The Role of Environmental Temperatures in Respiratory Control

Warfighters often face thermal stressors that increase the WOB, even with life-support systems in place. Both cold and heat stress elevate the WOB independently, without requiring increased inspiratory resistance. Cold stress stimulates ventilation and causes a biphasic bronchiolar response: inhaling cold air during hyperventilation leads to initial bronchodilation followed by bronchoconstriction, tightening the bronchioles and increasing airflow resistance, and thus the WOB. Warfighters are also exposed to extreme heat and hyperthermia-induced hyperventilation occurs when core body temperature reaches around 38.0°C, significantly correlating with increased WOB during heat stress. Warfighters frequently experience these environmental stressors alongside elevated breathing resistance, especially during underwater diving missions in varying temperatures or in high-performance aircraft with OBOGs exposed to extreme heat.

A critical gap in knowledge exists regarding whether high inspiratory resistance combined with thermal stress amplifies the WOB, altering the perception of breathing and cognitive and physiological responses. The study will investigate the WOB, breathing perception, cognitive function, and physiological responses under combined inspiratory resistance and thermal stress (thermoneutral, heat, and cold). It's hypothesized that WOB will increase during heat and cold stress, resulting in greater perceptions of breathing difficulty and decreased cognitive performance compared to thermoneutral conditions.

Participants will complete 4 study visits: a screening/familiarization visit (Study Day 0) followed by three experimental visits (Study Day 1, Day 2, and Day 3). Participants will be instructed to avoid caffeine, alcohol, stimulant medication, pain/anti-inflammatory medication, cannabis and cannabis related products, and vigorous exercise for at least 24 hours prior to experimental visits. On Study Day 0, participants will complete a short familiarization breathing task in which they will breathe for 10 minutes through an 8-10mm hole at the end of a customized device, generating a pre-determined inspiratory resistance of 6-9.5 centimeters of water per liter per second (cmH2O/L/s). During the breathing task, cerebral vascular, cardiovascular and autonomic activity responses will be measured. Every 5 minutes during the breathing test, participants will be asked to rate breathing intensity and unpleasantness, and perform an inspiratory capacity maneuver. Cognitive assessments will be administered every10 minutes. After the breathing task, participants will complete lung and respiratory muscle function tests.

Prior to the experimental visits, participants will be randomized to the order in which they are exposed to the interventional conditions (hot, cold, or thermoneutral). Upon arrival, an esophageal balloon will be placed to measure the pressure around the heart and lungs. Participants will then be placed into an environmental chamber (to control humidity) while wearing a special suit which allows different temperatures of water to be circulated through tubes which will expose them to the temperature conditions for roughly 30 minutes before starting the full-length breathing tasks. During thermoneutral conditions 34°C water will be perfused through special suit while participants resting the chamber set to 24°C and 40% room humidity. During the cold condition, 4°C water will be perfused through the special suit while participants rest in the chamber set to 4°C and 10% room humidity. The breathing task will commence when esophageal temperature reaches -1°C and -2°C relative to baseline esophageal temperature. During the hot condition, 50°C water will be perfused through the special suit while participants rest in the chamber set to 40°C and 40% room humidity. The breathing task will commence when esophageal temperature reaches +1°C and +2°C relative to baseline esophageal temperature. At each experimental visit, participants will complete a full-length breathing task, in which they inspire against a predetermined resistive load for 60 minutes. Biometric monitoring will be continuously performed, and cognitive assessments and participant ratings during the breathing tasks will be performed at 45- and 90-minutes of the condition exposure. A 7 day washout period will be observed between the experimental visits.

• Change in Diaphragm Thickness [Time frame: Before and after each breathing task on Days 1, 2, 3 (each approximately 90 minutes in duration)]
• Change in Heart Rate Variability [Time frame: Before and after each breathing task on Days 1, 2, 3 (each approximately 90 minutes in duration)]
• Change in Peripheral Oxygen Saturation [Time frame: Before and after each breathing task on Days 1, 2, 3 (each approximately 90 minutes in duration)]
• Change in Blood Pressure - Brachial Artery [Time frame: Before and after each breathing task on Days 1, 2, 3 (each approximately 90 minutes in duration)]
• Change in Blood Pressure - Finger Photoplethysmography [Time frame: Before and after each breathing task on Days 1, 2, 3 (each approximately 90 minutes in duration)]
• Change in Heart Rate [Time frame: Before and after each breathing task on Days 1, 2, 3 (each approximately 90 minutes in duration)]
• Change in Cerebral Blood Oxygen Kinetics [Time frame: Before and after each breathing task on Days 1, 2, 3 (each approximately 90 minutes in duration)]
• Change in Cerebral Blood Velocity [Time frame: Before and after each breathing task on Days 1, 2, 3 (each approximately 90 minutes in duration)]