Ligation of members of the beta 1 or the beta 2 subfamilies of integrins by antibodies triggers eosinophil respiratory burst and spreading.

Eosinophils interact with extracellular matrix proteins and endothelial cells through adhesion proteins belonging to the beta 1 and beta 2 subfamilies of integrins. Extending previous observations, we found that tumour necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor stimulated generation of superoxide anion by eosinophils plated on fibronectin-coated surfaces. As studies with adherent neutrophils indicated that TNF might act as activating leucocyte integrins to deliver signals involved in activation of cell functions, we investigated the effects of monoclonal antibodies (mAb) directed against VLA-4 (CD49d/CD29), LFA-1 (CD11a/CD18), CR3 (CD11b/CD18) or the common beta 2 subunit (CD18) on generation of eosinophil toxic oxygen molecules and spreading. We show that cross-linking of members of both the beta 1 and the beta 2 integrin subfamilies triggers eosinophil respiratory burst and spreading. Evidence for the selectivity of anti-integrin mAb effects is derived from the findings that isotype-matched mAb of other specificities (anti-class I MHC Ag, anti-beta 2-microglobulin, anti-CD4) did not trigger eosinophil functions. The findings presented in this paper suggest that integrin-dependent, eosinophil adhesion in sites of allergic reaction may be accompanied by release of toxic oxygen molecules involved in tissue damage.

Effects of nedocromil sodium on the binding of N-formyl-methionyl-leucyl-phenylalanine in human neutrophils.

In the present study the inhibition by nedocromil sodium of the specific receptor binding of FMLP was evaluated in human neutrophils (PMNs) using a FMLP-(3H) binding assay. The time course of the binding was markedly influenced by nedocromil sodium used at a concentration of 300 microM. No significant inhibition was obtained when the cells were treated with nedocromil sodium 3 microM or with sodium cromoglycate 300 microM. FMLP binding is essentially eliminated by the highest dose of nedocromil sodium. The biologic meaning of this effect in asthmatic patients should be further evaluated.

Perception of bronchoconstriction in chronic asthma.

Twenty-nine asthmatic children were studied to assess their ability to detect the severity of their bronchoconstriction. First (STEP 0): each child was asked if he "felt asthma," inviting him to give a self-estimated obstruction score (SEOS) from 0 (no asthma) to 3 (severe asthma) and a baseline FEV1 was recorded. Then (STEP 1): methacholine was administered to all except 9 children with an FEV1 less than 80% of predicted who received saline nebulization and a second SEOS was recorded. Finally: salbutamol aerosol was administered and a third SEOS and FEV1 were obtained (STEP 2). Spearman's correlation coefficients r between SEOS and FEV1 were for the overall population -0.602, -0.517, and -0.104 at STEP 0, STEP 1, and STEP 2, respectively. The r values reduction during the trial can be due either to a decrease of children's concentration during the study or to a real difficulty in recognizing repeated changes in airway status. Some children tend to underestimate their bronchospasm. For these patients an accurate assessment of the severity of the bronchoconstriction requires an objective measurement during acute changes in asthmatic children.

Inhibition of different dosages of oxatomide or placebo on skin prick test and nasal allergen provocation.

In this two-stage, double-blind study, we evaluated the effects of different dosages of oxatomide (1 and 2 mg/kg/day) on nasal provocation and skin reaction wheal induced by grass-pollen challenge. Children with a positive history of allergic rhinoconjunctivitis and positive responses to skin prick test and nasal provocation test to grass pollen were studied out of season. The results obtained with 1 mg/kg/day of oxatomide demonstrated no significant difference in wheal areas and nasal secretion induced by allergen challenge between treated and untreated patients. The administration of 2 mg/kg/day demonstrated a significant suppression in wheal reaction and nasal secretion induced by specific challenge.

Relationships between skin prick test, radioallergosorbent test, and chemiluminescent assays in allergic children.

The results of skin prick tests (SPT), radioallergosorbent tests (RAST), and multiple chemiluminescent tests (DHS-CLA) to grass mix, parietaria, D. farinae, and D. pteronyssinus were evaluated in 43 allergic children. All CLA tests had valid positive and negative control threads. Chemiluminescent assays class 4 matched with RAST class 3 and/or 4 and CLA class 3 with RAST class 2. The D. farinae, D. pteronyssinus, and grass results obtained with CLA, RAST, and SPT were investigated by principal components analysis that showed a good association between different methods of measuring allergenicity. The results of the present study confirm that DHS-CLA is an effective "in vitro" method for the detection of IgE-allergen specific antibody.

Effect of inhaled beclomethasone dipropionate on bronchial hyperreactivity in asthmatic children during maximal allergen exposure.

In this double blind study we evaluated the effect of a 2 months long treatment with inhaled beclomethasone dipropionate (300 micrograms/day) on methacholine responses in asthmatic children, during a period of maximal allergen exposure. Baseline values of methacholine PC20-FEV1 were 0.66 +/- 0.22 mg/mL (mean +/- SEM) in 10 children treated with the active drug and 0.78 +/- 0.21 mg/mL in 10 children treated with placebo. After 1 month of treatment PC20-FEV1 was 1.91 +/- 0.64 and 0.80 +/- 0.33 mg/mL, respectively, in the groups treated with beclomethasone versus placebo. A statistically significant reduction in bronchial hyperreactivity (PC20-FEV1, 5.49 +/- 1.86 mg/mL) but no systemic side effects were observed after 2 months of treatment with beclomethasone dipropionate. This is compared with a PC20-FEV1 of 1.38 +/- 0.52 mg/mL in the placebo group. The results confirm the effect of inhaled corticosteroids in reducing bronchial hyperreactivity, even during a period of maximal allergen exposure.

Double-blind evaluation of effectiveness and safety of flunisolide aerosol for treatment of bronchial asthma in children.

A double-blind study was carried out in 20 asthmatic children in order to evaluate the therapeutic efficacy and safety of inhaled corticosteroid flunisolide. 0.5 mg of the drug was administered by a jet nebulizer twice daily for 2 months. Respiratory symptoms, pulmonary function values and methacholine PC20-FEV1 were evaluated, as also morning cortisol levels, plasma cortisol increase after ACTH test, and 24-h urinary cortisol excretion. The data obtained show the efficacy of the drug in reducing symptoms. No significant difference was observed in pulmonary function values and in bronchial reactivity results between the two groups. No effect of flunisolide was observed on hypothalamic-pituitary-adrenal function. This study confirms the efficacy and safety of flunisolide (0.5 mg b.i.d.) in the treatment of asthmatic children.

Additive effect of albuterol and ipratropium bromide in the treatment of bronchospasm in children.

Inhaled albuterol (A) (salbutamol) alone and albuterol plus ipratropium bromide (IB) were administered to 12 asthmatic children. Following administration of A alone or in combination with IB, there was a significant increase in FEV1 and FEF. Significant statistical difference in favor of the association A plus IB was observed at 120 and 240 minutes for FEV1 and in the period 120, 180, and 240 minutes for FEF. The additive effect was present both in the large and small airways. The short-lived additive effect of A plus IB suggests the opportunity to increase the frequency of drug administration in patients with severe bronchial obstruction.