Annals ofthe Rheumatic Diseases 1990; 49: 921-925

1. Annals ofthe Rheumatic Diseases 1990; 49: 921-925 Relation between chest expansion, pulmonary function, and exercise tolerance in patients with ankylosingspondylitis Lorna R Fisher, M I D Cawley, S T Holgate Ankylosingspondylitis(AS) is a condition characterised by inflammation of ligamentous insertions or entheses and joints, especially of the axial skeleton (la gobba).Bony ankylosis may occur in the numerous joints around the thorax, resulting in limited movement of the chest wall.PULMONARY FUNCTION TESTS The following pulmonary function tests were performed: peak expiratory flow rate; dynamic spirometry (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC (%)); transfer factor of the lung for carbon monoxide; static spirometry (vital capacity, residual volume, total lung capacity, and functional residual capacity) performed using the helium rebreathingmethod. Predicted normal values were obtained for all the above tests using the patient's height before disease where this was reliably known. Arm span measurement was not found to be a useful predictor of height before disease.

2. Maximum predicted exercise tolerance was calculated from the formula described by Jones et al taking into account the patient's age, sex, and height: VO2max = height x 0.046 – age x 0.021 - 0(M)/0.62(F) – 4.314 where height is in cm and age in years. Significantassociationbetweenchestexpansion and vitalcapacity.Vital capacity showed a significant associationwithexercisetolerance, Chest expansion showed no significant associationwithexercisetolerance. Active patients had a higher mean VO2max(83±3%) than the sedentary group (58±6%). Therewas a lessmarked but significant difference in mean values for vital capacity (p<0.02), but chest expansion was similar in the two groups (p<0.5). These results suggest that although restriction of chest expansion may result in reduction of vital capacity, it is not a major factor determining exercise tolerance. In this study there were examples of patients taking a moderate amount of daily exercise who were able to achieve a VO2max close to their predicted normal despite having very restricted chest expansion.

3. J. Physiol. (1984), 355, pp. 161-175 161 EXERCISE-INDUCED ARTERIAL HYPOXAEMIA IN HEALTHY HUMAN SUBJECTS AT SEA LEVEL BY JEROME A. DEMPSEY, PETER G. HANSON AND KATHLEEN S. HENDERSON It is generally presumed that 02 transport by the healthy pulmonary system is more than adequate to meet the increased metabolic demands imposed by steady-state exercise at sea level. At heavy or maximal levels of metabolic rate in healthy persons, it has been demonstrated that ventilatory requirements are well below the maximum voluntary ventilation, that the pulmonary capillary blood volume expands to near maximum morphologic limits, and topographical distribution of ventilation to perfusion ratios is near uniform and that diffusion capacity of the lung is far in excess of that required to maintain full HbO2 saturation of end-pulmonary capillary blood. On the other hand, there are some suggestions that these apparently substantial 'reserves' for gas exchange may be surpassable and that homoeostatic regulation within these limits may be imprecise. Thus, although arterial PO2 is maintained during exercise, it is well established that the alveolar to arterial PO2 difference widens almost linearly with increasing 02 uptake (PO2) and widening of the arterial to mixed venous difference for 02 content.

4. We suspected, then, that exercise-induced arterial hypoxaemia might be more prevalent than generally believed in highly-fit subjects capable of working at extraordinarily high levels of metabolic demand. This study tests this hypothesis in sixteen trained athletes and examines some of the determinants of pulmonary gas exchange in maximal exercise.

5. We have documented a significant level of arterial hypoxaemiaduring heavy exercise at sea level in the majority of a sample of sixteen fit, endurance-trained athletes. These data imply that the large 'reserves' for gas exchange available to the healthy pulmonary system are insufficient to meet the extraordinary metabolic requirements achievable by many trained individuals. The occurrence of arterial hypoxaemia with an increased [(A-a)DO2] during heavy exercise may be attributed to significant amounts of ventilation-perfusion (VA:QC) non-homogeneity, to veno-arterial shunt and/or to failure of alveolar-end-pulmonary capillary equilibrium for 02. The determinants of alveolar-capillary diffusion are more than adequate to ensure alveolar-end-pulmonary capillary 02 equilibrium: (a) transit time of the red blood cell in the pulmonary capillary is reduced as pulmonary blood flow increases but an expanded pulmonary blood volume remains greater than the right heart stroke volume; thus transit time remains adequate (>0,4 s) to ensure equilibrium; (b) the diffusion gradient (alveolar to mean capillary ΔPO2) increases with exercise, thereby sparing the need for extremely high alveolar PO2 and/or diffusing capacity; and (c) the distance for diffusion which is already exceedingly short under resting conditions is believed to remain unchanged as extravascular fluid volume in the lung is unaltered with even heavy exercise

6. The magnitude of the ventilatory response to heavy exercise was a major determinant of exercise-induced hypoxaemia. In almost all cases of the most severe hypoxaemia, little or no hyperventilatory response occurred. Metabolic acidosis, hypoxaemia and exercise represent known stimuli to breathe which when combined exert a powerful synergistic effect on total ventilatory output. However, we had many instances during very heavy exercise in our athletes where compensatory hyperventilation was either minimal or absent and uncorrelated with the magnitude of metabolic acidosis and/or hypoxaemia. In some cases priority may be given to a sparing of chest wall mechanics at the expense of homoeostasis of arterial oxygenation and compensation of metabolic acidosis.

7. Does gender affect pulmonary function and exercise capacity? Craig A. Harms∗ 1A Natatorium, Department of Kinesiology, Kansas State University, Manhattan, KS 66506, USA Accepted 21 October 2005 The basis for sex differences in pulmonary function and exercise tolerance is primarily from two sources; namely hormones (especially progesterone and estrogen), and in structural /morphological differences. There may be subtle physiological variations in vascular volume dynamics, ventilation, thermoregulation, and substrate metabolism throughout the normal menstrual cycle. Effects of progesterone on the pulmonary system include hyperventilation, a partially compensated respiratory alkalosis, and an increase in both the resting hypercapnic ventilatory response (HCVR) and the hypoxic ventilatory response (HVR). Progesterone also increases central ventilatory drive, which may affect breathing responsiveness during exercise. Increased estrogen levels tend to increase fluid retention and therefore increase blood volume, which could potentially affect gas exchange in the lung.

8. Morphology : height-matched men have larger diameter airways and larger lung volumes and diffusion surfaces compared with postpubertal women. It has been suggested that sex differences in lung diffusing capacity can be explained by fewer total number of alveoli (smaller surface area) and smaller airway diameter relative to lung size in women. Gender and chemosensitivity : It is currently believed that endurance athletes commonly have altered respiratory drives, with a decreased ventilatory response to hypoxia (HVR) and hypercapnia (HCVR). Such changes may benefit these athletes by allowing less ventilation during exercise (providing it does not lead to increased arterial desaturation) and by decreasing the subjective sensation of dyspnea that may be a factor in limiting maximal exercise performance, as well as allowing them to continue exercising despite the onset of hypoxia. It is known that there are sex related differences in HVR that tend to vary with ovarian hormones. It has been suggested that the endogenous surge of progesterone during the menstrual cycle may exert a deleterious effect on performance through alterations in these respiratory drives. Progesterone and estrogen raises both alveolar ventilation and HVR via central and peripheral receptor-mediated mechanisms

9. Hyperventilation of exercise: The hyperventilation of heavy exercise leads to significant increases in both inspiratory and expiratory muscle work and in both the resistive and elasticwork of breathing. Nevertheless, a substantial reserve exists for increases in ventilation in the young to middle aged normal, healthy untrained man, even at maximal exercise. However, the endurance trained man with a higher maximal oxygen uptake (˙V O2 max) and CO2 production, producing a high ventilatory demand, begins to approach the mechanical limits for inspiratory and expiratory pressure and flow development. Because women tend to show reduced airway diameter compared to men (see above), women are more likely to show greater mechanicallimits to expiratory flow creating a smaller maximal flow:volume envelope compared to men. As a result, women would probably show increased hyperinflation, marked increases in both the elastic and flow resistive work of breathing, and dyspnea at a given ˙VE compared to the average man. Also, it would be expected that women would experience a lack of substantial hyperventilation at a ˙V O2 (and ˙V CO2) that men typically would not. The active healthy female may be especially vulnerable to high fatiguing levels of the work of breathing during heavy exercise.

10. Gender and gas exchange Sufficient studies in young adult men have been conducted to document clearly that untrained subjects normally widen their A-aDO2 two- to three-fold from rest to maximal exercise, and that they also hyperventilate, which raises alveolar PO2 sufficiently during strenuous exercise to prevent PaO2 from falling below resting levels. However, a significant reduction in the arterial partial pressure of oxygen (PaO2) (<90 mmHg) during heavy exercise, termed exercise induced arterial hypoxemia (EIAH) has been well documented in some fit adult men over the past several decades. Given gender-based pulmonary structural differences that exist between men and women (see above), it is tempting to propose that women are more susceptible to EIAH than men. To date, there are few published temperature corrected arterial blood gas data directly comparing pulmonary gas exchange between genders.

11. Respiratory muscle work compromises leg blood flow during maximal exercise CRAIG A. HARMS, MARK A. BABCOCK, STEVEN R. MCCLARAN, DAVID F. PEGELOW, GLENN A. NICKELE, WILLIAM B. NELSON, AND JEROME A. DEMPSEY J.Appl. Physiol. 82(5): 1573–1583, 1997 Wehypothesizedthatduringexercise at maximal O2consumption (V˙ O2max), high demand for respiratory muscle blood flow (Q˙ ) would elicit locomotor muscle vasoconstriction and compromise limb Q ˙ . Seven male cyclists (V˙ O2max 64 ± 6 ml· kg-1·min-1) each completed 14 exercise bouts of 2.5-min duration at V ˙ O2max on a cycle ergometer during two testing sessions. Inspiratory muscle work was either 1) reduced via a proportional-assist ventilator, 2) increased via graded resistive loads, or 3) was not manipulated (control). Arterial (brachial) and venous (femoral) blood samples, arterial blood pressure, legQ ˙ (Q˙ legs; thermodilution), esophageal pressure, and O2 consumption (V˙ O2) weremeasured.

12. Our findings demonstrate a significant effect of the Wbduring maximal exercise on locomotor muscle perfusion and V ˙ O2 in the healthy trained human. Significant regressions of Q ˙ legs to Wb were obtained both within individual subjects and across all subjects. The changes in Q ˙ legs were not accompanied by changes in O2 extraction across the limb; thusV ˙ O2legs also changed directly with Q ˙ legs and with the Wb. Changes in NE spillover across the working limb suggested active, sympathetically mediated alterations in limb vascular resistance triggered by changes in respiratory muscle work, possibly mediated by a respiratory muscle chemoreflex effect. Different approaches consistently confirmed a significant association of respiratory muscle work with limb locomotor Q ˙ at maximal exercise. Furthermore, observed changes in Q ˙ legs and in LVR were indirectly supported by appropriate directional changes in measurements of NE spillover across the working muscle

13. Effects of respiratory muscle work on cardiac output and its distribution during maximal exercise. Harms, Craig A., Thomas J. Wetter, Steven R. McClaran, David F. Pegelow, Glenn A. Nickele, William B. Nelson, Peter Hanson, and Jerome A. Dempsey. J. Appl. Physiol. 85(2):609–618, 1998. Our present study examined the effects of changes in the work of breathing on cardiac output (CO) during maximal exercise. Eight male cyclists [maximal O2 consumption (V˙ O2max): 62±5 ml·kg-1 ·min-1] performed repeated 2.5-min bouts of cycle exercise at V ˙ O2max. Inspiratory muscle work was either 1) at control levels [inspiratory esophageal pressure (Pes): 227.8 ± 0.6 cmH2O], 2) reduced via a proportional assist ventilator (Pes: 216.3 ± 0.5 cmH2O), or 3) increased via resistive loads (Pes: 235.6 ± 0.8 cmH2O). Stroke volume, CO, and O2 consumption (V˙ O2) were not different between control and loaded trials at V ˙ O2max but were lower (28, 29, and 27%, respectively) with inspiratory muscle unloading. The arterial-mixed venous O2 difference was unchanged. The respiratory muscle work normally expended during maximal exercise has two significant effects on the cardiovascular system: 1) up to 14–16% of the CO is directed to the respiratory muscles; and 2) local reflex vasoconstriction significantly compromises blood flow to leg locomotor muscles

14. Effects of respiratory muscle training versus placebo on endurance exercise performance David A. Sonetti, Thomas J. Wetter, David F. Pegelow, Jerome A. Dempsey Respiration Physiology 127 (2001) 185–199 The effects of respiratory muscle training (RMT) on exercise performance in healthy persons are controversial. We evaluated the effects of a 5 week (25 sessions); (30–35 min/day, 5 days/week), respiratory muscle training (RMT) program in nine competitive male cyclists. The experimental design included inspiratory resistance strength training (3–5 min/session) and hyperpnea endurance training (30 min/session), a placebo group which used a sham hypoxic trainer (n=8), and three exercise performance tests, including a highly reproducible 8 km time trial test. RMT intensity, measured once a week in terms of accumulated inspiratory pressure and the level of sustainable hyperpnea increased significantly after 5 weeks (+64% and +19%, respectively). The RMT group showed a significant 8% increase in maximal inspiratory pressure (P<.05) while the placebo group showed only a 3.7% increase (P>.10).

15. RMT and placebo groups both showed significant increases in the fixed work-rate endurance test performance time (+26% and +16%, respectively) and in the peak work-rate achieved during the incremental maximal oxygen consumption (V O2 max) test (+9 and +6%). The 8 km time trial performance increased 1.8±.2% (or 15 ± 10 sec; P<.01) in the RMT group with 8 of 9 subjects increasing; the placebo group showed a variable non-significant change in 5 of 8 subjects (−0.3 ± 2.7%, P=0.07). The changes observed in these three performance tests were not, however, significantly different between the RMT and placebo groups. Heart rate, ventilation, or venous blood lactate, at equal work-rates during the incremental exercise test or at equal times during the fixed work-rate endurance test were not changed significantly across these exercise trials in either group. We propose that the effect of RMT on exercise performance in highly trained cyclists does not exceed that in a placebo group. Significant placebo and test familiarization effects must be accounted for in experimental designs utilizing performance tests which are critically dependent on volitional effort