Menthol in the upper airway depresses ventilation in newborn dogs.

Upper airway cooling depresses ventilation in the newborn dog. Since airway cooling stimulates laryngeal cold receptors and inhibits laryngeal mechanoreceptors, the type of afferent ending responsible for this reflex cannot be easily identified. l-menthol, a specific stimulant of cold receptors in the absence of any cooling, has been used to ascertain the discrete role of upper airway cold receptors in this ventilatory depression. Experiments were carried out in 8 anesthetized 7-14-day-old dogs breathing through a tracheostomy with the upper airway functionally isolated. Constant flows of warm air (37 degrees C), with and without addition of l-menthol, and cold air (25 degrees C) were delivered through the upper airway in the expiratory direction. As compared to warm air trials, cold air and warm air + l-menthol trials greatly reduced ventilation (57.5 +/- 10.7% and 52.8 +/- 11.7% of control, respectively; P less than 0.01) mostly due to a prolongation of Te (291.2 +/- 106.4% and 339.2 +/- 90.0%, respectively, P less than 0.01). Section of the superior laryngeal nerve abolished the response to cold air. However, a residual depressive effect of l-menthol was still present in 3 of 5 animals and was abolished by nasal anesthesia, suggesting the involvement of nasal cold receptors. The results suggest that in the newborn dog stimulation of laryngeal cold receptors, without any concurrent inhibition of laryngeal mechanoreceptors, is a sufficient stimulus to cause respiratory depression.     

Breathing response of the tegu lizard to 1-4% CO2 in the mouth and nose or inspired into the lungs

This study investigated the influence on ventilation of elevated CO2 in the nasal and buccal cavities (NaBuCO2) vs the effect of elevated CO2 levels inspired into the lungs (LuCO2). Separate gas sources were used to independently alter NaBuCO2 and LuCO2. As little as 1% NaBuCO2 or LuCO2 significantly increased the pause duration between the active expiratory-inspiratory cycles. Elevated NaBuCO2 caused minor changes in tidal volume, mean inspiratory and expiratory flow, and inspiratory and expiratory durations with a significant reduction in total ventilation. Elevated LuCO2 had little effect on inspiratory or expiratory durations but unlike CO2 in the upper airways, significantly increased tidal volume and mean inspiratory and expiratory flows. This study demonstrates that the increased pause duration seen in the tegu lizard to elevated environmental CO2 is due to a receptor response in the buccal or nasal cavities and also to elevated CO2 concentrations inspired into the lungs. Sensitivity of the ventilatory responses to CO2 in the upper airways is well within a physiologically relevant range.     

Work of breathing and respiratory drive in obesity

Obesity, particularly severe central obesity, affects respiratory physiology both at rest and during exercise. Reductions in expiratory reserve volume, functional residual capacity, respiratory system compliance and impaired respiratory system mechanics produce a restrictive ventilatory defect. Low functional residual capacity and reductions in expiratory reserve volume increase the risk of expiratory flow limitation and airway closure during quiet breathing. Consequently, obesity may cause expiratory flow limitation and the development of intrinsic positive end expiratory pressure, especially in the supine position. This increases the work of breathing by imposing a threshold load on the respiratory muscles leading to dyspnoea. Marked reductions in expiratory reserve volume may lead to ventilation distribution abnormalities, with closure of airways in the dependent zones of the lungs, inducing ventilation perfusion mismatch and gas exchange abnormalities. Obesity may also impair upper airway mechanical function and neuromuscular strength, and increase oxygen consumption, which in turn, increase the work of breathing and impair ventilatory drive. The combination of ventilatory impairment, excess CO(2) production and reduced ventilatory drive predisposes obese individuals to obesity hypoventilation syndrome.     

Breathing pattern in rats with chronic section of the superior laryngeal nerves

In a first set of experiments we registered the integrated afferent activity of the superior laryngeal nerve (SLN) in adult anaesthetized rats. The activity increased with positive upper airway pressure (Pua); with progressively more negative Pua, the SLN activity at first declined then increased again. A second set of adult rats underwent bilateral section of the SLN (SLN denervated) or a sham operation (controls). Both groups appeared to recover promptly from the operation and 6 days later their resting breathing pattern was recorded by the barometric method. SLN denervated rats had a shorter inspiratory time (80%), hence higher frequency and mean inspiratory flow, than controls. During hypoxia (10 min at 10% O2) both groups hyperventilated with an almost identical pattern. The rats were then again anaesthetized and the right vagus cut in an attempt to reduce the afferent component from the lower airways, which may have masked the SLN regulatory contribution. One week after this second operation both SLN denervated and controls breathed more deeply and slowly than before vagotomy, but the pattern was not significantly different between the two groups, either in normoxia or hypoxia. Finally, the rats were anaesthetized and integrated diaphragm activity recorded during spontaneous breathing and the first effort against closure of the nostrils. With both vagi cut, the duration of the occluded effort was slightly longer in SLN denervated than in controls. These results suggest that in adult awake rats laryngeal afferent activity tends to decrease mean inspiratory flow. However, this regulatory contribution is small during eupnea and insignificant during hypoxic hyperventilation.     

The respiratory activity of the superior laryngeal nerve in the rat.

The aim of this study was to characterize the laryngeal afferent activity of the rat. The animals were anesthetized and breathing spontaneously. Laryngeal afferent activity was recorded from both the whole superior laryngeal nerve (SLN) and from single fibers isolated from this nerve. An overall inspiratory augmenting activity was observed in the whole SLN during tracheostomy breathing, tracheal occlusion and upper airway breathing, but an expiratory augmenting activity was present during upper airway occlusion. The inspiratory modulated activity was abolished by bilateral section of the hypoglossal nerves but not the recurrent laryngeal nerves. A great number of receptors (46/80, 58%) were identified as 'drive' receptors, and others as 'pressure' (22/80, 28%) and 'irritant' type receptors (9/80, 11%). Nineteen pressure receptors were stimulated by positive transmural pressure, while only three stimulated by negative pressure. Nine drive receptors were also stimulated by positive pressure and inhibited by negative pressure. Such response to pressure was further evaluated by applying maintained pressures to the functionally isolated upper airway. These results are essentially consistent with findings obtained in the rabbit, but differ from those reported for the dog.     

Effect of laryngeal anesthesia on pulmonary function testing in normal subjects

Pulmonary function tests (PFT) were performed on 11 normal subjects before and after topical anesthesia of the larynx. The PFT consisted of flow volume loops and body box determinations of functional residual capacity and airway resistance, each performed in triplicate. After the first set of tests, cotton pledgets soaked in 4% lidocaine were held in the pyriform sinuses for 2 min to block the superior laryngeal nerves. In addition, 1.5 ml of 10% cocaine was dropped on the vocal cords via indirect laryngoscopy. PFT were repeated 5 min after anesthesia. Besides routine analysis of the flow volume loops, areas under the inspiratory (Area I) and expiratory (Area E) portions of the loops were calculated by planimetry. Area I, peak inspiratory flow (PIF), as well as forced inspiratory flow at 25, 50, and 75% forced vital capacity (FVC), decreased after anesthesia. Peak expiratory flow decreased after anesthesia, but Area E and forced expiratory flow at 25, 50, and 75% FVC were unchanged. This protocol also was performed in 12 normal subjects with isotonic saline being substituted for the lidocaine and cocaine. In this group, no significant differences were observed when flow volume loop parameters were compared before and after topical application of saline. In 5 spontaneously breathing anesthetized dogs, posterior cricoarytenoid muscle and afferent superior laryngeal nerve activity were recorded before and after laryngeal anesthesia performed with the same procedure used in the human subjects. Laryngeal anesthesia resulted in a substantial decrease or a complete disappearance of afferent SLN activity recorded during unobstructed and obstructed respiration. The data suggest that laryngeal receptors help modulate upper airway patency in man.     

Influence of vagal afferents on diphasic ventilatory response to hypoxia in newborn lambs

The effect of vagal afferents on the ventilatory response to hypoxia was studied in eleven awake newborn lambs. Tests were repeated before and after vagotomy in the same lambs in two conditions: with intact upper airways and after intubation. During hypoxia, a diphasic pattern of ventilatory response was observed in both vagotomized and intact lambs. However, face mask-breathing vagotomized lambs had a blunted increase in ventilation (V̇i) to hypoxia as compared with intact lambs (P = 0.0001) and they showed an expiratory braking during all hypoxic time. Furthermore, the normal increase in frequency (f) to hypoxia was abolished after vagotomy. After intubation, expiratory braking disappeared and, consequently, magnitude of the V̇i response to hypoxia was similar in intact and vagotomized lambs. These changes were due to improved tidal volume response in vagotomized intubated lambs (P < 0.002) with no significant change in f response. We concluded that, in awake newborn lambs, vagal afferents are essential for maintaining the pattern and the magnitude of the ventilatory response to hypoxia, the latter by controlling the motor output to the larynx.     

Cooling mediates the ventilatory depression associated with airflow through the larynx

Although constant airflow through the upper airway has been shown to induce ventilatory depression in anesthetized newborn animals, the role of laryngeal temperature in this response has not been studied. Experiments were performed in fourteen 1-5 day-old anesthetized puppies breathing through a tracheostomy. Tidal volume and laryngeal temperature were recorded while a constant stream of air (15-25 ml/sec) at room temperature was passed in the expiratory direction for 20 sec through the isolated upper airway. Warm (35-37 degrees C), humidified air at the same flow served as control. When laryngeal temperature was decreased by 7.5 +/- 0.9 degrees C, a marked change in breathing pattern was observed (VT = 54 +/- 5, TI = 187 +/- 33, TE = 636 +/- 179, VT/TI = 45 +/- 10% of control; n = 9). Warm air at the same flow induced no significant changes. Superior laryngeal nerve section abolished the effects of cooling on breathing pattern. In 5 puppies we compared the effect of 'fast' and 'slow' laryngeal cooling. Fast trials altered breathing pattern earlier than slow trials. We conclude that the depressant effect of airflow through the upper airway is entirely due to a decrease in laryngeal temperature and is mediated by superior laryngeal nerve afferents.     

Ventilatory response of the conscious or anesthetized cat to oxygen breathing

In conscious intact cats, oxygen breathing for up to 1 h does not modify ventilation, and the ventilatory response to CO2 in hyperoxia is not consistently decreased. However, oxygen breathing induces sustained hyperventilation in conscious cats after carotid body denervation. In anesthetized cats, oxygen breathing provokes a hypoventilation which is transient under light anesthesia but more sustained under deeper levels of anesthesia. At all levels of anesthesia, the ventilatory response to CO2 is decreased in hyperoxia as compared with normoxia. These results suggest that: the effects of hyperoxia include a central stimulating component, seen only in conscious animals, which offsets the decreased ventilatory drive from peripheral chemoreceptors; this central component is sensitive to anesthesia, thus allowing an explanation for the permanent decrease in ventilation and decrease in ventilatory response to CO2 observed when oxygen is given during deep anesthesia; and anesthesia may help to purposefully unmask factors involved in the control of breathing, but it markedly alters the normal functioning of the respiratory network.     

Reflex effects on breathing of laryngeal denervation, negative pressure and SO2 in upper airways

Respiratory reflex effects of laryngeal denervation, negative pressure and SO2 in upper airways were studied in anesthetized rabbits. Inspiratory efforts with nasal occlusion had longer duration (TIo) and smaller diaphragm activity (Adi) than with tracheal occlusion. After section of superior laryngeal nerves (SLN) these differences disappeared: values with tracheal occlusion became similar to those with nasal occlusion before denervation. This suggests that laryngeal pressure receptors, firing at zero pressure and decreasing their discharge with negative pressures, increase central inspiratory activity. After SO2 TIo, both with tracheal and nasal occlusion, increased even after laryngeal denervation, provided SO2 flowed through nasal pathway. Hence, nose and/or rhinopharynx contain receptors affected by SO2. After laryngeal denervation and SO2 TIo was shorter with nasal than with tracheal occlusion, despite equal Adi. This, combined with the above findings, suggests two groups of pressure receptors in nose and/or rhinopharynx with opposite effects on inspiratory off-switch: one unaffected and the other probably blocked by SO2. During nose breathing section of SLN produced only a slight decrease in mean inspiratory flow.     

Phrenic and hypoglossal neural responses to cold airflow in the upper airway.

Cold air flowing through the larynx is known to alter the activities of laryngeal receptors with afferents in the superior laryngeal nerves (SLNs) and to induce reflex apnea in neonatal mammals. To examine the ventilatory response in adult animals and to explore associated upper airway motor responses, we recorded phrenic and hypoglossal neural responses to cooling the isolated larynx with cold air in decerebrate, vagotomized, paralyzed, ventilated cats. The most consistent response was phrenic inhibition, which occurred in all animals tested. Either excitation or inhibition of hypoglossal activity was seen consistently in individual cats, with the result that the group response was not statistically significant. All responses to laryngeal cooling were abolished by section of the SLNs. The findings confirm that directing cold air through the larynx causes reflex inhibition of ventilatory (phrenic) activity, but raise new questions as to how the two, directionally opposite hypoglossal responses are mediated.     

Carotid body chemoreceptor and ventilatory responses to sustained hypoxia and hypercapnia in the cat

To understand the role of carotid chemoreceptor activity in the ventilatory responses to sustained hypoxia (30 min) the following measurements were made in cats anesthetized with alpha-chloralose: (1) carotid chemoreceptor and ventilatory responses to isocapnic hypoxia and to hypercapnia during hyperoxia; (2) carotid chemoreceptor responses to isocapnic hypoxia after dopamine receptor blockade; and (3) ventilatory responses to hypoxia after bilateral section of carotid sinus nerves (CSN). Transition to hypoxia (PaO2 approximately equal to 52 Torr) from hyperoxia gradually increased carotid chemoreceptor activity by ten fold and ventilation by two fold without any detectable overshoot. Termination of isocapnic hypoxia with hyperoxia (PaO2 greater than 300 Torr) at 30 min promptly restored the carotid chemoreceptor activity to prehypoxic level. Ventilation also decreased promptly, but remained above the control value. Induction of hypercapnia (from 31.8 Torr to 43.9 Torr) during hyperoxia was followed by a prompt increase in the chemoreceptor activity by four fold which subsequently diminished, and by a gradual four fold increase in ventilation. Termination of hypercapnia after 30 min was followed by a prompt return of chemoreceptor activity and by a slow return of ventilation to near control levels. Dopamine receptor blockade increased carotid chemoreceptor responsiveness to acute hypoxia but did not alter the response pattern during sustained hypoxia. After bilateral CSN section, ventilation decreased during maintained hypoxia. Thus, a stimulatory peripheral and inhibitory central effects of hypoxia could produce a biphasic ventilatory response to short-term hypoxia in the anesthetized cat with intact CSN but did not manifest it. The results suggest that the chemosensory input not only promptly stimulates ventilation but also prevents the subsequent depressant effect of hypoxia on the brain-stem respiratory mechanisms and hence presumably a biphasic ventilatory response in the anesthetized cat.     

Sulphur dioxide block of laryngeal receptors in rabbits

In 6 rabbits moving average of activity of superior laryngeal nerve(SLN) increased when pressure in upper airways (Pua) was positive and decreased when it was negative. After SO2 exposure of upper airways SLN activity at Pua = 0 decreased to 40% and was no longer affected by changes in Pua. Activity of 67 fibers of SLN was recorded in 11 rabbits: 35 came from 'pressure' receptors, 27 from 'drive', and 5 from 'flow'. Thirty-three pressure receptors discharged at Pua = 0: 32 increased their firing rate with positive Pua and decreased it with negative Pua, one did the reverse. One pressure receptor silent at Pua = 0 fired with positive Pua, the other with negative Pua. Pressure receptors were slowly adapting. SO2 blocked within 3-9 min 84% of pressure receptors, 56% of drive receptors, and 4 out of 5 flow receptors. The receptors recovered control activity within 5-10 min after SO2 removal. SO2 block of laryngeal receptors may represent a convenient experimental tool for studies of laryngeal reflexes.     

Respiratory effects of cold air breathing in anesthetized cats

Respiratory effects of cold air breathing were studied in anesthetized cats. Two different protocols were used: the air temperature was either lowered in an isolated segment, constituted by the larynx and oropharynx or in lower airways, so that the cats inspired the cold air directly. Temperatures ranged between 37 and 8 degrees C (first protocol) or between 37 and 15 degrees C (second protocol). When the temperature fell below 15 degrees C in the upper segment, marked increase in lung resistance occurred, without any significant changes in ventilatory variables nor in diaphragmatic electrical activity. The section of superior laryngeal nerves abolished this bronchomotor effect. In present experimental circumstances, thermal changes measured in lower airways when cats breathed cold air were mainly located in the cervical trachea. An increase in lung resistance and weak but significant changes in the diaphragmatic electromyogram began when the inspired air temperature fell below 25 degrees C. A selective local block of conduction in small vagal fibres by procaine or section of vagus nerves suppressed all these effects. In all cases the cold-induced changes in lung mechanics began very early (less than 10 sec) but continued for few minutes after the physiological temperature range had been restored in airways. The present data strongly suggest that the bronchomotor response to cold air breathing is a reflex, mediated by afferent fibres in the superior laryngeal nerves and in the vagus nerves.     

Role of airway mechanoreceptors in the inhibition of inspiration during mechanical ventilation in humans

The purpose of this study was to demonstrate a neuromechanical inhibitory effect on respiratory muscle activity during mechanical ventilation and to determine whether upper and lower airway receptors provide this inhibitory feedback. Several protocols were completed during mechanical ventilation: (1) positive and negative pressure changes in the upper airway, (2) airway anesthesia to examine the consequences of receptor blockade on respiratory muscle activity, (3) increasing FRC with positive end-expiratory pressure to study the effect of hyperinflation or stretch on respiratory muscle activity, and (4) use of heart-lung transplant patients to determine the effects of vagal denervation on respiratory muscle activity. All subjects were mechanically hyperventilated with positive pressure until inspiratory muscle activity was undetectable and the end-tidal PCO2 decreased to less than 30 mm Hg. End-tidal PCO2 (PETCO2) was increased by either adding CO2 to the inspired gas or decreasing tidal volume (50 ml/min). The PETCO2 where a change in inspiratory muscle activity occurred was taken as the recruitment threshold (PCO2RT). Neuromechanical feedback caused significant inspiratory muscle inhibition during mechanical ventilation, as evidenced by the difference between PCO2RT and PETCO2 during spontaneous eupnea (45 +/- 4 versus 39 +/- 4 mm Hg) and a lower PCO2RT when tidal volume was reduced with a constant frequency and fraction of inspired CO2. Recruitment threshold was unchanged during positive and negative pressure ventilation, during upper and lower airway anesthesia, and in vagally denervated lung transplant patients. These findings demonstrate that neuromechanical feedback causes highly significant inhibition of inspiratory muscle activity during mechanical ventilation; upper and lower airway receptors do not appear to mediate this effect.     

Relevance of a portable spirometer for detection of small airways obstruction

While portable spirometers are increasingly used, little attention has been paid to test their validity for measurement of flows in small airways. The aim of this study was to compare the Spirotel portable spirometer to a laboratory spirometer (Jeager PFT), with regard to accuracy in measuring forced expiratory flows, and more specifically those influenced by small airways (FEF(25-75)). Fifty-nine children (mean age, 12 years; range, 7-17), were studied at baseline and after a bronchodilator inhalation. Spirometers were tested separately in a randomly designed order. A total of 117 sessions of flow-volume curves was performed with each spirometer. We obtained at least two acceptable and reproducible curves in 88% and 76% of the sessions, with the laboratory and the portable spirometers, respectively. Unacceptable curves were easily detected by visual inspection of flow-time and flow-volume waveforms. Agreement was excellent between spirometers for the measurement of all expiratory flows, both at baseline and postbronchodilator. More specifically, agreement between spirometers was as high for measurements of FEF(25-75) (intraclass correlation coefficients 0.97) as for proximal flows. High correlations were found between baseline expiratory flows measured by each spirometer (and expressed as percent of predicted values), both in large and small airways (P < 0.001). The portable spirometer was highly sensitive for detecting small airways obstruction, as compared to the laboratory spirometer. Finally, the magnitudes of bronchodilator-related flow changes were also highly correlated, both in large and small airways (P < 0.001 and P = 0.004, respectively). We conclude that the Spirotel portable spirometer is reliable for measurement of forced expiratory flows, in large and small airways, provided that all curve waveforms can be stored and available for visual inspection.     

Effects of halothane,enflurane, and isoflurane on laryngeal receptors in dogs

The effects of halothane, enflurane, and isoflurane on laryngeal receptors were investigated in 6 anethetized dogs breathing spontaneously through a tracheostomy. Single unit actiion potentials were recorded from the peripheral cut end of the superior laryngeal nerve (SLN) while different concentrations of volatile anesthetics (1.25, 2.5., 5.0%) were administered in the expiratory direction at a constant air-flow (6 1/min) for 1 min through the functionally isolated upper airway. A total of 21 respiratory-modulated mechanoreceptors, 18 “irritant” receptors, and 7 cold receptors were studied. The overall results obtained from the 16 respiratory-modulated mechanoreceptors challenged with the 3 anesthetic gases disclosed a prevalent inhibitory effect and halothane proved to be the most effective of the 3 gases. The activity during both the inspiratory and expiratory phase was significantly reduced only by halothane (inspiratory phase, P<0.01; expiratory phase, P<0.05), while neither isoflurane nor enflurane caused significant changes in receptor activity. Of the 18 irritant receptors, 14 receptors increased their activity in a dose-related manner in response to one or more of the anesthetics although the effect of halothane was more pronounced than those of enflurane and isoflurane. All of the 7 cold receptos consistently increased their activity in a dose-related manner in response to halothane whereas 3 of 7 receptors were insensitive to enflurane and 4 of 7 receptors were insensitive to isoflurane. Our results indicate that, while all three commonly used anethetics can have an effect on different types of laryngeal receptors, the effects of halothane are more pronounced than those of the other two gases in terms of changes in receptor activity.     

Laryngeal muscle activities with cerebral hypoxia-ischemia in newborn lambs

This study tested the hypotheses that (1) acute cerebral hypoxia-ischemia changes laryngeal adductor, laryngeal abductor, and diaphragmatic activities, resulting in central apnea with laryngeal closure; and (2) these laryngeal muscle activities act to maintain absolute lung volume. The respiratory pattern was determined in three asphyxiated, awake preterm lambs after cesarean section birth and in 12 awake, term lambs, with normal lung function, after induction of acute cerebral hypoxia-ischemia by occlusion of the brachiocephalic artery. Electrocorticogram activity, flow, volume, electromyograms of laryngeal abductor and adductor muscles and diaphragm, and, in the term lambs, trans-upper airway pressure and carotid blood flow were recorded. With either preterm birth asphyxia or induced acute cerebral hypoxia-ischemia, minute ventilation initially increased, and then hypopnea occurred. During the hypopnea, laryngeal adductor activity was prominent, accompanied by an increased upper airway pressure and a maintained/raised absolute lung volume. Thus, when acute hypoxia-ischemia limited to the upper body is induced in lambs with normal lung function, expiratory laryngeal adduction with closure of the upper airway occurs and likely functions to aid autoresuscitation.     

Influence of laryngeal CO2 on respiratory activities of motor nerves to accessory muscles.

Intralaryngeal CO2 in decerebrate, vagotomized cats decreases phrenic nerve activity and increases the respiratory activity of the hypoglossal (HG) nerve. These responses are mediated by afferents in the superior laryngeal nerves. To explore the responses of other respiratory motor nerves to this stimulus, we have recorded the activities of the nasolabial (NL) branch of the facial nerve, the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) branches of the recurrent laryngeal nerve and the nerve to triangularis sterni (TS) muscle. In response to 5 and 10% CO2 in the surgically isolated upper airway, we found dose-related decreases in phrenic activity, increases in HG and NL activity and characteristic, but intermittent, exaggeration of early expiratory bursts of TA activity. The activities of the PCA and TS nerves showed no consistent responses. These results broaden the definition of the reflex response to intralaryngeal CO2, revealing components that reflect ventilatory inhibition, upper airway dilation and laryngeal protection.     

Physical performance in patients with thalassemia before and after transfusion

Patients with thalassemia who are on chronic transfusion programs have chronic ventilatory and cardiocirculatory abnormalities. We studied flow-volume curves, blood gas exchange, and cardiorespiratory responses to exercise in 12 patients with thalassemia major (TM) before and 24 hours after transfusions. Cardiorespiratory fitness was assessed with an exercise tolerance test on a cycle-ergometer. Ten healthy controls underwent the same protocol twice, first at baseline and then 24 hours later, without having had transfusions. We identified two subgroups of patients with a questionnaire: 1) those with no history of airway disease; and 2) those with a history of airway obstruction. Patients with no history of airway disease had normal baseline expiratory flows and no posttransfusion changes; those with a history of airway obstruction had lower pretransfusion expiratory flows rates and significantly decreased posttransfusion forced expiratory volume in 1 second (FEV₁) and forced expiratory flow at 25–75% of forced vital capacity (FEV_25–75%). As a group, TM patients had significantly lower pretransfusion cardiorespiratory function than controls; TM patients' maximum workload was 33% lower, maximum ventilation was 38% lower, maximum oxygen uptake was 25.7% lower, oxygen pulse was 28.6% lower, dyspnea index was 10.6% lower, and ventilatory equivalent for oxygen was 27.1% lower than in control subjects. Although cardiorespiratory responses to exercise improved in both subgroups after transfusion, patients with a history of airways obstruction had a significant posttransfusion increase in their dyspnea index (P = 0.05) and further increased their already abnormally high values of P_ETCO₂ (43 mmHg). These results suggest that the transfusion worsened relative hypoventilation at the maximum workload only in the subgroup with a history of airway obstruction. Pediatr Pulmonol. 1996; 21:367–372. © 1996 Wiley-Liss, Inc.