Denis E. O’Donnell

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2007 update

Chronic obstructive pulmonary disease (COPD) is a major respiratory illness in Canada that is both preventable and treatable. Our understanding of the pathophysiology of this complex condition continues to grow and our ability to offer effective treatment to those who suffer from it has improved considerably. The purpose of the present educational initiative of the Canadian Thoracic Society (CTS) is to provide up to date information on new developments in the field so that patients with this condition will receive optimal care that is firmly based on scientific evidence. Since the previous CTS management recommendations were published in 2003, a wealth of new scientific information has become available. The implications of this new knowledge with respect to optimal clinical care have been carefully considered by the CTS Panel and the conclusions are presented in the current document. Highlights of this update include new epidemiological information on mortality and prevalence of COPD, which charts its emergence as a major health problem for women; a new section on common comorbidities in COPD; an increased emphasis on the meaningful benefits of combined pharmacological and nonpharmacological therapies; and a new discussion on the prevention of acute exacerbations. A revised stratification system for severity of airway obstruction is proposed, together with other suggestions on how best to clinically evaluate individual patients with this complex disease. The results of the largest randomized clinical trial ever undertaken in COPD have recently been published, enabling the Panel to make evidence-based recommendations on the role of modern pharmacotherapy. The Panel hopes that these new practice guidelines, which reflect a rigorous analysis of the recent literature, will assist caregivers in the diagnosis and management of this common condition.

Canadian Thoracic Society Recommendations for Management of Chronic Obstructive Pulmonary Disease – 2008 Update – Highlights for Primary Care

Chronic obstructive pulmonary disease (COPD) is a major respiratory illness in Canada that is preventable and treatable but unfortunately remains underdiagnosed. The purpose of the present article from the Canadian Thoracic Society is to provide up-to-date information so that patients with this condition receive optimal care that is firmly based on scientific evidence. Important summary messages for clinicians are derived from the more detailed Update publication and are highlighted throughout the document. Three key messages contained in the update are: use targeted screening spirometry to establish a diagnosis and initiate prompt management (including smoking cessation) of mild COPD; improve dyspnea and activity limitation in stable COPD using new evidence-based treatment algorithms; and understand the importance of preventing and managing acute exacerbations, particularly in moderate to severe disease.

Effect of indacaterol on exercise endurance and lung hyperinflation in COPD

BACKGROUND Indacaterol is a novel, inhaled, once-daily ultra long-acting β(2)-agonist (ultra-LABA) for the treatment of COPD. This study investigated the effect of indacaterol on exercise endurance, and on lung hyperinflation during exercise and at rest in patients with moderate-to-severe COPD. METHODS In this double-blind, placebo-controlled, two-period crossover study (3-week treatment, 3-week washout between treatments), patients were randomized to receive indacaterol 300 μg once-daily or matching placebo. The primary efficacy variable was exercise endurance time after 3 weeks of treatment, measured through constant-load cycle ergometry testing performed at 75% of the peak work rate in a screening incremental exercise test. RESULTS Of 90 patients randomized (mean age: 62.8 years; post-bronchodilator FEV(1): 61.2% predicted and FEV(1)/FVC: 51.6%), 74 completed the study. Pre-treatment exercise tolerance averaged 459 s. Improvement in exercise endurance time was higher with indacaterol 300 μg than with placebo both after the first dose (treatment difference: 101 s; p < 0.001) and after 3 weeks (treatment difference: 111 s; p = 0.011). In addition, indacaterol increased end-exercise inspiratory capacity (IC) versus placebo after 3 weeks (0.28 L, p = 0.002). Significant improvements were also observed in resting IC (0.17 L, p = 0.001), FEV(1) (0.25 L, p < 0.001) and FVC (0.26 L, p < 0.001) with indacaterol compared with placebo at 75 min post-dose after 3 weeks. CONCLUSION In conclusion, indacaterol treatment improved the ability of patients with COPD to exercise. In addition, the improvements observed in resting and end-exercise IC indicate reductions in lung hyperinflation after 3 weeks treatment (ClinicalTrials.gov registration number: NCT00620022).

State of the Art Compendium: Canadian Thoracic Society Recommendations for Management of Chronic Obstructive Pulmonary Disease

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 Societys evidence-based guidelines is to optimize early diagnosis, prevention and management of COPD in Canada. The main message of the guidelines is that COPD is a preventable and treatable disease. Targeted spirometry is strongly recommended to expedite early diagnosis in smokers and former smokers who develop respiratory symptoms, and who are at risk for COPD. Smoking cessation remains the single most effective intervention to reduce the risk of COPD and to slow its progression. Education, especially self-management plans, are key interventions in COPD. Therapy should be escalated on an individual basis in accordance with the increasing severity of symptoms and disability. Long-acting anticholinergics and beta-2-agonist inhalers should be prescribed for patients who remain symptomatic despite short-acting bronchodilator 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. 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. Management strategies, consisting of combined modern pharmacotherapy and nonpharmacotherapeutic interventions (eg, pulmonary rehabilitation and exercise training) can effectively improve symptoms, activity levels and quality of life, even in patients with severe COPD.

Optimizing pulmonary rehabilitation in chronic obstructive pulmonary disease - practical issues: A Canadian Thoracic Society Clinical Practice Guideline

Pulmonary rehabilitation (PR) participation is the standard of care for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite bronchodilator therapies. However, there are questions about specific aspects of PR programming including optimal site of rehabilitation delivery, components of rehabilitation programming, duration of rehabilitation, target populations and timing of rehabilitation. The present document was compiled to specifically address these important clinical issues, using an evidence-based, systematic review process led by a representative interprofessional panel of experts. The evidence reveals there are no differences in major patient-related outcomes of PR between nonhospital- (community or home sites) or hospital-based sites. There is strong support to recommend that COPD patients initiate PR within one month following an acute exacerbation due to benefits of improved dyspnea, exercise tolerance and health-related quality of life relative to usual care. Moreover, the benefits of PR are evident in both men and women, and in patients with moderate, severe and very severe COPD. The current review also suggests that longer PR programs, beyond six to eight weeks duration, be provided for COPD patients, and that while aerobic training is the foundation of PR, endurance and functional ability may be further improved with both aerobic and resistance training.

Pulmonary Gas Exchange Abnormalities in Mild Chronic Obstructive Pulmonary Disease. Implications for Dyspnea and Exercise Intolerance.

RATIONALE Several studies in mild chronic obstructive pulmonary disease (COPD) have shown a higher than normal ventilatory equivalent for carbon dioxide ([Formula: see text]e/[Formula: see text]co2) during exercise. Our objective was to examine pulmonary gas exchange abnormalities and the mechanisms of high [Formula: see text]e/[Formula: see text]co2 in mild COPD and its impact on dyspnea and exercise intolerance. METHODS Twenty-two subjects (11 patients with GOLD [Global Initiative for Chronic Obstructive Lung Disease] grade 1B COPD, 11 age-matched healthy control subjects) undertook physiological testing and a symptom-limited incremental cycle exercise test with arterial blood gas collection. MEASUREMENTS AND MAIN RESULTS Patients (post-bronchodilator FEV1: 94 ± 10% predicted; mean ± SD) had evidence of peripheral airway dysfunction and reduced peak oxygen uptake compared with control subjects (80 ± 18 vs. 113 ± 24% predicted; P<0.05). Arterial blood gases were within the normal range and effective alveolar ventilation was not significantly different from control subjects throughout exercise. The alveolar-arterial O2 tension gradient was elevated at rest and throughout exercise in COPD (P<0.05). [Formula: see text]e/[Formula: see text]co2, dead space to tidal volume ratio (Vd/Vt), and arterial to end-tidal CO2 difference were all higher (P<0.05) in patients with COPD than in control subjects during exercise. In patients with COPD versus control subjects, there was significant dynamic hyperinflation and greater tidal volume constraints (P<0.05). Standardized dyspnea intensity ratings were also higher (P<0.05) in patients with COPD versus control subjects in association with higher ventilatory requirements. Within all subjects, Vd/Vt correlated with the [Formula: see text]e/[Formula: see text]co2 ratio during submaximal exercise (r=0.780, P<0.001). CONCLUSIONS High Vd/Vt was the most consistent gas exchange abnormality in smokers with only mild spirometric abnormalities. Compensatory increases in minute ventilation during exercise maintained alveolar ventilation and arterial blood gas homeostasis but at the expense of earlier dynamic mechanical constraints, greater dyspnea, and exercise intolerance in mild COPD.

Inhaled Fentanyl Citrate Improves Exercise Endurance During High-Intensity Constant Work Rate Cycle Exercise in Chronic Obstructive Pulmonary Disease

CONTEXT Activity limitation and dyspnea are the dominant symptoms of chronic obstructive pulmonary disease (COPD). Traditionally, efforts to alleviate these symptoms have focused on improving ventilatory mechanics, reducing ventilatory demand, or both of these in combination. Nevertheless, many patients with COPD remain incapacitated by dyspnea and exercise intolerance despite optimal therapy. OBJECTIVES To determine the effect of single-dose inhalation of nebulized fentanyl citrate (a μ-opioid agonist drug) on exercise tolerance and dyspnea in COPD. METHODS In a randomized, double-blind, placebo-controlled, crossover study, 12 stable patients with COPD (mean ± standard error of the mean post-β(2)-agonist forced expiratory volume in one second [FEV(1)] and FEV(1) to forced vital capacity ratio of 69% ± 4% predicted and 49% ± 3%, respectively) received either nebulized fentanyl citrate (50 mcg) or placebo on two separate days. After each treatment, patients performed pulmonary function tests and a symptom-limited constant work rate cycle exercise test at 75% of their maximum incremental work rate. RESULTS There were no significant postdose differences in spirometric parameters or plethysmographic lung volumes. Neither the intensity nor the unpleasantness of perceived dyspnea was, on average, significantly different at isotime (5.0 ± 0.6 minutes) or at peak exercise after treatment with fentanyl citrate vs. placebo. Compared with placebo, fentanyl citrate was associated with 1) increased exercise endurance time by 1.30 ± 0.43 minutes or 25% ± 8% (P=0.01); 2) small but consistent increases in dynamic inspiratory capacity by ∼0.10 L at isotime and at peak exercise (both P≤0.03); and 3) no concomitant change in ventilatory demand, breathing pattern, pulmonary gas exchange, and/or cardiometabolic function during exercise. The mean rate of increase in dyspnea intensity (1.2 ± 0.3 vs. 2.9 ± 0.8 Borg units/minute, P=0.03) and unpleasantness ratings (0.5 ± 0.2 vs. 2.9 ± 1.3 Borg units/minute, P=0.06) between isotime and peak exercise was less after treatment with fentanyl citrate vs. placebo. CONCLUSION Single-dose inhalation of fentanyl citrate was associated with significant and potentially clinically important improvements in exercise tolerance in COPD. These improvements were accompanied by a delay in the onset of intolerable dyspnea during exercise near the limits of tolerance.

Chronic Obstructive Pulmonary Disease: Clinical Integrative Physiology

Peripheral airway dysfunction, inhomogeneous ventilation distribution, gas trapping, and impaired pulmonary gas exchange are variably present in all stages of chronic obstructive pulmonary disease (COPD). This article provides a cogent physiologic explanation for the relentless progression of activity-related dyspnea and exercise intolerance that all too commonly characterizes COPD. The spectrum of physiologic derangements that exist in smokers with mild airway obstruction and a history compatible with COPD is examined. Also explored are the perceptual and physiologic consequences of progressive erosion of the resting inspiratory capacity. Finally, emerging information on the role of cardiocirculatory impairment in contributing to exercise intolerance in patients with varying degrees of airway obstruction is reviewed.

Physiological mechanisms of hyperventilation during human pregnancy

This study examined the role of pregnancy-induced changes in wakefulness (or non-chemoreflex) and central chemoreflex drives to breathe, acid-base balance and female sex hormones in the hyperventilation of human pregnancy. Thirty-five healthy women were studied in the third trimester (TM(3); 36.3+/-1.0 weeks gestation; mean+/-S.D.) and again 20.2+/-7.8 weeks post-partum (PP). An iso-oxic hyperoxic rebreathing procedure was used to evaluate wakefulness and central chemoreflex drives to breathe. At rest, arterialized venous blood was obtained for the estimation of arterial PCO(2) (PaCO(2)) and [H(+)]. Blood for the determination of plasma strong ion difference ([SID]), albumin ([Alb]), as well as serum progesterone ([P(4)]) and 17beta-estradiol ([E(2)]) concentrations was also obtained at rest. Wakefulness and central chemoreflex drives to breathe, [P(4)] and [E(2)], ventilation and V CO(2) increased, whereas PaCO(2) and the central chemoreflex ventilatory recruitment threshold for PCO(2) (VRTCO(2)) decreased from PP to TM(3) (all p<0.01). The reductions in PaCO(2) were not related to the increases in [P(4)] and [E(2)]. The alkalinizing effects of reductions in PaCO(2) and [Alb] were partly offset by the acidifying effects of a reduced [SID], such that arterial [H(+)] was still reduced in TM(3) vs. PP (all p<0.001). A mathematical model of ventilatory control demonstrated that pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid-base balance, V CO(2) and cerebral blood flow account for the reductions in PaCO(2), [H(+)] and VRTCO(2). This is the first study to demonstrate that the hyperventilation and attendant hypocapnia/alkalosis of human pregnancy results from a complex interaction of pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid-base balance, metabolic rate and cerebral blood flow.

When Obesity and Chronic Obstructive Pulmonary Disease Collide. Physiological and Clinical Consequences

In many parts of the world, the prevalence of both chronic obstructive pulmonary disease (COPD) and obesity is increasing at an alarming rate. Such patients tend to have greater respiratory symptoms, more severe restriction of daily activities, poorer health-related quality of life, and greater health care use than their nonobese counterparts. Physiologically, increasing weight gain is associated with lung volume reduction effects in both health and disease, and this should be considered when interpreting common pulmonary function tests where lung volume is the denominator, such as FEV1/FVC and the ratio of diffusing capacity of carbon monoxide to alveolar volume, or indeed when evaluating the physiological consequences of emphysema in obese individuals. Contrary to expectation, the presence of mild to moderate obesity in COPD appears to have little deleterious effect on respiratory mechanics and muscle function, exertional dyspnea, and peak symptom-limited oxygen uptake during cardiopulmonary exercise testing. Thus, in evaluating obese patients with COPD reporting activity restriction, additional nonpulmonary factors, such as increased metabolic loading, cardiocirculatory impairment, and musculoskeletal abnormalities, should be considered. Care should be taken to recognize the presence of obstructive sleep apnea in obese patients with COPD, as effective treatment of the former condition likely conveys an important survival advantage. Finally, morbid obesity in COPD presents significant challenges to effective management, given the combined effects of erosion of the ventilatory reserve and serious metabolic and cardiovascular comorbidities that collectively predispose to an increased risk of death from respiratory failure.