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G W Canonica

Publications and source records attributed to G W Canonica.

At least 127 records · Page 7Linked to original sources
PubMed1998

Local immunotherapy.

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Drug Administration Routes↗
PubMed1998

Allergen-specific nasal challenge: response kinetics of clinical and inflammatory events to rechallenge.

Allergen-specific nasal challenge is a valid and reliable tool for studying the pathophysiological mechanisms involved in allergic inflammation. Nasal challenge induces an immediate clinical response in allergic subjects and a concomitant appearance of an inflammatory infiltrate. The mucosal inflammation may persist up to 48-72 h after allergen exposure. If the subjects are rechallenged within this period the response is more pronounced: the so-defined priming effect. The aim of the study was to evaluate the effects of the nasal rechallenge, performed at different time intervals: 3 days, 1, 2 and 4 weeks after the first challenge. Forty allergic subjects underwent two nasal challenges: at baseline and after the periods mentioned above (10/group). Symptoms and inflammatory cells (eosinophils and neutrophils recovered by nasal brushing) were assessed. The 3-day-interval group showed a hyperreactive response (priming effect), the 1- and 4-week-interval groups showed a response similar to baseline, and the 2-week-interval group showed a hyporeactive response ('tolerogenic effect'). The last phenomenon may be due to a possible immunologic response similar to that achievable during local specific immunotherapy. The present results further elucidate the kinetics of allergen-driven inflammatory events and highlight the importance of the time period chosen for rechallenge. The latter fact may be of primary importance in clinical trials involving specific challenge.

Adolescent↗
PubMed1997

Seasonal rhinitis and azelastine: long- or short-term treatment?

BACKGROUND: Azelastine is a topical antihistamine, clinically demonstrated to be effective in allergic rhinitis. OBJECTIVE: We evaluated the clinical efficacy and the antiallergic activity of azelastine nasal spray, administered 0.56 mg per day, 0.28 mg per day, or on demand over a 3-month period during natural allergen exposure, in a double-blind, placebo-controlled fashion. METHODS: Thirty patients, sensitized to grass or Parietaria pollen, were allocated to three treatment groups: those receiving the standard dosage (0.14 mg/nostril two times a day), half the dosage (0.07 mg/nostril two times a day), or placebo daily for 3 months. All patients were allowed to take additional doses of azelastine when needed. Evaluation parameters were as follows: clinical symptoms recorded on a diary card, number of additional, on-demand azelastine puffs, nasal inflammatory cell count, intercellular adhesion molecule-1 expression on nasal epithelial cells, and pollen count. RESULTS: This study showed the following: (1) the half dose (0.28 mg/day) and the standard dose (0.56 mg/day) were equally effective in reducing clinical symptoms (p = NS), although the standard dosage required fewer additional puffs during times of peak pollen counts (p < 0.05); (2) both dosages were able to reduce the allergic inflammation (p < 0.05 vs placebo); and (3) on-demand use achieved acceptable clinical control but did not significantly reduce allergic inflammation. CONCLUSION: Continuous treatment was more effective than on-demand use as assessed by both clinical evaluation and antiinflammatory action.

Administration, Intranasal↗
PubMed1997

Absorption and distribution kinetics of the major Parietaria judaica allergen (Par j 1) administered by noninjectable routes in healthy human beings.

BACKGROUND AND OBJECTIVE: The clinical effectiveness of noninjectable routes for specific immunotherapy has been demonstrated in many studies, but no data are available on the kinetics of allergens administered by these routes. Therefore we studied the kinetics of the radiolabeled purified major Parietaria judaica allergen (Par j 1) after sublingual, oral, and intranasal administration to healthy human beings. METHODS: After tracer administration (10 to 12.5 microg of Par j 1 labeled with iodine 123) to nonallergic volunteers, scintigraphic images were recorded at various times. Blood samples were also obtained at serial intervals to evaluate the absorption and distribution of radioactivity in plasma and to identify circulating radioactive species by molecular exclusion gel chromatography. RESULTS: When the sublingual route was used, no circulating radioactivity was detected until the tracer was kept under the tongue. The labeled allergen was rapidly degraded and absorbed in the gastrointestinal tract after swallowing. Plasma radioactivity peaked at about 1.5 to 3 hours and was mostly represented by free radioiodine and small radiolabeled peptides. Some activity not caused by free 123I remained associated with the oral mucosa up to 18 to 20 hours after administration. When the oral route was used, the results were similar to those observed after swallowing the sublingually administered allergen but without any persistence of the tracer in the mouth. When the intranasal route was used, the pattern of plasma radioactivity mimicked that of the sublingual and oral routes, with absorption of activity from the radiolabeled allergen occurring in the gastrointestinal tract after transport to the pharynx by mucociliary clearance. A relevant fraction of the tracer was retained on the nasal mucosa up to 48 hours after administration. CONCLUSION: The data in this study provide the first experimental basis for exploring the in vivo kinetics of allergen administered through noninjectable routes for specific immunotherapy in human beings.

Abdomen↗
PubMed1997

Continuous versus on demand treatment with cetirizine for allergic rhinitis.

BACKGROUND: Cetirizine is an antihistamine used in the treatment of allergic rhinoconjunctivitis, that has antiallergic activity. OBJECTIVE: The aim of this double-blind, placebo-controlled, parallel group study was to evaluate the clinical efficacy and the antiallergic activity of cetirizine, administered either continuously or on demand over a 4-week period of natural allergen exposure. METHODS: Twenty patients, with allergic rhinoconjunctivitis due to grass and/or Parietaria pollen, were enrolled. They were randomized into 2 parallel groups: one group received the standard dose of 10 mg cetirizine daily and the other received placebo, all patients were allowed to take an additional daily dose of cetirizine when needed. Variables evaluated were clinical symptoms (recorded on diary cards), number of additional on demand cetirizine doses, nasal inflammatory cells, and pollen counts. RESULTS: The results of the present study show that patients treated with continuous administration of cetirizine achieved significant symptomatic relief and inflammatory control (decreases in numbers of infiltrating neutrophils and eosinophils) in comparison to patients treated on demand. CONCLUSION: Continuous treatment with cetirizine is more effective than on demand treatment. Continuous treatment reduces clinical and inflammatory variables more than symptomatic treatment and the on demand therapy can determine acceptable clinical control, but does not reduce allergic inflammation.

Adult↗
PubMed1997

Cetirizine treatment of allergic cough in children with pollen allergy.

Cetirizine, an antihistamine widely used in the treatment of allergic rhinoconjunctivitis, also has antiallergic activity. The present study aimed to evaluate cetirizine as a treatment for children with allergic cough due to pollen allergy. This was a parallel-group, double-blind, placebo-controlled, randomized study. Twenty children with pollinosis were enrolled: they were subdivided into two groups receiving a 1-month treatment during the pollen season. The following variables were monitored: 1) clinical symptoms and respiratory data (spirometry and PEF) evaluated at baseline and at the end of the study by allergists and by a daily diary card, and 2) pollen count. This study shows that cetirizine treatment reduces cough intensity (P < 0.05) and frequency (P < 0.01). In conclusion, cetirizine does clinically improve cough due to pollen allergy.

Adolescent↗
PubMed1997

Inhibition of adhesion molecules by budesonide on a human epithelial cell line (lung carcinoma).

Inhaled corticosteroids in the treatment of asthma have been shown to produce marked reductions in the number of inflammatory cells (mainly mast cells and eosinophils) and their products at bronchial level (such as cytokines). Recently, it has been demonstrated that epithelial cells express ICAM-1/CD54 in allergic patients both during natural allergen exposure and after allergen challenge. We have previously demonstrated that deflazacort (a systemic steroid) reduces the expression of ICAM-1 on conjunctival epithelial cells. The present study aimed to evaluate the effects exerted by budesonide on adhesion molecule expression by a human epithelial cell line (lung carcinoma: DM) and on soluble ICAM-1. Budesonide was added at concentrations corresponding to 10(-8), 10(-7), and 10(-6) mol/l in cultured epithelial cells, either in the absence of any stimulus or in the presence of interferon-gamma (IFN-gamma) at 500 U/ml. After 24 h of incubation, cytofluorometric analysis was performed for ICAM-1 and CD29/VLA beta 1. The 24-h supernatants of the same cultures were collected and then evaluated for soluble ICAM-1 (sICAM-1). The results showed that budesonide inhibits ICAM-1 and CD29 basal expression on the cells studied (P < 0.05): budesonide was effective in a dose-dependent manner. In addition, budesonide reduced surface ICAM-1 upregulation induced by IFN-gamma at 500 U/ml (P < 0.05). Finally, cell cultures with budesonide showed decreased levels of soluble ICAM-1 in basal condition, but not after IFN-gamma stimulation.

Anti-Inflammatory Agents↗
PubMed1997

Aerobiologic particle sampling by a new personal collector (Partrap FA52) in comparison to the Hirst (Burkard) sampler.

A new personal portable sampler of biologic particles (Partrap FA52, Coppa, Biella, Italy) was used for pollen sampling in comparison with Hirst's (Burkard) fixed device. The aerobiologic samplings were carried out simultaneously outdoors with the two devices coupled on the same axis, during the daytime of 10 dry, nonconsecutive spring days. The total amount and the percentages of the pollens most often trapped by the two collectors were compared by Student's t-test for paired samples. The Partrap FA52 showed a highly significant efficacy, quite comparable to that of the Burkard device, in pollen trapping for both the total number (P < 0.0001) and the percentages of Parietaria (P < 0.0001), pine (P < 0.002), and grass (P < 0.0001) pollens. Therefore, Partrap FA52 proved to be highly effective in obtaining quantitative and qualitative aerobiologic samples in comparison with the commonly used fixed samplers.

Air Pollution↗
PubMed1997

Intercellular adhesion molecule-1 on cultured human epithelial cell lines: influence of proinflammatory cytokines.

The expression of intercellular adhesion molecule-1 (CD54 or ICAM-1) on epithelial cells during acute or chronic inflammation may favor the interaction between epithelial cells and leukocytes expressing the natural ligands of ICAM-1, LFA-1 (CD11a/CD18), and Mac-1 (CD11b/CD18). We have evaluated in vitro the expression of ICAM-1 by a conjunctival (WK) and an intestinal (I407) human continuous epithelial cell line. Cells were cultured for 24 h in the presence or absence of IFN-gamma, TNF-alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, and TGF-beta 1. Both epithelial cell lines showed a constitutive expression of ICAM-1. IFN-gamma at 500 U/ml and TNF-alpha at 200 ng/ml upregulated ICAM-1 expression; IL-1 beta at 100 pg/ml upregulated ICAM-1 on WK cells only. Cells cultured in the presence of both IFN-gamma and TNF-alpha exhibited a mean fluorescence intensity far greater than those cultured with IFN-gamma or TNF-alpha alone. I407 and WK cells were able to release soluble ICAM-1. IFN-gamma and TNF-alpha enhanced the release of sICAM-1. IL-4, IL-6, IL-8, IL-10, and TGF-beta 1 did not affect either ICAM-1 expression or sICAM-1 release. In conclusion, continuously cultured human epithelial cells may express ICAM-1 on their surface and release it in culture medium. These phenomena are upregulated by proinflammatory cytokines.

Cell Adhesion↗
PubMed1997

Local nasal immunotherapy: experimental evidences and general considerations.

The possibility of local hyposensitization in allergies was envisaged since the first decades of the century and then sporadically employed, whereas controlled clinical trials of local nasal immunotherapy (LNIT) were performed only during the last 20 years. Studies currently available agree on the clinical efficacy of the treatment. LNIT was demonstrated capable of reducing symptoms both in pollen- and mite-induced rhinitis, and of modifying the specific target organ responsivity. Indeed, aqueous extracts appeared to be more effective than modified ones but were also charged by troublesome local side effects, while the recently introduced powdered extracts seemed to overcome this problem, maintaining a favourable clinical effectiveness. In a recent study we demonstrated a significant effect of LNIT on local allergic inflammation. LNIT reduced both the inflammatory infiltration and ICAM-1 expression on nasal epithelial cells upon specific nasal challenge. The effects on specific challenge appeared long-lasting, but the clinical efficacy seemed to depend strictly upon preseasonal treatment. LNIT with powdered extracts appears an effective, safe and well-tolerated treatment for allergic rhinitis. Nevertheless, its particular administration technique requires a careful choice of patients. Finally, a socioeconomical analysis shows a favourable cost/benefit ratio for LNIT if compared to classic subcutaneous immunotherapy.

Administration, Intranasal↗
PubMed1997

Molecular events in allergic inflammation: experimental models and possible modulation.

In recent years, a complex molecular network involving cytokines kinins and adhesion molecules has been demonstrated to operate in allergic inflammation. In particular, the adhesion machinery plays a crucial role for the recruitment and locomotion of the inflammatory cells and the Intercellular Adhesion Molecule 1 (ICAM-1) is a hallmark of the allergic inflammatory process. The role and possible modulation of ICAM-1 can be investigated using both eye and nose experimental models. Conjunctival and nasal epithelium are easy to study either under natural allergen exposure or after specific/aspecific provocation tests; furthermore the nasal/conjunctival challenge is well tolerated by the patients. These experimental models have allowed us to investigate in vivo the antiallergic properties of several compounds. Many of the new antihistamines, but also deflazacort and local nasal immunotherapy, were demonstrated capable of reducing both inflammatory infiltration and ICAM-1 expression on epithelia. Because of the central role of adhesion molecules in allergic inflammation, their pharmacological modulation can be regarded as a promising therapeutic approach.

Anti-Inflammatory Agents↗
PubMed1997

Allergen-specific conjunctival challenge in asthma. An additional diagnostic tool to define sensitization.

Reversible airway obstruction and airway inflammation following allergen exposure represent crucial pathophysiological features of allergic asthma. In order to investigate these events, bronchial-specific challenge is commonly employed although it may be complicated and may not be free of possible risks. Therefore, we evaluated the applicability of allergen-specific conjunctival challenge (ASCC) in adults with asthma to define the diagnosis of specific sensitization and the grade of specific sensitization, and to detect the presence of allergic inflammation. As recently described, conjunctival challenge represents an easy diagnostic tool in allergic inflammation. We studied 30 symptomless patients with a history of mild asthma, including 20 allergic patients, 10 females and 10 males (18-48 years old), sensitized to Parietaria judaica only, with a history of recurrent asthma attacks during seasonal natural exposure to allergen, 10 nonallergic patients, 7 females and 3 males (28-55 years old), with a history of recurrent asthma attacks unrelated to any allergen exposure, and 10 healthy volunteers as controls. The study was performed outside the pollen season. The ASCC induced a highly significant early-phase clinical reaction and a highly significant inflammatory cell infiltrate in the asthmatic patients sensitized to P. judaica when compared to other study groups (p < 0.001). The ASCC showed as 100% sensitivity, specificity, predictive value of positive and negative results in the group of sensitized asthmatic patients when compared to unsensitized ones and to healthy subjects. The study confirms the reproducibility and usefulness of ASCC to diagnose allergy and to define its grade. These data strongly suggest ASCC employment also in patients with a single history of allergic asthma.

Adolescent↗