The ethics of bronchoscopic research in children
Authors: D. Payne
Journal: Allergy (2007)

For many years the study of asthma and other wheezing disorders in childhood has been hampered by limited access to airway tissue. In 1978, Cutz et al. (1) described the airway features of four children with asthma, using tissue obtained from open lung biopsy and postmortem. However, it took more than 20 years before other investigators began to describe the airway pathology in larger groups of children with and without asthma, using the technique of endobronchial biopsy (2–7).The current study by Kim et al., published in this edition of the Journal, adds to this literature (8). However, such research involving analysis of airway biopsies in children is far from widespread and those researchers undertaking this work know only too well the difficulties encountered. From a practical point of view, performance of endobronchial biopsy requires expertise which can only been gained in a limited number of centres. More importantly, there are obvious ethical constraints, which limit the ability to obtain airway tissue. Particular concerns centre around the safety of endobronchial biopsy and the legitimacy or asking parents to volunteer their children for a procedure that may not have any benefit for the individual. Guidelines for research involving children, published by the Royal College of Paediatrics and Child Health in the UK, state that children should not undergo high-risk procedures for the purpose of research, unless the procedure carries some benefit to the individual (9). Endobronchial biopsy is considered to fall into this high-risk category. However, a number of paediatric studies have established that bronchoscopy with endobronchial biopsy is a safe procedure, with minimal risk, providing it is performed in a specialist centre, by appropriately-trained personnel (10–13). At present, the majority of research groups have restricted their bronchoscopic studies to children who are already undergoing bronchoscopy for a specific clinical indication. This is in keeping with other published guidelines that state that bronchoscopy should not be performed in children purely for research purposes (14, 15). Biopsy findings have been reported from children undergoing bronchoscopy for a variety of clinical indications, such as severe asthma, troublesome preschool wheeze, cystic fibrosis, persistent chest X-ray changes and investigation of stridor. While these studies provide valuable information, this approach limits the range of subjects that can be studied. In particular, control tissue is very hard to obtain as healthy children do not undergo bronchoscopy. From the scientific perspective, the lack of a control group makes accurate interpretation of findings difficult. Given the established safety of endobronchial biopsy in specialist centres, another option is to perform bronchoscopy and biopsy in children purely for research purposes, without any specific benefit to the individual. The advantages of this approach are clear and are well established in adult practice. Research studies could focus on children with a variety of diseases and a range of severity, as well as obtaining control tissue from genuinely healthy children. There would also be the option to perform repeated bronchoscopies – before and after an intervention, for example. Viewed from a purely scientific perspective, this approach is to be encouraged. However, it is clear that the ethics of such an approach need to be the subject of vigorous debate. In the article published by Kim et al. (8), the authors once again investigated children undergoing bronchoscopy for clinical indications, with the research findings an important, but secondary, consideration. However, treatment was discontinued prior to bronchoscopy. Currently, only one published study has included subjects on whom bronchoscopy was performed solely for the purpose of research. In this earlier study, Cokugras et al. investigated the airway pathology in endobronchial biopsies obtained from 10 children with asthma, in whom treatment had been discontinued prior to bronchoscopy (2). Subsequent correspondence in the journal Thorax ensured that ethical aspects of the study did not go unchallenged (16). So which is the right way to proceed? Clearly our current understanding of the pathophysiology of childhood asthma is inadequate. Airway research is necessary and such research should follow sound scientific and ethical principles. A recent debate in the American Journal of Respiratory and Critical Care Medicine has argued for and against the use of animal models vs human studies in asthma (17, 18). Whatever the merits of animal models, human subjects, including infants and children, need to be studied. The safety of bronchoscopy and endobronchial biopsy in established paediatric centres has been demonstrated. Perhaps it is now time to reconsider the ethical barriers to bronchoscopic research in children and to encourage ethics committees to allow parents and children to adopt a more altruistic approach, rather than focusing exclusively on the risks and benefits to the individual.