Michael K. Stickland

Intra‐pulmonary shunt and pulmonary gas exchange during exercise in humans

In young, healthy people the alveolar–arterial P  O 2 difference (A‐aDO2) is small at rest, but frequently increases during exercise. Previously, investigators have focused on ventilation/perfusion mismatch and diffusion abnormalities to explain the impairment in gas exchange, as significant physiological intra‐pulmonary shunt has not been found. The aim of this study was to use a non‐gas exchange method to determine if anatomical intra‐pulmonary (I‐P) shunts develop during exercise, and, if so, whether there is a relationship between shunt and increased A‐aDO2. Healthy male participants performed graded upright cycling to 90% while pulmonary arterial (PAP) and pulmonary artery wedge pressures were measured. Blood samples were obtained from the radial artery, cardiac output was calculated by the direct Fick method and I‐P shunt was determined by administering agitated saline during continuous 2‐D echocardiography. A‐aDO2 progressively increased with exercise and was related to (r= 0.86) and PAP (r= 0.75). No evidence of I‐P shunt was found at rest in the upright position; however, 7 of 8 subjects developed I‐P shunts during exercise. In these subjects, point bi‐serial correlations indicated that I‐P shunts were related to the increased A‐aDO2 (r= 0.68), (r= 0.76) and PAP (r= 0.73). During exercise, intra‐pulmonary shunt always occurred when A‐aDO2 exceeded 12 mmHg and was greater than 24 l min−1. These results indicate that anatomical I‐P shunts develop during exercise and we suggest that shunt recruitment may contribute to the widened A‐aDO2 during exercise.

Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline.

BACKGROUND COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD. CONCLUSIONS This guideline is unique because it provides an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data regarding the prevention of COPD exacerbations.

Hyperoxia prevents exercise-induced intrapulmonary arteriovenous shunt in healthy humans

The 100% oxygen (O2) technique has been used to detect and quantify right‐to‐left shunt for more than 50 years. The goal of this study was to determine if breathing 100% O2 affected intrapulmonary arteriovenous pathways during exercise. Seven healthy subjects (3 females) performed two exercise protocols. In Protocol I subjects performed an incremental cycle ergometer test (60 W + 30 W/2 min; breathing room air, ) and arteriovenous shunting was evaluated using saline contrast echocardiography at each stage. Once significant arteriovenous shunting was documented (bubble score = 2), workload was held constant for the remainder of the protocol and was alternated between 1.0 (hyperoxia) and 0.209 (normoxia) as follows: hyperoxia for 180 s, normoxia for 120 s, hyperoxia for 120 s, normoxia for 120 s, hyperoxia for 60 s and normoxia for 120 s. For Protocol II, subjects performed an incremental cycle ergometer test until volitional exhaustion while continuously breathing 100% O2. In Protocol I, shunting was seen in all subjects at 120–300 W. Breathing oxygen for 1 min reduced shunting, and breathing oxygen for 2 min eliminated shunting in all subjects. Shunting promptly resumed upon breathing room air. Similarly, in Protocol II, breathing 100% O2 substantially decreased or eliminated exercise‐induced arteriovenous shunting in all subjects at submaximal and in 4/7 subjects at maximal exercise intensities. Our results suggest that alveolar hyperoxia prevents or reduces blood flow through arteriovenous shunt pathways.

Using Telehealth technology to deliver pulmonary rehabilitation to patients with chronic obstructive pulmonary disease

BACKGROUND: Pulmonary rehabilitation (PR) is an effective therapeutic strategy to improve health outcomes in patients with chronic obstructive pulmonary disease (COPD); however, there is insufficient PR capacity to service all COPD patients, thus necessitating creative solutions to increase the availability of PR.

Reductions in cerebral blood flow during passive heat stress in humans: partitioning the mechanisms

Non‐technical summary  Heat stress reduces brain blood flow and impairs orthostatic tolerance. Brain blood flow is largely controlled by the partial pressure of arterial . Indeed, hyperthermia‐induced over‐breathing and related reductions in arterial account for ∼50% of the reduction in brain blood flow. This investigation tested the unique hypothesis that the distribution of cardiac output during heat stress (challenged by thermoregulatory increases in skin blood flow and sweat loss) contributes to the remaining 50%. We show that cardiac output is not related to brain blood flow, but rather arterial plays a much larger role than previously suggested. These findings help us understand the mechanisms relating heat stress with an increased likelihood of fainting, and are also relevant to pathological conditions that are accompanied by elevations in body temperature.

Exercise-Induced Intrapulmonary Arteriovenous Shunting and Pulmonary Gas Exchange

Recent research suggests the recruitment of intrapulmonary shunt vessels during exercise, which may contribute to the exercise-induced impairment in pulmonary gas exchange. These findings are consistent with substantial anatomical data demonstrating large-diameter (>25 &mgr;m) anatomical shunts in the lung, but are contrary to the considerable functional gas exchange-dependent research that has not detected right-to-left physiological shunt during exercise.

Assessing Exercise Limitation Using Cardiopulmonary Exercise Testing

The cardiopulmonary exercise test (CPET) is an important physiological investigation that can aid clinicians in their evaluation of exercise intolerance and dyspnea. Maximal oxygen consumption (V˙O2max) is the gold-standard measure of aerobic fitness and is determined by the variables that define oxygen delivery in the Fick equation (V˙O2 = cardiac output × arterial-venous O2 content difference). In healthy subjects, of the variables involved in oxygen delivery, it is the limitations of the cardiovascular system that are most responsible for limiting exercise, as ventilation and gas exchange are sufficient to maintain arterial O2 content up to peak exercise. Patients with lung disease can develop a pulmonary limitation to exercise which can contribute to exercise intolerance and dyspnea. In these patients, ventilation may be insufficient for metabolic demand, as demonstrated by an inadequate breathing reserve, expiratory flow limitation, dynamic hyperinflation, and/or retention of arterial CO2. Lung disease patients can also develop gas exchange impairments with exercise as demonstrated by an increased alveolar-to-arterial O2 pressure difference. CPET testing data, when combined with other clinical/investigation studies, can provide the clinician with an objective method to evaluate cardiopulmonary physiology and determination of exercise intolerance.

Heart rate variability and muscle sympathetic nerve activity response to acute stress: the effect of breathing

Previous research has suggested a relationship between low-frequency power of heart rate variability (HRV; LF in normalized units, LFnu) and muscle sympathetic nerve activity (MSNA). However, investigations have not systematically controlled for breathing, which can modulate both HRV and MSNA. Accordingly, the aims of this experiment were to investigate the possibility of parallel responses in MSNA and HRV (LFnu) to selected acute stressors and the effect of controlled breathing. After data were obtained at rest, 12 healthy males (28 +/- 5 yr) performed isometric handgrip exercise (30% maximal voluntary contraction) and the cold pressor test in random order, and were then exposed to hypoxia (inspired fraction of O(2) = 0.105) for 7 min, during randomly assigned spontaneous and controlled breathing conditions (20 breaths/min, constant tidal volume, isocapnic). MSNA was recorded from the peroneal nerve, whereas HRV was calculated from ECG. At rest, controlled breathing did not alter MSNA but decreased LFnu (P < 0.05 for all) relative to spontaneous breathing. MSNA increased in response to all stressors regardless of breathing. LFnu increased with exercise during both breathing conditions. During cold pressor, LFnu decreased when breathing was spontaneous, whereas in the controlled breathing condition, LFnu was unchanged from baseline. Hypoxia elicited increases in LFnu when breathing was controlled, but not during spontaneous breathing. The parallel changes observed during exercise and controlled breathing during hypoxia suggest that LFnu may be an indication of sympathetic outflow in select conditions. However, since MSNA and LFnu did not change in parallel with all stressors, a cautious approach to the use of LFnu as a marker of sympathetic activity is warranted.

The effects of dobutamine and dopamine on intrapulmonary shunt and gas exchange in healthy humans

The development of intrapulmonary shunts with increased cardiac output during exercise in healthy humans has been reported in several recent studies, but mechanisms governing their recruitment remain unclear. Dobutamine and dopamine are inotropes commonly used to augment cardiac output; however, both can increase venous admixture/shunt fraction (Qs/Qt). It is possible that, as with exercise, intrapulmonary shunts are recruited with increased cardiac output during dobutamine and/or dopamine infusion that may contribute to the observed increase in Qs/Qt. The purpose of this study was to examine how dobutamine and dopamine affect intrapulmonary shunt and gas exchange. Nine resting healthy subjects received serial infusions of dobutamine and dopamine at incremental doses under normoxic and hyperoxic (inspired O(2) fraction = 1.0) conditions. At each step, alveolar-to-arterial Po(2) difference (A-aDo(2)) and Qs/Qt were calculated from arterial blood gas samples, intrapulmonary shunt was evaluated using contrast echocardiography, and cardiac output was calculated by Doppler echocardiography. Both dobutamine and dopamine increased cardiac output and Qs/Qt. Intrapulmonary shunt developed in most subjects with both drugs and paralleled the increase in Qs/Qt. A-aDo(2) was unchanged due to a concurrent rise in mixed venous oxygen content. Hyperoxia consistently eliminated intrapulmonary shunt. These findings contribute to our present understanding of the mechanisms governing recruitment of these intrapulmonary shunts as well as their impact on gas exchange. In addition, given the deleterious effect on Qs/Qt and the risk of neurological complications with intrapulmonary shunts, these findings could have important implications for use of dobutamine and dopamine in the clinical setting.

Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease: Predictors of Program Completion and Success

Abstract Although participation in pulmonary rehabilitation (PR) improves the health outcomes in patients with Chronic Obstructive Pulmonary Disease (COPD), there are insufficient resources to provide PR to all patients with COPD. Thus, predicting which patients are at risk for drop-out and non-response to rehabilitation is necessary in order to optimize limited resources. This study examined which patient characteristics are predictive of PR drop-out and non-response. 814 patients with COPD took part in standard out-patient PR for 8 weeks. Demographic and standard clinical data were collected before the rehabilitation program had started. Data was analyzed retrospectively to determine if baseline patient characteristics could predict drop-out and non-response to rehabilitation. Drop-out was defined as participation in less than 50% of the rehabilitation sessions. Non-response was defined as improvement less than 4% on the St. Georges Respiratory Questionnaire (SGRQ). A discriminant function analysis identified age, smoking history, and health status as predictors of patient drop-out, p < .0001, with younger, current smokers and patients with lower health status being at risk for drop-out. No variables measured significantly predicted who those at risk would be for non-response to rehabilitation, p > .05. Pulmonary function data did not predict drop-out or non-response to PR. These findings indicate that perceived impairment (i.e., health status) is more likely to influence completion of rehabilitation than actual pulmonary impairment and that demographic and standard clinical data do not adequately predict patient drop-out and non-response to rehabilitation.