Relevance of animal research on the effects of postnatal exposure to environmental tobacco smoke

The recent letter to the editor by Pfister et al. ¹ raises crucial ethical questions on animal experimentation. As our recent publication on environmental tobacco smoke (ETS) exposure in lambs ² was directly mentioned to exemplify their ethical issues, we are pleased to provide further information to relieve their concerns.

In Canada, the Canadian Council on Animal Care (CCAC) is responsible for setting and maintaining standards for the ethical use and care of animals in science. As clearly stated on their website (http://www.ccac.ca/en_), ‘each program of participating institutions is subject to regular peer review by the CCAC, which involves an assessment of the institutional animal care and use program structure, the effectiveness of an institution's Animal Care Committee to oversee all animal care and use, and the appropriateness of its animal facilities, practices and procedures’. Of note, during the last on-site visit of our institution in 2010, the CCAC report specifically mentioned that they were impressed with the high quality of the new facilities and equipment used for lambs, including the room and installations dedicated to the automatic smoking machine (ASM).

In our study under question, ² we believe we made significant efforts to optimize animal utilization and wellbeing in the spirit of the 3Rs of Russell and Burch: ³ (1) Reduction: all lambs used in the ASM validation study reported in our publication ² were simultaneously involved in another study on the effect of environmental smoke exposure on laryngeal chemoreflexes; ⁴ thus, lambs did not incur further procedure beyond those needed for the latter study. (2) Refinement: experimental exposure under close surveillance of our personnel, during daytime only, to detect any problem and ensure the animals’ wellbeing; exposure of two animals together (animal enrichment) in a Plexiglas chamber fulfilling the CCAC rules for sheep, use of radiotelemetry to allow the study of freely moving lambs.

Pfister et al. questioned the ‘benefits for human health that this technical paper contributes to’ and concluded with the following request: ‘We ask the editors to … assure that enough information are provided by the authors to assess the prospective benefits to society of studies involving animals.’

As clearly reported in our publication, the aim was to describe the design, building and validation of an ASM, which displayed certain unique characteristics mainly relevant for research on the postnatal effects of ETS exposure. Beyond the need to validate our ASM rigorously and transparently in order to pave the way for our forthcoming studies, our aim was to provide interested colleagues with detailed information, enabling them to replicate our apparatus, if they so wished. Interestingly, following publication of our article, a German academic researcher has contacted our group asking whether we could build a replica of our ASM for his research programme.

What are the benefits for human health to pursue research on tobacco smoke exposure in the perinatal period? As reported in our publication, ² prenatal smoke exposure is considered by experts to be a leading cause of preventable death by sudden infant death syndrome (SIDS). However, as concluded in a thorough review in 2006, ⁵ the effects of postnatal exposure have yet to be clarified, both from a scientific/clinical standpoint, to fully understand its physiological consequences, and from a societal standpoint, to be better armed to fight the tobacco industry on the specific grounds of infant ETS exposure.

We contend that the ‘benefit for human health’ was repeatedly clarified in our publication, especially by providing examples in the conclusion: ‘In conclusion, … our newborn ovine models will be used to better ascertain the effect of cigarette smoke exposure on laryngeal chemoreflexes, swallowing–breathing coordination, control of heart rhythm variability, all of which are involved in apparent life-threatening events (ALTE) of infancy and sudden infant death syndrome.’ We are not aware of previous studies having answered these specific questions, and we believe the latter hold promise in terms of prospective benefits to society, especially in our unique and highly clinically relevant ovine model, the preterm lamb. Our arguments are in line with sections of the NHLBI report on Developmental Aspects of the Upper Airway aiming at prioritizing future research directions in paediatric respiratory biology and disease (see p. 516, Priority Area 1, Developmental Plasticity in Upper Airway Control). ⁶

Furthermore, our scientific interest in assessing the effects of postnatal smoke exposure on ovine models has been repeatedly judged valuable by our peers; beyond obtaining an operating research grant by the Canadian Institutes of Health Research (the Canadian counterpart of the US National Institutes of Health) on the subject, a publication on the effect of smoke exposure on the laryngeal chemoreflexes in lambs has been accepted by the highly respected Journal of Applied Physiology. ⁴

We must confess, we do not quite understand the point made by Pfister et al. with regard to the ‘very sensitive public health issue like environmental tobacco smoke’. As a paediatric pulmonologist involved daily in the care of infants suffering from ETS consequences, as well as in the follow-up of ALTE infants and parents of all SIDS victims referred to our hospital, the senior author (JPP) has been actively engaged against ETS exposure for 30 years now. Furthermore, no co-authors of our publication ² have any relationship of any kind whatsoever with the tobacco industry.

In conclusion, we genuinely believe that our publication follows the recently published ARRIVE guidelines for reporting animal research. ⁷ While still amazed by the pointed concerns expressed by Pfister et al. on our publication, ² we fully concur with them on the heart of the matter they vehemently defend.