Maturation Modulates Pharyngeal-Stimulus Provoked Pharyngeal and Respiratory Rhythms in Human Infants

Abstract

Pharyngeal-provocation induced aerodigestive symptoms in infants remain an enigma. Sources of pharyngeal provocation can be anterograde as with feeding, and retrograde as in gastroesophageal reflux. We determined maturational and dose-response effects of targeted pharyngeal-stimulus on frequency, stability, and magnitude of pharyngeal and respiratory waveforms during multiple pharyngeal swallowing responses in preterm-born infants when they were of full-term postmenstrual age (PMA). Eighteen infants (11 male) were studied longitudinally at 39.8 ± 4.8 weeks PMA (time-1) and 44.1 ± 5.8 weeks PMA (time-2). Infants underwent concurrent pharyngo-esophageal manometry, respiratory inductance plethysmography, and nasal airflow thermistor methods to test sensory-motor interactions between the pharynx, esophagus, and airway. Linear mixed models were used and data presented as mean ± SEM or %. Overall, responses to 250 stimuli were analyzed. Of the multiple pharyngeal swallowing responses (n = 160), with maturation (a) deglutition apnea duration decreases (p < 0.01), (b) number of pharyngeal waveform peaks and duration decreases for initial responses (p < 0.01), and subsequent responses have lesser variation and greater stability (p < 0.01). With increment in stimulus volumes we noted (a) increased prevalence (%) of pharyngeal responses (p < 0.05), (b) increased number of pharyngeal peaks (p < 0.05), yet pharyngeal frequency (Hz), variability, and stability remain unaffected (p > 0.05), and (c) respiratory changes were unaffected (p > 0.05). Initial and subsequent pharyngeal responses and respiratory rhythm interactions become more distinct with maturation. Interval oromotor experiences and volume-dependent increase in adaptive responses may be contributory. These mechanisms may be important in modulating and restoring respiratory rhythm normalcy.

Mechanisms of Aerodigestive Symptoms in Infants with Varying Acid Reflux Index Determined by Esophageal Manometry

“…However, these signs, if associated with other systemic signs, can also be an exaggerated airway-sensory-pain response suggesting recruitment of more neural pathways and its effects on different muscular (somatic and esophageal) functions such as may happen during persistent cough. 16,[24][25][26]32 We noted that provocative stimulus volume is the strongest determinant of symptom prevalence as well as peristaltic reflex frequency-recruitment, irrespective of ARI severity or the composition of the stimulus (Figure 3, A and B). This finding supports that the mechano-, osmo-or chemo-sensitivity (determined using air insufflation, water infusion and apple juice infusion, respectively) of the esophageal mucosa or esophageal muscles is increasingly activated with stimulus volume increments, regardless of the ARI severity categories.…”

“…Such cluster of symptoms/signs interpreted as 'troublesome symptoms of GERD' are likely to be cumulative mechanisms of aerodigestive vigilance, clearance and protection. 18,21,25,26,32 This clinical reasoning stems from the proof of concept (Figure 3) that increasing stimulus volume likely activates esophageal, supra-esophageal and extraesophageal reflexes, and therefore the occurrence of symptoms. Further studies are needed to clarify the pathophysiology in the context of chronic lung disease or neuropathology, both of which are uniquely common in preterm-born infants.…”

Differentiating esophageal sensitivity phenotypes using pH–impedance in intensive care unit infants referred for gastroesophageal reflux symptoms

“…However, the actual number of apnea/bradycardia/desaturation events reported were only 0 (0–1) events per day, which were not associated with any of the esophageal sensitivity profiles. We and others have shown that these events are rarely associated with GER mechanisms and is more likely due to dysfunctional swallowing, which may be modified by maturation and stimulus volume ( 15 , 47 , 49 , 50 ).…”

Pharyngeal contractile and regulatory characteristics are distinct during nutritive oral stimulus in preterm‐born infants: Implications for clinical and research applications

“…We have previously used water perfusion manometry to study pharyngeal rhythms, UES, and esophageal peristalsis in preterm infants . However, this method is limited to one pressure sensor in the pharyngeal region.…”

“…We have previously used water perfusion manometry to study pharyngeal rhythms, UES, and esophageal peristalsis in preterm infants. 17,18 However, this method is limited to one pressure sensor in the pharyngeal region. In adults, high-resolution manometry (HRM) techniques have made it possible to study both the regulatory and contractile functions in greater detail with the presence of multiple sensors in the pharyngeal region.…”