Distinguishing science from pseudoscience in commercial respiratory interventions: an evidence-based guide for health and exercise professionals.

Respiratory function has become a global health priority. Not only is chronic respiratory disease a leading cause of worldwide morbidity and mortality, but the COVID-19 pandemic has heightened attention on respiratory health and the means of enhancing it. Subsequently, and inevitably, the respiratory system has become a target of the multi-trillion-dollar health and wellness industry. Numerous commercial, respiratory-related interventions are now coupled to therapeutic and/or ergogenic claims that vary in their plausibility: from the reasonable to the absurd. Moreover, legitimate and illegitimate claims are often conflated in a wellness space that lacks regulation. The abundance of interventions, the range of potential therapeutic targets in the respiratory system, and the wealth of research that varies in quality, all confound the ability for health and exercise professionals to make informed risk-to-benefit assessments with their patients and clients. This review focuses on numerous commercial interventions that purport to improve respiratory health, including nasal dilators, nasal breathing, and systematized breathing interventions (such as pursed-lips breathing), respiratory muscle training, canned oxygen, nutritional supplements, and inhaled L-menthol. For each intervention we describe the premise, examine the plausibility, and systematically contrast commercial claims against the published literature. The overarching aim is to assist health and exercise professionals to distinguish science from pseudoscience and make pragmatic and safe risk-to-benefit decisions.

Stabilising function of the human diaphragm in response to involuntary augmented breaths induced with or without lower-limb movements.

NEW FINDINGS: What is the central question of this study? Is the stabilising function of the diaphragm altered differentially in response to involuntary augmented breaths induced with or without lower-limb movements? What is the main finding and its importance? At equivalent levels of ventilation, the diaphragm generated higher passive pressure but moved significantly less during incremental cycle ergometry compared with progressive hypercapnia. Diaphragm excursion velocity and power output did not differ between the two tasks. These findings imply that the power output of the diaphragm during stabilising tasks involving the lower limbs may be preserved via coordinated changes in contractile shortening. ABSTRACT: Activity of key respiratory muscles, such as the diaphragm, must balance the demands of ventilation with the maintenance of stable posture. Our aim was to test whether the stabilising function of the diaphragm would be altered differentially in response to involuntary augmented breaths induced with or without lower-limb movements. Ten healthy volunteers (age 21 (2) years; mean (SD)) performed progressive CO2 -rebreathe (5% CO2 , 95% O2 ) followed 20 min later by incremental cycle exercise (15-30 W/min), both in a semi-recumbent position. Ventilatory indices, intrathoracic pressures and ultrasonographic measures of diaphragm shortening were assessed before, during and after each task. From rest to iso-time, inspiratory tidal volume and minute ventilation increased two- to threefold. At equivalent levels of tidal volume and minute ventilation, mean inspiratory transdiaphragmatic pressure ( P ¯ di ${\bar P_{{\rm{di}}}}$ ) was consistently higher during exercise compared with CO2 -rebreathe due to larger increases in gastric pressure and the passive component of P ¯ di ${\bar P_{{\rm{di}}}}$ (i.e., mechanical output due to static contractions), and yet diaphragm excursion was consistently lower. This lower excursion during exercise was accompanied by a reduction in excursion time with no difference in the active component of P ¯ di ${\bar P_{{\rm{di}}}}$ . Consequently, the rates of increase in excursion velocity (excursion/time) and power output (active P ¯ di ${\bar P_{{\rm{di}}}}$ × velocity) did not differ between the two tasks. In conclusion, the power output of the human diaphragm during dynamic lower-limb exercise appears to be preserved via coordinated changes in contractile shortening. The findings may have significance in settings where the ventilatory and stabilising functions of the diaphragm must be balanced (e.g., rehabilitation).

Manipulation of mechanical ventilatory constraint during moderate intensity exercise does not influence dyspnoea in healthy older men and women.

KEY POINTS: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex-differences in respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single-blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate-intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. ABSTRACT: We aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60-80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6-min bouts of cycling at ventilatory threshold, in a single-blind randomized manner, while breathing: (i) normoxic helium-oxygen (HEL) to reduce the work of breathing (Wb ) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2 O L-1  s-1 to increase Wb ; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category-ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in Wb (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea.

Mechanical-ventilatory responses to peak and ventilation-matched upper- versus lower-body exercise in normal subjects.

NEW FINDINGS: What is the central question of this study? To what extent are the mechanical-ventilatory responses to upper-body exercise influenced by task-specific locomotor mechanics? What is the main finding and its importance? When compared with lower-body exercise performed at similar ventilations, upper-body exercise was characterized by tidal volume constraint, dynamic lung hyperinflation and an increased propensity towards neuromechanical uncoupling of the respiratory system. Importantly, these responses were independent of respiratory dysfunction and flow limitation. Thus, the mechanical ventilatory responses to upper-body exercise are attributable, in part, to task-specific locomotor mechanics (i.e. non-respiratory loading of the thorax). ABSTRACT: The aim of this study was to determine the extent to which the mechanical ventilatory responses to upper-body exercise are influenced by task-specific locomotor mechanics. Eight healthy men (mean ± SD: age, 24 ± 5 years; mass, 74 ± 11 kg; and stature, 1.79 ± 0.07 m) completed two maximal exercise tests, on separate days, comprising 4 min stepwise increments of 15 W during upper-body exercise (arm-cranking) or 30 W during lower-body exercise (leg-cycling). The tests were repeated at work rates calculated to elicit 20, 40, 60, 80 and 100% of the peak ventilation achieved during arm-cranking ( V̇E,UBE ). Exercise measures included pulmonary ventilation and gas exchange, oesophageal pressure-derived indices of respiratory mechanics, operating lung volumes and expiratory flow limitation. Subjects exhibited normal resting pulmonary function. Arm-crank exercise elicited significantly lower peak values for work rate, O2 uptake, CO2 output, minute ventilation and tidal volume (p < 0.05). At matched ventilations, arm-crank exercise restricted tidal volume expansion relative to leg-cycling exercise at 60% V̇E,UBE (1.74 ± 0.61 versus 2.27 ± 0.68 l, p < 0.001), 80% V̇E,UBE (2.07 ± 0.70 versus 2.52 ± 0.67 l, p < 0.001) and 100% V̇E,UBE (1.97 ± 0.85 versus 2.55 ± 0.72 l, p = 0.002). Despite minimal evidence of expiratory flow limitation, expiratory reserve volume was significantly higher during arm-cranking versus leg-cycling exercise at 100% V̇E,UBE (39 ± 8 versus 29 ± 8% of vital capacity, p = 0.002). At any given ventilation, arm-cranking elicited greater inspiratory effort (oesophageal pressure) relative to thoracic displacement (tidal volume). Arm-cranking exercise is sufficient to provoke respiratory mechanical derangements (restricted tidal volume expansion, dynamic hyperinflation and neuromechanical uncoupling) in subjects with normal pulmonary function and expiratory flow reserve. These responses are likely to be attributable to task-specific locomotor mechanics (i.e. non-respiratory loading of the thorax).

Exercise-induced quadriceps muscle fatigue in men and women: effects of arterial oxygen content and respiratory muscle work.

KEY POINTS: High work of breathing and exercise-induced arterial hypoxaemia (EIAH) can decrease O2 delivery and exacerbate exercise-induced quadriceps fatigue in healthy men. Women have a higher work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles and develop EIAH. Despite a greater reduction in men's work of breathing, the attenuation of quadriceps fatigue was similar between the sexes. The degree of EIAH was similar between sexes, and regardless of sex, those who developed the greatest hypoxaemia during exercise demonstrated the most attenuation of quadriceps fatigue. Based on our previous finding that women have a greater relative oxygen cost of breathing, women appear to be especially susceptible to work of breathing-related changes in quadriceps muscle fatigue. ABSTRACT: Reducing the work of breathing or eliminating exercise-induced arterial hypoxaemia (EIAH) during exercise decreases the severity of quadriceps fatigue in men. Women have a greater work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles, and demonstrate EIAH, suggesting women may be especially susceptible to quadriceps fatigue. Healthy subjects (8 male, 8 female) completed three constant load exercise tests over 4 days. During the first (control) test, subjects exercised at ∼85% of maximum while arterial blood gases and work of breathing were assessed. Subsequent constant load exercise tests were iso-time and iso-work rate, but with EIAH prevented by inspiring hyperoxic gas or work of breathing reduced via a proportional assist ventilator (PAV). Quadriceps fatigue was assessed by measuring force in response to femoral nerve stimulation. For both sexes, quadriceps force was equally reduced after the control trial (-27 ± 2% baseline) and was attenuated with hyperoxia and PAV (-18 ± 1 and -17 ± 2% baseline, P < 0.01, respectively), with no sex difference. EIAH was similar between the sexes, and regardless of sex, subjects with the lowest oxyhaemoglobin saturation during the control test had the greatest quadriceps fatigue attenuation with hyperoxia (r2  = 0.79, P < 0.0001). For the PAV trial, despite reducing the work of breathing to a greater degree in men (men: 60 ± 5, women: 75 ± 6% control, P < 0.05), the attenuation of quadriceps fatigue was similar between the sexes (36 ± 4 vs. 37 ± 7%). Owing to a greater relative V̇O2 of the respiratory muscles in women, less of a change in work of breathing is needed to reduce quadriceps fatigue.

Influence of inspiratory resistive loading on expiratory muscle fatigue in healthy humans.

NEW FINDINGS: What is the central question of this study? This study is the first to measure objectively both inspiratory and expiratory muscle fatigue after inspiratory resistive loading to determine whether the expiratory muscles are activated to the point of fatigue when specifically loading the inspiratory muscles. What is the main finding and its importance? The absence of abdominal muscle fatigue suggests that future studies attempting to understand the neural and circulatory consequences of diaphragm fatigue can use inspiratory resistive loading without considering the confounding effects of abdominal muscle fatigue. Expiratory resistive loading elicits inspiratory as well as expiratory muscle fatigue, suggesting parallel coactivation of the inspiratory muscles during expiration. It is unknown whether the expiratory muscles are likewise coactivated to the point of fatigue during inspiratory resistive loading (IRL). The purpose of this study was to determine whether IRL elicits expiratory as well as inspiratory muscle fatigue. Healthy male subjects (n = 9) underwent isocapnic IRL (60% maximal inspiratory pressure, 15 breaths min-1 , 0.7 inspiratory duty cycle) to task failure. Abdominal and diaphragm contractile function was assessed at baseline and at 3, 15 and 30 min post-IRL by measuring gastric twitch pressure (Pga,tw ) and transdiaphragmatic twitch pressure (Pdi,tw ) in response to potentiated magnetic stimulation of the thoracic and phrenic nerves, respectively. Fatigue was defined as a significant reduction from baseline in Pga,tw or Pdi,tw . Throughout IRL, there was a time-dependent increase in cardiac frequency and mean arterial blood pressure, suggesting activation of the respiratory muscle metaboreflex. The Pdi,tw was significantly lower than baseline (34.3 ± 9.6 cmH2 O) at 3 (23.2 ± 5.7 cmH2 O, P < 0.001), 15 (24.2 ± 5.1 cmH2 O, P < 0.001) and 30 min post-IRL (26.3 ± 6.0 cmH2 O, P < 0.001). The Pga,tw was not significantly different from baseline (37.6 ± 17.1 cmH2 O) at 3 (36.5 ± 14.6 cmH2 O), 15 (33.7 ± 12.4 cmH2 O) and 30 min post-IRL (32.9 ± 11.3 cmH2 O). Inspiratory resistive loading elicits objective evidence of diaphragm, but not abdominal, muscle fatigue. Agonist-antagonist interactions for the respiratory muscles appear to be more important during expiratory versus inspiratory loading.

Effect of cadence on locomotor-respiratory coupling during upper-body exercise.

INTRODUCTION: Asynchronous arm-cranking performed at high cadences elicits greater cardiorespiratory responses compared to low cadences. This has been attributed to increased postural demand and locomotor-respiratory coupling (LRC), and yet, this has not been empirically tested. This study aimed to assess the effects of cadence on cardiorespiratory responses and LRC during upper-body exercise. METHODS: Eight recreationally-active men performed arm-cranking exercise at moderate and severe intensities that were separated by 10 min of rest. At each intensity, participants exercised for 4 min at each of three cadences (50, 70, and 90 rev min-1) in a random order, with 4 min rest-periods applied in-between cadences. Exercise measures included LRC via whole- and half-integer ratios, cardiorespiratory function, perceptions of effort (RPE and dyspnoea), and diaphragm EMG using an oesophageal catheter. RESULTS: The prevalence of LRC during moderate exercise was highest at 70 vs. 50 rev min-1 (27 ± 10 vs. 13 ± 9%, p = 0.000) and during severe exercise at 90 vs. 50 rev min-1 (24 ± 7 vs. 18 ± 5%, p = 0.034), with a shorter inspiratory time and higher mean inspiratory flow (p < 0.05) at higher cadences. During moderate exercise, [Formula: see text] and f C were higher at 90 rev min-1 (p < 0.05) relative to 70 and 50 rev min-1 ([Formula: see text] 1.19 ± 0.25 vs. 1.05 ± 0.21 vs. 0.97 ± 0.24 L min-1; f C 116 ± 11 vs. 101 ± 13 vs. 101 ± 12 b min-1), with concomitantly elevated dyspnoea. There were no discernible cadence-mediated effects on diaphragm EMG. CONCLUSION: Participants engage in LRC to a greater extent at moderate-high cadences which, in turn, increase respiratory airflow. Cadence rate should be carefully considered when designing aerobic training programmes involving the upper-limbs.

Oxygen cost of exercise hyperpnoea is greater in women compared with men.

KEY POINTS: The oxygen cost of breathing represents a significant fraction of total oxygen uptake during intense exercise. At a given ventilation, women have a greater work of breathing compared with men, and because work is linearly related to oxygen uptake we hypothesized that their oxygen cost of breathing would also be greater. For a given ventilation, women had a greater absolute oxygen cost of breathing, and this represented a greater fraction of total oxygen uptake. Regardless of sex, those who developed expiratory flow limitation had a greater oxygen cost of breathing at maximal exercise. The greater oxygen cost of breathing in women indicates that a greater fraction of total oxygen uptake (and possibly cardiac output) is directed to the respiratory muscles, which may influence blood flow distribution during exercise. ABSTRACT: We compared the oxygen cost of breathing (V̇O2 RM ) in healthy men and women over a wide range of exercise ventilations (V̇E). Eighteen subjects (nine women) completed 4 days of testing. First, a step-wise maximal cycle exercise test was completed for the assessment of spontaneous breathing patterns. Next, subjects were familiarized with the voluntary hyperpnoea protocol used to estimate V̇O2 RM . During the final two visits, subjects mimicked multiple times (four to six) the breathing patterns associated with five or six different exercise stages. Each trial lasted 5 min, and on-line pressure-volume and flow-volume loops were superimposed on target loops obtained during exercise to replicate the work of breathing accurately. At ∼55 l min(-1) V̇E, V̇O2 RM was significantly greater in women. At maximal ventilation, the absolute V̇O2 RM was not different (P > 0.05) between the sexes, but represented a significantly greater fraction of whole-body V̇O2 in women (13.8 ± 1.5 vs. 9.4 ± 1.1% V̇O2). During heavy exercise at 92 and 100% V̇O2max, the unit cost of V̇E was +0.7 and +1.1 ml O2 l(-1) greater in women (P < 0.05). At V̇O2max, men and women who developed expiratory flow limitation had a significantly greater V̇O2 RM than those who did not (435 ± 44 vs. 331 ± 30 ml O2  min(-1) ). In conclusion, women have a greater V̇O2 RM for a given V̇E, and this represents a greater fraction of whole-body V̇O2. The greater V̇O2 RM in women may have implications for the integrated physiological response to exercise.

Supraspinal fatigue after normoxic and hypoxic exercise in humans.

Inadequate cerebral O2 availability has been proposed to be an important contributing factor to the development of central fatigue during strenuous exercise. Here we tested the hypothesis that supraspinal processes of fatigue would be increased after locomotor exercise in acute hypoxia compared to normoxia, and that such change would be related to reductions in cerebral O2 delivery and tissue oxygenation. Nine endurance-trained cyclists completed three constant-load cycling exercise trials at ∼80% of maximal work rate: (1) to the limit of tolerance in acute hypoxia; (2) for the same duration but in normoxia (control); and (3) to the limit of tolerance in normoxia. Throughout each trial, prefrontal cortex tissue oxygenation and middle cerebral artery blood velocity (MCAV) were assessed using near-infrared spectroscopy and trans-cranial Doppler sonography, respectively. Cerebral O2 delivery was calculated as the product of arterial O2 content and MCAV. Before and immediately after each trial, twitch responses to supramaximal femoral nerve stimulation and transcranial magnetic stimulation were obtained to assess neuromuscular and cortical function, respectively. Exercise time was reduced by 54%in hypoxia compared to normoxia (3.6 ± 1.3 vs. 8.1 ± 2.9 min; P<0.001). Cerebral O2 delivery,cerebral oxygenation and maximum O2 uptake were reduced whereas muscle electromyographic activity was increased in hypoxia compared to control (P <0.05).Maximum voluntary force and potentiated quadriceps twitch force were decreased below baseline after exercise in each trial;the decreases were greater in hypoxia compared to control (P<0.001), but were not different in the exhaustive trials (P>0.05). Cortical voluntary activation was also decreased after exercise in all trials, but the decline in hypoxia (Δ18%) was greater than in the normoxic trials (Δ5-9%)(P <0.05). The reductions in cortical voluntary activation were paralleled by reductions in cerebral O2 delivery. The results suggest that curtailment of exercise performance in acute severe hypoxia is due, in part, to failure of drive from the motor cortex, possibly as a consequence of diminished O2 availability in the brain.

Assessment of pulmonary restriction in cervical spinal cord injury: a preliminary report.

OBJECTIVE: To compare the prevalence of pulmonary restriction on the basis of a vital capacity (VC) below the lower limit of normal (LLN) and a normal or high forced expiratory volume in 1 second (FEV(1))/VC ratio with the criterion standard of total lung capacity (TLC) less than LLN in individuals with spinal cord injury (SCI) and able-bodied (AB) controls. DESIGN: Method comparison with criterion standard. SETTING: University research center. PARTICIPANTS: Individuals with cervical SCI (n=12; injury level, C5-7) and AB controls (n=12) matched for age, stature, and body mass. INTERVENTIONS: None. MAIN OUTCOME MEASURES: TLC via plethysmography; FEV(1) and VC via spirometry; and maximum inspiratory and expiratory pressures (P(Imax) and P(Emax)). RESULTS: All participants with SCI exhibited a VC less than LLN and a normal-to-high FEV(1)/VC ratio, whereas significantly fewer (8 of 12) participants with SCI exhibited a TLC less than LLN (P=.046). For the AB group, no participant exhibited a VC or TLC less than LLN. Percent-predicted VC was lower than the percent-predicted TLC in SCI (P=.013), whereas percent-predicted VC was higher than percent-predicted TLC in AB controls (P=.001). Percent-predicted P(Imax) was higher than P(Emax) in SCI (P=.001) but not AB controls (P=.146). CONCLUSIONS: A VC less than LLN with a normal-to-high FEV(1)/VC ratio does not accurately predict pulmonary restriction in cervical SCI. When using spirometry to infer pulmonary restriction in cervical SCI, we recommend using a VC below 60% of the AB predicted value.

Effect of "Pose" cycling on efficiency and pedaling mechanics.

The purpose of this study was to determine the effect of "Pose" cycling (a combination of specific bicycle setup and pedaling technique) on metabolic efficiency and pedaling mechanics. Eighteen recreational cyclists were tested for efficiency and pedaling mechanics during steady-state cycling (90% gas-exchange threshold) using two different bicycle setups (preferred and "Pose") and three different pedaling rates (70, 90 and 110 rpm). Nine of the participants underwent a coaching intervention (4 × 1 h) consisting of drills based on the "Pose" instruction manual. The remaining nine participants did not receive an intervention. All participants were tested before and after the intervention period. Analyses of variance were performed to test the independent effects of the "Pose"-specific bicycle setup and pedaling technique on gross efficiency and pedaling mechanics. The "Pose"-specific bicycle setup resulted in increased gross efficiency at each pedaling rate compared to the participants' preferred bicycle position (P < 0.05). This increase in efficiency was accompanied by a significant increase in trunk frontal area (P < 0.05). The coaching intervention resulted in decreased gross efficiency at 110 rpm (P < 0.05); at this pedaling rate the intervention resulted in a slight increase in the non-muscular contribution to pedal power in the experimental group and a decrease in the control group. The combination of changed bicycle setup and pedaling technique had no effect on gross efficiency and only small effects on pedaling mechanics. Our findings add to a growing body of literature that short-term interventions in pedaling technique can change pedaling mechanics but do not improve efficiency during steady-state cycling.

Systemic but not local rehydration restores dehydration-induced changes in pulmonary function in healthy adults.

Water transport and local (airway) hydration are critical for the normal functioning of lungs and airways. Currently, there is uncertainty regarding the effects of systemic dehydration on pulmonary function. Our aims were 1) to clarify the impact of exercise- or fluid restriction-induced dehydration on pulmonary function in healthy adults; and 2) to establish whether systemic or local rehydration can reverse dehydration-induced alterations in pulmonary function. Ten healthy participants performed four experimental trials in a randomized order (2 h exercise in the heat twice and 28 h fluid restriction twice). Pulmonary function was assessed using spirometry and whole body plethysmography in the euhydrated, dehydrated, and rehydrated states. Oral fluid consumption was used for systemic rehydration and nebulized isotonic saline inhalation for local rehydration. Both exercise and fluid restriction induced mild dehydration (2.7 ± 0.7% and 2.5 ± 0.4% body mass loss, respectively; P < 0.001) and elevated plasma osmolality (P < 0.001). Dehydration across all four trials was accompanied by a reduction in forced vital capacity (152 ± 143 mL, P < 0.01) and concomitant increases in residual volume (216 ± 177 mL, P < 0.01) and functional residual capacity (130 ± 144 mL, P < 0.01), with no statistical differences between modes of dehydration. These changes were normalized by fluid consumption but not nebulization. Our results suggest that, in healthy adults: 1) mild systemic dehydration induced by exercise or fluid restriction leads to pulmonary function impairment, primarily localized to small airways; and 2) systemic, but not local, rehydration reverses these potentially deleterious alterations.NEW & NOTEWORTHY This study demonstrates that, in healthy adults, mild systemic dehydration induced by exercise in the heat or a prolonged period of fluid restriction leads to negative alterations in pulmonary function, primarily localized to small airways. Oral rehydration, but not nebulized isotonic saline, is able to restore pulmonary function in dehydrated individuals. Our findings highlight the importance of maintaining an adequate systemic fluid balance to preserve pulmonary function.

Transpulmonary passage of 99mTc macroaggregated albumin in healthy humans at rest and during maximal exercise.

We have demonstrated that 50-mum-diameter arteriovenous pathways exist in isolated, healthy human and baboon lungs, ventilated and perfused under physiological pressures. These findings have been confirmed and extended by demonstrating the passage of 25-microm microspheres through the lungs of exercising dogs, but not at rest. Determination of blood flow through these large-diameter intrapulmonary arteriovenous pathways would be an important first step to establish a physiological role for these vessels. Currently, we sought to estimate blood flow through these arteriovenous pathways using technetium-99m ((99m)Tc)-labeled macroaggregated albumin (MAA) in healthy humans at rest and during maximal treadmill exercise. We hypothesized that the percentage of (99m)Tc MAA able to traverse the pulmonary circulation (%transpulmonary passage) would increase during exercise. Seven male subjects without patent foramen ovale were injected with (99m)Tc MAA at rest on 1 day and during maximal treadmill exercise on a separate day (>6 days). Within 5 min after injection, subjects began whole body imaging in the supine position. Six of the seven subjects showed an increase in transpulmonary passage of MAA with maximal exercise. Using two separate analysis methods, percent transpulmonary passage significantly increased with exercise from baseline to absolute values of 1.2 +/- 0.8% (P = 0.008) and 1.3 +/- 1.0% (P = 0.016), respectively (means +/- SD; paired t-test). We conclude that MAA may be traversing the pulmonary circulation via large-diameter intrapulmonary arteriovenous conduits in healthy humans during exercise. Recruitment of these pathways may divert blood flow away from pulmonary capillaries during exercise and compromise the lung's function as a biological filter.

Physiological and Pathophysiological Consequences of a 25-Day Ultra-Endurance Exercise Challenge.

Background: This case-report characterized the respiratory, cardiovascular, and nutritional/gastrointestinal (GI) responses of a trained individual to a novel ultra-endurance exercise challenge. Case Presentation: A male athlete (age 45 years; V ˙ O2max 54.0 mL⋅kg-1⋅min-1) summited 100 mountains on foot in 25 consecutive days (all elevations >600 m). Measures: Laboratory measures of pulmonary function (spirometry, whole-body plethysmography, and single-breath rebreathe), respiratory muscle function (maximum static mouth-pressures), and cardiovascular structure and function (echocardiography, electrocardiography, large vessel ultrasound, and flow-mediated dilatation) were made at baseline and 48 h post-challenge. Dietary intake (four-day food diary), self-reported GI symptoms and plasma endotoxin concentrations were assessed at baseline, pre/post mid-point, pre/post end-point, and 48 h post-challenge. Results: The challenge was completed in a total exercise time of 142 h (5.3 ± 2.8 h⋅d-1), with a distance of 1141 km (42.3 ± 43.9 km⋅d-1), and energy expenditure of 80460 kcal (2980 ± 1451 kcal⋅d-1). Relative to baseline, there were post-challenge decreases in pulmonary capacities and expiratory flows (≤34%), maximum expiratory mouth-pressure (19%), and maximum voluntary ventilation (29%). Heart rate variability deteriorated, manifesting as a 48% decrease in the root mean square of successive differences and a 70% increase in the low-frequency/high-frequency ratio. Pre- to post-challenge endotoxin concentrations were elevated by 60%, with a maximum increase of 130% after a given stage, congruent with an increased frequency and severity of GI symptoms. Conclusion: The challenge resulted in pulmonary and autonomic dysfunction, endotoxaemia, and GI distress. The findings extend our understanding of the limits of physiological function and may inform medical best-practice for personnel supporting ultra-endurance events.

Exercise-induced respiratory muscle fatigue: implications for performance.

It is commonly held that the respiratory system has ample capacity relative to the demand for maximal O(2) and CO(2) transport in healthy humans exercising near sea level. However, this situation may not apply during heavy-intensity, sustained exercise where exercise may encroach on the capacity of the respiratory system. Nerve stimulation techniques have provided objective evidence that the diaphragm and abdominal muscles are susceptible to fatigue with heavy, sustained exercise. The fatigue appears to be due to elevated levels of respiratory muscle work combined with an increased competition for blood flow with limb locomotor muscles. When respiratory muscles are prefatigued using voluntary respiratory maneuvers, time to exhaustion during subsequent exercise is decreased. Partially unloading the respiratory muscles during heavy exercise using low-density gas mixtures or mechanical ventilation can prevent exercise-induced diaphragm fatigue and increase exercise time to exhaustion. Collectively, these findings suggest that respiratory muscle fatigue may be involved in limiting exercise tolerance or that other factors, including alterations in the sensation of dyspnea or mechanical load, may be important. The major consequence of respiratory muscle fatigue is an increased sympathetic vasoconstrictor outflow to working skeletal muscle through a respiratory muscle metaboreflex, thereby reducing limb blood flow and increasing the severity of exercise-induced locomotor muscle fatigue. An increase in limb locomotor muscle fatigue may play a pivotal role in determining exercise tolerance through a direct effect on muscle force output and a feedback effect on effort perception, causing reduced motor output to the working limb muscles.

Effect of expiratory muscle fatigue on exercise tolerance and locomotor muscle fatigue in healthy humans.

High-intensity exercise (> or =90% of maximal O(2) uptake) sustained to the limit of tolerance elicits expiratory muscle fatigue (EMF). We asked whether prior EMF affects subsequent exercise tolerance. Eight male subjects (means +/- SD; maximal O(2) uptake = 53.5 +/- 5.2 ml.kg(-1).min(-1)) cycled at 90% of peak power output to the limit of tolerance with (EMF-EX) and without (CON-EX) prior induction of EMF and for a time equal to that achieved in EMF-EX but without prior induction of EMF (ISO-EX). To induce EMF, subjects breathed against an expiratory flow resistor until task failure (15 breaths/min, 0.7 expiratory duty cycle, 40% of maximal expiratory gastric pressure). Fatigue of abdominal and quadriceps muscles was assessed by measuring the reduction relative to prior baseline values in magnetically evoked gastric twitch pressure (Pga(tw)) and quadriceps twitch force (Q(tw)), respectively. The reduction in Pga(tw) was not different after resistive breathing vs. after CON-EX (-27 +/- 5 vs. -26 +/- 6%; P = 0.127). Exercise time was reduced by 33 +/- 10% in EMF-EX vs. CON-EX (6.85 +/- 2.88 vs. 9.90 +/- 2.94 min; P < 0.001). Exercise-induced abdominal and quadriceps muscle fatigue was greater after EMF-EX than after ISO-EX (-28 +/- 9 vs. -12 +/- 5% for Pga(tw), P = 0.001; -28 +/- 7 vs. -14 +/- 6% for Q(tw), P = 0.015). Perceptual ratings of dyspnea and leg discomfort (Borg CR10) were higher at 1 and 3 min and at end exercise during EMF-EX vs. during ISO-EX (P < 0.05). Percent changes in limb fatigue and leg discomfort (EMF-EX vs. ISO-EX) correlated significantly with the change in exercise time. We propose that EMF impaired subsequent exercise tolerance primarily through an increased severity of limb locomotor muscle fatigue and a heightened perception of leg discomfort.

Intrapulmonary shunting and pulmonary gas exchange during normoxic and hypoxic exercise in healthy humans.

Exercise-induced intrapulmonary arteriovenous shunting, as detected by saline contrast echocardiography, has been demonstrated in healthy humans. We have previously suggested that increases in both pulmonary pressures and blood flow associated with exercise are responsible for opening these intrapulmonary arteriovenous pathways. In the present study, we hypothesized that, although cardiac output and pulmonary pressures would be higher in hypoxia, the potent pulmonary vasoconstrictor effect of hypoxia would actually attenuate exercise-induced intrapulmonary shunting. Using saline contrast echocardiography, we examined nine healthy men during incremental (65 W + 30 W/2 min) cycle exercise to exhaustion in normoxia and hypoxia (fraction of inspired O(2) = 0.12). Contrast injections were made into a peripheral vein at rest and during exercise and recovery (3-5 min postexercise) with pulmonary gas exchange measured simultaneously. At rest, no subject demonstrated intrapulmonary shunting in normoxia [arterial Po(2) (Pa(O(2))) = 98 +/- 10 Torr], whereas in hypoxia (Pa(O(2)) = 47 +/- 5 Torr), intrapulmonary shunting developed in 3/9 subjects. During exercise, approximately 90% (8/9) of the subjects shunted during normoxia, whereas all subjects shunted during hypoxia. Four of the nine subjects shunted at a lower workload in hypoxia. Furthermore, all subjects continued to shunt at 3 min, and five subjects shunted at 5 min postexercise in hypoxia. Hypoxia has acute effects by inducing intrapulmonary arteriovenous shunt pathways at rest and during exercise and has long-term effects by maintaining patency of these vessels during recovery. Whether oxygen tension specifically regulates these novel pathways or opens them indirectly via effects on the conventional pulmonary vasculature remains unclear.

Respiratory system determinants of peripheral fatigue and endurance performance.

We briefly summarize recent evidence pertaining to how mechanisms primarily under the control of the respiratory system-namely, arterial oxyhemoglobin desaturation, respiratory muscle work and fatigue, and cyclical fluctuations in intrathoracic pressure-may contribute to exercise limitation. Respiratory influences on cardiac output and on sympathetic vasoconstrictor activity and blood flow distribution are shown to be important determinants of performance. We also address how a compromised O2 transport exacerbates the rate of development of peripheral muscle fatigue and, in turn, precipitates central fatigue and exercise limitation.