Integrated care pathways for airway diseases (AIRWAYS-ICPs).

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs.

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

Practical guide to skin prick tests in allergy to aeroallergens.

This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.

Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper.

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.

[ARIA (Allergic Rhinitis and its Impact on Asthma) achievements in 10 years and future needs]. / ARIA (allerjik rinit ve astim üzerine etkisi) 10 yildaki kazanimlar ve gelecekteki gereksinimler.

Allergic rhinitis and asthma represent global health problems for all age groups. Asthma and rhinitis frequently co-exist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization (WHO) workshop in 1999 and was published in 2001. ARIA has reclassified allergic rhinitis as mild/moderate-severe and intermittent/persistent. This classification schema closely reflects the impact of allergic rhinitis on patients. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of allergic rhinitis and asthma co-morbidities based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation). ARIA has been disseminated and implemented in over 50 countries of the world. In Turkey, it is important to make a record of ARIA achievements and to identify the still unmet clinical, research and implementation needs in order to strengthen the 2011 EU Priority on allergy and asthma in children.

How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA(2) LEN statement.

Specific immunotherapy (SIT) is one of the treatments for allergic rhinitis. However, for allergists, nonspecialists, regulators, payers, and patients, there remain gaps in understanding the evaluation of randomized controlled trials (RCTs). Although treating the same diseases, RCTs in SIT and pharmacotherapy should be considered separately for several reasons, as developed in this study. These include the severity and persistence of allergic rhinitis in the patients enrolled in the study, the problem of the placebo, allergen exposure (in particular pollen and mite), the analysis and reporting of the study, the level of symptoms of placebo-treated patients, the clinical relevance of the efficacy of SIT, the need for a validated combined symptom-medication score, the differences between children and adults and pharmacoeconomic analyses. This statement reviews issues raised by the interpretation of RCTs in sublingual immunotherapy. It is not possible to directly extrapolate the rules or parameters used in medication RCTs to SIT. It also provides some suggestions for the research that will be needed. Interestingly, some of the research questions can be approached with the available data obtained from large RCTs.

Systematic review on the efficacy of fexofenadine in seasonal allergic rhinitis: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials.

RATIONALE: Evidence-based medicine represents the effort to highlight the best intervention for patients, clinicians, and policy makers, each from their respective viewpoint, to solve a particular health condition. According to a recently diffused grading system of evidence and recommendations for medical interventions, efficacy and safety represent 2 of the most important features to consider, and data from meta-analyses of randomized controlled clinical trials (RCTs) is the strongest supporting demonstration. Fexofenadine has been used for its efficacy and safety in the treatment of allergic rhinitis (AR) for many years although no meta-analyses supporting its use currently exist. The aim of this study is to assess for the first time the efficacy and safety of fexofenadine in the treatment of AR by means of a meta-analytic analysis of existing RCTs. Since specific evidence should be provided to address recommendations in a pediatric population, the quality of the estimates of this subgroup analysis is assessed. METHODS: All double-blind, placebo-controlled randomized trials assessing the efficacy of fexofenadine in AR were searched for in OVID, Medline, and Embase databases up to December 2007. Outcomes were extracted from original articles; when this information was not available, the authors of each trial were contacted. Some graphics were digitalized. The RevMan 5 program was used to perform the analysis. GradePro 3.2.2 was used to assess the quality of the evidence for a pediatric population. RESULTS: Of 2,152 identified articles, 20 were potentially relevant trials. Eight studies satisfied the inclusion criteria and were included in the meta-analysis. The main reasons for exclusion were: unnatural exposure, strong study limitations, an atypical outcome measurement, a design for other outcomes, and not being a placebo-controlled, single-blind study. Seven trials investigated a mixed population of adults and children, 1 trial investigated only children, and 1 trial only adults. In 1,833 patients receiving fexofenadine (1,699 placebo), a significant reduction of the daily reflective total symptom scores (TSS) (SMD ­0.42; 95% CI ­0.49 to ­0.35, p < 0.00001) was found. Positive results were also found for morning instantaneous TSS and individual nasal symptom scores (sneezing, rhinorrhea, itching, and congestion). The safety analysis did not show a significant difference in reported adverse events (AE) between the active and placebo treatment groups (OR = 1.03; 95% CI 0.87­1.22, p = 0.75). A very low heterogeneity between the studies was detected, so a fixed-effects model was used. The mean quality level of the included trials was medium. Specific information for a pediatric population may be assumed with a moderate quality of evidence from only 1 study and with a low quality of evidence, mainly due to indirectness, from the others. CONCLUSIONS: This study has 5 major strengths: it represents the first attempt to evaluate the efficacy and safety of fexofenadine in the treatment of AR by means of a meta-analysis of RCTs; there was consistency between positive results in terms of efficacy in TSS and in individual symptoms; a large population was studied; there was an irrelevant interstudy heterogeneity, and the AE frequency was similar in both groups. All of these values encourage the recommendation of fexofenadine for AR. Further research focused on the benefits and disadvantages for a pediatric population is needed.

Prioritised research agenda for prevention and control of chronic respiratory diseases.

The 2008-2013 World Health Organization (WHO) action plan on noncommunicable diseases (NCDs) includes chronic respiratory diseases as one of its four priorities. Major chronic respiratory diseases (CRDs) include asthma and rhinitis, chronic obstructive pulmonary disease, occupational lung diseases, sleep-disordered breathing, pulmonary hypertension, bronchiectiasis and pulmonary interstitial diseases. A billion people suffer from chronic respiratory diseases, the majority being in developing countries. CRDs have major adverse effects on the life and disability of patients. Effective intervention plans can prevent and control CRDs, thus reducing morbidity and mortality. A prioritised research agenda should encapsulate all of these considerations in the frame of the global fight against NCDs. This requires both CRD-targeted interventions and transverse NCD programmes which include CRDs, with emphasis on health promotion and disease prevention.

Development and implementation of guidelines in allergic rhinitis ­ an ARIA-GA2LEN paper.

The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.

Evidence of bacterial biofilms in nasal polyposis.

INTRODUCTION: The pathogeny of chronic rhinosinusitis with nasal polyposis (CRS/NP) has not been elucidated. Bacterial exotoxins have been implicated in many inflammatory chronic diseases, such as chronic otitis, chronic tonsillitis, cholesteatomas, and more recently CRS/NP. We propose that the bacteria in CRS/NP are not only present in a planktonic state, but also occur in microbial communities as biofilms. OBJECTIVE: To determine and characterize the presence of biofilms in CRS/NP. METHODS: We performed a prospective study in 12 patients undergoing endoscopic sinus surgery for nasal polyposis. Ten patients without CRS/NP who underwent septoplasty were included as a control group. Tissue samples were obtained from the inferior turbinate mucosae. The bacteria were isolated and typified and the material was examined in vitro using a spectrophotometer, and in vivo using optical microscopy and confocal scanning laser microscopy. RESULTS: Moderate to high in vitro biofilm-forming capacity was detected in 9 out of 12 patients with CRS/NP (mean [SD] optical density values of between 0.284 [0.017] and 3.337 [0.029]). The microorganisms isolated were Staphylococcus (5 patients), Streptococcus viridans, Pseudomonas aeruginosa, Enterococcus faecalis and Streptococcus viridans/Corynebacterium. Biofilms were demonstrated in vivo in 2 patients and no biofilm structures were evident in any of the controls. CONCLUSION: This study demonstrates the presence of bacterial biofilms in patients with CRS/NP. This chronic inflammatory factor might contribute to nasal mucosa damage, increased inflammatory cells in tissue, and the subsequent hyperplasic process.

GAPP Italy: "A survey on asthma on Italian physicians and patients".

Guidelines recognize the importance of achieving and maintaining asthma control: the treatment strategies nw available allow the control of the great majority of patients with asthma but despite many efforts only 5% of patients achieve guideline-defined asthma control. The GAPP (The Global Asthma Physician and Patient survey) is a global quantitative survey with the aiim of identifying barriers to optimal management of asthma. Physicians and adult patients with persistent asthma have been interviewed with closed-ended questions questionnaire. This study has been conducted in 16 countries. In Italy the survey has revealed that physicians prescribe a combination of ICS and LABA more often in the other countries. They consider ICS the first-line treatment for mild persistent asthma. They are not completely satified with ICS because of local and systemic side effects. At the same time, the reason why patients change asthma medication is the potential for side effects. The two group responses were found to differ about the time spent discussing how to improve the management of asthma. A better communication between physician and patient and a new treatment option with lower side effect profile could be the key point to achieve asthma control in a larger number of patients.

Adolescent smokers are at greater risk for current asthma and rhinitis.

BACKGROUND: The association of tobacco smoke with the prevalence of asthma and rhinitis has not been well-characterized in adolescents. METHODS: As part of the International Study of Asthma and Allergies in Childhood (ISAAC), we conducted a cross-sectional survey of 3000 adolescents aged 13-14 years in northern Argentina. Data included questions about asthma and rhinitis symptoms and about parental and personal smoking. Logistic regression and Pearson chi(2) statistics were used to estimate these associations. RESULTS: Over 13% of respondents described themselves as current smokers, and half indicated that at least one parent smoked at home. Active smoking was associated with both asthma (OR 1.83, 95%CI 1.42-2.35) and rhinitis (OR 1.61, 95%CI 1.33-1.92) in unadjusted analysis. These associations persisted after adjusting for parental smoking status, mother's educational level and sex. Boys were significantly less likely than girls to report current asthma or rhinitis. CONCLUSIONS: Active and passive smoking are both risk factors for asthma and rhinitis in adolescents. Assuming that some children with asthma never started smoking due to symptoms, then the true risk could be higher than reported here. These results reinforce the need to develop better strategies for primary and secondary prevention of tobacco exposure in children.

Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis. Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials.

RATIONALE: Several randomized, double-blind, placebo-controlled clinical trials have demonstrated the efficacy of mometasone furoate nasal spray (MFNS) in the treatment of allergic rhinitis (AR) thus allowing for a meta-analysis to determine the overall treatment effect. METHODS: A comprehensive search of the MEDLINE, LILACS, SCOPUS, and the Cochrane Library databases up to 31 October, 2007 was carried out. Randomized, double-blind, placebo-controlled, clinical trials evaluating the efficacy of MFNS in patients with AR compared to placebo were included. Total nasal symptom scores (TNSS), individual nasal symptoms, total non-nasal symptom scores (TNNSS) and nasal airflow were analysed as the standardized mean difference (SMD). Meta-analysis was performed with the random or the fixed effect models depending on heterogeneity, by using revman 5 software. DATA SYNTHESIS: Sixteen of the 113 identified articles met the inclusion criteria. For MFNS efficacy on TNSS, 2998 participants were analysed: 1534 received MFNS and 1464 placebo. Mometasone furoate nasal spray was associated with a significant reduction in TNSS (SMD -0.49, 95% CI: -0.60 to -0.38; P < 0.00001; I(2) = 50.1%). A significant effect on SMD for nasal stuffiness/congestion (-0.41; 95% CI: -0.56 to -0.27), rhinorrhoea (-0.44; 95% CI: -0.66 to -0.21), sneezing (-0.40; 95% CI: -0.57 to -0.23) and nasal itching (-0.39; 95% CI: -0.53 to -0.25) was also demonstrated. Mometasone furoate nasal spray treated subjects also showed a significant reduction in TNNSS (-0.30; 95% CI: -0.43 to -0.18). The proportion of patients with adverse events was similar for MFNS and placebo (0.99; 95% CI: 0.81-1.20; P = 0.91). CONCLUSIONS: This meta-analysis provides a level Ia evidence for the efficacy of MFSN in the treatment of AR vs placebo. Adverse events frequency was similar in both groups.

Methodology for development of the Allergic Rhinitis and its Impact on Asthma guideline 2008 update.

BACKGROUND: We describe the methodology for the 2008 update of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The methodology differs from the 2001 edition in several respects. The most prominent change is the application of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to compiling evidence, assessing the quality of evidence and grading of recommendations. METHODS AND RESULTS: Representatives of the GRADE working group joined the ARIA guideline panel to achieve these tasks. While most recommendations result from existing systematic reviews, systematic reviews were not always available and the panel compiled the best available evidence in evidence profiles without conducting actual reviews. The panel conducted two meetings and used the GRADE criteria to assess the quality of evidence (four categories of high, moderate, low and very low) and the strength of recommendation (strong and weak) based on weighing up the desirable and undesirable effects of management strategies, considering values and preferences influencing recommendations, and resource implications. The guideline panel has chosen the words 'we recommend'--for strong recommendations and 'we suggest'--for weak recommendations. Both categories indicate the best course of action for a given patient population, but their implementation, requires different considerations as we describe subsequently in this article. CONCLUSIONS: The 2008 update of the ARIA guidelines has become more evidence-based. Future iterations of the guidelines will further be improved by following the described processes even closer, such as ensuring availability of updated high quality systematic reviews for each question.

Role of food allergy in asthma in childhood.

Atopy is the major predisposing factor for asthma identified up to now, and allergen exposure, particularly indoor allergens, is considered as a causal factor for asthma. Food allergy is frequently underestimated in association with asthma, however food allergy has been shown to trigger or exacerbate broncho-obstruction in 2 to 8.5% of children with asthma. There is also evidence that double-blind placebo-controlled oral challenge is able to increase unspecific bronchial hyperresponsiveness. Sensitization to food can occur early in life involving T cell response, mainly of the Th2 phenotype, but also IgE-mediated hypersensitivity. Moreover, it has been shown that sensitization to food allergens early in life is a risk factor for sensitization to inhalent allergens and respiratory symptoms later on. Epidemiological studies suggest that changes in the dietary composition, such as trans-fatty acids, could be involved in the increase of asthma prevalence. The introduction of formula during the first trimester of life increases the risk of having asthma. The diagnosis of food allergy associated with asthma is not easy, nevertheless is important for allergists, pulmonologists and paediatricians to consider food allergy in children with respiratory symptoms, especially when asthma symptoms start early in life and when they are associated with other manifestations of food allergy. Children sensitized to cow's milk proteins and also having atopic eczema are at higher risk for asthma. Since avoidance of the offending food is the first step in the management of children with asthma associated with food allergy, a careful identification should be done in order to avoid unnecessary elimination of foods.

Asthma mortality in Latin America.

There are not enough data concerning asthma mortality in Latin America. The Latin American Society of Allergy and Immunology coordinated this project to provide reliable data for gaining knowledge about our present situation, which is a condition indispensable to changing it. The following countries participated in this study: Argentina, Brazil, Chile, Colombia, Costa Rica, Cuba, Mexico, Paraguay, Peru, Uruguay and Venezuela. A uniform protocol was designed in Santa Fe, Argentina. Asthma mortality rates were analyzed in accordance with two variables: age-adjusted rates (5-34) and total death rates. The total population studied was 107, 122, 529 inhabitants. The highest death rates were found in Uruguay and Mexico (5.63), and the lowest in Paraguay (0.8) and Colombia (1.35). Age-adjusted (5-34) rates were higher in Costa Rica (1.38) and lower in Chile (0.28). Regarding sex, the analysis of the information provided by seven countries showed a predominance of females (51.8%) over males (48.18%). In the southern Latin American countries such as Chile, Uruguay, Paraguay and Argentina, which have marked climatic differences, deaths occurred mainly in the winter. It is important to emphasize that, in most countries, deaths from asthma occurred at home: Chile (60.7%), Argentina (63.4%) and Paraguay (88%). However, in Uruguay, 58.6% occurred during hospitalization. Mortality rates from bronchial asthma are high in most of the Latin American countries studied, even though further studies are needed. Asthma is a serious global health problem. People of all ages in countries throughout the world are affected by this chronic airway disorder that can be severe and sometimes fatal. The health ministries of each country do not believe asthma is a significant issue. Therefore, we should provide them with sound epidemiological studies to convince them to change their attitude toward this disease.

Cutaneous sensitivity to six mite species in asthmatic patients from five Latin American countries.

The prevalence of positive skin prick tests to the mite species Dermatophagoides pteronyssinus, D. farinae, Blomia tropicalis, Chortoglyphus arcuatus, Lepidoglyphus destructor and Aleuroglyphus ovatus was determined in 297 asthmatic adults and children living in seven cities of five Latin American countries. A standardized protocol and a common battery of extracts were used at each site. The mean wheal diameters were measured after 15 min, and those > or = 3 mm were considered positive. Sensitization to D. pteronyssinus varied from 60.7% in Cartagena to 91.2% in São Paulo; to D. farinae from 53.3% in Córdoba to 97.2% in Caracas; to A. ovatus from 26.6% in Bogotá to 71.2% in São Paulo; to B. tropicalis from 46.5% in Mexico City to 93.7% in São Paulo; to C. arcuatus from 33.3% in Mexico City to 75% in São Paulo; and to L. destructor from 30% in Mexico City to 76.2% in São Paulo. This study reported the results of skin test sensitivities in both children and adults. The studies from São Paulo and Córdoba were confined to children and thus could be compared; there was a significantly higher prevalence of cutaneous sensitivity to mite allergens in the children of São Paulo than in those of Córdoba (p < 0.001 for all mite species). Cutaneous sensitivity to mite allergens is very common in young and adult asthmatics in Latin America, in areas both at sea level and at high altitudes. Environmental control measures should be reinforced in the treatment of asthmatics in Latin America.

Clinical signs and symptoms are not enough for the correct diagnosis of allergic conjunctivitis.

BACKGROUND: Allergic Conjunctivitis (AC) has a high incidence in the general population and sometimes it is difficult to make a correct diagnosis, distinguish among the different subtypes of AC, and therefore, to indicate the suitable therapy. OBJECTIVE: To determine the best way to carry out an appropriate diagnosis of AC. METHODS: Thirty-one patients with clinical manifestations of AC and eleven controls were studied by measuring allergic and immunologic parameters. Only those patients confirmed as having AC were treated with ketotifen fumarate and further evaluated. RESULTS: According to allergic and immunological parameters, patients were divided into two groups. Group I patients had positive prick test toward at least one allergen, 60% exhibited high levels of tear-IgE, and only 36% conjunctival eosinophils. By contrast, patients from Group II had negative prick tests and laboratory findings similar to the control group. In group I there was a good correlation between levels of tear-IgE and eosinophils (r = 0.55; p = 0.009); key symptoms and signs and prick test (r = 0.52; p = 0.015), and prick test and eosinophils (r = 0.50 p = 0.022). The cardinal signs and symptoms scores dropped significantly in Group I as a consequence of the treatment (p < 0.0001). CONCLUSION: In order to have a reliable AC diagnosis, allergen-skin prick test, IgE in tears, and conjunctival eosinophils must be studied. Serum IgE is less important.