Antioxidant foods consumption and childhood asthma and other allergic diseases: the Greek cohorts of the ISAAC II survey

BACKGROUND: Antioxidant intake changes have been implicated with the increase in asthma and allergies outcomes, but no clear association has been revealed. In this cross sectional study, the overall effect of antioxidants on asthma and allergic diseases was studied. METHODS: Data from the cohorts of the phase II ISAAC survey (2023 children 9-10 years old) in two metropolitan Greek cities were analysed. Using a semi-quantitative food frequency questionnaire, an Antioxidant Eating Index (AEI, range 0-6) was created with the pro-antioxidant (vegetables, fruits, fresh juice, fish) and the non-antioxidant (meat, burgers) food intake and was evaluated with allergic diseases. Higher values of the score suggest closer to an "antioxidant" and lesser to a "saturated fatty" diet. RESULTS: Prevalence of lifetime and current asthma, current rhinitis and sensitisation were higher in Thessaloniki compared to Athens. The AEI score of the entire cohort was 4.2 ± 1.2 (median 4.0) and was higher in Athens compared to Thessaloniki (4.3 ± 1.2 vs. 4.0 ± 1.2, p = 0.001) and in girls than boys (4.3 ± 1.1 vs. 4.0 ± 1.2, p = 0.001). AEI was inversely associated with lifetime asthma (OR: 0.87, 95%CI 0.77, 0.99) in either cities independently of other cofounders such as family history, sensitisation, exercise, house smoking, breast feeding, pet or dampness in houses. No association with other allergic disease or sensitisation was detected. CONCLUSION: Antioxidant foods seem to be a non-pharmacological, protective dietary pattern for asthma development in children irrespectively of atopy or heredity; AEI was a rough indicator and the role of antioxidants in allergic diseases is still under consideration

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Antioxidant foods consumption and childhood asthma and other allergic diseases: The Greek cohorts of the ISAAC II survey.

BACKGROUND: Antioxidant intake changes have been implicated with the increase in asthma and allergies outcomes, but no clear association has been revealed. In this cross sectional study, the overall effect of antioxidants on asthma and allergic diseases was studied. METHODS: Data from the cohorts of the phase II ISAAC survey (2023 children 9-10 years old) in two metropolitan Greek cities were analysed. Using a semi-quantitative food frequency questionnaire, an Antioxidant Eating Index (AEI, range 0-6) was created with the pro-antioxidant (vegetables, fruits, fresh juice, fish) and the non-antioxidant (meat, burgers) food intake and was evaluated with allergic diseases. Higher values of the score suggest closer to an "antioxidant" and lesser to a "saturated fatty" diet. RESULTS: Prevalence of lifetime and current asthma, current rhinitis and sensitisation were higher in Thessaloniki compared to Athens. The AEI score of the entire cohort was 4.2 ± 1.2 (median 4.0) and was higher in Athens compared to Thessaloniki (4.3 ± 1.2 vs. 4.0 ± 1.2, p=0.001) and in girls than boys (4.3 ± 1.1 vs. 4.0 ± 1.2, p=0.001). AEI was inversely associated with lifetime asthma (OR: 0.87, 95%CI 0.77, 0.99) in either cities independently of other cofounders such as family history, sensitisation, exercise, house smoking, breast feeding, pet or dampness in houses. No association with other allergic disease or sensitisation was detected. CONCLUSION: Antioxidant foods seem to be a non-pharmacological, protective dietary pattern for asthma development in children irrespectively of atopy or heredity; AEI was a rough indicator and the role of antioxidants in allergic diseases is still under consideration.

Comparison in asthma and allergy prevalence in the two major cities in Greece: the ISAAC phase II survey

Background: Variability in the prevalence of allergic diseases has been detected not only between different countries, but also between cities with similar national and different socio-economic or climatic characteristics. The aim of this study was to determine the prevalence of childhood asthma and allergies and which factors are associated with them, in the two largest Greek cities, Athens and Thessaloniki. Methods: Two thousand and twenty-three Greek 9-10-year-old schoolchildren from Athens (Central Greece) and Thessaloniki (North Greece, more humid), were included in ISAAC-II study. All participants followed the ISAAC-II protocol by questionnaire, skin prick testing and flexural dermatitis examination. Results: Compared with Athens, the prevalence of current wheezing (8.4% vs. 5.7%, p=0.002), lifetime asthma (11.5% vs. 7.7%, p=0.004), atopic current asthma (3.2% vs. 1.6%, p=0.02), allergic rhinitis (8.2% vs. 5.2%, p=0.007), and hay fever (21.7% vs. 12.5%, p<0.001) were higher in Thessaloniki. The overall sensitisation rate was also higher in Thessaloniki than in Athens (25.2% vs. 16%, p<0.001) with more prevalent sensitising due to the perennial allergens (D. pteronyssinus, D. farinae, Alternaria tenuis) and cat dander. Perennial allergens sensitisation was a risk factor for current asthma in both cities. Conclusion: A higher prevalence of asthma symptoms, allergic rhinitis, and sensitisation rate was detected in Greek schoolchildren living in Thessaloniki compared to those in Athens. Allergy to mites and mould was more prevalent in Thessaloniki. The more humid weather of Thessaloniki may be implicated (AU)

Comparison in asthma and allergy prevalence in the two major cities in Greece: the ISAAC phase II survey.

BACKGROUND: Variability in the prevalence of allergic diseases has been detected not only between different countries, but also between cities with similar national and different socio-economic or climatic characteristics. The aim of this study was to determine the prevalence of childhood asthma and allergies and which factors are associated with them, in the two largest Greek cities, Athens and Thessaloniki. METHODS: Two thousand and twenty-three Greek 9-10-year-old schoolchildren from Athens (Central Greece) and Thessaloniki (North Greece, more humid), were included in ISAAC-II study. All participants followed the ISAAC-II protocol by questionnaire, skin prick testing and flexural dermatitis examination. RESULTS: Compared with Athens, the prevalence of current wheezing (8.4% vs. 5.7%, p=0.002), lifetime asthma (11.5% vs. 7.7%, p=0.004), atopic current asthma (3.2% vs. 1.6%, p=0.02), allergic rhinitis (8.2% vs. 5.2%, p=0.007), and hay fever (21.7% vs. 12.5%, p<0.001) were higher in Thessaloniki. The overall sensitisation rate was also higher in Thessaloniki than in Athens (25.2% vs. 16%, p<0.001) with more prevalent sensitising due to the perennial allergens (D. pteronyssinus, D. farinae, Alternaria tenuis) and cat dander. Perennial allergens sensitisation was a risk factor for current asthma in both cities. CONCLUSION: A higher prevalence of asthma symptoms, allergic rhinitis, and sensitisation rate was detected in Greek schoolchildren living in Thessaloniki compared to those in Athens. Allergy to mites and mould was more prevalent in Thessaloniki. The more humid weather of Thessaloniki may be implicated.

Breath markers of oxidative stress and airway inflammation in Seasonal Allergic Rhinitis.

Oxidative stress (OS) is well documented in asthma, but so far, little data has been reported in nonasthmatic patients with Seasonal Allergic Rhinitis (SAR). The aim of this study is to investigate the degree of OS and airway inflammation in patients with SAR, with and without concomitant asthma (SAR+A), using breath markers in exhaled air and in Exhaled Breath Condensate (EBC). In addition, the effects of natural allergen exposure and intranasal steroid treatment on these markers were evaluated. Exhaled NO (eNO) and CO, combined with measurements of 8-Isoprostane (Iso-8), Leukotriene B4 (LTB4) and nitrate/nitrite in EBC, were performed in 23 patients, 11 with SAR and 12 with SAR+A, and 16 healthy subjects. Iso-8 and LTB4 were significantly increased in both groups of patients (median values 43.6 pg/ ml and 138.4 pg/ml in SAR group; 38.9 pg/ml, and 164.6 pg/ml in SAR+A group respectively; p>0.05) compared to healthy subjects (18.6 pg/ml and 7.8 pg/ml; p<0.05). Nitrate/nitrite and eNO levels were elevated in both groups compared to controls, but were significantly higher in the SAR+A compared to SAR group (nitrate/nitrite 9 microM and 3.9 microM; p=0.025; and eNO 18.5 ppb and 12.5 ppb, respectively; p>0.05). Nasal steroids caused significant reduction in LTB4 and 8-isoprostane levels in both groups of patients (p<0.05), while nitrate levels and eNO concentration were little affected by nasal treatment. OS markers were decreased at normal levels out of pollen season. Natural allergen exposure induces OS and airway inflammation, as assessed by measurements of markers in EBC and exhaled air, in patients with SAR who have no clinical signs of lower airway involvement. Besides, intranasal steroid treatment may have a regulatory role in the OS.

Smoking cessation in patients with respiratory diseases: a high priority, integral component of therapy.

Smoking cessation is the one of the most important ways to improve the prognosis of patients with respiratory disease. The Task Force on guidelines for smoking cessation in patients with respiratory diseases was convened to provide evidence-based recommendations on smoking cessation interventions in respiratory patients. Based on the currently available evidence and the consensus of an expert panel, the following key recommendations were made. 1) Patients with respiratory disease have a greater and more urgent need to stop smoking than the average smoker, so respiratory physicians must take a proactive and continuing role with all smokers in motivating them to stop and in providing treatment to aid smoking cessation. 2) Smoking cessation treatment should be integrated into the management of the patient's respiratory condition. 3) Therapies should include pharmacological treatment (i.e. nicotine replacement therapy, bupropion or varenicline) combined with behavioural support. 4) Respiratory physicians should receive training to ensure that they have the knowledge, attitudes and skills necessary to deliver these interventions or to refer to an appropriate specialist. 5) Although the cost of implementing these recommendations will partly be offset by a reduction in attendance for exacerbations, etc., a budget should be established to enable implementation. Research is needed to establish optimum treatment strategies specifically for respiratory patients.

Exhaled nitric oxide in seasonal allergic rhinitis: influence of pollen season and therapy.

Exhaled nitric oxide (eNO) has been proposed as a potential indirect marker of lower airway inflammation in asthma. To investigate the existence of lower airways inflammation in allergic rhinitis eNO measurements were performed in 32 patients with symptomatic and asymptomatic seasonal allergic rhinitis early in and out of pollen seasons and in 80 healthy volunteers. To further define how exhaled NO is modified by therapy, NO levels were detected following 1-month treatment with either inhaled steroids or non-steroids therapy with nedocromil. Exhaled NO (mean +/- SE) was significantly elevated in patients with seasonal allergic rhinitis with and without symptoms (24.2 + 2.5 and 13.9 + 2.9 ppb, respectively) as compared to healthy volunteers (4.5 + 0.3 ppb) both in and out of pollen season (21.2 + 2.1 and 9.0 + 1.4 p.p.b., respectively) with a higher increase during the allergen exposure in season. Higher levels of exhaled NO were detected in patients with symptoms, either from the upper or lower airways, and with bronchial hyperreactivity. The increased exhaled NO in symptomatic patients was reduced only by inhaled steroids and not by nedocromil. These findings possibly suggest the existence of lower airway inflammation in both symptomatic and asymptomatic patients with seasonal allergic rhinitis in and out of pollen season. Thus, exhaled NO may be used as a non-invasive index for early detection of lower airway inflammation and for monitoring the optional treatment in patients with seasonal allergic rhinitis.

Influence of atopy on exhaled nitric oxide in patients with stable asthma and rhinitis.

The level of exhaled NO is increased in patients with allergic asthma and seasonal rhinitis. The aim of this study was to investigate the significance of atopy on NO production in the lower airways. Measurements of exhaled NO were performed in 131 stable asthmatic patients with chronic mild asthma (95 atopics and 36 nonatopics), 72 patients with perennial rhinitis (57 atopics and 15 nonatopics) and 100 healthy controls (20 atopics and 80 non-atopics). Patients with either asthma or rhinitis had higher exhaled NO values (13.3+/-1.2 parts per billion (ppb) and 11.7+/-1.1 ppb) than control subjects (4.8+/-0.3 ppb, p<0.01). Exhaled NO levels were significantly higher in atopic asthmatics (19+/-3.6 ppb) compared with nonatopic patients (5.6+/-0.8 ppb, p<0.001). Similar findings were observed in patients with rhinitis (13.3+/-1.3 ppb in atopics and 5.8+/-1.2 ppb in nonatopics, p<0.001). No difference was found in NO levels between atopic and nonatopic control subjects (4.8+/-0.8 ppb, and 4.5+/-0.3 ppb). In summary, this study has shown that increased exhaled NO levels are detected only in atopic patients with asthma and/or rhinitis and not in nonatopic patients. These findings may suggest that it is rather the allergic nature of airways inflammation, which is mainly responsible for the higher NO production in the lower airways.

The long-acting beta2-agonist salmeterol xinafoate: effects on airway inflammation in asthma.

Salmeterol xinafoate is an inhaled long-acting beta2-adrenoceptor agonist recently introduced for the treatment of asthma. Both in vitro and animal studies suggest that it may have anti-inflammatory activities of benefit in this disease. To assess this directly, the effects of 6 weeks' treatment with salmeterol on indices of clinical activity, airway dysfunction and inflammation in subjects with stable atopic asthma were investigated. In a double blind study, asthmatic patients were randomized to 6 weeks' treatment with either salmeterol 50 microg twice daily (n=14) or placebo (n=12). They underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy immediately before starting treatment and again after 6 weeks. Treatment with salmeterol improved clinical indices of asthma activity, but there were no changes in BAL differential cell counts or mediator levels, and no change in T-cell numbers or activation status. In the biopsy specimens there were no changes in numbers of inflammatory cells, sub-basement membrane collagen deposition or mast cell degranulation. Regular treatment with salmeterol improves clinical indices of asthma but has no effect on the underlying inflammatory process. These findings strengthen guideline recommendations that long-acting beta2-agonists should not be prescribed as sole antiasthma medication.

Endobronchial allergen challenge.

LEAC offers a very practical means of studying the pathophysiology of asthma. Despite the local nature of the challenge, LEAC often has a significant effect on FEV1 and may cause short-term destabilization of asthma. In common with other bronchoscopic methods used to study human asthma, samples obtained by LEAC show a considerable degree of variability and it is therefore necessary to use groups of 12-15 subjects to minimize the risk of Type II statistical errors. Comparisons between different studies of allergen exposure are made difficult by a variety of technical considerations. Chief among these are subject selection, the technique used for allergen exposure, the timing of sampling, and the analysis techniques. Dose-response studies in nonasthmatic allergic subjects indicate that the degree of BAL eosinophilia is related to the dose of antigen [17] but there is as yet no agreement on how LEAC might be standardized. Notwithstanding these reservations, local endobronchial allergen challenge has already yielded valuable information on the pathophysiology of asthma and will remain a useful complement to other investigational techniques in the future exploration of this disease.

Chronic respiratory symptoms, skin test results, and lung function as predictors of peak flow variability.

We examined how chronic respiratory symptoms, reported in a questionnaire, and results of skin prick tests and spirometry predicted variability in peak expiratory flow (PEF) among 6-12-yr-old children (n = 1,854). After characterization with skin tests and spirometry, children were followed for 2-3 mo during the winter of 1993-1994. Peak expiratory flow was measured daily in the morning and evenings. Children with asthmatic symptoms (wheeze and/or attacks of shortness of breath with wheeze in the past 12 mo and/or ever doctor diagnosed asthma) had a greater variation in PEF than children with dry nocturnal cough as their only chronic respiratory symptom. Similarly, doctor-diagnosed asthma was associated with a greater variation in PEF, also among children with asthmatic symptoms. Peak flow variability increased with an increasing number of symptoms reported in the questionnaire. Atopy, positive skin test reactions to house dust mite and cat and lowered level (as % of predicted) in FEV1 and in MMEF were also associated with an increased variation in PEF. All the differences were observed in both diurnal and day-to-day variation in PEF. In conclusion, chronic respiratory symptoms reported in a questionnaire, spirometric lung function and skin prick test results among asthmatic children predicted variation in PEF measured during a 2-3 mo follow-up. The difference in morning PEF coefficient of variation (CV) between children with asthmatic symptoms and children with cough only was somewhat bigger in girls than in boys. The effect of atopy on morning PEF CV was somewhat bigger in young than in older children.

The effect of treatment with oral corticosteroids on asthma symptoms and airway inflammation.

To improve understanding of the mechanisms of action of oral corticosteroids in asthma, we have conducted a double-blind, placebo-controlled study with prednisolone (20 mg for 2 wk followed by 10 mg for 4 wk) or placebo in 14 and 13 atopic corticosteroid-naive asthmatic subjects, respectively. Before and after treatment subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy. Treatment with prednisolone, but not placebo, significantly reduced asthma symptoms (from mean +/- SEM total weekly score of 34 +/- 6.2 to 15.7 +/- 3.2, p = 0.02) and albuterol usage (from mean +/- SEM number of puffs/wk of 29.7 +/- 6.2 to 18.2 +/- 3.7, p = 0.01) and significantly increased FEV1 (from 89.8 +/- 4.4% to 99.3 +/- 4.1% of predicted, p = 0.03). There were no significant changes in inflammatory or epithelial cell counts, levels of T-cell activation or albumin concentration in BAL. However, immunohistochemistry of bronchial biopsies showed that in the submucosa prednisolone significantly decreased numbers of mast cells by 62% (from median 45 to 17/mm2, p = 0.01), eosinophils by 81% (from median 30.1 to 5.7/mm2, p = 0.004), and CD4+ T-cells by 68% (from median 64.6 to 18.5/mm2, p = 0.02). In the epithelium only the reduction in the numbers of eosinophils was significant (from median 1.1 to 0/mm of epithelium, p = 0.02). There were no significant changes in any cell counts in the subjects receiving placebo, and comparison of the changes between the treatment groups identified a significant prednisolone-related reduction in submucosal eosinophil and mast cell counts (p = 0.003 and 0.03, respectively). The temporal association between the clinical and physiologic improvement, and the correlation between the magnitude of change in CD4+ T-cell counts in the submucosa and increase in PC20 methacholine (rs = 0.60, p = 0.049) suggests that the reduction in airways inflammatory cell numbers underlies the clinical efficacy of oral corticosteroids.

Effect of natural allergen exposure during the grass pollen season on airways inflammatory cells and asthma symptoms.

BACKGROUND: Bronchial challenge with allergen causes a specific form of airways inflammation consisting of an influx of neutrophils, eosinophils, and T cells. Because the relevance of the challenge model to clinical asthma is uncertain, the cellular changes that occur in the lungs of asthmatic subjects during natural seasonal allergen exposure were investigated. METHODS: Seventeen grass pollen sensitive asthmatic subjects with previously reported seasonal exacerbations of asthma kept records of symptoms and underwent fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial biopsy before and during the peak of the grass pollen season. The BAL cells were analysed for differential cell counts and by flow cytometry for T cell subsets and surface activation markers. The biopsy samples were processed into glycol methacrylate resin and immunohistochemical analysis was performed for mast cells, activated eosinophils, T cells and interleukin 4 (IL-4), a cytokine with a pivotal role in allergen-induced inflammation. RESULTS: In the pollen season there was an increase in T lymphocyte activation in the BAL fluid as identified by increased expression of interleukin 2 receptor (IL-2R). In the submucosa these changes were paralleled by an increase in CD4+ T cells. By contrast, the numbers of metachromatic cells in BAL fluid staining with toluidine blue were reduced, possibly because of degranulation following allergen stimulation. In keeping with mast cell activation, the number of mucosal mast cells staining for secreted IL-4 increased during the season. In comparison with the period shortly before the onset of the season, all but two subjects experienced an asthma exacerbation which followed the rise in pollen counts but, compared with the period preceding the first bronchoscopic examination, asthma symptoms were not increased during the pollen season. CONCLUSIONS: The data suggest that natural allergen exposure, leading to a clinical exacerbation of asthma, may induce an inflammatory response involving T cells, mast cells and eosinophils. The relationship between allergen exposure, cellular infiltration and activation, and clinical symptoms appears to be complex, with factors other than allergen also contributing to asthmatic activity.

Safety aspects of local endobronchial allergen challenge in asthmatic patients.

Local endobronchial allergen challenge is being increasingly used to investigate the role of allergic inflammation in asthma. However, little information is available about the safety of this procedure and the changes induced in airway physiology. BAL and biopsy were performed at 10 min and at 4 to 6 h, or 24 h after segmental allergen challenge in 49 patients with atopic asthma. Two hours after challenge, FEV1 was reduced from 97.6 +/- 13.9 (mean +/- SD) to 83.4 +/- 21.7% predicted. FEV1 remained reduced at 4 to 6 h (87.7 +/- 20.4%), but it had nearly returned to baseline by 24 h (93.2 +/- 14.0%). When endobronchial challenge was combined with BAL and biopsy, the initial fall in FEV1 was slightly greater (from 101.8 +/- 14.2 to 78.5 +/- 13.6%). Bronchial responsiveness to methacholine was measured in 10 subjects, and it showed a twofold increase 24 h after local challenge and lavage. Significant changes in FEV1 and methacholine PC20 were still detectable 72 h after challenge. Widespread wheezing occurred in 29% of the subjects, but none of the them had to be admitted to hospital. We conclude that local endobronchial allergen challenge, although producing measurable changes in airway physiology, is in general well tolerated and is an acceptable method to investigate airway pathophysiologic processes in patients with mild to moderate asthma.

Inflammatory and T-cell profile of asthmatic airways 6 hours after local allergen provocation.

T cells in the airways are considered to play a key role in orchestrating the inflammatory response of asthma through the elaboration of specific cytokines. Using flow cytometry we have investigated the T-cell response of sensitized asthmatic airways 6 h after local allergen provocation. Twelve subjects with atopic asthma underwent bronchoalveolar lavage (BAL) before and 6 h after local instillation of allergen into the right middle lobe (RML) and saline into the right upper lobe (RUL). Allergen challenge produced a significant 26% fall in FEV1, an increase in eosinophils in BAL at 6 h, and at 24 h an increase in methacholine responsiveness compatible with late-phase airway inflammation. When compared with saline challenge, allergen produced an overall decrease in the number of BAL lymphocytes from 21.3 +/- 2.8% to 16.0 +/- 3.08% of total cells but no change in the proportion of CD4+, CD8+, CD25+, or HLA-DR+ cells. Allergen provocation reduced the proportion of T cells expressing the beta 2 integrin lymphocyte functional antigen-1 (LFA-1) from 72.5 +/- 30 to 43.9 +/- 9.1 mean fluorescent units (p < 0.01) and a similar trend in intercellular adhesion molecule-1 (ICAM-1) (p = 0.08). These results indicate that late-phase inflammatory events 6 h after local allergen provocation involve the selective retention of airway T cells expressing specific cell adhesion molecules.

Bronchial biopsy evidence for leukocyte infiltration and upregulation of leukocyte-endothelial cell adhesion molecules 6 hours after local allergen challenge of sensitized asthmatic airways.

We have examined the mucosal changes occurring in bronchial biopsies from six atopic asthmatics 5-6 h after local endobronchial allergen challenge and compared them with biopsies from saline-challenged segments from the same subjects at the same time point. All the subjects developed localized bronchoconstriction in the allergen-challenged segment and had a decrease in forced expiratory volume in 1 s (FEV1) (P < 0.01) and a decrease in their methacholine provocative concentration of agonist required to reduce FEV1 from baseline by 20% (P < 0.05) 24 h postchallenge. At 6 h we observed an increase in neutrophils (P = 0.03), eosinophils (P = 0.025), mast cells (P = 0.03), and CD3+ lymphocytes (P = 0.025), but not in CD4+ or CD8+ lymphocyte counts. We also detected an increase in endothelial intercellular adhesion molecule type 1 (P < 0.05) and E-selectin (P < 0.005), but not vascular cell adhesion molecule type 1 expression with a correlative increase in submucosal and epithelial LFA+ leucocytes (P < 0.01). Thus, in sensitized asthmatics, local endobronchial allergen instillation leads to an increased inflammatory cell infiltrate of the airway mucosa that involves upregulation of specific adhesion molecules expressed on the microvasculature.

Intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects.

Bronchial lavage and biopsy studies suggest the involvement of eosinophils and T-lymphocytes in allergic inflammation in asthma. There is evidence suggesting that the expression of adhesion molecules on endothelial cells and of their receptors on leucocytes is involved in this process. To investigate these mechanisms we have obtained bronchial mucosal biopsies from 10 normal subjects and from 10 symptomatic atopic asthmatics. Six of the asthmatics were re-biopsied after 6 weeks of inhaled beclomethasone dipropionate (BDP) during which time their clinical response was monitored. Frozen sections were stained by the immunoperoxidase method using monoclonal antibody (MoAb) 6.5B5 to identify expression of intercellular adhesion molecule (ICAM-1) and MoAb 1.2B6 for endothelial leucocyte adhesion molecule (ELAM-1). Araldite-embedded sections were also stained for eosinophils using MoAb EG2 to identify eosinophilic cationic protein (ECP). A significant mucosal eosinophilia was apparent in the asthmatic but not in the normal biopsies. Immunostaining for ICAM-1 was observed in both the epithelium and endothelium and ELAM-1 in endothelium, with no significant differences being apparent between the asthmatic and normal subjects. Topical BDP markedly reduced the mucosal eosinophilia without affecting the expression of either adhesion molecule. Using this method, we conclude that there is basal expression of ICAM-1 and ELAM-1 in normal human bronchial mucosa, which is not significantly different from that in asthmatics, and that it is insensitive to suppression with corticosteroids at an inhaled dose that causes clinical improvement.

Early changes in T lymphocytes recovered by bronchoalveolar lavage after local allergen challenge of asthmatic airways.

To assess the role of T lymphocytes in the initiation of the allergic asthmatic response we have investigated T-cells subsets and their activation markers in bronchoalveolar lavage (BAL) fluid recovered 10 min after local challenge of the bronchial mucosa with allergen or saline. Endobronchial challenge was performed in 13 mildly atopic asthmatic patients (FEV1% predicted range, 78.2 to 116.5) and 10 normal volunteers. In all of the asthmatics but in none of the normal subjects allergen but not saline exposure resulted in visible bronchoconstriction. Analysis of BAL by flow cytometry showed no differences in the overall number of T cells (CD3+) and their CD4+ and CD8+ subsets per milliliter of BAL between the groups of normal subjects and asthmatics. However, within 10 min of allergen challenge, in the asthmatics but not in the normal subjects, there occurred a significant loss of CD3+ cells (p less than 0.01) comprising mostly CD4+ (p less than 0.05) but also CD8+ cells, with a consequent decrease in the CD4:CD8 ratio. At this early time point no differences in the extent of expression of the T-cell activation markers, IL-2 receptor, and HLA-DR were found. These results provide evidence to support a role of T lymphocytes early in the allergen-induced inflammatory response in asthma.