Tuberculin-primed PBMC fail to produce TH2-type cytokines.
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Publications and source records attributed to E O Terho.
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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.
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.
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.
Local reactions and pertussis toxin specific immunoglobulin E antibodies (PT-IgE) were investigated in healthy children following primary and booster immunization with a combined diphtheria tetanus acellular pertussis vaccine (DTPa) including pertussis toxin, filamentous haemagglutinin and pertactin. A primary series of DTPa was administered to 150 infants, and 104 of them received a booster dose of DTPa combined with inactivated polio vaccine at 2 years of age. PT-IgE was measured in serum samples from 72 children using a modified nitrocellulose RAST. Primary immunization was associated with low incidence of local reactions (1%-5%). After the booster dose 21% of children had a local reaction >/=20 mm. Local reactions after the booster dose tended to be more common in children who had experienced reaction at primary immunization. PT-IgE was detected in 18% and 86% of children following primary and booster vaccinations, respectively. Allergic and non-allergic children did not differ in PT-IgE responses. After primary immunization, elevated PT-IgE levels were found more often in children with a family history of allergy than in those without known allergy in the family. Children with local reactions had significantly higher pre- and post-booster PT-IgE levels and median post-booster pertactin IgG and diphtheria-IgG levels than children without local reactions. Conclusion Acellular pertussis immunization induces IgE antibodies to pertussis toxin, especially after booster vaccination. The higher median pre- and post-booster levels of pertussis toxin specific immunoglobulin E and post-booster levels of IgG to pertactin and diphtheria in children with local side-effects reflect a multifactorial immunological mechanism of such reactions.
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Atopic dermatitis (AD) patients often demonstrate positive skin prick test results and serum IgE antibodies to a range of different yeasts. This has been thought to be due to cross-reactivity. In this study, the cross-reactivity of IgE and IgG antibodies between mannan and crude antigens of Pityrosporum ovale, Candida albicans, and Saccharomyces cerevisiae and crude antigens of Cryptococcus albidus and Rhodotorula rubra was examined by RAST and ELISA inhibition with two serum pools of AD patients. We found cross-reacting IgE and IgG antibodies. In the IgE response, the main cross-reacting pattern was the mannan region, although inhibition could be achieved also with crude antigens of C. albicans, S. cerevisiae, and, to some extent, C. albidus. P. ovale was the most potent inhibitor of IgE-binding components, and against it the highest IgE antibody levels were detected in AD serum pools. In contrast, C. albicans was found to be the most important inducer of IgG antibodies, since the IgG level against P. ovale mannan in both AD serum pools was very low. Cross-reacting antibodies were also seen in ELISA inhibition with both crude and mannan antigens, but since the IgG antibody level of P. ovale mannan in AD serum pools was low, further studies are needed to confirm the IgG results.
We measured IgG antibody levels against eight different microbes in farmer's lung (FL) patients an average of 14 years after the first diagnosed episode of FL and in matched controls. The study population consisted of 87 FL patients and 81 control farmers, matched by age, sex, and smoking habits. Clinical studies included the measurement of IgG antibody levels against Absidia corymbifera, Aspergillus umbrosus, A. fumigatus, Humicola grisea, Saccharopolyspora rectivirgula, Penicillium brevicompactum, Rhodotorula glutinis, and Thermoactinomyces vulgaris, in addition to spirometry, pulmonary diffusing capacity (DL(CO)), and the evaluation of chronic bronchitis. Median IgG antibody levels were two or more times higher in FL patients than control farmers against Ab. corymbifera, S. rectivirgula, and T. vulgaris (P<0.001). Against A. fumigatus, H. grisea, and R. glutinis, FL patients also had significantly higher antibody levels. FL patients often had positive antibody titers against several microbes, whereas control farmers usually had a positive titer against one or two microbes. A positive association between IgG antibody levels and chronic bronchitis and DL(CO) was observed in FL patients, but not in control farmers. It is suggested that the high antibody levels noted in FL patients were due not only to high exposure but also to individual sensitivity to environmental microbes.
BACKGROUND: The cytokine observed most often in atopic dermatitis (AD) is IL-4, but a role for IL-5 and IFN-gamma in the late and delayed phase reactions has been suggested. In AD with head, neck and shoulder distribution, hypersensitivity to saprophytic yeasts is an important pathogenetic factor. The yeast allergens include both the mannan polysaccharides and the proteins. Mannans are major cross-reacting allergens likely to be involved in the pathogenesis of AD. OBJECTIVE: To characterize the humoral, lymphoproliferative and cytokine (IL-2, 4, 5 and IFN-gamma) responses of peripheral blood mononuclear cells (PBMCs) induced by Candida albicans mannan and protein antigens in AD. METHODS: Fifteen AD patients and seven healthy controls were included. Ficoll-isolated PBMCs were stimulated by PHA and laboratory-generated mannan and protein extracts of C. albicans. Lymphocyte proliferation was measured and cytokine production was studied by ELISA. The antigen-specific IgG and IgE antibodies were analysed by ELISA and nitrocellulose RAST. RESULTS: In AD mannan (P < 0.005) and protein (P < 0.002), specific IgE levels were higher than in healthy controls. Both mannan and protein-specific lymphoproliferations (both: P < 0.02) were higher in AD than in healthy controls. Mannan, but not protein, induced long lasting IL-2 and IL-4 productions from 24 h lasting up to 66-96 h and IL-5 and IFN-gamma productions with elevated levels at 66 and 96 h. The mannan-induced IL-2 (P = 0.015) and IFN-gamma (P < 0.005) were increased in AD as compared with healthy controls. Significant correlations were seen between the protein-induced proliferation responses and both serum total IgE (r = 0.59, P < 0.01) and protein-specific IgE (r = 0.65, P < 0.005). The mannan-induced IL-2 responses correlated with the specific IgE (r = 0.62, P < 0.01) and proliferation (r = 0.51, P < 0.02) and S-IgE level (r = 0.71, P < 0. 002). Mannan-induced IL-4 and IFN-gamma productions also correlated (r = 0.43, P < 0.05). CONCLUSIONS: C. albicans mannan induced elevated IL-2 and IFN-gamma responses in AD patients. The correlations of the cytokine responses with mannan-induced IgE and proliferation responses suggest that C. albicans mannan induced TH1 type cytokine responses are involved in AD.
STUDY OBJECTIVES: To investigate the prevalence of gastroesophageal reflux (GER) among patients with asthma and to determine the effect of omeprazole on the outcome of asthma in patients with GER. DESIGN: A double-blind, placebo-controlled crossover study. SETTING: Asthmatic patients who attended the pulmonary outpatient clinic of Turku University Central Hospital, Finland. PATIENTS: One hundred seven asthmatic patients. INTERVENTIONS: The patients who were found to have GER in ambulatory esophageal pH monitoring were randomized to receive either omeprazole, 40 mg qd, or placebo for 8 weeks. After a 2-week washout period, the patients were crossed over to the other treatment. Spirometry was performed at baseline and immediately after both treatment periods. Peak expiratory values, use of sympathomimetics, and pulmonary and gastric symptoms were recorded daily in a diary. RESULTS: Pathologic GER was found in 53% of the asthmatic patients. One third of these patients had no typical reflux symptoms. Daytime pulmonary symptoms did not improve significantly (p = 0.14), but a reduction in nighttime asthma symptoms (p = 0.04) was found during omeprazole treatment. In the patients with intrinsic asthma, there was a decline in [corrected] FEV(1) values (p = 0.049). Based on symptom scores, 35% of the patients were regarded as responders to 8-week omeprazole treatment. The reflux (time [percent] of pH < 4) was found to be more severe (p = 0. 002) in the responders. CONCLUSIONS: There is a high prevalence of GER in the asthmatic population. This reflux is often clinically "silent." After an 8-week omeprazole treatment, there was a reduction in nocturnal asthma symptoms, whereas daytime asthma outcome did not improve. There seems to be a subgroup of asthma patients who benefit from excessive antireflux therapy.
OBJECTIVE: A double-blind, randomized, placebo-controlled trial was conducted to study the effect of the intranasal corticosteroid, fluticasone propionate (FP), in the naturally occurring common cold. METHODS: One hundred ninety-nine young adults received high-dose FP (200 microg four times daily) or placebo beginning 24 to 48 hours after onset of the common cold for 6 days. All symptoms were recorded on diary cards on days 1 to 20, and clinical examinations were carried out on days 1, 7, and 21. Nasopharyngeal aspirates were collected on days 1 and 7 for detection of rhinoviruses (found in 105 subjects) and Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis (found in 52 subjects) in the nasopharynx. RESULTS: In general, FP treatment had no clinically recognizable effects on the symptoms of the common cold, although it significantly reduced nasal congestion and cough on some study days. After treatment, rhinoviruses were cultured more often in the FP treatment group (37% vs 14%, p < 0.001), but this had no effect on the symptoms of common cold. FP treatment produced no changes in the colonization of pathogenic bacteria in the nasopharynx. Some symptoms of common cold were significantly more severe during days 1 to 10 (p < 0.05) in subjects found to have positive cultures for S. pneumoniae, H. influenzae, or M. catarrhalis in the nasopharynx on day 1 (n = 33). CONCLUSION: FP treatment does not have any marked effects on the symptoms of the common cold. FP treatment induced prolonged shedding of viable rhinoviruses. Some symptoms of the common cold were significantly more severe in subjects with pathogenic bacteria in the nasopharynx.
BACKGROUND: Pityrosporum ovale is a common saprophyte on the skin capable to induce IgE antibody production in atopic dermatitis. Generally IgE response to P. ovale has been established with skin-prick test, but the stability of P. ovale skin test allergens is not known. OBJECTIVE AND METHODS: In this study we analysed the stability of identified allergens of P. ovale in skin test solutions during storage. The stability was checked with immunoblotting and densitometry after different time periods and at various temperatures. RESULTS: Coomassie Brilliant blue staining clearly showed, that proteins were preserved poorly at + 20 degrees C in 50% glycerol. Even extracts stored at + 4 degrees C during 6 and 12 months in 50% glycerol were degraded. Only extract stored at + 4 degrees C for 1 month in 50% glycerol was quite well preserved. According to densitometry results the 9 kDa band was the most stable main protein allergen. The 20 kDa and especially the 96 kDa bands were far more labile. The stability of low molecular allergens was in general better than the stability of high molecular weight allergens. CONCLUSIONS: The stability of P. ovale extracts stored for more than 1 month was poor even when kept at + 4 degrees C temperature. Reliability of negative skin prick results should be questioned when older extracts are used. In skin test negative cases, the sensitization should be evaluated also with the measurement of specific serum IgE antibodies to P. ovale.
A standardized, controlled procedure for preparation of an in-house reference (IHR) preparation of an allergen extract of Candida albicans is described. The procedure, based on previous studies of allergens of C. albicans, is designed to yield a maximum of allergens in optimum extraction conditions and to provide a reference preparation for further extract production. The SDS-PAGE, IgE-immunoblotting, and crossed radioimmunoelectrophoresis (CRIE) analyses showed that the procedure is reproducible with acceptable batch-to-batch variation. The variation in the content of the most important allergens, namely, proteins with molecular weights of 46, 29, and 27 kDa in the pooled final batches, is acceptable (coeff. of variation < 15%), although in the intermediate batches of different strains, the coefficient of variation may occasionally exceed 20%. A comparison with other C. albicans allergen preparations used in our previous studies is also presented. The resulting extract can be used as a reference in further extract production and also in experimental in vitro and in vivo studies.
This study was undertaken to analyze the differences in exposure and sensitization to five common environmental yeasts. The responses of IgG, IgA, and IgE to Candida albicans, C. utilis, Cryptococcus albidus, Rhodotorula rubra, and Saccharomyces cerevisiae and purified S. cerevisiae enolase were analyzed by immunoblotting (IgE-IB), and the cross-reactivity of their IgE-binding components by IgE-IB inhibition. Twenty atopic subjects, with asthma, allergic rhinitis, or atopic dermatitis were included. In skin prick tests (SPT), 12 of the patients showed simultaneous reactivity to at least two of the five yeasts, four reacted to one of the yeasts, and four had no responses. Antigens run in SDS-PAGE and transferred to nitrocellulose were probed with enzyme-labeled IgA-, IgG-, and IgE-specific antibodies. The IgE immunoblotting revealed most IgE-binding bands in C. albicans (11 bands) followed by C. utilis (eight bands), S. cerevisiae (five bands), R. rubra (five bands), and Cr. albidus (four bands). Six of the IgE-binding bands of C. albicans and C. utilis shared molecular weight, and only two bands shared molecular weight with other yeasts. These were the 46-kDa band, shared by all five yeasts, and a 13-kDa band shared by four yeasts. Prominent IgE binding was seen to a 46-kDa band of C. albicans (seven patients), C. utilis (five patients), and S. cerevisiae (one patient) and to corresponding weak bands of Cr. albidus and R. rubra (one patient). The possible cross-reactivity of the 46-kDa band was analyzed by IgE-IB inhibition and densitometry, revealing clear C. albicans inhibition of C. utilis (80%) and enolase (98%) (autoinhibition 100%). The strongest IgG responses were seen against S. cerevisiae and C. albicans. The responses were mainly against mannans of C. albicans and S. cerevisiae, suggesting that most of the exposure is to these yeasts. Yeasts with different types of exposure, from saprophytic growth on human mucous membranes to exposure by air and food, were shown to cross-react at the allergenic level. Atopic patients primarily sensitized by C. albicans and S. cerevisiae may develop allergic symptoms by exposure to other environmental yeasts due to cross-reacting IgE antibodies.
We evaluated the long-term outcome of farmer's lung (FL) patients and matched control farmers using high-resolution computed tomography (HRCT). The study population consisted of 88 FL patients and 83 control farmers, matched by age, sex, and smoking habits. The mean time after the first diagnosed episode of FL was 14 yr. The great majority, 82%, of the studied subjects were nonsmokers. Clinical studies included HRCT, spirometry, and pulmonary diffusing capacity. Emphysema was found significantly more often (23%) in FL patients than in control farmers (7%) (p = 0.006). The presence of emphysema was 18% in nonsmoking and 44% in smoking FL patients, the respective values being 4% and 20% in control farmers. Patients with recurrent attacks of FL tended to have emphysema more often (p = 0. 08) than patients who had experienced only a single attack. Fibrosis was observed in 17% of the FL patients and in 10% of the control farmers (p = 0.2). Miliary changes were found in 12% of the FL patients compared with 4% of the control farmers (p = 0.07). Both emphysematous and fibrotic but not miliary changes correlated significantly with impaired pulmonary function. In conclusion, farmer's lung disease seems to be associated with an increased risk of developing emphysema.
STUDY OBJECTIVES: The aim of this study was to determine the role of complement components in pleural effusion measured with novel markers of complement activation, to assess which pathway of activation is predominant in different diseases, and to find out whether the analysis of complement components and their activation products could help in diagnostic procedure differentiating the etiologies of pleural effusion. PATIENTS: The study population consisted of 71 patients who had pleural effusion secondary to tuberculosis (n=23), rheumatic disease (n=10), or malignancy (n=38). MEASUREMENTS: Complement components and their activation products, including the soluble terminal complex SC5b-9, were measured in plasma and pleural fluid. RESULTS: In all patients with rheumatic pleurisy, pleural fluid SC5b-9 was higher than 2 AU/mL and in all patients with malignant pleural fluid it was lower than 2 AU/mL. The mean level of SC5b-9 in rheumatic pleural effusion was also significantly higher than in tuberculosis. In addition, the concentrations of pleural fluid C3 and C4 were significantly lower and the ratio C4d/C4 was significantly higher in rheumatic compared with tuberculous or malignant pleurisy. In plasma, both SC5b-9 and C1s-C1r-C1INH-complexes were significantly higher in rheumatic subjects than in other patients. In stepwise multinominal logistic regression analyses, the most significant predictors for rheumatic pleural fluid were high pleural fluid SC5b-9 and low C4. CONCLUSIONS: These observations indicate that the complement cascade is activated through both the classic and the alternative pathways in rheumatic pleurisy. Determinations of SC5b-9 and C4d/C4 in pleural fluid were the best variables differentiating rheumatic, tuberculous, and malignant effusions.
OBJECTIVES: This study investigated the value of powered dust respirator helmets in the treatment of farmers with occupational asthma. METHODS: The study population consisted of 33 asthmatic agricultural workers, 24 with occupational asthma induced by cow dander or grains, 2 with other forms of atopic asthma, and 7 with nonatopic asthma. The efficiency of a powered dust respirator helmet with a P2-class filter in preventing asthmatic symptoms was assessed for 1 year. Morning and evening peak expiratory flow rates and daily symptoms of the subjects were monitored for 3 months without the use of the helmet and for 10 months with the helmet. RESULTS: Objective evidence of protection was obtained for farmers with occupational asthma. The morning peak flow rate increased and the variation in daily peak flow rate and the symptoms of cow-barn rhinitis diminished significantly during the helmet period. In the group of farmers with nonatopic asthma there was no improvement in peak flow rate or symptoms of asthma, although some of these farmers also seemed to benefit from helmet use. CONCLUSIONS: The results of this study suggest that especially dairy farmers with occupational asthma benefit from the use of a powered dust respirator helmet.
IgG and IgA antibodies against fungus Aspergillus umbrosus have been found in the sera of patients with farmer's lung (FL) disease and healthy exposed farmers in Finland. To determine the IgE response to antigens of A. umbrosus and Candida albicans, sera from 20 patients with FL, 20 healthy farmers and 20 nonfarming controls were tested by nitrocellulose radioallergosorbent test (RAST). The values of RAST indices were low in each group and the only statistically significant difference was found between the groups of FL patients and nonfarming controls against A. umbrosus polysaccharide antigen. Individual IgE responses to polysaccharide antigens of A. umbrosus and C. albicans correlated among FL patients, however, no cross-reacting IgE antibodies could be shown. To conclude, the IgE antibody levels of A. umbrosus polysaccharide and crude antigens were low in FL patients, healthy exposed farmers and nonfarming controls. Neither polysaccharide nor crude antigen-specific IgE antibodies of A. umbrosus have any diagnostic value in FL disease.