Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2004;19(9):895–903. doi: 10.1023/B:EJEP.0000040530.98310.0c

The Wheezing Illnesses Study Leidsche Rijn (WHISTLER): Rationale and Design

N Katier 1, CSPM Uiterwaal 1,2, BM de Jong 1, JLL Kimpen 3, TJ Verheij 2, DE Grobbee 2, B Brunekreef 4, ME Numans 2, CK van der Ent 1,✉
PMCID: PMC7087709  PMID: 15499901

Abstract

The Wheezing Illnesses Study Leidsche Rijn (WHISTLER) was initiated in December 2001 as a single-centre prospective birth cohort study and will include a population-based sample of at least 2000 healthy newborns. The aims of WHISTLER are to investigate determinants for wheezing illnesses (including neonatal lung function, viral infections, asthma-susceptibility genes and endotoxin exposure) and to derive a comprehensive risk score, that is appropriate for use in primary health care and allows for efficient planning of early preventive strategies. Baseline examination includes a questionnaire evaluating known risk factors for wheezing illnesses; anthropometric measurements; measurements of infant and parental lung function; and sampling of infant and parental DNA. Participants will be followed for respiratory events using data from a daily respiratory symptom questionnaire; visits to the general practitioner (primary health care visits, drugs prescriptions and hospital referral); viral sampling during wheezing episodes; and house dust sampling. Based on actual neonatal care practice and embedded in a larger epidemiological study, the Utrecht Health Project, WHISTLER will provide an unique framework to address issues in childhood respiratory disease that are currently insufficiently understood. In particular, WHISTLER will provide a well-balanced view on the prognostic power of neonatal lung function and genetic and environmental factors (including viral infections and endotoxin exposure) to predict wheezing illnesses from birth to young adulthood and beyond. In the scope of prevention, WHISTLER is expected to support the design of solid based prevention measures to reduce respiratory morbidity, mortality and associated costs, and to improve quality of life.

Keywords: Birth cohort, Etiology, Infants, Lung function, Wheezing

References

  • 1.Koopman LP, Brunekreef B, de Jongste JC, Neijens HJ. Definition of respiratory symptoms and disease in early childhood in large prospective birth cohort studies that predict the development of asthma. Pediatr Allerg Immunol. 2001;12:118–124. doi: 10.1034/j.1399-3038.2001.012003118.x. [DOI] [PubMed] [Google Scholar]
  • 2.Stevens CA, Turner D, Kuehni CE, Couriel JM, Silverman M. The economic impact of preschool asthma and wheeze. Eur Respir J. 2003;21:1000–1006. doi: 10.1183/09031936.03.00057002. [DOI] [PubMed] [Google Scholar]
  • 3.Kuehni CE, Davis A, Brooke AM, Silverman M. Are all wheezing disorders in very young (preschool) children increasing in prevalence? Lancet. 2001;357(9271):1821–1825. doi: 10.1016/S0140-6736(00)04958-8. [DOI] [PubMed] [Google Scholar]
  • 4.Sears MR. Epidemiology of childhood asthma. Lancet. 1997;350(9083):1015–1020. doi: 10.1016/S0140-6736(97)01468-2. [DOI] [PubMed] [Google Scholar]
  • 5.Vonk JM, Jongepier H, Panhuysen CI, Schouten JP, Bleecker ER, Postma DS. Risk factors associated with the presence of irreversible airflow limitation and reduced transfer coefficient in patients with asthma after 26 years of follow up. Thorax. 2003;58:322–327. doi: 10.1136/thorax.58.4.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Martinez FD. Links between pediatric and adult asthma. J Allergy Clin Immunol. 2001;107(5Suppl):S449–S455. doi: 10.1067/mai.2001.114993. [DOI] [PubMed] [Google Scholar]
  • 7.Martinez FD. Development of wheezing disorders and asthma in preschool children. Pediatrics. 2002;109(2Suppl):S362–S367. [PubMed] [Google Scholar]
  • 8.Fuhlbrigge AL, Adams RJ, Guilbert TW, Grant E, Lozano P, Janson SL, et al. The burden of asthma in the United States: Level and distribution are dependent on interpretation of the national asthma education and prevention program guidelines. Am J Respir Crit Care Med. 2002;166:1044–1049. doi: 10.1164/rccm.2107057. [DOI] [PubMed] [Google Scholar]
  • 9.Halpern MT, Stanford RH, Borker R. The burden of COPD in the USA: Results from the Confronting 901. COPD survey. Respir Med. 2003;97(SupplC):S81–S89. doi: 10.1016/s0954-6111(03)80028-8. [DOI] [PubMed] [Google Scholar]
  • 10.Taussig LM, Wright AL, Holberg CJ, Halonen M, Morgan WJ, Martinez FD. Tucson Children's Respiratory Study:1980 to present. J Allerg Clin Immunol. 2003;111:661–675. doi: 10.1067/mai.2003.162. [DOI] [PubMed] [Google Scholar]
  • 11.Lau S, Nickel R, Niggemann B, Gruber C, Sommerfeld C, Illi S, et al. The development of childhood asthma: Lessons from the German Multicentre Allergy Study (MAS) Paediatr Respir Rev. 2002;3:265–272. doi: 10.1016/s1526-0542(02)00189-6. [DOI] [PubMed] [Google Scholar]
  • 12.Wijga A, Smit HA, Brunekreef B, Gerritsen J, Kerkhof M, Koopman LP, et al. Are children at high familial risk of developing allergy born into a low risk environment? The PIAMA birth cohort study. Prevention and incidence of asthma and mite allergy. Clin Exp Allergy. 2001;31:576–581. doi: 10.1046/j.1365-2222.2001.01072.x. [DOI] [PubMed] [Google Scholar]
  • 13.Koopman LP, Smit HA, Heijnen ML, Wijga A, van Strien RT, Kerkhof M, et al. Respiratory infections in infants: Interaction of parental allergy, child care, and siblings–The PIAMA study. Pediatrics. 2001;108:943–948. doi: 10.1542/peds.108.4.943. [DOI] [PubMed] [Google Scholar]
  • 14.Martinez FD, Morgan WJ, Wright AL, Holberg CJ, Taussig LM. Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N Engl J Med. 1988;319:1112–1117. doi: 10.1056/NEJM198810273191702. [DOI] [PubMed] [Google Scholar]
  • 15.Martinez FD, Wright AL, Holberg CJ, Morgan WJ, Taussig LM. Maternal age as a risk factor for wheezing lower respiratory illnesses in the rst year of life. Am J Epidemiol. 1992;136:1258–1268. doi: 10.1093/oxfordjournals.aje.a116434. [DOI] [PubMed] [Google Scholar]
  • 16.Diez U, Kroessner T, Rehwagen M, Richter M, Wetzig H, Schulz R, et al. Effects of indoor painting and smoking on airway symptoms in atopy risk children in the first year of life results of the LARS-study. Leipzig Allergy High-Risk Children Study. Int J Hyg Environ Health. 2000;203:23–28. doi: 10.1078/s1438-4639(04)70004-8. [DOI] [PubMed] [Google Scholar]
  • 17.Remes ST, Castro-Rodriguez JA, Holberg CJ, Martinez FD, Wright AL. Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy. J Allerg Clin Immunol. 2001;108:509–515. doi: 10.1067/mai.2001.117797. [DOI] [PubMed] [Google Scholar]
  • 18.Leadbitter P, Pearce N, Cheng S, Sears MR, Holdaway MD, Flannery EM, et al. Relationship between fetal growth and the development of asthma and atopy in childhood. Thorax. 1999;54:905–910. doi: 10.1136/thx.54.10.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Koopman LP, Wijga A, Smit HA, de Jongste JC, Kerkhof M, Gerritsen J, et al. Early respiratory and skin symptoms in relation to ethnic background: The importance of socioeconomic status; the PIAMA study. Arch Dis Child. 2002;87:482–488. doi: 10.1136/adc.87.6.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Oddy WH, Holt PG, Sly PD, Read AW, Landau LI, Stanley FJ, et al. Association between breast feeding and asthma in 6 year old children: Findings of a prospective birth cohort study. BMJ. 1999;319(7213):815–819. doi: 10.1136/bmj.319.7213.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Martinez FD. Toward asthma prevention-does all that really matters happen before we learn to read? New Engl J Med. 2003;349:1473–1475. doi: 10.1056/NEJMe030041. [DOI] [PubMed] [Google Scholar]
  • 22.Hide DW, Matthews S, Tariq S, Arshad SH. Allergen avoidance in infancy and allergy at 4 years of age. Allergy. 1996;51:89–93. [PubMed] [Google Scholar]
  • 23.Zeiger RS, Heller S. The development and prediction of atopy in high-risk children: Follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance. J Allerg Clin Immunol. 1995;95:1179–1190. doi: 10.1016/s0091-6749(95)70074-9. [DOI] [PubMed] [Google Scholar]
  • 24.Dezateux C, Stocks J, Dundas I, Fletcher ME. Impaired airway function and wheezing in infancy: The influence of maternal smoking and a genetic predisposition to asthma. Am J Respir Crit Care Med. 1999;159:403–410. doi: 10.1164/ajrccm.159.2.9712029. [DOI] [PubMed] [Google Scholar]
  • 25.Young S, Arnott J, O'Keeffe PT, Le Souef PN, Landau LI. The association between early life lung function and wheezing during the first 2 years of life. Eur Respir J. 2000;15:151–157. doi: 10.1183/09031936.00.15115100. [DOI] [PubMed] [Google Scholar]
  • 26.Dezateux C, Stocks J, Wade AM, Dundas I, Fletcher ME. Airway function at 1 year: Association with premorbid airway function, wheezing, and maternal smoking. Thorax. 2001;56:680–686. doi: 10.1136/thorax.56.9.680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Clarke JR, Salmon B, Silverman M. Bronchial responsiveness in the neonatal period as a risk factor for wheezing in infancy. Am J Respir Crit Care Med. 1995;151:1434–1440. doi: 10.1164/ajrccm.151.5.7735597. [DOI] [PubMed] [Google Scholar]
  • 28.Adler A, Tager IB, Brown RW, Ngo L, Hanrahan JP. Relationship between an index of tidal flow and lower respiratory illness in the first year of life. Pediatr Pulmonol. 1995;20:137–144. doi: 10.1002/ppul.1950200303. [DOI] [PubMed] [Google Scholar]
  • 29.Lesouef PN, England SJ, Bryan AC. Passive respiratory mechanics in newborns and children. Am Rev Respir Dis. 1984;129:552–556. [PubMed] [Google Scholar]
  • 30.Fletcher ME, Baraldi B, Steinbrugger B. Passive respiratory mechanics. In: Stock J, Sly PD, Tepper RS, Morgan WJ, editors. Infant respiratory function testing. New York: Wiley-Liss; 1996. pp. 283–327. [Google Scholar]
  • 31.Mortola JP, Saetta M. Measurements of respiratory mechanics in the newborn: A simple approach. Pediatr Pulmonol. 1987;3:123–130. doi: 10.1002/ppul.1950030215. [DOI] [PubMed] [Google Scholar]
  • 32.Stocks J, Nothen U, Sutherland P, Hatch D, Helms P. Improved accuracy of the occlusion technique for assessing total respiratory compliance in infants. Pediatr Pulmonol. 1987;3:71–77. doi: 10.1002/ppul.1950030206. [DOI] [PubMed] [Google Scholar]
  • 33.Gappa M, Colin AA, Goetz I, Stocks J. Passive respiratory mechanics: The occlusion techniques. Eur Respir J. 2001;17:141–148. doi: 10.1183/09031936.01.17101410. [DOI] [PubMed] [Google Scholar]
  • 34.Whittaker PA. Genes for asthma: Much ado about nothing? Curr Opin Pharmacol. 2003;3:212–219. doi: 10.1016/s1471-4892(03)00035-3. [DOI] [PubMed] [Google Scholar]
  • 35.Gern JE, Busse WW. Relationship of viral infections to wheezing illnesses and asthma. Nat Rev Immunol. 2002;2:132–138. doi: 10.1038/nri725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Umetsu DT, McIntire JJ, Akbari O, Macaubas C, De-Kruy RH. Asthma: An epidemic of dysregulated immunity. Nat Immunol. 2002;3:715–720. doi: 10.1038/ni0802-715. [DOI] [PubMed] [Google Scholar]
  • 37.Braun-Fahrlander C, Riedler J, Herz U, Eder W, Waser M, Grize L, et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med. 2002;347:869–877. doi: 10.1056/NEJMoa020057. [DOI] [PubMed] [Google Scholar]
  • 38.Lambert H, Wood M., editors. ICPC: International Classification of Primary Care. Oxford: Oxford University Press; 1987. [Google Scholar]
  • 39.Standardization of Spirometry, 1994 Update. American Thoracic Society Am J Respir Crit Care Med. 1995;152:1107–1136. doi: 10.1164/ajrccm.152.3.7663792. [DOI] [PubMed] [Google Scholar]
  • 40.Lum A, Le Marchand L. A simple mouthwash method for obtaining genomic DNA in molecular epidemiological studies. Cancer Epidemiol Biomarkers Prev. 1998;7:719–724. [PubMed] [Google Scholar]
  • 41.van Strien RT, Koopman LP, Kerkhof M, Spithoven J, de Jongste JC, Gerritsen J, et al. Mite and pet allergen levels in homes of children born to allergic and nonallergic parents: The PIAMA study. Environ Health Perspect. 2002;110:A693–A698. doi: 10.1289/ehp.021100693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.van Strien RT, Koopman LP, Kerkhof M, Oldenwening M, de Jongste JC, Gerritsen J, et al. Mattress encasings and mite allergen levels in the Prevention and Incidence of Asthma and Mite Allergy study. Clin Exp Allerg. 2003;33:490–495. doi: 10.1046/j.1365-2222.2003.01626.x. [DOI] [PubMed] [Google Scholar]

Articles from European Journal of Epidemiology are provided here courtesy of Nature Publishing Group

RESOURCES