Protocol and population
Through the 6 Cities Study, the French section of the second phase of ISAAC investigation conducted in France in 2000–1, 9,615 primary schoolchildren were invited in the six French cities (Bordeaux, Clermont-Ferrand, Créteil, Marseille, Strasbourg and Reims) to undergo clinical tests and their parents to complete a standardized medical questionnaire derived from the International ISAAC questionnaire . The clinical tests, performed at school by qualified physicians, included a skin examination to detect atopic eczema, a test of bronchial hyperactivity to effort, and skin prick tests (SPT) to identify the existence of an allergic hypersensitivity.
The standardized questionnaire included sections on socio-demographic and risk factors, health (asthma, allergic rhinitis, eczema, allergies), management, use of care facilities, treatment, compliance, lifestyle, housing, early events of life. Children were also interviewed also on school absenteeism due to asthma. Details of the survey are presented elsewhere .
Asthma definition and characterization
Exact standardized questions used to identify through the questionnaire children with asthma and to characterize them by the existence of a diagnosis or treatment were:
During the past 12 months, has your child (he/she) ever had wheezing or whistling in the chest at any time? (“YES” corresponded to have ever had wheezing or whistling)
Has your child ever had asthma? (“YES” corresponded to have ever had asthma)
Has your child ever been diagnosed with asthma by a doctor? (“YES” corresponded to have had a diagnosis of asthma).
Then, if the child was treated, the question was asked:
During the last 12 months, has your child (he/she) taken medication for wheezing or asthma also during or after physical effort? If the answer to this question was “YES”, the child was considered treated for his/her asthma. If the answer to this question was “NO”, the child was considered untreated.
The following three definitions of asthma (statistical variable) were used in our study:
· "Current asthma" as defined by report of wheezing or whistling in the chest in the last twelve months and ever asthma in life (dichotomous variable).
· "Asthma diagnosed by a physician" (dichotomous variable).
· "Treated asthma" (dichotomous variable).
In addition, to better characterize asthma the following characteristics were considered:
· Clinical severity of asthma according to GINA (http://www.gina.org), the number of crises during the past 12 months, the number of wheezing episodes that have awakened the child in the last 12 months, the number of asthma attacks, the number of crises that prevented him/her from speaking in the past 12 months, the number of wheezing episodes during or after exercise in the last 12 months, hospitalization during the last 12 months, and the number of school days missed in the last 12 months.
· Therapeutic intervention: asthma medication, asthma attacks prevention by parents, knowledge of medication to give for asthma attacks by parents, health care of the child's asthma, including prevention of asthma attacks, and the use of a peak flow-meter.
Allergic history and Exercise-Induced Asthma (EIA)
· Allergic sensitization was defined on the basis of positive skin allergy tests. The skin tests were performed by the SPT technique according to the ISAAC protocol with indoor and outdoor allergens ( e.g. Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat hair, Alternaria, cockroach, grass, etc.) and food allergens (e.g., the trophoallergenes, milk, fish, eggs, peanuts, etc.), with a positive and negative control to eliminate false positives and negatives . Three variables were considered: the SPT positivity to indoor allergens, SPT positivity to outdoor allergens, and SPT positivity to trophoallergens.
· Exercise-induced Asthma (EIA) was assessed by measuring changes in peak expiratory flow before and after a running test lasting six minutes. We defined a test as positive when the peak expiratory flow rate fell to either less than 10% or less than 15%, respectively. In the analysis, we have used these two variables: BHR10 (bronchial hyper-responsiveness to effort with decreased lung function of 10%) and BHR15 (bronchial hyper-responsiveness to effort with decreased lung function of 15%).
· Allergic comorbidities: lifetime eczema, lifetime allergic rhinitis and other serious health problems.
The following factors were considered as co-variables in the statistical models:
· Individual factors: the city (Bordeaux, Clermont-Ferrand, Créteil, Marseille, Strasbourg and Reims), sex, age in years, the Body Mass Index (BMI) defined by the ratio of weight to height squared in kg/m2, the heritability of asthma (i.e., maternal asthma) and number of siblings.
· Socio-demographic factors: ethnicity of the two parents, educational level of the two parents, paternal Socio-Economic-Status (SES) as defined by the classification of INSEE, i.e., the French National Institute for Statistics (e.g., farmers, employees,…), and marital status of the child’s parents and medical coverage (i.e., health insurance, mutual payment, free medical care, personal insurance, no welfare at all) of the family.
· Environmental condition at the period of the survey (e.g., smoking, pets, housing situation, tasks, moisture, exposure to traffic, etc.).
· Early life events, i.e., prematurity, birth weight, breastfeeding.
Dichotomous or categorical variables with the exception of BMI were considered in the analysis.
Statistical and epidemiological analyses
The type of asthma (“diagnosed or not”, “treated or not”) was investigated with respect to child’s characteristics, clinical characteristics of asthma, co-morbidity, asthma management, environmental exposure at the period of the survey and early life events in order to identify factors that were associated with the absence of asthma diagnosis and treatment. The chi-square test was used to compare percentages between groups. Analysis of variance (ANOVA) was used to compare differences between continuous variables. Through a logistic regression analysis adjusting for age, sex, city and BMI, the factors associated with the different types of asthma were identified. Associations were expressed in terms of Odds Ratios (OR) and 95% confidence intervals (95% CI). The study on the use of asthma medications was restricted to children diagnosed with asthma, since not being diagnosed greatly diminished the chances of being treated for this disease. All statistical analyses were performed using SAS ® version 9.