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Biomedical subjects

Denis E O'Donnell

Publications and source records attributed to Denis E O'Donnell.

At least 19 recordsLinked to original sources
PubMed2006

Effects of human pregnancy and advancing gestation on respiratory discomfort during exercise.

This study examined the effects of human pregnancy and advancing gestation on the intensity of respiratory discomfort (dyspnea) during cycle exercise. Fourteen pregnant women (PG) performed a progressive cycle ergometer exercise test involving 20 W/min increases in work rate to symptom limitation and/or a heart rate of 170-175 beats/min at 19.7+/-1.2 weeks (ENTRY), 28.2+/-0.3 weeks (TM2) and 36.3+/-0.3 weeks (TM3) gestation. Eight, age-matched, sedentary non-pregnant women (CG) were also studied for comparison purposes. Measurements included dyspnea intensity (Borg scale), minute ventilation (VE), breathing pattern and other cardiorespiratory parameters. At peak exercise, neither pregnancy nor advancing gestation had an effect on dyspnea, VE, breathing pattern, oxygen uptake or work rate (p>0.05). VE was significantly greater (by 11 L/min at 100 W) in the PG at TM3 versus CG (p<0.05) at all submaximal work rates. VE also increased progressively from ENTRY to TM2 and TM3 during submaximal exercise. Dyspnea was not significantly different at any submaximal work rate in the PG at TM3 versus CG or with advancing gestation in the PG. In addition, dyspnea at a standardized exercise VE of 40 L/min was not different at TM3 versus ENTRY or in the PG at TM3 versus CG. Neither pregnancy nor advancing gestation were associated with increased respiratory discomfort during strenuous non-weight bearing cycle ergometer exercise, despite substantial increases in VE and progressive mechanical adaptations of the respiratory system to accommodate the increasing size of the gravid uterus.

Analysis of Variance↗
PubMed2006

Sensory-mechanical relationships during high-intensity, constant-work-rate exercise in COPD.

During constant-work-rate exercise in chronic obstructive pulmonary disease, dyspnea increases steeply once inspiratory reserve volume (IRV) falls to a critical level that prevents further expansion of tidal volume (Vt). We studied the effects of this mechanical restriction on the quality and intensity of exertional dyspnea and examined the impact of an anticholinergic bronchodilator. In a randomized, double-blind, crossover study, 18 patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 s = 40 +/- 3%predicted; mean +/- SE) inhaled tiotropium 18 mug or placebo once daily for 7-10 days each. Pulmonary function tests and symptom-limited cycle exercise at 75% of each patient's maximal work capacity were performed 2 h after dosing. Dyspnea intensity (Borg scale), operating lung volumes, breathing pattern, and esophageal pressure (n = 11) were measured during exercise. Dynamic hyperinflation reached its maximal value early in exercise and was associated with only mild increases in dyspnea intensity and the effort-displacement ratio, which is defined as the ratio between tidal swings of esophageal pressure (expressed relative to maximum inspiratory pressure) and Vt (expressed relative to predicted vital capacity). After a minimal IRV of 0.5 +/- 0.1 liter was reached, both dyspnea and the effort-displacement ratio rose steeply until an intolerable level was reached. Tiotropium did not alter dyspnea-IRV relationships, but the increase in resting and exercise inspiratory capacity was associated with an improved effort-displacement ratio throughout exercise. Once a critically low IRV was reached during exercise, dyspnea rose with the disparity between respiratory effort and the Vt response. Changes in dyspnea intensity after tiotropium were positively correlated with changes in this index of neuromechanical coupling.

Administration, Inhalation↗
PubMed2006

Muscle blood-flow dynamics at exercise onset: do the limbs differ?

Common approaches to understanding control of muscle blood flow in exercise focus on the contributions of various putative vasoregulatory mechanisms to the magnitude of the steady-state response. The application of systems-control principles offers a unique approach to characterizing and quantifying the non-steady-state adaptation of muscle blood flow with exercise onset. Information gained from this approach provides novel insight into the nature of control mechanisms governing physiological responses to exercise. This review is intended to provide the reader with an understanding of 1) exercise models, methodology for measuring muscle blood flow, and analysis approaches for quantifying muscle blood-flow dynamics; 2) what is currently known about the dynamic response of muscle blood-flow control mechanisms in humans; and 3) the similarities and differences in exercising muscle blood-flow control in the upper versus the lower limbs in humans.

Arm↗
PubMed2006

Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD.

STUDY OBJECTIVE: To examine the effect of fluticasone propionate, 250 microg/salmeterol, 50 microg combination (FSC 250/50) twice daily on lung hyperinflation and associated measures of exercise performance in patients with COPD. DESIGN: This was a randomized, double-blind, parallel-group study. PATIENTS: Eligible patients were > or = 40 years old with a diagnosis of COPD, prealbuterol FEV(1) < 70% of predicted, FEV1/FVC ratio > or = 0.70, and functional residual capacity (FRC) > or = 120% of predicted normal. INTERVENTIONS: Patients were randomized to FSC 250/50; salmeterol, 50 microg; or placebo twice daily for 8 weeks. Predose and postdose spirometry, plethysmography, and constant-load cycle cardiopulmonary exercise test evaluations were compared. The primary comparison was FSC 250/50 with placebo. The salmeterol group was included for exploratory comparisons with FSC 250/50. RESULTS: A total of 185 patients (mean baseline FEV1 of 41% predicted) were enrolled. At rest, FSC 250/50 significantly reduced postdose FRC and increased inspiratory capacity (IC) compared with placebo (differences of - 0.35 +/- 0.12 L and 0.33 +/- 0.06 L [mean +/- SE], respectively, at week 8; p > or = 0.003) and increased exercise endurance time (difference, 132 +/- 45 s; p = 0.004). At a standardized time during exercise (isotime), FSC 250/50 increased postdose IC by 0.20 +/- 0.05 L over placebo with associated improvements in tidal volume and minute ventilation (p < 0.05 vs placebo at week 8). Improvement in exercise time was significantly correlated with the increase in IC (r = 0.45, p < 0.001) but not FEV1 (r = 0.23, p = 0.08). Predose comparisons of FSC 250/50 with salmeterol and placebo favored FSC 250/50. CONCLUSION: We conclude that FSC 250/50 decreases lung hyperinflation at rest and during exercise with an associated increase in exercise endurance time when compared with placebo.

Adrenergic beta-Agonists↗
PubMed2006

Dynamic hyperinflation during bronchoconstriction in asthma: implications for symptom perception.

OBJECTIVE: The objective of this study was to examine the relationship between respiratory symptom intensity and quality and dynamic lung hyperinflation (DH) during induced bronchoconstriction in asthma. PATIENTS AND METHODS: Subjects with asthma (n = 116) underwent baseline spirometry and lung volume measurement followed by high-dose methacholine challenge testing (MCT) [maximum decrease in FEV(1) of 50% from baseline]. Dyspnea intensity (Borg scale) was measured after each dose of methacholine. Qualitative descriptors of breathlessness and functional residual capacity (FRC) were measured at the doses nearest to the provocative concentration of methacholine causing a 20% fall in FEV (PC(20)) and at the highest dose of methacholine (maximum response). RESULTS: FEV(1) decreased by 24.7 +/- 0.7% (mean +/- SEM) at the dose nearest to PC(20) and by 46.1 +/- 1.1% at maximum response. Inspiratory capacity decreased by 0.62 +/- 0.04 L at the dose nearest to PC(20) and 1.06 +/- 0.06 L at maximum response. The descriptor clusters "inspiratory difficulty," "chest tightness," "unsatisfied inspiration," and "work" were selected at the dose nearest to PC(20) but were more frequently selected at maximum response (p < 0.0001). Individuals who reported chest tightness at maximum response had greater airflow obstruction and higher FRC (percentage of predicted) than those who did not report chest tightness. CONCLUSIONS: Four dominant qualities of dyspnea in asthma (inspiratory difficulty, chest tightness, unsatisfied inspiration, and work) were reported early in the course of MCT and evolved in parallel, becoming more prevalent at maximum response. Significant DH accompanied even mild bronchoconstriction during MCT in asthma, making it difficult to separate mechanisms of chest tightness from other dominant respiratory sensations.

Adult↗
PubMed2006

Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease.

Expiratory flow limitation is the pathophysiologic hallmark of chronic obstructive pulmonary disease (COPD), but dyspnea (breathlessness) is its most prominent and distressing symptom. Acute dynamic lung hyperinflation, which refers to the temporary increase in operating lung volumes above their resting value, is a key mechanistic consequence of expiratory flow limitation, and has serious mechanical and sensory repercussions. It is associated with excessive loading and functional weakness of inspiratory muscles, and with restriction of normal VT expansion during exercise. There is a strong correlation between the intensity of dyspnea at a standardized point during exercise, the end-expiratory lung volume, and the increased ratio of inspiratory effort to volume displacement (i.e., esophageal pressure relative to maximum: Vt as a % of predicted VC). This increased effort-displacement ratio in COPD crudely reflects the neuromechanical dissociation of the respiratory system that arises as a result of hyperinflation. The corollary of this is that any intervention that reduces end-expiratory lung volume will improve effort-displacement ratios and alleviate dyspnea. In flow-limited patients, bronchodilators act by improving dynamic airway function, thus enhancing lung emptying and reducing lung hyperinflation. Long-acting bronchodilators have recently been shown to reduce hyperinflation during both rest and exercise in moderate to severe COPD. This lung deflation allows greater Vt expansion for a given inspiratory effort during exercise with consequent improvement in dyspnea and exercise endurance.

Bronchodilator Agents↗
PubMed2005

Effects of human pregnancy on the ventilatory chemoreflex response to carbon dioxide.

This study examined the effects of human pregnancy on the central chemoreflex control of breathing. Subjects were two groups (n=11) of pregnant subjects (PG, gestational age, 36.5+/-0.4 wk) and nonpregnant control subjects (CG), equated for mean age, body height, prepregnant body mass, parity, and aerobic fitness. All subjects performed a hyperoxic CO2 rebreathing procedure, which includes prior hyperventilation and maintenance of iso-oxia. Resting blood gases and plasma progesterone and estradiol concentrations were measured. During rebreathing trials, end-tidal Pco2 increased, whereas end-tidal Po2 was maintained at a constant hyperoxic level. The point at which ventilation (Ve) began to rise as end-tidal Pco2 increased was identified as the central chemoreflex ventilatory recruitment threshold for CO2 (VRTco2). Ve levels below (basal Ve) and above (central chemoreflex sensitivity) the VRTco2 were determined. The VRTco2 was significantly lower in the PG vs. CG (40.5+/-0.8 vs. 45.8+/-1.6 Torr), and both basal Ve (14.8+/-1.1 vs. 9.3+/-1.6 l/min) and central chemoreflex sensitivity (5.07+/-0.74 vs. 3.16+/-0.29 l.min-1.Torr-1) were significantly higher in the PG vs. CG. Pooled data from the two groups showed significant correlations for resting arterial Pco2 with basal Ve, central chemoreflex sensitivity, and the VRTco2. The VRTco2 was also correlated with progesterone and estradiol concentrations. These data support the hypothesis that pregnancy decreases the threshold and increases the sensitivity of the central chemoreflex response to CO2. These changes may be due to the effects of gestational hormones on chemoreflex and/or nonchemoreflex drives to breathe.

Adult↗
PubMed2005

The role of tiotropium bromide, a long-acting anticholinergic bronchodilator, in the management of COPD.

Bronchodilator therapy forms the mainstay of treatment for symptomatic patients with COPD. Long-acting bronchodilators, which maintain sustained airway patency over a 24-hour period, represent an advance in therapy. Tiotropium bromide is a new long-acting inhaled anticholinergic agent with superior pharmacodynamic properties compared with the short-acting anticholinergic, ipratropium bromide. Tiotropium bromide has been consistently shown to have a greater impact than ipratropium bromide on clinically important outcome measures such as health status. The mechanisms of clinical benefit with tiotropium bromide are multifactorial, but improved airway function, which enhances lung emptying and allows sustained deflation of over-inflated lungs, appears to explain improvements in dyspnea and exercise endurance in COPD. Inhaled tiotropium bromide therapy has also been associated with reduction in acute exacerbations of COPD as well as reduced hospitalizations. The safety profile of tiotropium bromide is impressive: dry mouth is the most common adverse event and rarely necessitates termination of the drug. No tachyphylaxis to tiotropium bromide has been demonstrated in clinical trials lasting up to 1 year. There is preliminary information that the combination of long-acting anticholinergics and long-acting beta2-adrenoceptor agonists provides additive physiological and clinical benefits. According to recent international guidelines, long-acting bronchodilators should be considered early in the management of symptomatic patients with COPD in order to achieve effective symptom alleviation and reduction in activity limitation. Tiotropium bromide, because of its once-daily administration and its established efficacy and tolerability profile, has emerged as an attractive therapeutic option for this condition.

Bronchodilator Agents↗
PubMed2004

Chemoreflex control of breathing during wakefulness in healthy men and women.

This study used a modified CO(2) rebreathing procedure to examine the effect of gender on the chemoreflex control of breathing during wakefulness in healthy men (n = 14) and women (n = 14). Women were tested in the follicular phase of the menstrual cycle. During rebreathing trials, subjects hyperventilated to reduce the partial pressure of end-tidal CO(2) (Pet(CO(2))) below 25 Torr and were then switched to a rebreathing bag containing a normocapnic hypoxic or hyperoxic gas mixture. During the trial, Pet(CO(2)) increased, while O(2) was maintained at a constant level. The point at which ventilation began to rise as Pet(CO(2)) increased was identified as the ventilatory recruitment threshold (VRT). Ventilation below the VRT was measured, and the slope of the ventilatory response above the VRT was determined. Gender had no effect on the hyperoxic or hypoxic VRT for CO(2). Central chemoreflex sensitivity was significantly greater in men than women but not after correction for forced vital capacity. Measures of peripheral chemoreflex sensitivity were similar between genders. However, the slope of the tidal volume (Vt) response to hyperoxic and hypoxic CO(2) rebreathing (corrected and uncorrected) was greater in men than women, respectively. We conclude that central chemoreflex sensitivity is greater in men compared with women as reflected by differences in ventilatory (uncorrected) and Vt (corrected and uncorrected) responses to CO(2). However, gender has no significant effect on the central chemoreflex VRT for CO(2). The peripheral chemoreflex control of breathing during wakefulness is similar between men and women.

Adult↗
PubMed2004

McArdle's disease presenting as unexplained dyspnea in a young woman.

McArdle's disease is a rare, inherited deficiency of myophosphorylase, an enzyme required for the utilization of glycogen. Patients with myophosphorylase deficiency classically present with exercise intolerance, leg pain and muscle fatigue. The case of a young woman with exertional dyspnea and leg cramps is described. Exercise testing confirmed the presence of exercise intolerance and demonstrated an accelerated heart rate response, despite the absence of an anaerobic threshold and a respiratory exchange ratio of less than 1.0. Subsequent ischemic forearm testing and muscle biopsy confirmed the diagnosis of myophosphorylase deficiency. Evaluation of lung mechanics with esophageal pressure measurements demonstrated the presence of respiratory muscle weakness and early fatiguability, suggesting that the patient's dyspnea might have been attributable to an increased respiratory effort. Dyspnea is not a classic symptom associated with myophosphorylase deficiency, although subclinical respiratory muscle impairment may be present. No previous studies have evaluated respiratory muscle function during exercise in patients with myophosphorylase deficiency.

Adult↗
PubMed2002

Exercise hypercapnia in advanced chronic obstructive pulmonary disease: the role of lung hyperinflation.

In severe chronic obstructive pulmonary disease (COPD), carbon dioxide retention during exercise is highly variable and is poorly predicted by resting pulmonary function and arterial blood gases or by tests of ventilatory control. We reasoned that in patients with compromised gas exchange capabilities, exercise hypercapnia could be explained, in part, by the restrictive consequences of dynamic lung hyperinflation. We studied 20 stable patients with COPD (FEV(1) = 34 +/- 3 percent predicted; mean +/- SEM) with varying gas exchange abnormalities (Pa(O(2)) range, 35 to 84 mm Hg; Pa(CO(2)) range, 31 to 64 mm Hg). During symptom-limited maximum cycle exercise breathing room air, Pa(CO(2)) increased 7 +/- 1 mm Hg (p < 0.05) from rest to peak exercise (range, -6 to 25 mm Hg). We measured the change in Pa(CO(2)) after hyperoxic breathing at rest as an indirect test of ventilation-perfusion abnormalities. The change in Pa(CO(2)) from rest to peak exercise correlated best with the acute change in Pa(CO(2)) during hyperoxia at rest (r(2) = 0.62, p < 0.0005) and with resting arterial oxygen saturation (r(2) = 0.30, p = 0.011). During exercise, the strongest correlates of serial changes in Pa(CO(2)) from rest included concurrent changes in end-expiratory lung volume expressed as a percentage of total lung capacity (partial correlation coefficient [r] = 0.562, p < 0.0005) and oxygen saturation (partial r = 0.816, p < 0.0005). In severe COPD, the propensity to develop carbon dioxide retention during exercise reflects marked ventilatory constraints as a result of lung hyperinflation as well as reduced gas exchange capabilities.

Carbon Dioxide↗
PubMed2002

Respiratory sensation and ventilatory mechanics during induced bronchoconstriction in spontaneously breathing low cervical quadriplegia.

Intensity of dyspnea during induced bronchoconstriction in asthma is strongly related to the reduction in inspiratory capacity (IC) as a result of dynamic hyperinflation. To determine the role of rib cage and intercostal muscle afferents in symptom perception during bronchoconstriction, we measured the relationship between dyspnea intensity and IC during induced bronchoconstriction in six subjects with complete C4-C7 quadriplegia who did not require assisted ventilation. Spirometry, lung volumes, breathing pattern, esophageal pressure (Pes), and dyspnea intensity (Borg Scale) were measured during high-dose methacholine bronchoprovocation up to 256 mg/ml or a maximum change (Delta) in FEV(1) of 50%. Contemporaneous control data from subjects with asthma (n = 12) who had completed the same protocol were used for comparison. At maximum response in quadriplegia, FEV(1) decreased by 1.42 +/- 0.18 L (62 +/- 4%predicted) (mean +/- SEM), and IC decreased by 0.89 +/- 0.12 L (30 +/- 4%predicted). Dyspnea at maximum response was rated "moderate" to "severe": Borg 3.6 +/- 0.3. The predominant qualitative respiratory sensations were inspiratory difficulty and unsatisfied inspiration. The best correlate of dyspnea (Borg) was DeltaIC(%predicted) (p < 0.0005), whereas changes in FEV(1), Pes-derived measurements and breathing pattern did not contribute further to the strength of this relationship. Dyspnea intensity, quality, and changes in spirometry and lung volumes at maximum response were similar to those reported previously in asthma. The relationship between dyspnea intensity and DeltaIC(%predicted) was linear and consistent across groups. We conclude that the quality and intensity of dyspnea during methacholine-induced bronchoconstriction and dynamic hyperinflation was not altered by extensive chest wall deafferentation.

Adult↗
PubMed2002

Response of lung volumes to inhaled salbutamol in a large population of patients with severe hyperinflation.

OBJECTIVES: Current criteria use FEV(1) to assess bronchodilator responsiveness, despite its insensitivity and inability to predict improvement in symptoms or exercise tolerance. Response in lung volumes remains largely unexplored even though volume parameters, such as inspiratory capacity (IC), closely correlate with functional improvements. Therefore, we assessed the response of lung volumes (i.e., by IC, total lung capacity [TLC], functional residual capacity [FRC], residual volume [RV], and FVC) to salbutamol and the relationship of these changes to improvements in the spirometry in these patients. DESIGN: A retrospective review of data extracted from a large database of patients who were undergoing spirometry and static lung volume measurements before and after the administration of 200 microg salbutamol. PATIENTS: Patients with an FEV(1)/FVC ratio of < 85% of predicted values were defined as being severely hyperinflated (SH) if TLC was > 133% of predicted and as being moderately hyperinflated (MH) if TLC was 115 to 133% of predicted. RESULTS: Two hundred eighty-one SH patients and 676 MH patients were identified. Salbutamol significantly reduced the mean (+/- SEM) TLC (SH patients, 222 +/- 23 mL; MH patients, 150 +/- 10 mL; p < 0.001), FRC (SH patients, 442 +/- 26 mL; MH patients, 260 +/- 39 mL; p < 0.001), and RV (SH patients, 510 +/- 28 mL; MH patients, 300 +/- 14 mL; p < 0.001) and increased both the IC (SH patients, 220 +/- 15 mL; MH patients, 110 +/- 11 mL; p < 0.001) and FVC (SH patients, 336 +/- 21 mL; MH patients, 204 +/- 13 mL; p < 0.001). FEV(1) improved in a minority of patients (SH patients, 33%; MH patients, 26%), but if lung volume measurements are also considered, the overall bronchodilator response may improve to up to 76% of the SH group and up to 62% of the MH group. Changes in volumes correlated poorly with changes in maximal airflows. CONCLUSIONS: Bronchodilators reduce hyperinflation. Measurements of lung volumes before and after bronchodilators add sensitivity when examining for bronchodilator responsiveness.

Aged↗
PubMedDate not supplied

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease--2003.

Chronic obstructive pulmonary disease (COPD) is a common cause of disability and death in Canada. Moreover, morbidity and mortality from COPD continue to rise, and the economic burden is enormous. The main goal of the Canadian Thoracic Society (CTS) Evidence-Based Guidelines is to optimize early diagnosis, prevention and management of COPD in Canada. Targeted spirometry is strongly recommended to expedite early diagnosis in smokers and exsmokers who develop respiratory symptoms, and who are at risk for COPD. Smoking cessation remains the single most effective intervention in accordance with the increasing severity of symptoms and disability. Long-acting anticholinergics and beta2-agonist inhalers should be prescribed for patients who remain symptomatic despite short-acting bronchodilatory therapy. Inhaled steroids should not be used as first-line therapy in COPD but have a role in preventing exacerbations in patients with more advanced disease who suffer recurrent exacerbations. Management strategies consisting of combined modern pharmacotherapy and nonpharmacotherapeutic interventions (eg, pulmonary rehabilitation/exercise training) can effectively improve symptoms, activity levels and quality of life, even in patients with severe COPD. Acute exacerbations of COPD cause significant morbidity and mortality and should be treated promptly with bronchodilators and a short course of oral steroids; antibiotics should be prescribed for purulent exacerbations. Patients with advanced COPD and respiratory failure require a comprehensive management plan that incorporates structured end-of-life care.

Canada↗