Introduction

Upper airway obstruction causing sudden death is well recognized. Examples include food aspiration, infectious disease such as diphtheria, and intentional or accidental suffocation.

Obstructive sleep apnea (OSA) has often been suggested as a cause of sudden and unexpected infant death (SUID). The fact that sudden infant death syndrome (SIDS)/SUID is believed to occur during sleep lends support for this theory. The cause of death in such a case would not be evident at post-mortem examination and so would be consistent with a SUID death. The severity of OSA increases with viral infections of the upper airway which increase nasal resistance. Additionally, epidemiological studies have found that a family history of OSA is a risk factor for SUID (1). However, were OSA to be a major cause of infant deaths, it would not explain the beneficial effect of back sleeping in reducing SUID/SIDS deaths. Significantly, brief episodes of upper airway obstruction during sleep are more common in infants who ultimately died of SIDS/SUID than in infants who survived (2).

The Role of Upper Airway Infection, Laryngeal Chemoreflex, Apnea, and Brain Cytokines in SUID/SIDS

It has been suggested that prolonged apnea, associated with the normally airwayprotective laryngeal chemoreflex (LCR) reflexes, might be causal in SIDS/SUID (3-6). The LCR combined responses are initiated when low chloride or acidic liquids stimulate intra-epithelial receptors in the inter-arytenoid space of the larynx (5, 7, 8). Such stimulation results in swallowing, apnea, vocal cord constriction, cough, and arousal from sleep (4, 8, 10). The apnea component of the LCR is particularly prominent in preterm infants, and later diminishes with maturation (8, 11). Stimulation of the LCR by introducing a drop of water onto the larynx can cause prolonged apnea, especially in preterm infants (12, 13).

The interaction between the LCR, infection, and circulating cytokines is particularly relevant to SIDS causal theories. Hypothetically, upper airway infection, particularly with respiratory syncytial virus (RSV), can result in a fatal course of events that leads to SIDS/SUID. Like the apnea caused by introducing water into an infant's larynx, RSV-related prolonged apnea is characterized by central apnea associated with obstructed inspiratory efforts, as with LCR apnea or prolonged central apnea during periodic breathing (14). Infants between 2 and 4 months of age are at highest risk for SIDS and normally have transient “physiologic” anemia. This is usually more prominent in preterm than in term infants.