Allergen-induced in vitro expression of IL-18, SLAM and GATA-3 mRNA in PBMC during sublingual immunotherapy.

BACKGROUND: Signalling lymphocytic activation molecule (SLAM) and interleukin (IL)-18 induce interferon (IFN)-gamma production from Th1 cells. The allergen-induced SLAM and IL-18 mRNA expressions are increased during subcutaneous immunotherapy (SCIT), but nothing is known about their role during sublingual immunotherapy (SLIT). Transcription factor GATA-3 is associated with Th2 cells but its role in SCIT and SLIT is yet unexplored. This study was undertaken to analyse the allergen induced in vitro mRNA expression of IL-18, SLAM and GATA-3 in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis (AR) during SLIT. METHODS: Ten patients with AR undergoing pollen SLIT with a weekly dose of 200,000 SQ-U, 10 with 24,000 SQ-U of mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa and 10 with placebo were included. Peripheral blood mononuclear cell were stimulated with birch extract prior to, after 1 and 2 years of the treatment. The mRNA expression was assessed using kinetic real-time RT-PCR (TaqMan); Applied Biosystems, Foster City, CA, USA). RESULTS: The expression of IL-18 mRNA was increased in the high-dose group in comparison to the placebo group after 1 year of therapy (P = 0.028) and had an inverse correlation with the late phase skin reaction after the second study year (r = -0.41, P = 0.041). SLAM mRNA expression increased in the high-dose group from baseline to 1 year (P = 0.028) and correlated with IL-10 (r = 0.96, P < 0.0001) and transforming growth factor-beta (r = 0.80, P = 0.0037) mRNA expression. No significant changes were seen in GATA-3 mRNA expression. CONCLUSIONS: During SLIT, IL-18 and SLAM are upregulated, suggesting that the Th2 type inflammatory response is downregulated during SLIT by increased Th1 type response.

The protective effect of rural living against atopy in Mongolia.

BACKGROUND: Farm environment in childhood protects against atopy. We investigated in a population-based study in Mongolia the effects of rural living and migration from rural to urban areas on the risk of atopy. METHODS: The screening study data of 9453 subjects, aged 10-60 years, were used for taking the sample for the clinical study in which 869 subjects were examined. Asthma, allergic rhinoconjunctivitis and sensitization were clinically defined and their risk factors analysed by logistic regression. RESULTS: The risks of allergic rhinoconjunctivitis [adjusted odds ratio (OR) 0.43, 95% confidence interval (CI) 0.19-0.98] and allergic sensitization (OR 0.26, 95% CI 0.13-0.55) were the lowest in subjects living in a village from birth and intermediate in subjects who had relocated from a village to a town (OR for rhinoconjunctivitis 0.68, 95% CI 0.36-1.27, OR for sensitization 0.62, 95% CI 0.35-1.12) compared with subjects living in a town from birth. Simultaneous exposure to herd animals and dung heating decreased the risk of atopy. Keeping animals was a risk-factor for asthma only in Ulaanbaatar city. CONCLUSIONS: Continuing farm exposure after childhood may be important in reducing the risk of atopy.

Prevalence of asthma, allergic rhinoconjunctivitis and allergic sensitization in Mongolia.

BACKGROUND: Studies in countries, such as Mongolia, which are in transition from farming to industrial society permit evaluation of the impact of environmental change on atopic diseases. METHODS: In the screening study, questionnaire data were obtained from 9453 subjects aged 10-60 years. In the clinical study, a subsample of 869 subjects (participation rate 50.0%) was examined. A questionnaire-based interview, clinical examination, skin prick tests, spirometry and bronchodilation test or methacholine challenge test were used to define the clinical diagnoses. The prevalences of atopic diseases were evaluated at the population level using two-phase data and sampling weights. RESULTS: The prevalences of asthma, allergic rhinoconjunctivitis and allergic sensitization with 95% confidence intervals were 1.1% (0.3-2.0%), 9.3% (4.0-14.6%) and 13.6% (7.4-19.9%) in Mongolian villages, 2.4% (1.4-3.5%), 12.9% (8.2-17.7%) and 25.3% (17.1-33.6%) in rural towns and 2.1% (1.3-3.0%), 18.4% (13.3-23.4%) and 31.0% (24.5-37.5%) in Ulaanbaatar city, respectively. The prevalence of allergic rhinoconjunctivitis (P = 0.02) and allergic sensitization (P = 0.003) increased significantly with increasing urbanization. CONCLUSIONS: The prevalences of atopic diseases were low in rural Mongolia and increased with increasing urbanization suggesting that rural living environment protects against atopy.

Immediate hypersensitivity to Malassezia furfur and Candida albicans mannans in vivo and in vitro.

BACKGROUND: Elevated and correlative Malassezia furfur (M. furfur) and Candida albicans (C. albicans) mannan-specific IgE have been demonstrated in atopic eczema dermatitis syndrome (AEDS) of the head, neck and shoulder (HNS) region of the skin. The significance of these antibodies in vivo has not been demonstrated. METHODS: Sixty-five AEDS patients with HNS distribution were included. Serum total IgE (S-IgE) and yeast antigen-specific (Cetavlon-purified mannan and whole extract antigens of M. furfur and C. albicans) IgE were measured and skin prick tests (SPT) were performed with the yeast antigens. RESULTS: Mannan-specific IgE and SPT were positive in 51 and 48% of patients with M. furfur and in 42 and 22% with C. albicans, respectively. Whole extract-specific IgE and SPT were positive in 85 and 95% of patients with M. furfur and in 91 and 57% with C. albicans, respectively. The highest correlation between specific IgE and SPT was seen with M. furfur mannan (r = 0.60; P < 0.0001). Both M. furfur mannan-specific IgE (r = 0.76; P < 0.0001) and SPT (r = 0.44; P = 0.0005) correlated with S-IgE. CONCLUSIONS: Mannan-induced immediate hypersensitivity in vivo was demonstrated in SPT. The significant correlation between M. furfur mannan-specific IgE and SPT suggests that mannan is an important allergen in yeast hypersensitive AEDS in vivo.

Increased expression of allergen-induced in vitro interleukin-10 and interleukin-18 mRNA in peripheral blood mononuclear cells of allergic rhinitis patients after specific immunotherapy.

BACKGROUND: During specific pollen immunotherapy (SIT) there is a local mucosal shift from Th2- to Th1- type cytokine predominance, with IL-12 having a major role in this shift. IL-10-induced tolerance is supposed to be a key phenomenon in venom immunotherapy (VIT). However, the role of Th1-promoting cytokines, on the one hand, and the role of regulatory cytokines, on the other hand, have not been studied in parallel during SIT. OBJECTIVE: This study was undertaken to analyse the allergen-induced in vitro mRNA expression of Th1-type effector cytokine IL-18 and regulatory cytokines IL-10 and TGF-beta during SIT in peripheral blood mononuclear cells (PBMC) of allergic rhinitis (AR) patients. METHODS: Thirty patients with AR undergoing pollen SIT and 10 patients with AR who were not treated with SIT were included in the study. The symptoms and medications were registered post-seasonally before the beginning of SIT and after 1 year of therapy. PBMC samples were collected and stimulated with pollen allergen extract prior to the treatment, at the maintenance phase in 12 patients and after 1 year of the treatment. The cytokine mRNA expression was assessed using kinetic real-time RT-PCR (TaqMan). RESULTS: There was a clear increase in the treated AR patients, in comparison with untreated AR patients, in the expression of both IL-10 (mean change from baseline (SEM): 3.1 (0.8) vs. -0.3 (0.3), P<0.002, Mann-Whitney U-test) and IL-18 (2.7 (0.9) vs. -0.2 (0.6), P<0.03) mRNA after 1 year. The clearest increase in IL-10 mRNA expression was seen in patients who did not benefit at all (6.0 (2.3), P<0.001 vs. untreated) and the least increase in patients that had the greatest reduction of symptoms (0.8 (0.6), n.s. vs. untreated) at 1 year. The clearest increase in IL-18 mRNA expression was seen in patients with moderate outcome (3.4 (1.6), P<0.04 vs. untreated). In intermediate samples, taken when the maintenance dose was reached, the peak expression of allergen-induced IL-10 mRNA was associated with the most favourable outcome of SIT (P=0.01, Fisher exact test). A similar trend was seen in IL-18 mRNA expression. CONCLUSIONS: The results suggest that an early and transient increase in allergen-specific IL-10 and IL-18 mRNA expression in PBMC is essential for the therapeutic outcome after 1 year of SIT.

Food hypersensitivity among Finnish university students: association with atopic diseases.

BACKGROUND: Food hypersensitivity (FH) is commonly suspected, especially among adults with atopic diseases. Symptoms of FH vary from oral allergy syndrome (OAS) to gastrointestinal, respiratory and systemic reactions. More data are needed regarding patient groups at risk for FH, and symptoms and foods responsible for the reactions. METHODS: FH was studied in 286 Finnish university students. Four study groups were selected: subjects (i) with current atopic dermatitis (AD) with or without allergic rhinoconjunctivits (ARC) or asthma (n = 41); (ii) with past AD with or without ARC or asthma (n = 89); (iii) with ARC or asthma (n = 69); (iv) without clinically confirmed atopic disease (n = 87). A thorough clinical examination was performed with a questionnaire specifying adverse events to foods. In addition, IgE specific to five foods, and skin prick tests to four foods were determined. RESULTS: FH was reported by 172 subjects (60.1%), more often by females (66.3%) than by males (47.9%) (P = 0.003). FH was most frequent among subjects with AD, among those with current AD in 73.2%, with past AD in 66.3%, and with ARC or asthma in 63.8%; 44.8% of subjects without any atopic disease reported FH. Kiwi fruit caused symptoms most frequently (38.4%), followed by milk (32.6%), apple (29.1%), tomato (27.9%), citrus fruits (25.0%), tree nuts (23.3%), and peanut (17.4%). A total of 720 separate symptoms to 25 food items were reported. OAS was most common (51.2%), followed by gastrointestinal symptoms (23.5%), worsening of AD (11.4%), urticaria (4.2%), rhinitis or conjunctivitis (5.7%) and asthma (4.0%). Severe reactions occurred in 3.5% (25/720). Negative IgE and skin prick test to foods predicted well negative history, but the value of positive test results was limited. CONCLUSIONS: FH was reported most often by students with current AD and multiple atopic diseases. Severe reactions occurred especially in patients with ARC and asthma. After excluding lactose intolerance, milk hypersensitivity was frequently reported.

In vitro kinetics of allergen- and microbe-induced IL-4 and IFN-gamma mRNA expression in PBMC of pollen-allergic patients.

BACKGROUND: According to a hypothesis allergens induce Th2 responses in allergic patients, and microbes induce Th1 responses. We studied the kinetics of in vitro allergen-, tuberculin (PPD)- and tetanus toxin (TT)-induced IFN-gamma and IL-4 mRNA expression in peripheral blood mononuclear cell (PBMC) cultures of pollen-allergic patients and healthy controls. METHODS: PBMC of 10 birch or timothy pollen-allergic patients and of 13 healthy controls were stimulated in vitro with allergen (birch or timothy), PPD or TT. Pellets and supernatants were collected at 24, 48, 72 and 96 h after stimulation. IFN-gamma and IL-4 production was measured by enzyme linked immunosorbent assay and mRNA expression using RT-PCR and time-resolved fluorometry. RESULTS: Allergen induced IFN-gamma production and mRNA expression in PBMC more in allergic patients than in healthy controls. Also allergen induced IL-4 mRNA expression more in allergic patients than in healthy controls. PPD induced IFN-gamma mRNA expression both in allergic patients and healthy controls, whereas IFN-gamma production was induced only in healthy controls and IL-4 was not induced at all. TT induced IFN-gamma mRNA expression in both groups, IFN-gamma production in allergic patients, and IL-4 mRNA expression in both allergic patients and healthy controls. CONCLUSIONS: In vitro stimulation with allergen induced both IFN-gamma and IL-4 mRNA expression of PBMC in allergic patients. These observations challenge the clearcut division of microbe-specific Th1 and allergen-specific Th2 responses in peripheral blood.

Childhood farm environment and asthma and sensitization in young adulthood.

BACKGROUND: Farm environment in childhood may protect against sensitization, allergic rhinitis, and asthma. METHODS: Subjects were obtained from 10 667 Finnish first-year university students who responded to a questionnaire survey on IgE-mediated diseases. Two random samples were selected from 1631 respondents in Turku: subjects with asthma or wheezing, and subjects without asthmatic symptoms. A total of 296 subjects (72%) participated. Skin prick tests (SPT), measurements of IgE-antibodies, methacholine challenge, and bronchodilation tests were performed. Weighted occurrence of current asthma and sensitization among students from "childhood farm" and "childhood nonfarm" environments were analyzed. RESULTS: Current asthma was found in 3.1% of subjects with childhood farm environment, and in 12.4% with nonfarm environment (odds ratio (OR) 0.22; 95% confidence interval (CI) 0.07-0.70). There were fewer positive SPT to birch (8.3 vs. 24.2%, OR 0.28, 95% CI 0.07-1.15) and timothy pollen (12.6 vs. 30.3%, OR 0.33, 95% CI 0.09-1.20) among subjects with childhood farm environment, but more sensitization to house-dust mite (22.0 vs. 4.9%, OR 5.43, 95% CI 1.60-18.46). Sensitization to cat (RAST class >/= 3) was less common in subjects with farm compared to nonfarm environments in childhood (1.5 vs. 13.1%; OR 0.10, 95% CI 0.02-0.47). CONCLUSIONS: Farm environment in childhood protects against adult asthma and sensitization-especially to cat-the most important asthma related allergen. In contrast, sensitization to house-dust mite was more common in farming subjects.

Stressful life events promote the manifestation of asthma and atopic diseases.

BACKGROUND: Psychosocial stress is known to aggravate asthma. Less is known about the impact of stressful life events on the expression of asthma and atopic disorders. OBJECTIVE: To determine whether the onset of asthma, allergic rhinitis or conjunctivitis, and atopic dermatitis, are associated with stressful life events. METHODS: A postal survey on risk factors for asthma and atopic diseases was carried out among 10 667 Finnish first-year university students aged 18-25 years. Stressful life events, (i) severe disease or death of a family member, and (ii) parental or personal conflicts, were retrospectively recorded during the preceding year, 1-5 years, 6-10 years, and more than 10 years prior to the survey response. In a case-control setting, conditional multiple logistic regression analysis was used to assess the temporal association between major stressful life events occurring during a period either preceding, concomitant or subsequent with subject's diagnoses. RESULTS: Concomitant parental and personal conflicts increased the risk of asthma (OR 1.72, 95% CI 1.10-2.69) when adjusted by parental asthma, education and passive smoking at early age. Concomitant severe disease or death of mother, father or spouse (OR 1.52, 95% CI 1.09-2.16) and precedent parental and personal conflicts (OR 1.75, 95% CI 1.15-2.77) increased the risk of manifestation of allergic rhinoconjunctivitis when adjusted for parental atopic disease, education and passive smoking. Subjects' asthma and atopic dermatitis, but not allergic rhinoconjunctivitis, were related to excess of subsequent stressful life events. CONCLUSION: An association between stressful life events and subjects' asthma, allergic rhinoconjunctivitis and atopic dermatitis is suggested.

Wood stove heating, asthma and allergies.

In two German studies household wood or coal stove use was negatively associated with atopic sensitization and allergic rhinitis in childhood. Wood stove heating is strongly related to 'traditional lifestyle and therefore subjected to confounding factors possibly yet not known. The study was conducted to study these factors and the independent impact of early exposure to wood stove heating on subsequent asthma and atopic disease. In a questionnaire survey among 10667 Finnish university students aged 18-25 years, we investigated the association between wood stove heating at age 0-6 years and asthma and allergies up to young adulthood. Adjustment was made for factors related to the heating system and atopic disorders by using multivariate regression. Unadjusted lifetime prevalence rates for physician-diagnosed asthma, allergic rhinoconjunctivitis, atopic dermatitis and self-reported wheezing were lower among subjects with wood stove heating compared to other heating systems. There was a significant negative association between childhood wood stove heating and allergic rhinitis or conjunctivitis in the univariate model (OR 0.61, 95% CI 0.61-0.91), but not for the other diseases. The significant association disappeared in the multivariate analysis after adjusting for various family indoor and outdoor (adjusted OR 0.96, 95% CI 0.77-1.20) factors. The association between wood stove heating and allergic rhinoconjunctivitis was mainly confounded by childhood residential environment, especially the farm environment. Farm environment was found to be the main confounding factor related to association between wood stove heating and asthma, and atopic diseases.

Asthma and gastro-oesophageal reflux: can the response to anti-reflux therapy be predicted?

The aim of the study was to investigate which features predict favourable response to omeprazole therapy in asthmatics with gastro-oesophageal reflux (GER). The study population consisted of 52 outpatient asthmatics with GER who had completed an intervention where they were randomized to receive omeprazole 40 mg once a day or placebo for 8 weeks. After a 2-week washout period the patients were crossed over. Asthma symptoms were found to be relieved > or = 20% in 18 (35%) patients who were thus regarded as responders. A logistic regression analysis was performed in order to identify which features separate the responders from the non-responders. More responders were found among the patients whose body mass index (BMI) was higher (P = 0.02) or whose distal esophageal reflux was more severe [total time (%) pH < 4 (P = 0.01) or time (%) pH < 4 in upright position (P = 0.04)]. Adding other predictors to the total time (%) pH < 4, which was the most significant predictor for response in multi-variate analysis, did not further increase the prediction for favourable outcome. It is concluded that severe distal oesophageal reflux and obesity predict amelioration in asthma symptoms after 8-week omeprazole treatment in asthmatics with GER. Adding more than one predictor does not seem to further increase prediction for favourable asthma response.

Validation of a new questionnaire on asthma, allergic rhinitis, and conjunctivitis in young adults.

BACKGROUND: Epidemiologic data on asthma and allergies among adults are mainly based on questionnaires: this study validates the questions on asthma, allergic rhinitis, and conjunctivitis of a new Finnish questionnaire. METHODS: To validate questions used in a country-wide study among university students aged 18-25 years, we examined 150 subjects who had ever reported asthma or wheezing, and 140 without asthma symptoms. Questions were validated in relation to current diseases including 1) symptoms detected during the preceding year at the physician's interview 2) objective measurements, such as methacholine challenge, skin prick tests, and specific IgE. Data were adjusted for original proportions of "asthmatics" and"nonasthmatics" in the questionnaire study. RESULTS: Questions on "reported asthma" and "doctor-diagnosed asthma" had good positive predictive value (PPV) and specificity in diagnosing current asthma. The question on "attacks of shortness of breath with wheezing", and especially the question on "cough with wheezing" were most sensitive. Questions on "allergic nasal symptoms" and "allergic eye symptoms" that were "related to pollen or animals" were sensitive, but a further question on doctor's diagnosis yielded higher specificity and PPV. CONCLUSION: Diagnosis-based questions were found suitable for risk-factor studies, because of their good specificity and PPV, and symptom-based questions for screening, because they were highest in sensitivity.

Home dampness, current allergic diseases, and respiratory infections among young adults.

BACKGROUND: The relation between home dampness and respiratory symptoms among adults is well confirmed, but data on specific allergic diseases and respiratory infections is more limited. Individual factors that may enhance susceptibility to the effects of home dampness are mainly unknown. METHODS: The association between home dampness and current physician diagnosed asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, common colds, and bacterial respiratory infections was studied in a questionnaire survey of 10 667 Finnish first year university students aged 18-25 years. The dampness categories analysed were visible mould and visible mould or damp stains or water damage during the last year. In multivariate analyses adjustment was made for parental education, active and passive smoking, type and place of residence, pets, and wall to wall carpets. The interaction effect of atopic heredity and dampness was investigated. RESULTS: Visible mould or damp stains or water damage was reported by 15.0% of the respondents. In multivariate models there was a positive association between home dampness and current asthma, allergic rhinitis, and atopic dermatitis, as well as common colds > or =4 times per year and other respiratory infections, but not between home dampness and allergic conjunctivitis. The strongest association was found between exposure to visible mould and asthma (OR 2.21, 95% CI 1.48 to 3.28) and common colds (OR 1.49, 95% CI 1.18 to 1.87). The risk of current asthma in damp homes was highest among subjects with atopic heredity. CONCLUSIONS: The risk of current asthma, allergic rhinitis, and atopic dermatitis was higher in damp homes. Of the respiratory infections, the risk of common colds was most clearly increased.

Pulmonary imaging and function in the common cold.

The common cold is generally considered to be an upper respiratory tract infection. We studied the lower respiratory tract in 76 otherwise healthy young adults with the common cold. Viral infection was diagnosed in 56 (74%) of the 76 subjects. Rhinovirus was detected in 42 (55%) subjects. Chest radiography (CR) and high-resolution computerized tomography (HRCT) were carried out in 40 subjects on day 7, and pulmonary function testing with bronchodilator challenge was carried out in 36 patients on days 7 and 21 of the study. Clinical examinations were carried out on days 1, 7 and 21. The subjects recorded their symptoms on a diary card for 20 d. The mean duration of cough was 8.4 (SD 6.5) d and that of sputum production 5.9 (SD 6.4) d. No abnormal findings were detected in the lungs on auscultation. CR and HRCT showed no pulmonary changes associated with the common cold. No clinically remarkable increases were seen in peak expiratory flow, forced expiration volume in 1 s or forced vital capacity after bronchodilator challenge on either days 7 or 21. All patients made a clinical recovery without antimicrobial therapy within 21 d. We conclude that the common cold in young otherwise healthy adults is an upper respiratory tract infection and that clinically important abnormalities in the lower respiratory tract are rare.

Prevalence of nickel allergy among Finnish university students in 1995.

Nickel allergy was studied in a sample of 1st-year university students starting their studies in 1995. A total of 296 subjects (72%) of 413 invited participated in the clinical examination, and 284, 96 male and 188 female, were patch tested (69%). A history of nickel sensitization was enquired for. Prick tests and serum specific IgE levels were determined. Occurrence of atopic dermatitis, hand eczema, and current exposure to metals were recorded. Nickel allergy was encountered in 39% of all female students, in 42% of females with pierced skin, and in 14% of females without pierced skin. The corresponding figures for males were 3%, 7% and 3%. In the multiple regression analysis, the risk factors for nickel allergy were female sex (OR 8.1, p<0.01), current metal exposure at examination (OR 4.1, p<0.01) and skin piercing (OR 3.6, p<0.05). Positive prick tests or elevated IgE levels to common allergens were not significantly associated with nickel allergy. In female students, the prevalence of nickel allergy has increased from 13% in 1986 to 39%. The prevalence among males has remained low at 3%. The results indicate that, in addition to skin piercing, current metal contacts are important risk factors for nickel allergy. This finding gives support to the EU Nickel Directive.

Pityrosporum and Candida specific and non-specific humoral, cellular and cytokine responses in atopic dermatitis patients.

BACKGROUND: Recent cytokine (RT-PCR, ELISA) analyses of inflammation in atopic dermatitis (AD) have suggested a role for IL-4, IL-5 and IFNgamma. Pityrosporum ovale and Candida albicans are important allergens in some patients with AD of the seborrhoic head, neck and shoulder region. In AD patients, the saprophytic yeasts induce IgE responses while they usually induce TH1 type responses. The cytokine responses induced by yeasts in AD are sparsely investigated. OBJECTIVE: To characterize the P. ovale- and C. albicans-specific and non-specific humoral, lymphoproliferative and cytokine (IL-2, 4, 5 and IFNgamma) responses in AD. METHODS: Fifteen AD patients and seven healthy controls (HC) were included. Ficoll-isolated PBMC were stimulated by PHA and laboratory-generated extracts of P. ovale and C. albicans. Lymphocyte proliferation was measured by 3H-thymidine incorporation and cytokine production by sandwich-ELISAs. The antigen-specific IgG and IgE antibodies were analysed by ELISA and nitrocellulose RAST. RESULTS: Pityrosporum ovale- and C. albicans-specific IgE (both P < 0.001) and P. ovale-induced PBMC proliferation (P < 0.02) were elevated in AD. In general, the IL-4/IFNgamma ratio induced by P. ovale was higher than that induced by C. albicans (P < 0.01). The PHA-induced IL-2 (P < 0.05) and IL-4 responses (P < 0.005), and the C. albicans-induced IL-5 response (P < 0.02) and IFNgamma response (P < 0.01), were elevated in AD. A network of correlations was seen between serum total and the yeast-specific IgE, P. ovale-specific lymphoproliferation, PHA-induced IL-2, IL-4 and IL-5, and C. albicans-induced IL-5. CONCLUSION: The cytokine profiles found in this study support the role of TH0 or TH1 cells by the side of TH2 cells in the pathogenesis of atopic dermatitis. Pityrosporum ovale appears to be associated more with IL-4 responses and C. albicans with IFNgamma responses.

Chronic cough and gastro-oesophageal reflux: a double-blind placebo-controlled study with omeprazole.

Gastro-oesophageal reflux (GOR) is an important cause of chronic cough. There has been a lack of placebo-controlled trials treating GOR related chronic cough with antireflux therapy. The aim of this study was to determine the efficacy of omeprazole on GOR related chronic cough. After excluding other common causes of cough, oesophageal pH monitoring was performed on 48 patients with chronic cough. Twenty-nine patients found to have GOR were randomized in a double-blind fashion to receive omeprazole 40 mg o.d. or placebo for 8 weeks. After a 2-week washout period, patients were crossed over to the other treatment. Symptoms were recorded daily in a diary. Twenty-one patients completed both treatment periods. Cough (p=0.02) and gastric symptoms (p=0.003) improved significantly during the omeprazole treatment in twelve patients who received placebo during the first and omeprazole during the second 8-week period. In nine patients who received omeprazole during the first 8-week period, amelioration in cough reached statistical significance only after cessation of omeprazole. Gastric symptoms also remained minor during placebo in these nine patients. Omeprazole 40 mg o.d. seems to improve chronic cough in patients with gastrooesophageal reflux and the effect of omeprazole in ameliorating both cough and reflux symptoms continues after treatment ceases.

Comparison of high and low dose of the inhaled steroid, budesonide, as an initial treatment in newly detected asthma.

The importance of early initiation of inhaled steroids even in mild asthma has been documented in several studies. It is not, however, clear whether the treatment should be started with a high or a low dose of the inhaled steroid. We have compared the effects of high and low dose inhaled steroid, budesonide, in patients with newly detected asthma. We studied 101 adult patients with newly detected bronchial asthma who were without inhaled steroid or any regular pharmacological treatment for their asthma. The patients were randomly allocated to two treatment groups: one to receive 800 microg inhaled budesonide per day and the other to receive 200 microg inhaled budesonide per day. The drugs were given with a Turbuhaler dry powder inhaler. During the 3-month treatment period, no significant differences between the treatment groups were noted in morning or evening PEF values, in spirometric parameters, in asthmatic symptoms or in the use of rescue beta2-agonists. The decrease in bronchial hyperresponsiveness was, however, more marked in the high dose budesonide group, reaching a borderline significance (P=0.10 high vs. low dose budesonide). In addition, in serum markers of asthmatic inflammation significant differences were shown between the treatment groups. The decrease in the number of blood eosinophils during the treatment was more marked in the high dose budesonide group (P=0.02; high vs. low dose budesonide). In serum ECP no change was observed in the low dose budesonide group, but a marked decrease in the high-dose budesonide group (P=0.008; high vs. low dose budesonide). The change was even more marked with regard to serum EPX (P=0.005; high vs. low dose budesonide). Our results support the view that the treatment of newly detected asthma should be started with a high dose of inhaled steroid. The low dose may not be enough to suppress asthmatic inflammation despite good clinical primary response.

Farm environment in childhood prevents the development of allergies.

BACKGROUND: A protective effect of infections in early life might explain the firmly reported finding of an inverse association between atopic disorders and large sibships. OBJECTIVE: To study the effect of childhood farm, rural non-farm and urban environment, as well as family size and other factors on the occurrence of asthma, wheezing and atopic disorders up to young adulthood. METHODS: Data on lifetime prevalence of physician-diagnosed asthma, allergic rhinitis and/or allergic conjunctivitis, atopic dermatitis, as well as self-reported episodic wheezing from 10 667 Finnish first-year university students aged 18-24 years were collected by a postal questionnaire. Associations of lifetime prevalence of the diseases with living on a farm, in a rural non-farm and urban environment during childhood were estimated by logistic regression analysis. Adjustment was made for potential confounding by gender, parental atopy, parental education, number of older siblings, day care outside the home and passive smoking. RESULTS: The childhood farm environment independently reduced the risk for physician-diagnosed allergic rhinitis and/or allergic conjunctivitis (adjusted odds ratio 0.63, 95% CI 0.50-0.79, P < 0.001), and for diagnosed asthma and episodic wheezing analysed together (OR 0.71, 95% CI 0.54-0.93, P < 0.05), but not for atopic dermatitis during lifetime. Urban childhood environment did not show independent increased risk when compared with rural non-farm residence. The inverse association of sibship size with the occurrence of allergic rhinitis and/or allergic conjunctivitis was found among subjects with one (OR 0.86, 95% CI 0.77-0.96, P < 0.01) or at least four older siblings (OR 0.47, 95% CI 0.26-0.84, P < 0.05). CONCLUSION: Childhood farm environment seems to have a protective effect against allergic rhinitis and/or conjunctivitis, and more weakly against asthma and wheezing irrespective of family size. Environmental exposure to immune modulating agents, such as environmental mycobacteria and actinomycetes, favouring manifestation of a nonatopic phenotype could explain the finding.