Journal of applied physiology
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Multicenter Study Comparative Study Clinical Trial
Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation.
Five to ten percent of asthma cases are poorly controlled chronically and refractory to treatment, and these severe cases account for disproportionate asthma-associated morbidity, mortality, and health care utilization. While persons with severe asthma tend to have more airway obstruction, it is not known whether they represent the severe tail of a unimodal asthma population, or a severe asthma phenotype. We hypothesized that severe asthma has a characteristic physiology of airway obstruction, and we evaluated spirometry, lung volumes, and reversibility during a stable interval in 287 severe and 382 nonsevere asthma subjects from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. ⋯ After maximal bronchodilation, FEV(1) reversed similarly from baseline in severe and nonsevere asthma, but the severe asthma classification was an independent predictor of residual reduction in FEV(1) after maximal bronchodilation. An increase in FVC accounted for most of the reversal of FEV(1) when baseline FEV(1) was <60% predicted. We conclude that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component.
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Comparative Study Clinical Trial
Noninvasively determined muscle oxygen saturation is an early indicator of central hypovolemia in humans.
Ten healthy human volunteers were subjected to progressive lower body negative pressure (LBNP) to the onset of cardiovascular collapse to compare the response of noninvasively determined skin and fat corrected deep muscle oxygen saturation (SmO2) and pH to standard hemodynamic parameters for early detection of imminent hemodynamic instability. Muscle SmO2 and pH were determined with a novel near infrared spectroscopic (NIRS) technique. Heart rate (HR) was measured continuously via ECG, and arterial blood pressure (BP) and stroke volume (SV) were obtained noninvasively via Finometer and impedance cardiography on a beat-to-beat basis. ⋯ SmO2 declined in parallel with SV and inversely with total peripheral resistance, suggesting, in this model, that SmO2 is an early indicator of a reduction in oxygen delivery through vasoconstriction. Muscle pH decreased later, suggesting an imbalance between delivery and demand. Spectroscopic determination of SmO2 is noninvasive and continuous, providing an early indication of impending cardiovascular collapse resulting from progressive reduction in central blood volume.
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Clinical Trial
Prostaglandin synthesis can be inhibited locally by infusion of NSAIDS through microdialysis catheters in human skeletal muscle.
Prostaglandins are known to be involved in the regulation of local blood flow within human skeletal muscles during exercise, and the concentration of prostaglandins increases locally and systemically in response to exercise. The systemic release of prostaglandins can be inhibited by oral intake of nonsteroidal anti-inflammatory drugs (NSAIDs). However, to study the local role of prostaglandins, the formation of prostaglandins within the tissue must be controlled. ⋯ Following 2 h of rest, the subjects performed 200 maximal eccentric contractions with each leg followed by 3 h of rest. The study revealed that infusion of NSAID reduced local prostaglandin E(2) concentration by approximately 30-50% (4 cm away from the infusion) and 85% (1 cm away from the infusion) compared with the contralateral (unblocked) thigh muscle. In conclusion, the present study shows that infusion of NSAIDs into human muscle via microdialysis catheters results in a graded blockade of prostaglandin synthesis.