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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

Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms, quality of life and inflammatory parameters.

Background Levocetirizine (LCZ) has been shown to be effective in allergic rhinitis. We evaluated its clinical efficacy, antinflammatory actions and its effects on quality of life (QoL) with a specific instrument in the asthma-rhinitis comorbidity. Methods Fifty adult patients with persistent rhinitis with/without asthma were enrolled. After a 1-week run-in for baseline evaluation, they were randomized to LCZ or placebo for 8 weeks. Cromolyn and salbutamol were permitted on demand. Rhinoconjunctivitis and asthma symptoms were evaluated by diary cards. QoL was assessed by the specific Rhinasthma questionnaire and the generic SF-36 at different time-points. Nasal scrapings and lavages were also performed for inflammatory cell count and mediator assessment. Results Ten patients dropped out for unrelated reasons and the remaining completed the study with no side-effect. Symptoms began to decrease in the active group at the second week of treatment when the difference with the placebo group became significant (0.05) and so remained until the end of the trial. Starting from 2 weeks of therapy, there was a significant decrease vs. baseline in all the four components of the Rhinasthma questionnaire only in the active group. The intergroup comparison became significant (P<0.05) at 4 weeks. The SF-36 detected only sporadic differences between groups. Eosinophils and neutrophils in nasal scraping were significantly decreased in the LCZ group vs. baseline at all times. Nasal mediators were under the detection limits and no analysis could be performed. In the active group, only two patients used rescue medications compared with 13 patients in the placebo group. Conclusions LCZ is clinically effective and capable of improving the rhinitis-asthma-related QoL.

Adolescent↗

Rhinitis and asthma in athletes: an ARIA document in collaboration with GA2LEN.

This consensus document is aimed at reviewing evidence that the rhinitis-asthma links have peculiar features in athletes. Beside a review of epidemological data on the high prevalence of rhinitis and asthma in athletes, the effects on intense physical exercise on the immune system and repiratory functions are discussed, with special reference to the role of allergens and pollutants. In extending the Allergic Rhinitis and its Impact on Asthma (ARIA) recommendations to athletes, the issue is addressed of adapting diagnosis and management to criteria set by the International Olympic Committee (IOC) and regulations adopted by the World Anti-Doping Agency (WADA).

Asthma↗

Randomized double-blind controlled study with sublingual carbamylated allergoid immunotherapy in mild rhinitis due to mites.

BACKGROUND: The clinical efficacy of sublingual immunotherapy (SLIT) in mite allergy and in mild disease is still a matter of debate, thus we performed a long-term clinical trial. METHODS: The study was randomized, double-blind and placebo-controlled. After a 1-year assessment, 68 patients with mild rhinitis with/without asthma due to mites were randomized to drugs + placebo or drugs + SLIT for 2 years. Sublingual immunotherapy was given as soluble tablets of monomeric carbamylated allergoid. Clinical scores for asthma and rhinitis (0, absent to 3, severe) and drug consumption were assessed by diary card in the period November-February. Quality of life was assessed before and after each observation period and pharmaco-economy data were evaluated as well. RESULTS: Fifty-six patients completed the study. The rate of dropouts was similar in the two groups. No relevant side effect was reported. There was a significant reduction of total clinical scores (P < 0.05) in the active group vs placebo at the first year, but not at the second whereas nasal obstruction significantly improved in both years (P < 0.05). The reduction of drug intake score was significant only at the first year. No change was observed concerning most of the Short Form-36 items, because at baseline all patients displayed a normal profile. A significant change in SLIT group was seen for the item 'change in health status'. The need for extra visits was significantly lower in the active group (25%vs 43%). CONCLUSIONS: Sublingual immunotherapy was clinically effective and safe in mite-induced mild disease.

Administration, Sublingual↗

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Animals↗

Sublingual immunotherapy in the treatment of adult allergic rhinitis patients.

Sublingual immunotherapy (SLIT) was accepted for clinical use by the medical community only 15 years after the first controlled trial published. The acceptance of SLIT has been driven by the evidence base of a large number of clinical trials confirming the efficacy and a recent meta-analysis study. Although SLIT is self-managed by the patient, this does not generate problems with compliance. The safety profile, assessed in clinical trials and postmarketing surveillance studies, is satisfactory with no reports of systemic adverse reactions. New data are available on the persisting, long-lasting effect of SLIT and on the association with the prevention of asthma in paediatric patients. However, there is only indirect evidence for such persistence and duration of effect in adult patients. Key priorities for further investigation are the mechanisms of action, the efficacy in asthma, the cost/effectiveness and the identification of those patients who will achieve the maximum benefit with SLIT.

Administration, Sublingual↗

The type of sensitizing allergen can affect the evolution of respiratory allergy.

BACKGROUND: Numerous factors affect the evolution of respiratory allergy, in children, but little is known in adults. We assessed in a prospective study the influence of the type of allergen on the progression of disease. METHODS: Outpatients, with respiratory allergy underwent skin tests and pulmonary function/methacholine challenge at baseline and after 3 years. Patients were subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In polysensitized subjects a single relevant allergen (mites, grasses, birch, Parietaria) was identified based on symptom distribution and when needed on nasal challenge. RESULTS: 6750 patients (age range 12-46) were studied. Of them, 17.8% were monosensitized but this percentage decreased to 10.4% after 3 years (P < 0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. After 3 years, the patients with bronchial responsiveness increased from 18% to 58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for Parietaria, with a significant difference among allergens (P < 0.05). Almost the same was seen in monosensitized subjects, being mites most likely to cause a worsening. All patients with BHR at baseline received immunotherapy. In these patients the onset of new sensitizations was significantly lower than in the group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared more frequently. CONCLUSION: The different type of allergen influences the course of the disease, as well as the use of immunotherapy.

Adolescent↗

Sleep disturbances in allergic diseases.

Sleep is fundamental for physical and mental health as well as daytime performance and represents a crucial aspect in the personal representations of well-being. Sleep disturbances in patients with chronic disorders constitute a factor that contributes to exacerbate symptoms, complicate management, and affect mood and quality of life (QoL). Allergic diseases are a global health problem of increasing prevalence that affects up to 15% of the population in Western countries. Sleep problems associated with allergic diseases may play a role in worsening the burden of illness, contributing to impairment of the QoL. The aim of this review was to describe the most common causes leading to sleep disturbance in allergic patients and their consequences on the QoL. The possible negative effects of treatment on sleep parameters has been also considered.

Anti-Allergic Agents↗

Tissue remodelling in upper airways: where is the link with lower airway remodelling?

Tissue remodelling reported in upper airways include epithelial hyperplasia, increased matrix deposition in the nasal or paranasal lining, matrix degradation and accumulation of plasma proteins. Genetic influences, foetal exposures and early life events may contribute to structural changes such as subepithelial fibrosis from an early age. Other structural alterations are related to duration of the disease and long-term uncontrolled inflammation. Structural changes may increase alteration of the protective functions of the upper airways namely by affecting mucociliary clearance and conditioning of inspired air. The sequences of tissue changes during wound repair of upper airway mucosa after surgery are illustrative of the complexicity of tissue modelling and remodelling and could be considered as an important source of information for a better understanding of the complex relationship between inflammatory reaction, of the subsequent tissue damages and fibroblast metabolism of upper airways.

Animals↗

Adherence to treatment: assessment of an unmet need in asthma.

BACKGROUND: In asthma, as in other chronic conditions, poor adherence to treatment and to medical advice is common and contributes to substantial worsening of the disease and increased health care costs. OBJECTIVE: The aim of the present study was to evaluate patients' self-reported adherence to asthma medication regimens and to identify possible correlations between treatment adherence and depression, anxiety, and coping strategies. METHODS: Sixty-three asthmatic outpatients (27 men and 36 women; mean age +/- SD, 38.5 +/- 14.1) were consecutively enrolled during their routine control visit. Patients were asked to complete 3 different questionnaires: the Adherence Schedule in Asthma, the Hospital Anxiety and Depression Scale, and the Coping Orientations to Problem Experienced questionnaires. RESULTS: Depression was detected in 32.3% of patients and anxiety in 34.9%. A negative correlation was found between older age and perception of family support (rho = -0.33). The presence of anxiety displayed a positive correlation with difficulty in accepting the illness (rho = 0.33) and a negative correlation with acceptance of illness limitations (p = -0.30); it was also positively correlated with fear of the side effects of medication (rho = 0.37). The presence of depression was negatively correlated with acceptance of illness limitations (rho = -0.32), knowledge of the illness (p = -0.29), and with ability to identify worsening signs (rho = -0.31). CONCLUSION: This study shows how different factors may modulate adherence to asthma treatment. The opportunity to identify reasons for nonadherence through a simple assessment will allow a tailored intervention to be planned for each patient.

Adaptation, Psychological↗

What do we need to learn to optimize the SLIT alternative?

Allergen-specific immunotherapy (IT) is the only treatment of allergy in adults and children capable of modifying the immune response at early steps. As a consequence, IT improves symptoms, prevents the onset of new sensitizations, reduces the risk of developing asthma and its clinical efficacy lasts many years. The main rationale for administering sublingually IT (SLIT) is to reduce the occurrence of side effects, still yet preserving the immunological effects. SLIT with the most common allergens have been used in many studies with significant clinical effectiveness in both asthma and rhinitis. The pharmacokinetic of allergens administered through non injection routes is complex. Peptide absorption across oral mucosa occurs mainly by passive diffusion but delivery of proteins has some limitations. Moreover, the molecular mechanisms responsible for the efficacy of SLIT are poorly defined. In this review we focus on the anatomy/histology of the oral cavity as well as on the associated immunological structures to envisage what may happen when an allergen is kept in the mouth. Moreover, the induction of immune responses in this particular immunological environment is also discussed.

Administration, Sublingual↗

Pharmacokinetics of radiolabelled Par j 1 administered intranasally to allergic and healthy subjects.

BACKGROUND: Local nasal immunotherapy is accepted as an alternative to the injection route for allergic rhinitis. Despite this, little is known about the kinetics of the allergen after nasal delivery in allergic subjects. OBJECTIVE: We aimed at assessing the biodistribution of 123I-radiolabelled Par j 1 in Parietaria-allergic subjects, in comparison with healthy volunteers. METHODS: Purified Par j 1 was radiolabelled with 123I and sprayed into the nostrils of three control subjects and three Parietaria-allergic volunteers. Dynamic and static scintigraphic images of the head were recorded at serial times and blood samples were obtained to measure the plasma radioactivity, and to assess the presence of circulating radiolabelled species by gel chromatography. RESULTS: In Parietaria-sensitized subjects, the radiolabelled allergen was rapidly cleared from the nasal cavity and transported to pharynx, and little local persistence was seen. This differed from healthy subjects where nasal clearance of the tracer was slower and nasal radioactivity persisted up to 24 h. The increase in plasma radioactivity paralleled swallowing of the allergen in both groups, and plasma chromatographic profile did not differ between allergic and healthy volunteers. CONCLUSIONS: Sensitization to the allergen affects its local biodistribution. Gastrointestinal absorption is relevant also for the intranasal route.

Administration, Intranasal↗

Evaluation of food-pollen cross-reactivity by nose-mouth cross-challenge in pollinosis with oral allergy syndrome.

BACKGROUND: Oral allergy syndrome (OAS) is often associated with pollen-induced rhinitis, and there are preferential associations between causative substances. If OAS and rhinitis are both immunoglobulin (Ig)E-mediated and there are cross-reacting proteins, it is expected that similar reactions can be elicited in the nose and mouth. In order to test this hypothesis we performed a series of 'cross-challenges' with foods and pollens in both the nose and the mouth. METHODS: Nine patients with ascertained OAS due to vegetables and rhinitis due to pollens were studied. On the first day a nasal challenge with pollen extracts and an oral challenge with fresh food was carried out. After a week, washout nasal challenge with food and an oral challenge with pollens were performed. Immediate symptoms, mucosal tryptase and soluble eosinophil cationic protein (ECP) were assessed after each challenge. RESULTS: The administration of pollen into the nose and food into the mouth elicited symptoms as expected, but the cross-challenge had no clinical effect. In parallel, tryptase and ECP increased after nasal challenge with pollens, whereas foods did not elicit a measurable response. CONCLUSION: The cross-reactivity between foods and pollens, when evaluated at the shock organ, was not clinically evident. This data can be explained with a low concentration of cross-reagent epitopes in pollen extracts and food homogenized because of degradation. The different behaviour upon challenge suggests that different immunological mechanisms may act in the nose and mouth.

Adolescent↗

Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE.

BACKGROUND: Patients with severe persistent asthma who are inadequately controlled despite Global Initiative for Asthma (GINA) 2002 step 4 therapy are a challenging population with significant unmet medical need. We determined the effect of omalizumab on clinically significant asthma exacerbations (requiring systemic corticosteroids) in the first omalizumab study to exclusively enrol patients from this difficult-to-treat patient population. METHODS: Following a run-in phase, patients (12-75 years) inadequately controlled despite therapy with high-dose inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA) with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicentre study. RESULTS: A total of 419 patients were included in the efficacy analyses. The clinically significant asthma exacerbation rate (primary efficacy variable), adjusted for an observed relevant imbalance in history of clinically significant asthma exacerbations, was 0.68 with omalizumab and 0.91 with placebo (26% reduction) during the 28-week treatment phase (P = 0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Omalizumab significantly reduced severe asthma exacerbation rate (0.24 vs 0.48, P = 0.002) and emergency visit rate (0.24 vs 0.43, P = 0.038). Omalizumab significantly improved asthma-related quality of life, morning peak expiratory flow and asthma symptom scores. The incidence of adverse events was similar between treatment groups. CONCLUSIONS: In patients with inadequately controlled severe persistent asthma, despite high-dose ICS and LABA therapy, and often additional therapy, omalizumab significantly reduced the rate of clinically significant asthma exacerbations, severe exacerbations and emergency visits. Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy.

Administration, Inhalation↗

Seasonal and perennial allergic rhinitis: is this classification adherent to real life?

BACKGROUND: Allergic rhinitis is traditionally subdivided into seasonal (SAR) and perennial (PAR), although the new definitions of persistent and intermittent were recently proposed. We assessed the validity of the traditional classification in a large group of subjects suffering from allergic rhinitis alone. METHODS: Young males referred to a Navy Military Hospital for routine fitness visit, and reporting symptoms of rhinitis alone were selected. According to the sensitization they were subdivided into (i) sensitized to pollens only (seasonal, SAR), (ii) to perennial allergens only (perennial, PAR) and (iii) to both (mixed, MAR). Spirometry, methacholine challenge, severity and characteristics of symptoms were assessed in all participants. RESULTS: Of 19 325 subjects, 2347 had allergic rhinitis. Seventy-two percent of the subjects had MAR, 17% SAR and 11% PAR. Ocular involvement and irritative symptoms were more frequent in SAR (P < 0.03), whereas obstruction was predominant in PAR (P < 0.01). Nasal symptoms varied according to the period of the year in SAR (P < 0.01) and PAR (P < 0.03). An overt bronchial obstruction was detected in 12% of PAR patients, in 7.8% of MAR, and in 4.2% of SAR. forced expiratory volume/1 s was significantly lower during season in SAR patients only (P < 0.05). The FEF25-75 was impaired in 22.5% MAR patients, 21% PAR, and 14% SAR, with a seasonal change in SAR (P < 0.05) and PAR (P < 0.001). Bronchial hyperreactivity was present in 82.2% of PAR, 73.6% of MAR, and 53.5% of SAR, with a seasonal change in SAR (P < 0.001) and MAR (P < 0.05). CONCLUSIONS: This study provides evidence that up to 80% of allergic rhinitics have a mixed form, and SAR and PAR definitions are poorly adherent to real life. Lung involvement is frequent in patients reporting nose symptoms alone.

Adolescent↗