Reviews and feature article
Natural history of asthma: Persistence versus progression—does the beginning predict the end?

https://doi.org/10.1016/j.jaci.2008.01.006Get rights and content

Environmental exposures during the early years and airway obstruction that develops during this time, in conjunction with genetic susceptibility, are important factors in the development of persistent asthma in childhood. Established risk factors for childhood asthma include frequent wheezing during the first 3 years, a parental history of asthma, a history of eczema, allergic rhinitis, wheezing apart from colds, and peripheral blood eosinophilia, as well as allergic sensitization to aeroallergens and certain foods. Risk factors for the development of asthma in adulthood remain ill defined. Moreover, reasons for variability in the clinical course of asthma—persistence in some individuals and progression in others—remain an enigma. The distinction between disease persistence and disease progression suggests that these are different entities or phenotypes. There is currently no consensus on whether disease progression requires either airway inflammation or airway remodeling or the combination of the two. For patients with irreversible airway obstruction, inflammation might, in part, be necessary but perhaps not entirely sufficient to induce the irreversible component, some of which could be attributed to alterations in the structure of the bronchial wall. Intervening with intermittent or daily inhaled corticosteroids in high-risk infants and children does not prevent disease progression or impaired lung growth. These findings, however, might not apply to adults, and further study in adults is needed to determine the effect of inhaled corticosteroid therapy on disease progression.

Section snippets

Wheezing before 3 years of age

Community-based longitudinal studies examining outcomes for early wheezers have provided insights into the development of asthma.2, 3, 4, 5, 6, 7 Although these study results differ to a certain extent, possibly because of different study populations and measured parameters, some general patterns have emerged.

Many children experience 1 or more wheezing episodes before the age of 3 years, often in association with a respiratory virus.8, 9 Some have asthma, but the majority do not. For example,

Airway remodeling and inflammation

There are currently no standard definitions for what constitutes disease persistence as opposed to disease progression in asthma or criteria on how and when progression should be measured or evaluated.29, 30 For the purpose of this review, disease persistence is defined as ongoing asthma symptoms, whereas disease progression is defined as a worsening of lung function, asthma symptoms, or both over time. All asthmatic patients have airway inflammation, with resultant altered airway function and

Diagnostic and therapeutic implications of current knowledge

Most children with asthma experience their first wheezing episode during their first 5 years of life,56 yet early identification of the children at greatest risk of asthma is a challenge for clinicians. Objective measures of disease activity are limited and difficult to perform in preschool children. Thus for very young children with recurrent wheezing, using a clinical index that incorporates risk elements, such as the modified API (Table I), might be the best indicator of probable asthma.

Areas of future research

Areas where further research is needed to address remaining questions include determining how wheezing patterns correlate with histopathologic findings and a better understanding of the characteristics and determinants of asthma progression. Study is needed of the contribution of the small airways to remodeling and disease progression, in addition to the relationships among remodeling, inflammation, and airway hyperresponsiveness and whether there exists any element of cause and effect.

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    Elizabeth Hillyer was supported by Merck & Co, Inc, Whitehouse Station, NJ.

    Disclosure of potential conflict of interest: R. Covar has received research support from AstraZeneca and Ross Abbott Laboratories, Inc. E. V. Hillyer has received freelance writing work from Merck and Aerocrine. L. Bacharier has consulting arrangements with Schering-Plough and is on the speakers' bureau for AstraZeneca, Genentech, GlaxoSmithKline, and Merck. The rest of the authors have declared that they have no conflict of interest.

    This article originated, in part, from a discussion at the National Respiratory Experts Forum, held June 15-17, 2006, in Chicago, IL. This was a scientific forum, sponsored by Merck, where specific topics and questions were explored for issues pertinent to the fields of asthma and respiratory medicine.

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