Ventilatory changes following head-up tilt and standing in healthy subjects

Passive tilting increases ventilation in healthy subjects; however, controversy surrounds the proposed mechanism. This study is aimed to evaluate the possible mechanism for changes to ventilation following passive head-up tilt (HUT) and active standing by comparison of a range of ventilatory, metabolic and mechanical parameters. Ventilatory parameters (V (T), V (E), V (E)/VO2, V (E)/VCO2, f and PetCO(2)), functional residual capacity (FRC), respiratory mechanics with impulse oscillometry; oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in 20 healthy male subjects whilst supine, following HUT to 70 degrees and unsupported standing. Data were analysed using a linear mixed model. HUT to 70 degrees from supine increased minute ventilation (V (E)) (P < 0.001), tidal volume (V (T)) (P=0.001), ventilatory equivalent for O-2 (V (E)/VO2) (P=0.020) and the ventilatory equivalent for CO2 (V (E)/VCO2) (P < 0.001) with no change in f (P=0.488). HUT also increased FRC (P < 0.001) and respiratory system reactance (X5Hz) (P < 0.001) with reduced respiratory system resistance (R5Hz) (P=0.004) and end-tidal carbon dioxide (PetCO(2)) (P < 0.001) compared to supine. Standing increased V (E) (P < 0.001), V (T) (P < 0.001) and V (E)/VCO2 (P=0.020) with no change in respiratory rate (f) (P=0.065), V (E)/VO2 (P=0.543). Similar changes in FRC (P < 0.001), R5Hz (P=0.013), X5Hz (P < 0.001) and PetCO(2) (P < 0.001) compared to HUT were found. In contrast to HUT, standing increased VO2 (P=0.002) and VCO2 (P=0.048). The greater increase in V (E) in standing compared to HUT appears to be related to increased VO2 and VCO2 associated with increased muscle activity in the unsupported standing position. This has implications for exercise prescription and rehabilitation of critically ill patients who have reduced cardiovascular and respiratory reserve.

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects

Background: Inflammatory markers are increased in chronic obstructive pulmonary disease ( COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. Methods: The Health Aging and Body Composition ( Health ABC) study is a prospective observational cohort of well functioning individuals aged 70 - 79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease ( OLD). Results: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H2O v 74.2 cm H2O, p< 0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p< 0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p< 0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV1) was associated with IL-6 ( adjusted regression coefficients (beta) = -5.3 (95% CI -9.1 to -1.5) and -3.1 (95% CI -4.3 to -1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (beta = -6.4 (95% CI -12.8 to -0.03) and -3.4 (95% CI -5.4 to -1.3), respectively, for IL-6 and beta = -10.1 (95% CI -18.7 to -1.5) and -3.8 (95% CI -7 to -0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. Conclusions: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV1, quadriceps strength, and exercise capacity.