Non-asthmatic Controls (non-asthmatic + control)

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Selected Abstracts

Bronchial hyperresponsiveness, atopy, and bronchoalveolar lavage eosinophils in persistent middle lobe syndrome

Kostas N. Priftis MD
Abstract Most cases of middle lobe syndrome (MLS) in children are considered to be due to asthma and may recover spontaneously; however, in persistent MLS, repeated episodes of infection often institute a vicious cycle that may lead to persistent symptoms and bronchial hyperresponsiveness (BHR). The present study was undertaken to investigate whether asthma, as an underlying diagnosis, is predictive of a favorable outcome of children with persistent MLS. We evaluated 53 children with MLS who underwent an aggressive management protocol that included fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). These patients were compared to two other groups: one consisting of children with current asthma but no evidence of MLS (N,=,40) and another of non-asthmatic controls (N,=,42), matched for age and sex. Prevalence of sensitization (,1 aeroallergen) did not differ between patients with MLS and "non-asthmatics" but was significantly lower than that of "current asthmatics." A positive response to methacholine bronchial challenge was observed with increased frequency among children with MLS when compared to "current asthmatic" and non-asthmatic children. Multivariate logistic regression analysis revealed a positive correlation between an increased number of eosinophils in the BAL fluid (BALF) and a favorable outcome, whereas no correlation was detected between sensitization or BHR and BAL cellular components. In conclusion, children with MLS have an increased prevalence of BHR, even when compared to asthmatics, but exhibit prevalence of atopy similar to that of non-asthmatics. An increased eosinophilic BALF count is predictive of symptomatic but not radiographic improvement of MLS patients after aggressive anti-asthma management. Pediatr Pulmonol. 2006 Wiley-Liss, Inc. [source]

Airway smooth muscle proliferation and survival is not modulated by mast cells

D. Kaur
Summary Background Airway smooth muscle (ASM) hyperplasia and mast cell localization within the ASM bundle are important features of asthma. The cause of this increased ASM mass is uncertain and whether it is a consequence of ASM,mast cell interactions is unknown. Objective We sought to investigate ASM proliferation and survival in asthma and the effects of co-culture with mast cells. Methods Primary ASM cultures were derived from 11 subjects with asthma and 12 non-asthmatic controls. ASM cells were cultured for up to 10 days in the presence or absence of serum either alone or in co-culture with the human mast cell line-1, unstimulated human lung mast cells (HLMC) or IgE/anti-IgE-activated HLMC. Proliferation was assessed by cell counts, CFSE assay and thymidine incorporation. Apoptosis and necrosis were analysed by Annexin V/propidium iodide staining using flow cytometry and by assessment of nuclear morphology using immunofluorescence. Mast cell activation was confirmed by the measurement of histamine release. Results Using a number of techniques, we found that ASM proliferation and survival was not significantly different between cells derived from subjects with or without asthma. Co-culture with mast cells did not affect the rate of proliferation or survival of ASM cells. Conclusion Our findings do not support a role for increased airway smooth proliferation and survival as the major mechanism driving ASM hyperplasia in asthma. Cite this as: D. Kaur, F. Hollins, R. Saunders, L. Woodman, A. Sutcliffe, G. Cruse, P. Bradding and C. Brightling, Clinical & Experimental Allergy, 2010 (40) 279, 288. [source]

Airway smooth muscle chemokine receptor expression and function in asthma

R. Saunders
Summary Background Chemokine receptors play an important role in cell migration and wound repair. In asthma, CCR3 and 7 are expressed by airway smooth muscle (ASM) and CCR7 has been implicated in the development of ASM hyperplasia. The expression profile of other chemokine receptors by ASM and their function needs to be further explored. Objective We sought to investigate ASM chemokine receptor expression and function in asthma. Methods ASM cells were derived from 17 subjects with asthma and 36 non-asthmatic controls. ASM chemokine receptor expression was assessed by flow cytometry and immunofluorescence. The function of chemokine receptors expressed by more than 10% of ASM cells was investigated by intracellular calcium measurements, chemotaxis, wound healing, proliferation and survival assays. Results In addition to CCR3 and 7, CXCR1, 3 and 4 were highly expressed by ASM. These CXC chemokine receptors were functional with an increase in intracellular calcium following ligand activation and promotion of wound healing [CXCL10 (100 ng/mL) 34 2 cells/high-powered field (hpf) vs. control 29 1; P=0.03; n=8]. Spontaneous wound healing was inhibited by CXCR3 neutralizing antibody (mean difference 7 3 cells/hpf; P=0.03; n=3). CXC chemokine receptor activation did not modulate ASM chemotaxis, proliferation or survival. No differences in chemokine receptor expression or function were observed between ASM cells derived from asthmatic or non-asthmatic donors. Conclusions Our findings suggest that the chemokine receptors CXCR1, 3 and 4 modulate some aspects of ASM function but their importance in asthma is uncertain. [source]

Airway cell and cytokine changes in early asthma deterioration after inhaled corticosteroid reduction

Y. H. Khor
Summary Background Back-titration of inhaled corticosteroid (ICS) dose in well-controlled asthma patients is emphasized in clinical guidelines, but there are few published data on the airway cell and cytokine changes in relation to ICS reduction. In our study, 20 mild-to-moderate persistent (inspite of low-moderate dose ICS treatment) asthmatic subjects prospectively rendered largely asymptomatic by high-dose ICS were assessed again by clinical, physiological, and airway inflammatory indices after 4,8 weeks of reduced ICS treatment. We aimed at assessing the underlying pathological changes in relation to clinical deterioration. Methods Patients recorded daily symptom scores and peak expiratory flows (PEF). Spirometry and airways hyperreactivity (AHR) were measured and bronchoscopy was performed with assessment of airway biopsies (mast cells, eosinophils, neutrophils, and T lymphoctyes), bronchoalveolar lavage (BAL) IL-5 and eotaxin levels and cellular profiles at the end of high-dose ICS therapy and again after ICS dose reduction. Baseline data were compared with symptomatic steroid-free asthmatics (n=42) and non-asthmatic controls (n=28). Results After ICS reduction, subjects experienced a variable but overall significant increase in symptoms and reductions in PEF and forced expiratory volume in 1 s. There were no corresponding changes in AHR or airways eosinophilia. The most relevant pathogenic changes were increased CD4+/CD8+ T cell ratio, and decreased sICAM-1 and CD18 macrophage staining (potentially indicating ligand binding). However, there was no relationship between the spectrum of clinical deterioration and the changes in cellular profiles or BAL cytokines. Conclusions These data suggest that clinical markers remain the most sensitive measures of early deterioration in asthma during back-titration of ICS, occurring at a time when AHR and conventional indices of asthmatic airway inflammation appear unchanged. These findings have major relevance to management and to how back-titration of ICS therapy is monitored. [source]

The protective role of country living on skin prick tests, immunoglobulin E and asthma in adults from the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy

F Kauffmann
Summary Background Farming environment and traditional lifestyle seem to protect from childhood allergy. Objective The aim is to analyse the relationships of living in the country to asthma, positive skin prick tests and IgE among adults considering various windows of exposure over the life-span. Methods The study concerns 805 adults drawn from the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy (EGEA) (asthmatic cases, non-asthmatic controls, and parents of cases with and without asthma). Ever living in the country concerned 55% of the subjects. Early (beginning <,1 years), childhood (beginning , 16 years), prolonged (duration , 10 years) and current life in the country were studied. Results The results based on the case control and family components of the study show that IgE levels were significantly lower in those who ever lived in the country and in particular in those who lived for , 10 years. Positive skin prick tests (SPT) were significantly less prevalent in those who ever lived in the country and in particular in those with childhood (, 16 years) exposure. These associations remained independent of age, sex, smoking or asthma with IgE levels of 64 vs. 88 IU/mL; P = 0.004 for those ever living in the country vs. others and odds ratio for SPT positivity of 0.72 (95% CI [0.53,0.98]). In the more specific group with traditional mode of heating in childhood (use of wood) associations were stronger. The association with asthma, studied in parents of asthmatic probands showed that fathers, but not mothers, of asthmatics were significantly less often asthmatic themselves in relation to country living. Conclusion Country life protects from asthma and adulthood allergy. The protective effect is not restricted to exposure in early childhood. [source]