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Biomedical subjects

G W Canonica

Publications and source records attributed to G W Canonica.

At least 19 recordsLinked to original sources
PubMed2003

Rhinasthma: a new specific QoL questionnaire for patients with rhinitis and asthma.

INTRODUCTION: To date we have available specific instruments assessing health-related quality of life (HRQL) in rhinoconjunctivitis or in asthma, but not instruments evaluating rhinitis and asthma together, although they often coexist. The aim of our study was to develop and validate a specific quality of life (QoL) questionnaire for adult patients with rhinoconjunctivitis, asthma or both. MATERIALS AND METHODS: A pool of 42 items covering the main symptoms and problems related to respiratory allergy, was generated based on literature review and clinical experience. The items were randomly listed and presented to 148 consecutive outpatients 46 suffering from asthma (age 32.9 +/- 14.3 years), 53 suffering from rhinoconjunctivitis (age 32.6 +/- 11.5 years) and 49 from asthma and rhinoconjunctivitis (age 35.6 +/- 12.2 years). The patients were asked to indicate which item they had directly experienced and for each of them, its importance on a four-point scale (1 = not important; 4 = very important). Twelve items were cancelled from the list, because of low importance or redundance. In the instrument validation phase, 104 patients (42 with rhinoconjunctivitis alone and 62 with asthma and rhinoconjunctivitis) were evaluated with the generic instrument SF-36 and the new questionnaire (RHINASTHMA). RESULTS: RHINASTHMA was able to differentiate patients with rhinitis from those with both rhinitis and asthma. In stable condition, RHINASTHMA showed good reliability. The factor analysis extracted three factors with a good reliability (0.93, 0.87, 0.76). DISCUSSION: RHINASTHMA is the first tool aimed at evaluating HRQL impairment in patients with rhinitis and/or asthma. It provides a short and simple assessment, and has overall psychometric properties. This is of relevance because of the frequent asthma-rhinitis comorbidity.

Adolescent↗
PubMed2003

Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study.

BACKGROUND: Subcutaneous immunotherapy for respiratory allergy has shown a long-lasting efficacy after its discontinuation, whereas this evidence is still lacking for sublingual immunotherapy, despite the fact that it is widely used. OBJECTIVE: We aimed to evaluate whether a long-lasting effect of SLIT occurs, in a prospective parallel group controlled study. METHODS: Sixty children (mean age 8.5 years) suffering from allergic asthma/rhinitis due to mites were subdivided into two matched groups: 35 underwent a 4- to 5-year course of SLIT with standardized extract and 25 received only drug therapy. The patients were evaluated at three time points (baseline, end of SLIT and 4 to 5 years after SLIT discontinuation) regarding presence of asthma, use of anti-asthma drugs, skin prick tests and specific IgE. RESULTS: We found that in the SLIT group there was a significant difference vs. baseline for the presence of asthma (P </= 0.001) and the use of asthma medications (P </= 0.01), whereas no difference was observed in the control group. The mean peak expiratory flow result was significantly higher in the active group than in the control group after 10 years. No change was seen as far as new sensitizations were concerned. Specific IgE showed a near-significant increase (baseline vs. 10 years, P = 0.06) only in the control group. CONCLUSION: Our study demonstrates that sublingual immunotherapy is effective in children and that it maintains the clinical efficacy for 4 to 5 years after discontinuation.

Administration, Sublingual↗
PubMed2003

Low concentrations of cytokines produced by allergen-stimulated peripheral blood mononuclear cells have potent effects on nasal polyp-derived fibroblasts.

Accumulating data show that fibroblasts are important regulators in the development and maintenance of allergic airway inflammation. However, most studies so far have used individual recombinant cytokines in high concentrations, unlikely to be found in vivo. We aimed to investigate how cytokines produced by peripheral blood mononuclear cells (PBMC) affect fibroblast functions. Primary airway fibroblasts where incubated with allergen-stimulated or non-stimulated PBMC supernatants from allergic patients. The levels of cytokines in PBMC supernatants were measured and the expression of CD54, CD40 and CD106 as well as the production of eotaxin, interleukin (IL)-6 and IL-8 were assessed in fibroblasts. Although the levels of single cytokines measured in PBMC supernatants were low, a significant up-regulation of the surface molecules as well as of IL-6 and IL-8 production was found in fibroblasts cultured with allergen-stimulated PBMC supernatants as compared to non-stimulated, while the increase in eotaxin production was not significant. The evaluation of correlations between cytokines produced by PBMC and effects seen on fibroblasts did not indicate a crucial role for any single cytokine. Furthermore, the addition of comparably low concentrations of recombinant interferon (rIFN)-gamma or recombinant tumour necrosis factor (rTNF)-alpha did not induce the same effects as PBMC supernatants, the only exception being TNF-alpha as a direct inducer of CD54 expression. Our results show that synergistic mechanisms has a more important role than single mediators, highlighting important differences between in vitro experiments, where effects of individual mediators are studied, versus the actual situation in vivo.

Cells, Cultured↗
PubMed2002

Introduction to nasal and pulmonary allergy cascade.

The early phase of an IgE-dependent allergic reaction is followed by the activation of a complex network of inflammatory phenomena - T lymphocytes, cytokines, mediators, and adhesion molecules - that mediate late and ongoing allergic symptoms. The kinetics of respiratory inflammation following allergen exposure involve the migration of inflammatory cells to the mucosa within about 30 min, increased inflammatory infiltration over the following hours, and then slow subsidence. A relationship between asthma and allergic rhinitis is supported by epidemiological, histological, physiological, and immunopathological data, and by the response of asthma symptoms in rhinitic patients to intranasal corticosteroids and antihistamines. For example, there is no morphological difference between the bronchial inflammatory response following allergen-specific challenge in patients suffering from asthma alone or rhinitis alone. It is the allergen dose that makes the difference in the airway response to allergen in allergic rhinitis and asthma. Recognition of the relationship between asthma and allergic rhinitis has led to the introduction of new diagnostic terminology and treatment recommendations: 1) patients with persistent rhinitis should be evaluated for asthma; 2) patients with persistent asthma should be evaluated for rhinitis; and 3) a strategy should combine the treatment of upper and lower airways in terms of efficacy and safety.

Asthma↗
PubMed2002

Cytokine pattern in allergic and non-allergic chronic rhinosinusitis in asthmatic children.

BACKGROUND: Rhinosinusitis represents one of the most common chronic diseases. The association of rhinosinusitis with asthma has been frequently reported. Eosinophils and Th2 cells play a pathogenic mechanism in asthma. OBJECTIVE: The aims of the study were to evaluate the cytokine pattern in chronic rhinosinusitis in asthmatic children and to compare the findings in allergic vs. non-allergic asthmatics. METHODS: Thirty-five asthmatic children were evaluated, 19 males and 16 females, with an average age of 8.7 years. All children were asthmatic and suffered from chronic rhinosinusitis. Twenty were allergic and 15 were non-allergic. Ten healthy children were studied as normal controls. Evaluated parameters were the levels of the following cytokines: IL-1beta, IL-4, IL-6, IL-8, IL-12, IFN-gamma and TNF-alpha. Cytokines were recovered from rhinosinusal lavage and measured by immunoassays. Nasal cytology was also performed in all subjects and inflammatory cells were counted by conventional staining. RESULTS: Allergic subjects showed a significant increase of IL-4 (P < 0.01) and TNF-alpha (P < 0.05) and a significant decrease of IL-12 (P < 0.05) and of IFN-gamma (P < 0.0001), whereas IL-1beta, IL-6 and IL-8 were not significantly increased. Non-allergic children showed a significant increase of IL-4 (P < 0.05) and a significant decrease of IFN-gamma (P < 0.0001), IL-12 was not significantly decreased, and IL-1beta, IL-6 and IL-8 were not significantly increased. A significant inflammatory infiltrate was present in all asthmatic children. Significant correlations were demonstrated between IL-4 and IL-12 (P < 0.001), IL-12 and IFN-gamma (P < 0.001), IL-8 and neutrophils (P < 0.01), and TNF-alpha and monocytes/macrophages (P < 0.05), in allergic asthmatics. IL-4 and IL-12 were significantly correlated (P < 0.05) as well as IL-8 and neutrophils (P < 0.01) in non-allergic asthmatics. CONCLUSION: This study shows that allergic asthmatic children with chronic rhinosinusitis have a typical Th2 cytokine pattern, but also non-allergic asthmatic children share a similar pattern. These findings would suggest the existence of a common pathophysiological mechanism shared by upper and lower airways and are consistent with the concept of united airways disease.

Asthma↗
PubMed2002

Effects of triamcinolone acetonide on adult human lung fibroblasts: decrease in proliferation, surface molecule expression and mediator release.

BACKGROUND: Lung fibroblasts may have a pivotal role in airway inflammation as they are involved in continuous cycles of mediator secretion, proliferation, activation and cross-talk with recruited inflammatory cells. The role of fibroblasts as intermediate participants in the inflammatory network suggests that they could represent an important target for drugs commonly used in asthma; thus, we investigated the effects of triamcinolone acetonide (TAA) on primary human lung fibroblasts. METHODS: The in vitro activity of increasing concentrations (10(-9) to 10(-7) M) of TAA in fibroblast cultures was evaluated as regards the following parameters: proliferation, extracellular matrix (ECM) release, cytokine/chemokine secretion and surface antigen expression. RESULTS: All concentrations of TAA decreased fetal calf serum (FCS)-induced fibroblast proliferation, whereas in the presence of FCS plus basic fibroblast growth factor TAA was only effective at 10(-8) and 10(-7) M. TAA failed to decrease ECM, whereas at 10(-8) and 10(-7) M it decreased IL-6 and IL-8 secretion to different extents. In the presence of IFN-gamma the drug was able to reduce VCAM-1 expression at all of the tested concentrations; on the other hand, in TGF-beta 1-driven cultures a decrease in CD54 expression was detected with TAA at 10(-8) and 10(-7) M. CONCLUSIONS: TAA acts on some functional properties of human lung fibroblasts that make these cells active participants in the inflammatory network. The ability of TAA to inhibit lung fibroblast proliferation may prevent or even reverse some of the histological changes that characterize airway remodeling in chronic inflammatory diseases; moreover, IL-6, IL-8 and surface molecule decreases by TAA may suggest a direct anti-inflammatory effect of the drug by suppression of resident lung cell function.

Cell Division↗
PubMed2002

The inflammatory network.

In the last few years the findings on allergic inflammation have improved, particularly in cellular signaling. Now we know that cytokines and other mediators are a network able to regulate the allergic inflammation (and inflammation in general). The new findings are important not only for basic science but also for the development of new therapeutic approaches to allergic diseases.

Humans↗
PubMed2001

Novel anti-inflammatory effects of the inhaled corticosteroid fluticasone propionate during lung myofibroblastic differentiation.

Asthma is characterized by an irreversible subepithelial fibrosis with the appearance of myofibroblasts, which can be now considered important early participants in inflammatory responses as well as potential targets for anti-inflammatory drugs. In this study, we show that fluticasone propionate (FP), a powerful inhaled corticosteroid (ICS), displays novel anti-inflammatory effects on human lung fibroblasts during their myofibroblastic differentiation. Indeed, FP inhibits in lung myofibroblasts, at a very early stage of differentiation, the activation of Janus kinase/STAT pathways induced by IL-13 (tyrosine kinase 2, STAT1, STAT3, STAT6, mitogen-activated protein kinase). Contrarily, in mildly or fully differentiated myofibroblastic cultures, FP still displays a potential anti-inflammatory activity even if it only inhibits tyrosine kinase 2 phosphorylation. Moreover, FP inhibits constitutive and TGF-beta-induced expression of alpha-smooth muscle actin, the main marker of myofibroblastic differentiation, both in very early and in mild differentiated myofibroblasts. Finally, FP displays an additional powerful anti-inflammatory effect, decreasing nuclear translocation of NF-kappaB independent of the degree of myofibroblastic differentiation. These data 1) suggest that myofibroblasts are priority targets for ICS, which is able to revert them to a normal phenotype even if they appear to be already engaged in their differentiation, and 2) may help to explain why asthma is improved by an early ICS treatment, whereas advanced asthma is more resistant to these drugs.

Actins↗
PubMed2001

Impact of rhinitis on airway inflammation: biological and therapeutic implications.

There is increasing evidence for a close link between the upper and the lower respiratory tracts and the fact that rhinitis has an important impact on asthma. Several clinical and experimental observations suggest a similar immunopathology between the upper and lower airways in allergic subjects. The common inflammatory process that develops in the respiratory tract explains some of the complex interactions among different clinical diseases such as rhinitis, sinusitis, asthma, bronchial hyperresponsiveness and viral infections. There are also non-inflammatory mechanisms that may contribute to the link between rhinitis and asthma. Moreover, the outcomes of various pharmacological treatments of rhinitis have recently provided further support for the hypothesis of the united airways. We discuss some of the recent observations on the nose-lung interaction and some of the novel therapeutic approaches used to treat rhinitis and asthma that arise from this.

Asthma↗
PubMed2001

Long-term cetirizine treatment reduces allergic symptoms and drug prescriptions in children with mite allergy.

BACKGROUND: Experimental data demonstrate that mite allergy is characterized by persistent chronic inflammation, even during asymptomatic periods. This suggests that long-term continuous treatment be included in the global strategy of allergy treatment. OBJECTIVE: We conducted a study to evaluate whether regularly administered cetirizine reduces allergic symptoms and drug prescriptions in children with mite allergy. METHODS: In this double-blind, randomized, placebo-controlled study, two parallel groups of 10 children with mite allergy (mean age: 6.5 years) received either cetirizine or placebo daily for 6 months. Participants were allowed to take rescue medications for rhinitis and/or mild asthma. The symptoms (nasal itching, sneezing, obstruction, rhinorrhea, conjunctival itching, lacrimation, conjunctival hyperemia, cough, wheezing, and chest tightness) were recorded on a diary card. The intake of cetirizine (as additional symptomatic treatment), antibiotics, acetaminophen, beta2-agonists, inhaled and systemic corticosteroids was also recorded. RESULTS: Symptom scores and drug consumption were significantly lower (P < 0.05) in the cetrizine-treated group versus the placebo group. The greatest reductions were in cetirizine itself, inhaled corticosteroids, beta2-agonists, and antibiotics. No side effects were reported in either group. CONCLUSIONS: In mite-allergic children, cetirizine administered daily for prolonged periods decreases symptoms of and drug prescriptions for allergic rhinitis and asthma compared with symptomatic treatment.

Allergens↗
PubMed2001

Intranasal mometasone furoate reduces late-phase inflammation after allergen challenge.

BACKGROUND: Allergen specific nasal challenge (ASNC) is an optimal model to study the pathophysiologic mechanisms sustaining allergic inflammation, particularly the adhesion molecules promoting cellular infiltration of nasal mucosa. Topical corticosteroids have been accepted as a highly effective anti-inflammatory therapy for allergic rhinitis. OBJECTIVE: The aim of this double-blind, randomized, placebo-controlled study was the evaluation of inflammatory events, during the late-phase, after a 2-week treatment with nasal mometasone furoate (MF), 200 microg daily, or placebo, using the model of ASNC. METHODS: A total of 42 patients with allergic rhinitis underwent nasal challenge before and after treatment. The following parameters were evaluated at baseline, and 6 hours (late-phase) after ASNC: 1) nasal symptoms (rhinorrhea, itching, sneezing, obstruction); 2) inflammatory cells (eosinophils and neutrophils); 3) eosinophil cationic protein (ECP) and tumor necrosis factor-alpha (TNF-alpha) in nasal lavage; and 4) intercellular adhesion molecule-1 expression on nasal epithelial cells. RESULTS: MF nasal spray was associated with late-phase reductions of: 1) clinical symptoms (P < 0.03); 2) eosinophil (P < 0.004) and neutrophil (P < 0.003) infiltration; 3) ECP (P < 0.001) and TNF-alpha (P < 0.05); and 4) intercellular adhesion molecule-1 expression on nasal epithelial cells (P < 0.001). CONCLUSIONS: The present results demonstrate that MF has a significant effect on late-phase events, reducing the cellular influx and activation.

Administration, Intranasal↗