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Biomedical subjects

Giorgio Walter Canonica

Publications and source records attributed to Giorgio Walter Canonica.

At least 19 recordsLinked to original sources

New insights in sublingual immunotherapy.

Sublingual immunotherapy (SLIT) is accepted in the official documents and is currently used in many European countries. In recent years, new clinical data on efficacy and safety have been published, including meta-analyses in adults and children and surveys of safety in children younger than age 5 years. Moreover, it has been shown that, similar to the injection route, SLIT can prevent the onset of new sensitizations and the onset of asthma. Additionally, the mechanisms of action are beginning to be systematically studied. Some points need further investigation, such as the effect in asthma, the mechanisms of action, and the optimal dose to be administered.

Administration, Sublingual↗

Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials.

OBJECTIVE: To evaluate the efficacy of sublingual immunotherapy (SLIT) in the treatment of allergic rhinitis in children. DATA SOURCES: A comprehensive search of the EMBASE, MEDLINE, LILACS, and CINAHL databases from January 1966 to February 10, 2006, was performed. STUDY SELECTION: Randomized, double-blind, placebo-controlled trials of SLIT in the treatment of allergic rhinitis in patients 18 years or younger were selected. Outcomes measured were symptom scores and rescue medication use. Analysis was performed with standardized mean differences (SMDs) and a random-effects model. RESULTS: Seventy articles were identified and reviewed. Ten studies, published between 1990 and 2004, fulfilled the selection criteria. Five hundred seventy-seven patients were initially included in the studies. Of these patients, 484 (245 SLIT and 239 placebo) had a final clinical evaluation and could be evaluated. A relevant heterogeneity due to widely differing scoring systems was found. Overall, there was a significant reduction in both symptoms (SMD, 0.56, 95% confidence interval, 1.01-0.10; P = .02) and medication use (SMD, 0.76; 95% confidence interval, 1.46-0.06; P = .03) after immunotherapy. The subanalyses performed for treatment duration and type of allergen showed that SLIT for more than 18 months and with pollen extracts was effective compared with SLIT courses shorter than 18 months and with mites. CONCLUSION: The results of this meta-analysis showed that,compared with placebo, SLIT with standardized extracts is effective in pediatric patients with allergic rhinitis.

Administration, Sublingual↗

Allergic diseases and their impact on quality of life.

OBJECTIVE: To review the results of studies that have evaluated the impact of allergic diseases on patients' health-related quality of life (HRQL). DATA SOURCES: We performed a MEDLINE search of the literature published between January 1990 and May 2006 (English language only) on HRQL and allergic diseases. STUDY SELECTION: Representative studies that used validated questionnaires that assessed the effect of allergic diseases on HRQL were selected for inclusion in this review. RESULTS: Allergic diseases can deeply interfere with patients' HRQL, with detrimental effects on the physical, psychological, and social dimensions of life. Numerous validated questionnaires that are now available can easily be adopted; most of them are specifically developed for rhinitis and asthma. CONCLUSIONS: HRQL has become an increasingly important aspect in outcome evaluation in health care research, providing a more comprehensive approach to the patient and proving that nowadays we cannot renounce this tool. Most of the studies evaluate patients with respiratory allergy. Further studies are needed to explore HRQL in other allergic conditions (urticaria, food allergy, sting allergy, drug allergy) by means of specific, validated questionnaires.

Adolescent↗

Economic evaluation of sublingual immunotherapy vs symptomatic treatment in adults with pollen-induced respiratory allergy: the Sublingual Immunotherapy Pollen Allergy Italy (SPAI) study.

BACKGROUND: Few data are available on the pharmacoeconomic aspects of immunotherapy. OBJECTIVE: To evaluate, from the health care system and societal perspectives, the costs and consequences of sublingual immunotherapy (SLIT) added to pharmacotherapy compared with drugs alone for respiratory allergy. METHODS: This study compared costs, clinical outcomes, and cost-effectiveness ratios of 2 strategies in the management of allergic rhinitis and asthma, namely, SLIT associated with pharmacotherapy and pharmacotherapy alone (no SLIT). A decision tree was developed and populated with epidemiologic and resource utilization data concerning approximately 2,200 patients. Direct costs included visits, tests, pharmacotherapy, immunotherapy, and hospitalizations. Indirect costs and out-of-pocket drugs were also included. Outcome was calculated as the number of improved patients and asthma cases avoided at 6 years. Sensitivity analysis was performed by varying costs and epidemiologic data. RESULTS: SLIT improved the symptoms of 399 of 1,000 patients and prevented asthma in 229 of 1,000 patients compared with drugs alone. For SLIT added to pharmacotherapy and pharmacotherapy alone, the direct cost per patient at more than 6 years was Euro2,400 and Euro3,026, whereas the indirect cost was Euro1,913 and Euro3,400. CONCLUSION: From both perspectives and for both effectiveness end points, SLIT is less expensive and more effective than pharmacotherapy alone.

Administration, Sublingual↗

Sublingual immunotherapy: update 2006.

PURPOSE OF REVIEW: Sublingual immunotherapy is currently accepted as a viable therapeutic option, and is widely used in many European countries. In the past 2 years, new data concerning clinical, immunological and practical aspects of sublingual immunotherapy have been published, and many critical points have been addressed. RECENT FINDINGS: In addition to the new data on clinical efficacy, the most recent studies have shown that, similar to the injection route, sublingual immunotherapy can also prevent the onset of new sensitizations and the onset of asthma. Moreover, several postmarketing surveys have confirmed the satisfactory safety profile, even in very young children, and compliance has been measured. The good safety profile has also suggested the possibility of using sublingual immunotherapy without the updosing phase. Finally, the mechanisms of action have been systematically investigated and the biodistribution of sublingual allergens has been further clarified. SUMMARY: More new data on sublingual immunotherapy are rapidly appearing in the international literature. These data consistently confirm the value of this treatment and show that sublingual immunotherapy is a viable and useful form of immunotherapy.

Administration, Sublingual↗

Safety profile of sublingual immunotherapy.

Sublingual immunotherapy (SLIT) was proposed for clinical practice about 20 years ago with the main aim of improving the safety and avoiding the adverse effects of traditional treatment for allergic airways disease. To date, 32 randomized controlled trials and 6 postmarketing surveys have been published that provide a robust documentation of the safety profile of the treatment.Looking at the randomized trials it emerges that the more frequent adverse event of SLIT is oral itching or swelling, followed by gastrointestinal complaints. These adverse events are invariably described as mild and easily managed by adjusting the dose. Relevant systemic adverse events (asthma, urticaria, angioedema) occur sporadically and, with the exception of oral/gastrointestinal adverse events, the incidence of adverse events seems not to differ between the placebo and active groups. The safety profile of SLIT does not differ between adults and children.The postmarketing surveys consistently show that the incidence of adverse events associated with SLIT is less than 10%, corresponding to less than 1 adverse event per 1000 doses, and is thus quite superior to the safety profile of subcutaneous immunotherapy. Of note, the most recent data show that the rate of adverse events with SLIT is not increased in children below the age of 5 years.

Administration, Sublingual↗

Non-injection routes for allergen immunotherapy: focus on sublingual immunotherapy.

Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The non-injection or local routes were developed with the main goal of improving the safety and minimizing the risk of those side effects, which can accompany the injection route. The pure oral route and the bronchial route showed, in the clinical trials, only a marginal efficacy with not negligible side effects. Therefore, these routes are no longer recommended for clinical use. The nasal route proved effective and safe, but its efficacy is strictly limited to the nose. Moreover, the practical problems with administration have made the use of nasal immunotherapy progressively declining. The efficacy of the sublingual route is confirmed by numerous controlled trials, and a meta analysis (in allergic rhinitis). The safety profile, as derived from clinical trials and post marketing surveillance studies, is satisfactory, with mild gastrointestinal complaints being the more frequent side effect reported. Recent studies have also demonstrated that SLIT has a long-lasting effect and a preventive effect on the onset of new skin sensitizations, and interesting data on adherence and mechanisms of action have become recently available. Based on these experimental data, SLIT is now officially accepted as a viable alternative to the subcutaneous route in adults and children. Several points still need to be elucidated, including: mechanisms of action, optimal dosages, and indications in pediatric patients.

Administration, Inhalation↗

Asthma mortality, inhaled steroids, and changing asthma therapy in Argentina (1990-1999).

BACKGROUND: The asthma managing strategy has evolved and inhaled corticosteroids (ICS) are now the cornerstone of asthma treatment. Their effect on symptoms and exacerbations are well ascertained, whereas their effects on asthma mortality are still matter of debate. This ecological study evaluated asthma mortality rates and drug sales in the decade 1990-1999 in Argentina. METHODS: Mortality (overall and adjusted for 5-34 years) was obtained from the Argentinean Epidemiological Institute, and data on the sales of antiasthma drugs were provided by the International Marketing Survey. RESULTS: There was a significant change in drug sales in the spanned period: ICS +479%, inhaled beta2 agonists +32%, theophylline -63%. The crude and adjusted mortality rates were 3.38 and 0.72 in the 1980-1989 decade, and 2.58 (P<0.05) and 0.38 (P<0.01) in the subsequent one. There was inverse correlation between inhaled corticosteroid sale and age-adjusted (5-34) asthma mortality (r=-0.84; P=0.003), and the same with global mortality rates (r=-0.81; P=0.005). A positive correlation was also seen between theophylline sales and mortality. CONCLUSION: The increased sale of ICS and possibly the decrease of theophylline use seem to be the more relevant factors associated with decreased asthma mortality in Argentina.

Administration, Inhalation↗

Pharmacokinetics of Der p 2 allergen and derived monomeric allergoid in allergic volunteers.

BACKGROUND: Presently, sublingual immunotherapy is widely used as an alternative to the injection route for respiratory allergy, but its pharmacokinetics in humans is poorly known, and data are available only for Par j 1 allergen. We aimed at assessing the biodistribution of iodine-123-radiolabelled Der p 2 in allergic volunteers. METHODS: Purified Der p 2 and its monomeric allergoid were radiolabelled with iodine-123 and administered sublingually to 7 allergic volunteers. The subjects were allowed to swallow 6 min after administration. Dynamic (up to 10 min) and static scintigraphic images (30 min, 1, 2, 3 and 20 h) were recorded, and blood samples were obtained at different time points to measure the plasma radioactivity and to assess the presence of circulating radiolabelled species by gel chromatography. RESULTS: The local pharmacokinetics did not differ between allergen and allergoid. Plasma radioactivity began to increase only after swallowing and peaked at 1-2 h. Both the allergen and the allergoid persisted in the mouth for several hours, and traces could be detectable up to 20 h. At radioactivity plasma peak, gel chromatography showed that a fraction of the allergoid, but not the allergen, was absorbed as an intact molecule. CONCLUSIONS: These results indicate that the pharmacokinetics of sublingual administration is independent of the allergen used and characterized by the long persistence in the mouth. The contribution of enteric absorption of the allergoid in the mechanism of action of sublingual immunotherapy remains to be defined.

Administration, Sublingual↗

A review of the evidence from comparative studies of levocetirizine and desloratadine for the symptoms of allergic rhinitis.

BACKGROUND: Levocetirizine and desloratadine are newer antihistamines indicated for the treatment of allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: This article discusses the pharmacokinetics and pharmacodynamics of levocetirizine and desloratadine and reviews studies that have directly compared the effects of these 2 drugs in allergic rhinitis and urticaria. METHODS: Relevant articles were identified through a search of MEDLINE from 1999 through 2004 using the main search terms levocetirizine and desloratadine. RESULTS: Levocetirizine is absorbed rapidly and reaches a steady-state plasma concentration more quickly than does desloratadine. It is also metabolized to a lesser extent than desloratadine, has a lower V(d), and has higher specificity for histamine(1) receptors. Eight well-controlled trials were identified that directly compared the effects of levocetirizine and desloratadine in the skin and nose of healthy individuals and patients with allergic rhinitis. Drug activity was measured in terms of wheal, flare, and itch reactions; nasal symptoms or symptom scores; increases in concentrations of inflammatory markers; or facial thermography. In most of these trials, levocetirizine had a faster onset and greater consistency of effect than desloratadine. The differences in the pharmacokinetic and pharmacodynamic profiles of the 2 drugs may partially explain these clinical findings. CONCLUSIONS: Levocetirizine may be preferred to desloratadine as a treatment option for allergic rhinitis because of its faster onset of action and greater consistency of effect. Although comparative studies in chronic idiopathic urticaria are not available, data from histamine-induced wheal and flare studies in healthy volunteers suggest that levocetirizine may be more effective in preventing itching than desloratadine.

Cetirizine↗

Clinical, functional, and immunologic effects of sublingual immunotherapy in birch pollinosis: a 3-year randomized controlled study.

BACKGROUND: Sublingual immunotherapy (SLIT) has been proved effective in allergic rhinitis, but there are few studies assessing its effects on inflammation and on the lower airways. OBJECTIVE: We sought to evaluate at the same time the effects of SLIT on rhinitis symptoms, nasal inflammation, and lower airways function in patients with birch pollinosis. METHODS: Adult patients with rhinitis and asthma monosensitized to birch were evaluated during a run-in pollen season and then randomized to receive openly either drugs alone or drugs plus SLIT and reevaluated in the subsequent 4 pollen seasons. Rhinitis symptoms and consumption of bronchodilators were assessed by means of diary card. A nasal smear for eosinophil count was carried out in and out of pollen seasons, and pulmonary function tests with methacholine challenge were performed at each season. RESULTS: Of 79 enrolled patients, 27 dropped out, with a significantly higher rate of dropouts in the control group. There was a decrease in symptoms and bronchodilator use in the SLIT group versus the control group, becoming significant at the second and third pollen seasons, respectively ( P < .01 at all times). Nasal eosinophils decreased significantly in the active group, starting from the third pollen season ( P < .01). In the SLIT group a significant increase in FEV 1 , specific airways conductance, and maximal expiratory flow at 25% of forced vital capacity was seen starting from the second year and was associated with an increase in the methacholine threshold dose ( P < .01). The differences were significant also at the intragroup comparison over time. CONCLUSION: SLIT achieved a significant clinical benefit in birch pollinosis, reduced the eosinophil infiltration in nasal mucosa, and significantly improved pulmonary function during the pollen seasons.

Administration, Sublingual↗

New insights in allergen avoidance measures for mite and pet sensitized patients. A critical appraisal.

It is widely acknowledged that avoidance of allergens such as those derived from foods, drugs, latex and stinging insects results in a complete disappearance of symptoms. By contrast, although it has been clearly shown that allergens are an important risk factor for the development of respiratory symptoms and that several avoidance measures reduce allergen levels, whether this gives clinical improvement in symptoms is debatable. Many reasons could be invoked to justify this evident discrepancy. Apart from the intrinsic methodological aspects (e.g. single or combined interventions measure, population studied, severity of respiratory symptoms, outcomes, evaluated parameters, etc.), it is important to outline that a successful approach requires that the avoided allergen is the only and real factor responsible for symptoms, the patient's education and the use of a comprehensive protocol to reduce allergen exposure. Other important factors include the involvement of the patient, the relevance of other allergens/non-specific agents, and exposure to sensitizing agents also outside patient's home. It is likely that the clinical phase of allergic airway disease and the degree of bronchial (and also nasal) remodelling, in each individual, represent relevant factors for the clinical outcome of allergen avoidance procedures. Since the management of respiratory allergy is a complex strategy (including drugs, allergen avoidance, immunological and educational interventions), it is difficult in real life to distinguish the efficacy of a single intervention in comparison to the others. A combined strategy is likely to produce better clinical results.

Adult↗

A model of allergen-driven human airway contraction: beta2 pathway dysfunction without cytokine involvement.

BACKGROUND: In our previous in vitro model, allergen incubation of passively sensitized human airways reduced the response to salbutamol. However, whether cytokines play a role in this model is still unknown. OBJECTIVE: To investigate interleukin 1beta and tumor necrosis factor a expression in allergen-challenged human airways. METHODS: Nonasthmatic airways (n = 13) were passively sensitized by overnight atopic serum incubation and then challenged with allergen for 1 hour (n = 9). After repeated washouts, airways were immersed in physiologic salt solution for 6 hours and finally in formaldehyde for immunohistochemical studies. The effect of co-incubation in anti-interleukin 1beta and anti-tumor necrosis factor a specific neutralizing antibodies on salbutamol response was also studied (n = 4). RESULTS: No differences were found among control, sensitized, and challenged rings in the number of inflammatory cells. The percentage of basement membrane covered by epithelium was similar in the different conditions. There was a higher percentage of degranulating to total mast cells in allergen-challenged rings than in sensitized rings (P < .001). A significant correlation was observed between allergen-induced contraction and mast cell degranulation (r = 0.88; P < .001). The sensitization procedure was validated by paired allergen-induced contractions. No expression of the 2 cytokines was detectable up to 6 hours after allergen challenge, and specific neutralizing antibodies did not attenuate the impaired response to salbutamol in allergen-challenged rings. CONCLUSION: These data suggest that in our in vitro model of allergic inflammation, beta2 pathway dysfunction can occur without cytokine involvement, thus supporting previous results that suggest a role for leukotrienes.

Adrenergic beta-Agonists↗

Comparison of the effects in the nose and skin of a single dose of desloratadine and levocetirizine over 24 hours.

BACKGROUND: Desloratadine (DL) and levocetirizine (LCZ) are the newest commercialized antihistamines. Pharmacokinetics, pharmacodynamics and clinical data are available for both drugs, but there is to date no direct comparison involving the nose and skin at the same time. We compared the effects of a single dose of the two drugs in the nose and skin over 24 h. METHODS: Twenty-three patients with symptomatic allergic rhinitis were enrolled in a randomized double-blind crossover administration of DL and LCZ. The histamine-induced wheal and flare was measured at baseline and 2 and 24 h after dosing. A reflective total symptom score (rTSS) for the previous 24 h was assessed before and after each dose. An instant symptom score was also measured at various time points after each drug. RESULTS: LCZ provided greater inhibition of the flare at 2 h (p = 0.05) and at 24 h (p = 0.007) and greater inhibition of the wheal only at 2 h (p = 0.02). The decrease in wheal and flare was significant versus baseline (p = 0.007) with both drugs. The rTSS of the previous 24 h decreased significantly with both LCZ (11.53 vs. 8.0; p < 0.05) and DL (11.3 vs. 7.9; p < 0.05). The instant TSS progressively decreased in parallel with both drugs, but a difference in favor of LCZ was seen 2 h after dosing. CONCLUSIONS: Single doses of DL and LCZ had a comparable effect on nasal symptoms, but LCZ was faster and displayed a greater effect on histamine wheal.

Adolescent↗

Sublingual and oral immunotherapy.

Sublingual immunotherapy (SLIT) is a viable alternative to the subcutaneous route for the treatment of respiratory allergy, whereas the pure oral route has been abandoned because of its lack of efficacy. The main distinctive feature of SLIT is its optimal safety profile, which has been demonstrated in adults and children. The indications for SLIT are similar to those for the subcutaneous route. A long-lasting effect has been demonstrated for the sublingual route, but data are needed to determine the optimal dose and the preventive effect in asthma.

Administration, Oral↗

Efficacy and safety of sublingual immunotherapy.

OBJECTIVE: To review the available published data concerning the use of sublingual immunotherapy (SLIT) in respiratory allergy to primarily evaluate the clinical efficacy and safety of the treatment and to secondarily consider the mechanisms of action and any unresolved questions. DATA SOURCES: Articles in the medical literature (starting from 1986 up to November 2003) derived from searching the MEDLINE database with the keywords sublingual immunotherapy, respiratory allergy, asthma, and rhinitis. Sources included review articles, randomized controlled clinical trials, postmarketing surveillance studies, and relevant reports from meeting proceedings. STUDY SELECTION: Articles concerning safety, efficacy, and mechanisms of SLIT published in English-language, peer-reviewed journals. RESULTS: SLIT proved effective and safe in adults and children. As with traditional subcutaneous immunotherapy, SLIT has long-lasting efficacy and a preventive effect on new sensitizations. CONCLUSION: SLIT is a viable alternative to subcutaneous immunotherapy. Its use in pediatric patients seems to be particularly promising.

Administration, Sublingual↗