1. COPD: Beyond the Wheeze KMA Scientific Conference Ali AlMusawi, BMBCh, FRCPC

2. Objective Treating COPD, NOT only the Wheeze

3. COPD: Definition Chronic obstructive pulmonary disease (COPD): a common preventable and treatable disease is characterized by airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. GOLD 2016 COPD is a respiratory disorder largely caused by smoking, and is characterized by progressive, partially reversible airway obstruction and lung hyperinflation, systemic manifestations, and increasing frequency and severity of exacerbations. O’Donnell et al, Can Respir J Vol 14 Suppl B September 2007

4. COPD: Risk Factors Cigarette smoke is the main inflammatory trigger in COPD. Alpha1-antitrypsin (AAT) deficiency History of severe childhood respiratory infections History of Asthma Occupational exposures (particularly biomass fuel use) and air pollution

5. COPD: Mortality In 2004, COPD was the fourth leading cause of death in both men and women in the world, a significant increase from 1999 when it was the fifth leading cause of death. http://www.who.int/mediacentre/factshe ets/fs310/en/

6. COPD: Prevalence The reported prevalence of COPD ranged from 0.2% in Japan to 37% in the USA, but this varied widely across countries and populations, by diagnosis method, and by age group analyzed. International Journal of COPD 2012:7 457–494 In Middle East ~3.5% based on BREATHE study Respiratory Medicine (2012) 106(S2), S25–S32

7. COPD is systemic disease In most patients, the disease process affects the airways (leading to airway remodeling) and parenchyma (leading to emphysema and poor gas exchange) leading to chronic (productive) cough and exertional dyspnea.

8. COPD is systemic disease However, a substantial proportion of COPD patients have extra-pulmonary symptoms and signs. COPD CVD Cognitive Decline Depression Anxiety Cancer OsteoporosisCachexia Muscle weakness Anemia Renal insufficiency Metabolic Syndrome & DM

9. COPD is systemic disease Prevalence of different comorbidities in COPD patients by gender and GOLD stage (Dal Negro et al. Multidisciplinary Respiratory Medicine (2015) 10:24) Cross-sectional of an Italian institutional data base over the period 2012–2015 At least one comorbidity of clinical significance was found in 78.6 % of patients, but at least two in 68.8 %, and three or more were found in 47.9 % of subjects.

10. COPD is systemic disease Comorbidities can occur in patients with mild, moderate or severe airflow limitation, influence mortality and hospitalizations independently, and deserve specific treatment. Therefore, comorbidities should be looked for routinely, and treated appropriately, in any patient with COPD.

11. Question W hat is the best predictor of having COPD exacerbation? 1. FEV1 2. History of previous COPD exacerbations 3. BMI 4. SGRQ

12. Assessment of COPD People with same FEV1 have different health status, dyspnea scores, comorbidities, exacerbation history, etc. Spirometry is essential for the diagnosis of COPD, but it doesn’t fully capture the impact of the disease on individual patients

13. Assessment of COPD There is only a weak correlation between FEV1, symptoms and impairment of a patient’s health-related quality of life. For this reason, formal symptomatic assessment is also required.

14. Assessment of COPD FEV1 mMRC BODE (BMI/Obstructive/Dyspnea/exercise capacity) – ADO (age/Dyspnea/ obstructive) HRQL: CRQ – SF-36 – SGRQ – CAT Combined COPD Assessment

17. Question What is single most important therapy that slows down the progression of airflow limitation in patients with COPD? 1. Tiotropium bromide 2. Combination of Inhaled corticosteroid and long acting beta agonist 3. Smoking cessation 4. Pneumonia vaccine

18. Beyond the Wheeze: Smoking cessation Cigarette smoking is the major cause of COPD. Smoking cessation is the single most important therapy to retard the progression of airflow limitation and positively influence survival.

19. Beyond the Wheeze: Smoking cessation The Lung Health Study showed that patients with early- stage asymptomatic COPD who took part in a smoking cessation program had a lower risk of all-cause mortality compared with those who had not (follow-up: 14.5 years) (Anthonisen et al. 2005)

20. Beyond the Wheeze: Education Education provides important information to the patient and family about the disease process, its comorbidity, and its treatment. This information encourages active participation in health care, promotes adherence to therapy and provide self-management skills. It also helps patient and family to find ways to cope with chronic illness and its comorbidities. NEJM 360:1329-1335, 2009

21. Beyond the Wheeze: Education Common topics included in education include: Normal pulmonary anatomy and physiology. Pathophysiology of lung disease. Description and interpretation of medical tests. Self-management strategies. (Daily activities/energy conservation, self-assessment & symptoms management) Breathing exercises. Medication use. Exercise principles.

22. Beyond the Wheeze: Education A multicenter, randomized clinical trial was carried out in 7 hospitals. All patients had advanced COPD with at least 1 hospitalization for exacerbation in the previous year. Patients were assigned to a self-management program or to usual care. Hospital admissions for exacerbation of COPD were reduced by 39.8% (P =.01) Admissions for other health problems were reduced by 57.1% (P =.01). Emergency department visits were reduced by 41.0% (P =.02) Unscheduled physician visits by 58.9% (P =.003). Arch Intern Med. 2003;163(5):585-591.

23. Beyond the Wheeze: Nutrition Cachexia and skeletal dysfunction: frequently observed in patients with COPD and are associated with poor functional capacity, reduced health status, and increased mortality. Overall, nutritional depletion has been found in ~20- 35% of patients with stable COPD. However, among patients with an FEV1 < 35 % predicted, 50% were undernourished. Respir med 87(Suppl B):45-47, 1993. Proc Am Thorac Soc. 2008 May;5(4):519-23.

24. Beyond the Wheeze: Nutrition PULMONARY CACHEXIA SYNDROME: Malnutrition associated with advanced lung disease and is characterized by loss of fat­free body mass. A weight <90 % of ideal body weight or BMI ≤20 The pulmonary cachexia syndrome is associated with an accelerated decline in functional status and is associated with increase mortality. Hallin et al. 2007, Respiratory Medicine (2007) 101, 1954–1960

25. Beyond the Wheeze: Nutrition Nutritional support in COPD (eg, dietary advice, oral supplementation) modestly improves some clinically important outcomes such as: 6MWT Inspiratory and expiratory muscle strength Quality of life Handgrip strength Weight X But not mortality, spirometric values, or ABGs.

26. Beyond the Wheeze: Nutrition Respirology. 2013;18(4):616.

27. Beyond the Wheeze: Nutrition Respirology. 2013;18(4):616.

28. Beyond the Wheeze: Nutrition Respirology. 2013;18(4):616.

29. Beyond the Wheeze: Nutrition Strategies to enhance caloric intake include eating small frequent meals with nutrient­dense foods (eg, liquid nutritional supplements), eating meals that require little preparation (eg, microwaveable), resting before meals, and taking a daily multivitamin. Exercise has been shown to improve the effectiveness of nutritional therapy and to stimulate appetite.

30. Beyond the Wheeze: Exercise training Limitations to activity/exercise in COPD include: 1. Ventilatory/ gas-exchange limitations 2. Peripheral muscle deconditioning 3. Cardiovascular deconditioning Result in early onset anaerobic metabolism and the production of lactic acidosis during exercise.

31. Beyond the Wheeze: Exercise training Mechanism of skeletal dysfunction: - Catabolic sate (systemic steroid, ? low level of testosterone) - Cytokines,especially TNF-α, can act synergistically to inhibit messenger RNA expression for myosin heavy chain, leading to decreased muscle protein synthesis. Vicious cycle: Dyspnea and fatigability (in advanced COPD)  ↓ exercise tolerance  immobility  muscle dysfunction especially in the thighs and upper arms.

32. Beyond the Wheeze: Exercise training

33. Effect of exercise training: 1. Improves endurance and aids in performance of activities of daily living. 2. Helps reduce systemic blood pressure 3. Improves lipid profiles 4. Counteract depression and reduce anxiety associated with dyspnea-producing activities. 5. Facilitates sleep 6. ? Reduce AECOPD and mortality

34. Beyond the Wheeze: Exercise training Am J Respir Crit Care Med 1999; 159:321

35. Beyond the Wheeze Vaccines (flu and pneumonia) Oxygen therapy Surgical option (Lung transplant, Bronchoscopic, LVRS) Treatment of AECOPD

36. Beyond the Wheeze The ultimate weapon

37. Beyond the Wheeze Pulmonary Rehabilitation ATS and ERS define Pulmonary Rehabilitation (PR): Comprehensive intervention based on thorough patient assessment followed by patient-tailored therapies that include, but not limited to, exercise training, education and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors.

38. Beyond the Wheeze Pulmonary Rehabilitation PR and exercise training have been incorrectly considered to be equivalent. Although exercise training is a necessary component of PR, other interventions are integral to rehabilitation program; such as: Patient assessment Education (especially self-management strategies, inhaler technique, promotion of activity in home and community) Breathing retraining exercise Nutritional intervention Psychosocial support Discussion of advance directives

39. Beyond the Wheeze Pulmonary Rehabilitation Other therapies provided in PR program if indicated: Smoking cessation Chest physical therapy Oxygen therapy Occupational therapy Managing sleep disorder breathing (OSA, CSA, …etc)

40. Beyond the Wheeze Pulmonary Rehabilitation GOLD 2016

41. Beyond the Wheeze Pulmonary Rehabilitation GOLD 2016

42. Beyond the Wheeze Take Home Message