Indirect assessment of mucosal surface temperatures in the airways: theory and tests

We developed and tested a method, based on conduction heat transfer analysis, to infer airway mucosal temperatures from airstream temperature-time profiles during breath-hold maneuvers. The method assumes that radial conduction of heat from the mucosal wall to inspired air dominates heat exchange during a breath-hold maneuver and uses a simplified conservation of energy analysis to extrapolate wall temperatures from air temperature vs. time profiles. Validation studies were performed by simultaneously measuring air and wall temperatures by use of a retractable basket probe in the upper airways of human volunteers and intrathoracic airways of paralyzed intubated dogs during breath holding. In both protocols, a good correlation was demonstrated between directly measured wall temperatures and those calculated from adjacent airstream temperature vs. time profiles during a breath hold. We then calculated intrathoracic bronchial wall temperatures from breath-hold airstream temperature-time profiles recorded in normal human subjects after cold air hyperpnea at 30 and 80 l/min. The calculations show airway wall temperatures in the upper intrathoracic airways that are below core body temperature during hyperpnea of frigid air and upper thoracic airways that are cooler than more peripheral airways. The data suggest that the magnitude of local intrathoracic heat/water flux is not represented by heat/water loss measurements at the airway opening. Both the magnitude and locus of heat transport during cold gas hyperventilation vary with changes in inspired gas temperature and minute ventilation; both may be important determinants of airway responses.     

Finite difference analysis of respiratory heat transfer

A numerical computer model of heat and water transfer within the tracheobronchial tree of humans was developed based on an integral formulation of the first law of thermodynamics. Simulation results were compared with directly measured intraluminal airway temperature profiles previously obtained in normal human subjects, and a good correlation was demonstrated. The model was used to study aspects of regional pulmonary heat transfer and to predict the outcomes of experiments not yet performed. The results of these simulations show that a decrease in inspired air temperature and water content at fixed minute ventilation produces a proportionately larger increase in heat loss from extrathoracic airways relative to intrathoracic, whereas an increase in minute ventilation at fixed inspired air conditions produces the opposite pattern, with cold dry air penetrating further into the lung, and that changes in breathing pattern (tidal volume and frequency) at fixed minute ventilation and fixed inspiratory-to-expiratory (I/E) ratio do not affect local air temperature profiles and heat loss, whereas changes in I/E ratio at fixed minute ventilation do cause a significant change.     

Distribution of airway narrowing during hyperpnea-induced bronchoconstriction in guinea pigs

Increasing minute ventilation of dry gas shifts the principal burden of respiratory heat and water losses from more proximal airway to airways farther into the lung. If these local thermal transfers determine the local stimulus for bronchoconstriction, then increasing minute ventilation of dry gas might also extend the zone of airway narrowing farther into the lung during hyperpnea-induced bronchoconstriction (HIB). We tested this hypothesis by comparing tantalum bronchograms in tracheostomized guinea pigs before and during bronchoconstriction induced by dry gas hyperpnea, intravenous methacholine, and intravenous capsaicin. In eight animals subjected to 5 min of dry gas isocapnic hyperpnea [tidal volume (VT) = 2-5 ml, 150 breaths/min], there was little change in the diameter of the trachea or the main stem bronchi up to 0.75 cm past the main carina (zone 1). In contrast, bronchi from 0.75 to 1.50 cm past the main carina (zone 2) narrowed progressively at all minute ventilations greater than or equal to 300 ml/min (VT = 2 ml). More distal bronchi (1.50-3.10 cm past the main carina; zone 3) did not narrow significantly until minute ventilation was raised to 450 ml/min (VT = 3 ml). The estimated VT during hyperpnea needed to elicit a 50% reduction in airway diameter was significantly higher in zone 3 bronchi [4.3 +/- 0.8 (SD) ml] than in zone 2 bronchi (3.5 +/- 1.1 ml, P less than 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)     

Model simulation of heat and water transport dynamics in an airway

Heat and water transport processes in the respiratory tract depend on environmental conditions, breathing patterns, and the physiological state of the respiratory system. To study these processes, we have developed a mathematical model of the dynamics of temperature and water vapor in the radial and axial directions of an idealized trachea. The model is expressed as two implicit finite-difference equations and solved using an alternating-direction algorithm. Using these equations, we simulated the effects of inspired gas temperature and humidity, velocity profile, and flow rate on heat and water transport between the gas and airway wall. Under inspired gas conditions of low temperature or high relative humidity, supersaturation occurs. Increasing either the velocity gradient at the wall or the flow rate increases the heat and water transport rates. However, these rates change by only 10 percent when the velocity gradient is doubled, and by about 35 percent when flow rate undergoes a two-fold change. The model can be used with in-vivo data from the trachea to test hypotheses concerning normal and abnormal heat and water transport.     

Role of tracheal and bronchial circulation in respiratory heat exchange

Due to their anatomic configuration, the vessels supplying the central airways may be ideally suited for regulation of respiratory heat loss. We have measured blood flow to the trachea, bronchi, and lung parenchyma in 10 anesthetized supine open-chest dogs. They were hyperventilated (frequency, 40; tidal volume 30-35 ml/kg) for 30 min or 1) warm humidified air, 2) cold (-20 degrees C dry air, and 3) warm humidified air. End-tidal CO2 was kept constant by adding CO2 to the inspired ventilator line. Five minutes before the end of each period of hyperventilation, measurements of vascular pressures (pulmonary arterial, left atrial, and systemic), cardiac output (CO), arterial blood gases, and inspired, expired, and tracheal gas temperatures were made. Then, using a modification of the reference flow technique, 113Sn-, 153Gd-, and 103Ru-labeled microspheres were injected into the left atrium to make separate measurements of airway blood flow at each intervention. After the last measurements had been made, the dogs were killed and the lungs, including the trachea, were excised. Blood flow to the trachea, bronchi, and lung parenchyma was calculated. Results showed that there was no change in parenchymal blood flow, but there was an increase in tracheal and bronchial blood flow in all dogs (P less than 0.01) from 4.48 +/- 0.69 ml/min (0.22 +/- 0.01% CO) during warm air hyperventilation to 7.06 +/- 0.97 ml/min (0.37 +/- 0.05% CO) during cold air hyperventilation.     

Cold-induced changes in breathing pattern as a strategy to reduce respiratory heat loss

Thermoregulatory benefits of cold-induced changes in breathing pattern and mechanism(s) by which cold induces hypoventilation were investigated using male Holstein calves (1-3 mo old). Effects of ambient temperatures (Ta) between 4 and 18 degrees C on ventilatory parameters and respiratory heat loss (RHL) were determined in four calves. As Ta decreased, respiratory frequency decreased 29%, tidal volume increased 35%, total ventilation and RHL did not change, and the percentage of metabolic rate attributed to RHL decreased 26%. Total ventilation was stimulated by increasing inspired CO2 in six calves (Ta 4-6 degrees C), and a positive relationship existed between respiratory frequency and expired air temperature. Therefore, cold-exposed calves conserve respiratory heat by decreasing expired air temperature and dead space ventilation. Compared with thermoneutral exposure (16-18 degrees C), hypoventilation was induced by airway cold exposure (4-6 degrees C) alone and by exposing the body but not the airways to cold. Blocking nasal thermoreceptors with topical lidocaine during airway cold exposure prevented the ventilatory response but did not lower hypothalamic temperature. Hypothalamic cooling (Ta 16-18 degrees C) did not produce a ventilatory response. Thus, airway temperature but not hypothalamic temperature appears to control ventilation in cold-exposed calves.     

Thermal mapping of the airways in humans

To characterize the intrathoracic thermal events that occur during breathing in humans, we developed a flexible probe (OD 1.4 mm) containing multiple thermistors evenly spaced over 30.2 cm, that could be inserted into the tracheobronchial tree with a fiberoptic bronchoscope. With this device we simultaneously recorded the airstream temperature at six points from the trachea to beyond the subsegmental bronchi in six normal subjects while they breathed ambient and frigid air at multiple levels of ventilation (VE). During quiet breathing of room air the average temperature ranged from 32.0 +/- 0.05 degrees C in the upper trachea to 35.5 +/- 0.3 degrees C in the subsegmental bronchi. As ventilation was increased, the temperature along the airways progressively decreased, and at a VE of 100+ 1/min the temperature at the above two sites fell to 29.2 +/- 0.5 and 33.9 +/- 0.8 degrees C, respectively. Interval points were intermediate between these extremes. With cold air, the changes were considerably more profound. During quiet breathing, local temperatures approximated those recorded in the maximum VE room-air trial, and at maximum VE, the temperatures in the proximal and distal airways were 20.5 +/- 0.6 and 31.6 +/- 1.2 degrees C, respectively. During expiration, the temperature along the airways progressively decreased as the air flowed from the periphery of the lung to the mouth: the more the cooling during inspiration, the lower the temperature during expiration. These data demonstrate that in the course of conditioning inspired air the intrathoracic and intrapulmonic airways undergo profound thermal changes that extend well into the periphery of the lung.     

Heat and water rate transfer processes in the human respiratory tract at various altitudes

The process of the respiratory air conditioning as a process of heat and mass exchange at the interface inspired air-airways surface was studied. Using a model of airways (Olson et al., 1970) where the segments of the respiratory tract are like cylinders with a fixed length and diameter, the corresponding heat transfer equations, in the paper are founded basic rate exchange parameters-convective heat transfer coefficient h(c)(W m(-2) degrees C(-1)) and evaporative heat transfer coefficient h(e)(W m(-2)hPa(-1)). The rate transfer parameters assumed as sources with known heat power are connected to airflow rate in different airways segments. Relationships expressing warming rate of inspired air due to convection, warming rate of inspired air due to evaporation, water diffused in the inspired air from the airways wall, i.e. a system of air conditioning parameters, was composed. The altitude dynamics of the relations is studied. Every rate conditioning parameter is an increasing function of altitude. The process of diffusion in the peripheral bronchial generations as a basic transfer process is analysed. The following phenomenon is in effect: the diffusion coefficient increases with altitude and causes a compensation of simultaneous decreasing of O(2)and CO(2)densities in atmospheric air. Due to this compensation, the diffusion in the peripheral generations with altitude is approximately constant. The elements of the human anatomy optimality as well as the established dynamics are discussed and assumed. The square form of the airways after the trachea expressed in terms of transfer supposes (in view of maximum contact surface), that a maximum heat and water exchange is achieved, i.e. high degree of air condition at fixed environmental parameters and respiration regime.     

Use of a heat transfer analogy for a mathematical model of respiratory tract deposition

Mathematical models predicting the aerosol deposition in the respiratory tract are reviewed. Data in the literature indicated not only that the air flow in the trachea and major bronchi may not be laminar, but also that the entrance effect of the tube or airway has not been considered. A new approach to a mathematical model of respiratory tract deposition, based on the analogy of the heat and mass transfer, is discussed.     

Boundary Conditions for Heat Transfer and Evaporative Cooling in the Trachea and Air Sac System of the Domestic Fowl: A Two-Dimensional CFD Analysis

Various parts of the respiratory system play an important role in temperature control in birds. We create a simplified computational fluid dynamics (CFD) model of heat exchange in the trachea and air sacs of the domestic fowl (Gallus domesticus) in order to investigate the boundary conditions for the convective and evaporative cooling in these parts of the respiratory system. The model is based upon published values for respiratory times, pressures and volumes and upon anatomical data for this species, and the calculated heat exchange is compared with experimentally determined values for the domestic fowl and a closely related, wild species. In addition, we studied the trachea histologically to estimate the thickness of the heat transfer barrier and determine the structure and function of moisture-producing glands. In the transient CFD simulation, the airflow in the trachea of a 2-dimensional model is evoked by changing the volume of the simplified air sac. The heat exchange between the respiratory system and the environment is simulated for different ambient temperatures and humidities, and using two different models of evaporation: constant water vapour concentration model and the droplet injection model. According to the histological results, small mucous glands are numerous but discrete serous glands are lacking on the tracheal surface. The amount of water and heat loss in the simulation is comparable with measured respiratory values previously reported. Tracheal temperature control in the avian respiratory system may be used as a model for extinct or rare animals and could have high relevance for explaining how gigantic, long-necked dinosaurs such as sauropoda might have maintained a high metabolic rate.     

Perceiving nasal patency through mucosal cooling rather than air temperature or nasal resistance

Adequate perception of nasal airflow (i.e., nasal patency) is an important consideration for patients with nasal sinus diseases. The perception of a lack of nasal patency becomes the primary symptom that drives these patients to seek medical treatment. However, clinical assessment of nasal patency remains a challenge because we lack objective measurements that correlate well with what patients perceive. The current study examined factors that may influence perceived patency, including air temperature, humidity, mucosal cooling, nasal resistance, and trigeminal sensitivity. Forty-four healthy subjects rated nasal patency while sampling air from three facial exposure boxes that were ventilated with untreated room air, cold air, and dry air, respectively. In all conditions, air temperature and relative humidity inside each box were recorded with sensors connected to a computer. Nasal resistance and minimum airway cross-sectional area (MCA) were measured using rhinomanometry and acoustic rhinometry, respectively. General trigeminal sensitivity was assessed through lateralization thresholds to butanol. No significant correlation was found between perceived patency and nasal resistance or MCA. In contrast, air temperature, humidity, and butanol threshold combined significantly contributed to the ratings of patency, with mucosal cooling (heat loss) being the most heavily weighted predictor. Air humidity significantly influences perceived patency, suggesting that mucosal cooling rather than air temperature alone provides the trigeminal sensation that results in perception of patency. The dynamic cooling between the airstream and the mucosal wall may be quantified experimentally or computationally and could potentially lead to a new clinical evaluation tool.     

Heat and water flux in the intrathoracic airways and exercise-induced asthma

To explore the relationship between the flux of heat and water within the respiratory tract during exercise and recovery to the development of exercise-induced asthma (EIA), we recorded airstream temperature at multiple points throughout the tracheobronchial tree in 10 normal and 10 asthmatic subjects before, during, and after cycle ergometry. In both groups, the intra-airway temperature fell progressively as ventilation increased, and there were no significant differences between the thermal profiles of the two populations at rest or during exercise. Calculation of water losses and the osmolality of the airway surface fluid failed to demonstrate significant airway drying in either group. With cessation of the work load, the airstream temperature increased abruptly, rising two times more rapidly in the asthmatics than the normals. Since the major source of heat in these experiments is the bronchial circulation, our findings suggest a reaction sequence consisting of vasoconstriction and airway cooling during exercise followed by a rapid resupply of heat when exercise ceases. The latter may cause the hyperplastic capillary bed in the airways of asthmatics to develop an exaggerated rebound hyperemia which may lead to airway edema and EIA.     

Thermal equilibrium of goats

The effects of air temperature and relative humidity on thermal equilibrium of goats in a tropical region was evaluated. Nine non-pregnant Anglo Nubian nanny goats were used in the study. An indirect calorimeter was designed and developed to measure oxygen consumption, carbon dioxide production, methane production and water vapour pressure of the air exhaled from goats. Physiological parameters: rectal temperature, skin temperature, hair-coat temperature, expired air temperature and respiratory rate and volume as well as environmental parameters: air temperature, relative humidity and mean radiant temperature were measured. The results show that respiratory and volume rates and latent heat loss did not change significantly for air temperature between 22 and 26 °C. In this temperature range, metabolic heat was lost mainly by convection and long-wave radiation. For temperature greater than 30 °C, the goats maintained thermal equilibrium mainly by evaporative heat loss. At the higher air temperature, the respiratory and ventilation rates as well as body temperatures were significantly elevated. It can be concluded that for Anglo Nubian goats, the upper limit of air temperature for comfort is around 26 °C when the goats are protected from direct solar radiation.     

Radial heat and water transport across the airway wall

The thermal profiles in the airways of healthy human volunteers and patients with asthma differ after cessation of hyperpnea. The asthmatic patients rewarm their airways more rapidly. To identify thermal properties and processes that could account for the difference between these populations, we developed a model describing the radial transport of heat and water across the trachea. A distinctive feature of the model is a variable parameter describing blood supply to the mucosal and submucosal layers. Simulations performed with the model are initiated by a breath-hold maneuver and are propagative in time. Blood perfusion rates in the airway wall, the thickness of the layer of airway surface liquid, and the mucosa-submucosa thickness, all thought to be more pronounced in asthmatic patients, were varied by changing model parameters and initial conditions. Increasing the thickness of the liquid layer by more than an order of magnitude had little effect on the temperature or water content in the airway lumen. Doubling the blood flow to the mucosa-submucosa resulted in a slight increase in airway temperature. When this effect was coupled, however, with an increase in the thickness of the mucosa-submucosa layer, the increase in temperature was more pronounced. Because the bronchial circulation is the major source of heat to the airway, these results indicate that differences in airway wall thickness coupled with differences in the magnitude or responsiveness of the bronchial microcirculation could account for the differences in intra-airway temperature between the two populations.     

Effect of season on thermoregulation, metabolism and ventilation of the southern brown bandicoot Isoodon obesulus (Marsupialia: Peramelidae)

Seasonal variation in various thermoregulatory, metabolic and ventilatory parameters was examined for southern brown bandicoots (Isoodon obesulus fusciventer) from a Mediterranean climate near Perth, Western Australia. There was significant seasonal variation over the four annual seasons at thermoneutrality (Ta=30 degrees C) in body temperature, oxygen consumption, carbon dioxide production, respiratory exchange ratio, total evaporative water loss, wet and dry thermal conductance and tidal volume but not mass, ventilatory frequency, minute volume or oxygen extraction efficiency. Only carbon dioxide production and respiratory exchange ratio showed an annual pattern that was significantly related to season, with both being significantly higher in winter, presumably as a result of greater and higher quality food availability.     

Mathematical modeling of heat and water transport in human respiratory tract

Excessive heat and water losses from the airways are stimuli to asthma. To study heat and water vapor transport in the human respiratory tract, a time-dependent model, based on a single differential equation with an analytical solution, was developed that could predict the intra-airway temperatures and water vapor contents. The key feature is the dependence of the temperature and water vapor along the respiratory tract as a function of the air residence time at each location. The model assumes disturbed laminar flow leading to enhanced transport mechanisms and wall temperature profiles modeled according to experimental data (E. R. McFadden, Jr., B. M. Pichurko, H. F. Bowman, E. Ingenito, S. Burns, N. Dowling, and J. Soloway. J. Appl. Physiol. 58: 564-570, 1985). It predicts that 1) the air equilibrates with the wall before it reaches body conditions (37 degrees C, 99.5% relative humidity); 2) conditioning of the inspired air involves several generations, with the number depending on the respiratory conditions; and 3) the walls of the upper airways are unsaturated, although it is difficult to judge at this state the depth of the respiratory tract affected.     

Is the evaporative water loss of Knot Calidris canutus higher in tropical than in temperate climates?

To test whether Knot Calidris canutus wintering in the tropics suffer higher rates of water loss through evaporation than do Knot wintering at temperate latitudes, we tried to develop a physically realistic model to predict evaporative heat loss from air temperature, wind and humidity. In separate experiments, involving respirometry and double-labelled water, we tried to estimate relevant parameters. In both sets of experiments, we were able to show significant effects of air temperature on evaporative water loss only. Knot which were able to eat and drink had an evaporative water loss three times that of postabsorptive Knot unable to drink when in a metabolic chamber. Water turnover rates of Knot feeding on bivalves under simulated field conditions were high and did not correlate with predicted evaporative water loss. Over 32 experimental bird-days, the average contribution of predicted evaporative water loss to daily water turnover was 20%. A comparison of predicted evaporative water loss in the north-temperate Dutch Wadden Sea and in the tropical Banc d'Arguin in Mauritania in midwinter showed that Knot wintering in the tropics may need only marginally more water for evaporative cooling than Knot wintering in the Dutch Wadden Sea. Knot foraging on intertidal invertebrates are able to maintain high water turnover rates with little need to drink seawater.     

Hydrating the respiratory tract: An alternative explanation why masks lower severity of COVID-19

The seasonality of respiratory diseases has been linked, among other factors, to low outdoor absolute humidity and low indoor relative humidity, which increase evaporation of water in the mucosal lining of the respiratory tract. We demonstrate that normal breathing results in an absorption-desorption cycle inside facemasks, in which supersaturated air is absorbed by the mask fibers during expiration, followed by evaporation during inspiration of dry environmental air. For double-layered cotton masks, which have considerable heat capacity, the temperature of inspired air rises above room temperature, and the effective increase in relative humidity can exceed 100%. We propose that the recently reported, disease-attenuating effect of generic facemasks is dominated by the strong humidity increase of inspired air. This elevated humidity promotes mucociliary clearance of pathogens from the lungs, both before and after an infection of the upper respiratory tract has occurred. Effective mucociliary clearance can delay and reduce infection of the lower respiratory tract, thus mitigating disease severity. This mode of action suggests that masks can benefit the wearer even after an infection in the upper respiratory tract has occurred, complementing the traditional function of masks to limit person-to-person disease transmission. This potential therapeutical use should be studied further.     

A mathematical model of the dynamic heat transfer from the respiratory tract of a chicken

A mathematical model of the dynamic (periodic) heat exchange from the respiratory tract of a chicken is postulated and solved analytically. The model expresses the periodic respiratory heat loss as a function of respiration rate, respiratory air velocity, ambient temperature and humidity ratio, and body (trachea) temperature. It is unique in that previous models have been formulated for steady state heat transfer. The processes of sensible and latent heat exchange are considered as uncoupled processes.