Correlation between nasal symptoms and asthma severity in patients with atopic and nonatopic asthma.

BACKGROUND: The association between allergic rhinitis and asthma has been well recognized, and it has been postulated that rhinitis may worsen asthma. OBJECTIVE: To investigate the severity of asthma among patients with atopic and nonatopic asthma with and without nasal symptoms. METHODS: Atopic asthmatic patients and nonatopic asthmatic patients were identified from the records of a university-based asthma clinic. A comparison of demographic clinical features was made within and between these 2 asthmatic groups, dichotomized according to the presence or absence of rhinitis. RESULTS: A total of 178 patients were classified as having atopic asthma and 218 as having nonatopic asthma. The atopic asthmatic patients with nasal symptoms compared with those without had a higher mean forced expiratory volume in 1 second (FEV1), a higher forced vital capacity (FVC), and a higher FEV1/FVC ratio, used fewer oral steroids, and had fewer hospitalizations. The nonatopic asthmatic patients with nasal symptoms compared with those without used more inhaled steroids (and they were also more likely to have nasal polyps on examination). Atopic, relative to nonatopic, asthmatic patients were younger, had a longer duration of asthma, had a higher FEV1/FVC ratio, and took fewer oral steroids. CONCLUSION: Contrary to current hypotheses, in this study the severity of asthma among atopic asthmatic patients was less in those with nasal symptoms. Conversely, among the nonatopic asthmatic patients, asthma was more severe among those with nasal symptoms than those without nasal symptoms.     

Taban-arshan: Immunocorrector in atopic bronchial asthma

Taban-Arshan extract decreased expression of T-lymphocyte activation markers, normalized T-cell-mediated immunity, and suppressed increased activity of natural killer receptors during culturing with lymphocytes of patients with atopic bronchial asthma. Taban-Arshan extract normalized activation processes in the B-cell immunity and stimulated expression of receptors of activation-induced apoptosis. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 76–78, July, 2004     

Production of interferon by leukocytes from patients with atopic and nonatopic asthma

Investigations were carried out on 62 patients with atopic and nonatopic asthma and 70 normal individuals. Leukocytes isolated according to the method of Mogensen and Cantell, were induced for interferon production with Newcastle virus, H strain for 24 h at 37 degrees C in a tube culture placed in rolling drum. Interferon was assayed in the culture of human fibroblasts (HAT). Leukocytes from patients with both types of asthma had reduced interferon-inducing activity. At acute viral infection, a transient increase of interferon titer was observed. The titer, however, never reached the values of interferon induced in leukocytes from healthy individuals.     

IL-5 expression in the sputum of patients with bronchial asthma

Expression of IL-5 mRNA and the content of IL-5 in the sputum of patients with asthma of different severity were studied before and after treatment. The expression of IL-5 mRNA in mild asthma differed from that in severe and moderate asthma before and after treatment. The level of IL-5 before therapy was different in patients with mild and severe disease. In patients with severe asthma the level of IL-5 differed before and after treatment.     

CCL5/RANTES chemokine gene promoter polymorphisms are not associated with atopic and nonatopic asthma in a Spanish population

CCL5/RANTES, a member of the C-C chemokine family, is a potent eosinophil, monocyte, basophile and lymphocyte chemo-attractant at the site of inflammation. Recent studies revealed that a functional mutation at the -403 position in the promoter may have significance for atopic dermatitis, bronchial asthma, sarcoidosis, rheumatoid arthritis and HIV infection, and others. Another polymorphism in the -28 position has been reported. Our objective was to investigate the possible influence of the CCL5/RANTES promoter polymorphisms in the different types of bronchial asthma. CCL5/RANTES genotyping was performed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) in 306 asthmatic patients with non-atopic (n = 145) and atopic (n = 161) asthma and 242 controls. The 81.9% of the atopic asthma patients for -403G/A had the G allele and the A allele frequency was 18%. Of the non-atopic asthma patients, the G allele frequency was 79.7% and the A allele was 20.3%. Concerning the -28C/G polymorphism, the frequency of the CCL5/RANTES -28G allele in our patients is 2.8%, which is similar to Spanish adult population. After comparing patients with asthma, atopic patients, non-atopic patients and control population, we found no significant deviation in the distribution of the alleles or genotypes of CCL5/RANTES promoter polymorphisms in any tested comparison. Therefore, human CCL5/RANTES gene promoter polymorphisms are not associated with the different types of bronchial asthma in Spanish population.     

T cell and eosinophil activation in mild and moderate atopic and nonatopic children's asthma in remission

BACKGROUND: Inflammation in the pathogenesis of asthma is associated with products of activated T cells and eosinophils. The aim of this study was to determine whether ongoing inflammation persists in children with different phenotypes of asthma despite the disease in remission. METHODS: Serum samples were collected from 68 children with atopic or nonatopic asthma in remission and from 15 healthy children. Soluble interleukin-2 receptor (sIL-2R), IL-2 and IL-4 were examined by using an enzyme-linked immunosorbent assay. Total and specific immunoglobulin E, and eosinophil cationic protein (ECP) were analysed by fluoroimmunoassay (Pharmacia CAP System). RESULTS: In patients with moderate persistent atopic asthma, sIL-2R was increased significantly when compared with mild persistent atopic asthma (P < 0.05). No changes of sIL-2R were seen in nonatopic asthmatics compared with atopics and controls. The level of IL-2 was elevated in moderate persistent atopic and nonatopic asthmatic children compared with controls (P < 0.05 and P < 0.05 respectively) and compared with mild persistent atopic asthmatics and mild persistent nonatopic asthmatics (P < 0.05 in both cases). The levels of IL-4 in most patients and controls remained below the sensitivity of the assay. Eosinophil cationic protein levels in moderate persistent atopic and nonatopic asthmatics were significantly higher than in mild persistent asthma severity cases (P < 0.001 and P < 0.01 respectively) and in healthy children (P < 0.01 in both cases). CONCLUSION: Changes in the concentration of sIL-2R, IL-2 and ECP reflect increased T cell and eosinophil activity in relation to the level of severity of asthma in atopic and nonatopic children, thereby proving the presence of persistent inflammation despite the absence of disease symptoms.     

IL-5, IL-8 and GM-CSF immunostaining of sputum cells in bronchial asthma and chronic bronchitis

Background: Granulocyte-macrophage colony stimulating factor (GM-CSF) and inlerleukin (IL)-5 or IL-8 have been .suggested to play an important role in the pathogenesis of eosinophilic airway inflammation in bronchial asthma or neutrophilic airway inflammation in chronic bronchitis, respectively, However, GM-CSF and IL-8 have biological activities to either eosinophils or neutrophils. Objective: To investigate the contribution of these cytokines to airway inflammation, we compared the cellular differential and immunolocalization of GM-CSF, IL-5 and IL-8 in sputum cells from patients with bronchial asthma and chronic bronchitis. Methods: Cytospins of sputum cells from 12 patients with bronchial asthma and 12 with chronic bronchitis were subjected to cellular differential counting and immunocytochemistry with antihuman GM-CSF, IL-5 and IL-8 antibody. Results: The predominant cells in bronchial asthma were eosinophils and lymphocytes, while those in chronic bronchitis were neutrophils. All cytokines examined were detected in either bronchial asthma or chronic bronchitis, although the percentage of GM-CSF and IL-5 positive cells in bronchial asthma (53.4 ± 6.0 [mean±sfm ]% and 9.7 ± 2.8%, respectively) was significantly higher than that in chronic bronchitis (11.4±2.5%; P < 0.001 and 1.7plusmn;0.3%; P < 0.007. respectively). In contrast, the percentage of IL-8 positive cells in chronic bronchitis (23.8 ± 7.0%) was significantly higher than that in bronchial asthma (7.7 ± 1.9%; P < 0.04). The cells positive for IL-5 were lymphocytes in bronchial asthma and chronic bronchitis. The cells positive for GM-CSF in bronchial asthma were predominantly eosinophils. while those in chronic bronchitis were monocytes/macrophages and neutrophils. In contrast, neutrophils are mainly positive for IL-8 in chronic bronchitis, while monocytes/macrophages and bronchial epithelial cells are positive for IL-8 in bronchial asthma. Conclusion: The immunochcmical comparison of GM-CSF and IL-8 localization in sputum cells between bronchial asthma chronic bronchitis suggests the differential regulation and roles of these cytokines in eosinophilic vs neutrophilic airway inflammation, resulting in the development of different types of airway inflammation.     

Presence of circulating autoantibodies against bronchial epithelia cell in patients with nonatopic asthma

Allergic response to common environmental agents has been regarded as a main pathogenetic mechanism of bronchial asthma. However, allergic sensitization (atopy) can not be detected in a siginificant number of adult asthmatic patients. The etiology of nonatopic asthma has not yet been defined. To evaluate the possible involvement of autoimmune response against bronchial mucosa in the pathogenesis of nonatopic asthma, we performed indirect immunofluorescence staining of fresh frozen human bronchial mucosa tissue using serum samples from patients with atopic and nonatopic asthma, healthy controls, and patients with systemic lupus erythematosus. On immunostaining, circulating IgG autoantibodies against bronchial mucosa were detected in 2 (9.1%) of 22 patients with nonatopic asthma and in none of 22 patients with atopic asthma and of 22 healthy controls. IgG autoantibodies from the two patients with nonatopic asthma predominantly stained the cytoplasmic membrane of basal cells in bronchial epithelium. Serum samples from 10 patients with systemic lupus erythematosus immunostained the nucleus of epithelial cells in whole layer of bronchial epithelium. This study showed the presence of circulating IgG autoantibodies against the bronchial epithelial cell in a small portion of patients with nonatopic asthma. Further studies may be necessary to evaluate the possible involvement of autoimmune mechanism in the pathogenesis of nonatopic asthma.     

Infectious and uterus related complications during pregnancy and development of atopic and nonatopic asthma in children

BACKGROUND: It has been suggested that environmental factors early in life, particularly related to hygiene and infections, seem to be involved in the increase of asthma and allergic disease observed recently in developed countries. The possible effect of these factors also in utero have yet to be completely clarified. The aim of this study was to investigate the association between infective and uterus related complications during pregnancy, as well as related drug factors, with atopic and nonatopic asthma in children. METHODS: This was a case-controlled study enrolling 338 children with asthma and 467 controls, who had never suffered from wheeze or asthma. Fever episodes, flu episodes, threatened abortions and related drug factors were retrospectively assessed by parental report via a standardized questionnaire. Atopy was determined by skin-prick tests to 10 prevalent allergens at the time of examination. RESULTS: Flu episodes during pregnancy were significantly associated with development of asthma in children [adjusted odds ratio (aOR) 1.91; 95% confidence interval (95% CI) 1.1-3.2], mainly with nonatopic asthma. Fever episodes showed similar results (aOR 2.16; 95% CI 1.2-3.9), but were associated with both atopic and nonatopic asthma. The effect seems mainly due to flu and fever episodes contracted in the third trimester. Exposure to isoxsuprine was significantly associated with asthma (aOR 1.54; 95% CI 1.08-2.19) while threatened abortions were more frequent in the asthma group than in controls, although the difference was statistically significant only when such events occurred in the second trimester (aOR 2.06; 95% CI 1.07-3.94). Both threatened abortions and exposure to isoxsuprine were associated only with nonatopic asthma. CONCLUSIONS: This study confirms that prenatal infective complications may contribute to the development of asthma in children and show a possible role for a new risk factor for asthma, that is exposure to isoxsuprine. Therefore, larger prospective studies, capable of separating atopic and nonatopic asthma, would serve to confirm these results and to explain the possible mechanism through which these factors may act.     

In vitro responsiveness to IL-18 in combination with IL-12 or IL-2 by PBMC from patients with bronchial asthma and atopic dermatitis

Interleukin (IL)-18 is a proinflammatory cytokine and is now recognized as an important regulator of both helper T cells (Th) 1 and 2 cytokine production. An increased IL-18 secretion has been reported in patients with allergic disorders. It is predominantly produced by activated macrophages, and synergizes with IL-12 and IL-2 to induce IFN-gamma synthesis, thereby promoting Th1 cytokine response. Paradoxically, IL-18, by itself, strongly induces immunoglobulin (Ig) E and allergic inflammation, indicating a role for IL-18 in promoting Th2 response. We investigated the inducing effect in vitro of combining IL-18 and Il-12 or Il-2 on Th1- and Th2-type cytokines production by peripheral blood mononuclear cells (PBMC) from patients with allergic diseases. PBMC derived from 44 allergic patients [23 bronchial asthma (BA) and 21 atopic dermatitis (AD)] and 20 healthy controls were cultured with IL-18 in the presence of phytohemagglutinin (PHA) and IL-12 or IL-2. The levels of IFN-gamma, IL-13, and IL-4 in the culture supernatants were measured using enzymatic immunoassaying. IFN-gamma production was detected in all cultures from nonallergic controls stimulated with IL-18 in the presence of IL-12; however, the results for five BA patients and five AD patients were under the detection limit for IFN-gamma. In collaboration with IL-2, IL-18 was able to induce IFN-gamma production by PBMCs from all nonallergic controls and all allergic patients, with the exception of one AD patient. Synergistic induction of IL-13 production was found in cultures with IL-18 + IL-2, and the IL-13 induction was significantly increased in BA patients when compared with that in nonallergic controls (P = 0.006). The stimulation by IL-18, even in combination with IL-2, failed to induce IL-4 production by PBMC from both nonallergic controls and allergic patients. Although the induction of IFN-gamma by IL-18 + IL-12 was impaired in around a quarter of the allergic patients, the impairment of the IFN-gamma production was completely restored by IL-2 in the presence of IL-18. Thus, IL-18 enhances IFN-gamma production through an IL-12-dependent pathway and exhibits synergism when combined with IL-2 in terms of enhanced IL-13 and IFN-gamma production, suggesting the involvement of IL-18/IL-12/IL-2 pathway in modulating Th1/Th2 cytokine response.     

Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma.

BACKGROUND. In atopic asthma, activated T helper lymphocytes are present in bronchial-biopsy specimens and bronchoalveolar-lavage (BAL) fluid, and their production of cytokines may be important in the pathogenesis of this disorder. Different patterns of cytokine release are characteristic of certain subgroups of T helper cells, termed TH1 and TH2, the former mediating delayed-type hypersensitivity and the latter mediating IgE synthesis and eosinophilia. The pattern of cytokine production in atopic asthma is unknown. METHODS. We assessed cells obtained by BAL in subjects with mild atopic asthma and in normal control subjects for the expression of messenger RNA (mRNA) for interleukin-2, 3, 4, and 5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon gamma by in situ hybridization with 32P-labeled complementary RNA. Localization of mRNA to BAL T cells was assessed by simultaneous in situ hybridization and immunofluorescence and by in situ hybridization after immunomagnetic enrichment or depletion of T cells. RESULTS. As compared with the control subjects, the subjects with asthma had more BAL cells per 1000 cell that were positive for mRNA for interleukin-2 (P less than 0.05), 3 (P less than 0.01), 4 (P less than 0.001), and 5 (P less than 0.001) and GM-CSF (P less than 0.001). There was no significant difference between the two groups in the number of cells expressing mRNA for interferon gamma. In the subjects with asthma, mRNA for interleukin-4 and 5 was expressed predominantly by T lymphocytes. CONCLUSIONS. Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the TH2-like T-cell population.     

Central obesity is associated with nonatopic but not atopic asthma in a representative population sample

BACKGROUND: Epidemiologic studies have consistently demonstrated the association between high body mass index (BMI) and asthma, yet the relationship between asthma and the alternative central obesity phenotypes, waist circumference (WC) and waist-to-hip ratio (WHR), has not been assessed in a representative population sample. OBJECTIVE: To determine the strength of the association of WC and WHR with current asthma and whether the association is modified by atopic status in a representative population sample. METHODS: The North West Adelaide Health Study, a biomedical population study of n = 4060, assessed current asthma, respiratory symptoms, and participant demographics by self-completed questionnaire. Clinic assessment included measures of WC and WHR, spirometry, and skin prick tests to a panel of allergens. RESULTS: Logistic regression analysis showed a significant, marginal increased adjusted risk of asthma associated with obese levels of WC and WHR and BMI > or =35.0 kg/m2 in female subjects only. When the association was considered stratified according to atopic status, the relationship between obese levels of WC and WHR with asthma held only for the nonatopic population in both males (WC: odds ratio [OR] 5.7, 95% confidence interval [CI] 1.1-28.8; WHR: OR 6.2, 95% CI, 1.1-32.9) and females (WC: OR 2.3, 95% CI, 1.2-4.4; WHR: OR 3.0, 95% CI, 1.5-5.9). BMI > or =35.0 kg/m2 showed an inconsistent pattern in the association with asthma. CONCLUSION: Central obesity was significantly associated with an increased risk of nonatopic asthma only. The causal pathway is unknown, but this study suggests the involvement of different pathophysiological mechanisms requiring further investigation. CLINICAL IMPLICATIONS: Asthma should be considered in older, nonatopic, centrally obese, symptomatic individuals.     

Prevalence,risk factors,and clinical outcomes of atopic and nonatopic asthma among rural children

Background

Because of time and cost constraints, objective classification of atopic and nonatopic asthma has been limited in large epidemiologic studies. However, as we try to better understand exposure-outcome associations and ensure appropriate treatment of asthma, it is important to focus on phenotype-defined asthma classification.