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Biomedical subjects

G W Canonica

Publications and source records attributed to G W Canonica.

At least 91 records · Page 5Linked to original sources
PubMed2001

Underdiagnosis and undertreatment of asthma: a 9-year study of Italian conscripts.

BACKGROUND: During the last 20 years, the epidemiology of asthma has been investigated in various populations, thus providing interesting data including the accuracy of diagnosis and the adequacy of treatment. METHODS: We studied for 9 years the epidemiological features of asthma in a homogeneous population of 18-year-old males referred to La Spezia Military Navy Hospital for a call-up visit (conscripts). RESULTS: During the period of 1990-1998, 91,700 men were screened at their call-up visit; out of them 5,371 (7%) had asthma, but in 7.4% the disease had not been previously diagnosed. During the observation period there was a significant decrease of the level III severity of asthma, but about one quarter of the asthmatic subjects received no treatment at all. On the other hand, a significant increase in the prescription of inhaled steroids was observed. CONCLUSION: Despite educational efforts, a not negligible underdiagnosis and inadequate treatment of asthma in young adults still persist.

Administration, Inhalation↗
PubMed2001

Allergen-specific sublingual immunotherapy for respiratory allergy.

Present knowledge regarding the clinical efficacy and safety of sublingual immunotherapy (SLIT) for the treatment of respiratory allergy is reviewed. Allergen-specific immunotherapy is presently considered a 'biological response modifier' for the treatment of respiratory allergy, to be used in association with drug therapy and allergen avoidance. Its value in the treatment of these conditions has been established in position papers from the World Health Organization and the European Academy of Allergology and Clinical Immunology. Immunotherapy is usually administered subcutaneously (SCIT), and with this route several severe adverse events and fatalities have been described. Therefore, in the last 15 years, novel and safer routes of administration (local routes) have been developed. SLIT, in particular, has been investigated in 18 randomised controlled clinical trials. SLIT's clinical efficacy (improvement in symptoms and reduction in drug intake) in both asthma and rhinitis has been clearly assessed in 16 of these studies and for the most common allergens. SLIT's safety profile, derived from the clinical trials and from post-marketing surveillance studies, was shown to be satisfactory in both adults and children. The most frequently reported adverse events are gastrointestinal complaints, which can be avoided through appropriate dosage adjustment. For these reasons, SLIT has been accepted as a viable alternative to SCIT in recent position papers. The main advantages of SLIT are its safety (no severe systemic adverse event has ever been described) and good patient acceptance, especially in children; in addition, SLIT is a self-administered treatment that can be carried out at home by the patient. In contrast to injection immunotherapy, knowledge of the mechanisms of action of SLIT is still developing, albeit rapidly, although interesting data about its pharmacokinetics in humans are available. Data are also required concerning the possible preventive and long-lasting effects. SLIT is a viable alternative to SCIT, with the same rationale and indications. It is intended to be used in association with proper pharmacological treatment, at the earliest stages of the disease, for optimal management of respiratory allergy.

Administration, Sublingual↗
PubMed2001

Controlled study of preseasonal immunotherapy with grass pollen extract in tablets: effect on bronchial hyperreactivity.

BACKGROUND: Based on experimental results, the sublingual route for immunotherapy (IT) has been accepted as a viable alternative to the injection route, but few data on the effects on asthma are so far available. OBJECTIVE: In the present open controlled trial we evaluated whether a preseasonal IT with grass polllen in orosoluble tablets added to pharmacotherapy, can improve non-specific bronchial hyperreactivity. The clinical efficacy was evaluated as well. METHODS: Fifty-one patients (mean age 27.4 years) suffering from rhinoconjunctivitis and/or mild-intermittent/mild-persistent asthma due to grass pollen were allocated to two groups receiving pharmacotherapy alone (n = 25) or pharmacotherapy plus IT in tablets (n = 26). A methacholine test was performed in asthmatic subjects out of the pollen seasons at baseline and after 3 years of treatment. Symptom scores and drug intake were evaluated during pollen seasons by a diary card. RESULTS: A significant increase p = .01) in the PD20 at the methacholine test was observed in the IT group compared to the control group. A significant clinical improvement both for rhinitis (p = .001) and asthma (p = .001) was observed in the IT group, and this improvement was paralleled by a clear-cut reduction of drug intake (p = .001). An improvement of rhinitis symptoms without modification of drug intake was seen in the control group (p = .01) The treatment was well tolerated and no relevant side effect was reported during the 3 years. CONCLUSION: The investigated local IT reduced the nonspecific bronchial hyperreactivity. Furthermore, it was clinically effective and safe.

Adult↗
PubMed2001

Role of leukotriene receptor antagonists in the management of mild-to-moderate asthma.

To date the position of Leukotriene Receptor Antagonists (LTRAs) in asthma is not yet fully established. Recent asthma guidelines consider LTRAs as 'alternative' to low doses of inhaled corticosteroids (ICS) for treatment of patients with mild persistent asthma, while in Europe LTRAs are licensed as additional therapy to ICS. Our aim in this paper is to review comparative studies between ICS and antileukotrienes in mild to moderate asthma, looking at their efficacy on asthma outcomes and on patient expectations (compliance, quality of life, and safety). Some studies report a superior efficacy of ICS, while others, in particular in patients aged < 12 years, found no differences. When considering patients' expectations LTRAs seem to be superior, with higher compliance and quality of life. Even if no differences in adverse effects have been found between ICS and LTRAs, whose safety profiles are not different from placebo, some concerns exist on long term treatment with ICS, even at low doses, in children and postmenopausal women. For this reason, even if ICS are superior to LTRAs in controlling asthma outcomes and in improving pulmonary function, in children and elderly patients LTRAs can be considered an alternative to low-dose ICS.

Adrenal Cortex Hormones↗
PubMed2000

Cetirizine-induced downregulation of airway fibroblast proliferation and function: a rationale for a different approach to allergy treatment?

Recently, airway fibroblasts captured the attention of both allergists and basic scientists since they are no longer considered as mere bystanders, as far as allergic airway diseases are concerned. The aim of the present study was to assess the effects of different Cetirizine (Cet) concentrations (0.01, 0.05, 0.1 mg/ml) on human airway fibroblast proliferation and on CD54 expression. By means of flow cytometry analysis, we evaluated CD54 expression by airway fibroblasts in basal conditions or after gammaIFN stimulation in the presence of Cetirizine; we also evaluated the effect of the drug on cell proliferation by a [3H]thymidine incorporation assay. All of the tested doses of Cetirizine were able to significantly reduce CD54 upregulation induced by gammaIFN; concerning the fibroblast proliferation, we observed a dose-dependent inhibition of [3H]thymidine incorporation. These results show that Cetirizine exerts a biologic effect directly on human airway fibroblasts, suggesting a new rationale in the use of this compound.

Anti-Allergic Agents↗
PubMed2000

Minimal persistent inflammation is also present in patients with seasonal allergic rhinitis.

BACKGROUND: The allergic reaction is characterized by an inflammatory response, which is correlated to the allergen exposure, and is detectable in mite allergic patients, even when symptoms are absent. OBJECTIVE: The study was aimed at assessing the presence of inflammation in patients with pollen allergy during a long observation period. METHODS: Six patients, sensitized only to Betula alba, were enrolled. Evaluated parameters were (1) nasal symptoms, (2) inflammatory markers (ie, neutrophil and eosinophil number and intercellular adhesion molecule-1 expression on nasal epithelial cells), and (3) pollen count. Patients were examined during the pollen season every 4 days for 40 days and were observed 3 times after the pollen season. RESULTS: A significant inflammatory reaction was evident throughout the pollen season, even during the days with a low pollen count and low or absent symptoms. CONCLUSIONS: The results of this study indicate that the global therapeutic strategy for allergic rhinitis should be revised and targeted to inflammatory phenomena rather than to symptoms alone.

Adolescent↗
PubMed2000

Quantitative flow cytometric analysis of the effects of cetirizine on the expression of ICAM-1/CD54 on primary cultured nasal cells.

An in vitro flow cytometric model has been developed to evaluate the effects of antiallergic drugs such as cetirizine (CTZ) on the expression of surface molecules on primary cultured normal cells. Quantitative analysis demonstrated that HLA class I and ICAM-1/CD54 molecules are present on both epithelial and stromal cells, and that their expression is strongly enhanced by treatment with interferon-gamma (IFN-gamma). Nevertheless, the IFN-gamma-mediated upregulation of ICAM-1/CD54 was inhibited by treatment with CTZ, demonstrating a direct effect on both cell types. This finding is particularly interesting because ICAM-1/CD54 is the main rhinovirus receptor, and rhinoviruses are the principal cause of asthma exacerbation in children. Thus, according to data derived from this in vitro model, CTZ should have an important role in the reduction of infectious exacerbation of asthma in atopic patients.

Adult↗
PubMed2000

Sublingual IT in OAS.

Explore the source record for details and available documents.

Administration, Sublingual↗
PubMed2000

Modulation of airway caliber by deep inhalation in children.

To elucidate whether deep inhalation (DI) modulates changes in airway caliber in childhood, we measured the effect of DI on respiratory impedance before and after inhaled methacholine or salbutamol in 4- to 7-yr-old children (n = 15) suffering from recurrent wheezing. In all children, the real part of impedance between 12 and 16 Hz (Re[Z](12-16)) increased after methacholine from 5.6 +/- 1.2 to 8.2 +/- 1.6 cmH(2)O. l(-1). s (P < 0.001) and resonance frequency from 18 +/- 3 to 25 +/- 5 Hz (P < 0.001). These changes were partially reversed by DI: Re[Z](12-16) decreased to 7.2 +/- 1.2 cmH(2)O. l(-1). s (P < 0.01) and resonance frequency to 19 +/- 5 Hz (P < 0.001). In nine children, on a separate occasion, Re[Z](12-16) decreased after salbutamol from 8.3 +/- 1.9 to 5.1 +/- 0.9 cmH(2)O. l(-1). s (P < 0.001) and resonance frequency from 21 +/- 6 to 15 +/- 3 Hz (P < 0.05). The decrease of Re[Z](12-16) was partially reversed by DI (to 6.2 +/- 1.4 cmH(2)O. l(-1). s, P < 0. 01), but resonance frequency did not change significantly (P = 0.75). We conclude that in 4- to 7-yr-old children pharmacologically induced changes in airway caliber are modulated by DI. These findings suggest that airway-to-parenchyma interdependence is operative in this age range.

Airway Resistance↗
PubMed2000

Effects of mizolastine in vitro on human immunocompetent and airway cells: evidence for safety and additional property.

BACKGROUND: Mizolastine is a potent, peripherally acting, selective H1-receptor antagonist with potential anti-inflammatory properties. The aim of the study was to evaluate the in vitro effects of mizolastine on the expression of adhesion molecules by primary human airway epithelial and stromal cultures; moreover, the activity of mizolastine on parameters which reflect the immune response efficacy was investigated. METHODS: Airway epithelial and stromal cells were collected from hypereosinophilic subjects by enzymatic digestion of polyps or turbinates. Cells were stimulated with interferon (IFN)-gamma (500 IU/ml) in the presence of various mizolastine concentrations (6 x 10(-8)-6 x 10(-6) M) for 24 h and the expression of CD106, CD54, CD58 and HLA class I was evaluated. Peripheral blood mononuclear cells from healthy volunteers were incubated with 1% phytohemagglutinin or anti-CD3 monoclonal antibody (20 ng/ml) in the presence of mizolastine, then T lymphocyte proliferation, HLA-DR expression and T cell subpopulations were evaluated. RESULTS: Both in epithelial and stromal cultures, IFN-gamma significantly upregulated all of the tested surface molecules (p<0.05). The highest dose of mizolastine (6 x 10(-6) M), corresponding to 10-fold the peak plasma level after a single oral administration of 10 mg, was able to act on fibroblasts, significantly downregulating the expression of CD54 (p<0.05). Regarding T lymphocyte proliferation, the addition of mizolastine did not induce any significant change; furthermore, mizolastine was ineffective at all of the tested concentrations on both HLA-DR expression and CD4+/CD8+ ratio. CONCLUSIONS: This study demonstrated that mizolastine is able to selectively downregulate CD54 expression on stimulated stromal but not epithelial cells without impairing the immune system effectors. The possible clinical significance of these results are an antiallergic property and CD54 modulation on fibroblasts with a good safety profile as far as the lymphocyte response is concerned.

Adolescent↗
PubMed2000

Relationship between degree of nonspecific hyperresponsiveness and number of positive skin tests in asthmatics.

Bronchial hyperresponsiveness (BHR) is a typical feature of asthma, and is, at least in part, related to the chronic inflammation. Allergen exposure is a major trigger and cause of allergic inflammation. The possible relationship between the degree of bronchial reactivity and the number of positive skin test was studied. One hundred and one patients with allergic asthma (and rhinitis) underwent skin-prick tests and methacholine bronchial challenge according to standard protocols. No significant relation was found between the degree of BHR and age or sex. Conversely, it was found that the number of positive skin tests correlated well with the degree of BHR (p = 0.046); in particular, those patients with three or more sensitivities showed greater bronchial reactivity. The present data support the hypothesis that allergic polysensitized patients may exhibit greater bronchial hyperresponsiveness, possibly due to an enhanced inflammatory component related to the exposure to multiple allergens.

Adolescent↗
PubMed2000

Evaluation of the effects of zafirlukast 40 mg b.i.d. in addition to preexisting therapy of high-dose inhaled steroids on symptomatic patients with reversible respiratory obstruction: preliminary data.

Clinical evidence of the efficacy of zafirlukast is available for mild-to-moderate asthma, but further evidence is needed on its use in the more severe forms, uncontrolled by traditional therapy. The aim of this study was to evaluate the efficacy of zafirlukast 40 mg b.i.d. as an add-on to high dose inhaled corticosteroids (HDICs). A secondary aim was to assess the drug's safety and the patients' evaluation of oral therapy and compliance. Twenty-two asthmatic patients (13 females, aged 12-70 years) taking short-acting beta 2-agonists as needed and HDICs as maintenance therapy, entered a 2-week screening phase. At the end, 18 patients with baseline forced expiratory volume (FEV)1 = 50-80% of predicted, a reversibility of > or = 15% and a > or = 10 weekly total of daytime symptom score, were given zafirlukast 40 mg b.i.d. and were reevaluated every 4 weeks for 12 weeks. Adverse events, withdrawals and changes in hematology were recorded. A diary and a questionnaire were used for subjective patient assessment. Sixteen patients (nine females, mean age 40) completed the study. Mean FEV1, (absolute value and percentage vs. predicted) was significantly higher (p < 0.05) vs. baseline after zafirlukast, with a mean improvement of 0.2 l/sec (2.4 vs. 2.2) or 6% (76% vs. 70%) of predicted. Similarly, a significant (p < 0.001) increase in peak expiratory flow was observed (6 vs. 5.5 l/sec). There was no statistically significant variation in forced expiratory flow 25-75. Analysis of the diaries showed a statistically significant reduction (p < 0.05) of morning symptoms (0.73 vs. 4.6) and of daytime symptoms score (2.3 vs. 5.3). There was no evidence of improvement in night time symptoms and use of beta 2-agonists. Three patients experienced adverse events and four suffered a single exacerbation not requiring hospital admission. Subjective evaluation was positive: 75% reported an improvement, 25% found no change and 40% particularly appreciated the oral therapy. In conclusion, treatment with zafirlukast (40 mg b.i.d.) showed a significant improvement in function parameters and symptoms. Zafirlukast was well tolerated and accepted by patients. Further research is needed, as the small number of patients does not allow definitive conclusions to be drawn.

Administration, Inhalation↗
PubMed1999

Distinct regulation of HLA class II and class I cell surface expression in the THP-1 macrophage cell line after bacterial phagocytosis.

Expression of HLA and CD1b molecules was investigated in the THP-1 macrophage cell line within 2 weeks following phagocytosis of mycobacteria or Escherichia coli. During the first 2-3 days, cell surface expression of HLA class II and CD1b was drastically down-modulated, whereas HLA class I expression was up-modulated. In the following days both HLA class II and CD1b expression first returned to normal, then increased and finally returned to normal with kinetics similar to that observed for the steadily increased HLA class I. The initial down-modulation of HLA class II and CD1b cell surface antigens was absolutely dependent on phagocytosis of bacteria. Further studies indicated that initial HLA class II cell surface down-modulation (1) was not due to reduced transcription or biosynthesis of mature HLA class II heterodimers, (2) was only partially, if at all, rescued by treatment with IFN-gamma, although both mRNA and corresponding intracellular proteins increased up to sixfold with respect to untreated cells, and (3) resulted in failure of THP-1 cells to process and present mycobacterial antigens to HLA-DR-restricted antigen-specific T cell lines. The existence of a transient block of transport of mature HLA class II heterodimers to the cell surface in the first days after phagocytosis of bacteria may have negative and positive consequences: it decreases APC function early but it may increase it later by favoring optimal loading of bacterial antigens in cellular compartments at high concentration of antigen-presenting molecules.

Antigen Presentation↗