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Ventilation and Respiratory Mechanics

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Abstract

During dynamic exercise, the healthy pulmonary system faces several major challenges, including decreases in mixed venous oxygen content and increases in mixed venous carbon dioxide. As such, the ventilatory demand is increased, while the rising cardiac output means that blood will have considerably less time in the pulmonary capillaries to accomplish gas exchange. Blood gas homeostasis must be accomplished by precise regulation of alveolar ventilation via medullary neural networks and sensory reflex mechanisms. It is equally important that cardiovascular and pulmonary system responses to exercise be precisely matched to the increase in metabolic requirements, and that the substantial gas transport needs of both respiratory and locomotor muscles be considered. Our article addresses each of these topics with emphasis on the healthy, young adult exercising in normoxia. We review recent evidence concerning how exercise hyperpnea influences sympathetic vasoconstrictor outflow and the effect this might have on the ability to perform muscular work. We also review sex‐based differences in lung mechanics. © 2012 American Physiological Society. Compr Physiol 2:1093‐1142, 2012.

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Figure 1. Figure 1.

Schematic example of the ventilatory responses to progressive increases in cycling work rate in a healthy young subject. Note the initial rise in tidal volume, which then plateaus. After this, further increases in ventilation are accomplished by increases in breathing frequency.

Figure 2. Figure 2.

Ventilatory response and hemoglobin saturation (SpO2) during the final minute of leg cycling exercise at four different workloads with (Fentanyl, gray bars) and without (Placebo, black bars) partially blocked somatosensory neural feedback from the working locomotor muscles. The P value indicates the overall main effect of fentanyl. *P < 0.05; 1P = 0.08. From Amann et al. 23.

Reprinted with permission of the American Physiological Society.
Figure 3. Figure 3.

The solid line represents the estimated relationship between the work of breathing and exercise ventilation based on a regression equation from Aaron et al. 3, where the work of breathing = −80.041 + 1.459 (VE) + 0.011 (VE)2. The dotted line represents the estimated relationship between the respiratory muscle oxygen cost and exercise ventilation based on a regression equation from Aaron et al. 5, where the respiratory muscle o2 = 0.081 + 0.001 (exercise Wv – resting Wv), where Wv = the work of breathing.

Figure 4. Figure 4.

Relative effects of changing work of breathing on leg blood flow ( legs; A) and leg oxygen consumption (o2legs; B). Note that as the work of breathing is reduced (proportional assist ventilator) or increased (graded resistive loads) there is a corresponding increase and decrease in  legs and o2legs, respectively. Also note that the increased  legs with unloading occurs in the face of a reduced stroke volume and cardiac output.

Adapted, with permission, from Harms et al. 210. Reprinted with permission of the American Physiological Society.
Figure 5. Figure 5.

Respiratory muscle indocyanine green dye (ICG) response measured by near‐infrared spectroscopy (NIRS) at four different ventilatory loads in a single representative subject. There is a progressive increase in slope and peak ICG concentration with increasing levels of , indicating a faster rate of dye accumulation and therefore a higher blood flow response. Actual blood flow values at 20, 42, 85, and 121 liter/min were 10.2, 23.5, 32.9, and 76.0 mL/100 mL/min, respectively.

Adapted, with permission, from Guenette et al. 197. Reprinted with permission of the American Physiological Society.
Figure 6. Figure 6.

Raw data traces showing arterial and venous blood velocity, blood pressure, esophageal (Pes) and gastric pressure (Pga), calf force, and airflow during mild contraction conditions. The shaded areas and a downward deflection in the airflow trace denote inspiration. Note that arterial inflow remains unaffected by the type of breathing pattern used by the subject, and is also relatively unaffected by the calf contraction cycle. However, significant respiratory modulation of femoral venous outflow persists in the face of mild calf contraction during both ribcage and diaphragm breathing, as the phasic increases in venous return associated with the calf muscle pump are most pronounced during a ribcage inspiration (denoted by upward arrows). In contrast, during a diaphragmatic inspiration, anterograde femoral venous blood flow occurs exclusively during the calf contraction phase (denoted by downward arrows).

Adapted, with permission, from Miller et al. 369. Reprinted with permission.
Figure 7. Figure 7.

A working hypothesis for the neurophysiological underpinnings of perceived respiratory discomfort (breathlessness) during exercise in healthy humans: a working hypothesis. Refer to text for details. o2 and , metabolic rates of oxygen consumption and carbon dioxide output; Type III and IV mechano‐ and metabosensitive afferents in the peripheral locomotor (and respiratory) muscles and their vasculature; SARs, slowly adapting receptors; RARs, rapidly adapting receptors; C‐fibers, bronchopulmonary C‐fibers; J‐receptors, juxtapulmonary capillary receptors; GTOs, Golgi tendon organs; PCO2, partial pressure of carbon dioxide; [H+], hydrogen ion concentration; [La], lactate ion concentration; Pao2, arterial partial pressure of oxygen; SaO2, arterial blood oxygen saturation.

Adapted, with permission, from Jensen et al. 243. Reprinted with permission.
Figure 8. Figure 8.

Thickness of tenascin immunoreactive band in subepithelial basement membrane zone in controls, elite cross‐country skiers with and without bronchial hyperresponsiveness (BHR), and asthmatic subjects. Horizontal bar = median value.

Adapted, with permission, from Karjalainen et al. 266. Reprinted with permission of the American Thoracic Society. Copyright(c) American Thoracic Society. Karjalainen EM, Laitinen A, Sue‐Chu M, Altraja A, Bjermer L, and Laitnen LA. 2000. Evidence of airway inflammation and remodeling in ski athletes with and without bronchial hyperresponsiveness to methacholine. American Journal of Respiratory and Crtical Care Medicine. 161:2086‐2091. Official journal of the American Thoracic Society.
Figure 9. Figure 9.

Typical responses of esophageal (Pes), gastric (Pga), and transdiaphragmatic (Pdi) pressures and diaphragm EMG (i.e., M‐waves) to 10‐Hz bilateral phrenic nerve stimulation before and immediately after whole‐body exercise at 90% o2 max. Pdi was significantly reduced following the whole‐body exercise. There was no change in the M‐wave response of the diaphragm to the supramaximal stimulation.

Adapted, with permission, from Johnson et al. 246. Reprinted with permission of Wiley‐Blackwell, copyright 1993.
Figure 10. Figure 10.

Abdominal muscle fatigue in response to dynamic exercise. (A) Group (n = 11) mean gastric pressure (Pga) in response to magnetic stimulation at 1 Hz (single twitch) through 25 Hz (tetanic stimulation) before, and up to 30 min after whole‐body exercise. At all frequencies of stimulation, Pga immediately postexercise was reduced below baseline values. (B) Identity plot for thoracic nerve stimulation at 1‐25 Hz. *P < 0.05; **P < 0.01, values less than 1‐min postexercise significantly different from preexercise values at the same stimulation frequency. *P < 0.05; **P < 0.01, values 30‐min postexercise significantly different from preexercise values at the same stimulation frequency.

Adapted, with permission, from Taylor et al. 516. Reprinted with permission of the American Physiological Society.
Figure 11. Figure 11.

Schematic of the proposed respiratory muscle metaboreflex and its effects. The metaboreflex is initiated by fatigue of the respiratory muscles, mediated supraspinally via group III/IV afferents, leading to sympathetically mediated vasoconstriction of limb locomotor muscle vasculature, exacerbating peripheral fatigue of working limb muscles, and (via feedback) intensifying effort perceptions, thereby contributing to limitation of heavy‐intensity endurance exercise performance.

Adapted, with permission, from Dempsey et al. 131 as published in Romer and Polkey 454. Reprinted with permission of the American Physiological Society.
Figure 12. Figure 12.

Effects of fatiguing the diaphragm on muscle sympathetic nerve activity (MSNA). Note that MSNA remains relatively unchanged at the onset of high levels of inspiratory muscle force output, but increased gradually over time in both frequency and amplitude.

Adapted, with permission, from St. Croix et al. 493. Reprinted with permission.
Figure 13. Figure 13.

Summary of effects of increasing and decreasing inspiratory muscle work on quadriceps muscle fatigue. Percent twitch force (Qtw) represents the reduction in the average quadriceps force output determined across four stimulation frequencies (1‐100 Hz) and compared between baseline (preexercise) and 2.5 min postexercise. Control versus respiratory muscle unloading (via mechanical ventilation) effects on quadriceps muscle fatigue were compared at equal cycle ergometer work rates and durations (the durations being determined by the time to exhaustion under control conditions). Control versus respiratory muscle resistive loading effects on quadriceps muscle fatigue were also compared at equal cycle work rates and durations (the duration being determined by the time to exhaustion under loaded conditions). Force output of the inspiratory muscles was measured as the time integral of the average esophageal pressure multiplied by breathing frequency and for the diaphragm was measured as the average transdiaphragmatic pressure time integral multiplied by breathing frequency. Differences in Qtw were significant (*P < 0.01) between control and unload, and control and load.

Data taken, with permission, from Romer et al. 449, figure as published in Romer and Polkey 454. Reprinted with permission of the American Physiological Society.
Figure 14. Figure 14.

Raw data from an individual subject during resistive breathing. Resistive breathing consisted of breathing at 60% of maximal inspiratory pressure, a prolonged duty cycle of 0.70 and a breathing frequency of 15 breath/min. Shown are values at baseline (A) and following 5 weeks of inspiratory muscle training (B). Note the attenuation of the blood pressure response following inspiratory muscle training.

Adapted, with permission, from Witt et al. 575. Reprinted with permission.
Figure 15. Figure 15.

Shown in (A) [adapted from reference 251] is the flow‐volume response to exercise in the average fit healthy young adult during incremental exercise plotted within the maximum flow volume loop. Note that in this population, end‐expiratory lung volume (EELV) progressively decreases with exercise, and expiratory flow limitation (EFL) is only present near EELV over a small portion of the tidal volume. Considerable room exists to increase ventilation even at peak exercise. Similar responses are also shown for the fit aged adult [(B); adapted from reference 250] and the young endurance athlete [(C); adapted from reference 251]. The older adult represents a group of subjects with a mild decline in lung function but maintenance of a high ventilatory demand. Flow limitation occurs at a low work intensity and ventilatory demand (40 liter/min) and EILV at peak exercise reaches a higher percent of TLC. This group has significant ventilatory constraint at peak exercise. The fit young athlete (C) represents a group of subjects with normal lung function but excessive ventilatory demands. EELV initially decreases during exercise like the average fit adult, but increases as significant expiratory flow limitation occurs. By peak exercise in the majority of these subjects, significant ventilatory constraint is observed similar to the aged, fit adult.

Figure as published in Johnson et al. 253. Reprinted with permission.
Figure 16. Figure 16.

Airway tree with assigned labels. Labels refer to segments but are assigned to terminating branchpoint of respective segment. Definition of abbreviations: LMB, left main bronchus; LUL, left upper lobe; LB, left bronchus; LLB, left lower lobe; RMB, right main bronchus; RUL, right upper lobe; RB, right bronchus; BRONINT, intermediate bronchus; RLL, right lower lobe. * indicates significant differences between men and women of varying body size (P < 0.05). † indicates significant differences between of subjects matched for lung size (P < 0.05).

Adapted, with permission, from Sheel et al. 475. Reprinted with permission of the American Physiological Society.
Figure 17. Figure 17.

Mean curve relating the work of breathing versus minute ventilation in men (thin line) and women (thick line). Each curve has been extrapolated to 200 liter/min for theoretical purposes only.

Adapted, with permission, from Guenette et al. 198. Reprinted with permission.
Figure 18. Figure 18.

Modified Campbell diagrams of an individual male and female subject matched approximately for absolute minute ventilation [100 vs. 101 liter/min, respectively] tidal volume (2.1 vs. 2.2 liters, respectively) and breathing frequency (52 vs. 49 breath/min). Oblique hatching represents the inspiratory resistive work of breathing (Ir). Horizontal hatching represents the inspiratory elastic work of breathing (Ie). Stippling represents the expiratory resistive work of breathing (Er). Vertical hatching represents the expiratory elastic work of breathing (Ee). Cl, dynamic lung compliance; Ccw, chest wall compliance. Upward arrow represents inspiration and downward arrow represents expiration. Small open circles represent zero flow points.

Adapted, with permission, from Guenette et al. 195. Reprinted with permission of the American Physiological Society.
Figure 19. Figure 19.

Individual tidal flow‐volume loops during the final stage of exercise in women (A; n = 10) and men (B; n = 8). Dark lines represent the control breath and thin lines represent the negative expiratory pressure (NEP) breath. Subjects were considered flow limited if part of the NEP breath overlapped the preceding control breath. One male subject (subject 3) was excluded in the analysis of expiratory flow limitation because the NEP caused a sustained decrease in expiratory flow. Expiratory flow limitation was observed three of the seven male subjects and nine of the ten female subjects during the final stage of exercise. Subject 3 was the only female that did not develop expiratory flow limitation. Of all female subjects she also had the largest lungs (134% predicted FVC) and the lowest work of breathing.

Adapted, with permission, from Guenette et al. 198. Reprinted with permission.
Figure 20. Figure 20.

Breathlessness/oxygen uptake (o2) slopes showed a significant aging effect with no significant sex‐related effect: slopes were greater in 60‐ to 80‐year‐old women [old female (OF) group] compared with 40‐ to 59‐year‐old women [young female (YF) group] but not in 60‐ to 80‐year‐old men [old male (OM) group] compared with 40‐ to 59‐year‐old men [young male (YM) group]. Breathlessness/ventilation () slopes showed a significant sex‐related effect only, such that women had steeper slopes than men. * indicates that ratings of dyspnea intensity at a standardized O2 of 20 mL/kg/min showed a significant age effect, as well as a significant interaction between aging and sex‐related effects: the age‐related increase in dyspnea ratings was greater in women.

Adapted, with permission, from Ofir et al. 400. Reprinted with permission of the American Physiological Society.


Figure 1.

Schematic example of the ventilatory responses to progressive increases in cycling work rate in a healthy young subject. Note the initial rise in tidal volume, which then plateaus. After this, further increases in ventilation are accomplished by increases in breathing frequency.



Figure 2.

Ventilatory response and hemoglobin saturation (SpO2) during the final minute of leg cycling exercise at four different workloads with (Fentanyl, gray bars) and without (Placebo, black bars) partially blocked somatosensory neural feedback from the working locomotor muscles. The P value indicates the overall main effect of fentanyl. *P < 0.05; 1P = 0.08. From Amann et al. 23.

Reprinted with permission of the American Physiological Society.


Figure 3.

The solid line represents the estimated relationship between the work of breathing and exercise ventilation based on a regression equation from Aaron et al. 3, where the work of breathing = −80.041 + 1.459 (VE) + 0.011 (VE)2. The dotted line represents the estimated relationship between the respiratory muscle oxygen cost and exercise ventilation based on a regression equation from Aaron et al. 5, where the respiratory muscle o2 = 0.081 + 0.001 (exercise Wv – resting Wv), where Wv = the work of breathing.



Figure 4.

Relative effects of changing work of breathing on leg blood flow ( legs; A) and leg oxygen consumption (o2legs; B). Note that as the work of breathing is reduced (proportional assist ventilator) or increased (graded resistive loads) there is a corresponding increase and decrease in  legs and o2legs, respectively. Also note that the increased  legs with unloading occurs in the face of a reduced stroke volume and cardiac output.

Adapted, with permission, from Harms et al. 210. Reprinted with permission of the American Physiological Society.


Figure 5.

Respiratory muscle indocyanine green dye (ICG) response measured by near‐infrared spectroscopy (NIRS) at four different ventilatory loads in a single representative subject. There is a progressive increase in slope and peak ICG concentration with increasing levels of , indicating a faster rate of dye accumulation and therefore a higher blood flow response. Actual blood flow values at 20, 42, 85, and 121 liter/min were 10.2, 23.5, 32.9, and 76.0 mL/100 mL/min, respectively.

Adapted, with permission, from Guenette et al. 197. Reprinted with permission of the American Physiological Society.


Figure 6.

Raw data traces showing arterial and venous blood velocity, blood pressure, esophageal (Pes) and gastric pressure (Pga), calf force, and airflow during mild contraction conditions. The shaded areas and a downward deflection in the airflow trace denote inspiration. Note that arterial inflow remains unaffected by the type of breathing pattern used by the subject, and is also relatively unaffected by the calf contraction cycle. However, significant respiratory modulation of femoral venous outflow persists in the face of mild calf contraction during both ribcage and diaphragm breathing, as the phasic increases in venous return associated with the calf muscle pump are most pronounced during a ribcage inspiration (denoted by upward arrows). In contrast, during a diaphragmatic inspiration, anterograde femoral venous blood flow occurs exclusively during the calf contraction phase (denoted by downward arrows).

Adapted, with permission, from Miller et al. 369. Reprinted with permission.


Figure 7.

A working hypothesis for the neurophysiological underpinnings of perceived respiratory discomfort (breathlessness) during exercise in healthy humans: a working hypothesis. Refer to text for details. o2 and , metabolic rates of oxygen consumption and carbon dioxide output; Type III and IV mechano‐ and metabosensitive afferents in the peripheral locomotor (and respiratory) muscles and their vasculature; SARs, slowly adapting receptors; RARs, rapidly adapting receptors; C‐fibers, bronchopulmonary C‐fibers; J‐receptors, juxtapulmonary capillary receptors; GTOs, Golgi tendon organs; PCO2, partial pressure of carbon dioxide; [H+], hydrogen ion concentration; [La], lactate ion concentration; Pao2, arterial partial pressure of oxygen; SaO2, arterial blood oxygen saturation.

Adapted, with permission, from Jensen et al. 243. Reprinted with permission.


Figure 8.

Thickness of tenascin immunoreactive band in subepithelial basement membrane zone in controls, elite cross‐country skiers with and without bronchial hyperresponsiveness (BHR), and asthmatic subjects. Horizontal bar = median value.

Adapted, with permission, from Karjalainen et al. 266. Reprinted with permission of the American Thoracic Society. Copyright(c) American Thoracic Society. Karjalainen EM, Laitinen A, Sue‐Chu M, Altraja A, Bjermer L, and Laitnen LA. 2000. Evidence of airway inflammation and remodeling in ski athletes with and without bronchial hyperresponsiveness to methacholine. American Journal of Respiratory and Crtical Care Medicine. 161:2086‐2091. Official journal of the American Thoracic Society.


Figure 9.

Typical responses of esophageal (Pes), gastric (Pga), and transdiaphragmatic (Pdi) pressures and diaphragm EMG (i.e., M‐waves) to 10‐Hz bilateral phrenic nerve stimulation before and immediately after whole‐body exercise at 90% o2 max. Pdi was significantly reduced following the whole‐body exercise. There was no change in the M‐wave response of the diaphragm to the supramaximal stimulation.

Adapted, with permission, from Johnson et al. 246. Reprinted with permission of Wiley‐Blackwell, copyright 1993.


Figure 10.

Abdominal muscle fatigue in response to dynamic exercise. (A) Group (n = 11) mean gastric pressure (Pga) in response to magnetic stimulation at 1 Hz (single twitch) through 25 Hz (tetanic stimulation) before, and up to 30 min after whole‐body exercise. At all frequencies of stimulation, Pga immediately postexercise was reduced below baseline values. (B) Identity plot for thoracic nerve stimulation at 1‐25 Hz. *P < 0.05; **P < 0.01, values less than 1‐min postexercise significantly different from preexercise values at the same stimulation frequency. *P < 0.05; **P < 0.01, values 30‐min postexercise significantly different from preexercise values at the same stimulation frequency.

Adapted, with permission, from Taylor et al. 516. Reprinted with permission of the American Physiological Society.


Figure 11.

Schematic of the proposed respiratory muscle metaboreflex and its effects. The metaboreflex is initiated by fatigue of the respiratory muscles, mediated supraspinally via group III/IV afferents, leading to sympathetically mediated vasoconstriction of limb locomotor muscle vasculature, exacerbating peripheral fatigue of working limb muscles, and (via feedback) intensifying effort perceptions, thereby contributing to limitation of heavy‐intensity endurance exercise performance.

Adapted, with permission, from Dempsey et al. 131 as published in Romer and Polkey 454. Reprinted with permission of the American Physiological Society.


Figure 12.

Effects of fatiguing the diaphragm on muscle sympathetic nerve activity (MSNA). Note that MSNA remains relatively unchanged at the onset of high levels of inspiratory muscle force output, but increased gradually over time in both frequency and amplitude.

Adapted, with permission, from St. Croix et al. 493. Reprinted with permission.


Figure 13.

Summary of effects of increasing and decreasing inspiratory muscle work on quadriceps muscle fatigue. Percent twitch force (Qtw) represents the reduction in the average quadriceps force output determined across four stimulation frequencies (1‐100 Hz) and compared between baseline (preexercise) and 2.5 min postexercise. Control versus respiratory muscle unloading (via mechanical ventilation) effects on quadriceps muscle fatigue were compared at equal cycle ergometer work rates and durations (the durations being determined by the time to exhaustion under control conditions). Control versus respiratory muscle resistive loading effects on quadriceps muscle fatigue were also compared at equal cycle work rates and durations (the duration being determined by the time to exhaustion under loaded conditions). Force output of the inspiratory muscles was measured as the time integral of the average esophageal pressure multiplied by breathing frequency and for the diaphragm was measured as the average transdiaphragmatic pressure time integral multiplied by breathing frequency. Differences in Qtw were significant (*P < 0.01) between control and unload, and control and load.

Data taken, with permission, from Romer et al. 449, figure as published in Romer and Polkey 454. Reprinted with permission of the American Physiological Society.


Figure 14.

Raw data from an individual subject during resistive breathing. Resistive breathing consisted of breathing at 60% of maximal inspiratory pressure, a prolonged duty cycle of 0.70 and a breathing frequency of 15 breath/min. Shown are values at baseline (A) and following 5 weeks of inspiratory muscle training (B). Note the attenuation of the blood pressure response following inspiratory muscle training.

Adapted, with permission, from Witt et al. 575. Reprinted with permission.


Figure 15.

Shown in (A) [adapted from reference 251] is the flow‐volume response to exercise in the average fit healthy young adult during incremental exercise plotted within the maximum flow volume loop. Note that in this population, end‐expiratory lung volume (EELV) progressively decreases with exercise, and expiratory flow limitation (EFL) is only present near EELV over a small portion of the tidal volume. Considerable room exists to increase ventilation even at peak exercise. Similar responses are also shown for the fit aged adult [(B); adapted from reference 250] and the young endurance athlete [(C); adapted from reference 251]. The older adult represents a group of subjects with a mild decline in lung function but maintenance of a high ventilatory demand. Flow limitation occurs at a low work intensity and ventilatory demand (40 liter/min) and EILV at peak exercise reaches a higher percent of TLC. This group has significant ventilatory constraint at peak exercise. The fit young athlete (C) represents a group of subjects with normal lung function but excessive ventilatory demands. EELV initially decreases during exercise like the average fit adult, but increases as significant expiratory flow limitation occurs. By peak exercise in the majority of these subjects, significant ventilatory constraint is observed similar to the aged, fit adult.

Figure as published in Johnson et al. 253. Reprinted with permission.


Figure 16.

Airway tree with assigned labels. Labels refer to segments but are assigned to terminating branchpoint of respective segment. Definition of abbreviations: LMB, left main bronchus; LUL, left upper lobe; LB, left bronchus; LLB, left lower lobe; RMB, right main bronchus; RUL, right upper lobe; RB, right bronchus; BRONINT, intermediate bronchus; RLL, right lower lobe. * indicates significant differences between men and women of varying body size (P < 0.05). † indicates significant differences between of subjects matched for lung size (P < 0.05).

Adapted, with permission, from Sheel et al. 475. Reprinted with permission of the American Physiological Society.


Figure 17.

Mean curve relating the work of breathing versus minute ventilation in men (thin line) and women (thick line). Each curve has been extrapolated to 200 liter/min for theoretical purposes only.

Adapted, with permission, from Guenette et al. 198. Reprinted with permission.


Figure 18.

Modified Campbell diagrams of an individual male and female subject matched approximately for absolute minute ventilation [100 vs. 101 liter/min, respectively] tidal volume (2.1 vs. 2.2 liters, respectively) and breathing frequency (52 vs. 49 breath/min). Oblique hatching represents the inspiratory resistive work of breathing (Ir). Horizontal hatching represents the inspiratory elastic work of breathing (Ie). Stippling represents the expiratory resistive work of breathing (Er). Vertical hatching represents the expiratory elastic work of breathing (Ee). Cl, dynamic lung compliance; Ccw, chest wall compliance. Upward arrow represents inspiration and downward arrow represents expiration. Small open circles represent zero flow points.

Adapted, with permission, from Guenette et al. 195. Reprinted with permission of the American Physiological Society.


Figure 19.

Individual tidal flow‐volume loops during the final stage of exercise in women (A; n = 10) and men (B; n = 8). Dark lines represent the control breath and thin lines represent the negative expiratory pressure (NEP) breath. Subjects were considered flow limited if part of the NEP breath overlapped the preceding control breath. One male subject (subject 3) was excluded in the analysis of expiratory flow limitation because the NEP caused a sustained decrease in expiratory flow. Expiratory flow limitation was observed three of the seven male subjects and nine of the ten female subjects during the final stage of exercise. Subject 3 was the only female that did not develop expiratory flow limitation. Of all female subjects she also had the largest lungs (134% predicted FVC) and the lowest work of breathing.

Adapted, with permission, from Guenette et al. 198. Reprinted with permission.


Figure 20.

Breathlessness/oxygen uptake (o2) slopes showed a significant aging effect with no significant sex‐related effect: slopes were greater in 60‐ to 80‐year‐old women [old female (OF) group] compared with 40‐ to 59‐year‐old women [young female (YF) group] but not in 60‐ to 80‐year‐old men [old male (OM) group] compared with 40‐ to 59‐year‐old men [young male (YM) group]. Breathlessness/ventilation () slopes showed a significant sex‐related effect only, such that women had steeper slopes than men. * indicates that ratings of dyspnea intensity at a standardized O2 of 20 mL/kg/min showed a significant age effect, as well as a significant interaction between aging and sex‐related effects: the age‐related increase in dyspnea ratings was greater in women.

Adapted, with permission, from Ofir et al. 400. Reprinted with permission of the American Physiological Society.
 1. Aaker A, Laughlin MH. Diaphragm arterioles are less responsive to alpha1‐ adrenergic constriction than gastrocnemius arterioles. J Appl Physiol 92: 1808‐1816, 2002a.
 2. Aaker A, Laughlin MH. Differential adenosine sensitivity of diaphragm and skeletal muscle arterioles. J Appl Physiol 93: 848‐856, 2002b.
 3. Aaron EA, Johnson BD, Seow CK, Dempsey JA. Oxygen cost of exercise hyperpnea: Measurement. J Appl Physiol 72: 1810‐1817, 1992.
 4. Aaron EA, Powell FL. Effect of chronic hypoxia on hypoxic ventilatory response in awake rats. J Appl Physiol 74: 1635‐1640, 1993.
 5. Aaron EA, Seow KC, Johnson BD, Dempsey JA. Oxygen cost of exercise hyperpnea: Implications for performance. J Appl Physiol 72: 1818‐1825, 1992.
 6. Abe T, Kusuhara N, Yoshimura N, Tomita T, Easton PA. Differential respiratory activity of four abdominal muscles in humans. J Appl Physiol 80: 1379‐1389, 1996.
 7. Abraham KA, Feingold H, Fuller DD, Jenkins M, Mateika JH, Fregosi RF. Respiratory‐related activation of human abdominal muscles during exercise. J Physiol 541: 653‐663, 2002.
 8. Adams L, Lane R, Shea SA, Cockcroft A, Guz A. Breathlessness during different forms of ventilatory stimulation: A study of mechanisms in normal subjects and respiratory patients. Clin Sci (Lond) 69: 663‐672, 1985.
 9. Agostoni E. A graphical analysis of thoracoabdominal mechanics during the breathing cycle. J Appl Physiol 16: 1055‐1059, 1961.
 10. Agostoni P, Swenson ER, Bussotti M, Revera M, Meriggi P, Faini A, Lombardi C, Bilo G, Giuliano A, Bonacina D, Modesti PA, Mancia G, Parati G, HIGHCARE Investigators. High‐altitude exposure of three weeks duration increases lung diffusing capacity in humans. J Appl Physiol 110: 1564‐1571, 2011.
 11. Ainsworth DM, Smith CA, Eicker SW, Henderson KS, Dempsey JA. The effects of locomotion on respiratory muscle activity in the awake dog. Respir Physiol 78: 145‐162, 1989.
 12. Akabas SR, Bazzy AR, DiMauro S, Haddad GG. Metabolic and functional adaptation of the diaphragm to training with resistive loads. J Appl Physiol 66: 529‐535, 1989.
 13. Akiyama Y, Garcia RE, Bazzy AR. Effect of inspiratory training on mitochondrial DNA and cytochrome‐c oxidase expression in the diaphragm. Am J Physiol 271: L320‐L325, 1996.
 14. Akiyama Y, Garcia RE, Prochaska LJ, Bazzy AR. Effect of chronic respiratory loading on the subunit composition of cytochrome c oxidase in the diaphragm. Am J Physiol 267: L350‐L355, 1994.
 15. Aldrich TK. Transmission fatigue of the rabbit diaphragm. Respir Physiol 69: 307‐319, 1987.
 16. Aldrich TK. Electrophysiological techniques for the assessment of respiratory muscle function. Am J Respir Crit Care Med 166: 548‐558, 2002.
 17. Aldrich TK, Adams JM, Arora NS, Rochester DF. Power spectral analysis of the diaphragm electromyogram. J Appl Physiol 54: 1579‐1584, 1983.
 18. Aliverti A, Bovio D, Fullin I, Dellaca RL, Lo Mauro A, Pedotti A, Macklem PT. The abdominal circulatory pump. PLoS ONE 4: e5550, 2009.
 19. Aliverti A, Cala SJ, Duranti R, Ferrigno G, Kenyon CM, Pedotti A, Scano G, Sliwinski P, Macklem PT, Yan S. Human respiratory muscle actions and control during exercise. J Appl Physiol 83: 1256‐1269, 1997.
 20. Aliverti A, Dellaca RL, Lotti P, Bertini S, Duranti R, Scano G, Heyman J, Lo Mauro A, Pedotti A, Macklem PT. Influence of expiratory flow‐limitation during exercise on systemic oxygen delivery in humans. Eur J Appl Physiol 95: 229‐242, 2005.
 21. Aliverti A, Stevenson N, Dellaca RL, Lo Mauro A, Pedotti A, Calverley PM. Regional chest wall volumes during exercise in chronic obstructive pulmonary disease. Thorax 59: 210‐216, 2004.
 22. Allen DG, Lamb GD, Westerblad H. Skeletal muscle fatigue: Cellular mechanisms. Physiol Rev 88: 287‐332, 2008.
 23. Amann M, Blain GM, Proctor LT, Sebranek JJ, Pegelow DF, Dempsey JA. Group III and IV muscle afferents contribute to ventilatory and cardiovascular response to rhythmic exercise in humans. J Appl Physiol 109: 966‐976, 2010.
 24. Amann M, Pegelow DF, Jacques AJ, Dempsey JA. Inspiratory muscle work in acute hypoxia influences locomotor muscle fatigue and exercise performance of healthy humans. Am J Physiol Regul Integr Comp Physiol 293: R2036‐R2045, 2007.
 25. Amann M, Proctor LT, Sebranek JJ, Eldridge MW, Pegelow DF, Dempsey JA. Somatosensory feedback from the limbs exerts inhibitory influences on central neural drive during whole body endurance exercise. J Appl Physiol 105: 1714‐1724, 2008.
 26. Amann M, Regan MS, Kobitary M, Eldridge MW, Boutellier U, Pegelow DF, Dempsey JA. Impact of pulmonary system limitations on locomotor muscle fatigue in patients with COPD. Am J Physiol Regul Integr Comp Physiol 299: R314‐R324, 2010.
 27. Ameredes BT, Zhan WZ, Prakash YS, Vandenboom R, Sieck GC. Power fatigue of the rat diaphragm muscle. J Appl Physiol 89: 2215‐2219, 2000.
 28. American Thoracic Society. Dyspnea: Mechanisms, assessment, and management: A consensus statement. Am J Respir Crit Care Med 159: 321‐340, 1999.
 29. Anderson SD, Fitch K, Perry CP, Sue‐Chu M, Crapo R, McKenzie D, Magnussen H. Responses to bronchial challenge submitted for approval to use inhaled beta2‐agonists before an event at the 2002 Winter Olympics. J Allergy Clin Immun 111: 45‐50, 2003.
 30. Anderson SD, Kippelen P. Exercise‐induced bronchoconstriction: Pathogenesis. Curr Allergy Asthma Rep 5: 116‐122, 2005.
 31. Anderson SD, Sue‐Chu M, Perry CP, Gratziou C, Kippelen P, McKenzie DC, Beck KC, Fitch KD. Bronchial challenges in athletes applying to inhale a beta2‐agonist at the 2004 Summer Olympics. J Allergy Clin Immun 117: 767‐773, 2006.
 32. Andrew GM, Becklake MR, Guleria JS, Bates DV. Heart and lung functions in swimmers and nonathletes during growth. J Appl Physiol 32: 245‐251, 1972.
 33. Andrezik JA, Dormer KJ, Foreman RD, Person RJ. Fastigial nucleus projections to the brain stem in beagles: Pathways for autonomic regulation. Neuroscience 11: 497‐507, 1984.
 34. Arbab‐Zadeh A, Dijk E, Prasad A, Fu Q, Torres P, Zhang R, Thomas JD, Palmer D, Levine BD. Effect of aging and physical activity on left ventricular compliance. Circulation 110: 1799‐1805, 2004.
 35. Armour J, Donnelly PM, Bye PT. The large lungs of elite swimmers: An increased alveolar number? Eur Respir J 6: 237‐247, 1993.
 36. Asmussen E, Johansen SH, Jorgensen M, Nielsen M. On the nervous factors controlling respiration and circulation during exercise. Experiments with curarization. Acta Physiol Scand 63: 343‐350, 1965.
 37. Asmussen E, Nielsen M. Ventilatory response to CO2 during work at normal and at low oxygen tensions. Acta Physiol Scand 39: 27‐35, 1957.
 38. Asmussen E, Nielsen M. Pulmonary ventilation and effect of oxygen breathing in heavy exercise. Acta Physiol Scnd 43: 365‐378, 1958.
 39. Asmussen E, Nielsen M. Experiments on nervous factors controlling respiration and circulation during exercise employing blocking of the blood flow. Acta Physiol Scand a 60: 103‐111, 1964.
 40. Aubier M, Farkas G, De Troyer A, Mozes R, Roussos C. Detection of diaphragmatic fatigue in man by phrenic stimulation. J Appl Physiol 50: 538‐544, 1981.
 41. Aubier M, Murciano D, Menu Y, Boczkowski J, Mal H, Pariente R. Dopamine effects on diaphragmatic strength during acute respiratory failure in chronic obstructive pulmonary disease. Annals Int Med 110: 17‐23, 1989.
 42. Babb TG. Ventilatory response to exercise in subjects breathing CO2 or HeO2. J Appl Physiol 82: 746‐754, 1997.
 43. Babcock MA, Harms CA, Pegelow DF, Dempsey JA. Effects of mechanical unloading of inspiratory muscles on exercise‐induced diaphragm fatigue. Am Rev Respir Dis 152: 178, 1997.
 44. Babcock MA, Johnson BD, Pegelow DF, Suman OE, Griffin D, Dempsey JA. Hypoxic effects on exercise‐induced diaphragmatic fatigue in normal healthy humans. J Appl Physiol 78: 82‐92, 1995.
 45. Babcock MA, Pegelow DF, Harms CA, Dempsey JA. Effects of respiratory muscle unloading on exercise‐induced diaphragm fatigue. J Appl Physiol 93: 201‐206, 2002.
 46. Babcock MA, Pegelow DF, Johnson BD, Dempsey JA. Aerobic fitness effects on exercise‐induced low‐frequency diaphragm fatigue. J Appl Physiol 81: 2156‐2164, 1996.
 47. Babcock MA, Pegelow DF, McClaran SR, Suman OE, Dempsey JA. Contribution of diaphragmatic power output to exercise‐induced diaphragm fatigue. J Appl Physiol 78: 1710‐1719, 1995.
 48. Babcock MA, Pegelow DF, Taha BH, Dempsey JA. High frequency diaphragmatic fatigue detected with paired stimuli in humans. Med Sci Sports Exerc 30: 506‐511, 1998.
 49. Bai TR, Rabinovitch BJ, Pardy RL. Near‐maximal voluntary hyperpnea and ventilatory muscle function. J Appl Physiol 57: 1742‐1748, 1984.
 50. Bailey SJ, Romer LM, Kelly J, Wilkerson DP, Dimenna FJ, Jones AM. Inspiratory muscle training enhances pulmonary O2 uptake kinetics and high‐intensity exercise tolerance in humans. J Appl Physiol.
 51. Balzamo E, Lagier‐Tessonnier F, Jammes Y. Fatigue‐induced changes in diaphragmatic afferents and cortical activity in the cat. Respir Physiol 90: 213‐226, 1992.
 52. Band DM, Cameron IR, Semple SJ. Effect of different methods of CO2 administration on oscillations of arterial pH in the cat. J Appl Physiol 26: 268‐273, 1969.
 53. Band DM, Linton RA, Kent R, Kurer FL. The effect of peripheral chemodenervation on the ventilatory response to potassium. Respir Physiol 60: 217‐225, 1985.
 54. Band DM, Wolff CB, Ward J, Cochrane GM, Prior J. Respiratory oscillations in arterial carbon dioxide tension as a control signal in exercise. Nature 283: 84‐85, 1980.
 55. Banner N, Guz A, Heaton R, Innes JA, Murphy K, Yacoub M. Ventilatory and circulatory responses at the onset of exercise in man following heart or heart‐lung transplantation. J Physiol 399: 437‐449, 1988.
 56. Bannister RG, Cunningham DJ. The effects on the respiration and performance during exercise of adding oxygen to the inspired air. J Physiol 125: 118‐137, 1954.
 57. Banzett RB, Lansing RW, Brown R, Topulos GP, Yager D, Steele SM, Londono B, Loring SH, Reid MB, Adams L, et al. ‘Air hunger’ from increased PCO2 persists after complete neuromuscular block in humans. Respir Physiol 81: 1‐17, 1990.
 58. Bartlett D Jr. Postnatal growth of the mammalian lung: Influence of exercise and thyroid activity. Respir Physiol 9: 50‐57, 1970.
 59. Bartlett D Jr, Areson JG. Quantitative lung morphology in Japanese waltzing mice. J Appl Physiol 44: 446‐449, 1978.
 60. Bazzy AR, Donnelly DF. Diaphragmatic failure during loaded breathing: Role of neuromuscular transmission. J Appl Physiol 74: 1679‐1683, 1993.
 61. Bazzy AR, Kim YJ. Effect of chronic respiratory load on cytochrome oxidase activity in diaphragmatic fibers. J Appl Physiol 72: 266‐271, 1992.
 62. Bechbache RR, Duffin J. The entrainment of breathing frequency by exercise rhythm. J Physiol 272: 553‐561, 1977.
 63. Bellemare F, Bigland‐Ritchie B. Assessment of human diaphragm strength and activation using phrenic nerve stimulation. Respir Physiol 58: 263‐277, 1984.
 64. Bellemare F, Bigland‐Ritchie B. Central components of diaphragmatic fatigue assessed by phrenic nerve stimulation. J Appl Physiol 62: 1307‐1316, 1987.
 65. Bellemare F, Grassino A. Effect of pressure and timing of contraction on human diaphragm fatigue. J Appl Physiol 53: 1190‐1195, 1982.
 66. Bennett FM, Tallman RD Jr, Grodins FS. Role of VCO2 in control of breathing of awake exercising dogs. J Appl Physiol 56: 1335‐1339, 1984.
 67. Biersteker MW, Biersteker PA. Vital capacity in trained and untrained healthy young adults in the Netherlands. Eur J Appl Physiol 54: 46‐53, 1985.
 68. Bisgard GE, Forster HV, Mesina J, Sarazin RG. Role of the carotid body in hyperpnea of moderate exercise in goats. J Appl Physiol 52: 1216‐1222, 1982.
 69. Bisschop A, Gayan‐Ramirez G, Rollier H, Gosselink R, Dom R, de Bock V, Decramer M. Intermittent inspiratory muscle training induces fiber hypertrophy in rat diaphragm. Am J Respir Crit Care Med 155: 1583‐1589, 1997.
 70. Blain GM, Smith CA, Henderson KS, Dempsey JA. Contribution of the carotid body chemoreceptors to eupneic ventilation in the intact, unanesthetized dog. J Appl Physiol 106: 1564‐1573, 2009.
 71. Bonsignore MR, La Grutta S, Cibella F, Scichilone N, Cuttitta G, Interrante A, Marchese M, Veca M, Virzi M, Bonanno A, Profita M, Morici G. Effects of exercise training and montelukast in children with mild asthma. Med Sci Sports Exerc 40: 405‐412, 2008.
 72. Botelho SY, Cander L. Post‐tetanic potentiation before and during ischemia in intact human skeletal muscle. J Appl Physiol 6: 221‐228, 1953.
 73. Boushel R, Langberg H, Olesen J, Gonzales‐Alonzo J, Bulow J, Kjaer M. Monitoring tissue oxygen availability with near infrared spectroscopy (NIRS) in health and disease. Scand J Med Sci Sports 11: 213‐222, 2001.
 74. Bower JS, Sandercock TG, Rothman E, Abbrecht PH, Dantzker DR. Time domain analysis of diaphragmatic electromyogram during fatigue in men. J Appl Physiol 57: 913‐916, 1984.
 75. Bradley ME, Leith DE. Ventilatory muscle training and the oxygen cost of sustained hyperpnea. J Appl Physiol 45: 885‐892, 1978.
 76. Bradley TD, Chartrand DA, Fitting JW, Killian KJ, Grassino A. The relation of inspiratory effort sensation to fatiguing patterns of the diaphragm. Am Rev Respir Dis 134: 1119‐1124, 1986.
 77. Brice AG, Forster HV, Pan LG, Funahashi A, Lowry TF, Murphy CL, Hoffman MD. Ventilatory and PaCO2 responses to voluntary and electrically induced leg exercise. J Appl Physiol 64: 218‐225, 1988.
 78. Briscoe WA, Dubois AB. The relationship between airway resistance, airway conductance and lung volume in subjects of different age and body size. J Clin Invest 37: 1279‐1285, 1958.
 79. Brown DR, Forster HV, Pan LG, Brice AG, Murphy CL, Lowry TF, Gutting SM, Funahashi A, Hoffman M, Powers S. Ventilatory response of spinal cord‐lesioned subjects to electrically induced exercise. J Appl Physiol 68: 2312‐2321, 1990.
 80. Buchanan GF, Richerson GB. Role of chemoreceptors in mediating dyspnea. Respir Physiol Neurobiol 167: 9‐19, 2009.
 81. Burr ML, Phillips KM, Hurst DN. Lung function in the elderly. Thorax 40: 54‐59, 1985.
 82. Bye PT, Esau SA, Walley KR, Macklem PT, Pardy RL. Ventilatory muscles during exercise in air and oxygen in normal men. J Appl Physiol 56: 464‐471, 1984.
 83. Calbet JA, Gonzalez‐Alonso J, Helge JW, Sondergaard H, Munch‐Andersen T, Boushel R, Saltin B. Cardiac output and leg and arm blood flow during incremental exercise to exhaustion on the cycle ergometer. J Appl Physiol 103: 969‐978, 2007.
 84. Campbell EJ, Howell JB. The sensation of breathlessness. Br Med Bull 19: 36‐40, 1963.
 85.Canadian Institute for Health Information CLA, Health Canada, Statistics Canada. Respiratory Disease in Canada. 2001.
 86. Casaburi R, Storer TW, Wasserman K. Mediation of reduced ventilatory response to exercise after endurance training. J Appl Physiol 63: 1533‐1538, 1987.
 87. Caskey CI, Zerhouni EA, Fishman EK, Rahmouni AD. Aging of the diaphragm: A CT study. Radiology 171: 385‐389, 1989.
 88. Cerny FC, Dempsey JA, Reddan WG. Pulmonary gas exchange in nonnative residents of high altitude. J Clin Invest 52: 2993‐2999, 1973.
 89. Chan ED, Welsh CH. Geriatric respiratory medicine. Chest 114: 1704‐1733, 1998.
 90. Chen HI, Li HT. Physical conditioning can modulate endothelium‐dependent vasorelaxation in rabbits. Arterioscler Thromb 13: 852‐856, 1993.
 91. Chen Z, Eldridge FL, Wagner PG. Respiratory‐associated rhythmic firing of midbrain neurones in cats: Relation to level of respiratory drive. J Physiol 437: 305‐325, 1991.
 92. Chen Z, Eldridge FL, Wagner PG. Respiratory‐associated thalamic activity is related to level of respiratory drive. Respir Physiol 90: 99‐113, 1992.
 93. Chevrolet JC, Tschopp JM, Blanc Y, Rochat T, Junod AF. Alterations in inspiratory and leg muscle force and recovery pattern after a marathon. Med Sci Sports Exerc 25: 501‐507, 1993.
 94. Chonan T, Mulholland MB, Leitner J, Altose MD, Cherniack NS. Sensation of dyspnea during hypercapnia, exercise, and voluntary hyperventilation. J Appl Physiol 68: 2100‐2106, 1990.
 95. Christopherson SK, Hlastala MP. Pulmonary gas exchange during altered density gas breathing. J Appl Physiol 52: 221‐225, 1982.
 96. Clanton TL, Ameredes BT, Thomson DB, Julian MW. Sustainable inspiratory pressures over varying flows, volumes, and duty cycles. J Appl Physiol 69: 1875‐1882, 1990.
 97. Clanton TL, Dixon GF, Drake J, Gadek JE. Effects of swim training on lung volumes and inspiratory muscle conditioning. J Appl Physiol 62: 39‐46, 1987.
 98. Clanton TL, Hartman E, Julian MW. Preservation of sustainable inspiratory muscle pressure at increased end‐expiratory lung volume. Am Rev Respir Dis 147: 385‐391, 1993.
 99. Clark JM, Sinclair RD, Lenox JB. Chemical and nonchemical components of ventilation during hypercapnic exercise in man. J Appl Physiol 48: 1065‐1076, 1980.
 100. Coast JR, Clifford PS, Henrich TW, Stray‐Gundersen J, Johnson RL Jr. Maximal inspiratory pressure following maximal exercise in trained and untrained subjects. Med Sci Sports Exerc 22: 811‐815, 1990.
 101. Coast JR, Haverkamp HC, Finkbone CM, Anderson KL, George SO, Herb RA. Alterations in pulmonary function following exercise are not caused by the work of breathing alone. Int J Sports Med 20: 470‐475, 1999.
 102. Coirault C, Chemla D, Lecarpentier Y. Relaxation of diaphragm muscle. J Appl Physiol 87: 1243‐1252, 1999.
 103. Cole P, Forsyth R, Haight JS. Respiratory resistance of the oral airway. Am Rev Respir Dis 125: 363‐365, 1982.
 104. Collett PW, Perry C, Engel LA. Pressure‐time product, flow, and oxygen cost of resistive breathing in humans. J Appl Physiol 58: 1263‐1272, 1985.
 105. Comroe JHJ, Schmidt CF. Reflexes from the limbs as a factor in the hyperpnea of muscular exercise. Am J Physiol 138: 536‐547, 1943.
 106. Connel DC, Fregosi RF. Influence of nasal airflow and resistance on nasal dilator muscle activities during exercise. J Appl Physiol 74: 2529‐2536, 1993.
 107. Cordain L, Rode EJ, Gotshall RW, Tucker A. Residual lung volume and ventilatory muscle strength changes following maximal and submaximal exercise. Int J Sports Med 15: 158‐161, 1994.
 108. Cordain L, Tucker A, Moon D, Stager JM. Lung volumes and maximal respiratory pressures in collegiate swimmers and runners. Res Q Exerc Sport 61: 70‐74, 1990.
 109. Courteix D, Obert P, Lecoq AM, Guenon P, Koch G. Effect of intensive swimming training on lung volumes, airway resistance and on the maximal expiratory flow‐volume relationship in prepubertal girls. Eur J Appl Physiol 76: 264‐269, 1997.
 110. Coxson HO, Chan IH, Mayo JR, Hlynsky J, Nakano Y, Birmingham CL. Early emphysema in patients with anorexia nervosa. Am J Respir Crit Care Med 170: 748‐752, 2004.
 111. Crater SE, Platts‐Mills TA. Searching for the cause of the increase in asthma. Curr Opin Pediatr 10: 594‐599, 1998.
 112. Cross BA, Davey A, Guz A, Katona PG, MacLean M, Murphy K, Semple SJ, Stidwill R. The role of spinal cord transmission in the ventilatory response to electrically induced exercise in the anaesthetized dog. J Physiol 329: 37‐55, 1982.
 113. Cunningham DJ, Hey EN, Lloyd BB. The effect of intravenous infusion of noradrenaline on the respiratory response to carbon dioxide in man. Q J Exp Physiol Cogn Med Sci 43: 394‐399, 1958.
 114. Davenport PW, Vovk A. Cortical and subcortical central neural pathways in respiratory sensations. Respir Physiol Neurobiol 167: 72‐86, 2009.
 115. Davies CT, White MJ. Muscle weakness following dynamic exercise in humans. J Appl Physiol 53: 236‐241, 1982.
 116. Davis JA, Frank MH, Whipp BJ, Wasserman K. Anaerobic threshold alterations caused by endurance training in middle‐aged men. J Appl Physiol 46: 1039‐1046, 1979.
 117. Dayer MJ, Hopkinson NS, Ross ET, Jonville S, Sharshar T, Kearney M, Moxham J, Polkey MI. Does symptom‐limited cycle exercise cause low frequency diaphragm fatigue in patients with heart failure? Eur J Heart Fail 8: 68‐73, 2006.
 118. Dayer MJ, Jonville S, Chatwin M, Swallow EB, Porcher R, Sharshar T, Ross ET, Hopkinson NS, Moxham J, Polkey MI. Exercise‐induced depression of the diaphragm motor evoked potential is not affected by non‐invasive ventilation. Respir Physiol Neurobiol 155: 243‐254, 2007.
 119. De Ruiter CJ, Jones DA, Sargeant AJ, De Haan A. The measurement of force/velocity relationships of fresh and fatigued human adductor pollicis muscle. Eur J Appl Physiol 80: 386‐393, 1999.
 120. de Torres JP, Casanova C, Montejo de Garcini A, Aguirre‐Jaime A, Celli BR. Gender and respiratory factors associated with dyspnea in chronic obstructive pulmonary disease. Respir Res 8: 18, 2007.
 121. De Troyer A, Estenne M, Ninane V, Van Gansbeke D, Gorini M. Transversus abdominis muscle function in humans. J Appl Physiol 68: 1010‐1016, 1990.
 122. De Troyer A, Kelly S. Chest wall mechanics in dogs with acute diaphragm paralysis. J Appl Physiol 53: 373‐379, 1982.
 123. De Troyer A, Wilson TA. Effect of acute inflation on the mechanics of the inspiratory muscles. J Appl Physiol 107: 315‐323, 2009.
 124. DeGraff AC Jr, Grover RF, Johnson RL Jr, Hammond JW Jr, Miller JM. Diffusing capacity of the lung in Caucasians native to 3100 m. J Appl Physiol 29: 71‐76, 1970.
 125. DeLorey DS, Babb TG. Progressive mechanical ventilatory constraints with aging. Am J Respir Crit Care Med 160: 169‐177, 1999.
 126. Dempsey JA. J.B. Wolffe memorial lecture. Is the lung built for exercise? Med Sci Sports Exerc 18: 143‐155, 1986.
 127. Dempsey JA, Adams L, Ainsworth DM, Fregosi RF, Gallagher CG, Guz A, Johnson BD, Powers SK. Airway, lung and respiratory muscle function during exercise. In: Rowell LB, Shepherd JT, editors. Handbook of Physiology: Exercise: Regulation and Integration of Multiple Systems. New York: Oxford University Press, 1996, pp. 448‐514.
 128. Dempsey JA, Forster HV, Ainsworth DM. Regulation of hyperpnea, hyperventilation and respiratory muscle recruitment during exercise. In: Dempsey JA, Pack AI, editors. Regulation of Breathing. New York: Marcel Dekker, 1995, pp. 1065‐1134.
 129. Dempsey JA, Hanson PG, Henderson KS. Exercise‐induced arterial hypoxaemia in healthy human subjects at sea level. J Physiol 355: 161‐175, 1984.
 130. Dempsey JA, Reddan WG, Birnbaum ML, Forster HV, Thoden JS, Grover RF, Rankin J. Effects of acute through life‐long hypoxic exposure on exercise pulmonary gas exchange. Respir Physiol 13: 62‐89, 1971.
 131. Dempsey JA, Romer L, Rodman J, Miller J, Smith C. Consequences of exercise‐induced respiratory muscle work. Respir Physiol Neurobiol 151: 242‐250, 2006.
 132. Dempsey JA, Vidruk EH, Mitchell GS. Pulmonary control systems in exercise: Update. Fed Proc 44: 2260‐2270, 1985.
 133. Dempsey JA, Wagner PD. Exercise‐induced arterial hypoxemia. J Appl Physiol 87: 1997‐2006, 1999.
 134. Derchak PA, Sheel AW, Morgan BJ, Dempsey JA. Effects of expiratory muscle work on muscle sympathetic nerve activity. J Appl Physiol 92: 1539‐1552, 2002.
 135. Dodd DS, Yarom J, Loring SH, Engel LA. O2 cost of inspiratory and expiratory resistive breathing in humans. J Appl Physiol 65: 2518‐2523, 1988.
 136. Dodd SL, Powers SK, Thompson D, Landry G, Lawler J. Exercise performance following intense, short‐term ventilatory work. Int J Sports Med 10: 48‐52, 1989.
 137. Doherty M, Dimitriou L. Comparison of lung volume in Greek swimmers, land‐based athletes, and sedentary controls using allometric scaling. Brit J Sports Med 31: 337‐341, 1997.
 138. Duffin J, Bechbache RR, Goode RC, Chung SA. The ventilatory response to carbon dioxide in hyperoxic exercise. Respir Physiol 40: 93‐105, 1980.
 139. Duron B. Intercostal and diaphragmatic muscle afferents. In: Hornbein TF, editor. Regulation of Breathing. New York: Marcel Decker, 1981, pp. 473‐540.
 140. Eckberg DL, Nerhed C, Wallin BG. Respiratory modulation of muscle sympathetic and vagal cardiac outflow in man. J Physiol 365: 181‐196, 1985.
 141. Edwards AM, Cooke CB. Oxygen uptake kinetics and maximal aerobic power are unaffected by inspiratory muscle training in healthy subjects where time to exhaustion is extended. Eur J Appl Physiol 93: 139‐144, 2004.
 142. Edwards AM, Wells C, Butterly R. Concurrent inspiratory muscle and cardiovascular training differentially improves both perceptions of effort and 5000 m running performance compared with cardiovascular training alone. Brit J Sports Med 42: 823‐827, 2008.
 143. Edwards RH, Hill DK, Jones DA, Merton PA. Fatigue of long duration in human skeletal muscle after exercise. J Physiol 272: 769‐778, 1977.
 144. Edwards RHT. Human muscle function and fatigue. In: Porter R, Whelan J, editors. Human Muscle Fatigue: Physiological Mechanisms. London: Pitman, 1981, pp. 1‐18.
 145. Eiken O, Bjurstedt H. Dynamic exercise in man as influenced by experimental restriction of blood flow in the working muscles. Acta Physiol Scand 131: 339‐345, 1987.
 146. Ekblom B. Effect of physical training in adolescent boys. J Appl Physiol 27: 350‐355, 1969.
 147. El‐Manshawi A, Killian KJ, Summers E, Jones NL. Breathlessness during exercise with and without resistive loading. J Appl Physiol 61: 896‐905, 1986.
 148. Eldridge FL, Millhorn DE, Kiley JP, Waldrop TG. Stimulation by central command of locomotion, respiration and circulation during exercise. Respir Physiol 59: 313‐337, 1985.
 149. Eldridge FL, Millhorn DE, Waldrop TG. Exercise hyperpnea and locomotion: Parallel activation from the hypothalamus. Science 211: 844‐846, 1981.
 150. England SJ, Bartlett D Jr. Changes in respiratory movements of the human vocal cords during hyperpnea. J Appl Physiol 52: 780‐785, 1982.
 151. England SJ, Bartlett D Jr, Knuth SL. Comparison of human vocal cord movements during isocapnic hypoxia and hypercapnia. J Appl Physiol 53: 81‐86, 1982.
 152. Engstrom I, Eriksson BO, Karlberg P, Saltin B, Thoren C. Preliminary report on the development of lung volumes in young girls swimmers. Acta Paed Scand S217: 73‐76, 1977.
 153. Enright PL, Kronmal RA, Manolio TA, Schenker MB, Hyatt RE. Respiratory muscle strength in the elderly. Correlates and reference values. Cardiovascular Health Study Research Group. Am J Respir Crit Care Med 149: 430‐438, 1994.
 154. Erickson BK, Forster HV, Pan LG, Lowry TF, Brown DR, Forster MA, Forster AL. Ventilatory compensation for lactacidosis in ponies: Role of carotid chemoreceptors and lung afferents. J Appl Physiol 70: 2619‐2626, 1991.
 155. Esau SA, Bye PT, Pardy RL. Changes in rate of relaxation of sniffs with diaphragmatic fatigue in humans. J Appl Physiol 55: 731‐735, 1983.
 156. Everett AD, Le Cras TD, Xue C, Johns RA. eNOS expression is not altered in pulmonary vascular remodeling due to increased pulmonary blood flow. Am J Physiol 274: L1058‐L1065, 1998.
 157. Fanta CH, Leith DE, Brown R. Maximal shortening of inspiratory muscles: Effect of training. J Appl Physiol 54: 1618‐1623, 1983.
 158. Feldman JL, Del Negro CA. Looking for inspiration: New perspectives on respiratory rhythm. Nat Rev 7: 232‐242, 2006.
 159. Fenn WO, Marsh BS. Muscular force at different speeds of shortening. J Physiol 85: 277‐297, 1935.
 160. Fernandes A, Galbo H, Kjaer M, Mitchell JH, Secher NH, Thomas SN. Cardiovascular and ventilatory responses to dynamic exercise during epidural anaesthesia in man. J Physiol 420: 281‐293, 1990.
 161. Field S, Kelly SM, Macklem PT. The oxygen cost of breathing in patients with cardiorespiratory disease. Am Rev Respir Dis 126: 9‐13, 1982.
 162. Fitch KD, Sue‐Chu M, Anderson SD, Boulet LP, Hancox RJ, McKenzie DC, Backer V, Rundell KW, Alonso JM, Kippelen P, Cummiskey JM, Garnier A, Ljungqvist A. Asthma and the elite athlete: Summary of the International Olympic Committee's consensus conference, Lausanne, Switzerland, January 22‐24, 2008. J Allergy Clin Immun 122: 254‐260, 260 e251‐257, 2008.
 163. Fitting JW, Bradley TD, Easton PA, Lincoln MJ, Goldman MD, Grassino A. Dissociation between diaphragmatic and rib cage muscle fatigue. J Appl Physiol 64: 959‐965, 1988.
 164. Flandrois R, Favier R, Pequignot JM. Role of adrenaline in gas exchanges and respiratory control in the dog at rest and exercise. Respir Physiol 30: 291‐303, 1977.
 165. Forster HV. Exercise hyperpnea: Where do we go from here? Exerc Sport Sci Rev 28: 133‐137, 2000.
 166. Forster HV, Pan LG. Control of breathing during exercise. In: Crystal RG, West JB, Weibel ER, Barnes PJ, editors. The Lung: Scientific Foundations. Philadelphia: Lippincott‐Raven Publishers, 1997, pp. 2001‐2010.
 167. Forsyth RD, Cole P, Shephard RJ. Exercise and nasal patency. J Appl Physiol 55: 860‐865, 1983.
 168. Franch J, Madsen K, Djurhuus MS, Pedersen PK. Improved running economy following intensified training correlates with reduced ventilatory demands. Med Sci Sports Exerc 30: 1250‐1256, 1998.
 169. Fredberg JJ, Inouye D, Miller B, Nathan M, Jafari S, Raboudi SH, Butler JP, Shore SA. Airway smooth muscle, tidal stretches, and dynamically determined contractile states. Am J Respir Crit Care Med 156: 1752‐1759, 1997.
 170. Frisancho AR. Functional adaptation to high altitude hypoxia. Science 187: 313‐319, 1975.
 171. Galbo H, Kjaer M, Secher NH. Cardiovascular, ventilatory and catecholamine responses to maximal dynamic exercise in partially curarized man. J Physiol 389: 557‐568, 1987.
 172. Gallagher CG, Younes M. Effect of pressure assist on ventilation and respiratory mechanics in heavy exercise. J Appl Physiol 66: 1824‐1837, 1989.
 173. Gandevia SC, Killian KJ, Campbell EJ. The effect of respiratory muscle fatigue on respiratory sensations. Clin Sci 60: 463‐466, 1981.
 174. Gandevia SC, Macefield G. Projection of low‐threshold afferents from human intercostal muscles to the cerebral cortex. Respir Physiol 77: 203‐214, 1989.
 175. Gandevia SC, McKenzie DK. Activation of the human diaphragm during maximal static efforts. J Physiol 367: 45‐56, 1985.
 176. Gandevia SC, Rothwell JC. Activation of the human diaphragm from the motor cortex. J Physiol 384: 109‐118, 1987.
 177. Gaultier C, Crapo R. Effects of nutrition, growth hormone disturbances, training, altitude and sleep on lung volumes. Eur Respir J 10: 2913‐2919, 1997.
 178. Gea J, Hamid Q, Czaika G, Zhu E, Mohan‐Ram V, Goldspink G, Grassino A. Expression of myosin heavy‐chain isoforms in the respiratory muscles following inspiratory resistive breathing. Am J Respir Crit Care Med 161: 1274‐1278, 2000.
 179. Gea JG. Myosin gene expression in the respiratory muscles. Eur Respir J 10: 2404‐2410, 1997.
 180. Gething AD, Williams M, Davies B. Inspiratory resistive loading improves cycling capacity: A placebo controlled trial. Brit J Sports Med 38: 730‐736, 2004.
 181. Goldman MD, Grimby G, Mead J. Mechanical work of breathing derived from rib cage and abdominal V‐P partitioning. J Appl Physiol 41: 752‐763, 1976.
 182. Gonzalez NC, Kirkton SD, Howlett RA, Britton SL, Koch LG, Wagner HE, Wagner PD. Continued divergence in VO2max of rats artificially selected for running endurance is mediated by greater convective blood O2 delivery. J Appl Physiol 101: 1288‐1296, 2006.
 183. Grassino A, Bellemare F, Laporta D. Diaphragm fatigue and the strategy of breathing in COPD. Chest 85: 51S‐54S, 1984.
 184. Grassino AE, Derenne JP, Almirall J, Milic‐Emili J, Whitelaw W. Configuration of the chest wall and occlusion pressures in awake humans. J Appl Physiol 50: 134‐142, 1981.
 185. Green M, Mead J, Turner JM. Variability of maximum expiratory flow‐volume curves. J Appl Physiol 37: 67‐74, 1974.
 186. Greksa LP, Spielvogel H, Paz‐Zamora M, Caceres E, Paredes‐Fernandez L. Effect of altitude on the lung function of high altitude residents of European ancestry. Am J Phys Anthropol 75: 77‐85, 1988.
 187. Griffiths LA, McConnell AK. The influence of inspiratory and expiratory muscle training upon rowing performance. Eur J Appl Physiol 99: 457‐466, 2007.
 188. Grimby G, Bunn J, Mead J. Relative contribution of rib cage and abdomen to ventilation during exercise. J Appl Physiol 24: 159‐166, 1968.
 189. Grimby G, Goldman M, Mead J. Respiratory muscle action inferred from rib cage and abdominal V‐P partitioning. J Appl Physiol 41: 739‐751, 1976.
 190. Grinton S, Powers SK, Lawler J, Criswell D, Dodd S, Edwards W. Endurance training‐induced increases in expiratory muscle oxidative capacity. Med Sci Sports Exerc 24: 551‐555, 1992.
 191. Griscom NT, Wohl ME. Dimensions of the growing trachea related to body height. Length, anteroposterior and transverse diameters, cross‐sectional area, and volume in subjects younger than 20 years of age. Am Rev Respir Dis 131: 840‐844, 1985.
 192. Griscom NT, Wohl ME. Dimensions of the growing trachea related to age and gender. Am J Rot 146: 233‐237, 1986.
 193. Gross D, Grassino A, Ross WR, Macklem PT. Electromyogram pattern of diaphragmatic fatigue. J Appl Physiol 46: 1‐7, 1979.
 194. Guenette JA, Dominelli PB, Reeve SS, Durkin CM, Eves ND, Sheel AW. Effect of thoracic gas compression and bronchodilation on the assessment of expiratory flow limitation during exercise in healthy humans. Respir Physiol Neurobiol 170: 279‐286, 2010.
 195. Guenette JA, Querido JS, Eves ND, Chua R, Sheel AW. Sex differences in the resistive and elastic work of breathing during exercise in endurance‐trained athletes. Am J Physiol Regul Integr Comp Physiol 297: R166‐R175, 2009.
 196. Guenette JA, Romer LM, Querido JS, Chua R, Eves ND, Road JD, McKenzie DC, Sheel AW. Sex differences in exercise‐induced diaphragmatic fatigue in endurance‐trained athletes. J Appl Physiol 109: 35‐46, 2010.
 197. Guenette JA, Vogiatzis I, Zakynthinos S, Athanasopoulos D, Koskolou M, Golemati S, Vasilopoulou M, Wagner HE, Roussos C, Wagner PD, Boushel R. Human respiratory muscle blood flow measured by near‐infrared spectroscopy and indocyanine green. J Appl Physiol 104: 1202‐1210, 2008.
 198. Guenette JA, Witt JD, McKenzie DC, Road JD, Sheel AW. Respiratory mechanics during exercise in endurance‐trained men and women. J Physiol 581: 1309‐1322, 2007.
 199. Guyenet PG. The 2008 Carl Ludwig Lecture: Retrotrapezoid nucleus, CO2 homeostasis, and breathing automaticity. J Appl Physiol 105: 404‐416, 2008.
 200. Guyenet PG. Neural structures that mediate sympathoexcitation during hypoxia. Respir Physiol 121: 147‐162, 2000.
 201. Habazettl H, Athanasopoulos D, Kuebler WM, Wagner HE, Roussos C, Wagner PD, Ungruhe J, Zakynthinos SG, Vogiatzis I. Near‐infrared spectroscopy and indocyanine green derived blood flow index for non‐invasive measurement of muscle perfusion during exercise. J Appl Physiol 108(4): 962‐967, 2010.
 202. Hagberg JM, Coyle EF, Carroll JE, Miller JM, Martin WH, Brooke MH. Exercise hyperventilation in patients with McArdle's disease. J Appl Physiol 52: 991‐994, 1982.
 203. Hagberg JM, Yerg JE II, Seals DR. Pulmonary function in young and older athletes and untrained men. J Appl Physiol 65: 101‐105, 1988.
 204. Hamilton AL, Killian KJ, Summers E, Jones NL. Symptom intensity and subjective limitation to exercise in patients with cardiorespiratory disorders. Chest 110: 1255‐1263, 1996.
 205. Hamnegard CH, Wragg S, Kyroussis D, Mills GH, Polkey MI, Moran J, Road J, Bake B, Green M, Moxham J. Diaphragm fatigue following maximal ventilation in man. Eur Respir J 9: 241‐247, 1996.
 206. Haouzi P. Counterpoint: Supraspinal locomotor centers do not contribute significantly to the hyperpnea of dynamic exercise. J Appl Physiol 100: 1079‐1082; discussion 1082‐1073, 2006a.
 207. Haouzi P. Theories on the nature of the coupling between ventilation and gas exchange during exercise. Respir Physiol Neurobiol 151: 267‐279, 2006b.
 208. Haouzi P, Chenuel B, Huszczuk A. Sensing vascular distension in skeletal muscle by slow conducting afferent fibers: Neurophysiological basis and implication for respiratory control. J Appl Physiol 96: 407‐418, 2004.
 209. Haouzi P, Fukuba Y, Casaburi R, Stringer W, Wasserman K. O2 uptake kinetics above and below the lactic acidosis threshold during sinusoidal exercise. J Appl Physiol 75: 1683‐1690, 1993.
 210. Harms CA, Babcock MA, McClaran SR, Pegelow DF, Nickele GA, Nelson WB, Dempsey JA. Respiratory muscle work compromises leg blood flow during maximal exercise. J Appl Physiol 82: 1573‐1583, 1997.
 211. Harms CA, Stager JM. Low chemoresponsiveness and inadequate hyperventilation contribute to exercise‐induced hypoxemia. J Appl Physiol 79: 575‐580, 1995.
 212. Harms CA, Wetter TJ, McClaran SR, Pegelow DF, Nickele GA, Nelson WB, Hanson P, Dempsey JA. Effects of respiratory muscle work on cardiac output and its distribution during maximal exercise. J Appl Physiol 85: 609‐618, 1998.
 213. Harms CA, Wetter TJ, St Croix CM, Pegelow DF, Dempsey JA. Effects of respiratory muscle work on exercise performance. J Appl Physiol 89: 131‐138, 2000.
 214. Hart N, Laffont I, de la Sota AP, Lejaille M, Macadou G, Polkey MI, Denys P, Lofaso F. Respiratory effects of combined truncal and abdominal support in patients with spinal cord injury. Arch Phys Med Rehab 86: 1447‐1451, 2005.
 215. Hart N, Nickol AH, Cramer D, Ward SP, Lofaso F, Pride NB, Moxham J, Polkey MI. Effect of severe isolated unilateral and bilateral diaphragm weakness on exercise performance. Am J Respir Crit Care Med 165: 1265‐1270, 2002.
 216. Hayashi F, McCrimmon DR. Respiratory motor responses to cranial nerve afferent stimulation in rats. Am J Physiol 271: R1054‐R1062, 1996.
 217. Heigenhauser GJ, Sutton JR, Jones NL. Effect of glycogen depletion on the ventilatory response to exercise. J Appl Physiol 54: 470‐474, 1983.
 218. Helenius I, Lumme A, Haahtela T. Asthma, airway inflammation and treatment in elite athletes. Sports Med 35: 565‐574, 2005.
 219. Helenius I, Rytila P, Sarna S, Lumme A, Helenius M, Remes V, Haahtela T. Effect of continuing or finishing high‐level sports on airway inflammation, bronchial hyperresponsiveness, and asthma: A 5‐year prospective follow‐up study of 42 highly trained swimmers. J Allergy Clin Immunol 109: 962‐968, 2002.
 220. Henke KG, Sharratt M, Pegelow D, Dempsey JA. Regulation of end‐expiratory lung volume during exercise. J Appl Physiol 64: 135‐146, 1988.
 221. Hewitt M, Estell K, Davis IC, Schwiebert LM. Repeated bouts of moderate‐intensity aerobic exercise reduce airway reactivity in a murine asthma model. Am J Respir Cell Mol Biol 42: 243‐249, 2010.
 222. Hill JM. Discharge of group IV phrenic afferent fibers increases during diaphragmatic fatigue. Brain Res 856: 240‐244, 2000.
 223. Hill NS, Jacoby C, Farber HW. Effect of an endurance triathlon on pulmonary function. Med Sci Sports Exerc 23: 1260‐1264, 1991.
 224. Hoffstein V. Relationship between lung volume, maximal expiratory flow, forced expiratory volume in one second, and tracheal area in normal men and women. Am Rev Respir Dis 134: 956‐961, 1986.
 225. Hogan MC, Grassi B, Samaja M, Stary CM, Gladden LB. Effect of contraction frequency on the contractile and noncontractile phases of muscle venous blood flow. J Appl Physiol 95: 1139‐1144, 2003.
 226. Holm P, Sattler A, Fregosi RF. Endurance training of respiratory muscles improves cycling performance in fit young cyclists. BMC Physiol 4: 9, 2004.
 227. Hopkinson NS, Dayer MJ, Moxham J, Polkey MI. Abdominal muscle fatigue following exercise in chronic obstructive pulmonary disease. Respir Res 11: 15, 2010.
 228. Hornbein TF, Schoene RB. High Altitude. New York: Marcel Dekker, Inc., 2001.
 229. Hornbein TF, Sorensen SC, Parks CR. Role of muscle spindles in lower extremities in breathing during bicycle exercise. J Appl Physiol 27: 476‐479, 1969.
 230. Howlett RA, Kirkton SD, Gonzalez NC, Wagner HE, Britton SL, Koch LG, Wagner PD. Peripheral oxygen transport and utilization in rats following continued selective breeding for endurance running capacity. J Appl Physiol 106: 1819‐1825, 2009.
 231. Hsia CC, Fryder‐Doffey F, Stalder‐Nayarro V, Johnson RL Jr, Reynolds RC, Weibel ER. Structural changes underlying compensatory increase of diffusing capacity after left pneumonectomy in adult dogs. J Clin Invest 92: 758‐764, 1993.
 232. Hsia CC, Johnson RL Jr, Wu EY, Estrera AS, Wagner H, Wagner PD. Reducing lung strain after pneumonectomy impairs oxygen diffusing capacity but not ventilation‐perfusion matching. J Appl Physiol 95: 1370‐1378, 2003.
 233. Hubmayr RD, Litchy WJ, Gay PC, Nelson SB. Transdiaphragmatic twitch pressure. Effects of lung volume and chest wall shape. Am Rev Respir Dis 139: 647‐652, 1989.
 234. Hughes EF, Turner SC, Brooks GA. Effects of glycogen depletion and pedaling speed on “anaerobic threshold”. J Appl Physiol 52: 1598‐1607, 1982.
 235. Hunter SK. Sex differences and mechanisms of task‐specific muscle fatigue. Exerc Sport Sci Rev 37: 113‐122, 2009.
 236. Hussain SN, Chatillon A, Comtois A, Roussos C, Magder S. Chemical activation of thin‐fiber phrenic afferents. 2. Cardiovascular responses. J Appl Physiol 70: 77‐86, 1991.
 237. Huszczuk A, Whipp BJ, Adams TD, Fisher AG, Crapo RO, Elliott CG, Wasserman K, Olsen DB. Ventilatory control during exercise in calves with artificial hearts. J Appl Physiol 68: 2604‐2611, 1990.
 238. Ingram RH Jr, Schilder DP. Effect of gas compression on pulmonary pressure, flow, and volume relationship. J Appl Physiol 21: 1821‐1826, 1966a.
 239. Ingram RH Jr, Schilder DP. Effect of thoracic gas compression on the flow‐volume curve of the forced vital capacity. Am Rev Respir Dis 94: 56‐63, 1966b.
 240. Inman MD, Watson RM, Killian KJ, and O'Byrne PM. Methacholine airway responsiveness decreases during exercise in asthmatic subjects. Am Rev Respir Dis 141: 1414‐1417, 1990.
 241. Jakes RW, Day NE, Patel B, Khaw KT, Oakes S, Luben R, Welch A, Bingham S, Wareham NJ. Physical inactivity is associated with lower forced expiratory volume in 1 second: European Prospective Investigation into Cancer‐Norfolk Prospective Population Study. Am J Epidem 156: 139‐147, 2002.
 242. Jammes Y, Balzamo E. Changes in afferent and efferent phrenic activities with electrically induced diaphragmatic fatigue. J Appl Physiol 73: 894‐902, 1992.
 243. Jensen D, Ofir D, O'Donnell DE. Effects of pregnancy, obesity and aging on the intensity of perceived breathlessness during exercise in healthy humans. Respir Physiol Neurobiol 167: 87‐100, 2009.
 244. Johansson JE. Ueber die einwirkung der muskeltaetigkeit auf di atmung und die herztaegkeit. Skand Arch Physiol 5: 20‐66, 1893.
 245. Johnson BD, Aaron EA, Babcock MA, Dempsey JA. Respiratory muscle fatigue during exercise: Implications for performance. Med Sci Sports Exerc 28: 1129‐1137, 1996.
 246. Johnson BD, Babcock MA, Suman OE, Dempsey JA. Exercise‐induced diaphragmatic fatigue in healthy humans. J Physiol 460: 385‐405, 1993.
 247. Johnson BD, Beck KC, Olson LJ, O'Malley KA, Allison TG, Squires RW, Gau GT. Ventilatory constraints during exercise in patients with chronic heart failure. Chest 117: 321‐332, 2000.
 248. Johnson BD, Beck KC, Zeballos RJ, Weisman IM. Advances in pulmonary laboratory testing. Chest 116: 1377‐1387, 1999.
 249. Johnson BD, Reddan WG, Pegelow DF, Seow KC, Dempsey JA. Flow limitation and regulation of functional residual capacity during exercise in a physically active aging population. Am Rev Respir Dis 143: 960‐967, 1991.
 250. Johnson BD, Reddan WG, Seow KC, Dempsey JA. Mechanical constraints on exercise hyperpnea in a fit aging population. Am Rev Respir Dis 143: 968‐977, 1991.
 251. Johnson BD, Saupe KW, Dempsey JA. Mechanical constraints on exercise hyperpnea in endurance athletes. J Appl Physiol 73: 874‐886, 1992.
 252. Johnson BD, Scanlon PD, Beck KC. Regulation of ventilatory capacity during exercise in asthmatics. J Appl Physiol 79: 892‐901, 1995.
 253. Johnson BD, Weisman IM, Zeballos RJ, Beck KC. Emerging concepts in the evaluation of ventilatory limitation during exercise: The exercise tidal flow‐volume loop. Chest 116: 488‐503, 1999.
 254. Johnson LR, Laughlin MH. Chronic exercise training does not alter pulmonary vasorelaxation in normal pigs. J Appl Physiol 88: 2008‐2014, 2000.
 255. Johnson LR, Rush JW, Turk JR, Price EM, Laughlin MH. Short‐term exercise training increases ACh‐induced relaxation and eNOS protein in porcine pulmonary arteries. J Appl Physiol 90: 1102‐1110, 2001.
 256. Johnson MA, Sharpe GR, Brown PI. Inspiratory muscle training improves cycling time‐trial performance and anaerobic work capacity but not critical power. Eur J Appl Physiol 101: 761‐770, 2007.
 257. Jones DA. High‐and low‐frequency fatigue revisited. Acta Physiol Scand 156: 265‐270, 1996.
 258. Jones DA, de Ruiter CJ, de Haan A. Change in contractile properties of human muscle in relationship to the loss of power and slowing of relaxation seen with fatigue. J Physiol 576: 913‐922, 2006.
 259. Jones DA, Turner DL, McIntyre DB, Newham DJ. Energy turnover in relation to slowing of contractile properties during fatiguing contractions of the human anterior tibialis muscle. J Physiol 587: 4329‐4338, 2009.
 260. Jones NL, Killian KJ. Exercise limitation in health and disease. New Eng J Med 343: 632‐641, 2000.
 261. Kabitz HJ, Walker D, Schwoerer A, Sonntag F, Walterspacher S, Roecker K, Windisch W. New physiological insights into exercise‐induced diaphragmatic fatigue. Respir Physiol Neurobiol 158: 88‐96, 2007.
 262. Kabitz HJ, Walker D, Sonntag F, Walterspacher S, Kirchberger A, Burgardt V, Roecker K, Windisch W. Post‐exercise diaphragm shielding: A novel approach to exercise‐induced diaphragmatic fatigue. Respir Physiol Neurobiol 162: 230‐237, 2008.
 263. Kaehny WD, Jackson JT. Respiratory response to HCl acidosis in dogs after carotid body denervation. J Appl Physiol 46: 1138‐1142, 1979.
 264. Kao FF. An experimental study of the pathways involved in exercise hyperpnea employing cross‐circulation techniques. In: Cunningham DJC, Lloyd BB, editors. The Regulation of Human Respiration. Philadelphia: F.A. Davis, Co., 1963, pp. 461‐502.
 265. Kao FF. The peripheral neurogenic drive: An experimental study. In: Dempsey JA, Deed CA, editors. Muscular Exercise and the Lung. Madison, WI: University of Wisconsin Press, 1977, pp. 71‐85.
 266. Karjalainen EM, Laitinen A, Sue‐Chu M, Altraja A, Bjermer L, Laitinen LA. Evidence of airway inflammation and remodeling in ski athletes with and without bronchial hyperresponsiveness to methacholine. Am J Respir Crit Care Med 161: 2086‐2091, 2000.
 267. Katsura H, Yamada K, Wakabayashi R, Kida K. Gender‐associated differences in dyspnoea and health‐related quality of life in patients with chronic obstructive pulmonary disease. Respirology 12: 427‐432, 2007.
 268. Kaufman M, Forster, HV. Reflexes Controlling Circulatory, Ventilatory and Airway Responses to Exercise. New York: Oxford University Press for the American Physiological Society, 1996, p. 381‐447.
 269. Kaufman MP, Rybicki KJ, Mitchell JH. Hindlimb muscular contraction reflexly decreases total pulmonary resistance in dogs. J Appl Physiol 59: 1521‐1526, 1985.
 270. Kay JM, de Sa DJ, Mancer JF. Ultrastructure of lung in pulmonary veno‐occlusive disease. Hum Pathol 14: 451‐456, 1983.
 271. Kay JM, Edwards FR. Ultrastructure of the alveolar capillary wall in mitral stenosis. J Pathol 109: Pvi, 1973.
 272. Keens TG, Chen V, Patel P, O'Brien P, Levison H, Ianuzzo CD. Cellular adaptations of the ventilatory muscles to a chronic increased respiratory load. J Appl Physiol 44: 905‐908, 1978.
 273. Kiernan MC, Lin CS, Burke D. Differences in activity‐dependent hyperpolarization in human sensory and motor axons. J Physiol 558: 341‐349, 2004.
 274. Kilding AE, Brown S, McConnell AK. Inspiratory muscle training improves 100 and 200 m swimming performance. Eur J Appl Physiol 108: 505‐511, 2010.
 275. Killian KJ, Gandevia SC, Summers E, Campbell EJ. Effect of increased lung volume on perception of breathlessness, effort, and tension. J Appl Physiol 57: 686‐691, 1984.
 276. Kirkton SD, Howlett RA, Gonzalez NC, Giuliano PG, Britton SL, Koch LG, Wagner HE, Wagner PD. Continued artificial selection for running endurance in rats is associated with improved lung function. J Appl Physiol 106: 1810‐1818, 2009.
 277. Klas JV, Dempsey JA. Voluntary versus reflex regulation of maximal exercise flow: Volume loops. Am Rev Respir Dis 139: 150‐156, 1989.
 278. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow‐volume curve with growth and aging. Am Rev Respir Dis 127: 725‐734, 1983.
 279. Kocis KC, Radell PJ, Sternberger WI, Benson JE, Traystman RJ, Nichols DG. Ultrasound evaluation of piglet diaphragm function before and after fatigue. J Appl Physiol 83: 1654‐1659, 1997.
 280. Konno K, Mead J. Measurement of the separate volume changes of rib cage and abdomen during breathing. J Appl Physiol 22: 407‐422, 1967.
 281. Koulouris N, Mulvey DA, Laroche CM, Goldstone J, Moxham J, Green M. The effect of posture and abdominal binding on respiratory pressures. Eur Respir J 2: 961‐965, 1989.
 282. Kowalchuk JM, Rossiter HB, Ward SA, Whipp BJ. The effect of resistive breathing on leg muscle oxygenation using near‐infrared spectroscopy during exercise in men. Exp Physiol 87: 601‐611, 2002.
 283. Krishnan B, Zintel T, McParland C, Gallagher CG. Lack of importance of respiratory muscle load in ventilatory regulation during heavy exercise in humans. J Physiol 490: 537‐550, 1996.
 284. Krogh A, Lindhard J. The regulation of respiration and circulation during the initial stages of work. J Physiol 47: 112‐136, 1913.
 285. Kuebler WM. How NIR is the future in blood flow monitoring? J Appl Physiol 104: 905‐906, 2008.
 286. Kufel TJ, Pineda LA, Junega RG, Hathwar R, Mador MJ. Diaphragmatic function after intense exercise in congestive heart failure patients. Eur Respir J 20: 1399‐1405, 2002.
 287. Kufel TJ, Pineda LA, Mador MJ. Comparison of potentiated and unpotentiated twitches as an index of muscle fatigue. Muscle Nerve 25: 438‐444, 2002.
 288. Kuna ST, Day RA, Insalaco G, Villeponteaux RD. Posterior cricoarytenoid activity in normal adults during involuntary and voluntary hyperventilation. J Appl Physiol 70: 1377‐1385, 1991.
 289. Kyroussis D, Mills GH, Polkey MI, Hamnegard CH, Koulouris N, Green M, Moxham J. Abdominal muscle fatigue after maximal ventilation in humans. J Appl Physiol 81: 1477‐1483, 1996.
 290. Kyroussis D, Mills GH, Polkey MI, Hamnegard CH, Wragg S, Road J, Green M, Moxham J. Effect of maximum ventilation on abdominal muscle relaxation rate. Thorax 51: 510‐515, 1996.
 291. Kyroussis D, Polkey MI, Keilty SE, Mills GH, Hamnegard CH, Moxham J, Green M. Exhaustive exercise slows inspiratory muscle relaxation rate in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 153: 787‐793, 1996.
 292. Laghi F, D'Alfonso N, Tobin MJ. Pattern of recovery from diaphragmatic fatigue over 24 hours. J Appl Physiol 79: 539‐546, 1995.
 293. Laghi F, Harrison MJ, Tobin MJ. Comparison of magnetic and electrical phrenic nerve stimulation in assessment of diaphragmatic contractility. J Appl Physiol 80: 1731‐1742, 1996.
 294. Lahiri S, DeLaney RG, Brody JS, Simpser M, Velasquez T, Motoyama EK, Polgar C. Relative role of environmental and genetic factors in respiratory adaptation to high altitude. Nature 261: 133‐135, 1976.
 295. Lai‐Fook SJ, Hyatt RE. Effects of age on elastic moduli of human lungs. J Appl Physiol 89: 163‐168, 2000.
 296. Lamb TW. Ventilatory responses to hind limb exercise in anesthetized cats and dogs. Respir Physiol 6: 88‐104, 1968.
 297. Lane R, Adams L, Guz A. The effects of hypoxia and hypercapnia on perceived breathlessness during exercise in humans. J Physiol 428: 579‐593, 1990.
 298. Lane R, Cockcroft A, Guz A. Voluntary isocapnic hyperventilation and breathlessness during exercise in normal subjects. Clin Sci (Lond) 73: 519‐523, 1987.
 299. Langdeau JB, Turcotte H, Bowie DM, Jobin J, Desgagne P, Boulet LP. Airway hyperresponsiveness in elite athletes. Am J Respir Crit Care Med 161: 1479‐1484, 2000.
 300. Laughlin MH, Klabunde RE, Delp MD, Armstrong RB. Effects of dipyridamole on muscle blood flow in exercising miniature swine. Am J Physiol 257: H1507‐H1515, 1989.
 301. Lawler JM, Powers SK. Oxidative stress, antioxidant status, and the contracting diaphragm. Can J Appl Physiol 23: 23‐55, 1998.
 302. Leddy JJ, Limprasertkul A, Patel S, Modlich F, Buyea C, Pendergast DR, Lundgren CE. Isocapnic hyperpnea training improves performance in competitive male runners. Eur J Appl Physiol 99: 665‐676, 2007.
 303. Leith DE, Bradley M. Ventilatory muscle strength and endurance training. J Appl Physiol 41: 508‐516, 1976.
 304. Levine BD, Lane LD, Buckey JC, Friedman DB, Blomqvist CG. Left ventricular pressure‐volume and Frank‐Starling relations in endurance athletes. Implications for orthostatic tolerance and exercise performance. Circ 84: 1016‐1023, 1991.
 305. Levine S, Gregory C, Nguyen T, Shrager J, Kaiser L, Rubinstein N, Dudley G. Bioenergetic adaptation of individual human diaphragmatic myofibers to severe COPD. J Appl Physiol 92: 1205‐1213, 2002.
 306. Levine S, Henson D. Low‐frequency diaphragmatic fatigue in spontaneously breathing humans. J Appl Physiol 64: 672‐680, 1988.
 307. Levine S, Kaiser L, Leferovich J, Tikunov B. Cellular adaptations in the diaphragm in chronic obstructive pulmonary disease. New Engl J Med 337: 1799‐1806, 1997.
 308. Levine S, Nguyen T, Kaiser LR, Rubinstein NA, Maislin G, Gregory C, Rome LC, Dudley GA, Sieck GC, Shrager JB. Human diaphragm remodeling associated with chronic obstructive pulmonary disease: Clinical implications. Am J Respir Crit Care Med 168: 706‐713, 2003.
 309. Levine S, Nguyen T, Shrager J, Kaiser L, Camasamudram V, Rubinstein N. Diaphragm adaptations elicited by severe chronic obstructive pulmonary disease: Lessons for sports science. Exerc Sport Sci Rev 29: 71‐75, 2001.
 310. Levison H, Cherniack RM. Ventilatory cost of exercise in chronic obstructive pulmonary disease. J Appl Physiol 25: 21‐27, 1968.
 311. Lewis G, Ponte J, Purves MJ. Fluctuations of PaCO2 with the same period as respiration in the cat. J Physiol 298: 1‐11, 1980.
 312. Liistro G, Veriter C, Dury M, Aubert G, Stanescu D. Expiratory flow limitation in awake sleep‐disordered breathing subjects. Eur Respir J 14: 185‐190, 1999.
 313. Lindstedt SL, Hokanson JF, Wells DJ, Swain SD, Hoppeler H, Navarro V. Running energetics in the pronghorn antelope. Nature 353: 748‐750, 1991.
 314. Linton RA, Band DM. The effect of potassium on carotid chemoreceptor activity and ventilation in the cat. Respir Physiol 59: 65‐70, 1985.
 315. Lloyd TC Jr. Respiratory system compliance as seen from the cardiac fossa. J Appl Physiol 53: 57‐62, 1982.
 316. Loke J, Mahler DA, Virgulto JA. Respiratory muscle fatigue after marathon running. J Appl Physiol 52: 821‐824, 1982.
 317. Lomax ME, McConnell AK. Inspiratory muscle fatigue in swimmers after a single 200 m swim. J Sports Sci 21: 659‐664, 2003.
 318. Louhevaara V, Sovijarvi A, Ilmarinen J, Teraslinna P. Differences in cardiorespiratory responses during and after arm crank and cycle exercise. Acta Physiol Scand 138: 133‐143, 1990.
 319. Luo YM, Hart N, Mustfa N, Lyall RA, Polkey MI, Moxham J. Effect of diaphragm fatigue on neural respiratory drive. J Appl Physiol 90: 1691‐1699, 2001.
 320. Luo YM, Moxham J, Polkey MI. Diaphragm electromyography using an oesophageal catheter: Current concepts. Clin Sci (Lond) 115: 233‐244, 2008.
 321. Mador MJ. Respiratory muscle fatigue and breathing pattern. Chest 100: 1430‐1435, 1991.
 322. Mador MJ, Acevedo FA. Effect of respiratory muscle fatigue on breathing pattern during incremental exercise. Am Rev Respir Dis 143: 462‐468, 1991a.
 323. Mador MJ, Acevedo FA. Effect of respiratory muscle fatigue on subsequent exercise performance. J Appl Physiol 70: 2059‐2065, 1991b.
 324. Mador MJ, Bozkanat E, Kufel TJ. Quadriceps fatigue after cycle exercise in patients with COPD compared with healthy control subjects. Chest 123: 1104‐1111, 2003.
 325. Mador MJ, Kufel TJ. Effect of inspiratory muscle fatigue on inspiratory muscle relaxation rates in healthy subjects. Chest 102: 1767‐1773, 1992.
 326. Mador MJ, Kufel TJ, Pineda LA, Sharma GK. Diaphragmatic fatigue and high‐intensity exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 161: 118‐123, 2000.
 327. Mador MJ, Magalang UJ, Kufel TJ. Twitch potentiation following voluntary diaphragmatic contraction. Am J Respir Crit Care Med 149: 739‐743, 1994.
 328. Mador MJ, Magalang UJ, Rodis A, Kufel TJ. Diaphragmatic fatigue after exercise in healthy human subjects. Am Rev Respir Dis 148: 1571‐1575, 1993.
 329. Mador MJ, Rodis A, Magalang UJ, Ameen K. Comparison of cervical magnetic and transcutaneous phrenic nerve stimulation before and after threshold loading. Am J Respir Crit Care Med 154: 448‐453, 1996.
 330. Mahler DA, Moritz ED, Loke J. Ventilatory responses at rest and during exercise in marathon runners. J Appl Physiol 52: 388‐392, 1982.
 331. Man WD‐C, Luo Y‐M, Mustfa N, Rafferty GF, Glerant J‐C, Polkey MI, Moxham J. Postprandial effects on twitch transdiaphragmatic pressure. Eur Respir J 20: 577‐580, 2002.
 332. Mancini DM, Henson D, LaManca J, Levine S. Respiratory muscle function and dyspnea in patients with chronic congestive heart failure. Circ 86: 909‐918, 1992.
 333. Manohar M. Blood flow to the respiratory and limb muscles and to abdominal organs during maximal exertion in ponies. J Physiol 377: 25‐35, 1986a.
 334. Manohar M. Vasodilator reserve in respiratory muscles during maximal exertion in ponies. J Appl Physiol 60: 1571‐1577, 1986b.
 335. Manohar M. Costal vs. crural diaphragmatic blood flow during submaximal and near‐maximal exercise in ponies. J Appl Physiol 65: 1514‐1519, 1988.
 336. Manohar M. Inspiratory and expiratory muscle perfusion in maximally exercised ponies. J Appl Physiol 68: 544‐548, 1990.
 337. Manohar M, Hassan AS. Diaphragmatic energetics during prolonged exhaustive exercise. Am Rev Respir Dis 144: 415‐418, 1991.
 338. Marciniuk D, McKim D, Sanii R, Younes M. Role of central respiratory muscle fatigue in endurance exercise in normal subjects. J Appl Physiol 76: 236‐241, 1994.
 339. Margaria R, Milic‐Emili G, Petit JM, Cavagna G. Mechanical work of breathing during muscular exercise. J Appl Physiol 15: 354‐358, 1960.
 340. Markov G, Spengler CM, Knopfli‐Lenzin C, Stuessi C, Boutellier U. Respiratory muscle training increases cycling endurance without affecting cardiovascular responses to exercise. Eur J Appl Physiol 85: 233‐239, 2001.
 341. Martin B, Heintzelman M, Chen HI. Exercise performance after ventilatory work. J Appl Physiol 52: 1581‐1585, 1982.
 342. Martin BJ, Stager JM. Ventilatory endurance in athletes and non‐athletes. Med Sci Sports Exerc 13: 21‐26, 1981.
 343. Martin TR, Castile RG, Fredberg JJ, Wohl ME, Mead J. Airway size is related to sex but not lung size in normal adults. J Appl Physiol 63: 2042‐2047, 1987.
 344. Massaro D, Massaro GD, Baras A, Hoffman EP, Clerch LB. Calorie‐related rapid onset of alveolar loss, regeneration, and changes in mouse lung gene expression. Am J Physiol Lung Cell Mol Physiol 286: L896‐L906, 2004.
 345. Massaro GD, Radaeva S, Clerch LB, Massaro D. Lung alveoli: Endogenous programmed destruction and regeneration. Am J Physiol Lung Cell Mol Physiol 283: L305‐L309, 2002.
 346. Mateika JH, Duffin J. The ventilation, lactate and electromyographic thresholds during incremental exercise tests in normoxia, hypoxia and hyperoxia. Eur J Appl Physiol 69: 110‐118, 1994.
 347. McCallister LW, McCoy KW, Connelly JC, Kaufman MP. Stimulation of groups III and IV phrenic afferents reflexly decreases total lung resistance in dogs. J Appl Physiol 61: 1346‐1351, 1986.
 348. McClaran SR, Babcock MA, Pegelow DF, Reddan WG, Dempsey JA. Longitudinal effects of aging on lung function at rest and exercise in healthy active fit elderly adults. J Appl Physiol 78: 1957‐1968, 1995.
 349. McClaran SR, Harms CA, Pegelow DF, Dempsey JA. Smaller lungs in women affect exercise hyperpnea. J Appl Physiol 84: 1872‐1881, 1998.
 350. McClaran SR, Wetter TJ, Pegelow DF, Dempsey JA. Role of expiratory flow limitation in determining lung volumes and ventilation during exercise. J Appl Physiol 86: 1357‐1366, 1999.
 351. McConnell AK, Lomax M. The influence of inspiratory muscle work history and specific inspiratory muscle training upon human limb muscle fatigue. J Physiol 577: 445‐457, 2006.
 352. McConnell AK, Romer LM. Dyspnoea in health and obstructive pulmonary disease: The role of respiratory muscle function and training. Sports Med 34: 117‐132, 2004a.
 353. McConnell AK, Romer LM. Respiratory muscle training in healthy humans: Resolving the controversy. Int J Sports Med 25: 284‐293, 2004b.
 354. McConnell AK, Sharpe GR. The effect of inspiratory muscle training upon maximum lactate steady‐state and blood lactate concentration. Eur J Appl Physiol 94: 277‐284, 2005.
 355. McCool FD, Hershenson MB, Tzelepis GE, Kikuchi Y, Leith DE. Effect of fatigue on maximal inspiratory pressure‐flow capacity. J Appl Physiol 73: 36‐43, 1992.
 356. McCool FD, McCann DR, Leith DE, Hoppin FG Jr. Pressure‐flow effects on endurance of inspiratory muscles. J Appl Physiol 60: 299‐303, 1986.
 357. McCoy M, Hargreaves M. Potassium and ventilation during incremental exercise in trained and untrained men. J Appl Physiol 73: 1287‐1290, 1992.
 358. McGregor M, Becklake MR. The relationship of oxygen cost of breathing to respiratory mechanical work and respiratory force. J Clin Invest 40: 971‐980, 1961.
 359. McKenzie DK, Bigland‐Ritchie B, Gorman RB, Gandevia SC. Central and peripheral fatigue of human diaphragm and limb muscles assessed by twitch interpolation. J Physiol 454: 643‐656, 1992.
 360. McKerrow CB, Otis AB. Oxygen cost of hyperventilation. J Appl Physiol 9: 375‐379, 1956.
 361. McMahon ME, Boutellier U, Smith RM, Spengler CM. Hyperpnea training attenuates peripheral chemosensitivity and improves cycling endurance. J Exp Biol 205: 3937‐3943, 2002.
 362. McParland C, Krishnan B, Lobo J, Gallagher CG. Effect of physical training on breathing pattern during progressive exercise. Respir Physiol 90: 311‐323, 1992.
 363. Mead J. The control of respiratory frequency. Ann N Y Acad Sci 109: 724‐729, 1963.
 364. Mead J. Dysanapsis in normal lungs assessed by the relationship between maximal flow, static recoil, and vital capacity. Am Rev Respir Dis 121: 339‐342, 1980.
 365. Mendes FA, Almeida FM, Cukier A, Stelmach R, Jacob‐Filho W, Martins MA, Carvalho CR. Effects of aerobic training on airway inflammation in asthmatic patients. Med Sci Sports Exerc 43: 197‐203, 2011.
 366. Meyer KC. Aging. Proc Am Thor Soc 2: 433‐439, 2005.
 367. Miller JD, Hemauer SJ, Smith CA, Stickland MK, Dempsey JA. Expiratory threshold loading impairs cardiovascular function in health and chronic heart failure during submaximal exercise. J Appl Physiol 101: 213‐227, 2006.
 368. Miller JD, Pegelow DF, Jacques AJ, Dempsey JA. Effects of augmented respiratory muscle pressure production on locomotor limb venous return during calf contraction exercise. J Appl Physiol 99: 1802‐1815, 2005a.
 369. Miller JD, Pegelow DF, Jacques AJ, Dempsey JA. Skeletal muscle pump versus respiratory muscle pump: Modulation of venous return from the locomotor limb in humans. J Physiol 563: 925‐943, 2005b.
 370. Miller JD, Smith CA, Hemauer SJ, Dempsey JA. The effects of inspiratory intrathoracic pressure production on the cardiovascular response to submaximal exercise in health and chronic heart failure. Am J Physiol 292: H580‐H592, 2007.
 371. Millhorn DE, Eldridge FL, Waldrop TG, Kiley JP. Diencephalic regulation of respiration and arterial pressure during actual and fictive locomotion in cat. Circ Res 61: I53‐I59, 1987.
 372. Mills GH, Kyroussis D, Hamnegard CH, Polkey MI, Green M, Moxham J. Bilateral magnetic stimulation of the phrenic nerves from an anterolateral approach. Am J Respir Crit Care Med 154: 1099‐1105, 1996.
 373. Mills GH, Kyroussis D, Hamnegard CH, Wragg S, Moxham J, Green M. Unilateral magnetic stimulation of the phrenic nerve. Thorax 50: 1162‐1172, 1995.
 374. Mink SN, Wood LD. How does HeO2 increase maximum expiratory flow in human lungs? J Clin Invest 66: 720‐729, 1980.
 375. Mitchell GS, Babb TG. Layers of exercise hyperpnea: Modulation and plasticity. Respir Physiol Neurobiol 151: 251‐266, 2006.
 376. Mizuno M. Human respiratory muscles: Fibre morphology and capillary supply. Eur Respir J 4: 587‐601, 1991.
 377. Moosavi SH, Topulos GP, Hafer A, Lansing RW, Adams L, Brown R, Banzett RB. Acute partial paralysis alters perceptions of air hunger, work and effort at constant PCO2 and VE. Respir Physiol 122: 45‐60, 2000.
 378. Moreno AH, Katz AI, Gold LD. An integrated approach to the study of the venous system with steps toward a detailed model of the dynamics of venous return to the right heart. IEEE Trans Bio‐Med Eng 16: 308‐324, 1969.
 379. Mota S, Casan P, Drobnic F, Giner J, Ruiz O, Sanchis J, Milic‐Emili J. Expiratory flow limitation during exercise in competition cyclists. J Appl Physiol 86: 611‐616, 1999.
 380. Moxham J, Edwards RH, Aubier M, De Troyer A, Farkas G, Macklem PT, Roussos C. Changes in EMG power spectrum (high‐to‐low ratio) with force fatigue in humans. J Appl Physiol 53: 1094‐1099, 1982.
 381. Moxham J, Morris AJ, Spiro SG, Edwards RH, Green M. Contractile properties and fatigue of the diaphragm in man. Thorax 36: 164‐168, 1981.
 382. Mulvey DA, Koulouris NG, Elliott MW, Laroche CM, Moxham J, Green M. Inspiratory muscle relaxation rate after voluntary maximal isocapnic ventilation in humans. J Appl Physiol 70: 2173‐2180, 1991.
 383. Mulvey DA, Koulouris NG, Elliott MW, Moxham J, Green M. Maximal relaxation rate of inspiratory muscle can be effort‐dependent and reflect the activation of fast‐twitch fibers. Am Rev Respir Dis 144: 803‐806, 1991.
 384. Murray JF. Oxygen cost of voluntary hyperventilation. J Appl Physiol 14: 187‐190, 1959.
 385. Musch TI. Elevated diaphragmatic blood flow during submaximal exercise in rats with chronic heart failure. Am J Physiol 265: H1721‐H1726, 1993.
 386. Nattie EE. Ventilation during acute HCl infusion in intact and chemodenervated conscious rabbits. Respir Physiol 54: 97‐107, 1983.
 387. Nguyen T, Shrager J, Kaiser L, Mei L, Daood M, Watchko J, Rubinstein N, Levine S. Developmental myosin heavy chains in the adult human diaphragm: Coexpression patterns and effect of COPD. J Appl Physiol 88: 1446‐1456, 2000.
 388. NHLBI. Respiratory muscle fatigue: Report of the respiratory muscle fatigue workshop group. Am Rev Respir Dis 142: 474‐486, 1990.
 389. Nicks CR, Morgan DW, Fuller DK, Caputo JL. The influence of respiratory muscle training upon intermittent exercise performance. Int J Sports Med 30: 16‐21, 2009.
 390. Niewoehner DE, Kleinerman J. Morphologic basis of pulmonary resistance in the human lung and effects of aging. J Appl Physiol 36: 412‐418, 1974.
 391. Niinimaa V, Shephard RJ. Training and oxygen conductance in the elderly. I. The respiratory system. J Gerentology 33: 354‐361, 1978.
 392. Noah JA, Boliek C, Lam T, Yang JF. Breathing frequency changes at the onset of stepping in human infants. J Neurophysiol 99: 1224‐1234, 2008.
 393. Nourry C, Deruelle F, Fabre C, Baquet G, Bart F, Grosbois JM, Berthoin S, Mucci P. Exercise flow‐volume loops in prepubescent aerobically trained children. J Appl Physiol 99: 1912‐1921, 2005.
 394. Nourry C, Deruelle F, Guinhouya C, Baquet G, Fabre C, Bart F, Berthoin S, Mucci P. High‐intensity intermittent running training improves pulmonary function and alters exercise breathing pattern in children. Eur J Appl Physiol 94: 415‐423, 2005.
 395. O'Donnell DE, Banzett RB, Carrieri‐Kohlman V, Casaburi R, Davenport PW, Gandevia SC, Gelb AF, Mahler DA, Webb KA. Pathophysiology of dyspnea in chronic obstructive pulmonary disease: A roundtable. Proc Am Thorac Soc 4: 145‐168, 2007.
 396. O'Donnell DE, Hong HH, Webb KA. Respiratory sensation during chest wall restriction and dead space loading in exercising men. J Appl Physiol 88: 1859‐1869, 2000.
 397. O'Donnell DE, Ora J, Webb KA, Laveneziana P, Jensen D. Mechanisms of activity‐related dyspnea in pulmonary diseases. Respir Physiol Neurobiol 167: 116‐132, 2009.
 398. O'Donnell DE, and Webb KA. Exertional breathlessness in patients with chronic airflow limitation. The role of lung hyperinflation. Am Rev Respir Dis 148: 1351‐1357, 1993.
 399. Offner B, Dembowsky K, Czachurski J. Characteristics of sympathetic reflexes evoked by electrical stimulation of phrenic nerve afferents. J Auto Nerv System 41: 103‐111, 1992.
 400. Ofir D, Laveneziana P, Webb KA, Lam YM, O'Donnell DE. Sex differences in the perceived intensity of breathlessness during exercise with advancing age. J Appl Physiol 104: 1583‐1593, 2008.
 401. Olafsson S, Hyatt RE. Ventilatory mechanics and expiratory flow limitation during exercise in normal subjects. J Clin Invest 48: 564‐573, 1969.
 402. Olson TP, Joyner MJ, Dietz NM, Eisenach JH, Curry TB, Johnson BD. Effects of respiratory muscle work on blood flow distribution during exercise in heart failure. J Physiol 588: 2487‐2501, 2010.
 403. Olson TP, Snyder EM, Johnson BD. Exercise‐disordered breathing in chronic heart failure. Exerc Sport Sci Rev 34: 194‐201, 2006.
 404. Onal E, Lopata M, O'Connor TD. Diaphragmatic and genioglossal electromyogram responses to CO2 rebreathing in humans. J Appl Physiol 50: 1052‐1055, 1981a.
 405. Onal E, Lopata M, O'Connor TD. Diaphragmatic and genioglossal electromyogram responses to isocapnic hypoxia in humans. Am Rev Respir Dis 124: 215‐217, 1981b.
 406. Ora J, Jensen D, O'Donnell DE. Exertional dyspnea in chronic obstructive pulmonary disease: Mechanisms and treatment approaches. Curr Opin Pulm Med 16: 144‐149, 2010.
 407. Otis A. Mechanics of breathing in man. J Appl Physiol 2: 592‐607, 1950.
 408. Otis AB, Fenn WO, Rahn H. Mechanics of breathing in man. J Appl Physiol 2: 592‐607, 1950.
 409. Pan LG, Forster HV, Bisgard GE, Kaminski RP, Dorsey SM, Busch MA. Hyperventilation in ponies at the onset of and during steady‐state exercise. J Appl Physiol 54: 1394‐1402, 1983.
 410. Pan LG, Forster HV, Bisgard GE, Murphy CL, Lowry TF. Independence of exercise hyperpnea and acidosis during high‐intensity exercise in ponies. J Appl Physiol 60: 1016‐1024, 1986.
 411. Pan LG, Forster HV, Wurster RD, Murphy CL, Brice AG, Lowry TF. Effect of partial spinal cord ablation on exercise hyperpnea in ponies. J Appl Physiol 69: 1821‐1827, 1990.
 412. Pardy RL, Bye PT. Diaphragmatic fatigue in normoxia and hyperoxia. J Appl Physiol 58: 738‐742, 1985.
 413. Paterson DJ. Potassium and ventilation in exercise. J Appl Physiol 72: 811‐820, 1992.
 414. Paterson DJ, Friedland JS, Bascom DA, Clement ID, Cunningham DA, Painter R, Robbins PA. Changes in arterial K+ and ventilation during exercise in normal subjects and subjects with McArdle's syndrome. J Physiol 429: 339‐348, 1990.
 415. Paterson DJ, Friedland JS, Oliver DO, Robbins PA. The ventilatory response to lowering potassium with dextrose and insulin in subjects with hyperkalaemia. Respir Physiol 76: 393‐398, 1989.
 416. Pelkonen M, Notkola I, Lakka T, Tukiainen HO, Kivinen P, Nissinen A. Delaying decline in pulmonary function with physical activity. Am J Respir Crit Care Med 168: 494‐499, 2003.
 417. Pellegrino R, Brusasco V, Rodarte JR, Babb TG. Expiratory flow limitation and regulation of end‐expiratory lung volume during exercise. J Appl Physiol 74: 2552‐2558, 1993.
 418. Pellegrino R, Violante B, Nava S, Rampulla C, Brusasco V, Rodarte JR. Expiratory airflow limitation and hyperinflation during methacholine‐induced bronchoconstriction. J Appl Physiol 75: 1720‐1727, 1993.
 419. Phillipson EA, Bowes G, Townsend ER, Duffin J, Cooper JD. Role of metabolic CO2 production in ventilatory response to steady‐state exercise. J Clin Invest 68: 768‐774, 1981.
 420. Phillipson EA, Duffin J, Cooper JD. Critical dependence of respiratory rhythmicity on metabolic CO2 load. J Appl Physiol 50: 45‐54, 1981.
 421. Pierce JA, Hocott JB. Studies on the collagen and elastin content of the human lung. J Clin Invest 39: 8‐14, 1960.
 422. Polkey MI, Duguet A, Luo Y, Hughes PD, Hart N, Hamnegard CH, Green M, Similowski T, Moxham J. Anterior magnetic phrenic nerve stimulation: Laboratory and clinical evaluation. Intensive Care Med 26: 1065‐1075, 2000.
 423. Polkey MI, Hamnegard CH, Hughes PD, Rafferty GF, Green M, Moxham J. Influence of acute lung volume change on contractile properties of human diaphragm. J Appl Physiol 85: 1322‐1328, 1998.
 424. Polkey MI, Harris ML, Hughes PD, Hamnegard CH, Lyons D, Green M, Moxham J. The contractile properties of the elderly human diaphragm. Am J Respir Crit Care Med 155: 1560‐1564, 1997.
 425. Polkey MI, Kyroussis D, Hamnegard CH, Hughes PD, Rafferty GF, Moxham J, Green M. Paired phrenic nerve stimuli for the detection of diaphragm fatigue in humans. Eur Respir J 10: 1859‐1864, 1997.
 426. Polkey MI, Kyroussis D, Hamnegard CH, Mills GH, Hughes PD, Green M, Moxham J. Diaphragm performance during maximal voluntary ventilation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 155: 642‐648, 1997.
 427. Polkey MI, Kyroussis D, Keilty SE, Hamnegard CH, Mills GH, Green M, Moxham J. Exhaustive treadmill exercise does not reduce twitch transdiaphragmatic pressure in patients with COPD. Am J Respir Crit Care Med 152: 959‐964, 1995.
 428. Powers SK, Coombes J, Demirel H. Exercise training‐induced changes in respiratory muscles. Sports Med 24: 120‐131, 1997.
 429. Powers SK, Criswell D. Adaptive strategies of respiratory muscles in response to endurance exercise. Med Sci Sports Exerc 28: 1115‐1122, 1996.
 430. Powers SK, Criswell D, Lawler J, Martin D, Ji LL, Herb RA, Dudley G. Regional training‐induced alterations in diaphragmatic oxidative and antioxidant enzymes. Respir Physiol 95: 227‐237, 1994.
 431. Powers SK, Criswell D, Lieu FK, Dodd S, Silverman H. Diaphragmatic fiber type specific adaptation to endurance exercise. Respir Physiol 89: 195‐207, 1992.
 432. Powers SK, Dodd S, Lawler J, Landry G, Kirtley M, McKnight T, Grinton S. Incidence of exercise induced hypoxemia in elite endurance athletes at sea level. Eur J Appl Physiol 58: 298‐302, 1988.
 433. Powers SK, Grinton S, Lawler J, Criswell D, Dodd S. High intensity exercise training‐induced metabolic alterations in respiratory muscles. Respir Physiol 89: 169‐177, 1992.
 434. Powers SK, Jacques M, Richard R, Beadle RE. Effects of breathing a normoxic HeO2 gas mixture on exercise tolerance and VO2max. Int J Sports Med 7: 217‐221, 1986.
 435. Powers SK, Lawler J, Criswell D, Silverman H, Forster HV, Grinton S, Harkins D. Regional metabolic differences in the rat diaphragm. J Appl Physiol 69: 648‐650, 1990.
 436. Qayyum MS, Barlow CW, O'Connor DF, Paterson DJ, Robbins PA. Effect of raised potassium on ventilation in euoxia, hypoxia and hyperoxia at rest and during light exercise in man. J Physiol 476: 365‐372, 1994.
 437. Rack PM, Westbury DR. The effects of length and stimulus rate on tension in the isometric cat soleus muscle. J Physiol 204: 443‐460, 1969.
 438. Rahn H, Otis AB, Chadwick LE, Fenn WO. The pressure‐volume diagram of the thorax and lung. Am J Physiol 146: 161‐178, 1946.
 439. Ramirez‐Sarmiento A, Orozco‐Levi M, Guell R, Barreiro E, Hernandez N, Mota S, Sangenis M, Broquetas JM, Casan P, Gea J. Inspiratory muscle training in patients with chronic obstructive pulmonary disease: Structural adaptation and physiologic outcomes. Am J Respir Crit Care Med 166: 1491‐1497, 2002.
 440. Remmers JE, Mithoefer JC. The carbon monoxide diffusing capacity in permanent residents at high altitudes. Respir Physiol 6: 233‐244, 1969.
 441. Renggli AS, Verges S, Notter DA, Spengler CM. Development of respiratory muscle contractile fatigue in the course of hyperpnoea. Respir Physiol Neurobiol 164: 366‐372, 2008.
 442. Reuschlein PS, Reddan WG, Burpee J, Gee JB, Rankin J. Effect of physical training on the pulmonary diffusing capacity during submaximal work. J Appl Physiol 24: 152‐158, 1968.
 443. Road J, Vahi R, del Rio P, Grassino A. In vivo contractile properties of fatigued diaphragm. J Appl Physiol 63: 471‐478, 1987.
 444. Robinson EP, Kjeldgaard JM. Improvement in ventilatory muscle function with running. J Appl Physiol 52: 1400‐1406, 1982.
 445. Rodman JR, Gosselin LE, Horvath PJ, Megirian D, Farkas GA. Diaphragm plasticity following intrinsic laryngeal muscle denervation in rats. Med Sci Sports Exerc 34: 251‐257, 2002.
 446. Rodman JR, Henderson KS, Smith CA, Dempsey JA. Cardiovascular effects of the respiratory muscle metaboreflexes in dogs: Rest and exercise. J Appl Physiol 95: 1159‐1169, 2003.
 447. Rohrer F. Der strömungswiderstand in den menschlichen atemwegen und der einfluss der unregelmässigen verzweigung des bronchialsystems auf den atmungsverlauf in verschiedenen lungenbezirken. Pflügers Arch Ges Physiol 162: 225‐299, 1915.
 448. Rollier H, Bisschop A, Gayan‐Ramirez G, Gosselink R, Decramer M. Low load inspiratory muscle training increases diaphragmatic fiber dimensions in rats. Am J Respir Crit Care Med 157: 833‐839, 1998.
 449. Romer LM, Lovering AT, Haverkamp HC, Pegelow DF, Dempsey JA. Effect of inspiratory muscle work on peripheral fatigue of locomotor muscles in healthy humans. J Physiol 571: 425‐439, 2006.
 450. Romer LM, McConnell AK, Jones DA. Effects of inspiratory muscle training upon recovery time during high intensity, repetitive sprint activity. Int J Sports Med 23: 353‐360, 2002a.
 451. Romer LM, McConnell AK, Jones DA. Effects of inspiratory muscle training upon time trial performance in trained cyclists. J Sports Sci 20: 547‐562, 2002b.
 452. Romer LM, McConnell AK, Jones DA. Inspiratory muscle fatigue in trained cyclists: Effects of inspiratory muscle training. Med Sci Sports Exerc 34: 785‐792, 2002c.
 453. Romer LM, Miller JD, Haverkamp HC, Pegelow DF, Dempsey JA. Inspiratory muscles do not limit maximal incremental exercise performance in healthy subjects. Respir Physiol Neurobiol 156: 353‐361, 2007.
 454. Romer LM, Polkey MI. Exercise‐induced respiratory muscle fatigue: Implications for performance. J Appl Physiol 104: 879‐888, 2008.
 455. Ross E, Middleton N, Shave R, George K, McConnell A. Changes in respiratory muscle and lung function following marathon running in man. J Sports Sci 26: 1295‐1301, 2008.
 456. Ross KA, Thurlbeck WM. Lung growth in newborn guinea pigs: Effects of endurance exercise. Respir Physiol 89: 353‐364, 1992.
 457. Rotto DM, Stebbins CL, Kaufman MP. Reflex cardiovascular and ventilatory responses to increasing H+ activity in cat hindlimb muscle. J Appl Physiol 67: 256‐263, 1989.
 458. Roussos C, Fixley M, Gross D, Macklem PT. Fatigue of inspiratory muscles and their synergic behavior. J Appl Physiol 46: 897‐904, 1979.
 459. Rowell LB. Human Cardiovascular Control. New York: Oxford University Press, 1993.
 460. Rowell LB, Hermansen L, Blackmon JR. Human cardiovascular and respiratory responses to graded muscle ischemia. J Appl Physiol 41: 693‐701, 1976.
 461. Rundell KW. Pulmonary function decay in women ice hockey players: Is there a relationship to ice rink air quality? Inhal Toxicol 16: 117‐123, 2004.
 462. Rybicki KJ, Kaufman MP. Stimulation of group III and IV muscle afferents reflexly decreases total pulmonary resistance in dogs. Respir Physiol 59: 185‐195, 1985.
 463. Sahebjami H, Wirman JA. Emphysema‐like changes in the lungs of starved rats. Am Rev Respir Dis 124: 619‐624, 1981.
 464. Saldana M, Oyola G. Morphometry of the high altitude lung. Lab Invest 22: 509‐512, 1970.
 465. Scichilone N, Morici G, Marchese R, Bonanno A, Profita M, Togias A, Bonsignore MR. Reduced airway responsiveness in nonelite runners. Med Sci Sports Exerc i 37: 2019‐2025, 2005.
 466. Scichilone N, Morici G, Zangla D, Chimenti L, Davi E, Reitano S, Paterno A, Santagata R, Togias A, Bellia V, Bonsignore MR. Effects of Exercise Training on Airway Responsiveness and Airway Cells in Healthy Subjects. J Appl Physiol.
 467. Scichilone N, Togias A. The role of lung inflation in airway hyperresponsiveness and in asthma. Curr Allergy Asthma Rep 4: 166‐174, 2004.
 468. Seals DR, Suwarno NO, Dempsey JA. Influence of lung volume on sympathetic nerve discharge in normal humans. Circ Res 67: 130‐141, 1990.
 469. Secher NH, Kjaer M, Galbo H. Arterial blood pressure at the onset of dynamic exercise in partially curarized man. Acta Physiol Scand 133: 233‐237, 1988.
 470. Senapati JM. Effect of stimulation of muscle afferents on ventilation of dogs. J Appl Physiol 21: 242‐246, 1966.
 471. Shaaban R, Leynaert B, Soussan D, Anto JM, Chinn S, de Marco R, Garcia‐Aymerich J, Heinrich J, Janson C, Jarvis D, Sunyer J, Svanes C, Wjst M, Burney PG, Neukirch F, Zureik M. Physical activity and bronchial hyperresponsiveness: European Community Respiratory Health Survey II. Thorax 62: 403‐410, 2007.
 472. Sheel AW, Derchak PA, Morgan BJ, Pegelow DF, Jacques AJ, Dempsey JA. Fatiguing inspiratory muscle work causes reflex reduction in resting leg blood flow in humans. J Physiol 537: 277‐289, 2001.
 473. Sheel AW, Derchak PA, Pegelow DF, Dempsey JA. Threshold effects of respiratory muscle work on limb vascular resistance. Am J Physiol Heart Circ Physiol 282: H1732‐H1738, 2002.
 474. Sheel AW, Foster GE, Romer LM. Exercise and its impact on dyspnea. Current Opin Pharmacol 11: 195‐203, 2011.
 475. Sheel AW, Guenette JA, Yuan R, Holy L, Mayo JR, McWilliams AM, Lam S, Coxson HO. Evidence for dysanapsis using computed tomographic imaging of the airways in older ex‐smokers. J Appl Physiol 107: 1622‐1628, 2009.
 476. Shephard RJ, Godin G, Campbell R. Characteristics of sprint, medium and long‐distance swimmers. Eur J Appl Physiol 32: 99‐116, 1974.
 477. Shephard RJ, Lavallee H. Effects of enhanced physical education on lung volumes of primary school children. J Sports Med Phys Fitness 36: 186‐194, 1996.
 478. Sieck GC, Fournier M. Changes in diaphragm motor unit EMG during fatigue. J Appl Physiol 68: 1917‐1926, 1990.
 479. Siegmund GP, Edwards MR, Moore KS, Tiessen DA, Sanderson DJ, McKenzie DC. Ventilation and locomotion coupling in varsity male rowers. J Appl Physiol 87: 233‐242, 1999.
 480. Similowski T, Duguet A, Straus C, Attali V, Boisteanu D, Derenne JP. Assessment of the voluntary activation of the diaphragm using cervical and cortical magnetic stimulation. Eur Respir J 9: 1224‐1231, 1996.
 481. Similowski T, Fleury B, Launois S, Cathala HP, Bouche P, Derenne JP. Cervical magnetic stimulation: A new painless method for bilateral phrenic nerve stimulation in conscious humans. J Appl Physiol 67: 1311‐1318, 1989.
 482. Simon M, LeBlanc P, Jobin J, Desmeules M, Sullivan MJ, Maltais F. Limitation of lower limb VO2 during cycling exercise in COPD patients. J Appl Physiol 90: 1013‐1019, 2001.
 483. Simon PM, Schwartzstein RM, Weiss JW, Lahive K, Fencl V, Teghtsoonian M, Weinberger SE. Distinguishable sensations of breathlessness induced in normal volunteers. Am Rev Respir Dis 140: 1021‐1027, 1989.
 484. Sinderby C, Weinberg J, Sullivan L, Lindstrom L, Grassino A. Electromyographical evidence for exercise‐induced diaphragm fatigue in patients with chronic cervical cord injury or prior poliomyelitis infection. Spinal Cord 34: 594‐601, 1996.
 485. Sinning WE, Adrian MJ. Cardiorespiratory changes in college women due to a season of competitive basketball. J Appl Physiol 25: 720‐724, 1968.
 486. Sinoway LI, Li J. A perspective on the muscle reflex: Implications for congestive heart failure. J Appl Physiol 99: 5‐22, 2005.
 487. Sliwinski P, Yan S, Gauthier AP, Macklem PT. Influence of global inspiratory muscle fatigue on breathing during exercise. J Appl Physiol 80: 1270‐1278, 1996.
 488. Smith J, Bellemare F. Effect of lung volume on in vivo contraction characteristics of human diaphragm. J Appl Physiol 62: 1893‐1900, 1987.
 489. Somers VK, Mark AL, Zavala DC, Abboud FM. Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans. J Appl Physiol 67: 2101‐2106, 1989.
 490. Somjen GG. The missing error signal: Regulation beyond negative feedback. News Physiol Sci 7: 184‐185, 1992.
 491. Spengler CM, Knopfli‐Lenzin C, Birchler K, Trapletti A, Boutellier U. Breathing pattern and exercise endurance time after exhausting cycling or breathing. Eur J Appl Physiol 81: 368‐374, 2000.
 492. Sporer BC, Foster GE, Sheel AW, McKenzie DC. Entrainment of breathing in cyclists and non‐cyclists during arm and leg exercise. Respir Physiol Neurobiol 155: 64‐70, 2007.
 493. St Croix CM, Morgan BJ, Wetter TJ, Dempsey JA. Fatiguing inspiratory muscle work causes reflex sympathetic activation in humans. J Physiol 529(Pt 2): 493‐504, 2000.
 494. Stark‐Leyva KN, Beck KC, Johnson BD. Influence of expiratory loading and hyperinflation on cardiac output during exercise. J Appl Physiol 96: 1920‐1927, 2004.
 495. Steinbrook RA, Javaheri S, Gabel RA, Donovan JC, Leith DE, Fencl V. Respiration of chemodenervated goats in acute metabolic acidosis. Respir Physiol 56: 51‐60, 1984.
 496. Stewart JM, Medow MS, Montgomery LD, McLeod K. Decreased skeletal muscle pump activity in patients with postural tachycardia syndrome and low peripheral blood flow. Am J Physiol 286: H1216‐H1222, 2004.
 497. Stickland MK, Miller JD, Smith CA, Dempsey JA. Carotid chemoreceptor modulation of regional blood flow distribution during exercise in health and chronic heart failure. Circ Res 100: 1371‐1378, 2007.
 498. Stickland MK, Welsh RC, Petersen SR, Tyberg JV, Anderson WD, Jones RL, Taylor DA, Bouffard M, Haykowsky MJ. Does fitness level modulate the cardiovascular hemodynamic response to exercise? J Appl Physiol 100: 1895‐1901, 2006.
 499. Strohl KP, Norcia MP, Wolin AD, Haxhiu MA, van Lunteren E, Deal EC Jr. Nasal and tracheal responses to chemical and somatic afferent stimulation in anesthetized cats. J Appl Physiol 65: 870‐877, 1988.
 500. Stubbing DG, Pengelly LD, Morse JL, Jones NL. Pulmonary mechanics during exercise in normal males. J Appl Physiol 49: 506‐510, 1980.
 501. Stuessi C, Spengler CM, Knopfli‐Lenzin C, Markov G, Boutellier U. Respiratory muscle endurance training in humans increases cycling endurance without affecting blood gas concentrations. Eur J Appl Physiol84: 582‐586, 2001.
 502. Sue‐Chu M, Larsson L, Moen T, Rennard SI, Bjermer L. Bronchoscopy and bronchoalveolar lavage findings in cross‐country skiers with and without “ski asthma”. Eur Respir J 13: 626‐632, 1999.
 503. Sugiura T, Morimoto A, Murakami N. Effects of endurance training on myosin heavy‐chain isoforms and enzyme activity in the rat diaphragm. Pflugers Arch 421: 77‐81, 1992.
 504. Sugiura T, Morimoto A, Sakata Y, Watanabe T, Murakami N. Myosin heavy chain isoform changes in rat diaphragm are induced by endurance training. Jpn J Physiol 40: 759‐763, 1990.
 505. Supinski GS, Clary SJ, Bark H, Kelsen SG. Effect of inspiratory muscle fatigue on perception of effort during loaded breathing. J Appl Physiol 62: 300‐307, 1987.
 506. Supinski GS, Fitting JW, Bellemare F. ATS/ERS statement on respiratory muscle testing ‐ assessment of respiratory muscle fatigue. Am J Respir Crit Care Med 166: 518‐624, 2002.
 507. Suzuki J, Tanaka R, Yan S, Chen R, Macklem PT, Kayser B. Assessment of abdominal muscle contractility, strength, and fatigue. A Am J Respir Crit Care Med 159: 1052‐1060, 1999.
 508. Suzuki S, Suzuki J, Ishii T, Akahori T, Okubo T. Relationship of respiratory effort sensation to expiratory muscle fatigue during expiratory threshold loading. Am Rev Respir Dis 145: 461‐466, 1992.
 509. Suzuki S, Suzuki J, Okubo T. Expiratory muscle fatigue in normal subjects. J Appl Physiol 70: 2632‐2639, 1991.
 510. Szal SE, Schoene RB. Ventilatory response to rowing and cycling in elite oarswomen. J Appl Physiol 67: 264‐269, 1989.
 511. Takakura AC, Moreira TS, Colombari E, West GH, Stornetta RL, Guyenet PG. Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO2‐sensitive neurons in rats. J Physiol 572: 503‐523, 2006.
 512. Takata M, Wise RA, Robotham JL. Effects of abdominal pressure on venous return: Abdominal vascular zone conditions. J Appl Physiol 69: 1961‐1972, 1990.
 513. Tallman RD Jr, Marcolin R, Howie M, McDonald JS, Stafford T. Cardiopulmonary response to extracorporeal venous CO2 removal in awake spontaneously breathing dogs. J Appl Physiol 61: 516‐522, 1986.
 514. Tamaki N. Effect of endurance training on muscle fiber type composition and capillary supply in rat diaphragm. Eur J Appl Physiol 56: 127‐131, 1987.
 515. Tarasiuk A, Scharf SM, Miller MJ. Effect of chronic resistive loading on inspiratory muscles in rats. J Appl Physiol 70: 216‐222, 1991.
 516. Taylor BJ, How SC, Romer LM. Exercise‐induced abdominal muscle fatigue in healthy humans. J Appl Physiol 100: 1554‐1562, 2006.
 517. Taylor BJ, Romer LM. Effect of expiratory muscle fatigue on exercise tolerance and locomotor muscle fatigue in healthy humans. J Appl Physiol 104: 1442‐1451, 2008.
 518. Taylor BJ, Romer LM. Effect of expiratory resistive loading on inspiratory and expiratory muscle fatigue. Respir Physiol Neurobiol 166: 164‐174, 2009.
 519. Taylor BJ, West CR, Romer LM. No effect of arm‐crank exercise on diaphragmatic fatigue or ventilatory constraint in Paralympic athletes with cervical spinal cord injury. J Appl Physiol 109: 358‐366, 2010.
 520. Taylor CR, Weibel ER. Design of the mammalian respiratory system. Respir Physiol 44: 1‐164, 1981.
 521. Thoden JS, Dempsey JA, Reddan WG, Birnbaum ML, Forster HV, Grover RF, Rankin J. Ventilatory work during steady‐state response to exercise. Fed Proc 28: 1316‐1321, 1969.
 522. Thornton JM, Guz A, Murphy K, Griffith AR, Pedersen DL, Kardos A, Leff A, Adams L, Casadei B, Paterson DJ. Identification of higher brain centres that may encode the cardiorespiratory response to exercise in humans. J Physiol 533: 823‐836, 2001.
 523. Thurlbeck WM. Postnatal human lung growth. Thorax 37: 564‐571, 1982.
 524. Tibes U. Reflex inputs to the cardiovascular and respiratory centers from dynamically working canine muscles. Some evidence for involvement of group III or IV nerve fibers. Circ Res 41: 332‐341, 1977.
 525. Tibes U, Hemmer B, Boning D, Schweigart U. Relationships of femoral venous [K+], PO2, osmolality, and [orthophosphate) with heart rate, ventilation, and leg blood flow during bicycle exercise in athletes and non‐athletes. Eur J Appl Physiol 35: 201‐214, 1976.
 526. Tikunov B, Levine S, Mancini D. Chronic congestive heart failure elicits adaptations of endurance exercise in diaphragmatic muscle. Circ 95: 910‐916, 1997.
 527. Tolep K, Higgins N, Muza S, Criner G, Kelsen SG. Comparison of diaphragm strength between healthy adult elderly and young men. Am J Respir Crit Care Med 152: 677‐682, 1995.
 528. Tolep K, Kelsen SG. Effect of aging on respiratory skeletal muscles. Clinics Chest Med 14: 363‐378, 1993.
 529. Tong TK, Fu FH, Chung PK, Eston R, Lu K, Quach B, Nie J, So R. The effect of inspiratory muscle training on high‐intensity, intermittent running performance to exhaustion. Appl Physiol Nutr Metabol 33: 671‐681, 2008.
 530. Twisk JW, Staal BJ, Brinkman MN, Kemper HC, van Mechelen W. Tracking of lung function parameters and the longitudinal relationship with lifestyle. Eur Respir J 12: 627‐634, 1998.
 531. Tzelepis G, McCool FD, Leith DE, Hoppin FG Jr. Increased lung volume limits endurance of inspiratory muscles. J Appl Physiol 64: 1796‐1802, 1988.
 532. Uribe JM, Stump CS, Tipton CM, Fregosi RF. Influence of exercise training on the oxidative capacity of rat abdominal muscles. Respir Physiol 88: 171‐180, 1992.
 533. Vagg R, Mogyoros I, Kiernan MC, Burke D. Activity‐dependent hyperpolarization of human motor axons produced by natural activity. J Physiol 507: 919‐925, 1998.
 534. Valta P, Corbeil C, Lavoie A, Campodonico R, Koulouris N, Chasse M, Braidy J, Milic‐Emili J. Detection of expiratory flow limitation during mechanical ventilation. Am J Respir Crit Care Med 150: 1311‐1317, 1994.
 535. Van de Graaff WB. Thoracic influence on upper airway patency. J Appl Physiol 65: 2124‐2131, 1988.
 536. Verges S, Flore P, Blanchi MP, Wuyam B. A 10‐year follow‐up study of pulmonary function in symptomatic elite cross‐country skiers–athletes and bronchial dysfunctions. Scand J Sports Med Sci Sports 14: 381‐387, 2004.
 537. Verges S, Lenherr O, Haner AC, Schulz C, Spengler CM. Increased fatigue resistance of respiratory muscles during exercise after respiratory muscle endurance training. Am J Physiol Regul Integr Comp Physiol 292: R1246‐R1253, 2007.
 538. Verges S, Sager Y, Erni C, Spengler CM. Expiratory muscle fatigue impairs exercise performance. Eur J Appl Physiol 101: 225‐232, 2007.
 539. Verges S, Schulz C, Perret C, Spengler CM. Impaired abdominal muscle contractility after high‐intensity exhaustive exercise assessed by magnetic stimulation. Muscle Nerve 34: 423‐430, 2006.
 540. Verin E, Ross E, Demoule A, Hopkinson N, Nickol A, Fauroux B, Moxham J, Similowski T, Polkey MI. Effects of exhaustive incremental treadmill exercise on diaphragm and quadriceps motor potentials evoked by transcranial magnetic stimulation. J Appl Physiol 96: 253‐259, 2004.
 541. Vincent HK, Powers SK, Demirel HA, Coombes JS, Naito H. Exercise training protects against contraction‐induced lipid peroxidation in the diaphragm. Eur J Appl Physiol 79: 268‐273, 1999.
 542. Vincent HK, Powers SK, Stewart DJ, Demirel HA, Shanely RA, Naito H. Short‐term exercise training improves diaphragm antioxidant capacity and endurance. Eur J Appl Physiol 81: 67‐74, 2000.
 543. Vincent HK, Shanely RA, Stewart DJ, Demirel HA, Hamilton KL, Ray AD, Michlin C, Farkas GA, Powers SK. Adaptation of upper airway muscles to chronic endurance exercise. Am J Respir Crit Care Med 166: 287‐293, 2002.
 544. Vogiatzis I, Athanasopoulos D, Habazettl H, Aliverti A, Louvaris Z, Cherouveim E, Wagner H, Roussos C, Wagner PD, Zakynthinos S. Intercostal muscle blood flow limitation during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 182: 1105‐1113, 2010.
 545. Vogiatzis I, Georgiadou O, Giannopoulou I, Koskolou M, Zakynthinos S, Kostikas K, Kosmas E, Wagner H, Peraki E, Koutsoukou A, Koulouris N, Wagner PD, Roussos C. Effects of exercise‐induced arterial hypoxaemia and work rate on diaphragmatic fatigue in highly trained endurance athletes. J Physiol 572: 539‐549, 2006.
 546. Vogiatzis I, Georgiadou O, Koskolou M, Athanasopoulos D, Kostikas K, Golemati S, Wagner H, Roussos C, Wagner PD, Zakynthinos S. Effects of hypoxia on diaphragmatic fatigue in highly trained athletes. J Physiol 581: 299‐308, 2007.
 547. Volianitis S, McConnell AK, Koutedakis Y, McNaughton L, Backx K, Jones DA. Inspiratory muscle training improves rowing performance. Med Sci Sports Exerc 33: 803‐809, 2001.
 548. Vrabas IS, Dodd SL, Powers SK, Hughes M, Coombes J, Fletcher L, Demirel H, Reid MB. Endurance training reduces the rate of diaphragm fatigue in vitro. Med Sci Sports Exerc 31: 1605‐1612, 1999.
 549. Wagner PD. Why doesn't exercise grow the lungs when other factors do? Exerc Sport Sci Rev 33: 3‐8, 2005.
 550. Wagner PD, Araoz M, Boushel R, Calbet JA, Jessen B, Radegran G, Spielvogel H, Sondegaard H, Wagner H, Saltin B. Pulmonary gas exchange and acid‐base state at 5260 m in high‐altitude Bolivians and acclimatized lowlanders. J Appl Physiol 92: 1393‐1400, 2002.
 551. Waldrop TG, Eldridge FL, Iwamoto GA, Mitchell JH. Central neural control of respiration and circulation during exercise. In: Rowell LB, Shepherd JT, editors. Handbook of Physiology: Exercise: Regulation and Integration of Multiple Systems. New York: Oxford University Press, 1996, pp. 333‐380.
 552. Waldrop TG, Iwamoto GA. Point: Supraspinal locomotor centers do contribute significantly to the hyperpnea of dynamic exercise. J Appl Physiol 100: 1077‐1079, 2006.
 553. Walker DJ, Walterspacher S, Schlager D, Ertl T, Roecker K, Windisch W, Kabitz HJ. Characteristics of diaphragmatic fatigue during exhaustive exercise until task failure. Respir Physiol Neurobiol 176: 14‐20, 2011.
 554. Ward ME, Eidelman D, Stubbing DG, Bellemare F, Macklem PT. Respiratory sensation and pattern of respiratory muscle activation during diaphragm fatigue. J Appl Physiol 65: 2181‐2189, 1988.
 555. Ward SA, Swain L, Frye‐Kryder S. Phase‐coupling of arterial blood gas oscillations and ventilatory kinetics during exercise in humans. Phase coupling and the exercise hyperpnoea. Adv Exp Med Biol 393: 219‐224, 1995.
 556. Ward SA, Whipp BJ. Effects of peripheral and central chemoreflex activation on the isopnoeic rating of breathing in exercising humans. J Physiol 411: 27‐43, 1989.
 557. Warner MM, Mitchell GS. Ventilatory responses to hyperkalemia and exercise in normoxic and hypoxic goats. Respir Physiol 82: 239‐249, 1990.
 558. Warren JB, Jennings SJ, Clark TJ. Effect of adrenergic and vagal blockade on the normal human airway response to exercise. Clin Sci (Lond) 66: 79‐85, 1984.
 559. Wasserman K, Whipp BJ, Castagna J. Cardiodynamic hyperpnea: Hyperpnea secondary to cardiac output increase. J Appl Physiol 36: 457‐464, 1974.
 560. Wasserman K, Whipp BJ, Koyal SN, Cleary MG. Effect of carotid body resection on ventilatory and acid‐base control during exercise. J Appl Physiol 39: 354‐358, 1975.
 561. Watson TW, Whitelaw WA. Voluntary hyperventilation changes recruitment order of parasternal intercostal motor units. J Appl Physiol 62: 187‐193, 1987.
 562. Weibel ER. Understanding the limitation of O2 supply through comparative physiology. Respir Physiol 118: 85‐93, 1999.
 563. Weibel ER, Taylor CR, Hoppeler H. The concept of symmorphosis: A testable hypothesis of structure‐function relationship. Proc Natl Acad Sci U S A 88: 10357‐10361, 1991.
 564. Weibel ER, Taylor CR, Hoppeler H. Variations in function and design: Testing symmorphosis in the respiratory system. Respir Physiol 87: 325‐348, 1992.
 565. Weil JV, Byrne‐Quinn E, Sodal IE, Kline JS, McCullough RE, Filley GF. Augmentation of chemosensitivity during mild exercise in normal man. J Appl Physiol 33: 813‐819, 1972.
 566. Weissman ML, Whipp BJ, Huntsman DJ, Wasserman K. Role of neural afferents from working limbs in exercise hyperpnea. J Appl Physiol 49: 239‐248, 1980.
 567. West JB. Invited review: Pulmonary capillary stress failure. J Appl Physiol 89: 2483‐2489; discussion 2497, 2000.
 568. Wetter TJ, Harms CA, Nelson WB, Pegelow DF, Dempsey JA. Influence of respiratory muscle work on VO2 and leg blood flow during submaximal exercise. J Appl Physiol 87: 643‐651, 1999.
 569. Wetter TJ, St Croix CM, Pegelow DF, Sonetti DA, Dempsey JA. Effects of exhaustive endurance exercise on pulmonary gas exchange and airway function in women. J Appl Physiol 91: 847‐858, 2001.
 570. Wexler L, Bergel DH, Gabe IT, Makin GS, Mills CJ. Velocity of blood flow in normal human venae cavae. Circ Res 23: 349‐359, 1968.
 571. Willeput R, Rondeux C, De Troyer A. Breathing affects venous return from legs in humans. J Appl Physiol 57: 971‐976, 1984.
 572. Williams JS, Janssen PL, Fuller DD, Fregosi RF. Influence of posture and breathing route on neural drive to upper airway dilator muscles during exercise. J Appl Physiol 89: 590‐598, 2000.
 573. Williamson JW, Raven PB, Foresman BH, Whipp BJ. Evidence for an intramuscular ventilatory stimulus during dynamic exercise in man. Respir Physiol 94: 121‐135, 1993.
 574. Wilson SH, Welch HG. Effects of varying concentrations of N2/O2 and He/O2 on exercise tolerance in man. Med Sci Sports Exer 12: 380‐384, 1980.
 575. Witt JD, Guenette JA, Rupert JL, McKenzie DC, Sheel AW. Inspiratory muscle training attenuates the human respiratory muscle metaboreflex. J Physiol 584: 1019‐1028, 2007.
 576. Wood HE, Fatemian M, Robbins PA. A learned component of the ventilatory response to exercise in man. J Physiol 553: 967‐974, 2003.
 577. Wragg S, Hamnegard C, Road J, Kyroussis D, Moran J, Green M, Moxham J. Potentiation of diaphragmatic twitch after voluntary contraction in normal subjects. Thorax 49: 1234‐1237, 1994.
 578. Xu F, Frazier DT. Modulation of respiratory motor output by cerebellar deep nuclei in the rat. J Appl Physiol 89: 996‐1004, 2000.
 579. Xu F, Frazier DT. Respiratory‐related neurons of the fastigial nucleus in response to chemical and mechanical challenges. J Appl Physiol 82: 1177‐1184, 1997.
 580. Xu F, Zhang Z, Frazier DT. Microinjection of acetazolamide into the fastigial nucleus augments respiratory output in the rat. J Appl Physiol 91: 2342‐2350, 2001.
 581. Yamamoto WS, Edwards MW Jr. Homeostasis of carbon dioxide during intravenous infusion of carbon dioxide. J Appl Physiol 15: 807‐818, 1960.
 582. Yamashiro SM, Grodins FS. Respiratory cycle optimization in exercise. J Appl Physiol 35: 522‐525, 1973.
 583. Yan S, Gauthier AP, Similowski T, Faltus R, Macklem PT, Bellemare F. Force‐frequency relationships of in vivo human and in vitro rat diaphragm using paired stimuli. Eur Respir J 6: 211‐218, 1993.
 584. Zeltner TB, Burri PH. The postnatal development and growth of the human lung. II. Morphology. Respir Physiol 67: 269‐282, 1987.
 585. Zhu E, Petrof BJ, Gea J, Comtois N, Grassino AE. Diaphragm muscle fiber injury after inspiratory resistive breathing. Am J Respir Crit Care Med 155: 1110‐1116, 1997.
 586. Zinman R, Gaultier C. Maximal static pressures and lung volumes in young female swimmers: One year follow‐up. Pediatr Pulmonol 3: 145‐148, 1987.
 587. Zocchi L, Fitting JW, Majani U, Fracchia C, Rampulla C, Grassino A. Effect of pressure and timing of contraction on human rib cage muscle fatigue. Am Rev Respir Dis 147: 857‐864, 1993.
 588. Zuntz N, Geppert J. Uber die Natur der normalen Atemreize und den Ort ihrer Wirkung. Arch Ges Physiol 38: 337‐338, 1886.
Further Reading
 1.The thorax. Roussos C, editor. Lung Biology in Health and Disease. Lenfant C, series editor. New York: Marcel Dekker, 1995.
 2.The Lung: Scientific Foundations. Crystal RG, West JB, Weibel ER, Barnes PJ, editors. Philadelphia: Lippincott‐Raven, 1997.
 3.West JB. Respiratory Physiology – The Essentials (8th ed). Baltimore: Lippincott Williams and Wilkins, 2008.
 4.Physiological Basis of Respiratory Disease. Hamid Q, Shannon J, Martin J, editors. Hamilton, ON: BC Dekker Inc, 2005.

Further Reading

The Thorax. Roussos C (Ed).  Lung Biology in Health and Disease. C. Lenfant (Series Ed).  New York: Marcel Dekker, 1995.

The Lung: Scientific Foundations. Crystal RG, West JB, Weibel ER and Barnes PJ.  Philadelphia: Lippincott-Raven, 1997.

West JB. Respiratory Physiology – The Essentials (8th Edition).  Baltimore: Lippincott Williams and Wilkins, 2008.

Physiological basis of respiratory disease.  Hamid Q, Shannon J and Martin J (Eds).  Hamilton, ON: BC Dekker Inc, 2005.

 


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Andrew William Sheel, Lee M. Romer. Ventilation and Respiratory Mechanics. Compr Physiol 2012, 2: 1093-1142. doi: 10.1002/cphy.c100046