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ABSTRACT: Although atopic asthma symptoms often seem to disappear around puberty, subjects in this age group may experience unexpected, often severe, asthma attacks. This may be related to persistence of untreated airway hyperresponsiveness/inflammation in a life period characterized by low perceptiveness of disease-related symptoms. This study was designed to evaluate the prevalence and the severity of bronchial hyperreactivity and the exhaled nitric oxide (FENO) levels in a group of steroid-naive asthmatic adolescents. Fifty-two patients with mild-intermittent asthma were studied, ages 12 to 16, sensitized to house dust mites; 22 age-matched controls, were also studied. Asthma patients showed FEV1, FEF25-75%, and FVC values not significantly different from controls, (p > 0.05, each comparison). By contrast, although none of the control subjects showed bronchial hyperreactivity, increased airway responsiveness to methacholine (MCh) was demonstrated in the majority of the patients and found to be severe in 36.5% (MCh PD20 > or = 400 microg or accumulative dose < or = 1220 microg) and moderate in 32.7% (MCh PD20 400-1400 microg or accumulative dose 1220-4620 microg). In addition, FENO concentrations were significantly higher in asthmatics, as compared with controls (20.4 +/- 5.3 ppb and 4.4 +/- 0.7 ppb, respectively; p < 0.01) and 83% of the patients had FENO levels higher than 8.9 ppb (i.e., > 2 standard deviations of the mean in control subjects). A positive, statistically significant correlation was found between FEF25-75% values and MCh PD20 (r = 0.358; p < 0.01) or MCh accumulative dose (r = 0.355; p < 0.05). No correlations were demonstrated between MCh responsiveness and FVC or FEV1 values or FENO levels and between FENO levels and pulmonary function parameters (p > 0.05). The high incidence of bronchial hyperresponsiveness to MCh and of airway inflammation (as demonstrated by the elevated FENO levels) in adolescents with mild asthma suggests the need for more accurate evaluation and, possibly, for early intervention with antiinflammatory drugs in a significant proportion of patients in this age group.
Journal of Asthma 06/2003; 40(3):301-10. · 1.52 Impact Factor
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ABSTRACT: In allergic patients with rhinoconjunctivitis (RNC), sublingual immunotherapy (SLIT) is effective in reducing both clinical symptoms and immuno-mediated local inflammatory responses. The study evaluates whether SLIT could reduce upper airway inflammation and improve clinical parameters also in children with rhinoconjunctivitis and asthma from house dust mite sensitization. Ten children with mild to intermittent asthma, monosensitized to house dust mites, received SLIT (Der p 1 monthly dose = 48 microg) for 2 years, in addition to "as needed" pharmacologic treatment. Before (T0) and after treatment (T2), changes were evaluated in (1) nasal eosinophilia, (2) intercellular adhesion molecule (ICAM)-1 expression by nasal epithelial cells, (3) RNC, asthma, and drug-intake scores, assessed by diary card, (4) pulmonary function parameters, and (5) bronchial reactivity to methacholine (MCh). RESULTS: All children completed the study without side or adverse effects. After the treatment period, we found no modification in nasal eosinophil values in mean fluorescence channel percentages, but a significant downregulation in ICAM-1 expression by nasal epithelial cells [mean (mfc): T0: 13.5 +/- 3.8 mfc; T2:4.6 +/- 0.5 mfc; p = 0.04]. These changes were associated with a reduction in RNC score [median values: T0: 3.4 (1.4-6.2); T2: 1.1 (0.6-2.4) p = 0.012], asthma score [median values: T0: 0.5 (0.4-1.0); T2: 0.3 (0.1-0.5); p = 0.005] and drug-intake score [median values: T0: 4.2 (3.1-5.3); T2: 1.1 (0-3.0); p = 0.005]. These clinical effects were not associated with changes in pulmonary function parameters (p > 0.05), but with improvement in bronchial reactivity to MCh [mean values: T0: 338.8 (91.5-1255.5); T2: 1698.2 (1,110.5-2,597.1); p = 0.02]. To what extent these observations may be related to the natural improvement of respiratory allergy symptoms with age remains to be determined.
Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2002; 12(1):52-9. · 2.27 Impact Factor
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ABSTRACT: ObjectiveTo investigate whether the state of activation of circulating T-cells in childhood asthma could be related to serum IgE levels and/or to blood eosinophilia.MethodsSeventeen atopic asthmatic children, sensitized to Dermatophagoides pteronyssinus (Der p), in stable condition at the time of the study and 15 sex-matched and age-matched controls were studied. The expression of activation surface markers (HLA-DR and CD25) on peripheral blood mononuclear cells (PBMCs) was tested by monoclonal antibodies and FACS analysis, while the PBMC proliferative response to Der p antigens was measured by tritiated thymidine (3HTdR) incorporation.ResultsAs compared to controls, atopic children showed higher eosinophil counts (P < .01), similar lymphocyte counts (P > .1, each comparison) but higher proportion of HLA-DR+ and CD25+ T-lymphocytes (P < .05, each comparison). A significant Der p allergen-induced PBMC proliferation was observed in atopic children (P < .01) but not in controls (P > .1). Both in controls and in atopic children, no correlations were found between lymphocyte counts and eosinophil counts or total or allergen-specific IgE levels (P > .1, each comparison). In contrast, weak correlations were detected between the degree of allergen-induced PBMC proliferation and: a) allergen-specific IgE levels in serum (P < .05) and b) eosinophil counts (P < .05).ConclusionThese data support the concept that the degree of activation of allergen-specific T-lymphocytes in blood may reflect the intensity of allergic sensitization in childhood asthma.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 04/2000; · 2.83 Impact Factor
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ABSTRACT: Sinusitis is a common complication of non-allergic and allergic rhinitis, and can trigger lower respiratory diseases, such as bronchitis and asthma. Standard radiography is unable to give any data about the underlying pathological mechanisms (infectious or allergic) involved and infectious rhinosinusitis is very common in pediatric age, even in allergic patients. We investigated the possibility of obtaining more useful diagnostic information, performing nasal brushing (NB) on 117 children with recurrent respiratory symptoms. The following hypothesis were evaluated: (1) whether NB neutrophil/eosinophil percentages and/or NB culture could predict the radiological evidence of maxillary sinusitis; and (2) whether differences between nonallergic and allergic patients could be detected. In the total patient group and in the nonallergic group, the comparison of NB neutrophil percentages in patients with and without maxillary sinusitis showed a statistically significant difference (median 2 and 18%, respectively; P<0.001). In the nonallergic group, a NB neutrophil rate ≥5% was chosen as a cut-off between positive and negative NB diagnosis of rhinosinusitis and NB data were compared with radiological investigations. The results obtained showed that NB was fairly sensitive (91%) and predictive (84%). In allergic patients, neither neutrophil nor eosinophil percentages significantly correlated with the presence of sinusitis. Microbiological studies showed that, even if the presence of bacteria in NB resulted associated with sinusitis, a negative culture was not predictive of the absence of the disease. We therefore suggest that NB describes the present inflammatory status of the upper airways, hence, it is more suitable to describe the inflammation related to ongoing upper respiratory tract infections rather than chronic inflammation due to allergic rhinitis, characterized by relapsing episodes of acute inflammation. In conclusion, we propose to consider NB a reliable tool in the diagnosis of rhinosinusitis, particularly in nonallergic pediatric patients. Compared to standard radiological techniques, NB makes it possible to avoid radiation exposure and gives information about the pathological mechanisms involved in the single patient.
International Journal of Pediatric Otorhinolaryngology 10/1999; · 1.17 Impact Factor
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ABSTRACT: ObjectiveTo test in vitro and in vivo the hypothesis that sodium nedocromil could modulate the expression of surface molecules on airway epithelial cells.MethodsHuman bronchial epithelial cells, obtained from surgically resected bronchi, were cultured and stimulated with recombinant IFN-γ in the presence of sodium nedocromil. The intensity of the expression of surface molecules HLA-DR and ICAM-1 molecules on bronchial epithelial cells in vitro, was quantified by specific antibody staining and flow-cytometry analysis. Furthermore, we studied the effect of the drug on airway inflammation in vivo and on allergic rhinitis patients sensitized to house dust mites. Nasal epithelial cells were collected by brushing, at baseline and 2 to 3 weeks after treatment with sodium nedocromil. The expression of HLA-DR and ICAM-1 molecules was measured by flow-cytometry, and the proportions of neutrophils and eosinophils “contaminating” the epithelial cells evaluated by light microscopy examination of nasal brushings.ResultsThe enhanced HLA-DR and ICAM-1 expression, induced by IFN-γ, was effectively downregulated, in a dose-dependent manner, by sodium nedocromil. At all the concentrations tested (10−9 to 10−4 M), the inhibitory activity of the drug was stronger on HLA-DR than on ICAM-1 expression (P<.05, all comparisons). As compared with healthy subjects, patients with allergic rhinitis had a higher expression of HLA-DR (P<.05) but not of ICAM-1 molecules (P>.05) on nasal epithelial cells, and higher proportions of nasal eosinophils (P<.05). Treatment with sodium nedocromil downregulated the expression of HLA-DR (P<.05), but not of ICAM-1 (P>.05), and induced a mild, but not statistically significant, decrease of nasal eosinophilia (P>.05).ConclusionThese data demonstrate that the antiinflammatory activity of sodium nedocromil may include modulation of surface molecule expression on airway epithelial cells.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 08/1999; · 2.83 Impact Factor
