Conflicts of interest. Pulmonary rehabilita8on. Objec8ves / Outline. Pulmonary rehabilita8on in COPD. Pulmonary rehabilita8on in COPD

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1 Conflicts of interest UBC I have no conflicts of interest related to this presenta8on Treatment op+ons From a global perspec+ve: Non- pharmaceu+cal treatments Pulmonary Fibrosis Founda8on Summit La Jolla, CA December 7, 2013 FRCPC Department of Medicine, UBC Vancouver, Canada I receive research and/or clinical funding from: Intermune Medimmune Actelion Gilead I receive advisory board/consulta8on fees from: Intermune Objec8ves / Outline Review evidence & recommenda8ons for non- pharmaceu8cal treatment op8ons of IPF Pulmonary rehabilita+on Vaccina8on Support groups & educa8on Diet / Nutri*on Lung transplanta*on Pulmonary rehabilita8on A structured exercise and educa8onal program that involves aerobic condi8oning, strength and flexibility training, educa8onal lectures, nutri8onal interven8ons, and psychosocial support Usually 2-3 hours per session, 2-3 sessions per week, total dura8on of 6-9 weeks Followed by a self- supervised home exercise program Nici et al, AJRCCM 2006;173:1390. Pulmonary rehabilita8on in COPD Pulmonary rehabilita8on in COPD Benefits Exercise capacity Intensity of breathlessness Health- related quality of life Anxiety and depression Number of hospitaliza8ons and days in the hospital Recovery acer hospitaliza8on Arm func8on Effects beyond dura8on of PR Effect of long- ac8ng bronchodilators Survival Respiratory muscle func8on Evidence Weak GOLD recommends PR in COPD pa8ents with breathlessness when walking at their own pace on level ground 1

2 ILD clinicians & researchers generally believe PR works PR works in COPD Many mechanisms of benefit in COPD likely apply to pa8ents with ILD (i.e. cardiovascular performance, peripheral muscle func8on, some educa8on components) Anecdotal clinical experience in pa8ents with ILD Several studies in ILD suggest similar effects to COPD 2 RCTs and several cohort studies Two RCTs of PR in ILD 6- minute walk distance (and several consistent cohort studies) All ILD Nishiyama et al, 2008 Holland et al, 2008 Popula+on IPF: n = 28 ILD: n = 57 (IPF n = 34) Interven+on 2 sessions per week x 10 weeks 2 sessions per week x 8 weeks Prescrip8on for long- term home exercise program Control Not stated Telephone support Outcomes 6MWD, QOL, dyspnea, exercise capacity Post- rehab only 6MWD, QOL, dyspnea, exercise capacity Post- rehab + 6- month follow- up PR improves 6MWD by 39 metres in ILD (95% CI: 15 to 62) No effect at 6 months: 7.4 metres (95% CI: - 36 to 51) (Holland study only) Nishiyama et al, Respirology 2008;13:394; Holland et al, Thorax 2008;63: minute walk distance Quality of life All ILD Baseline IPF only Follow- up PR improves 6MWD by 27 metres in IPF (95% CI: 3 to 50) PR improves QOL, but unclear long- term effect 2

3 Dyspnea Baseline Follow- up The majority of pa8ents with IPF should be treated with pulmonary rehabilita8on (weak recommenda8on, low- quality evidence) IPF Clinical Prac8ce Guideline The panel voted: 19 to 0 in favor of PR in IPF PR transiently improves dyspnea Raghu et al, AJRCCM 2011;183:788. Symptoma8c endpoints Quality of life Dyspnea Depression Func8onal endpoints Exercise capacity Physical ac8vity Short- term Long- term? p=0.15 Who should be treated? RCT & one cohort study suggest greater improvement with earlier PR Higher FVC & nadir SpO 2, lower RVSP à Greater benefit users benefit less Other cohort studies suggest greater improvement in more advanced disease Benefit in hospitalized ILD pa8ents Muscle func8on? p=0.06 Ryerson et al, Respiratory Medicine published online December 5, Holland et al, RespMed 2012;106:429; Ferreira et al, Chest 2009;135:442; Huppmann et al, ERJ 2013;42:444; Johnson- Warrington et al, JCardiopulmRehabPrev 2013;33:189. Who should be treated? Change in 6MWD (follow-up - baseline), m Improved!6MWD! IPF Other ILD Line of best fit (all patients) r!=!0.49! P!=!0.0004! is not a drug (?) Center for Medicare and Medicaid Services considers oxygen to be equipment Baseline 6MWD, m Selected pa8ents with a severely impaired func8onal capacity can s8ll benefit from rehabilita8on hrp:// therapy.html 3

4 Mul8ple RCTs in COPD, including MRC & NOTT trials that showed improved survival with long- term oxygen therapy in pa8ents with significant hypoxemia Similar improvements in quality of life and other endpoints Cumula8ve survival Con8nuous oxygen Nocturnal oxygen General recommenda8ons PaO 2 55 mmhg (or SpO 2 <88%) PaO 2 59 mmhg (or SpO 2 <89%) + right heart dysfunc8on Time from randomiza8on Con8nuous or nocturnal oxygen therapy in hypoxemic chronic obstruc8ve lung disease: a clinical trial. Nocturnal Therapy Trial Group. Ann Intern Med 1980; 93:391. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complica8ng chronic bronchi8s and emphysema. Report of the Medical Research Council Working Party. Lancet 1981; 1: and- Educa8on/Medicare- Learning- Network- MLN/MLNProducts/downloads/ OxgnThrpy_DocCvg_FactSheet_ICN pdf in ILD/IPF No studies of con8nuous oxygen therapy Benefit is extrapolated from COPD studies (NOTT, MRC) Dyspnea improved when transiently breathing 28% FiO 2 compared to room air in 10 pa8ents with ILD Ambulatory oxygen improves dyspnea & walk distance Weak data from small series IPF guideline recommenda8on Pa8ents with IPF and clinically significant res8ng hypoxemia should be treated with long- term oxygen therapy (strong recommenda8on, very low- quality evidence) IPF Clinical Prac8ce Guideline Bajwah et al, Thorax 2013;68:867; Swinburn et al, Am Rev Respir Dis 1991;143:913; Visca et al, ERJ 2011;38:987; Frank et al, ERJ 2012;40:269. Raghu et al, AJRCCM 2011;183:788. Influenza vaccines Influenza vaccines are typically trivalent (include 3 strains likely to cause outbreaks in a given year), although newer quadrivalent strains are replacing these Influenza vaccines Inac8vated influenza vaccine (IIV) IM Injec8on This is the typical influenza vaccine recommended annually for all individuals 6 months of age Newer intranasal live arenuated influenza vaccine (LAIV) Causes a very low- grade infec8on in virtually all pa8ents More serious infec8ons possible in severe immunocompromised pa8ents (e.g. bone marrow transplant) Not recommended for pa8ents with chronic lung disease 4

5 Pneumococcal vaccines Polysaccharide vaccine (PPSV23; Pneumovax) Provides protec8on from approximately 2/3 of recent pneumococcal infec8ons Recommended by the US Advisory Commiree on Immuniza8on Prac8ces (ACIP) for all adults with chronic lung disease Conjugate vaccine (PCV13; Prevnar) Includes 12 of the an8gens included in Pneumovax Carrier protein may increase immunogenicity & mucosal immunity à decreases carriers à herd immunity Recommenda8ons for pneumococcal vaccina8on Vaccinate with PPSV23 (Pneumovax) at diagnosis of ILD and again at or acer age 65 if at least 5 years have elapsed since the first dose Some advocate re- vaccina8on every 5 years in pa8ents with chronic respiratory disease Advisory Commiree on Immuniza8on Prac8ces Adults aged 19 years with immunocompromising condi8ons should receive PCV13 (Prevnar), followed by PPSV23 (Pneumovax) at least 8 weeks later Support groups & educa8on The majority of IPF pa8ents lack knowledge about their condi8on Educa8onal resources ocen contain incorrect or outdated informa8on ILD/IPF support groups exist at many ILD centers Individual educa8onal components vary among centers and there is no evidence to guide the design of support groups Summary There are likely clinically significant benefits to pulmonary rehabilita8on, oxygen therapy, and vaccina8ons This is based on low quality evidence, but obtaining defini8ve data may not be feasible given the widespread acceptance of these therapies Selected pa8ents with severely impaired func8onal capacity can s8ll benefit from rehabilita8on Addi8onal research is required to determine the op8mal design and components of support groups and educa8onal programs Collard HR et al. Respir Med 2007;101:1350; Lindell KO et al, Heart Lung 2010;39: