The Journal of Allergy and Clinical Immunology
Volume 124, Issue 5 , Pages 1121-1122, November 2009

Reply

  • Kecia N. Carroll, MD, MPH

      Affiliations

    • Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn
    • Division of General Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn
  • ,
  • Tebeb Gebretsadik, MPH

      Affiliations

    • Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tenn
  • ,
  • Marie R. Griffin, MD, MPH

      Affiliations

    • Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn
    • Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, Tenn
    • Division of General Internal Medicine, Vanderbilt University School of Medicine, Nashville, Tenn
    • Center for Education and Research on Therapeutics, Vanderbilt University School of Medicine, Nashville, Tenn
    • Mid-South Geriatric Research Education and Clinical Center, and Clinical Research Center of Excellence, Veterans Affairs Tennessee Valley Health Care System, Nashville, Tenn
  • ,
  • Tina V. Hartert, MD, MPH

      Affiliations

    • Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn
    • Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tenn
    • Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, Tenn

Article Outline

 

To the Editor:

In response to our recent article,1 Piippo-Savolainen et al2 share data from their well studied cohort of 83 subjects followed from early childhood for more than 25 years for asthma and other pulmonary outcomes. Several factors make it difficult to make comparisons to our recent findings from the work highlighted by Piippo-Savolainen et al,2 including the small sample size, the fact that their study was neither designed nor powered to address our study questions, differences between studies in how exposure and outcome variables were defined, and the lack of both a spectrum of bronchiolitis severity and a comparison group without bronchiolitis.

Our population-based retrospective birth cohort study, the Tennessee Asthma Bronchiolitis Study (TABS), was designed to investigate the relationship between infant bronchiolitis and early childhood asthma. The definition of the risk factor of interest, bronchiolitis during infancy, differs significantly between the studies. Our measure of bronchiolitis severity was based on level of health care for bronchiolitis, including clinic visits, emergency department visits, and hospitalizations, as determined by bronchiolitis diagnosis using the International Classification of Diseases, Ninth Revision, Clinical Modification, with the risk period only during infancy. Our inclusion of a comparison group of infants, who had no visit for bronchiolitis in their first year, allowed for the hypothesis-driven investigation of whether there was a severity-response relationship between the most advanced level of health care for bronchiolitis and subsequent early childhood asthma risk and morbidity. Piippo-Savolainen et al2 have followed 83 children who were all hospitalized for bronchiolitis at <24 months. Piippo-Savolainen et al2 also compare results from subanalyses aimed at investigating the relationship of what they term “invasiveness” of the child index illness as determined by infiltrate on chest radiograph, and subsequent asthma outcomes to previously published work by Castro-Rodríguez et al.3 Our study was not designed to investigate this question.

In regard to the authors' concluding comments regarding asthma after nonrespiratory syncytial virus bronchiolitis, we have previously shown that bronchiolitis occurring during rhinovirus-predominant months was associated with an estimated 25% increased risk of early childhood asthma compared with bronchiolitis occurring during respiratory syncytial virus–predominant months.4 This work supports recent findings that early rhinovirus-wheezing illnesses are associated with higher risk of subsequent asthma than other viruses.5 However, as we have seen in our Tennessee Children's Respiratory Initiative prospective investigation, the burden of respiratory syncytial virus bronchiolitis during infancy is much greater than rhinovirus bronchiolitis. Therefore, the expected number of asthma cases after infant respiratory syncytial virus bronchiolitis would likely be much greater.

Importantly, the work by Piippo-Savolainen et al2 does highlight what has been demonstrated in other longitudinal investigations, that the proportion of children who persist in having a postinfant bronchiolitis asthma phenotype may vary with age through childhood.6, 7, 8 The report of the high prevalence of subnormal lung function after infant infection in their cohort is also interesting. This suggests that either early severe viral respiratory infections may lead to lung function abnormalities, or infants with abnormal lung function are predisposed to develop these infections. Clinical trials aimed at preventing severe viral infections during infancy will ultimately elucidate the nature of the association between infant viral respiratory tract illnesses and the development of early childhood asthma.

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References 

  1. Carroll KN, Wu P, Gebretsadik T, Griffin MR, Dupont WD, Mitchel EF, et al. The severity-dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma. J Allergy Clin Immunol. 2009;123:1055–1061
  2. Piippo-Savolainen E, Ruotsalainen M, Korppi M. Long-term outcome after bronchiolitis: No association with the invasiveness of the infection. J Allergy Clin Immunol. 2009;124:1121
  3. Castro-Rodríguez JA, Holberg CJ, Wright AL, Halonen M, Taussig LM, Morgan WJ, et al. Association of radiologically ascertained pneumonia before age 3 yr with asthmalike symptoms and pulmonary function during childhood: a prospective study. Am J Respir Crit Care Med. 1999;159:1891–1897
  4. Carroll KN, Wu P, Gebretsadik T, Griffin MR, Dupont WD, Mitchel EF, et al. Season of infant bronchiolitis and estimates of subsequent risk and burden of early childhood asthma. J Allergy Clin Immunol. 2009;123:964–966
  5. Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008;178:667–672
  6. Stein RT, Sherrill D, Morgan WJ, Holberg CJ, Halonen M, Taussig LM, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999;354:541–545
  7. Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med. 2000;161:1501–1507
  8. Sigurs N, Gustafsson PM, Bjarnason R, Lundberg F, Schmidt S, Sigurbergsson F, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med. 2005;171:137–141

 Supported in part by research grants from the National Institutes of Health U01 HL 072471 (T. V. H.), KO1 AI070808 (K. N. C.), National Institutes of Health K24 AI 077930 (T. V. H.), and the Parker B. Francis Research Foundation (K. N. C.). The funding sources played no role in any of the following: study design; collection, analysis, and interpretation of data; the writing of the article; the decision to submit the article for publication. M. R. G. reports receiving investigator initiated grant support from MedImmune.

 Disclosure of potential conflict of interest: K. N. Carroll has received research support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases and Parker B. Francis Research Foundation. T. V. Hartert has received research support from the National Institutes of Health, the Thrasher Research Fund, and the Centers for Disease Control and Prevention and has served as an adviser for the Merck Research Advisory Board. M. R. Griffin has received research support from Merck, Pfizer, MedImmune, and Wyeth. T. Gebretsadik declares no relevant conflicts of interest to disclose.

PII: S0091-6749(09)01256-1

doi:10.1016/j.jaci.2009.07.060

Refers to article:

  • Long-term outcome after bronchiolitis: No association with the invasiveness of the infection

    Eija Piippo-Savolainen, Marja Ruotsalainen, Matti Korppi
    The Journal of Allergy and Clinical Immunology November 2009 (Vol. 124, Issue 5, Page 1121)

The Journal of Allergy and Clinical Immunology
Volume 124, Issue 5 , Pages 1121-1122, November 2009