Biomedical subjects

R Sale

Publications and source records attributed to R Sale.

4 recordsLinked to original sources

PubMed2005

Early decrease in nasal eosinophil proportion after nasal allergen challenge correlates with baseline bronchial reactivity to methacholine in children sensitized to house dust mites.

BACKGROUND: Allergic rhinitis is induced by an IgE mediated inflammation after allergen exposure of the membranes lining the nose which, in predisposed individuals, may constitute a risk factor for the occurrence of asthma. OBJECTIVE: To detect early changes in nasal inflammation after allergen exposure, 11 children [9.0 (7, 11) yrs], sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and an age- and gender-matched control group (Ctr) were studied. METHODS: The following parameters were evaluated: i) pulmonary function; ii) bronchial reactivity to methacholine (MCh), expressed as Pd20MCh; iii) nasal brushing (NB) 'at baseline' and, on a separate day, 30 min after nasal allergen challenge (NAC). On NBs, the following markers of inflammation were evaluated: a) neutrophil and eosinophil proportion, b) 'intact to degranulated eosinophil' ratio, and c) expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR by nasal epithelial cells. RESULTS: 'At baseline', allergic children showed elevated nasal eosinophilia and increased ICAM-1 and HLA-DR expression (p<0.05), as compared to Ctr. In allergic children, nasal eosinophilia correlated with Pd20MCh (p=0.002). The significant decrease in nasal eosinophilia observed after NAC (p=0.002) was associated with a significant decrease in the 'intact to degranulated eosinophil' ratio (p=0.001). Interestingly, correlations were still present between Pd20MCh and 'post NAC' eosinophilia (p=0.004) or the NAC-induced decrease in eosinophilia (p=0.010). CONCLUSIONS: In children sensitized to HDM, experimental allergen exposure is followed by an early depletion of nasal eosinophils. The correlation between allergen-induced changes in nasal eosinophilia and bronchial reactivity to MCh further supports the concept of a tight link between upper and lower respiratory tract involvement in respiratory allergy.

Allergens↗

PubMed2003

Cytokine release and adhesion molecule expression by stimulated human bronchial epithelial cells are downregulated by salmeterol.

Summary beta2-adrenoreceptor agonists are able to modulate various aspects of airway cell functions involved in the inflammatory and repair processes characterizing a variety of respiratory disorders. Human bronchial epithelial cells (HBECs), which can act as immune effector cells and express beta2-adrenoreceptors, were used to test the effects of different concentrations (0.1-100.0 nM) of salmeterol (Salm) on adhesion molecule expression and chemokine/cytokine release. HBECs, freshly isolated from resected bronchi at the time of surgery in ex-smokers with lung cancer, constitutively expressed over 3 times more ICAM-1 than VCAM-1 (P<0.05) and secreted greater amounts of IL-8 than of GM-CSF or RANTES (P<0.001). Stimulation of HBECs with IL-4, TNF-alpha or IL-4 plus TNF-alpha-upregulated ICAM-1 expression (P<0.05) and increased GM-CSF and IL-8 secretion (P<0.05). Similarly, VCAM-1 expression was significantly increased by IL-4 plus TNF-alpha, while RANTES release was significantly enhanced by IL-4 or by IL-4 plus TNF-alpha (P<0.05), but not by TNF-alpha alone (P>0.05). Dose-response curves showed that Salm, at concentration >1.0 nM, was effective in inhibiting adhesion molecule expression and cytokine release by HBECs (P<0.05). At a Salm concentration of 10 nM the degree of inhibition observed was similar for ICAM-1 and VCAM-1 expression (37.2 +/- 9.3% and 32.9 +/- 9.6%, respectively; P>0.05), but higher for RANTES (88.4 +/- 4.4%), as compared to IL-8 (21.8 +/- 7.0%) or GM-CSF (30.1 +/- 6.6%; P<0.05, each comparison). Thus, adhesion molecules and cytokines may be expressed/released at very different levels by unstimulated or stimulated HBECs and those activities appear to be modulated by Salm.

Adult↗

PubMed2003

Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling.

Lung fibroblasts play a key role in the pathogenesis of airway inflammation and remodeling through the release of mediators and the expression of surface molecules connected with cell-cell and cell-extracellular matrix interaction. The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-beta]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-alpha in the presence of different concentrations (0.01-100.0nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF (p<0.05), whereas TNF-alpha induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release (p<0.05, each comparison). No changes in HCAM expression and in TGF-beta release were observed (p>0.05, each comparison). The addition of MOM or DEX at the beginning of the cell cultures induced a significant downregulation in fibroblast DNA synthesis and proliferation, ICAM-1 and HCAM expression and chemokine/cytokine release (p<0.05, each comparison). At all the concentrations tested, MOM was more effective than DEX in inhibiting ICAM-1 expression and MCP-1 release (p<0.05, each comparison), whereas no potency advantage for MOM was detected in DNA synthesis, cell proliferation, HCAM expression and in eotaxin, IL-6 and TGF-beta release (p>0.05, each comparisons). These results extend the profile of the anti-inflammatory activity of mometasone furoate to lung fibroblast functions involved in airway inflammation and remodeling.

Airway Obstruction↗

PubMed2003

Nasal inflammation and bronchial reactivity to methacholine in atopic children with respiratory symptoms.

BACKGROUND: In atopic subjects, dysfunctions of the upper and lower airways frequently coexist and allergic rhinitis seems to constitute a risk factor for the occurrence of asthma in predisposed individuals. AIM OF THE STUDY: To evaluate whether in atopic subjects nasal inflammation could reflect changes in respiratory functions, 11 allergic children, sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and 10 nonatopic controls (ctrs) were studied. METHODS: All subjects underwent nasal brushing to detect percentages of nasal eosinophils (Eos %) and intercellular adhesion molecule-1 (ICAM-1) expression by nasal epithelial cells. In the same day pulmonary function tests, i.e. forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flows at 25-75% of the vital capacity (FEF25-75%) and methacholine (MCh) bronchial inhalation challenge were also evaluated. RESULTS: Pulmonary function parameters were not significantly different in allergic children and in ctrs (P > 0.05), while a significant increase in bronchial reactivity to MCh, expressed as Pd20 MCh, was detected in the former population (P < 0.05). As compared with ctrs, allergic children showed elevated Eos % and ICAM-1 expression (P < 0.05). When nasal inflammation and pulmonary function parameters were compared, a significant correlation was found between nasal Eos % and bronchial reactivity to MCh (P = 0.002). CONCLUSIONS: These data support the concept of significant links between upper and lower respiratory tract involvement in atopic children sensitized to HDM.

Adolescent↗