with more than a year's duration of the disease. Decrease in bronchial hyperresponsiveness to histamine was observed in 10 out of the 33 (30%) antiallergic-agents-treated patients (group A, mean duration = 7.8 months), in 12 of 19 (63.2%) BDI-treated patients (group B, 6.2 months), but only 2 of the 20 (10%) control patients (group C, 7.8 months). Improvement of histamine PC₂₀ was from 310 to 597 μg/ml ( P <0.01) in group A, from 308 to 1622 μg/ml ( P <0.0005) in group B, and from 575 to 525 μg/ml (NS) in group C. A significant decrease in the peripheral eosinophil count was observed only in group B. The improvement in bronchial hyperresponsiveness was parallel with that of asthmatic symptoms; the percentage of patients becoming symptom-free rose from 12 to 42%, 5 to 89%, and 5 to 20% in groups A, B, and C, respectively. Out of 11 unimproved patients in group A, 7 showed a significant improvement in their histamine PC₂₀ by BDI treatment (mean PC₂₀: 311 → 1828 μg/ml). These results suggest that BDI might be more effective than antiallergic agents in the treatment of patients with long-standing bronchial asthma.     

The effect of astemizole on bronchial hyperresponsiveness and exercise-induced asthma in children

The ability of the new generation H1-receptor antagonist, astemizole, to prevent histamine-induced airway obstruction and exercise-induced asthma (EIA) was studied in 20 children with asthma. The study was a randomised clinically controlled trial of oral astemizole versus placebo in a cross-over study. In each of the two treatment periods the children were tested at days 0, 6, 15 and 22 of therapy. The two treatment periods were separated by a washout period of 50 days, and at each visit a bronchial challenge with increasing concentrations of histamine followed by an exercise test was performed, and peak flow and asthmatic symptom score were recorded daily. The children tolerated significantly higher mean concentrations of histamine when treated with astemizole compared with placebo (P less than 0.001). Astemizole postponed the response to exercise, but no change in the maximal response was found. No differences between the treatment periods were found regarding frequency of asthmatic symptoms or the daily recording of peak flow.     

Primary and secondary effector cells in the pathogenesis of bronchial asthma

The immediate and late asthmatic reactions provoked by inhaled allergens have provided useful models enabling the dissection of individual inflammatory cells and their mediators that may contribute to the pathogenesis of asthma. The immediate reaction is considered to be mast cell-mediated on the basis that about 50% of the response is inhibitable by potent and selective H1-receptor antagonists such as terfenadine and astemizole. Additional inhibition (approximately 30%) by the potent cyclooxygenase inhibitor flurbiprofen implies an important role for prostanoids in the immediate response, the most likely mast cell-derived product being prostaglandin (PG) D2. In man, PGD2 is selectively metabolised to 9 alpha 11 beta-PGF2, a unique prostaglandin which shares with PGD2 contractile properties on guinea-pig and human airways smooth muscle. The inability of piriprost, a potent leukotriene synthesis inhibitor, to influence the allergen-provoked immediate reaction raises the possibility that sulphidopeptide leukotrienes play a minor role in this response. The late asthmatic reaction is considered to resemble clinical asthma since it is accompanied by increased responsiveness of the airways to a wide range of stimuli. The late reaction in man is inhibited by nedocromil sodium (4 mg) but only marginally attenuated by salbutamol (200 micrograms) if both drugs are administered prior to allergen challenge. Since salbutamol, in the dose administered, is a potent mast cell-stabilising agent, these findings must question the obligatory role of mast cell mediator release in the pathogenesis of the late response.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of pulmonary hypertension in the pathogenesis of bronchial asthma

In patients with bronchial asthma, when blood pressure in the pulmonary artery is measured, very often hypertension is registered. This pulmonary hypertension is not secondary to hypoventilation, as in patients with chronic bronchitis or pulmonary emphysema, since patients with bronchial asthma are hyperventilating. The pulmonary hypertension in them must be therefore classified as primary. It is probable that its origin is in an allergic vasoconstriction of the pulmonary artery, occurring simultaneously with the well known bronchoconstriction.     

New concepts in the pathogenesis of atopic dermatitis

Atopic dermatitis is a chronic, relapsing, inflammatory skin disease that is characterized by pruritic, eczematoid skin lesions. The disease results from interactions between susceptibility genes, the host environment, skin barrier defects, susceptibility to infection and immunological factors. An increased prevalence of atopic dermatitis has generated increased interest and research into each of these areas, and new treatment strategies are being developed based upon an increased understanding of these issues.     

The participation of epithelial desquamation in the increase of bronchial hyperresponsiveness after antigen challenge in patients with bronchial asthma

Bronchial hyperresponsiveness (BHR) was evaluated before and after antigen challenge in 12 patients with bronchial asthma as allergic reaction to house dust mites. Six out of the 12 showed an increase in BHR 48 hours after antigen challenge. Although there was no difference in the decrease of FEV1.0 in IAR and LAR between patients with (group A) and without (group B) the increase of BHR after antigen challenge, patients in group A expectorated a significantly larger number of clumps of respiratory epithelial cells (Creola bodies, CrB) in their sputum in both IAR and LAR. In addition, the degree of the increase of BHR significantly correlated with the CrB score, which was determined from the number and the size of CrB. These results suggest that epithelial desquamation participates in the increase of BHR after antigen challenge. The concentration of the eosinophil cationic protein (ECP) in their sputum did not change significantly in IAR and LAR compared with that before antigen challenge. There was no difference in the concentration of ECP in their sputum between the two groups either. One antigen challenge seemed to be too mild to induce an elevation of the concentration of ECP in their sputum. Judging from the fact that CrB could be observed not only at LAR but also IAR, epithelial desquamation seemed to be dependent on the degree of damage before antigen challenge rather than on the activation of eosinophils after antigen challenge.     

Relationship between presence of Creola bodies and airway hyperresponsiveness in patients with bronchial asthma

It has recently been suggested that epithelial damage participates in the development of bronchial hyperresponsiveness. In this study we investigated the relationship between the presence of clusters of desquamated respiratory epithelial cells (Creola body. CrB) in sputum and airway responsiveness. Sputa were collected from asthmatic patients and acetylcholine inhalation tests were performed to assess airway responsiveness. Smears of 100 microliters of sputum were spread in pairs of two glass slides. One slide was stained with Papanicolaou's stain, the other with Giemsa stain. CrBs were detected on the whole glass slide stained with Papanicolaou's stain and the CrB score was determined by summing up the points given to each CrB on a glass slide according to the number of epithelial cells composing one CrB. The CrB score was significantly higher in patients with CrBs than in patients without CrBs. The patients with higher CrB score (CrB score greater than or equal to 6) had significantly greater number of eosinophils in sputa than the patients without CrBs. These results suggest the participation of damage to the respiratory epithelium in the development of airway hyperresponsiveness in bronchial asthma. The detection of CrBs is easy and we consider it clinically useful in the estimation of airway hyperresponsiveness.