Authors' response

Abstract

We thank Dr Vanderhelst and colleagues for their interest in our manuscript [[1]Welsh L. Nesci C. Tran H. Tomai M. Ranganathan S. Lung clearance index during hospital admission in school-age children with cystic fibrosis.J Cyst Fibros. 2014; ([Electronic publication ahead of print])Abstract Full Text Full Text PDF Scopus (17) Google Scholar]. However, the data they have provided does not convince us to change our position with regard to the use of multiple breath washout (MBW) to assess intravenous (IV) antibiotic treatment response during pulmonary exacerbation in children with cystic fibrosis (CF) [[2]Vanderhelst E. De Meirleir L. Schuermans D. Malfroot A. Vincken W. Verbanck S. Evidence of an acinar response following treatment for exacerbation in adult patients with cystic fibrosis.Respiration. 2014; 87: 492-498Crossref PubMed Scopus (10) Google Scholar]. Indeed, it further highlights the heterogeneous nature of MBW outcomes in this disease group. Over 50% of their study patients did not have an improvement in lung clearance index (LCI) and this is in keeping with a growing list of similar studies that have included a wide range of ages and disease severity [3Horsley A.R. Davies J.C. Gray R.D. Macleod K.A. Donovan J. Aziz Z.A. Bell N.J. Rainer M. Mt-Isa S. Voase N. Dewar M.H. Saunders C. Gibson J.S. Parra-Leiton J. Larsen M.D. Jeswiet S. Soussi S. Bakar Y. Meister M.G. Tyler P. Doherty A. Hansell D.M. Ashby D. Hyde S.C. Gill D.R. Greening A.P. Porteous D.J. Innes J.A. Boyd A.C. Griesenbach U. Cunningham S. Alton E.W. Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation.Thorax. 2013; 68: 532-539Crossref PubMed Scopus (109) Google Scholar, 4Robinson P.D. Cooper P. Van Asperen P. Fitzgerald D. Selvadurai H. Using index of ventilation to assess response to treatment for acute pulmonary exacerbation in children with cystic fibrosis.Pediatr Pulmonol. 2009; 44: 733-742Crossref PubMed Scopus (56) Google Scholar, 5Yammine S. Bigler A. Casaulta C. Singer F. Latzin P. Reasons for heterogeneous change in LCI in children with cystic fibrosis after antibiotic treatment.Thorax. 2014; 69: 183Crossref PubMed Scopus (20) Google Scholar]. Importantly though, the MBW measurements in the Vanderhelst study were performed after the administration of 400 μg bronchodilator. This deviation from the recommended guidelines [[6]Robinson P.D. Latzin P. Verbanck S. Hall G.L. Horsley A. Gappa M. Thamrin C. Arets H.G. Aurora P. Fuchs S.I. King G.G. Lum S. Macleod K. Paiva M. Pillow J.J. Ranganathan S. Ratjen F. Singer F. Sonnappa S. Stocks J. Subbarao P. Thompson B.R. Gustafsson P.M. Consensus statement for inert gas washout measurement using multiple- and single-breath tests.Eur Respir J. 2013; 41: 507-522Crossref PubMed Scopus (526) Google Scholar] not only precludes comparison with the extant literature, but also brings into question their findings. Considering the onset of action and half-life of bronchodilator, the timing of the MBW measurement following bronchodilator administration is crucial. During washout, larger breaths can lead to the release of significant amounts of trapped gas which invalidates the SnIII analysis and can also result in increased LCI values. It is feasible to suggest that additional lung units, including previously trapped gas, could be recruited as bronchodilator takes effect, and this may be ongoing throughout the testing session. Moreover, individual bronchodilator response may be different at admission compared to discharge. While we can only speculate about the degree of influence this methodology would yield, it may partly explain the acinar contribution the authors now report. Several of the aforementioned studies have reported improvements in LCI at group level, but the individual response to treatment has been noticeably variable. It therefore remains difficult to see MBW playing a useful role in such a clinical setting. We also express our concern for the extension of modelled derivations and assumptions as to what measurements made by MBW mean to interpretations of structure–function relationships in the clinical setting. Can such assumptions, for example, be relevant to the growing child, or to pre-school children during rapid lung development? We maintain that LCI should not be used to gauge the short-term clinical response to IV antibiotics in school-age children with CF. Until the data are compelling and tested in a large number of subjects of different ages, with disease of varying severity, and the findings used in the clinical setting to determine or monitor response to IV antibiotics, we question the utility of any MBW measurement in this setting.