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Correspondence |

Endobronchial Biopsy in ChildhoodResponse FREE TO VIEW

Nicolas Regamey, MD; Tom N. Hilliard, MD; Sejal Saglani, MD; Jie Zhu, PhD; Ian M. Balfour-Lynn, MD; Marc Rosenthal, MD; Peter K. Jeffery, DSc (Med); Eric W. F. W. Alton, FMedSci; Andrew Bush, MD; Jane C. Davies, MD
Author and Funding Information

Affiliations: Royal Brompton Hospital and Imperial College, London, UK,  Miller School of Medicine, University of Miami, Miami, FL

Correspondence to: Nicolas Regamey, MD, Department of Gene Therapy, National Heart and Lung Institute, Imperial College London, 1B Manresa Rd, London SW3 6LR, UK; e-mail: N.Regamey@imperial.ac.uk



Chest. 2008;133(1):312-313. doi:10.1378/chest.07-1735
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Published online

We thank Drs. Colin and Ali-Dinar for their carefully written and cogently argued editorial in CHEST (June 2007)1on our report2on the quality of endobronchial biopsies (EBBs) in children with cystic fibrosis (CF). We wish to take this opportunity to develop their arguments further by considering this technique in a clinical as well as a research context. In the setting of asthma, we have shown that, whereas there is reasonable agreement between the numbers of eosinophils in induced sputum and BAL fluid, both of which correlate with the numbers in exhaled nitric oxide (fraction of exhaled nitric oxide at expiratory flow of 50 mL/s), none of these parameters correlate with the EBB eosinophil count.3Further studies are needed to determine whether eosinophils in EBB or BAL fluid samples are most significant clinically in patients with asthma,4 but pediatric clinicians should be clear that information obtained from sputum and BAL fluid samples may not reflect the tissue pathology assessed by EBB; data from these samples cannot be used interchangeably.

Our recent reports on safety5 and quality2 of biopsies in CF children arose from a hypothesis-driven research project, exploring early changes of remodeling and inflammation in the CF pediatric airway. We would like to draw attention to our recent article,6 in which we show that there are elements of airway wall remodeling in CF patients that correlate with inflammation, but also others that appear early and are likely to be independent of infection and inflammation. These changes may represent novel therapeutic targets with which to preserve airway structure and function.

In terms of the safety of EBB, the arguments have been rehearsed already.7 Colin and Ali-Dinar1 argued correctly that the reporting of problems may be incomplete, a position that is impossible, scientifically, to refute. However, we would like to assure them that all our bronchoscopy records are open to full inspection by any proper authority, including our own institutional research services and ethical review boards (who regularly audit the governance of research projects), and as part of the annual appraisal process, which we are all required to undergo.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Colin, AA, Ali-Dinar, T (2007) Endobronchial biopsy in childhood.Chest131,1626-1627. [PubMed] [CrossRef]
 
Regamey, N, Hilliard, TN, Saglani, S, et al Quality, size and composition of paediatric endobronchial biopsies in cystic fibrosis.Chest2007;131,1710-1717. [PubMed]
 
Lex, C, Ferreira, F, Zacharasiewicz, A, et al Airway eosinophilia in children with severe asthma: predictive values of non-invasive tests.Am J Respir Crit Care Med2006;174,1286-1291. [PubMed]
 
Bush, A Inflammometry and asthma: on to the next level.Pediatr Pulmonol2007;42,569-572. [PubMed]
 
Molina-Teran, A, Hilliard, TN, Saglani, S, et al Safety of endobronchial biopsy in children with cystic fibrosis.Pediatr Pulmonol2006;41,1021-1024. [PubMed]
 
Hilliard TN, Regamey N. Shute JK, et al. Airway remodeling in children with cystic fibrosis. Thorax May 25, 2007 [Epub ahead of print].
 
Bush, A, Davies, JC Rebuttal: you are wrong, Dr. Mallory . . .Pediatr Pulmonol2006;41,1017-1020
 
To the Editor:

We thank Dr. Regamey and colleagues for their correspondence in response to our editorial in CHEST (June 2007)1on endobronchial biopsy (EBB) in childhood a propos their report2 on the quality, size, and composition of bronchial biopsies in children with cystic fibrosis.

We thought that our editorial was carefully worded to clarify that it should not be read as a criticism of the innovative work done by this group of respected researchers. We clearly stated that their research exemplified what we viewed as being appropriate, in that it was a hypothesis-driven protocol, which stated a clear scientific purpose, had been approved by an institutional review board, had given an honest and open presentation to the patients’ families, and had defined the goal of research. Such studies, as pointed out in their letter, generate new knowledge and open new horizons. We, therefore, do not think that these studies are inherently inappropriate, as previously discussed in the literature alluded to by Dr. Regamy and colleagues.34 We wrote the following: “The comments that follow express our thoughts on the state of EBB in pediatric bronchoscopy, in both research and clinical practice, as it emerges from this study in the wider context of recent literature and not limited to CF [cystic fibrosis].” The message to the wider pediatric bronchoscopy community should be that their work is not be interpreted as legitimizing or giving license to EBB. Generalization of the use of EBB should be advocated when its diagnostic and therapeutic edge over existing practices will have been defined within a carefully regulated research environment.

Regarding the comments on safety, since their article2 did not include a discussion on safety, obviously our comments are of a general nature, as was stated up front in our editorial. Our concerns emanate from long experience in the field of pediatric bronchoscopy and our sense that we do not have the tools to define what “important complications” are. We also lack the benchmarks to assess their severity or a platform to easily report them. The single large study5 that analyzed complications in bronchoscopy reported “At least one complication” at 6.9%. At Children’s Hospital Boston, as part of a quality control project, we monitored complications immediately at the end of each bronchoscopy and found that we had an overall complication rate of 6%. While the design was prospective, we belatedly recognized that we failed to include contact with the families following the procedure and thus may have missed late complications such as hemoptysis and fever. The data were used for internal control and have not yet been submitted for publication. The recognition that complications are underappreciated is the likely reason that the government of the Netherlands is now mandating that hospitals develop mechanisms and benchmarks to report complications of their various procedures.

In a previous review on bronchoscopy,6 one of the authors of the article and letter wrote: “As it is an invasive procedure, the following should be asked: what question am I trying to answer by bronchoscopy? Will the answer justify the risks of the procedure?” We are in full agreement with this approach and would only comment that when an invasive element to an already invasive procedure is added, one should bear in mind the adage primum non nocere. We are advocating caution when adding a further invasive procedure to our routine bronchoscopy/BAL unless it carries benefits that remain to be defined or serves legitimate research purposes.

References
Colin, AA, Ali-Dinar, T Endobronchial biopsy in childhood.Chest2007;131,1626-1627. [PubMed] [CrossRef]
 
Regamey, N, Hilard, T, Saglani, S, et al Quality, size and composition of paediatric endobronchial biopsies in cystic fibrosis.Chest2007;131,1710-1717. [PubMed]
 
Mallory, GB Pitfalls in non-therapeutic research in children.Pediatr Pulmonol2006;41,1014-1016. [PubMed]
 
Bush, A, Davies, JC Rebuttal: you are wrong, Dr. Mallory …Pediatr Pulmonol;41,1017-1020
 
de Blic, J, Marchac, V, Scheinmann, P Complications of flexible bronchoscopy in children: prospective study of 1328 procedures.Eur Respir J2002;20,1271-1276. [PubMed]
 
Rosenthal, M Bronchoscopy and infection.Paediatr Respir Rev2003;4,143-146. [PubMed]
 

Figures

Tables

References

Colin, AA, Ali-Dinar, T (2007) Endobronchial biopsy in childhood.Chest131,1626-1627. [PubMed] [CrossRef]
 
Regamey, N, Hilliard, TN, Saglani, S, et al Quality, size and composition of paediatric endobronchial biopsies in cystic fibrosis.Chest2007;131,1710-1717. [PubMed]
 
Lex, C, Ferreira, F, Zacharasiewicz, A, et al Airway eosinophilia in children with severe asthma: predictive values of non-invasive tests.Am J Respir Crit Care Med2006;174,1286-1291. [PubMed]
 
Bush, A Inflammometry and asthma: on to the next level.Pediatr Pulmonol2007;42,569-572. [PubMed]
 
Molina-Teran, A, Hilliard, TN, Saglani, S, et al Safety of endobronchial biopsy in children with cystic fibrosis.Pediatr Pulmonol2006;41,1021-1024. [PubMed]
 
Hilliard TN, Regamey N. Shute JK, et al. Airway remodeling in children with cystic fibrosis. Thorax May 25, 2007 [Epub ahead of print].
 
Bush, A, Davies, JC Rebuttal: you are wrong, Dr. Mallory . . .Pediatr Pulmonol2006;41,1017-1020
 
Colin, AA, Ali-Dinar, T Endobronchial biopsy in childhood.Chest2007;131,1626-1627. [PubMed] [CrossRef]
 
Regamey, N, Hilard, T, Saglani, S, et al Quality, size and composition of paediatric endobronchial biopsies in cystic fibrosis.Chest2007;131,1710-1717. [PubMed]
 
Mallory, GB Pitfalls in non-therapeutic research in children.Pediatr Pulmonol2006;41,1014-1016. [PubMed]
 
Bush, A, Davies, JC Rebuttal: you are wrong, Dr. Mallory …Pediatr Pulmonol;41,1017-1020
 
de Blic, J, Marchac, V, Scheinmann, P Complications of flexible bronchoscopy in children: prospective study of 1328 procedures.Eur Respir J2002;20,1271-1276. [PubMed]
 
Rosenthal, M Bronchoscopy and infection.Paediatr Respir Rev2003;4,143-146. [PubMed]
 
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