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Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease

Marjan Kerkhof1, H Marike Boezen1, Raquel Granell2

  • 1Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; GRIAC Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

The Journal of Allergy and Clinical Immunology
|July 27, 2013
PubMed

Insights

Genetic predisposition to COPD may manifest in childhood, with specific genes influencing early lung function and wheezing. Smoke exposure further impacts lung development in genetically susceptible children.

Area of Science:

  • Pulmonary Medicine
  • Genetics
  • Environmental Health

Background:

  • Early lung development is crucial for lifelong respiratory health.
  • Susceptibility to chronic obstructive pulmonary disease (COPD) may originate from disturbed lung development.
  • The role of genetic predisposition and early-life environmental exposures in childhood lung function is not well understood.

Purpose of the Study:

  • To investigate associations between COPD-related genes and early childhood wheeze and lung function.
  • To determine if in utero and early-life environmental tobacco smoke (ETS) exposure modifies these genetic associations.
  • To identify specific COPD susceptibility genes impacting lung development in children.

Main Methods:

  • Utilized data from the PIAMA, KOALA, and ALSPAC birth cohorts (totaling nearly 2000 children).
  • Examined associations between genotypes of 20 single nucleotide polymorphisms in 15 COPD-related genes and transient early wheeze (TEW), FEV1, FVC, and FEV1/FVC ratio.
  • Investigated interactions between genetic factors and environmental tobacco smoke (ETS) exposure.

Main Results:

  • AGER, TNS1, SERPINE2, FAM13A, HHIP, MMP12, and TGFB1 genes showed significant associations with lung function parameters and/or TEW.
  • TNS1 and HHIP gene variants interacted with ETS exposure, impacting lung function.
  • Specific gene-smoke interactions suggested differential effects based on genetic risk for COPD, with some protective effects observed in non-exposed children.

Conclusions:

  • At least three COPD-associated genes play a significant role in early lung development and growth, indicated by associations with reduced airway caliber.
  • COPD-related genes influence an infant's lung response to both in utero and early-life smoke exposure.
  • These findings highlight the importance of early-life factors in COPD pathogenesis and suggest potential targets for early intervention.
Abstract

Keywords:
ALSPACAvon Longitudinal Study of Parents and ChildrenCOPDChild, parents and health: lifestyle and genetic constitutionChronic obstructive pulmonary diseaseETSEnvironmental tobacco smokeFVCForced vital capacityKOALAOROdds ratioPIAMAPrevention and Incidence of Asthma and Mite AllergyRAGEReceptor for advanced glycation end productsSNPSingle nucleotide polymorphismTEWTransient early wheezein utero exposurelung function growthtransient early wheeze

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