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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 1335-1336, (2004)
© 2004 American Thoracic Society


Correspondence

Interrupter Resistance and Wheezing at 4 Years

To the Editor:

Without wishing to disparage the huge effort that has gone into collecting the data described by Brussee and coworkers (1) in the recent study of 4-year-old children, I wish to comment on the exaggerated claims that the authors make for its relevance.

To summarize, the authors have demonstrated that in those 4-year-old children whose wheezing has persisted since early infancy, airway resistance measured by the interrupter technique (Rint) is 14% greater (or 0.5 SD units greater) than in those who had never wheezed. The difference was independent of the presence or absence of atopy, and we are told that adjustment for a range of potential confounders did not alter the result (although no data to substantiate this claim are given).

One might ask the simple question: if a group of healthy individuals of any age is compared with a group with persistent wheeze, 34% of whom had respiratory symptoms within the previous fortnight, would it be surprising to find a difference in airway function? If these data are to have any clinical value as a diagnostic or predictive tool, we need to know the sensitivity and specificity of Rint in differentiating healthy children from those with persistent wheeze; and more importantly, we need to be given information on the bronchodilator response of these children. It would then be possible to make a reasonable claim that lung function measurements at the age of 4 years can help to differentiate significant asthma from transient airway dysfunction.

It is surely not too much to ask that any epidemiologic data that are designed to shed light on the natural history of asthma should attempt to record postbronchodilator lung function, as well as prebronchodilator values.

Michael Silverman

University of Leicester Leicester, United Kingdom

FOOTNOTES

Conflict of Interest Statement: M.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this letter.

REFERENCES

  1. Brussee JE, Smit HA, Koopman LP, Wijga AH, Kerkhof M, Corver K, Vos APH, Gerritsen J, Grobbee DE, Brunekreef B, et al. Interrupter resistance and wheezing phenotypes at 4 years of age. Am J Respir Crit Care Med 2004;169:209–213.[Abstract/Free Full Text]

 

From the Authors:

We agree with Dr. Silverman that it might be expected to find differences in airway resistance between healthy young children and children with persistent wheeze. However, although previous studies have shown elevated Rint values in preschool children with physician-diagnosed asthma (1) and children referred to hospital because of wheeze (2), few studies have investigated the usefulness of Rint in discriminating between symptomatic and asymptomatic children from the general population (3). Irrespective of Rint being elevated in children with physician-diagnosed asthma, it would not be a potential diagnostic tool as long as it cannot discriminate between symptomatic and asymptomatic children in the general population, because these are the children in whom Rint could contribute to establish the diagnosis of asthma. The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study is one of the first large-scale epidemiologic studies showing elevated Rint values in symptomatic preschool children from the general population (4).

However, this does not necessarily imply that Rint is useful as a diagnostic tool. Therefore, the sensitivity and specificity of Rint in diagnosing asthma will be investigated prospectively in the PIAMA study.

We agree that children are more likely to have elevated Rint values if they had respiratory symptoms in the 2 weeks before Rint measurement. However, because recent respiratory symptoms are part of the persistent wheezing phenotype, excluding these children from the analysis would mean excluding children from the more severe part of the spectrum. Moreover, these children only partly explain the higher mean Rint values in children with persistent wheeze (mean Rint value in persistent wheezers, after exclusion of those with recent respiratory symptoms: 1.04 kPa · L–1 · second, p < 0.05 as compared with never and early wheezing phenotypes).

Indeed, adjustment for potential confounders did not alter the results of the analyses (adjusted mean Rint value in total study population after adjustment for potential confounders: 1.06 kPa · L–1 · second, p < 0.05 as compared with never and early wheezing phenotypes).

We entirely agree with Dr. Silverman that assessment of prebronchodilator and postbronchodilator Rint values would have been extremely important, and it was part of our original protocol. Unfortunately, the medical ethics committees involved in the evaluation of the study protocol did not allow studying this in healthy children from the general population.

Jessica E. Brusseea, Henriëtte A. Smita, Alet H. Wijgaa, Marjan Kerkhofb, Karen Corverc, Peter J.F.M. Merkusc and Johan C. de Jongstec

a National Institute for Public Health and the Environment Bilthoven, The Netherlands
b University of Groningen Groningen, The Netherlands
c Erasmus University Medical Center Rotterdam, The Netherlands

FOOTNOTES

Conflict of Interest Statement: J.E.B., H.A.S., A.H.W., M.K., K.C., and J.C.d.J. do not have a financial relationship with a commercial entity that has an interest in the subject of this letter. P.J.F.M.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this letter; he received &euro;500 in 2003 for speaking at a Roche-sponsored meeting, and &euro;300 for participating in an AstraZeneca-sponsored postgraduate course in 2004.

REFERENCES

  1. Beydon N, Pin I, Matran R, Chaussain M, Boule M, Alain B, Bellet M, Amsallem F, Alberti C, Denjean A, et al. Pulmonary function tests in preschool children with asthma. Am J Respir Crit Care Med 2003;168:640–644.[Abstract/Free Full Text]
  2. Mckenzie SA, Bridge PD, Healy MJR. Airway resistance and atopy in preschool children with wheeze and cough. Eur Respir J 2000;15:833–838.[Abstract]
  3. Merkus PJFM, Mijnsbergen JY, Hop WCJ, De Jongste JC. Interrupter resistance in preschool children: measurement characteristics and reference values. Am J Respir Crit Care Med 2001;163:1350–1355.[Abstract/Free Full Text]
  4. Brussee JE, Smit HA, Koopman LP, Wijga AH, Kerkhof M, Corver K, Vos AP, Gerritsen J, Grobbee DE, Brunekreef B, et al. Interrupter resistance and wheezing phenotypes at 4 years of age. Am J Respir Crit Care Med 2004;169:209–213.




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