Exploring inspiratory occlusion metrics to assess respiratory drive in patients under acute intermittent hypoxia.

Patients living with Amyotrophic Lateral Sclerosis (ALS) experience respiratory weakness and, eventually, failure due to inspiratory motor neuron degeneration. Routine pulmonary function tests (e.g., maximum inspiratory pressure (MIP)) are used to assess disease progression and ventilatory compromise. However, these tests are poor discriminators between respiratory drive and voluntary respiratory function at rest. To better understand ALS disease progression, we can look into compensatory strategies and how patients consciously react to the occlusion and the effort produced to meet the ventilatory challenge of the occlusion. This ventilatory challenge, especially beyond the P0.1 (200 ms and 300 ms), provides information regarding the patient's ability to recruit additional respiratory muscles as a compensatory strategy. Utilizing a standard P0.1 protocol to assess respiratory drive, we extend the occlusion time analysis to 200 ms and 300 ms (Detected Occlusion Response (DOR)) in order to capture compensatory respiratory mechanics. Furthermore, we followed an Acute Intermittent Hypoxia (AIH) protocol known to increase phrenic nerve discharge to evaluate the compensatory strategies. Inspiratory pressure, the rate of change in pressure, and pressure generation normalized to MIP were measured at 100 ms, 200 ms, and 300 ms after an occlusion. Airway occlusions were performed three times during the experiment (i.e., baseline, 30 and 60 minutes post-AIH). Results indicated that while AIH did not elicit change in the P0.1 or MIP, the DOR increased for ALS patients. These results support the expected therapeutic role of AIH and indicate the potential of the DOR as a metric to detect compensatory changes.

Characterizing and Modeling Breathing Dynamics: Flow Rate, Rhythm, Period, and Frequency.

The characterization of breathing dynamics provides researchers and clinicians the ability to differentiate respiratory compensation, impairment, disease progression, ventilator assistance, and the onset of respiratory failure. However, within many sub-fields of respiratory physiology, we still have challenges identifying changes within the breathing dynamics and critical respiratory states. We discuss one fundamental modeling of breathing and how modeling imprecise assumptions decades ago regarding breathing are still propagating into our quantitative analysis today, limiting our characterization and modeling of breathing. The assumption that breathing is a continuous sinusoidal wave that can consist of a single frequency which is composed of a stationary time-invariant process has limited our expanded discussion of breathing dynamics, modeling, functional testings, and metrics. Therefore, we address major misnomers regarding breathing dynamics, specifically rate, rhythm, frequency, and period. We demonstrate how these misnomers impact the characterization and modeling through the force equations that are linked to the Work of Breathing (WoB) and our interpretation of breathing dynamics through the fundamental models and create possible erroneous evaluations of work of breathing. This discussion and simplified non-periodic WoB models ultimately sets the foundation for improved quantitative approaches needed to further our understanding of breathing dynamics, compensation, and adaptation.