The Plea for Rigorous Studies on Cough in Children

The Plea for Rigorous Studies on Cough in Children To the Editor: Although we applaud Khoshoo et al1 on performing such a comprehensive series of investigations in these 40 children with chronic cough, as reported in a recent issue of CHEST (September 2009), we have major reservations with their conclusions. In particular, we question the assumption that the improvement in cough (assessed at 8 weeks by parent on a subjective visual analog scale cough score) was caused by the respective interventions. In the absence of a control group, this improvement after 8 weeks could simply be due to a period effect2 andⲐor a placebo effect.3,4 This is particularly likely when the clinicians have taken such a great interest in the child’s cough and have carried out an elaborate series of investigations. This problem is further exacerbated by the manner in which the subjective nature of their outcome measure was measured. Clearly, given the open nature of the intervention, any assessment of outcome must be objective. This time-period effect with cough was well described in the 1980s by Evald and colleagues.2 Indeed, the placebo effect is reported to be as high as 80% in cough studies.4 Thirty-six children in the study by Khoshoo et al1 had a nonproductive cough. According to the American College of Chest Physicians (ACCP)5 and Australian6 guidelines, in children with nonproductive cough, a “watch, wait, and review” approach should be considered. We have demonstrated that a nonproductive (dry) cough in children spontaneously totally resolves (as opposed to just a reduction in cough score) by 8 weeks in 69%.3 Unfortunately, Khoshoo et al have also misinterpreted the ACCP guidelines; these do not advocate the use of antibiotics for all children with chronic cough but only those with a productive (wet) cough. Children with wet cough are likely to have protracted bronchitis, as documented in a number of clinical studies, including those using BAL with quantitative bacterial counts.7 This study by Khoshoo et al1 highlights the need for high-quality randomized controlled trials to determine an evidence-based approach to children with chronic cough as we have consistently reiterated. There is always a need to balance any risk of late diagnosis with that of over-servicing. Although the study by Khoshoo et al is interesting, clinicians need to be aware of the major flaws in the methodology used, and the potential for misleading information regarding the best approach to managing children with chronic cough. Anne B. Chang, MBBS, MPHTM, PhD Brisbane, QLD, Australia Lou I. Landau, MBBS, MD Perth, WA, Australia Peter P. van Asperen, MBBS, MD Sydney, NSW, Australia I. Brent Masters, MBBS, PhD Brisbane, QLD, Australia Craig M. Mellis, MBBS, MD Sydney, NSW, Australia Affiliations: From the Queensland Children’s Respiratory Centre, Royal Children’s Hospital (Drs Chang and Masters); School of Paediatrics and Child Health, University of Western Australia (Dr Landau); Department of Respiratory Medicine, The Children’s Hospital at Westmead (Dr van Asperen); and Central Clinical School (Dr Mellis), University of Sydney. FinancialⲐnonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companiesⲐorganizations whose products or services may be discussed in this article. www.chestpubs.org

Correspondence to: Anne Chang, MBBS, MPHTM, PhD, Department of Respiratory Medicine, Royal Children’s Hospital, Herston, QLD, Australia 4029; e-mail: [email protected] © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.orgⲐ siteⲐmiscⲐreprints.xhtml). DOI: 10.1378Ⲑchest.09-2204

References 1. Khoshoo V, Edell D, Mohnot S, Haydel R, Jr, Saturno E, Kobernick A. Associated factors in children with chronic cough. Chest. 2009;136(3):811-815. 2. Evald T, Munch EP, Kok-Jensen A. Chronic non-asthmatic cough is not affected by inhaled beclomethasone dipropionate. A controlled double blind clinical trial. Allergy. 1989;44(7):510-514. 3. Marchant JM, Masters IB, Taylor SM, Chang AB. Utility of signs and symptoms of chronic cough in predicting specific cause in children. Thorax. 2006;61(8):694-698. 4. Eccles R. The powerful placebo in cough studies? Pulm Pharmacol Ther. 2002;15(3):303-308. 5. Chang AB, Glomb WB. Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 suppl):260S-283S. 6. Chang AB, Landau LI, van Asperen PP, et al. Thoracic Society of Australia and New Zealand. Cough in children: definitions and clinical evaluation. Med J Aust. 2006;184(8):398-403. 7. Chang AB, Faoagali J, Cox NC, et al. A bronchoscopic scoring system for airway secretions-airway cellularity and microbiological validation. Pediatr Pulmonol. 2006;41(9):887-892.

Response To the Editor: The comments by Chang and colleagues are based on their experiences and data generated from a unique population. Although several practitioners can relate to their data, our population, patient selection, methods, investigation protocols, and treatment strategies are somewhat different, and hence the differences. Based on the overwhelming response we have received from pediatricians, family physicians, gastroenterologists, allergists, and pulmonologists from all over the world following the publication of our article,1 we can confidently state that numerous practitioners worldwide can relate to our data as well. We would like to clarify a few issues so that the readership can understand the differences and interpret the data accordingly. Definition of Chronic Cough: Chang’s group has used an arbitrary definition of chronic cough (duration . 4 weeks). Like most other board-certified pediatric pulmonologists in the United States, we use the . 8-week-duration cutoff for chronic cough, similar to the American College of Chest Physicians (ACCP)-recommended definition for adults. Technically, Chang’s group has labeled what we and others call subacute cough (3-8 weeks) as chronic cough (. 8 weeks). That is the starting point of the difference.1-3 It is then no surprise that their definition has permeated into the recommendations of the ACCP for pediatric cough authored by them. The definition has survived probably because there have been no additional data on the etiology of chronic cough in children. Hopefully, our data will help provide another perspective that the ACCP will consider for future recommendations. Reason for Referral for Chronic Cough: We, as subspecialists, rarely see subacute cough because the network of our primary care physicians have diagnosed, intervened, and treated infection and other common noninfectious causes before the cough becomes chronic unless there is antibiotic resistance or difficult-to-treat CHEST / 137 / 3 / MARCH, 2010

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