Open Access, Peer-reviewed
pISSN 2288-0402
eISSN 2288-0410
    Allergy Asthma Respir Dis. 2013 Mar;1(1):11-19. Korean.
    Published online Mar 31, 2013.
    https://doi.org/10.4168/aard.2013.1.1.11
    © 2013 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma, Allergy and Clinical Immunology
    Review

    Long-term asthma remission during adolescence

    Young Yull Koh
      • Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
    • Correspondence to: Young Yull Koh. Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. Tel: +82-2-2072-3631, Fax: +82-2-747-5130, Email: kohyy@plaza.snu.ac.kr
    Received March 06, 2013; Accepted March 15, 2013.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).

    Abstract

    Asthma is a heterogeneous disorder with a variable course, characterized by episodes of cough, wheezing and shortness of breath, reversible airflow limitation, and bronchial hyperresponsiveness (BHR). It begins early in life in many subjects, and it is well recognized that over 50% of asthmatic children go into long-term clinical remission, defined as the complete absence of asthmatic symptoms and no asthma medication for at least 24 months, during adolescence. Several studies have shown spirometric abnormalities and BHR during clinical remission. It is unknown whether these functional abnormalities, which are supposed to be indicative of asthma severity with respect to symptomatic asthma, reflect persistent airway inflammation or merely indicate residual airway damage or are related to another mechanism such as a familial predisposition. It is likely that the nature of BHR in asthma remission is not same as that in symptomatic asthma. We have shown that the former condition is associated with lower levels of blood eosinophils and eosinophilic cationic protein, a lower degree of bronchial responsiveness to exercise, and a more common formation of plateau on the dose-response curve to high-dose inhaled methacholine (i.e., limited maximal airway narrowing), compared to the latter condition. It is still controversial whether BHR in adolescents with asthma remission is reduced by inhaled corticosteroids. Better understanding of the mechanisms that lead to asthma remission, especially that seen during adolescence, is likely to lead to significant advances in our understanding of asthma pathogenesis, and should provide insights into how remission might be induced with therapy. We still have minimal understanding of the mechanism underlying BHR in adolescents with asthma remission. Elucidation of this mechanism would be an important step towards new perspectives that see remission as the next therapeutic frontier in asthma.

    Keywords
    Adolescence; Asthma; Bronchial hyperresponsiveness; Clinical remission

    Figures

    Fig. 1
    Prevalence of current asthma among males and females aged 1-85 years, by age: United States, annual average 2001-2009. Adapted from Centers for Disease Control and Prevention.12)

    Fig. 2
    PD20 AMP (micrograms, not cumulative) values of currently asthmatic subjects, of subjects in clinical remission of atopic asthma, and of healthy controls. Nonresponders are arbitrarily given a value of twice the highest dose administered. Horizontal bars represent geometric mean values. The y axis shows PD20 AMP values logarithmically. AMP, adenosine 5'-monophosphate. Reprinted from van den Toorn et al. Am J Respri Crit Care Med 2000;162:953-7, with permission of American Thoracic Society.16)

    Fig. 3
    Thickness of the reticular basement membrane (RBM) in biopsy specimens from currently asthmatic subjects, subjects in clinical remission of atopic asthma, and healthy control subjects. Horizontal bars represent median values. Reprinted from van den Toorn et al. Am J Respri Crit Care Med 2001;164:2107-13, with permission of American Thoracic Society.23)

    Fig. 4
    Theoretical relationship between the severity of inflammation and the likelihood of developing a remission over time. The vertical axis refers to 'inflammation', but this could be used inter-changeably with other measures of asthma that fluctuate over time such as 'airflow obstruction' or 'airway hyperresponsiveness'. Reprinted from Upham and James. Pharmacol Ther 2011;130:38-45, with permission of Elsevier.1)

    Fig. 5
    Scatter plot of peripheral blood eosinophil total counts (A) and serum concentrations of eosinophil cationic protein (ECP) (B) in the four groups studied. Horizontal bars represent means±standard deviation. Reprinted from Koh et al. Ann Allergy Asthma Immunol 2003;91:297-302, with permission of Elsevier.28)

    Fig. 6
    Comparison of maximal airway response to methacholine between adolescents with asthma remission and adolescents with symptomatic asthma. Open circle: subject with a maximal response plateau; closed circle: subject with forced expiratory volume in 1 second fall > 50% without a plateau. Horizontal bars represent mean±standard deviation. Reprinted from Koh et al. Chest 2002;122:1214-21, with permission of American College of Chest Physicians.30)

    Fig. 7
    Levels of maximal airway response before (Baseline), and after 3 months (3 mo) and 6 months (6 mo) of treatment for the three groups (budesonide/remission group, n=15; placebo/remission group, n=15; budesonide/symptomatic group, n=17). Mean and 1 standard deviation are shown. *P<0.01 compared to the value before treatment. Reprinted from Koh et al. Chest 2002;122:1214-21, with permission of American College of Chest Physicians.30)

    Fig. 8
    ΔFVC values of the three study groups. Horizontal bars represent mean±standard deviation. ΔFVC, % decrease in forced vital capacity at the methacholine PC20; BHR, bronchial hyperresponsiveness: methacholine PC20 <16 mg/mL. , subjects with symptomatic asthma; , subjects with asthma remission and a PC20 <100 mg/mL; , subjects with asthma remission and a PC20 >100 mg/mL. Reprinted from Yoo et al. Chest 2006;129:272-7, with permission of American College of Chest Physicians.31)

    Fig. 9
    Peak expiratory flow (PEF) variability in the three study groups. Horizontal bars represent means±standard deviation. Reprinted from Koh et al. J Asthma 2005;42:17-23, with permission of Informa plc.32)

    Fig. 10
    Bronchial response to exercise (BRE) in the three study groups. Horizontal bars represent means±standard deviation. Reprinted from Koh et al. J Asthma 2005;42:17-23, with permission of Informa plc.32)

    Fig. 11
    PD20 methacholine (MCh) values (A) and PD20 adenosine 5'-monophosphate (AMP) values (B) pretreatment and post-treatment for 3 months with the sfc product (n=14) or placebo (n=14). Each line represents one subject. Nonresponders are arbitrarily given a value of twice the highest cumulative dose given. Horizontal bars represent mean values. sfc, salmeterol/fluticasone propionate combination. Reprinted from van den Toorn et al. Respir Med 2005;99:779-87, with permission of Elsevier.36)

    Tables

    Table 1
    Sputum markers in each group of subjects

    Table 2
    Methacholine PC20 values before and after treatment in the studied groups26)

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    MeSH Terms
    Adolescent
    Adrenal Cortex Hormones
    Asthma
    Child
    Cough
    Dyspnea
    Eosinophils
    Humans
    Inflammation
    Methacholine Chloride
    Respiratory Sounds
    Metrics
    Share
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