The Avian Respiratory System: a Unique Model for Studies of Respiratory Toxicosis and for Monitoring Air Quality

The avian respiratory system: a unique model for studies of respiratory toxicosis and for monitoring air quality

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Citation Brown, R E, J D Brain, and N Wang. 1997. “The Avian Respiratory System: a Unique Model for Studies of Respiratory Toxicosis and for Monitoring Air Quality.” Environmental Health Perspectives 105 (2) (February 1): 188–200. doi:10.1289/ehp.97105188.

Published Version doi:10.1289/ehp.97105188

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Revievvs The Avian Respiratory System: A Unique Model for Studies of Respiratory Toxicosis and for Monitoring Air Quality Richard E. Brown, Joseph D. Brain, and Ning Wang Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115 USA

the avian respiratory system is to add to our .~~~~~~~~~~~~~~~~~~...... There a distinct dandm understanding of respiratory toxicosis, if we bird's lung-irsa resraorys d the mm bg In thi papr, are to maintain the health of birds in agri- we review physiologf the avia spi e with tO oe inisms cultural and wild settings, and if birds are to that may lad to signifitly diret ults, eate .totse in _mm, f i eosre become valuable monitors of air quality, to toxic gaseai:_d airbore p . We s. n C dbe then we must study the pathophysiology of e..xp.loimdto ther our understanding of thebasii ..... d ... olg...... a.d a broad range of toxic gases and airborne part~cuIae) The larg niass-pd isa ah...... gs. ut:t..' particulates in a wide variety of species. cdafy dunngm;:reise could be epotdasaenv ontrcarmmiy id hav iu&u offer in our of respiratory cx realiedtby Functional Morphology of the investigating, in a wide variety ofavian the oloc n onse a b Avian Respiratory System of wl ozants on the bird's unique rspa sym. Kiyw anatomy, birds, s uptake, kpat deposition, physiology, i ilog, vantilatiion En'Exi Hsalth Anatomy ofthe avian lung-ar-sac Pmp (OM88200(19) system Upper respiratory tract. The bird's respiratory tract cranial to the tracheal bifurcation To what extent do the pathophysiologic sity demands that we also understand the is qualitatively similar to that of mammals; effects of inhaled substances, gaseous and interactions between the bird's unique respi- it has a nasal cavity with communicating particulate, depend on the particular struc- ratory system, gas uptake, and the patho- sinuses, a larynx supported by cartilaginous tural and physiologic features of an animal's physiologic effects of contaminating toxic plates, and a tracheal lumen supported by respiratory system? The anatomy, physiolo- gases and airborne particulates. Birds such cartilaginous or ossified rings. However, the gy, and mechanics of the avian respiratory as chickens and turkeys represent an impor- length of the bird's trachea is, on average, system are distinctly different from that of tant and expanding source ofanimal protein 2.7 times that ofcomparably sized mammals mammals (1). We suggest that, due to their for human nutrition. The environment (6). A small increase in tracheal diameter unique respiratory apparatus, birds may within modern poultry and egg production (1.29 times that of comparably sized mam- represent valuable experimental models in facilities, in which birds are densely housed, mal) ameliorates any increases in resistance the study of respiratory toxicosis. Such commonly exposes birds to high levels of to flow expected from the considerably comparative knowledge concerning the aerosolized particulates and toxic gases such longer trachea. Although the bird's trachea pathophysiology of inhaled substances may as ammonia and methane. Surprisingly, lit- is lined with a secretory (mucous), ciliated offer insights otherwise not available. Here de research has been carried out in birds on epithelium, there is no information about we describe the structure, ventilation, and gas uptake (other than 02 and CO2), parti- the performance of the mucociliary trans- gas flow pattern of the bird's lung-air-sac cle deposition, and the toxicity and patho- port mechanism. Further, there are a few system relative to the analogous features, if physiology ofinhaled substances. avian taxa (e.g., swans, cranes, birds of par- any, of the mammalian bronchoalveolar Toxic gases and/or airborne particulates adise) that have tracheal lengths up to four lung. We point out those anatomical and contaminate the environment and can have times that of comparably sized birds, the physiologic features of the bird's respiratory debilitating or destructive effects on birds redundant coils of which are considered apparatus that may produce significantly (and other wildlife) via a variety ofdistribu- adaptations for phonation (7). Tracheal different responses from the normal tion modes (e.g., air or water) and bio- lengths 10 times that of comparably sized response to inhaled substances, gases, and chemical mechanisms (2-5). Here we are particulates in mammals. concerned only with those gaseous and par- Address correspondence to N. Wang, Physiology Concems about the hazardous effects of ticulate contaminants that enter the bird Program, Department of Environmental Health, gas and particle emissions from expanding via its respiratory tract, of which little is Harvard School of Public Health, 665 Huntington industrial and agricultural (and natural) known or understood. Ifwe understood the Avenue, Boston, MA 02115 USA. RE. Brown is currently at Zoologiska Institutionen, sources supporting a burgeoning population pathophysiology of inhaled environmental Zoomorfologiska Avdedningen, Goteborg Universitt, have led to considerable efforts toward contaminants (gas and particulate) on birds S-413-90, G6teborg, Sweden. understanding the effects of air quality on (adult and embryonic), they could serve as Received 20 August 1996; accepted 5 November human health. Maintenance ofnatural diver- sensitive, direct monitors of air quality. If 1996.

188 Volume 105, Number 2, February 1997 * Environmental Health Perspectives Reviews * Avian respiratory toxicology mammals suggest the need ofpossible novel mechanisms to assist in dearance. In sharp contrast to the C-shaped cartilaginous rings supporting the tracheal lumen ofmammals, the bird's tracheal rings are complete (i.e., 0-shaped and commonly ossified). In the mammalian trachea, the collapsible membrane spanning the gap between the ends of the incomplete tracheal rings is considered an important feature of the dearance mechanism ofthe mammalian cough (8). Although birds do perform a coughlike action, we do not know if such behavior represents an effective mechanism for clearing debris from their longer tracheas. And if such a dearance mechanism exists, what are the mechanics involved? The avian vocal apparatus, the syrinx, is located at the point the main stem bronchi diverge from the caudal trachea (Fig. 1). At that site there are significant departures Fgure 1. Diagram of the components of the avian lung-air-sac respiratory system. From the bird's intrapulmonary primary bronchus (Bronchus primarius, pars intrapulmonalis) arise two clusters of secondary from the round geometry ofthe trachea and bronchi: from its cranial end arise four ventrobronchi (Bronchi medioventrales), and, prior to its termination at main stem bronchi which may influence the orifice of the abdominal air sac, arise the 8-14 dorsobronchi (Bronchi mediodorsales) and the latero- particle deposition. bronchus (LB) (Bronchi lateroventrales), which connects the caudal thoracic air sac to the intrapulmonary Bronchial system. Whereas the mam- bronchus. The constant-volume gas-exchange area of the avian lung-air-sac system, i.e., the parabronchi malian bronchial system ramifies (23 gen- (for simplicity only a few are shown), is connected between dorsobronchi and ventrobronchi and is ventilated erations) like the roots of a tree throughout unidirectionally (arrows). The several air sacs are the sites of volume expansion and act as bellows to move the pulmonary parenchyma (Fig. 2), the gas through the bird's lung (parabronchi). [Modified from Wang et al., (38); reprinted with permission from bird's primary bronchus extending from John Wiley & Sons, Inc.] tracheal bifurcation to the ostium of the abdominal air sac has only two dusters of secondary bronchi (Fig. 1). From the cranial end of the bird's intrapulmonary primary bronchus arise 4 approximately equal-sized ventrobronchi, and from its caudal segment arise 7-14 variably sized dorsobronchi and a variable number (<6) of laterobronchi. The epithelium lining the primary bronchi and the initial segments of the secondary bronchi is similar to that seen in larger mammalian airways: pseu- dostratified ciliated epithelium with mucous-secreting goblet cells. The mammalian bronchial system ter- minates in myriad (300 million in Homo) small, blind-end alveoli, which are the site of gas exchange and volume (tidal) expansion. In sharp contrast, birds have a nearly constant volume, flow-through lung in which the site ofgas exchange is the parallel Figure 2. Bronchial tree of the human lung, latex cast, ventral view, left lung. The caudal trachea (large asterisk) gives rise to the primary bronchi (left main stem bronchi; small asterisk), from which the dichoto- tertiary bronchi, i.e., parabronchi (few hun- mously branching (32 divisions) airway system leads to the blind-end alveolar ducts with their clustered dred to <2,000 depending on taxa), con- alveoli (removed from this preparation), which are the site of both gas exchange and volume expansion in nected between the ventrobronchi and the the mammalian lung. (Photo courtesy of W. Webes, Institute of Anatomy, University of Bern.) dorsobronchi or laterobronchi (Figs. 1 and 3). The parabronchi complete an airway loop from the caudal primary bronchus to mammals, resulting from their anatomical into two categories based on their pattern of the cranial primary bronchus (via secondary differences, have several important implica- connections to secondary bronchi and flow bronchi), through which a unidirectional tions for gas-exchange physiology, toxic gas regime. The majority of the parabronchial stream of fresh gas flows (Figs. 1 and 4). uptake, and particle deposition. lung is composed of paleopulmonic That is, birds have a flow-through lung Gas exchange tissues. The parabronchi parabronchi, connected between ventro- (parabronchi) in contrast to the tidal venti- are densely packed in a hexagonal array, and dorsobronchi, through which gas flows lation that occurs in mammalian alveoli. similar to the wax-comb of honeybees (Fig. unidirectionally (Fig. 1). A highly variable The differences in ventilation of the pul- 3). Although there are no morphometric number of neopulmonic parabronchi [0 to monary parenchyma between birds and differences (9,10), parabronchi are separated <20% (usually <10%) of lung volume

Environmental Health Perspectives * Volume 105, Number 2, February 1997 189 Reviews * Brown et al. depending on taxon] conduct air in an oscil- fied, nonciliated epithelium. In sharp con- present within the bird's lung tissue, which latory pattern and are variously connected trast to the lungs of most mammals where may lead to significandy different responses between any two of the following: primary resident macrophages are common, such to inhaled toxicants (11,1X. bronchus, ventrobronchi, dorsobronchi, lat- janitorial cells are rarely present in the avian Parabronchial dimensions are variable erobronchi, and air sacs. The parabronchial respiratory system. Additionally, important among avian taxa. The lumen (0.3-2.0 mm lumen is lined by a nonsecretory, nonstrati- differences exist as to the enzymatic systems diameter) of each parabronchus (1-4 cm long) is surrounded by a mantle of gas- exchange tissue (0.2-0.5 mm thick) consist- ing of coextensive networks of narrow (3-10 pm diameter) air capillaries and blood capillaries (Figs. 3 and 5). The air capillaries communicate with the parabronchial lumen. The bird's gas- exchange barrier, formed by the air capillaries' squamous epithelium, the blood capillaries' endothelium, and the interposed basal lamina, is qualitatively similar to that of the mammalian alveolus and its pulmonary blood capillaries (13). Surfictant is

Figure 4. Air flow diagrams (arrows) of the avian respiratory system during inspiration and expiration. The air sacs act as bellows, contributing equally to the movement of gas through the bird's nearly constant-volume lung, filling simultaneously with inspiration and emptying simultaneously with expiration (arrowheads about air sacs). The unidirectional pattern of flow (large arrows) through the major exchange area of the bird's lung (paleopulmonic parabronchi) is maintained throughout inspiration and expiration. During inspiration there is no or little flow (*) in the ventrobronchi (VB) (i.e., inspiratory valving). Instead, nearly all the gas passes caudally through the Figure 3. Diagram of parabronchial anatomy, gas-exchange region of the bird's lung-air-sac respiratory intrapulmonary bronchus, half passing to the cau- system. The few hundred to thousand parabronchi, one of which is fully shown here, are packed tightly dal air sacs and half entering the lung via the dor- into a hexagonal array. The central parabronchial lumen, through which gas flows unidirectionally during sobronchi (DB). During expiration there is little or both inspiration and expiration (large arrows), is surrounded by a mantle (m) of gas-exchange tissue com- no flow (*) in the intrapulmonary portion of the posed of an intertwined network of blood and air capillaries. Several air capillaries coalesce into a small primary bronchus (IPB) (i.e., expiratory valving). manifold, i.e., the infundibulum (arrowheads), several of which in turn open into an atria (*) found along the Instead, nearly all the gas exiting the caudal tho- parabronchial lumen. Air moves convectively through the parabronchial lumen, while 02 diffuses radially racic (PTAS) and abdominal air sacs (AAS) pass- (CO2 diffuses centrally) into the air capillary network. Blood flows centrally from the pulmonary arteries (a) es through the parabronchi. ICAS, intraclavicular located along the periphery of the parabronchi to pulmonary veins located along the parabronchial lumen, air sac; CTAS, cranial thoracic air sac. [Modified which then are drained back to the peripheral veins (v). [Modified from Duncker (107); reprinted with per- from Scheid (108); reprinted with permission from mission from Springer-Verlag.] Springer-Verlag.]

190 Volume 105, Number2, February 1997 * Environmental Health Perspectives Reviews * Avian respiratorv toxicologv present in the bird's nearly constant-volume narrow air capillaries relative to the size pressure of the gas in the air capillary; and lung (parabronchial lumen and air capillar- (>300 pm diameter) of mammalian alveoli. P- is the partial pressure in mixed venous ies), although its functional significance is The mean harmonic thickness of the bird's blood. Since the Th of the bird's gas- poorly understood. The mechanism that gas-exchange barrier is only about half that exchange barrier is about half that of mam- prevents collapse or flooding of the air cap- of the mammalian lung. However, other malian lung, given identical effective venti- illaries secondary to the high surface ten- parameters of lung morphometry (body lation of gas-exchange tissues, a bird can sions across the air-tissue interface of these weight basis) are nearly identical between take up approximately twice the amount of structure's small radius (1-5 pm) of curva- these two groups of homeotherms (15): a gas from its ventilatory stream compared ture is unknown. Arranged as a series of lung volume, surface area of exchange tis- to a mammal. In addition, the unidirection- parallel units along the length of the sue, surface area ofexchange tissue per body al flow of fresh gas through the gas- parabronchi, the pulmonary blood flows weight, and pulmonary blood volume. exchange region of the bird's lung permits radially into the mande of exchange tissue The thinness of birds' gas-exchange bar- larger P,C-P differences, in contrast to the from the arteries located along its periphery rier has important implications for gas situation in the mammalian lung where the toward the parabronchial lumen, along uptake. Uptake of a gas across the tissue bar- gas-exchange region is filled with a func- which are located the pulmonary veins that rier ofthe lung and into the blood (Mg-b) is: tionally stagnant reservoir of gas, the PO of drain the oxygenated blood back toward the which is governed by diffusive mechanidns. and In following sections we describe several periphery (Figs. 3 6) (14). M = D J(P - Significant differences between birds g-b T AC V other morphologic and physiologic features and mammals (excluding bats) exist in h)(1) ofthe bird's lung that enhance gas uptake. comparisons (body weight basis) of the sur- where D is the diffusion constant of the gas, Air sac system of birds. The avian face density and the mean harmonic thick- which depends on its solubility in blood bronchial system communicates with a sys- ness of pulmonary gas-exchange tissues (nb) and molecular weight (MW), i.e., tem of air sacs filling >30% of the volume of (9,15). Birds' lungs have about twice the DocPb/MW-l/2; A is the surface area; Th is the bird's thorax and abdomen (16) (Figs. 1 surface density of gas-exchange tissue, the thickness of the tissue barrier across and 7). The air sacs are the sites of tidal vol- resulting from the dense packing of their which the gas moves; PAC is the partial ume expansion, functioning like bellows to move air through the avian lung-air-sac respiratory system. Changes in coelomic volume mediated by body-wall deformations are almost singularly reflected in volume changes within the several air sacs (Fig. 4). There is no analogous structure to the bird's air sacs in the mammalian respiratory system, in which the alveoli are both the site of gas exchange and volume expansion. The air sac walls are composed ofa simple, nonstratified epithelium with a sparse distribution ofsmall islands of ciliated cells and secretory cells supported by a diffise connective tissue network composed primarily of elastin (13). In the absence ofboth a widespread mucociliary surface and airway macrophages, we do not know how air sac homeostasis is maintained. It is usually considered that little to no gas exchange occurs across the poorly vascular- ized walls of the air sacs; this is true for CO (17,18) yet there is toxicological evidence that highly soluble compounds such as SO2 may indeed cross the air sac membrane (19). The individual air sacs are anatomically (by site of connection to bronchial system) and functionally (see Gas Flow Patterns) divided into two main groups (Figs. 1, 4, 7): the cranial group, arising from the ventrobronchi, is composed of the paired cervical sacs, an unpaired intraclavicular sac, and paired cranial thoracic sacs; and the caudal group, arising from the caudal end of the intrapulmonary bronchus and connecting laterobronchus, is composed of the paired caudal thoracic sacs and paired abdominal sacs. The elastic walls ofthese air Figure 5. Confocal micrograph of gas-exchange region of parabronchus, goose. A) Three-dimensional tiin, highly reconstruction; (B) and (C) are two individual sections. Note the intimately intertwined network of blood sacs, in contact with adjacent sacs over a large capillaries, labeled with the presence of erythrocytes (*), and air capillaries (AC) that make up the percentage oftheir area (Fig. 7), are incapable parabronchi's mantle of gas-exchange tissue. Several air capillaries coalesce into an infundibulum (INF). of supporting pressure differences between

Environmental Health Perspectives * Volume 105, Number 2, February 1997 191 Reviews * Brown et al. adjacent sacs. This fact is important in light Convective transport of a particle through- mixing of gas or particulates across stream- ofthe inability ofthe air sacs to influence the out the respiratory system is mainly deter- lines. When Re is >2,000, flow becomes unidirectional flow through the parabronchi mined by that particle's density and size, turbulent with extensive mixing. In the (see Gas Flow Patterns). The several air sacs specifically its aerodynamic equivalent diam- short, branched, curved tubes containing have communicating diverticula that invade eter, Dae (Dae oc geometric diameter xpl/2). numerous choke points (site of sudden most bones, nearly filling the medullary cavi- With larger Dae, particle deposition is change in diameter or geometry) that make ties of many, and extend between layers of strongly influenced by inertial and sedimen- up the avian respiratory system, turbulent soft tissues [e.g., between the layers of the tation mechanisms. As Dae becomes smaller, flow should be expected at flow regimes large pectoral (flight) musdes]. These com- inertia and sedimentation play smaller roles considerably less than Re = 2,000. municating diverticula and the small cervical in particle deposition, while Brownian diffu- Inertial impaction. Inertia is the tenden- air sacs lying along the neck are not consid- sion becomes more important. cy of a moving particle to resist changes in ered to contribute to ventilation. In a long, straight tube, the operative direction and speed and is a function of the Avian airway geometry and particle flow regime is mainly determined by the momentum (Da2 and the local flow rate) of deposition. Several physical mechanisms magnitude of the Reynolds number (Re), a that partide. The highest linear flow veloci- operate on inspired particles to increase the dimensionless ratio of local inertial forces ties are found in the upper respiratory tract likelihood that a particle will contact (and to viscous forces: and central airways. At sites where there is deposit on) a respiratory surface, the most puD an abrupt change in airflow direction (e.g., important being inertial forces, gravitational convoluted nasal passages or branching sedimentation, and Brownian diffusion. The 9 (2) points of central airways), a partide, if it has extent to which each mechanism contributes sufficient momentum, will continue in its to the deposition of a specific particle where p is gas density; u is mean gas veloci- original direction crossing airflow stream- depends on that partide's physical character- ty; D is tube diameter; and p is gas viscosi- lines and impacting on the airway wall istics (size, shape, density, p), airway geome- ty. When Re is <1, flow is primarily deter- instead of following the curvature of the air- try, flow pattern, and flow regime found mined by viscous mechanisms, and inertial way with the airflow. In avian lungs, inertial within each component of the respiratory forces can be neglected. When Re is impaction operates in central airways (bends tract. Anesthetized chickens inhaling 1251- 10-2,000, both viscous forces and inertial in the trachea, syrinx, and branching points labeled latex particles of a wide range of forces are important, and at Re >2,000, of secondary bronchi) and convoluted areas diameters (0.091, 0.176, 0.312, 1.1, 3.7, inertial forces predominate. At Re <2,000 of extrathoracic (oropharynx, nasopharynx, and 7 jim) showed regional deposition in a long, straight tube, the flow is usually and larynx). Associated flow regimes (for strongly linked to particle size (20). laminar, which means there is little to no geese) found in those anatomical locations are the nose and bends in the trachea (u = 100 cm/sec, Re = 700); the narrowed syrinx and bends in the primary bronchi (u = 130 cm/sec, Re = 600); and the narrowed caudal end of the primary bronchus (u = 200 cm/sec, Re = 550). The expected sites of inertial impaction in the bird are similar to those in mammalian airways. Gravitational sedimentation. Gravita- tional forces accelerate the fall of partides, and the terminal (constant) settling velocity is reached when viscous resistive forces of the air are equal and opposite in direction to gravitational forces. Respirable particles, under the influence of gravity alone, reach this terminal sedimentation velocity in less than 0.1 msec. The probability that a particle will deposit by gravitational settling is proportional to the product of its D 2 and the residence time within airspaces in which velocities are low. In bird lungs, aerosol deposition by sedimentation would be important within the parabronchi and air sacs, where air flow velocities are low (parabronchi, u = 3 cm/sec, Re = 2) and residence times may be exceptionally long (e.g., possibly >1.0 min for complete Figure 6. (Upper panel) Schematic of air flow (large arrows) and blood flow (small arrows) patterns constitut- change of air sac gas at rest). In the human ing the cross-current gas-exchange mechanism operating in the avian lung. Note the serial arrangement of lung, sedimentation is an important mecha- blood capillaries running from the periphery to the lumen of the parabronchus and the air capillaries radially nism for particle deposition (D >0.2 im) departing from the parabronchial lumen. (Lower panel) Pressure profiles of 02 and CO2 from initial- within peripheral airways and alveoli (21). parabronchial (P,) to end-parabronchial values (PE); and in blood capillaries from mixed venous (PR) to arterial blood (P.). The Po2of arterial blood is derived from a mixture of all serial air-blood capillary units and Brownian diffusionm Brownian motion exceeds that of PE. In mammals, the Pa02 cannot exceed that of end-expiratory gas, (i.e., P [From Scheid is a random process caused by collisions (108); with permission from Springer-Verlag.] between particles and between partides and

192 Volume 105, Number 2, February 1997 * Environmental Health Perspectives Reviews * Avian respiratory toxicolo-,y gas molecules, and it may be a contributing factor in deposition of inhaled particulates. Diffusion is significant for particles with Dae

Environmental Health Perspectives * Volume 105, Number 2, February 1997 193 Reviews * Brown et al. dorsobronchi and caudal intrapulmonary nous mixture of different aerodynamic the air capillary network and then into pul- bronchus. Yet we know from flow measure- environments (e.g., viscous flow in termi- monary capillary blood across the thin ments that during inspiration there is little nal bronchi and turbulent flow in larger blood-gas barrier, with CO2 moving in the to no flow from the primary bronchus to airways). In sharp contrast, the various opposite direction (Figs. 3 and 6). Blood in ventrobronchi (i.e., inspiratory valving) and components within the bird's respiratory the pulmonary capillaries flows opposite to during expiration there is little to no flow system, and their correspondingly different that of the diffusive movement of 02 in the craniad through the intrapulmonary flow regimes, are found as discrete and iso- air capillaries, i.e., radially and centrally from bronchus between dorso- and ventrobronchi lated components. The unidirectional flow pulmonary arteries located at the (i.e. expiratory valving) (Fig. 4). Originally, through the bird's primary and secondary parabronchial periphery (Fig. 8). The anatomic valves were postulated as the bronchi and parabronchi allow the patterns air-blood capillary units are arranged serially mechanism controlling flow in the bird's of partide deposition to be examined with- along the luminal axis ofa parabronchus. respiratory system (29-31), but the presence out the confounding variable of bidirec- Because systemic arterial blood is a mix- ofsuch valves was never established (16). tional flow. These differences suggest that ture of blood from all the serially arranged Inspiratory valving. It is now known birds may represent a valuable tool in fur- air-blood capillary units, arterial P02 can that an aerodynamic mechanism (i.e., con- thering our understanding of the deposi- actually be greater than end-expired P02 (see vective inertia) is responsible for controlling tion and dearance ofinhaled particulates. Fig. 6); this cannot occur in the mammalian the direction of flow in the bird's respirato- Dotterweich (44) was among the first to lung. While parabronchial Po2 decreases ry system during inspiration (32. The con- expose birds to soot particles under con- with distance traveled through the lumen vective inertial momentum (pu2, where p = trolled laboratory conditions. He found that (and PCO increases), the actual profiles of02 gas density and u = flow velocity) of the the particles deposited much more in the and CO22along the parabronchus are a func- inspiratory gas stream flowing through the dorsobronchi than in the ventrobronchi. tion of ventilation; that is, with increases in primary bronchus prevents the flow from Later, Vos (45) and Hazelhoff (46) exposed ventilation, the end-parabronchial P02 can turning the corner, so to speak, and enter- the birds to air laden with powdered char- be increased with corresponding decreases ing the ventrobronchial orifices (33,34). coal and deduced the unidirectional gas flow in end-parabronchial C02. Thus the diffii- Expiratory valving. Convective inertial pattern in the avian lung. Adult, fully con- sion gradients of the gases (parabronchial forces do not contribute to the operational scious chickens exposed to an aerosol of lumen to blood capillaries) can be increased mechanics of the expiratory valve (35). 99mTc-labeled particles (Dae = 0.45 pm) and along the distal portion of the parabronchi Instead, it appears that during expiration examined immediately thereafter had a pre- with increased ventilation. dynamic compliance of the membranous dominance ofpartides deposited in the cau- Counter-current gas exchange mecha- intrapulmonary bronchus results in a reduc- dal areas of the respiratory system (47). All nism at level of air capillary. Oxygen dif- tion of the caliber of the bronchus and an these investigations demonstrated the highly fusing peripherally from the parabronchial increase in resistance to craniad flow nonrandom pattern of partide deposition in lumen and pulmonary blood flowing cen- through the intrapulmonary bronchus. The the avian lung-air-sac system. trally toward the parabronchial lumen increase in resistance is a direct function of along their common diffusion barrier pro- the expiratory flow velocity and produces Avian Respiratory Physiology duces a counter-current gas-exchange an expiratory valve with an efficacy (dorso- Gas-exchangephysiology in theparabronchi. mechanism at the level of individual air bronchial flow:total flow exiting caudal Gas flows convectively through the lumen of capillaries (48,49) (Fig. 8). In such an sacs) of95% at physiologic flows. the parabronchi, whereas movement of gases arrangement, as blood travels centrally Valve failure. During panting in ther- from the parabronchial lumen out into the along the diffusion barrier separating it mally stressed birds, the resulting non- air capillary network where gas exchange steady flow regimes lead to conditions in takes place is considered to be an entirely dif- which the valving mechanisms lose effec- fusive mechanism. As is true for avian as well tiveness compared to the highly effective as mammalian lungs, 02 in inspired air dif- valving of nonpanting birds (36,37). As gas fuses passively into the pulmonary capillary composition can affect airway caliber [e.g., blood and CO2 diffuses in the opposite CO2 (38)], and airway fibrosis secondary direction. However, the structure and physi- to particle deposition (39-43) could affect ology of the avian parabronchial lung is dif- airway caliber and compliance, the bird's ferent from the bronchoalveolar mammalian respiratory valving mechanisms may be lung and thus gas transport patterns are also Figure 8. Schematic of the counter-current gas- adversely affected by environmental conta- different. These differences may have impor- exchange mechanism operating at the level of the mination. Airway caliber strongly influ- tant implications in respiratory toxicology. air capillary. Air flows convectively through the ences both the relative resistances to flow in Cross-current gas exchange mechanism parabronchial lumen (large arrow), from which 02 the various parts of the bird's bronchial sys- at the level of parabronchi. Uptake of 02 diffuses radial from the opening of the air capillary of the stream, and CO2 loss via the bird's parabronchial (PIC) to its end (PEC). Blood flows opposite to the tem and the velocity gas diffusion direction of 02- Po2 in the air capillary which is a direct determinant of its convec- lung is unaffected by direction of gas flow falls continuously from its opening to its end, while tive inertia. Further, reduced airway com- through the parabronchi, craniocaudal versus P02 in pulmonary blood rises continuously from pliance from tissue fibrosis secondary to caudocranial (48). Such evidence demon- that of mixed venous blood (PV) to a peak found in particle deposition could greatly diminish strates that at the level of the parabronchi, the blood capillary at its termination at the or eliminate effective expiratory valving. there is a cross-current gas exchange mecha- parabronchial lumen (PC); with Pco2 following the homogeneous divi- nism in the avian lung (Fig. 6), which is in opposite courses. This arrangement favors 02 Particle deposition: uptake (and CO2 off-loading) by the blood as at all sions ofthe avian system versus the hetero- strong contrast to the cocurrent gas exchang- points along the air-blood capillary diffusion barri- geneous mammalian system. In human er operating in mammalian lungs. From air er (0): there is a higher Po in the air capillary ver- lungs, below the level of the paired main flowing convectively through the para- sus that in the blood capilfary. [From Scheid (108); stem bronchi, there is a highly heteroge- bronchial lumen, 02 diffiuses radially into with permission from Springer-Verlag].

194 Volume 105, Number 2, February 1997 * Environmental Health Perspectives Reviews * Avian respiratory toxicologqy from the air capillary and takes up 02, the tions fit the following mass-specific rela- capacity but by wing aerodynamics sec- concentration of 02 in the blood is always tionships (53): ondary to a low density atmosphere (80% less than the increasing concentration of He, 20% 02), was approximately 70 02 in the air capillary as it nears its VT = 7.69(Mb'.04) (11) ml/g/hr (61). Maximum oxygen consump- parabronchi's lumen (the opposite is true tion, VO2,MAX' is reached when V02 no of the blood's PC02). As such, the concen- f= 53.5(M-026) (12) longer increases with increasing exercise tration gradients along the radial length of intensity, and anaerobic glycolysis must an air capillary continually favor more 02 V= 379.0(Mb0 80) (13) account for the additional energy consumed uptake and CO2 release by the pulmonary by the muscles. capillary blood. We can calculate effective ventilation Ventilation. Tracheal volume in birds is (ml/min) of the gas-exchange regions of the Gas Uptake by the Avian about 4.5-fold that of comparably sized lung (VP = parabronchial ventilation in Parabronchial Lung mammals due mainly to the considerably birds and VA = alveolar ventilation in mam- The differences in respiratory anatomy and longer tracheal length of birds (6). In birds, mals), from minute ventilation (V) and physiology in birds versus mammals results tracheal volume approximates respiratory anatomic dead space ventilation (VD =VD X in several important differences in expected dead space (VD) as all air passing the tra- 0: for resting birds, gas uptake, M. cheal bifurcation also passes over the gas- Gasphase. In the gas phase NC depends exchange tissues of the parabronchial lung on effective ventilation (VP or VA), the solu- due to the effective valving of airflow in the VP = V-VD (14) bility of the gas in question (PG), and the bird's respiratory system and the mainte- difference between the partial pressures of nance of a unidirectional air flow through VP = 291.0Mb074)]_[630(MbO.7)] (15) that gas in the inspired (Pi) and expired the lung per se (50,51): (PE) air in the following relationship:

Avian tracheal = VD = 3.724(Mbj109), (3) and for mammals, MG = - PE). volume (ml) VPPG(PI (18) where Mb = body mass in kilograms. Birds, VA=V-VD (16) The solubility of a gas depends only on at least partially, compensate for their larger temperature (T), that is ,G =1/(RT), where tracheal dead space by increasing tidal vol- 3 0.8 R is the ideal gas constant (62). There ume and decreasing respiratory frequency =[ ( b ( bM ).(17) would, ofcourse, be a slight (<1%) decrease relative to that of equally sized mammals in gas solubility due to the bird's higher (52). That behavioral adaptation reduces The above values and calculations for avian body temperature (104-1070C) relative to the percentage of the bird's tidal volume respiration are valid only in nonpasserine that of mammals (99-1020C). However, wasted in dead space ventilation with each taxa. The order Passeriformes includes many from the above relationship, it can be seen breath so that minute tracheal ventilation in of the common species such as song birds that the higher (up to 160+% that of com- birds is only 1.5 to 1.9 times that ofcompa- and sparrows, flycatchers, jays, and warblers. parably sized mammals) effective ventilation rable mammals. In contrast to that of birds, In passeriforms, under resting conditions, in birds has important consequences in respiratory dead space in mammals includes mass-specific oxygen consumption is total gas uptake. not only the volume of the trachea but also approximately 65% higher, hence V and/or Gas to bloodphase. As described earlier, the volume of nearly all conducting airways VP are proportionally higher than those of the thinness of the bird's gas-exchange tis- above the level ofthe alveolar duct (53): nonpasserine taxa (656,57). sue, approximately half the thickness of Comparisons of ventilation between mammals, has important implications for Mammalian M 0.96) birds and mammals. How then does venti- the uptake of gas into the blood from the dead space (ml) = VD = 2.76 b) (4) lation in birds compare to that in mam- surrounding air spaces. Given identical mals? Mass-specific ventilation, V, in rest- effective ventilation of exchange tissues, a For resting birds, the following mass- ing birds (nonpasserines) is 20-80% higher bird will take up more (approximately specific respiratory relationships (at BPTS) than mammalian values. Effective twice as much) of a given gas (63). In addi- are found (54,55): (parabronchial) ventilation, VP, in birds tion, due to the cross-current arrangement under resting conditions is 30-160% high- of the air flow relative to blood flow Title volume (ml) = VT = 16.9(Mbl 05) (5) er than the alveolar ventilation, VA, of com- through the avian lung, the partial pressure parably sized mammals. Those values are of a gas in arterial blood can exceed that of Frequency (per min) = f = 17.2(Mb-031) (6) not surprising in light of mass-specific oxy- the end expiratory gas. gen consumptions (V02), again under rest- Bloodphase. Finally, the transport of a Ventilation (ml/min) = V= 291.0(Mbo 74)(7) ing conditions, for birds that are 50% to gas in the blood, MB, depends on pul- >160% higher than that for mammals. monary blood flow (0), gas solubility (nb), and for flying birds: Flight is the most metabolically expensive and the difference in partial pressures of (02 ml/min/Mb) form of locomotion on a the gas in arterial (PA) and mixed venous VT = 27.8(Mb0-89) (8) unit time basis (58-60). Mass-specific oxy- (Pv) blood: gen consumption in flying birds, which f = independent ofMb (9) may or may not reach VO 2MA is MB = Q3G(PA-PV) (19) 10-170+% higher than the maximum oxy- V= 5,000.0(M 0°74) (10) gen consumption in mammals. Peak 02 Mass-specific pulmonary capillary consumption, measured in hovering hum- blood volume, heart size, and heart rates In contrast, mammals under resting condi- mingbirds that were limited not by aerobic are quite similar between birds and mam-

Environmental Health Perspectives * Volume 105, Number2 February 1997 195 Reviews * Brown et al. mals (15). Further, the binding properties coefficient (69). Environmental factors results in significantly decreased performance ofhemoglobin (e.g., to 02, CG2, and CO) affecting laying hens, such as nutritional (production) and observable pathologic are nearly identical between avian and stress, heat stress on laying hens, and envi- changes (45-47,73,74). Such conditions also mammalian blood. ronmental toxicants (e.g., organochlorine represent significant threats to the health of Local concentration gradients in the pesticides) can result in changes in eggshell the humans (45). What are the mechanisms avianparabronchi Because ofthe cross-cur- thickness (70,71). The effects of eggshell responsible for the dearance of particulates rent gas-exchange mechanism in the avian thinning on gas-exchange physiology and from the bird's respiratory system following lung, large concentration gradients can the possible existence of concomitant high and prolonged dust exposures? develop along the length ofthe parabronchi. changes in pore architecture with changes in We are unaware of any studies examin- That is, for a given VW if the equilibration shell thickness are not known. ing the pathophysiology of such particle time constant [= 4 Vcx (T/(A x D)), where Mechanisms ofgas uptake by avian exposures. Airway macrophages, responsible Vc = capillary blood volume] from gas phase embryos. The flux of a gas transferred for much of the particulate dearance from to blood is much shorter than the gas transit across the shell per unit time, Ms, is (64): the lower airways of mammals, are rarely time in the parabronchi, the local concentra- found in the bird's respiratory tract. Do tion at the dorsobronchial (inflow) end of such phagocytic cells appear only when the parabronchi will be significandy higher Ms = [APST TSG(PA-PCEL) needed? Under experimental conditions than that at the ventrobronchial (outflow) ~~~~(20) (e.g., stimulation with Freund's adjuvant or end. Thus, within the avian lung, local tis- Sephadex instilled into air spaces) phagocyt- sue exposures (doses) can be much higher where AP = effective pore area ofshell; Ds = ic cells physiologically similar to mammalian than the average exposure; this is not the diffusion coefficient of the gas across the alveolar macrophages can be induced to case in the mammalian lung, where all alve- shell; Ts = shell thickness; and the relative enter the bird's pulmonary spaces (75,76). oli are exposed to nearly the same concentra- partial pressures of the gas in question Birds, like mammals, have bronchus-associ- tion ofa gas. between the air cell within the shell (PCELL) ated lymphoid tissue within the epithelium and ambient (PA). The flux of gas per unit lining their lungs and bronchi, which con- Gas Uptake in Avian Embryos time from the air cell within the shell to tributes to dearance (dissolution and anti- During avian development there are three the embryo's blood, MAC,B, is: body labeling) of paticulates from the respi- sequential stages ofrespiration (64): prena- ratory tract ofmammals (72). tal (embryonic), paranatal (hatching), and In chickens, after exposure to aerosols of postnatal (posthatching). During the pre- MCELL,B [ACELL{DGBJ1G(PCELL-PC), relatively small respirable partides, no parti- natal stage respiratory gas exchange occurs (21) des were found in the vascular system, kid- via diffusion between the external environ- neys, ovaries, or the heart, indicating that the ment and the initial gas exchanger (i.e., the where ACELL = gas-exchange area between air partides were not absorbed across the epithe- area vasculosa) in early embryonic life and cell and blood capillaries of extraembryonic lial membranes of the respiratory tract (26). later the vascular bed ofthe chorioallantois. membranes; DG,B = the diffusion coefficient Ofthe initial lung deposition, 54% remained The paranatal stage starts when the beak from gas to blood; T = thickness ofdiffusion 1 hr after exposure and 35% remained 36 hr penetrates into the air pocket (air cell) barrier from air cell to extraembryonic mem- after exposure, suggesting an early fast phase between the inner and outer shell membranes; and Pc = partial pressures of the gas of lung dearance followed by a slower phase branes (both internal to shell; i.e., internal in the blood capillaries. In the blood phase, as found in mammals. The fast component pipping) this occurs during the last 2-3 the controlling equation is the same as pre- of dearance is assumed to result from parti- days of incubation. During this stage, the sented above for blood in adult animals, cles deared from the respiratory tract via lungs begin to replace the chorioallantois as except in the case of the embryo, Q is the mucociliary transport and then eliminated the gas exchanger, yet diffusion remains the blood flow in the embryo's allantois. For a via the gastrointestinal tract. What are the major mechanism moving gas across the given egg at a given ambient gas concentra- mechanisms involved in the slow phase of shell per se. The postnatal stage begins tion, the higher the diffusion coefficient and partide dearance? Inspired partides (nontox- when the beak penetrates the shell (i.e., the higher the solubility of the gas in blood, ic iron oxide) within the lung have been external pipping). Here we are interested the more the gas uptake into the eggshell or found trapped in the trilaminar substance only in the prenatal stage (65,66). into the embryonic circulation. In addition, (assumed to be a surfactantlike material), in The eggshelL The eggshell protects the a lipid-soluble gas will deposit primarily in the respiratory epithelial cells, and in adjacent embryo from variations in the environment, the yolk due to its high fat content. interstitial macrophages (43,78). It is possible supplies necessary nutrients (most impor- that the partides were phagocytosed by the tandy calcium) and regulates gas exchange Avian Respiratory Toxicology epithelial cells at the air side and exocytosed and water loss between egg contents and the Inhaled Particulates into the interstitium and then phagocytosed environment external to the egg. The regu- by interstitial macrophages. lation of gas exchange and water loss (diffu- Birds living in environments contaminated sion coefficient) is primarily a function of with aerosolized particulates show significant Toxic Gases the density, diameter, and structure of the pathology after only a short duration of Observation of caged canaries served as the pores traversing the eggshell (67,68). Shell exposure, for example, Kiwis foraging within standard for mine safety during the nine- pore parameters vary between species and loose dust and sand (43), birds living in or teenth and early twentieth centuries in regard within a single species inhabiting different near desertlike conditions (44), or birds to the highly toxic gases carbon monoxide niches, e.g., humidity and altitudinal gradi- exposed to volcanic ash (72). Modem, popu- and methane (79). Despite the early recogni- ents (67,68). Further, shell thickness and lation-intensive confinement methods of tion ofthe substantial differences in metabol- pore architecture change during incubation poultry production often expose birds con- ic rate, toxic gas uptake, and pathophysiolo- (calcium reabsorbed for embryonic develop- tinuously to extremely high levels of gy between birds and mammals, little addi- ment), leading to changes in a gas's diffusion aerosolized particulates, which commonly tional investigation has followed.

196 Volume 105, Number2 February 1997 * Environmental Health Perspectives Reviews * Avian respiratorv toxicologv

Su4fiur dioxide. Sulfur dioxide (SO2) is exposure to 1-4 ppm ozone (97). Exposure What are the unique features of the bird's well known to be capable of producing of young chicks to 0.3-0.7 ppm ozone respiratory physiology and/or physiology in pathologic changes in animals, including results in pulmonary hemorrhage within general (e.g., metabolic rate, exercise pat- birds, as well as causing generalized degra- the bronchi and air capillaries (98). terns, enzymatic makeup) that lead to dation to the environment (e.g., acid rain). Carbon dioxide. The effects of CO2 on intoxification by at least some inhaled sub- However, there are only a few high-dose avian respiration and acid-base balance are stances sooner than other animals and prior laboratory studies of the effects of SO2 on not reviewed here because CO2 is viewed as to the development of potentially lethal sedentary, domesticated geese and chickens nontoxic, although this gas has been shown pathology in those other animals? (19,80-83). to have pathophysiologic effects. Addition- Reviewing the dose-related pathophysi- Carbon monoxide. The pathophysio- ally, CO2 may have important effects on ology of a spectrum of orally administered logic effects ofcarbon monoxide on a range avian airway geometry (35,38). toxicants to a range of domestic animals of animal taxa have been well documented Polytetrafluroethylene. Teflon and suggests that, in general, birds (most and indicate the following relative sensitivi- Silverstone (EI Du Pont de Nemours and research has been completed using domestic ties (84-89): canaries (most sensitive), Co., Inc., Wllmington, Delaware) are com- fowl) are not automatically and predictably sparrows, pigeons, chickens, mice, guinea mon nonstick coatings on cooking utensils more sensitive to orally administered toxi- pigs, rabbits, and dogs (least sensitive). In and appliances. When heated to tempera- cants than comparably sized mammals the beginning of this century, Burrell et al. tures above 2600C, this otherwise stable (103). That is, birds may have a higher or (84) cited Haldane as stating that "a mouse material emits several fluorinated pyrolysis lower, depending on the specific intoxicant, weighing one-half an ounce consumes products (e.g., carbonyl fluoride, hydrogen sensitivity to an orally administered toxicant about 15 times as much oxygen as one-half fluoride, and perfluoroisobutylene) that are or environmental contaminant relative to ounce of the human body would consume known to be rapidly lethal to birds comparably sized mammals. Not only is the in the same time" and strongly recom- (99-101). Severe necrotizing and hemor- direction (higher or lower) often not pre- mended the use of small animals such as rhagic respiratory pathology is found after dictable a priori as to differences in sensitiv- mice and canaries for the purpose of exposure, but the pathologic mechanism ity between mammals and birds in regard to detecting CO in the aftermath of explo- underlying this condition is not understood, a specific toxicant, but there are differences sions and fires in mines. Yet, despite all the as there are several breakdown products, among related (below ordinal level) avian studies of the toxicity of CO in a variety of gases and particulates, emitted. Would caged taxa (104,105). In comparative investiga- animals, we do not know the physiologic birds be a valuable adjunct to kitchen safety tions of susceptibilities to toxicants, it basis for the different sensitivities among in regard to the presence oftoxic gases? appears that often no attempt was made to the different kinds of animals. A list of examine the effect of differences in meta- physiologic possibilities would include ven- Discussion bolic rate (104,105). In regard to inhaled tilatory demands, gas-exchange physiology, The morphology and physiology of the toxicants (gas and particulate), there is the design of the respiratory system, and avian lung-air-sac respiratory system is strik- insufficient information to make any pre- specific biochemical sensitivity. ingly different from that ofthe bronchoalve- dictions concerning relative sensitivities. Ammonia Exposure of chickens to the olar lung of mammals. We suggest that the Some gases (e.g., CO) have a toxicity levels of ammonia occurring in confinement bird's unique respiratory apparatus can be that appears to be a direct function of poultry houses (about 20 ppm) produced productively exploited from two different metabolic rate and its associated ventilatory gross and microscopic damage to the respi- viewpoints as a valuable resource in our demands, such as carbon monoxide (85). ratory tract (e.g., loss of cilia) and made the understanding of respiratory (inhalant) toxi- But the available information regarding the birds more susceptible to infection (73,90). cosis. First, the comparative study ofanimals pathophysiology of toxic gases in birds can- Other investigators showed acute physiolog- with significant differences in their respira- not be explained simply as a result of their ic changes on initial exposure (5-10 sec) to tory anatomy and physiology (e.g., birds higher metabolic demands. Although some ammonia at low doses (1-100 ppm) versus mammals) may produce insights oth- gases have been shown to have an increased (80,82), similar to the effects of ammonia erwise unobtainable (102). Second, the toxicity in birds [e.g., breakdown products on the mammalian respiratory tract. ubiquitous distribution of birds makes these of Teflon, polytetrafluroethylene Hydrogen sulfide. Hydrogen sulfide animals potentially valuable in the study and (99,100)], others have been found to be (H2S) is a toxic gas that inhibits enzyme monitoring ofenvironmental contamination less toxic in birds [e.g., hydrogen sulfide systems in animals (91), and a single (4,5). If birds are to be utilized to fulfill (92,96)] and still other gases show about inhalation of 1,800 ppm can produce those broad scientific goals, we need to sys- the same toxicity in mammals and birds death in mammals (dog and humans) (92). tematically study, on a wide variety of avian [e.g., ammonia (74,80)]. These limited Inhaling 500-1,500 ppm for long periods taxa (adult and embryonic), the short- and results suggest that there is a complex rela- can lead to respiratory failure and death long-term pathophysiologic effects of the tionship between a species' respiratory (93-95). Chickens inhaling 500 ppm H2S inhaled toxic gases and particulates that are physiology, its pathophysiologic response for 30 min did not exhibit changes in ven- present or released in the environment. to a potentially toxic gas, and other physio- tilation; inhaling 2,000-3,000 ppm H2S logic factors. for 30 min resulted in irregular and vari- Comparative Respiratory Physiology The respiratory apparatus of birds has able tidal volume and respiratory frequen- and Toxic Gases evolved from the primitive, saclike, falveo- cy; inhaling 4,000 ppm H2S for 15 min Observation of caged canaries, with experi- lar lungs of reptiles in response to the large caused death (96). It is not clear why mental validation (79,84), served as the metabolic demands of flight. That evolu- chickens are more resistant to H2S toxicity standard for mine safety during the nine- tionary process has produced a respiratory than humans or dogs. teenth and early twentieth centuries. The system with substantial physiological differ- Ozone. Newly hatched chicks are espe- popular press continues to occasionally ences relative to the comparable features of cially susceptible to the toxic effects of report situations in which caged birds are other vertebrates. Among the most impor- ozone and died after 5 days of continuous used to detect the presence of toxic gases. tant of these respiratory differences are that

Environmental Health Perspectives * Volume 105, Number 2, February 1997 197 Reviews * Brown et al.

birds have higher mass-specific minute ven- from the lower airways in mammals? Oddly, gy of an inhaled toxicant on a species, tilation, V; higher mass specific effective it appears that in birds the phagocytic func- would it not then be possible to detect ventilation of gas-exchange tissues, VP; tion of the mammalian airway macrophage environmental contamination prior to the cross-current (parabronchi) and counter- has been taken over by epithelial cells lining appearance of clinical signs (e.g., analysis of current (air capillaries) gas-exchange mech- parts of the birds respiratory tract. Much expired gas, body fluids such as blood or anisms; and a gas diffusion barrier half the more work needs to be done using different examination of tissues)? Embryonic birds, thickness of that of mammals. We suggest avian species on the fate and distribution of once the egg is laid in the nest, experience a that such differences can be usefully inhaled particles, collection efficiency, avian much more local exposure to gases (partic- exploited in our understanding of the responses (pathophysiology), and compari- ulates not considered here) than their for- uptake and pathophysiology of toxic gases, son with mammals of similar body mass aging parents who may cover large dis- but only ifwe study the interactions of res- under similar experimental conditions. tances in search of food. Examination of piratory system structure and function and Early observations of the highly nonran- the embryo (and other egg constituents) the species-specific pathophysiologic dom distribution of particle deposition in within the immobile egg could be utilized responses to inhaled gases and particulates the avian respiratory tract provided the ini- as a monitor of local air quality. That is, in a broad range of avian taxa. tial clues as to the strikingly unusual unidi- with the dilution of a contaminant with rectional pattern of gas flow through the increasing distance from its source, eggs at Comparative Respiratory Physiology bird's lung (23-25). We suggest that the different distances from the source would and Aerosolized Particulates contrasting flow patterns found in the vari- be expected to take up (embryonic respira- Birds often live in environments, especially ous components of the bird's lung-air-sac tion) different quantities of the gaseous those found in population dense, poultry system can be advantageously exploited in contaminant. The differential uptake of a production buildings, in which they are our understanding of the deposition and contaminant by eggs found in different exposed to high levels of aerosolized partic- clearance of inhaled particulates, e.g., unidi- locations might provide information as to ulates. Although it is well established that rectional flow in several well-defined areas; the dispersion pattern or point to the birds suffer pathological consequences to discrete regions of the bird's respiratory source of a contaminant. the deposition of inhaled particles, we are tract with distinct flow patterns and flow If we are to prevent loss of the natural unaware ofany investigation into the mech- regimes versus the heterogeneous mam- diversity, then it is essential that we under- anisms responsible for such damage in malian lung; and comparatively stagnant stand, on a broad range of taxa, the patho- birds. Further, we have little knowledge flow in the air sacs and their diverticulae. physiologic effects of the substances that concerning the clearance mechanisms ofthe are released into the environment. The sur- bird's lung-air-sac system. Comparative res- Birds as Monitors ofAir Quality vival of birds depends on the condition of piratory physiology, in regard to the Birds are ubiquitously distributed in essen- the environment that humans intimately response to inhaled particulates, has much tially all of the environments inhabited by share with these flying dinosaurs. Yet to teach us from two dichotomous stand- humans; thus, if we understood the effects whether we are interested in birds as moni- points. First, we may find broad physiologi- of a broad range of inhaled environmental tors of air quality or as tools to understand cal generalizations in the manner by which contaminants (gas and particulate) on a the pathophysiology of inhaled gases and animals respond to certain environmental wide variety of avian species, they could articulates from a comparative viewpoint, stresses that increases our understanding of serve as highly effective and sensitive moni- we need to study the relationships between basic physiological mechanisms. Second, we tors of air quality (2-5). Several common the physiology of the bird's unique may find animal-specific physiological avian species such as House sparrows (Passer lung-air-sac respiratory system and the processes for maintenance of the homeosta- domestics, and closely related allies) and pathophysiology of inhaled substances, sis of the respiratory system when contami- starlings (Sternus vulgarus) have colonized gases, and articulates (including those not nated with aerosolized particles, which will almost every environmental niche (urban, now considered toxic to Homo sapiens) on a provide insights into alternative responses suburban, and rural) across a wide expanse wide variety ofavian taxa. to such insults. of the regions inhabited, utilized, and cont- Are there modifications in the bird's aminated by Homo sapiens. 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198 Volume 105, Number 2February 1997 * Environmental Health Perspectives Reviews * Avian respiratory toxicology

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The 28th Annual Environmental Mutagen Society Meeting recent findings in the fields of mutagenesis and will be held at the Hyatt Regency Hotel in Minneapolis, molecular genetics and their application to regulation and Minnesota, April 19-24,1997. The Environmental safety evaluation. Mutagen Society is an international society whose purpose For more information, please contact Sid Aaron, is to engage in scientific investigation and dissemination Pharmacia and Upjohn Inc., 301 Henrietta St., Kalamazoo, of information relating to the field of mutagenesis and to MI 49007; (616) 833-1399, Fax (616) 833-9722, email: encourage the study of mutagens in the human environ- saaron~am.pnu.com or the EMS business ment in particular, how mutagens may affect public office, 11250-8 Roger Bacon Dr., Suite 8, health. The annual meeting brings together scientists from Reston, VA 22090; (703) 437-4377, Fax academia, industry, and government to discuss (703) 435-4390, email: emsdmg~aol.com

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