Adherence: the goal to control asthma.

Asthma management requires adequate adherence to many recommendations, including therapy, monitoring of asthma control, avoidance of environmental triggers, and attending follow-up appointments. Poor adherence is common in patients with asthma and is often associated with increased health care use, morbidity, and mortality. Many determinants of poor adherence have been identified and should be addressed, but there is no clear profile of the nonadherent patient. Interventions to improve adherence therefore demand tailoring to the individual by including patient-specific education, addressing patient fears and misconceptions, monitoring adherence, and developing a shared decision process.

Asthma control assessed in the EGEA epidemiological survey and health-related quality of life.

BACKGROUND: The aims were to assess 1) the relationship of asthma control assessed by combining epidemiological survey questions and lung function to Health-Related Quality of Life (HRQL) and 2) whether individuals with controlled asthma reach similar generic HRQL levels as individuals without asthma. METHODS: The analysis included 584 individuals without asthma and 498 with asthma who participated in the follow-up of the Epidemiological study on Genetics and Environment of Asthma (EGEA). Asthma control was assessed from survey questions and lung function, closely adapted from the 2006-2009 Global Initiative for Asthma guidelines. The Asthma Quality of Life Questionnaire (AQLQ, scores range:1-7) and the generic SF-36 (scores range: 0-100) were used. RESULTS: Adjusted mean total AQLQ score decreased by 0.5 points for each asthma control steps (6.4, 5.9 and 5.4 for controlled, partly-controlled and uncontrolled asthma respectively, p < 0.0001). The differences in SF-36 scores between individuals with controlled asthma and those without asthma were minor and not significant for the PCS (-1, p = 0.09), borderline significant for the MCS (-1.6, p = 0.05) and small for the 8 domains (<5.1) although statistically significant for 4 domains. CONCLUSION: These results support the discriminative properties of the proposed asthma control grading system and its use in epidemiology.

Air pollution and asthma control in the Epidemiological study on the Genetics and Environment of Asthma.

BACKGROUND: The associations between exposure to air pollution and asthma control are not well known. The objective of this study was to assess the association between long-term exposure to NO(2), O(3) and PM(10) and asthma control in the follow-up of the Epidemiological study on the Genetics and Environment of Asthma (EGEA2) (2003-2007). METHODS: Modelled outdoor NO(2), O(3) and PM(10) estimates were linked to each residential address using the 4 km grid air pollutant surface developed by the French Institute of Environment in 2004. Asthma control was assessed in 481 subjects with current asthma using a multidimensional approach following the 2006-2009 Global Initiative for Asthma guidelines. Multinomial and ordinal logistic regressions were conducted adjusted for sex, age, body mass index, education, smoking and use of inhaled corticosteroids. The association between air pollution and the three domains of asthma control (symptoms, exacerbations and lung function) was assessed. ORs are reported per IQR. RESULTS: Median concentrations (in micrograms per cubic metre) were 32 (IQR 25-38) for NO(2) (n=465), 46 (41-52) for O(3) and 21 (18-21) for PM(10) (n=481). In total, 44%, 29% and 27% had controlled, partly controlled and uncontrolled asthma, respectively. The ordinal ORs for O(3) and PM(10) with asthma control were 1.69 (95% CI 1.22 to 2.34) and 1.35 (95% CI 1.13 to 1.64), respectively. When including both pollutants in the same model, both associations persisted. Associations were not modified by sex, smoking status, use of inhaled corticosteroids, atopy, season of examination or body mass index. Both pollutants were associated with each of the three main domains of control. CONCLUSIONS: The results suggest that long-term exposure to PM(10) and O(3) is associated with uncontrolled asthma in adults, defined by symptoms, exacerbations and lung function.

Immunological differences in the global release of the major cat allergen Fel d 1 are influenced by sex and behaviour.

The biological function of Fel d 1, the major cat allergen released in the environment, is still unclear despite studies suggesting a putative role in chemical communication. Structural and immunological polymorphisms of Fel d 1 have been described. This study examined how Fel d 1 immunological polymorphism may have a physiological origin by estimating a potential relationship with the sex of cats and cat-human interactions. Samples from bath washes of 21 cats were screened to study antibody binding to Fel d 1 using an ELISA. Personality and Tolerance Handling scores were used to assess the behaviour of the cats. In the washes, Fel d 1 concentrations were significantly lower in females than in males (P<0.05). Slopes from the ELISA dose-dependent curves varied among the cats: males secreted Fel d 1 variants with higher antibody recognition than females (P<0.01). Females that were aggressive and difficult to handle displayed a diminished slope value, and therefore a weaker Fel d 1 immunoreactivity in global washes, compared to females that were sociable (P=0.09) and easy to handle (P=0.07). This study shows a variable immunological polymorphism of Fel d 1 within a cat population, particularly between males and females, and this polymorphism appears to be related to cat-human interactions.

Differences in allergen-induced T cell activation between allergic asthma and rhinitis: Role of CD28, ICOS and CTLA-4.

BACKGROUND: Th2 cell activation and T regulatory cell (Treg) deficiency are key features of allergy. This applies for asthma and rhinitis. However with a same atopic background, some patients will develop rhinitis and asthma, whereas others will display rhinitis only. Co-receptors are pivotal in determining the type of T cell activation, but their role in allergic asthma and rhinitis has not been explored. Our objective was to assess whether allergen-induced T cell activation differs from allergic rhinitis to allergic rhinitis with asthma, and explore the role of ICOS, CD28 and CTLA-4. METHODS: T cell co-receptor and cytokine expressions were assessed by flow cytometry in PBMC from 18 house dust mite (HDM) allergic rhinitics (R), 18 HDM allergic rhinitics and asthmatics (AR), 13 non allergic asthmatics (A) and 20 controls, with or without anti-co-receptors antibodies. RESULTS: In asthmatics (A+AR), a constitutive decrease of CTLA-4+ and of CD4+CD25+Foxp3+ cells was found, with an increase of IFN-γ+ cells. In allergic subjects (R + AR), allergen stimulation induced CD28 together with IL-4 and IL-13, and decreased the proportion of CTLA-4+, IL-10+ and CD4+CD25+Foxp3+ cells. Anti-ICOS and anti-CD28 antibodies blocked allergen-induced IL-4 and IL-13. IL-13 production also involved CTLA-4. CONCLUSIONS: T cell activation differs between allergic rhinitis and asthma. In asthma, a constitutive, co-receptor independent, Th1 activation and Treg deficiency is found. In allergic rhinitis, an allergen-induced Treg cell deficiency is seen, as well as an ICOS-, CD28- and CTLA-4-dependent Th2 activation. Allergic asthmatics display both characteristics.

Environmental home inspection services in Western Europe.

This review deals with environmental home inspection services in Western Europe provided for patients at the request of attending physicians to improve patient management. Such requests are usually motivated by respiratory or general symptoms which occur or worsen at home. The visit includes a standardised questionnaire as well as environmental sampling such as mite-allergen measurement, mould identification and volatile organic compound (VOC) measurements. Besides, some non-respiratory indoor risks are also taken into account. Following the visit, a report is sent to the family and the attending physician. These services have been developed since the early 1990s, but evaluation of their efficacy is still limited. Some studies have demonstrated a reduction in mite-allergen levels and clinical improvement following the visit and implementation of advice provided to the family. However, more studies are needed to further document efficacy and also perform cost-benefit analysis of these services.

Insights into severe asthma control as assessed by guidelines, pulmonologist, patient, and partner.

INTRODUCTION: The most recent guidelines on asthma management advocate a treatment strategy based on control of the disease rather than severity, a switch based on reported evidence. AIMS: This observational, questionnaire-based study set out to investigate how control of the disease is assessed by the physician as well as the patient and his/her live-in partner and to compare these assessments with an assessment made according to the guidelines. METHODS: In 169 patients with severe, persistent asthma on at least a high-dose inhaled corticosteroid plus an inhaled long-acting ß2-agonist, control of the disease was assessed by the pulmonologist, the patient, and the patient's live-in partner. These assessments were compared with an assessment based on the guidelines. Results. Both patients and partners tended to judge disease control as better than their pulmonologists who, in turn, estimated control as acceptable in 58% of their patients in whom the guidelines would advocate more aggressive treatment. The most common guidelines criteria defining inadequate control in the "uncontrolled" 87.4% of this population were "limitation of physical activity" (72.3%) and "FEV1" ≤ 85% of personal best" (63.3%). CONCLUSIONS: To assess control in severe asthma, the patient's opinion is of limited value, as is that of their partners. Although a guidelines-based strategy has been shown to be effective in clinical trials conducted on large-scale populations in which mild or moderate disease is predominant, more aggressive treatment to achieve definitive control may not be appropriate in the 10% of asthma sufferers with severe disease; in everyday practice, lung specialists appear to implement such a strategy.

Distribution of core fragments from the major cat allergen Fel d 1 is maintained among the main anatomical sites of production.

BACKGROUND: Polymorphism of Fel d 1 has long been observed, but structural characterization of Fel d 1 variants among the various sites of production and animals is still missing. This study was aimed at elucidating the structural polymorphism of this protein as a function of the site of production and the resulting influence on the immunological behavior of the allergen. METHODS: Fel d 1 was water-extracted from the 4 main sites of production, i.e. cheek zone, interdigital zone, anal sac (AS), and chest area and a panel of 10 cats. Fel d 1-like materials were immunoblotted, immunopurified and characterized by MALDI-TOF MS. Immunoreactivity was studied using ELISA dose-dependent curves at equilibrium. RESULTS: In all areas, 4-10 isoforms ranging from 7 to 40 kDa were detected by MS. Essentially two truncated heterodimers of 13-14 and 16-17 kDa were identified together with intact Fel d 1 in all compartments and they were largely predominant in AS. These core fragments were found to contribute to a variable recognition by antibodies in a panel of ELISA. CONCLUSIONS: Our study identified truncated dimers of Fel d 1, probably resulting from proteolytic degradation of both chains and present in all cats. Core fragments are largely distributed among anatomical sites of production and especially well represented in AS. They are recognized as intact allergens by antibodies and may therefore introduce discrepancies in allergen measurement depending on the variable amount of intact and degraded Fel d 1 produced by the cat.

Phenotypic determinants of uncontrolled asthma.

BACKGROUND: Although uncontrolled asthma remains frequent, determinants of asthma control are poorly studied. OBJECTIVES: The aim was to estimate the distribution and the phenotypic characteristics of asthma control in 2 groups of subjects defined by the use of inhaled corticosteroids (ICS) in the past 12 months, in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). METHODS: Five hundred one adult current patients with asthma who participated in the follow-up of the EGEA study were included. Asthma control was assessed from survey questions reflecting asthma control, as defined in the 2006 Global Initiative for Asthma guidelines. The factors analyzed were age, sex, educational level, body mass index, active and passive smoking, sensitization to aeroallergens, total IgE, rhinitis, chronic cough/phlegm, and age at asthma onset. Analyses were stratified according to ICS use. RESULTS: Uncontrolled asthma was more frequent in ICS users (27.6%, 35.0%, and 37.4% with controlled, partly-controlled, and uncontrolled asthma respectively) compared with non-ICS users (60.0%, 23.9%, and 16.1%, respectively). In ICS users, chronic cough or phlegm and female sex were independently and significantly related to uncontrolled asthma. In non-ICS users, high total IgE and sensitization to molds were associated with uncontrolled asthma. Smoking and rhinitis were not associated with asthma control. CONCLUSION: Optimal asthma control remained unachieved in the majority of patients with asthma in this study. Factors associated with uncontrolled asthma were different in ICS users (chronic cough/phlegm, female sex) and non-ICS users (high total IgE and sensitization to molds).

Allergen-specific immunotherapy in allergic rhinitis and asthma. Mechanisms and proof of efficacy.

Appeared at the beginning of the 20th century, allergen-specific immunotherapy (SIT) has long been used in allergic rhinitis and asthma without any knowledge of its mechanisms of action or any tangible proof of its efficacy. However, from the beginning of the era of evidence-based medicine, a number of placebo-controlled studies have been published and reached a sufficient number to assess the cellular events induced by SIT and allow meta-analysis to provide guidelines based on proofs. Controlled studies and meta-analysis concerned not only subcutaneous immunotherapy but also the sublingual route, demonstrating an effect of SIT on symptoms and medication use. Most recently sublingual tablets were proposed in allergic rhinitis. This paper reviews the mechanisms of SIT, the evidence of efficacy of SIT from the injective to the sublingual route and reminds the current guidelines.

Effect of 17q21 variants and smoking exposure in early-onset asthma.

BACKGROUND: A genomewide association study has shown an association between variants at chromosome 17q21 and an increased risk of asthma. To elucidate the relationship between this locus and disease, we examined a large, family-based data set that included extensive phenotypic and environmental data from the Epidemiological Study on the Genetics and Environment of Asthma. METHODS: We tested 36 single-nucleotide polymorphisms (SNPs) in the 17q21 region in 1511 subjects from 372 families for an association with asthma. We also tested for genetic heterogeneity according to the age at the onset of asthma and exposure to environmental tobacco smoke in early life. RESULTS: Eleven SNPs were significantly associated with asthma (P<0.01), of which three (rs8069176, rs2305480, and rs4795400) were strongly associated (P<0.001). Ordered-subset regression analysis led us to select an onset at 4 years of age or younger to classify patients as having early-onset asthma. Association with early-onset asthma was highly significant (P<10(-5) for four SNPs), whereas no association was found with late-onset asthma. With respect to exposure to environmental tobacco smoke in early life, we observed a significant association with early-onset asthma only in exposed subjects (P<5x10(-5) for six SNPs). Under the best-fitting recessive model, homozygous status (GG) at the most strongly associated SNP (rs8069176) conferred an increase in risk by a factor of 2.9, as compared with other genotypes (AG and AA) in the group exposed to environmental tobacco smoke (P=2.8x10(-6); P=0.006 for the test for heterogeneity of the SNP effect on early-onset asthma between groups with tobacco exposure and those without such exposure). CONCLUSIONS: This study shows that the increased risk of asthma conferred by 17q21 genetic variants is restricted to early-onset asthma and that the risk is further increased by early-life exposure to environmental tobacco smoke. These findings provide a greater understanding of the functional role of the 17q21 variants in the pathophysiology of asthma.

Asthma and allergy: short texts and recommendations of the expert conference of the French Speaking Pneumology Society (SPLF), in partnership with the French Society of Allergology and Clinical Immunology (SFAIC), the French Society of Occupational Medicine (SFMT) and the "Asthma-Allergy" association.

The Asthma Plan published by the French Health Ministry in 2002, the experts conferences edited by ANAES on therapeutic education and follow-up of asthma, the inclusion of this disease in the Public Health Law have been remarkable steps in France during the last few years. The medical community, more particularly the pneumological community, has shown its commitment in the treatment of this public health problem. But allergy was not sufficiently taken into account, although it is responsible for nearly 50 to 60% cases of asthma. In most so-called developed countries the prevalence of asthma and of allergies has increased in the last twenty years. Its progress varies according to country and age group: the increased prevalence of allergy, more specifically of rhinitis and eczema, is most marked in children aged 6-7 year. The prevalence of asthma seems to have reached a plateau in certain northern countries or seems to have decreased in 13-14 year olds (Anglo-Saxon countries). There were multiple reasons, generally attributed to changes in life-style. Asthma is the result of an interaction between a genetic predisposition and the environment, where allergens are present, but also smoking. The relationships between allergy and asthma are complex. This conference discussed the various essential issues that face doctors who treat patients with asthma in their daily practice. The risk factors, the methods of exploration in children and adults and the specific treatments are, indeed, essential issues to be evaluated in a frequent pathology that interests a large number of physicians. The variety of experts is wide, representing pneumology (French Speaking Pneumology Society), the occupational medicine world (French Society of Occupational Medicine), the allergic pathology (French Society of Allergology and Clinical Immunology), and patients with the patient association "Asthma & Allergy", physicians belonging to the general medicine community, general hospitals, private hospitals and academic hospitals in France. The proposed guidelines are aimed at helping practitioners in distinguishing what is established from what remains to be demonstrated and/or assessed with respect to the different modalities for the exploration or treatment of allergic asthma.

Evidence for linkage of a new region (11p14) to eczema and allergic diseases.

Asthma, allergic rhinitis (AR) and atopic dermatitis also called eczema are allergic co-morbidites, which are likely to depend on pleiotropic genetic effects as well as on specific genetic factors. After a previous genome-wide linkage screen conducted for asthma and AR in a sample of 295 French EGEA families ascertained through asthmatic subjects, the aim here was to search for genetic factors involved in eczema and more particularly the ones shared by the three allergic diseases using the same EGEA data. In this sake, eczema and phenotypes of "allergic disease" accounting for the joint information on the presence/absence of the three diseases were examined by linkage analyses using the maximum likelihood binomial method. A fine mapping was carried out in regions detected for potential linkage, followed by association studies using the family-based association test (FBAT). Evidence for linkage to 11p14 region was shown for "allergic disease" and eczema. Linkage was also indicated between eczema and 5q13 and between "allergic disease" and both 5p15 and 17q21 regions. Fine mapping supported the evidence of linkage to 11p14 and FBAT analyses showed the association between "allergic disease" and a marker located at the linkage peak on 11p14. Further investigations in this region will allow identifying genetic factor(s) which could have pleiotropic effect in the three allergic diseases.

[Exacerbation in asthma: definitions and immunopathology]. / Exacerbations dans l'asthme: définitions et immunopathologie.

There is no unequivocal definition of exacerbation in asthma. These are defined as episodes of increased or aggravated respiratory symptoms or as use of oral corticosteroid therapy. Viral infection is the most frequent cause of exacerbations. Inflammation during exacerbations is heterogeneous. It may be associated with bronchial hypereosinophilia, which is used as a predictive marker for exacerbation, and with neutrophilia, which is more resistant to corticosteroids. During viral infection, an inappropriate Th1 antiviral inflammation develops, associated with the intrinsic Th2 activity that leads to an aberrant immune response. Exacerbations secondary to allergen exposure are classically described as due to a Th2-type inflammation; but Th1 response also seems to play a role. Exposure to air pollutants appears able not only to induce bronchial inflammation but also to potentiate the inflammatory reactions of patients with exacerbations.

Assessment of a therapeutic education programme for asthma patients: "un souffle nouveau".

The aim of this study was to evaluate the impact of a new patient education programme on adults with asthma. This self-management programme included an individual assessment of patient's needs and two educational group sessions. Teaching methods and session content are described as well as caregivers training programme. The training sessions included a written asthma action plan based on symptoms and personal peak expiratory flow. Patients (n = 238) aged from 18 to 60 years were allocated to the intervention (group A) or control group (group B). Patients filled during 1 year a daily diary and questionnaire and they were administered telephone interviews. 127 patients were included in the treatment program and 111 in the control group. There was a significant improvement in the educated group with regard to symptoms free days (P = 0.03), number of awakenings (P = 0.04), consumption of corticosteroids (P = 0.03), consumption of beta2-agonists (P = 0.03), and quality of life score (P = 0.01). In conclusion, this study validates a specific educational approach named "un souffle nouveau".

[Epidemiology of seasonal spring-time allergic rhinitis in adults in France]. / Epidémiologie des rhinites allergiques saisonnières printanières chez l'adulte en France.

OBJECTIVE: Describe the profile of patients consulting a general practitioner or allergologist for seasonal spring-time allergic rhinitis (SAR) in France. METHODS: 3.348 physicians (3.284 general practitioners and 64 allergologists) recruited in 4 monthly episodes from March to June 1998, 34.851 patients consulting for SAR. Using a questionnaire, demographical data concerning the practitioners consulted and all the patients were collected. For 12,420 patients the symptomatology, history of asthma and ongoing treatment for SAR were analysed by comparing the population consulting a general practitioner (A) or an allergologist (B). RESULTS: Mean age for all patients with suspected SAR was of 37.1 +/- 15.7 years with a majority of women (54.90%). For 1,441 patients, it was the first consultation for this disorder, notably with a general practitioner, (11.1 vs. 2.4%). Aqueous rhinorrhea, sneezing and nasal obstruction were the most frequent symptoms noted, without significant difference between the type of practitioner consulted. 5.711 patients had undergone previous allergy tests, with more skin tests in the group consulting an allergologist (78 vs. 44.9%). Association with history of asthma was similar in both groups (30%). Impact on daily life was almost identical, whether isolated or associated with past history of asthma (56 vs. 51.6%), but differed with regard to sleep (56.7 vs. 21.1%). During the consultation, 5.889 patients were already treated with antihistamines (83.2%), whatever the type of practitioner consulted. CONCLUSION: Seasonal spring-time allergic rhinitis is a frequent pathology, which significantly impairs quality of life. There is little difference in patients' profile whether they consult a general practitioner or an allergologist.

Phenotypes of asthma revisited upon the presence of atopy.

Immunological studies claimed that atopic and non-atopic asthma share more similarities than differences. However, these two phenotypes of asthma are considered to be distinguishable upon distinct clinical patterns, which were not systematically assessed before in a large population. We studied characteristics discriminating atopic from non-atopic asthma among 751 asthmatic patients and 80 factors were analysed in univariate and multivariate analysis. Age, age of onset of asthma, female/male ratio were higher in non-atopic (n=200) than in atopic (n=551) asthmatics. Familial asthma, seasonal symptoms, rhinitis, conjunctivitis, allergen-triggered symptoms, improvement in altitude, exercise-induced asthma were associated with atopy. Non-atopic asthmatics displayed lower FEV(1) and FVC. Smoking was more frequent and asthma was more severe in these patients. Younger age, early onset, male sex, rhinitis and smoking were independent factors discriminating atopic from non-atopic asthma. This study establishes in a large population of asthmatics that although similarities exist between atopic and non-atopic asthma, two clinical phenotypes can still distinguish both kinds of asthma.

[Pathophysiological mechanisms of asthma and atopy: old and new concepts]. / Mécanismes physiopathologiques de l'asthme et de l'atopie: anciens et nouveaux concepts.

After the discovery of IgE, fundamental immunology studies done during the 1980s and 1990s established that allergic reactions were a particular form of inflammatory reaction governed by Th2 lymphocytes. However, this model, while relevant to atopy, is insufficient to explain allergies, and notably asthma, in which Th1 inflammation is associated. The recent concept that natural tolerance is deficient in atopic subjects, increased in allergic subjects, and maximal in symptomatic allergic subjects, reconciles these conflicting findings by proposing a model in which three axes of T cell activation are involved, namely Th2, Th1 and regulatory T cells.

Clustering patterns of LOD scores for asthma-related phenotypes revealed by a genome-wide screen in 295 French EGEA families.

A genome-wide scan for asthma phenotypes was conducted in the whole sample of 295 EGEA families selected through at least one asthmatic subject. In addition to asthma, seven phenotypes involved in the main asthma physiopathological pathways were considered: SPT (positive skin prick test response to at least one of 11 allergens), SPTQ score being the number of positive skin test responses to 11 allergens, Phadiatop (positive specific IgE response to a mixture of allergens), total IgE levels, eosinophils, bronchial responsiveness (BR) to methacholine challenge and %predicted FEV(1). Four regions showed evidence for linkage (P