Respiratory tract infections, reflex apnea and sudden infant death : experimental and epidemiological studies with special reference to respiratory syncytial virus, Bordetella pertussis and sleep position

Abstract

The seasonal distribution of Sudden infant death syndrome (SIDS) followed the prevalence of respiratory tract infections (RTI) when prone sleeping position was recommended, but this covariation has recently been attenuated. Airway infections in the young infant are known to produce respiratory disturbances. Irregular breathing, apnea and cyanotic spells are clinical signs of a RTI caused by Respiratory syncytial virus (RSV) and Bordetella pertussis. Neither the mechanism of apnea in conjunction with infection in the young infant, nor the protective effect of supine sleeping position have been elucidated. Hypothesis Upper respiratory tract infections reinforces the laryngeal chemoreflex (LCR) to a potentially life-threatening process, leading to prolonged apnea, failure to arouse from sleep, hypoxemia and cardiovascular collapse in the vulnerable infant.

Aims of the study: 1. To determine the effect of RSV infection on reflex induced apnea, arousal from sleep and resumption of regular breathing in the newborn lamb and in RSV infected infants; 2. To correlafe the LCR response to laryngeal epithelial pathology in lambs and to concentrations of pro-inflammatory mediators in airway secretions in RSV infected infants; 3. To investigate the relationship between SIDS mortality rate and prevalence of pertussis in relation to different immunisation status; and 4. To examine whether the recent decline in SIDS mortality rate de facto has been accompanied by decreased prevalence of prone sleeping position.

Methods: The response to laryngeal chemostimulation (LCS) was studied during wakefulnes amd in different sleep states in experimentally RSV infected young lambs and during sleep in infants with naturally acquired RSV infection. Concentrations of pro-inflammatory mediators in airway secretions in infants were related to LCR apnea and to spontaneous sleep apnea. Monthly fluctuations in SIDS mortality rate and prevalence of pertussis dunng 1983-1988 in two infant populations (Norway and Sweden) were analysed by linear regression. 1028 parental couples were interviewed about feeding and smoking habits, and what infant sleep position was used at three months of age.

Results: RSV infection signrficantly decreased minute ventilation and prolonged both apnea and recovery-time in response to LCS in the young lamb. Arousal was less likely to occur in active sleep (AS). Pronounced bradycardia, hypoventilation and loss of muscular tone were noted if the LCR response was not associated with arousal. Vacuolisation and disruption of airway receptor cells were found 4-6 weeks after RSV infection in lambs. Prolonged LCR apnea was found in RSV infected infants, however the cardio-respiratory response was not severe in the supine sleeping position. An inverse correlation between LCR apnea and concentration of Interleukin 1beta in airway secretions was observed. Covariation between sudden unexpected death and clinical cases of pertussis was observed in a non-immunised infant population living in a densely populated area. The reduced SIDS mortality rate in Sweden has been accompanied by a reduction of prone sleeping position.

Conclusions: RSV infection reinforces the response to LCS and may interfere with arousal mechanisms. The reinforced response to LCS may become life-threatening if not associated with arousal from sleep. Covariations between SIDS incidence and prevalence of pertussis may be related to immunisation status and transmission rate in the population. The reduced mortality rate and the attenuation of the seasonal distribution of SIDS in Sweden have been concurrent with decreased prevalence of prone sleeping position.

Speculation: During RTI the physiological defence mechanism, LCR, intended to prevent foreign substances to be inhaled, is reinforced to the extent that the response to LCS may be life-threatening for the vulnerable infant sleeping prone. The recent reduction in SIDS mortality rate and the attenuation of seasonal distribution might to some extent, be attributed to the reduced risk of laryngeal chemoreceptors being stimulated by stagnated airway secretions in the supine sleeping position.