1. CHRONIC OBSTRUCTIVE PULMONARY DISEASE CLINICAL PRACTICE GUIDELINES REVIEW WEEK 2: THERAPY AMBULATORY INTERNAL MEDICINE GROUP PRACTICE UNIVERSITY HEALTH NETWORK / MSH OCTOBER 2007 Prepared by: Dr. D. Panisko

2. COPD: Guidelines for this Seminar  Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Celli BR et al. Eur Respir J 2004; 23: 932-46. Full document, with updates, available at: www.thoracic.org, accessed Sept 2007www.thoracic.org  Canadian Thoracic Society recommendations for the management of chronic obstructive pulmonary disease - 2003. O’Donnell DE et al. Can Respir J 2003; 10(SupplA): 11A- 33A  Global Initiative for Chronic Obstructive Lung Disease. (GOLD). A collaborative of the NIH and WHO. Updated Nov 2006, accessed Sept 2007. Available at www.goldcopd.com

3. COPD: other useful references:  2 recent review series on COPD: 5 article series on exacerbations: Thorax Feb – June, 2006 12 article series: BMJ May 13 th to July 22 nd, 2006  Excellent recent update: Update in Chronic Obstructive Pulmonary Disease 2006: Rabe KF, et al. Am J Resp Crit Care 2007; 175: 1222-1232

4. COPD Therapy: Objectives  This seminar deals with chronic stable COPD, not with acute exacerbations.  After this seminar you should: be aware of therapeutic clinical practice guidelines for stable chronic COPD be able to describe interventions that improve quality of life and mortality in stable COPD be able familiar with a guideline based therapeutic cascade for chronic stable COPD

5. COPD II:THERAPY CASE: As you recall from last week, you are seeing Mr. X. a 61 year old man who comes to your clinic as a new patient for follow up. He had just been admitted to hospital for his first exacerbation of COPD. He has completed a 10 day antibiotic course and 10 days of oral Prednisone. Spirometry reveals FEV1 of 65% pred and FEV1/FVC = 60% pred. He is now only on an ipratropium puffer, two puffs qid.

6. COPD II:THERAPY Mr. X. indicates his ipratropium puffer has helped, especially when compared to his symptoms before his hospitalization, when he was using no pharmacotherapy. However, he still has excess shortness of breath on exertion, occasional periods of dyspnea during the day, and awakens at about 5 am with shortness of breath. You now begin to consider therapeutic options for this patient.

7. COPD II:THERAPY What is Mr. X’s... clinical stage of COPD ? (See the next slide for a review of spirometric staging)

9. Copyright ©2005 BMJ Publishing Group Ltd. Cooper, C B et al. BMJ 2005;330:640-644 Fig 1 Clinical algorithm for the treatment of chronic obstructive pulmonary disease (COPD). Clinical stages are defined symptomatically (see footnote). GOLD stage refers to the classification of COPD on the basis of spirometry after using a bronchodilator

10. COPD II:THERAPY What is Mr. X’s clinical stage of COPD ? Mr. X has: persistent symptoms and stage 2 (Moderate COPD) The previous slide indicates a progressive management cascade that will be discussed further in this seminar. The next slide demonstrates the relationship between symptoms, disease progression, and the need for intervention.

12. COPD II:THERAPY  1)What preventive interventions are important for this COPD patient ? Do they have survival benefit ?

13. COPD II:THERAPY  1)Smoking cessation/vaccines If the patient can stop smoking, the decline of his FEV1 curve becomes less steep and survival is prolonged. Some authorities feel this is the most important intervention of all (Rabe et al 2007)! The effect of the vaccinations on survival is less definitive; survival and morbidity benefit of influenza vaccination has been shown for patients over the age of 65 and patients with COPD. There is less, Gr. B, evidence for benefit from pneumovax in COPD. Antiviral agents could be considered as preventive agents or as therapy in early influenzal infection in non- immunized patients.

14. COPD II:THERAPY  2)What are various methods available for smoking cessation in specialized programs ?  3)Where can you refer patients?

15. COPD II:THERAPY  2) The entire topic of smoking cessation will be covered in an AIMGP Clinic later in the year. Briefly: support groups, behaviour modification, reinforcement in pulmonary rehabilitation programs, and physician and nurse directives are used. Pharmacological methods include nicotine therapy (patch, gum, inhaler, spray), bupropion (Zyban) - a centrally acting noradrenergic agonist and novel antidepressant, and Buspirone - an anxiolytic. Combined nicotine and bupropion therapy, with a support program, achieved a 35% cessation rate at 1 year in one trial. A new agent, varencline, a nicotininc Ach receptor antagonist is undergoing clinical trials and has had some success.

16. COPD II:THERAPY  3) Smoking cessation resources: Asthma Clinic (run by the clinical nurse specialist), and Pulmonary Wellness Clinic (hospital operator can give you current telephone numbers) at the UHN.

17. COPD II:THERAPY  4)What pharmacologic therapy can be offered for Mr. X.'s:  a)intermittent dyspnea during the day ?  b)excess dyspnea on exertion ?  c)dyspnea in the early a.m. ?

18. COPD II:THERAPY 4a) If symptoms become regular and more frequent than those treated by a prn short acting agent, evidence indicates that regular use of a long acting bronchodilator provides more effective treatment than multiple daily usage of short acting inhalers.

19. COPD II:THERAPY 4a) cont. Add a beta agonist inhaler, preferably a long acting agent like salmeterol 2 puffs bid. The long acting anticholinergic inhaler tiotropium, 18 mcg od, can also be substituted for the ipratropium. The dose response for ipratropium is linear up to about 6 or 8 puffs q4h... so you can push puffer doses to this level if your patient is still symptomatic. WE TEND TO UNDERDOSE !!! A therapeutic cascade for bronchodilators for the ATS/ERS guidelines is shown on the next slide

20. SA-BD = Short Acting Bronchodilator, LA-BD = Long-Acting Bronchodilator, ICS = Inhaled Corticosteroid

21. COPD II:THERAPY What pharmacologic therapy can be offered for Mr. X.‘s  b)excess dyspnea on exertion ?  b) Use salbutamol puffer 2 to 4 puffs prn pre- exercise, and improve baseline daytime control as in a) above. Entry into a pulmonary rehab day program may improve conditioning and exercise tolerance.

22. COPD II:THERAPY 4)c) Nocturnal Symptoms:  Use a long acting beta agonist (salmeterol) qhs or the long acting anticholinergic tiotropium, 18 mcg od.  A long acting oral theophylline preparation qhs may also work. Theophylline preparations do not need to be titrated to full therapeutic doses as levels of 30-50 mmol/l are probably as effective as usual "therapeutic" levels of 55-110 mmol/l. The recent Canadian guidelines also recommend these agents as 4 th line for chronic maintenance therapy in COPD.

23. COPD II:THERAPY 4)c) cont.  For early am or nocturnal symptoms also consider need for sleep study and examination for night time desaturations, especially if there is LV or RV dysfunction. Also consider non-pulmonary reasons for night time exacerbations of shortness of breath like microaspiration from esophageal reflux, and paroxysmal nocturnal dyspnea.

24. COPD II:THERAPY  5)Mr. X. has moderate, regularly symptomatic COPD and therefore needs multiple medications. In contrast, what would you prescribe for a patient with mild and only occasional symptoms from Chronic Obstructive Pulmonary Disease ?

25. COPD II:THERAPY  5) A short acting beta agonist puffer prn. Consider which is the optimal metered dose inhaler (puffer, turbuhaler, etc.), whether a spacer device is required (aerochamber, etc.), and observation of the patient to ensure effective delivery of medication.

26. COPD II:THERAPY Mr. X. returns in 4 weeks after you have added salbutamol 2-4 puffs prn with exercise and replaced his regular ipratropium with tiotropium. You have prescribed rescue salbutamol/ipratropium combination (Combivent) You have monitored his puffer technique, felt it was very good and did not prescribe a spacer. He has enrolled in a smoking cessation program and feels he is making progress.

27. COPD II:THERAPY His nocturnal symptoms have markedly improved with 2 puffs of salmeterol qam and qhs. He continues to have productive cough of whitish yellow sputum - 2 tablespoons each morning and less, intermittently, throughout the day. However, while feeling much better overall, he still notes residual dyspnea on exercise and some dyspnea and discomfort at rest.

28. COPD II:THERAPY  7)What is the next step in the therapeutic cascade for this patient ? How do you implement this therapy ?

29. COPD II:THERAPY  7)Could also consider inhaled corticosteroids. ATS/ERS guidelines now suggest initiation of this therapy with FEV1<50% predicted or if the patient is experiencing frequent exacerbations. Could consider regular long acting theophylline therapy (Canadian and ATS/ERS guidelines). The next slide illustrates (again) the cascade of therapy recommended and based on ATS/ERS guidelines.

30. COPD II:THERAPY  7)The TORCH trial (Calverley et al N Engl J Med 2007; 356: 775-89) did not show a mortality benefit for combined LABA/CS but demonstrated an improvement in many clinical outcomes for this combined mode of therapy (i.e. quality of life measures, decrease in exacerbations). Another randomized trial showed no additive preventive effect of LABA/CS for COPD exacerbations on top of existing tiotropium therapy. However combined therapy improved lung function, quality of life, and did decrease hospitalizations (Aaron et al 2007; 146: 545-555).

31. SA-BD = Short Acting Bronchodilator, LA-BD = Long-Acting Bronchodilator, ICS = Inhaled Corticosteroid

32. COPD II:THERAPY Two years later, Mr. X. has begun to feel much more short of breath, despite compliance with maximal medical therapy. Spirometry reveals an FEV1 of 38% predicted. You now note some peripheral cyanosis at rest, even though Mr. X. is at baseline and not in an exacerbation.

33. COPD II:THERAPY  9)What additional diagnostic and potential therapeutic interventions are appropriate ?  10)How can you refer patients for pulmonary rehabilitation from the AIMGP clinic ?

34. COPD II:THERAPY 9) Diagnostic and Therapeutic Interventions:  Resting, exercise, and possibly overnight oximetry.  ABG to determine whether long term oxygen therapy is indicated. ABG required for ODB approval for funding of O2 therapy (PaO2<55mmHg or <60mmHg if cor pulmonale is present). Call Respiratory Therapist to your clinic for home O2 forms and for help in setting up home O2. Consider ABG whenever FEV1 falls below 50% predicted.

35. COPD II:THERAPY 9) Diagnostic and Therapeutic Interventions:  Consider a complication accounting for the decline (like recurrent chronic pulmonary embolization).  Consider referral to a respirologist.  Consider referral to a pulmonary rehabilitation program.  If advance directives for care have not been established, they should be discussed with the patient now or at an opportune time.

36. COPD II:THERAPY 9) Diagnostic and Therapeutic Interventions:  Bullectomy and lung volume reduction surgery may result in improved spirometry, lung volume, exercise capacity, dyspnoea, health-related quality of life and possibly survival in highly selected patients (e.g. with assymetrical bullae and poor exercise capacity).  Lung transplantation results in improved pulmonary function, exercise capacity, quality of life and possibly survival in highly selected patients. 10) Referral to Pulmonary Rehab:  Pulmonary Wellness Clinic at the University Health Network (call hospital operator for clinic #) or Residential and outpatient programs at West Park Hospital.