Prediction of asthma in young adults using childhood characteristics: Development of a prediction rule

doi:10.1016/j.jclinepi.2006.02.011

Journal of Clinical Epidemiology

Volume 59, Issue 11, November 2006, Pages 1207-1212

https://doi.org/10.1016/j.jclinepi.2006.02.011 Get rights and content

Abstract

Objective

To develop an easily applicable prediction rule for asthma in young adulthood using childhood characteristics.

Methods

A total of 1,055 out of 1,328 members of a Dutch birth cohort were followed from 2 to 21 years of age. Univariate and multivariate logistic regression analyses were used to evaluate the predictive value of childhood characteristics on asthma at 21 years of age. A prognostic function was developed, and the area under the receiving operating characteristic (ROC) curve was used to estimate the predictive ability of the prognostic models.

Results

Of the 693 responding subjects, 86 (12%) were diagnosed with asthma. Independent prognostic factors at ages 2 and 4 years were female gender (odds ratios (OR) 1.9 and 2.1; 95% confidence intervals (CI) 1.2–3.2 and 1.3–2.5), smoking mother (OR 1.6 and 1.6; CI 1.0–2.7 and 1.0–2.6), lower respiratory tract illness (OR 1.9 and 2.4; CI 1.0–3.6 and 1.4–4.0), and atopic parents (OR 2.1 and 1.9; CI 1.3–3.4 and 1.2–3.1). The predictive power of both models was poor; area under ROC curve was 0.66 and 0.68, respectively.

Conclusion

Asthma in young adulthood could not be predicted satisfactorily based on childhood characteristics. Nevertheless, we propose that this method is further tested as a tool to predict development of asthma.

Introduction

Asthma is an increasing health problem in Western societies [1]. Its pressure on health care facilities and budget is considerable. It is a challenge for primary health care to find ways to prevent and treat asthma, particularly in high-risk patients, who will benefit most from interventions. Early treatment of asthmatic symptoms might for instance prevent airway remodeling [2]. Adequate risk assessment, preferably by using easily obtainable information, is however, still difficult to achieve. Once it is possible to assess the individual risk of young children in the general population, both preventive and therapeutic intervention strategies as well as proper prognostic information to parents can be targeted at this group.

Prediction models, which estimate the probability of occurrence of a relevant outcome as a combined function of the levels of various predictors, are a helpful tool in the assessment of individual prognosis [3], [4]. Such clinical prediction models would be useful to distinguish individual children at high risk of developing asthma during adulthood from those at low risk.

So far, previous studies on this topic have focused on single childhood risk factors associated with persistence or recurrence of asthma in adulthood, such as severe asthma in childhood, other atopic disease, parental asthma, female gender, active cigarette smoking, positive skin prick test, decreased lung function, and bronchial hyperresponsiveness [5], [6], [7], [8]. Although these studies show that the presence of such factors will increase the relative risk for developing asthma in adulthood, they do not enable us to quantify an absolute risk score for an individual subject. Only very few studies attempted to provide an individual risk assessment of asthma or persistence of wheezing in childhood [9], [10].

So far, only Toelle et al. [11] have reported on a risk score to assess individual prognoses in adulthood based on data from the Belmont cohort study. The authors described a diagnostic algorithm of independent likelihood ratios. However, they did not develop a clinical prediction rule. The aim of the present study is to define prognostic factors and to develop an easily applicable prediction model that can be used in a primary health care setting to identify children at risk for asthma in young adulthood.

Section snippets

Study population and follow-up

All children born in the city of Nijmegen between September 1982 and September 1983, were invited to participate in a study on otitis media at their second birthday (N = 1,439). Of this birth cohort, subjects have been followed up prospectively from 2 to 4 years (N = 1,328) [12], [13].

At age 2 years a thorough history was taken of both upper respiratory tract infections (URTI) and lower respiratory tract illness (LRTI) during the first 2 years of life. Baseline parameters such as duration of

Results

At the age of 21 years, addresses of 1,055 subjects (79%) of the 1,328 original cohort members could be traced; 693 (66%) of these 1,055 subjects returned the questionnaire.

The 693 study members evaluated at age 21 years and the original cohort of 1,328 members did not differ significantly regarding gender distribution, history of breast feeding, family size, day care attendance, parental smoking habits, maternal educational level, recurrent URTI, LRTI, and antibiotic treatment at age 2 years (

Discussion

Independent predictors of asthma in young adulthood in children aged 2 to 4 years were female gender, smoking mother, LRTI, and parental atopic disease. The performance of a prognostic model including these parameters in terms of the occurrence of asthma in young adulthood was poor. It was not possible to find a cut-off point in the risk score that classified the children satisfactorily. In both models too many children were misclassified for each arbitrary threshold to be of any clinical use.

Acknowledgments

The authors thank Sonja van Oosterhout and Miriam Olling for secretarial work and Eline van Hattum for developing the database.

References (23)

G.A. Zielhuis et al.
Screening for otitis media with effusion in preschool children
Lancet
(1989)
G.A. Diamond
What price perfection? Calibration and discrimination of clinical prediction models
J Clin Epidemiol
(1992)
G.L. Grunkemeier et al.
Receiver operating characteristic curve analysis of clinical risk models
Ann Thorac Surg
(2001)
S. Illi et al.
Multicenter Allergy Study Group. The pattern of atopic sensitization is associated with the development of asthma in childhood
J Allergy Clin Immunol
(2001)
E.S. Ford
The epidemiology of obesity and asthma
J Allergy Clin Immunol
(2005)
K.G. Moons et al.
Penalized maximum likelihood estimation to directly adjust diagnostic and prognostic prediction models for overoptimism: a clinical example
J Clin Epidemiol
(2004)
T.M. Eagan et al.
Nonresponse in a community cohort study: predictors and consequences for exposure–disease associations
J Clin Epidemiol
(2002)
The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee
Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC)
Eur Respir J
(1998)
T. Haatela
Airway remodelling takes place in asthma—what are the clinical implications
Clin Exp Allergy
(1997)
J.H. Wasson et al.
Clinical prediction rules: applications and methodological standards
N Engl J Med
(1985)

A. Laupacis et al.

Clinical prediction rules: a review and suggested modifications of methodological standards

JAMA

(1997)

Cited by (33)

Asthma transition from childhood into adulthood
2017, The Lancet Respiratory Medicine
Citation Excerpt :
Many studies have followed up patients who have matured from the care of their paediatrician and the transition into adulthood either in a clinical35–37 or population-based setting. These population-based studies that cross the gap between childhood and adulthood address: persistence,3,20,24,34,38–63 remission,20,34,38–50,54–57 relapse,20,34,38,39,51–57,64 and new-onset of symptoms in adulthood (table).20,54–57,65–70 In contrast to paediatrics, adult asthma care has a definitive absence of longitudinal studies that start tracking the course of the disease at early adulthood and follow patients up for an adequate length of time.
Asthma is the most prevalent chronic respiratory disease both in children and adults and resembles a complex syndrome rather than a single disease. Different methods have been developed to better characterise distinct asthma phenotypes in childhood and adulthood. In studies of adults, most phenotyping relies on biomaterials from the lower airways; however, this information is missing in paediatric studies because of restricted accessibility. Few patients show symptoms throughout childhood, adolescence, and adulthood. Risk factors for this might be genetics, family history of asthma and atopy, infections early in life, allergic diseases, and lung function deficits. In turn, a large proportion of children with asthma lose their symptoms during school age and adolescence. This improved prognosis, which might also reflect a better treatment response, is associated with being male and with milder and less allergic disease. Importantly, whether clinical remission of symptoms equals the disappearance of underlying pathology is unknown. In fact, airway hyper-responsiveness and airway inflammation might remain despite the absence of overt symptoms. Additionally, a new-onset of asthma symptoms is apparent in adulthood, especially in women and in the case of impaired lung function. However, many patients do not remember childhood symptoms, which might reflect relapse rather than true initiation. Both relapse and adult-onset of asthma symptoms have been associated with allergic disease and sensitisation in addition to airway hyper-responsiveness. Thus, asthma symptoms beginning in adults might have originated in childhood. Equivocally, persistence into, relapse, and new-onset of symptoms in adulthood have all been related to active smoking. However, underlying mechanisms for the associations remain unclear, and future asthma research should therefore integrate standardised molecular approaches in identical ways in both paediatric and adult populations and in longitudinal studies.
Environmental and socioeconomic data do not improve the Predicting Asthma Risk in Children (PARC) tool
2015, Journal of Allergy and Clinical Immunology
Maternal second-hand smoke exposure in pregnancy is associated with childhood asthma development
2014, Journal of Allergy and Clinical Immunology: In Practice
Childhood asthma development has been associated with active maternal smoking during pregnancy, but its association with maternal second-hand smoke exposure in pregnancy needs to be evaluated.
We investigated longitudinal associations between maternal smoke exposure in pregnancy and childhood asthma development.
In a population-based cohort of 5619 seven-year-old Toronto children, parents reported age of physician-diagnosed asthma development, maternal smoking during pregnancy, home second-hand smoke exposure from pregnancy until 7 years, demographics, and family history of atopy. By using Cox proportional and discrete-time hazard survival analyses, we evaluated associations between asthma and maternal smoking or home second-hand smoke exposure in pregnancy.
During pregnancy, 5.0% of mothers smoked and 6.2% were nonsmokers and exposed to home second-hand smoke; 15.5% of children developed asthma. Children whose mothers smoked or were exposed to home second-hand smoke during pregnancy were more likely to develop asthma (adjusted hazard ratio [HR] 1.30 [95% CI, 1.06-1.60]). The association persisted for children of nonsmoking mothers with home second-hand smoke exposure during pregnancy (adjusted HR 1.34 [95% CI, 1.01-1.76]), children with asthma symptoms in the past year (adjusted HR 1.36 [95% CI, 1.03-1.79]), and after adjusting for home second-hand smoke exposure from birth to age 7 years.
Maternal home second-hand smoke exposure during pregnancy is associated with incident physician-diagnosed childhood asthma, even if the mother does not smoke actively during pregnancy. Childhood asthma prevention programs should include smoking cessation strategies targeted toward smokers who live in the homes of smoking and nonsmoking pregnant women as well as pregnant women who smoke.
A simple asthma prediction tool for preschool children with wheeze or cough
2014, Journal of Allergy and Clinical Immunology
Citation Excerpt :
It showed good internal validity and is distinguished by ease of use in primary care and epidemiologic studies. Several prediction models have been proposed for estimating the risk of persistent asthma in preschool children.8-16 Table III8,9,13,36 summarizes inclusion criteria, outcome, methods used to derive the tool, predictors, and performance for 3 tools that used a similar prediction interval as ours and had a sample size of greater than 300.
Many preschool children have wheeze or cough, but only some have asthma later. Existing prediction tools are difficult to apply in clinical practice or exhibit methodological weaknesses.
We sought to develop a simple and robust tool for predicting asthma at school age in preschool children with wheeze or cough.
From a population-based cohort in Leicestershire, United Kingdom, we included 1- to 3-year-old subjects seeing a doctor for wheeze or cough and assessed the prevalence of asthma 5 years later. We considered only noninvasive predictors that are easy to assess in primary care: demographic and perinatal data, eczema, upper and lower respiratory tract symptoms, and family history of atopy. We developed a model using logistic regression, avoided overfitting with the least absolute shrinkage and selection operator penalty, and then simplified it to a practical tool. We performed internal validation and assessed its predictive performance using the scaled Brier score and the area under the receiver operating characteristic curve.
Of 1226 symptomatic children with follow-up information, 345 (28%) had asthma 5 years later. The tool consists of 10 predictors yielding a total score between 0 and 15: sex, age, wheeze without colds, wheeze frequency, activity disturbance, shortness of breath, exercise-related and aeroallergen-related wheeze/cough, eczema, and parental history of asthma/bronchitis. The scaled Brier scores for the internally validated model and tool were 0.20 and 0.16, and the areas under the receiver operating characteristic curves were 0.76 and 0.74, respectively.
This tool represents a simple, low-cost, and noninvasive method to predict the risk of later asthma in symptomatic preschool children, which is ready to be tested in other populations.
Predicting asthma in preschool children with asthma-like symptoms: Validating and updating the PIAMA risk score
2013, Journal of Allergy and Clinical Immunology
Citation Excerpt :
For example, when follow-up actions are invasive or costly, false-positive results should be kept as low as possible. Compared with the predictive performance of previously reported models to predict asthma at age 6 to 7 years,1,3-9 the predictive probability of the updated PIAMA risk score at a cutoff point of 8 showed a high sensitivity (64% vs 9% to 57%1) but a low PPV (12% vs 24% to 75%1). Compared with the LR+ range of previously reported models to predict asthma at age 6 to 7 years (LR+ range, 1-121), the LR+ range of the updated PIAMA risk score was similar (1-10, depending on the selected cutoff).
The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) risk score predicts the probability of having asthma at school age among preschool children with suggestive symptoms.
We sought to externally validate the PIAMA risk score at different ages and in ethnic and socioeconomic subgroups of children in addition to updating it.
We studied 2877 children with preschool asthma-like symptoms participating in the multiethnic, prospective, population-based cohort study Generation R. The PIAMA risk score was assessed at preschool age, and asthma was predicted at age 6 years. Discrimination (concordance index [C-index]) and calibration were calculated. The PIAMA risk score was updated, and its performance was similarly analyzed.
At age 6 years, 6% (168/2877) of the children had asthma. The discriminative ability of the original PIAMA risk score to predict asthma in Generation R was similar compared with that in the PIAMA cohort (C-index = 0.74 vs 0.71). The predicted risks by using the original PIAMA risk score for having asthma at the age of 6 years tended to be slightly higher than the observed risks (8% vs 6%). No differences in discriminative ability were found at different ages or in ethnic and socioeconomic subgroups (P > .05). The updated PIAMA risk score had a C-index of 0.75.
The PIAMA risk score showed good external validity. The discriminative ability was similar at different ages and in ethnic and socioeconomic subgroups of preschool children, which suggests good generalizability. Further studies are needed to reproduce the predictive performance of the updated PIAMA risk score in other populations and settings and to assess its clinical relevance.
The evolution of the wheezy allergic infant
2010, Revue Francaise d'Allergologie
Une nouvelle classification des sifflements préscolaires récurrents est proposée, elle se fonde sur les circonstances temporelles d’apparition de l’atteinte respiratoire, distincte de celle utilisée dans les études épidémiologiques antérieures qui repose sur la durée et la chronologie des sifflements établies de manière rétrospective. Un phénotype clinique défini selon la présence ou l’absence de sifflements reste insuffisant. Une sensibilisation précoce persistante influe sur le développement futur d’un asthme. L’asthme est principalement considéré comme un trouble inflammatoire des voies aériennes dominé par un profil Th2. Il est maintenant évident que le développement d’une atteinte respiratoire sifflante précoce viro-induite, surtout par le rhinovirus, prédit le développement ultérieur d’un asthme. Une autre vision de l’asthme serait d’impliquer un défaut primaire de la fonction barrière de l’épithélium respiratoire facilitant l’abord aux tissus respiratoires des allergènes environnementaux, des micro-organismes et des polluants. L’asthme doit ne pas être considéré simplement en termes d’une réponse univoque cellulaire et systémique aux allergènes inhalés, mais comme une conséquence d’une interaction complexe entre l’environnement et l’appareil respiratoire. Malgré le contrôle des symptômes et la preuve de l’efficacité d’un traitement de fond par des stéroïdes inhalés à faible dose, les stratégies actuelles de traitement ne semblent pas modifier l’histoire naturelle de l’asthme préscolaire. Les leucotriènes sont clairement impliqués dans l’inflammation des voies respiratoires et probablement sont les principaux médiateurs du remodelage bronchique précoce.
A new classification of recurrent preschool wheezing is proposed, being based on the temporal circumstances of the onset of the respiratory attack. It is distinct from the classification used in prior epidemiological studies which was based retrospectively on the duration and time sequence of the wheezing. A clinical phenotype defined according to the presence or absence of wheezing is insufficient. Early persistent sensitization has an influence on the future development of asthma. Asthma is considered mainly as an inflammatory disorder of the airways dominated by a Th2-type pattern. It is now also evident that the development of a virus-associated wheezing illness, above all with rhinovirus, predicts the future development of asthma. An alternative view is that asthma is primarily a defect of epithelial barrier function that allows greater access of environmental allergens, microorganisms, and pollutants into the respiratory tissues. Asthma can no longer be considered simply in terms of a single cellular and mediator response to inhaled allergens, but rather as a complex interaction between the environment and the respiratory tract. Despite controlling symptoms and evidence for the efficacy of maintenance therapy with low-dose inhaled steroids, current treatment strategies do not change the natural history of preschool asthma. Leukotrienes are clearly involved in airway inflammation and are probably key mediators of early bronchial remodeling.

View all citing articles on Scopus

View full text

Original ArticlePrediction of asthma in young adults using childhood characteristics: Development of a prediction rule

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Study population and follow-up

Results

Discussion

Acknowledgments

Lancet

J Clin Epidemiol

Ann Thorac Surg

J Allergy Clin Immunol

J Allergy Clin Immunol

J Clin Epidemiol

J Clin Epidemiol

Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC)

Eur Respir J

Airway remodelling takes place in asthma—what are the clinical implications

Clin Exp Allergy

Clinical prediction rules: applications and methodological standards

N Engl J Med

Clinical prediction rules: a review and suggested modifications of methodological standards

JAMA

Original Article
Prediction of asthma in young adults using childhood characteristics: Development of a prediction rule