Phenotypic determinants of uncontrolled asthma

doi:10.1016/j.jaci.2009.06.010

Journal of Allergy and Clinical Immunology

Volume 124, Issue 4, October 2009, Pages 681-687.e3

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https://doi.org/10.1016/j.jaci.2009.06.010 Get rights and content

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).

Section snippets

Population

This is a cross-sectional study using data from the case control and family-based EGEA2 study, the 12-year follow-up of the EGEA1 study. Protocol and descriptive characteristics of the EGEA1 study have been previously published.15, 16 Briefly, 2047 subjects were enrolled at baseline, including 388 children (<16 years) and adult patients with asthma from chest clinics, their 1244 first-degree relatives, and 415 population-based controls. Approximately 10 years later, this population was

Description of the population

Main personal, sociodemographic, and clinical characteristics of the population with asthma are presented in Table I. The mean age of the population was 39 years, and half of the subjects were nonsmokers and not exposed to tobacco smoke at the time of the survey. Regarding allergic phenotypes, 60.2% reported allergic rhinitis, 61.3% had total IgE ≥100 IU/mL, and 80.8% were sensitized to any of the 11 allergens. Chronic cough or phlegm was reported by 16% of the subjects. Patients with asthma

Discussion

Less than half (44%) of this population of patients with asthma participating in the phase 2 of the EGEA study had a controlled asthma, on the basis of characteristics of asthma control as defined in the current GINA guidelines. The proportion of controlled asthma was lower in ICS users, in whom only one fourth of the asthmatics had a controlled asthma. The determinants for uncontrolled asthma were different in ICS users and non-ICS users. In ICS users, chronic cough or phlegm and female sex

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A systematic literature review of burden of illness in adults with uncontrolled moderate/severe asthma
2022, Respiratory Medicine
There are limited published data on the burden of moderate/severe uncontrolled asthma.
We conducted a systematic literature review to better understand the impact of moderate-to-severe asthma in the US, the UK, Germany, France, Italy, Spain, Canada, Japan, and Australia in terms of prevalence, clinical measures, health-related quality of life (HRQoL) and economic burden, for patients whose asthma is uncontrolled despite inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) therapy.
The prevalence of uncontrolled asthma among patients with moderate/severe disease varied but was as high as 100% in some subgroups. Patients with uncontrolled asthma generally had poor lung function (mean/median pre-bronchodilator forced expiratory volume in 1 second [FEV₁]: 1.69–2.45 L; mean/median pre-bronchodilator percent predicted FEV₁: 57.2–79.7). There was also a substantial but variable exacerbation burden associated with uncontrolled asthma, with the annualised rate of exacerbations ranging from 1.30 to 7.30 when considering various patient subgroups. Furthermore, the annualised rate of severe exacerbations ranged from 1.66 to 3.60. The HRQoL burden measured using disease-specific and generic instruments consistently demonstrated substantial impairment of HRQoL for those with uncontrolled asthma; Asthma Quality of Life Questionnaire scores ranged from 3.00 to 5.20, whilst EurQol-5 Dimensions index scores ranged from 0.53 to 0.59. Direct, indirect and total costs together with consumption of other healthcare resources associated with managing uncontrolled asthma were also substantial in the population studied; no caregiver burden was identified.
Our findings suggest that significant unmet needs exist for patients with uncontrolled asthma despite the availability of ICS/LABA therapy. Novel treatments are needed to help reduce the burden to patients, healthcare systems and society.
Long-term air pollution exposure is associated with increased severity of rhinitis in 2 European cohorts
2020, Journal of Allergy and Clinical Immunology
Citation Excerpt :
The EGEA18,19 (https://egeanet.vjf.inserm.fr/) is a French cohort of 2047 participants (patients with asthma—adults or children—enrolled from hospital chest clinics, their first-degree relatives, and controls who were recruited from other hospital wards or from electoral lists) enrolled between 1991 and 1995 from 5 French cities. The first follow-up was conducted between 2003 and 2007 (EGEA2, N = 212119,20) and the second between 2011 and 2013 (EGEA3, N = 155821). The ECRHS22 is a population-based cohort of young adults, enriched with participants with respiratory symptoms, recruited from 1992 to 1994 in 28 western European cities (ECRHS I, N = 17,880; http://www.ecrhs.org/) and followed up twice: between 2000 and 2002 (ECRHS II, N = 10,93323) and between 2011 and 2013 (ECRHS III, N = 7,040).
Very few studies have examined the association between long-term outdoor air pollution and rhinitis severity in adults.
We sought to assess the cross-sectional association between individual long-term exposure to air pollution and severity of rhinitis.
Participants with rhinitis from 2 multicenter European cohorts (Epidemiological Study on the Genetics and Environment on Asthma and the European Community Respiratory Health Survey) were included. Annual exposure to NO₂, PM₁₀, PM_2.5, and PM_coarse (calculated by subtracting PM_2.5 from PM₁₀) was estimated using land-use regression models derived from the European Study of Cohorts for Air Pollution Effects project, at the participants’ residential address. The score of rhinitis severity (range, 0-12), based on intensity of disturbance due to symptoms reported by questionnaire, was categorized into low (reference), mild, moderate, and high severity. Polytomous logistic regression models with a random intercept for city were used.
A total of 1408 adults with rhinitis (mean age, 52 years; 46% men, 81% from the European Community Respiratory Health Survey) were included. The median (1st quartile-3rd quartile) score of rhinitis severity was 4 (2-6). Higher exposure to PM₁₀ was associated with higher rhinitis severity (adjusted odds ratio [95% CI] for a 10 μg/m³ increase in PM₁₀: for mild: 1.20 [0.88-1.64], moderate: 1.53 [1.07-2.19], and high severity: 1.72 [1.23-2.41]). Similar results were found for PM_2.5. Higher exposure to NO₂ was associated with an increased severity of rhinitis, with similar adjusted odds ratios whatever the level of severity. Adjusted odds ratios were higher among participants without allergic sensitization than among those with, but interaction was found only for NO_2.
People with rhinitis who live in areas with higher levels of pollution are more likely to report more severe nasal symptoms. Further work is required to elucidate the mechanisms of this association.
Woman's asthma throughout life: Towards a personalized management?
2020, Revue des Maladies Respiratoires
Au cours de la vie de la femme, l’asthme peut affecter de façon diverse celle-ci avec l’apparition d’un asthme prémenstruel actuellement sous diagnostiqué. On estime environ à 20 % la proportion de femmes asthmatiques ayant un asthme prémenstruel, plus fréquent chez les patientes ayant un asthme sévère. Les femmes asthmatiques sont à haut risque d’exacerbations et d’asthme sévère. L’asthme est la maladie chronique la plus fréquente au cours de la grossesse avec des complications potentielles materno-fœtales. Les médicaments de l’asthme présentent une innocuité pour le fœtus et il est indispensable de poursuivre le traitement préexistant et de l’adapter à l’évolution de l’asthme pendant la grossesse. Les stéroïdes sexuels modulent la structure et la fonction des cellules bronchiques et immunitaires. La compréhension de leur rôle dans la pathogénie de l’asthme est compliquée par les effets ambivalents des œstrogènes bronchodilatateurs et pro-inflammatoires ainsi que la diversité de réponse à leur association à la progestérone. L’asthme de la ménopause est une entité clinique et fait partie d’un des phénotypes d’asthme sévère non-allergique et peu corticosensible. L’évaluation ciblée environnementale domestique et professionnelle permet d’optimiser la prise en charge de l’asthme.
In a woman's life, asthma can affect her in a variety of ways, with the onset of premenstrual asthma currently under-diagnosed. It is estimated that about 20% of women with asthma have premenstrual asthma, which is more common in patients with severe asthma. Women with asthma are at high risk of exacerbations and of severe asthma. Asthma is the most common chronic disease during pregnancy with potential maternal and foetal complications. Asthma medications are safe for the foetus and it is essential to continue pre-existing treatment and adapt it to the progress of asthma during the pregnancy. Sex steroids modulate the structure and function of bronchial and immune cells. Understanding their role in asthma pathogenesis is complicated by the ambivalent effects of bronchodilating and pro-inflammatory oestrogens as well as the diversity of response to their association with progesterone. Menopausal asthma is a clinical entity and is part of one of the phenotypes of severe non-allergic and low steroid-sensitive asthma. Targeted assessment of the domestic and professional environment allows optimization of asthma management.
Control of Allergic Rhinitis and Asthma Test for Children (CARATKids): Validation in Brazil and cutoff values
2017, Annals of Allergy, Asthma and Immunology
The Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) assesses asthma and allergic rhinitis control in children younger than 12 years.
To validate the Brazilian Portuguese version of the CARATKids and to define the cutoff values for identifying uncontrolled disease.
Children aged 6 to 12 years with asthma and allergic rhinitis were studied (n = 102). CARATKids, childhood Asthma Control Test (cACT), total nasal symptom score (TNSS), and visual analog scale (VAS) scores were obtained at baseline and after 4 to 6 weeks. Internal consistency, test-retest reliability, responsiveness, and validity of the Brazilian CARATKids were assessed according to the Consensus-based Standards for the Selection of Health Measurements Instruments checklist. The minimal clinically important difference (MCID) was evaluated using distribution and anchor methods. Spearman correlations were used to compare CARATKids scores with external measures of control. Receiver operating characteristic curve analysis was performed to establish cutoff values.
Fifty children completed both visits. The Cronbach α and intraclass correlation coefficient of CARATKids were 0.81 and 0.85, respectively. The Guyatt responsiveness index was −1.34, and within-patient change in clinically unstable patients (n = 31) was significant (P = .02). As for cross-sectional and longitudinal validity, correlation coefficients ranged from 0.58 to 0.77 (P < .001) and 0.30 to 0.57 (P < .05), respectively. The estimated MCID for CARATKids was 3. The optimal cutoffs (sensitivity and specificity) to exclude uncontrolled and controlled disease were 3 or less (97% and 67%) and 6 or greater (56% and 96%), respectively.
CARATKids is a reliable and valid tool to assess asthma and allergic rhinitis control in Brazilian children. A score of 6 or higher on CARATKids identifies uncontrolled disease, and a score of 3 or lower excludes poor disease control.
Specific IgE and IgG measured by the MeDALL allergen-chip depend on allergen and route of exposure: The EGEA study
2017, Journal of Allergy and Clinical Immunology
Citation Excerpt :
Subjects were recruited through self-completed questionnaires and an overall matching by months at examination, age (decade), sex, and center. About 11 years later, this population was invited for a follow-up (EGEA2) and 1601 participants (77.1% of the original cohort + 58 new family members) were subjected to a complete examination, which included serum samples.21 EGEA collection is certified ISO 9001 and referenced in the Biobank network by the number BB-0033-00043.
The nature of allergens and route and dose of exposure may affect the natural development of IgE and IgG responses.
We sought to investigate the natural IgE and IgG responses toward a large panel of respiratory and food allergens in subjects exposed to different respiratory allergen loads.
A cross-sectional analysis was conducted in 340 adults of the EGEA (Epidemiological study of the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy) (170 with and 170 without asthma) cohort. IgE and IgG responses to 47 inhalant and food allergen components were analyzed in sera using allergen microarray and compared between 5 French regions according to the route of allergen exposure (inhaled vs food allergens).
Overall 48.8% of the population had allergen-specific IgE levels of 0.3 ISAC standardized units (ISU) or more to at least 1 of the 47 allergens with no significant differences across the regions. For ubiquitous respiratory allergens (ie, grass, olive/ash pollen, house dust mites), specific IgE did not show marked differences between regions and specific IgG (≥0.5 ISU) was present in most subjects everywhere. For regionally occurring pollen allergens (ragweed, birch, cypress), IgE sensitization was significantly associated with regional pollen exposure. For airborne allergens cross-reacting with food allergens, frequent IgG recognition was observed even in regions with low allergen prevalence (Bet v 1) or for allergens less frequently recognized by IgE (profilins).
The variability in allergen-specific IgE and IgG frequencies depends on exposure, route of exposure, and overall immunogenicity of the allergen. Allergen contact by the oral route might preferentially induce IgG responses.
Socioeconomic position and outdoor nitrogen dioxide (NO<inf>2</inf>) exposure in Western Europe: A multi-city analysis
2017, Environment International
Citation Excerpt :
The main objective of the present analysis was to test the environmental justice hypothesis that people with lower SEP (defined at both individual and neighborhood level) were more exposed to traffic related air pollution exposure than people with higher SEP in Western Europe. This cross-sectional study included participants of three multicenter epidemiological European cohorts that had previously collaborated together (Boudier et al., 2013) and were involved in the ESCAPE study: the French Epidemiological family-based study of the Genetics and Environment of Asthma (EGEA2) (2003–2007) (Siroux et al., 2009), and two population-based studies: the European Community Respiratory Health Survey (ECRHSII) (1999–2002) (Jarvis, 2002) and The Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA2) (2001 − 2003) (Ackermann-Liebrich et al., 2005). Details on each cohort are given elsewhere (Siroux et al., 2009; Jarvis, 2002; Ackermann-Liebrich et al., 2005) and summarized in the supplementary materials.
Inconsistent associations between socioeconomic position (SEP) and outdoor air pollution have been reported in Europe, but methodological differences prevent any direct between-study comparison.
Assess and compare the association between SEP and outdoor nitrogen dioxide (NO₂) exposure as a marker of traffic exhaust, in 16 cities from eight Western European countries.
Three SEP indicators, two defined at individual-level (education and occupation) and one at neighborhood-level (unemployment rate) were assessed in three European multicenter cohorts. NO₂ annual concentration exposure was estimated at participants' addresses with land use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE; http://www.escapeproject.eu/). Pooled and city-specific linear regressions were used to analyze associations between each SEP indicator and NO₂. Heterogeneity across cities was assessed using the Higgins' I-squared test (I²).
The study population included 5692 participants. Pooled analysis showed that participants with lower individual-SEP were less exposed to NO₂. Conversely, participants living in neighborhoods with higher unemployment rate were more exposed. City-specific results exhibited strong heterogeneity (I² > 76% for the three SEP indicators) resulting in variation of the individual- and neighborhood-SEP patterns of NO₂ exposure across cities. The coefficients from a model that included both individual- and neighborhood-SEP indicators were similar to the unadjusted coefficients, suggesting independent associations.
Our study showed for the first time using homogenized measures of outcome and exposure across 16 cities the important heterogeneity regarding the association between SEP and NO₂ in Western Europe. Importantly, our results showed that individual- and neighborhood-SEP indicators capture different aspects of the association between SEP and exposure to air pollution, stressing the importance of considering both in air pollution health effects studies.

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: Supported by grants from Merck Sharp & Dohme (MSD); Hospital program of clinical research (PHRC)-Paris; National Research Agency - Health environment, health-work program; National Research Agency (ANR)- Biological collections for health program; French Agency of health safety, environment and work (AFSSET) and the Isere committee against respiratory diseases (COMARES).

: Disclosure of potential conflict of interest: C. Pison has served as a consultant for GlaxoSmithKline, Boehringer Ingelheim France, AstraZeneca, Nutricia, Numico, and Actéllion and has received research support from AB Science. The rest of the authors have declared that they have no conflict of interest.

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Asthma and lower airway diseasePhenotypic determinants of uncontrolled asthma

Background

Objectives

Methods

Results

Conclusion

Section snippets

Population

Description of the population

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

Respir Med

Respir Med

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

Respir Med

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Persistent asthma: disease control, resource utilisation and direct costs

Eur Respir J

The control of asthma in Italy: a multicentre descriptive study on young adults with doctor diagnosed current asthma

Allergy

Lack of control of severe asthma is associated with co-existence of moderate-to-severe rhinitis

Allergy

Role of symptoms and lung function in determining asthma control in smokers with asthma

Allergy

Relationships of active smoking to asthma and asthma severity in the EGEA study. Epidemiological study on the Genetics and Environment of Asthma

Eur Respir J

Asthma and lower airway disease
Phenotypic determinants of uncontrolled asthma