The Journal of Allergy and Clinical Immunology
Volume 120, Issue 2 , Pages 271-272, August 2007

Family history, environmental exposures in early life, and childhood asthma

  • Ngoc P. Ly, MD, MPH

      Affiliations

    • From the Channing Laboratory
    • Division of Pediatric Pulmonary Medicine, Department of Pediatrics, Massachusetts General Hospital
    • Department of Medicine, Harvard Medical School
    • ,
  • Juan C. Celedón, MD, DrPH

      Affiliations

    • From the Channing Laboratory
    • Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital
    • Department of Medicine, Harvard Medical School
    • Corresponding Author InformationReprint requests: Juan C. Celedón, MD, DrPH, Channing Laboratory; 181 Longwood Avenue, Boston, MA 02115.

Received 16 May 2007; accepted 25 May 2007.

Boston, Mass

Article Outline

 

Asthma is a major public health problem in industrialized nations and incurs significant health care costs. Asthma is a complex disease influenced by interactions among insufficiently characterized genetic, environmental, and behavioral factors. Because a significant number of cases of asthma are diagnosed in childhood,1 early-life exposures are likely to influence its pathogenesis.2, 3 Identification of such exposures is thus important and could lead to better means of asthma prevention, particularly among children at high risk (eg, those with a positive family history).

In this issue of the JACI, Kuiper et al4 report a modification of the effect of family history of asthma on respiratory morbidity in Dutch infants by environmental exposures in early life as follows: postnatal parental smoking and high indoor dust mite allergen levels accentuated the increased risk of wheeze associated with a positive family history, whereas breast-feeding attenuated the increased risk of tonsillitis and otitis media associated with a positive family history. A major strength of this study is its assessment of family history (defined as an asthma diagnosis in at least 1 first-degree relative of a participating child) by review of records from general practitioners (GPs) and not exclusively by parental report. As acknowledged by the authors, a thorough assessment of the interaction between family history and environmental exposures on asthma pathogenesis was not possible because of the limited follow-up of study participants (up to age 2 years), which precludes a confident diagnosis of asthma and/or an adequate assessment of wheeze phenotypes.5

Few studies have examined a potential interaction between parental history of asthma and environmental exposures in early life.6, 7, 8, 9, 10, 11 Previous reports of modification of the effect of 2 particular exposures (allergen exposure and breast-feeding) on asthma and/or asthma symptoms by parental history7, 8, 9, 10, 11 differ from the findings of Kuiper et al.4 Birth cohort studies of children followed up for at least 4 years have reported no significant association between exposure to dust mite allergen and wheeze, even after stratification by parental6 and/or maternal history of asthma.6, 7 In contrast to the negative findings of Kuiper et al,4 2 birth cohort studies have reported an association between cat allergen exposure and an increased risk of wheeze among children with maternal history of asthma.7, 8 Although previous studies of the relation between breast-feeding and asthma and allergy have yielded conflicting results,12, 13 those that accounted for potential effect modification by maternal history have shown increased risks of allergy9 and asthma10 among children with maternal history of asthma who were breast-fed. Discrepancies in the results of the study by Kuiper et al4 and those of others could be explained by differences in duration of follow-up, definition of family history of asthma (see text above), and ascertainment of the exposures (eg, allergen levels) and outcomes (eg, wheeze) of interest.

Although both paternal and maternal history have been associated with asthma, the relative contributions of paternal and maternal history to childhood asthma vary with age. Whereas maternal history is consistently associated with asthma at all ages, paternal history becomes a more important risk factor for asthma after age 5 years.14, 15 Among schoolchildren with asthma, paternal history has been recently shown to be associated with increased airway responsiveness, a marker of asthma severity.16 Whereas observed effects of maternal history on childhood asthma may be due to genetics and/or environmental exposures shared in utero or in early postnatal life (eg, breast-feeding), effects of paternal history on childhood asthma are more likely to be genetic in origin. Previous studies have often examined potential modification of the effect of environmental exposures on asthma by maternal,6, 7, 8, 11 but not paternal, history. Potential modification of the effect of dust mite allergen exposure and postnatal parental smoking by either maternal or paternal history could not be specifically assessed by Kuiper et al4 because of limited statistical power.

Because of concerns regarding multiple testing, any reported interactions between familial and environmental factors should be interpreted with caution pending replication studies. However, known detrimental effects of smoking and the report by Kuiper et al4 lend further support to current efforts for parental smoking cessation, which should be vigorously pursued in general and among high-risk children in particular. Future studies of the interaction among familial and environmental factors on the development of childhood asthma should have adequate duration of follow-up and sufficiently large sample size, which would result in adequate statistical power to examine differential effects of paternal, maternal, and sibling histories of asthma. The ultimate goal should be to identify modification of the effect of early-life environmental exposures by genetic factors (including imprinting) and nongenetic variables (eg, in utero exposures shared by mother and child) for which family history is a surrogate marker. Birth cohort studies are ideally suited for this purpose.

Back to Article Outline

References 

  1. Yunginger JW, Reed CE, O'Connell EJ, Melton LJ, O'Fallon WM, Silverstein MD. A community-based study of the epidemiology of asthma. Incidence rates, 1964-1983. Am Rev Respir Dis. 1992;146:888–894
  2. Devereux G, Seaton A. Diet as a risk factor for atopy and asthma. J Allergy Clin Immunol. 2005;115:1109-17; quiz 1118
  3. Schaub B, Lauener R, von Mutius E. The many faces of the hygiene hypothesis. J Allergy Clin Immunol. 2006;117:969-77; quiz 978
  4. Kuiper S, Muris JW, Dompeling E, Kester ADM, Wesseling G, Knottnerus JA, et al. Interactive effect of family history and environmental factors on respiratory tract–related morbidity in infancy. J Allergy Clin Immunol. 2007;120:388–395
  5. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. N Engl J Med. 1995;332:133–138
  6. Cole Johnson C, Ownby DR, Havstad SL, Peterson EL. Family history, dust mite exposure in early childhood, and risk for pediatric atopy and asthma. J Allergy Clin Immunol. 2004;114:105–110
  7. Polk S, Sunyer J, Munoz-Ortiz L, Barnes M, Torrent M, Figueroa C, et al. A prospective study of Fel d1 and Der p1 exposure in infancy and childhood wheezing. Am J Respir Crit Care Med. 2004;170:273–278
  8. Celedon JC, Litonjua AA, Ryan L, Platts-Mills T, Weiss ST, Gold DR. Exposure to cat allergen, maternal history of asthma, and wheezing in first 5 years of life. Lancet. 2002;360:781–782
  9. Mandhane PJ, Greene JM, Sears MR. Interactions between breast-feeding, specific parental atopy, and sex on development of asthma and atopy. J Allergy Clin Immunol. 2007;119:1359–1366
  10. Wright AL, Holberg CJ, Taussig LM, Martinez F. Maternal asthma status alters relation of infant feeding to asthma in childhood. Adv Exp Med Biol. 2000;478:131–137
  11. Celedon JC, Litonjua AA, Weiss ST, Gold DR. Day care attendance in the first year of life and illnesses of the upper and lower respiratory tract in children with a familial history of atopy. Pediatrics. 1999;104:495–500
  12. Sears MR, Greene JM, Willan AR, Taylor DR, Flannery EM, Cowan JO, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet. 2002;360:901–907
  13. Dell S, To T. Breastfeeding and asthma in young children: findings from a population-based study. Arch Pediatr Adolesc Med. 2001;155:1261–1265
  14. Litonjua AA, Carey VJ, Burge HA, Weiss ST, Gold DR. Parental history and the risk for childhood asthma. Does mother confer more risk than father?. Am J Respir Crit Care Med. 1998;158:176–181
  15. Ly NP, Gold DR, Weiss ST, Celedón JC. Recurrent wheeze in early childhood and asthma among children at risk for atopy. Pediatrics. 2006;117:e1132–e1138
  16. Raby BA, Van Steen K, Celedón JC, Litonjua AA, Lange C, Weiss ST. Paternal history of asthma and airway responsiveness in children with asthma. Am J Respir Crit Care Med. 2005;172:552–558

 Supported by National Institutes of Health grants HL66289, HL079966, and HL073373.Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

PII: S0091-6749(07)01040-8

doi:10.1016/j.jaci.2007.05.045

The Journal of Allergy and Clinical Immunology
Volume 120, Issue 2 , Pages 271-272, August 2007

Article Tools