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• Comments regarding the ethical aspects of using radiolabelled aerosols in research
  David A Spencer
  Published on: 22 March 2016

• Published on: 22 March 2016

  Comments regarding the ethical aspects of using radiolabelled aerosols in research

  • David A Spencer, Consultant in Respiratory Paediatrics
  • Other Contributors:
    • Nuala Byrne, Pauline Keavey, Terry Hawkins

  Dear Editor

  We read with interest Dr Everard’s leading article related to the ethics of using radiolabelled aerosols for research in children and wish to add our comments. There can be few areas that have been so comprehensively covered by legislation and practitioner guidance as the use of radioactivity in patients. These impose the highest standards of ethical care in diagnosis, treatment and research. The questio...

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  Dear Editor

  We read with interest Dr Everard’s leading article related to the ethics of using radiolabelled aerosols for research in children and wish to add our comments. There can be few areas that have been so comprehensively covered by legislation and practitioner guidance as the use of radioactivity in patients. These impose the highest standards of ethical care in diagnosis, treatment and research. The questions posed by Dr Everard are essentially those addressed by the radiation and nuclear medicine authorities through their publications and committees.

  We agree wholeheartedly with Dr Everard in his conclusion that the risk of such studies appears to be extremely low. We would, however, add that it is important to consider the severity of the disease and the effectiveness of currently available therapies when making such judgements. Wheeze in infants is extremely common but thankfully it is unusual for this to become life threatening and effective therapies are already available. Cystic fibrosis remains a condition which eventually kills most affected patients and over a much shorter time scale than any conceivable adverse effects from the doses of radiation used in our study. Currently available treatments merely delay this eventuality and we would argue that it is therefore of greater practical importance for us to optimise treatment in this condition.

  Dr Everard quotes his own work to claim that results similar to ours could probably have been obtained using a breathing simulator.[1] We think that he overstates the significance of his own findings. Everard found no difference in budesonide deposition to a filter in eight normal adults compared to two experimental sites with the breathing simulator. While this may be a coarse indicator of total inhaled mass, it obviously gives no indication as to the pattern of drug delivery within the airways. It is difficult to justify extrapolation of findings from normal adults to young patients with diseased lungs and the very small number of subjects studied suggests the risk of a type two error.

  Whilst we accept that more is not necessarily better in terms of some drugs, we think that this is difficult to argue in the context of nebulised Colistin. It has been used for decades in Europe without any evidence of toxicity other than subjective chest tightness and a small decrease in lung function if used without pre bronchodilation.[2] The Danish group now routinely use twice the nominal dose quoted in our studies [3] and the Cystic Fibrosis Trust antibiotic group also recommends use of this higher dosage in patients over the age of two years.[4] Everard’s own work on neutrophil elastase is of theoretical interest but does not show any evidence of clinical toxicity.[5] This situation is significantly different to that with nebulised aminoglycosides which have been shown to have potentially very important adverse effects on renal tubular function,[6] a fact which does not seem to have been appreciated by those conducting clinical trials on preservative free tobramycin.[7]

  We agree that further carefully designed clinical studies are required to answer outstanding questions but a multi-centred controlled randomised trial would be required to provide the necessary statistical power. The Cystic Fibrosis Trust has made admirable advances in initiating such collaborations but there are practical limitations to the number of such studies which can be performed on this patient group, and studies such as ours are a necessary preliminary before they could be initiated.[8]

  References

  (1) Nikander K, Denyer J, Everard M et al. Validity of a new breathing simulator generating and measuring inhaled aerosol with adult breathing patterns. Journal of Aerosol Medicine 2000; 13:139-46.

  (2) Dodd ME, Abbott J, Maddison J, Moorcroft AJ, Webb AK. Effect of the tonicity of nebulised colistin on chest tightness and pulmonary function in adults with cystic fibrosis. Thorax 1997; 52:656-658.

  (3) Frederiksen B, Koch C, Hoiby N. Antibiotic treatment of initial colonisation with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatric Pulmonolgy 1997;23:330-335.

  (4) Antibiotic treatment for cystic fibrosis. Report of the UK Cystic Fibrosis Trust Antibiotic Group. Second Edition, September 2002.

  (5) Ring E, Eber E, Erwa W, Zach MS. Urinary N-acetyl-beta–D-glucosaminiadase activity in patients with cystic fibrosis on long term gentamycin inhalation. Arch Dis Child 1998;78: 540-543.

  (6) Jones A, Elphick H, Pettitt E et al. Colistin stimulates the activity of neutrophil elastase and Pseudomonas aeruginosa elastase. European Respiratory Journal 2002; 19:1136-41

  (7) Ramsey BW, Pepe MS, Quan JM et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. The New England Journal of Medicine 1999;340:23-30.

  (8) Byrne NM, Keavey PM, Perry JD et al. Comparison of lung deposition of Colomycin using the HaloLite and the Pari LC Plus nebulisers in children with cystic fibrosis. Archives of Disease in Childhood 2003; 88: 715-8

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  Conflict of Interest:
  None declared.

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