Biomedical subjects

Giorgio Walter Canonica

Publications and source records attributed to Giorgio Walter Canonica.

33 records · Page 2Linked to original sources

PubMed2004

Sublingual immunotherapy: an update.

PURPOSE OF REVIEW: Sublingual immunotherapy is now officially accepted as a viable alternative to the traditional subcutaneous route, and it is widely used especially in European countries. Despite the large amount of experimental evidence on the safety and efficacy of the method, some concerns still exist, and several aspects need to be clarified: magnitude of the efficacy, adherence, long-lasting effect and others. Recently published studies have provided answers to some of these points. RECENT FINDINGS: The most recent studies have shown that sublingual immunotherapy exerts a long-lasting effect up to 5 years after discontinuation and that it is able to prevent the onset of new sensitizations. Moreover, when systematically assessed, the adherence to treatment is quite satisfactory, despite the treatment being self-administered. In addition, evidence has been provided that sublingual immunotherapy is effective in treating allergic conjunctivitis, and a metaanalysis has confirmed its efficacy in rhinitis. Moreover, some studies have addressed the possibility of simplifying the schedule of administration by shortening the build-up phase. SUMMARY: More and more new data on sublingual immunotherapy are rapidly appearing in the international literature. These data confirm the clinical value of this treatment and show that it is comparable to subcutaneous immunotherapy from several points of view.

Administration, Sublingual↗

PubMed2004

An update on the asthma-rhinitis link.

PURPOSE OF REVIEW: For the present article we collected and reviewed the more relevant experimental results concerning the asthma-rhinitis link in allergic diseases, published since January 2002. RECENT FINDINGS: During the last 2 years, particular attention has been devoted to the behaviour of the immune response in the two compartments of the airways. The recent experimental data, mainly obtained with specific nasal or bronchial allergen challenges, have confirmed that the link between the nose and the bronchi is bidirectional, and that a systemic cross-talk occurs. Furthermore, the pathogenic role of paranasal sinus infections in respiratory allergy has been better elucidated. It was shown that, in sinusitis, a T helper type 2 polarization exists, which can be reverted by proper therapy. On the other hand, despite the abundant experimental evidence, our view of the united airways is still not complete, and several points need to be developed. SUMMARY: The new findings on the asthma-rhinitis link have confirmed the current pathogenic view of respiratory allergy. These findings have important implications from a therapeutic point of view, and therefore encourage and promote the search for novel integrated treatment strategies.

Asthma↗

PubMed2003

Effects of fexofenadine and other antihistamines on components of the allergic response: adhesion molecules.

Intercellular adhesion molecules (ICAMs), in particular ICAM-1, appear to play a crucial role in the recruitment and migration of inflammatory cells to the site of an allergic reaction. Glucocorticoids and allergen-specific immunotherapy have been shown to exert effects on selected components of this system, both in vitro and in vivo, but further research is required to better understand the effects of these therapies. Nasal and conjunctival challenge models (including natural and experimental allergen exposure) represent useful and safe tools for studying the activity of antiallergy drugs in vivo. These tests allow the investigation of a wide variety of parameters including inflammatory infiltrate, ICAM-1 expression, and changes in the concentration of soluble inflammatory mediators. With these tools, anti-inflammatory activity related to the modulation of epithelial cell adhesion molecules has been demonstrated in vivo for several H(1)-receptor antagonists (azelastine, cetirizine, loratadine, levocabastine, oxatomide, and terfenadine). Fexofenadine is a nonsedating, long-acting antihistamine with highly selective H(1)-receptor antagonist activity and a particularly favorable safety profile. In addition, fexofenadine has proven anti-inflammatory activity and has been shown to inhibit a number of mediators at clinically relevant concentrations, including in vitro inhibition of ICAM-1 expression on conjunctival and nasal epithelial cells.

Anti-Allergic Agents↗

PubMed2003

Medical treatment reverses cytokine pattern in allergic and nonallergic chronic rhinosinusitis in asthmatic children.

A Th2 cytokine pattern has recently been reported both in allergic and nonallergic chronic rhinosinusitis in asthmatic children. The aim of the study was to evaluate the cytokine pattern in chronic rhinosinusitis in allergic and nonallergic asthmatic children before and after medical treatment. Thirty asthmatic children were evaluated, 18 males and 12 females (mean age 9.1 years). Sixteen were allergic and 14 were nonallergic. All children were asthmatic and suffered from chronic rhinosinusitis, whose diagnosis was confirmed by endoscopy. All of them were treated with amoxicilline-clavulanate (20 mg/kg b.i.d.) and fluticasone propionate aqueous nasal spray (100 microg daily) for 14 days; a short course of oral corticosteroid was also prescribed (deflazacort 1 mg/kg daily for 2 days, 0.5 mg/kg daily for 4 days and 0.25 mg/kg daily for 4 days). Rhinosinusal lavage and nasal cytology were performed in all subjects before and after medical treatment. IL4 and IFNgamma were measured by immunoassay and inflammatory cells were counted by conventional staining. Thirteen allergic children and 12 nonallergic children showed a negative endoscopy after the treatment. Allergic subjects showed a significant decrease of IL4 (p = 0.0002) and a significant increase of IFNgamma (p = 0.03) after the treatment. Nonallergic children showed a significant decrease of IL4 (p = 0.0007) and a nonsignificant increase of IFNgamma. A significant reduction of the inflammatory infiltrate was detected in all asthmatic children (p < 0.05). This study confirms a Th2 polarization in chronic rhinosinusitis both in allergic and nonallergic asthmatic children. Moreover, the medical treatment of chronic rhinosinusitis reversed the cytokine pattern from a Th2 towards a Th1 profile both in allergic and nonallergic children.

Amoxicillin-Potassium Clavulanate Combination↗

PubMed2003

Clinical and therapeutic aspects of allergic asthma in adolescents.

Little is known about the management of asthma in adolescents. We aimed at evaluating these aspects, through a specific questionnaire, in the real life of adolescents with allergic asthma. The questionnaire was administered to a group of adolescents after a diagnosis of allergic asthma. The diagnosis was based on history, clinical examination, pulmonary function tests and allergy tests. One hundred and fifteen adolescents (65 males, mean age 16.5 years) fulfilled the criteria for allergic asthma. The questionnaire explored demography, family history, clinical history, previous diagnosis, therapy, attitude towards therapy and social aspects. The mean actual FEV1 was 87 +/- 10%. Methacholine challenge was carried out in 79 patients and was always positive (PD20 < 1,200 microg), whereas 36 patients underwent reversibility test. According to GINA guidelines, severity of asthma resulted intermittent in 62, mild persistent in 31, moderate in 19 and severe in three patients. In 61% of cases teachers were not aware of the disease. Asthma was managed by general practitioners, allergists and pulmonologists, but PFT/allergy tests had never been performed in 14% of patients. Forty-two per cent of the adolescents received no therapy at all, and only 15% of those with persistent asthma were receiving a stable treatment. Seventy-four per cent of adolescents preferred the inhaled, as against the oral, route. From a clinical and functional point of view, asthma in adolescents did not differ from other age ranges. Nevertheless, the management (diagnosis and therapy) emerged to be unsatisfactory from many points of view.

Activities of Daily Living↗

PubMed2003

Noninjection routes for immunotherapy.

Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The traditional subcutaneous route is burdened with the risk of severe adverse events; therefore, safer routes of administration (noninjection or local routes) have been investigated and developed. Controlled trials failed to demonstrate the clinical efficacy and the safety of oral and bronchial administration, and these routes have been abandoned. Local nasal immunotherapy proved effective and safe in 17 of 18 controlled trials; thus it is considered a viable route of immunotherapy. Nevertheless, nasal immunotherapy is effective in rhinitis only and requires a particular administration technique; therefore its use is slowly declining. The sublingual route is supported by numerous controlled trials showing its efficacy in asthma and rhinitis in adults and children. The safety profile, assessed in clinical trials and postmarketing surveillance studies, is satisfactory; the most frequent side effects are gastrointestinal complaints, which can be easily managed by proper dose adjusting. Sublingual immunotherapy is now accepted by the World Health Organization as a valid alternative to the subcutaneous route also in children. Although the long-lasting efficacy has been recently documented for the sublingual route, several points still need to be elucidated, including mechanisms of action, optimal dosage, cost-effectiveness, and adherence.

Administration, Intranasal↗

PubMed2003

Treatment of acquired cold urticaria with cetirizine and zafirlukast in combination.

Acquired cold urticaria is an infrequent physical urticaria that can provoke severe systemic reactions. Histamine is the primary mediator, but leukotrienes are also involved in the pathogenesis. H(1) antihistamines are recommended as first-choice treatment, but their efficacy is sometimes unsatisfactory. On the basis of pathogenic knowledge, it can be hypothesized that a combination therapy with antihistamines and leukotriene receptor antagonists is more effective than each drug given alone. We tested this hypothesis in 2 patients with severe systemic cold urticaria poorly responsive to conventional therapy. The patients underwent 3 consecutive treatment regimens (each of 2 weeks): cetirizine (10 mg once a day); zafirlukast (20 mg twice a day); and their combination. They were clinically evaluated, after each regimen, by means of a visual analog scale and ice-cube test. The combination therapy was superior to the 2 drugs given alone, as testified by subjective and objective evaluations.

Adult↗

PubMed2003

Oral and sublingual immunotherapy in paediatric patients.

PURPOSE OF REVIEW: Sublingual immunotherapy is becoming a routine treatment for respiratory allergy in several countries and it has been validated in international documents. This article will review the available literature on oral and sublingual immunotherapy, discussing the possible use of sublingual immunotherapy in paediatric patients. RECENT FINDINGS: As oral immunotherapy was found to be poorly effective in clinical trials, its use has been discontinued. In contrast, several controlled studies have shown the efficacy of sublingual immunotherapy in children with allergic asthma and rhinitis, and a postmarketing survey has confirmed its safety. Moreover, new data on the long-lasting efficacy of this treatment and on the absence of local immunological effects have recently been published. SUMMARY: The clinical efficacy and the optimal safety profile of sublingual immunotherapy make it a good candidate for treating respiratory allergy in children. Some aspects, such as the dose-response relationship and preventive effect, will be a research challenge for future developments and better definition of indications in children.

Administration, Oral↗

PubMed2003

Safety of allergen-specific sublingual immunotherapy and nasal immunotherapy.

Allergen-specific immunotherapy is a well-established treatment for respiratory allergy. It is usually administered subcutaneously, and with this route several severe adverse events and fatalities have been described. Therefore, in the last 15 years, novel routes of administration (local routes) were developed. Sublingual and local nasal immunotherapy are now considered as viable alternatives to the injection route, mainly due to their optimal safety. The use of nasal immunotherapy is at present declining. On the other hand, sublingual immunotherapy was investigated in twenty-two randomized controlled trials and two postmarketing surveys: its safety profile turned out to be satisfactory in both adults and children, gastrointestinal complaints being the most frequently reported side effects. These side effects were always mild and could be treated with proper dose adjusting. At variance with injection immunotherapy, no severe systemic adverse event has ever been described. Its safety is also supported by pharmacokinetics and immunological data. Experimental data on the safety of sublingual and nasal immunotherapy will be reviewed.

Administration, Intranasal↗

PubMed2003

Focus on cat allergen (Fel d 1): immunological and aerodynamic characteristics, modality of airway sensitization and avoidance strategies.

The increasing frequency of pet ownership (especially cats) in many industrialized countries has raised the level of exposure to the allergens produced by these animals. Moreover, it is likely that modern energy-saving systems and the wide use of upholstered furniture has resulted in closer contact between cats (and their allergens) and humans. Many different methods have been developed to quantify the main cat allergen (Fel d 1) in settled dust and in ambient air. The threshold levels of cat allergen inducing sensitization or triggering respiratory symptoms in sensitized patients have been calculated in settled dust, but airborne amounts of Fel d 1 probably represent a more reliable index of allergen exposure. Noticeably, the amount of Fel d 1 may be relatively high also in confined environments where cats have never been kept. It has been demonstrated that clothes of cat owners are the main source for dispersal of allergens in cat-free environments. This fact may be of relevance, because recent studies have shown that allergic sensitization to cats is more likely to develop in children exposed to moderate levels of this allergen than in children exposed to high amounts of Fel d 1. The ubiquity of cat allergen may justify the common observation that allergen avoidance is often insufficient to reduce the risk of developing allergic sensitization and/or symptom exacerbation in highly susceptible patients. Further efforts are needed to improve the efficacy of Fel d 1 avoidance strategies to try to reduce the risk of allergic sensitization to this allergen.

Air Pollution, Indoor↗

PubMed2003

Nimesulide and meloxicam are a safe alternative drugs for patients intolerant to nonsteroidal anti-inflammatory drugs.

BACKGROUND: Pseudoallergic reactions to ASA and NSAIDs in general are frequent and difficult to manage. The challenge with the suspected drug is considered unethical, therefore the only possible approach is a challenge with alternative drugs. Selective COX2 inhibitors are considered the most suitable alternative drugs. We describe the comparative results and follow-up of an oral challenge with nimesulide and meloxicam, in NSAIDs intolerant patients. METHODS: 381 patients (118 male, 263 female, mean age 53.2 years) with a well documented pseudoallergic reaction to NSAIDs underwent an oral challenge with these alternative drugs. All 381 patients were given nimesulide 88 of them were also given meloxicam. All patients were re-interviewed at six-month intervals up to two years after challenge. RESULTS: 98.4% of the patients tolerated nimesulide and 95.4% tolerated meloxicam. The reactions occurred during challenges were mild and easily manageable. Three out of the six nimesulide-intolerant patients could tolerate meloxicam, whereas only one of the four meloxicam-intolerant patients could tolerate nimesulide. At the follow-up, 96% of patients with previous negative challenge could tolerate nimesulide and within the patients which took meloxicam after challenge no pseudoallergic reaction occurred. CONCLUSIONS: The herein described challenge with alternative drugs, meloxicam and nimesulide, is a safe tool for the management of NSAIDs-intolerant patients. The two tested drug are safe and reliable alternatives for these patients.

Adolescent↗

PubMed2002

Human lung myofibroblasts as effectors of the inflammatory process: the common receptor gamma chain is induced by Th2 cytokines, and CD40 ligand is induced by lipopolysaccharide, thrombin and TNF-alpha.

The common gamma (gamma c) chain, shared by Th1 and Th2 cytokines, is fundamental for the activation of hematopoietic cells, but its role in non-hematopoietic tissues has not been explored. Here we show that in normal lung fibroblasts IL-4 and IL-13 induce the expression of the gamma c chain and its association with Janus kinase (JAK) 3, while lung myofibroblasts constitutively express a gamma c chain displaying a limited association with JAK3. In the latter cells, without exogenous cytokines, gamma c/JAK3 controls, through autocrine loops, tyrosine kinase (TYK) 2 phosphorylation and the balance between functional (IL-4Ralpha, IL-13Ralpha 1) and decoy (IL-13Ralpha 2) high-affinity receptors. Moreover, JAK3 is also associated with a pre-phosphorylated IL-4Ralpha and CD40. This novel "heterotrimer" (p-IL-4Ralpha, CD40/JAK3) is functional and controls STAT3 phosphorylation and CD40 expression, as shown by use of the specific JAK3 inhibitor WHI-P31. In basal culture conditions, CD40 signaling could be induced by the transient establishment of inter-fibroblastic CD40/CD40 ligand (CD40L) functional bridges. Indeed, powerful pro-inflammatory stimuli such as lipopolysaccharide and thrombin can rapidly mobilize CD40L at the surface of lung myofibroblasts. These interactions are modified by IL-13, which triggers the formation of a new type of functional receptor (p-IL-4Ralpha /IL-13Ralpha 1/gamma c) and also the recruitment and the phosphorylation of JAK3. Treatment with JAK3 inhibitors blocks IL-13-induced phosphorylation of JAK2, TYK2 and STAT3, but not of JAK1 and STAT6. These data underline (1) the pivotal role of the gamma c chain, CD40/CD40L, JAK3 and IL-13 in the inflammatory-like activation of lung myofibroblasts, (2) the cell-type restraint effects of IL-13 on these cells, and (3) the potential usefulness of JAK3 inhibitors in the treatment of asthma.

Anti-Asthmatic Agents↗

PubMed2002

Harmful effect of immunotherapy in children with combined snail and mite allergy.

BACKGROUND: With respect to allergy, the possibility of cross-reactivity between snail and mite is well recognized, and anecdotal reports suggesting that allergen immunotherapy with mite extract can worsen snail-induced allergy exist. OBJECTIVE: We describe the effect of immunotherapy in 4 children with snail-mite allergy. METHODS: Four children (1 boy and 3 girls; 9-13 years of age) had consistent clinical histories (mild immediate respiratory symptoms after ingestion) and positive skin reactions for allergy to snail. They also had mite-induced asthma and were therefore prescribed subcutaneous specific immunotherapy and subsequently followed. RESULTS: Several months (8-25) after starting immunotherapy, all children experienced life-threatening reactions, anaphylaxis, and respiratory failure after inadvertent ingestion of snail. Skin reactivity to the fresh food increased in all patients. CONCLUSIONS: This observation confirms that in patients with combined mite-snail allergy, immunotherapy should be avoided.

Adolescent↗

PubMedDate not supplied

Randomized open comparison of the safety of SLIT in a no-updosing and traditional updosing schedule in patients with Parietaria allergy.

BACKGROUND: Due to optimal safety of sublingual immunotherapy (SLIT), it was suggested that a slow up-dosing phase maybe not necessary, and therefore the treatment will be more patient-friendly, avoiding dosing mistakes. PATIENTS: Twenty adult patients suffering allergic rhinitis due to Parietaria, were enrolled. Half of them received the traditional schedule and the other half immediately started with 200 STU. RESULTS: No difference was observed between the traditional up-dosing treatment schedule and no-up-dosing treatment schedule in terms of side effects, even mild local side effects, even mild local side effects was greater with traditional regimen.

Administration, Sublingual↗

PubMedDate not supplied

Sublingual immunotherapy.

Allergen-specific immunotherapy, together with drug therapy and allergen avoidance, is a cornerstone in the management of respiratory allergy in both adults and children. Since the introduction of sublingual administration of immunotherapy (SLIT), it was regarded as the most promising approach, especially because of its optimal safety profile. After 15 years of clinical trials, the WHO officially accepted SLIT as a routine clinical option in both adults and children. This paper reviews the up-to-date aspects about clinical efficacy, safety and pharmacokinetics of sublingual immunotherapy.

Administration, Sublingual↗