Factors inducing periodic breathing in humans: a general model

Area of Science:

• Respiratory Physiology
• Control Systems Engineering
• Sleep Medicine

Background:

• Periodic breathing (PB) is a complex respiratory disorder observed in various physiological and pathological conditions.
• Instability in the respiratory control system is a known cause of PB.
• Previous models have not comprehensively addressed all forms of PB.

Purpose of the Study:

• To develop a general mathematical model for periodic breathing (PB).
• To identify key factors influencing respiratory control system stability and PB.
• To validate the model's predictions against experimental data.

Main Methods:

• Development of a general mathematical model for respiratory control.
• Analysis of system stability under varying physiological conditions (hypoxia, hypercapnia, altitude).
• Incorporation of peripheral and central controller dynamics, lung washout, and chemoreceptor delays.

Main Results:

• The model accounts for PB in normals (sleep, high altitude), infants, and patients with cardiovascular/neurologic lesions.
• Peripheral controller predominantly mediates ventilatory oscillations in most cases.
• Hypoxia, hypercapnia, increased lung washout, prolonged delays, and high controller sensitivity decrease stability.
• Large lung CO2 and O2 storage volumes enhance stability.
• Model predicts a decrease in PB cycle time with increasing altitude, matching experimental data.
• Allometric scaling validates model predictions in infants.

Conclusions:

• A unified model successfully explains diverse forms of periodic breathing.
• Peripheral chemoreceptor dynamics are central to PB.
• Environmental and physiological factors significantly modulate respiratory control stability.
• The model provides a valuable tool for understanding and potentially treating PB.