COPD Robert Schilz DO, PhD Pulmonary, Critical Care and Sleep Medicine University Hospitals Case Medical Center

COPD 2018 GOLD 2017 Report Global Initiative for Chronic Obstructive Lung D isease COPYRIGHTED MATERIAL- DO NOT COPY OR DISTRIBUTE GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE 2017 REPORT Robert Schilz DO, PhD Pulmonary, Critical Care and Sleep Medicine University Hospitals Case Medical Center

Conflict of Interest Declaration None

CHALLENGE: Re-evaluate your COPD treatment paradigm, therapies and documentation

Areas of Active Change in COPD Management and Approach 4x more drugs than in 2000 New guidelines (GOLD, ATS) as of 2016, 2017 Focus on risk classification, phenotyping and comorbidities Change management paradigm to favor long acting bronchodilators (Steroid Controversies) Introduce clear guidelines for follow up and evaluation of stable patients and exacerbations Make first time recommendations for management of severe patients with nocturnal ventilation and lung volume reduction surgery

Summary of GOLD 2017 Updates Chapter 1 The definition of COPD has been revised to include the impact of respiratory symptoms and the role of lung tissue and airway abnormalities in the development of COPD. The origin of COPD development is discussed relative to interactions of host factors and environmental exposures. Chapter 2 The ABCD assessment tool has been refined to utilize respiratory symptoms and exacerbations alone to assign ABCD categories. The role of spirometry in overall management of COPD has been updated. Chapter 3 Assessment and regular evaluation of inhaler technique has been added to attempt to improve therapeutic outcomes. Increased evidence for self-management, pulmonary rehabilitation, integrated care and palliative care is presented. Recommendations for noninvasive ventilation, oxygen therapy and lung volume reduction are provided based on new information. Chapter 4 Examination of symptoms and future risk of exacerbations should provide the map for pharmacologic management of stable COPD. A shift towards more personalized approach to treatment is introduced, with strategies for escalation and de-escalation of pharmacotherapy. Chapter 5 Detailed hospital discharge and follow up criteria are presented and include integrated team care. Chapter 6 The strategies for the management of cardiovascular and other important comorbidities are presented in detail. The complex issues of multimorbidity and polypharmacy are outlined. From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org.

2011+ Paradigm Shift in Global Recommendations for COPD Management 1) Reduce Symptoms Relieve symptoms FEV1 Based Management Strategy with Some Escalation Based on Symptom Control Improve exercise tolerance Improve health status 2) Reduce Risk Prevent disease progression Prevent and treat exacerbations Reduce mortality

Previous Treatment Paradigm: Therapy at Each Stage of COPD * I: Mild FEV 1 /FVC < 70% FEV 1 > 80% predicted II: Moderate FEV 1 /FVC < 70% 50% < FEV 1 < 80% predicted III: Severe FEV 1 /FVC < 70% 30% < FEV 1 < 50% predicted Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed) IV: Very Severe FEV 1 /FVC < 70% FEV 1 < 30% predicted or FEV 1 < 50% predicted plus chronic respiratory failure Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations *Postbronchodilator FEV 1 is recommended for the diagnosis and assessment of severity of COPD Add long term oxygen if chronic respiratory failure. Consider surgical treatments

Exacerbation Frequency and Severity Both Increase Mortality Risk 1.0 1.0 Probability of surviving 0.8 0.6 0.4 0.2 A P<0.0002 B P=0.069 C P<0.0001 Probability of surviving 0.8 0.6 0.4 0.2 (1) NS (2) P=0.005 (3) NS (4) P<0.0001 P<0.0001 0.0 0 10 20 30 40 50 60 Time (months) 0.0 0 10 20 30 40 50 60 Time (months) Group A Group B Group C patients with no acute exacerbations patients with 1 2 acute exacerbations requiring hospital management patients with 3 acute exacerbations Group (1) Group (2) Group (3) Group (4) no acute exacerbations acute exacerbations requiring emergency service visits without admission patients with acute exacerbations requiring one hospital admission patients with acute exacerbations requiring readmissions Soler-Cataluña JJ, et al. Thorax. 2005;60:925-931.

Combined Assessment of COPD Risk (GOLD Classification of Airflow Limitation) 4 3 2 1 (C) (D) (A) (B) CAT < 10 CAT > 10 Symptoms 2 or > 1 leading to hospital admission 1 (not leading to hospital admission) 0 Risk (Exacerbation history) If GOLD 3 or 4 or 2 exacerbations per year or > 1 leading to hospital admission: High Risk (C or D) If GOLD 1 or 2 and only 0 or 1 exacerbations per year (not leading to hospital admission): Low Risk (A or B) mmrc 0 1 mmrc > 2 Breathlessness 2015 Global Initiative for Chronic Obstructive Lung Disease

Tools Involved in Risk Assessment in Current GOLD Treatment Paradigm Simple spirometry COPD Assessment Test (CAT) Modified Medical Research Council Dyspnea Scale (mmrc)

Global Strategy for Diagnosis, Management and Prevention of COPD Classification of Severity of Airflow Limitation in COPD* GOLD 1 Mild FEV 1 > 80% predicted GOLD 2 Moderate 50% < FEV 1 < 80% predicted GOLD 3 Severe 30% < FEV 1 < 50% predicted GOLD 4 Very Severe FEV 1 < 30% predicted *Based on Post-Bronchodilator FEV 1 2015 Global Initiative for Chronic Obstructive Lung Disease

COPD Assessment Test (CAT)

Modified Medical Research Council Dyspnea Scale (mmrc) Grade 0: breathless with strenuous exercise Grade I: short of breath when hurrying on the level or walking up a slight hill Grade II: walking slower than people of the same age on the level because of breathlessness or having to stop for breath when walking at own pace on the level Grade III: stopping for breath after walking about 100 yards or after a few minutes on the level Grade IV: too breathless to leave the house or breathless when dressing or undressing

Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD When assessing risk, choose the highest risk according to GOLD grade or exacerbation history. One or more hospitalizations for COPD exacerbations should be considered high risk.) Patient Characteristic Spirometric Classification Exacerbations per year CAT mmrc A B C Low Risk Less Symptoms Low Risk More Symptoms High Risk Less Symptoms GOLD 1-2 1 < 10 0-1 GOLD 1-2 1 > 10 > 2 GOLD 3-4 > 2 < 10 0-1 D High Risk More Symptoms GOLD 3-4 > 2 > 10 > 2 2014 Global Initiative for Chronic Obstructive Lung Disease

BODE Index for COPD Survival http:www.qxmd.com

Variables and Point Values Used for the Computation of the Body-Mass Index, Degree of Airflow Obstruction and Dyspnea, and Exercise Capacity (BODE) Index Celli, B. et al. N Engl J Med 2004;350:1005-1012

Kaplan-Meier Survival Curves for the Four Quartiles of the Body-Mass Index, Degree of Kaplan-Meier Airflow Obstruction Survival and Curves Dyspnea, for the and Four Exercise Quartiles Capacity of the Body-Mass Index (Panel Index, A) and Degree the Three of Airflow Stages Obstruction of Severity and of Chronic Dyspnea, Obstructive and Exercise Pulmonary Capacity Disease Index (Panel as Defined A) and by the the Three Stages of Severity American of Chronic Thoracic Obstructive Society Pulmonary (Panel B) Disease as Defined by the American Thoracic Society (Panel B) Celli, B. et al. N Engl J Med 2004;350:1005-1012

An Example of Updated Office Documentation for COPD 1) COPD FEV1 = 40% predicted, GOLD Spirometry Class 3, CAT Score = 8, Type C, BODE 5 (0+2+2+1).

COPD Treatment

Number of Drugs FDA Approved for COPD by Year Cumulative # of FDA Drugs 25 20 15 10 5 Atrovent Combivent Advair Foradil,, Duoneb Spiriva Brovana Symbicort 0 1985 1990 1995 2000 2005 2010 2015 2020

Current FDA Approved COPD Combination Agents Short-acting anticholinergics + short acting beta agonists (SABA/SAMA) Ipratropium bromide + albuterol (Combivent, Duoneb) Long-acting beta agonists + Long-acting anti-muscarinics (LABA/LAMA) Umeclidinium + Villaterol (Anoro Elipta) Indacaterol + Glycopyrrolate (Utibron Neohaler) Olodaterol + Tiotropium Bromide (Stiolto Respimat ) Formoterol + Glycopyrrolate (Bevespi Aerosphere ) Long-acting beta agonists + Long acting Inhaled corticosteroids (LABA/ICS) Salmeterol + Fluticasone (Advair ) Formoterol + Budesonide (Symbicort ) Fluticasone furoate + vilanterol (Breo Ellipta ) Long-acting beta agonists + Long-acting anti-muscarinics + Long-acting inhaled corticosteroids (LABA/LAMA/ICS) Vilanterol + Umeclidinium + Fluticasone furoate (Trelegy Elipta )

Roflumilast (Daliresp) Phosphodiesterase E4 inhibitor Approval: 2011 Indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Dose 500 ug once daily

Q: Does the recent proliferation of new therapeutic agents for really change our treatment of COPD? A: Probably Q: Should I think about COPD Patients Differently? A: Almost Certainly

Summary 2017 GOLD Pharmacologic Therapy C D A Continue, stop or try alternative class of bronchodilator B Evaluate Effect A bronchodilator

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Non-pharmacologic Patient Group Essential Recommended Depending on local guidelines A Smoking cessation (can include pharmacologic treatment) Physical activity Flu vaccination Pneumococcal vaccination B, C, D Smoking cessation (can include pharmacologic treatment) Pulmonary rehabilitation Physical activity Flu vaccination Pneumococcal vaccination 2014 Global Initiative for Chronic Obstructive Lung Disease

2017 GOLD Group A Pharmacologic Therapy Continue, stop or try alternative class of bronchodilator Evaluate Effect A bronchodilator

Short Acting Bronchodilators DRUG TRADE NAME Mechanism of Action DOSING INTERVAL MISC Albuterol Proventil Proair Short Acting Beta 2 Agonist (SABA) Q 4-6 hours Also available as nebulized agent Pirbuterol Maxair Short Acting Beta 2 Agonist (SABA) Q 4-6 hours Ipratropium Bromide Atrovent Short Acting Antimuscarinic (SAMA) Q 4-6 hours Also available as nebulized agent Albuterol + Ipratropium Bromide Combivent SABA + SAMA Q 6 hours Also available as nebulized agent

Group B COPD Patients Patients have more significant symptoms but still a low risk of exacerbations Long-acting bronchodilators are recommended as first choice Choice is dependent on individual patient s perception of symptom relief In patients with severe breathlessness, a combination of long-acting bronchodilators is recommended as second choice Alternative choices include short-acting bronchodilators and theophylline B Long-acting anticholinergic or Long-acting beta 2 -agonist Long-acting anticholinergic and long-acting beta 2 -agonist Short-acting beta 2 -agonist and/or Short-acting anticholinergic Theophylline From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014. Available from: http://www.goldcopd.org. 2014 Global Initiative for Chronic Obstructive Lung Disease, all rights reserved.

2017 GOLD Group B Pharmacologic Therapy LAMA + LABA Persistent Symptoms A long-acting bronchodilator (LAMA or LABA)

Long Acting Antimuscarinics (LAMA)

Long Acting Anti-muscarinics (LAMA) DRUG TRADE NAME INDICATION DOSING INTERVAL MISC Tiotropium Bromide Spiriva Bronchodilation qd Decreased exacerbations Umeclidinium Incruse Ellipta Bronchodilation qd Decreased exacerbations Aclidinium Tudorza Pressair Bronchodilation BID Decreased exacerbations Glycopyrrolate Seebri Neohaler Broncho- Dilation BID Maintained bronchodilation

Long Acting Beta- Agonist (LABA)

Long Acting Beta- Agonist (LABA) DRUG TRADE NAME INDICATION Formoterol Foradil Performist Bronchodilation DOSING INTERVAL BID MISC Decreased exacerbations, nebulized Olodaterol Incruse Ellipta Bronchodilation qd Decreased exacerbations Indacaterol Arcapta Bronchodilation qd Salmeterol Serevent Bronchodilation BID Aformoterol Brovana Bronchodilation BID Neubulized only Villaterol qd Only in combination

Combination LABA/LAMA

Combination LABA/LAMA DRUG TRADE NAME INDICATION DOSING INTERVAL MISC Indacaterol + Glycopyrronium Olodaterol + Tiotropium Bromide Formoterol + Glycopyrrolate Villaterol + Umeclidinium Ultibro Breezehaler Stiolto Respimat Bevespi Aerosphere Anoro Ellipta Maintenance qd Bronchodilation Maintenance qd Bronchodilation Maintenance BID Bronchodilation Maintenance qd Bronchodilation

From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014. Available from: http://www.goldcopd.org. 2014 Global Initiative for Chronic Obstructive Lung Disease, all rights reserved. Group C COPD Patients Long-acting anticholinergic and long-acting beta 2 - agonist C Inhaled corticosteroid + long-acting beta 2 - agonist or Long-acting anticholinergic or Long-acting anticholinergic and phosphodiesterase 4 inhibitor or Long-acting beta2- agonist and phosphodiesterase inhibitor Short-acting beta 2 - agonist and/or Short-acting anticholinergic Theophylline

2017 GOLD Group C Pharmacologic Therapy LAMA + LABA LABA + ICS Persistent Symptoms LAMA

Combination LABA/ICS

Long Acting Combination LABA + Inhaled Corticosteroids (ICS) DRUG TRADE NAME INDICATION Fluticasone Propionate + Salmeterol Budesonide + Formoterol Fluticasone furoate + vilanterol Advair Symbicort Breo Ellipta Maintenance + Decrease Exacerbations Maintenance + Decrease Exacerbations Maintenance + Decrease Exacerbations DOSING INTERVAL 1 puff BID 2 puffs BID 1 puff qd

Long Acting Combination LABA + LAMA + Inhaled Corticosteroids (ICS) DRUG TRADE NAME INDICATION Fluticasone Propionate + Salmeterol Budesonide + Formoterol Fluticasone furoate + vilanterol Fluticasone furoate + vilanterol + Umclidinium Advair Symbicort Breo Ellipta Trelegy Ellipta Maintenance + Decrease Exacerbations Maintenance + Decrease Exacerbations Maintenance + Decrease Exacerbations Reducing exacerbations + improving lung function + health related quality of life DOSING INTERVAL 1 puff BID 2 puffs BID 1 puff qd 1 puff qd

Inhaled Steroids in COPD Pros Exacerbation reduction when added to LABA in placebocontrolled trials Improvement in FEV 1 in combination with beta-agonists Burge PS, et al. BMJ. 2000;320(7245):1297-1303. Calverley PM, et al. NEJM. 2007;356:775-789. Festic E, et al. AJRCCM. 2015;191:141-148. Kaplan AG. Int J COPD. 2015;10:2535-2548. Suissa S, et al. EurResp J. 2015;46:1232-1235. Cons Clinical trial evidence No reduction in COPD progression No mortality reduction Side effect profile Risk of pneumonia Risk of osteoporosis, adrenal suppression Oral Thrush

Increased risk of pneumonia with ICS use in patients with COPD: metaanalysis Significantly increased risk of serious pneumonia for ICS vs placebo: risk ratio 1.51 (95%CI 1.08 2.10) 285 events/3,881 patients vs 180 events/3,633 patients ICS + LABA vs LABA: risk ratio 1.72 (95%CI 1.28 2.30) 356 events/4,754 patients vs 217 events/4,728 patients Total: ICS vs no ICS: risk ratio 1.60 (95%CI 1.33 1.92) 641 events/8,635 patients vs 397 events/8,361 patients OR 1.56, 95% CI 1.30 to 1.86, 6235 participants* CI, confidence interval; COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting β 2 -agonist. Singh S, et al. Arch Intern Med 2009;169:219 29 Yang IA, Clarke MS, Sim EH, Fong KM. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012; 7(7): CD002991.

Inhaled corticosteroids do not improve symptoms of breathlessness Mean breathlessness symptom score after 52 weeks 2 1 0 Fluticasone propionate p=ns Placebo ns = not significant Calverley PMA et al. Lancet 2003;361:449 56

Group D COPD Patients D Inhaled corticosteroid + long-acting beta 2 -agonist and/or Long-acting anticholinergic Inhaled corticosteroid plus long-acting anticholinergic and longacting beta 2 -agonist or Inhaled corticosteroid plus long-acting beta 2 agonist and phosphodiesterase 4 inhibitor or Long-acting beta 2 agonist and long-acting anticholinergic or Long-acting anticholinergic and phosphodiesterase 4 inhibitor Carbocysteine Short-acting beta 2 - agonist and/or Short-acting anticholinergic Theophylline

2017 GOLD Group D Pharmacologic Therapy Consider roflumilast if FEV 1 < 50% and patient has chronic bronchitis Consider macrolide (in former smokers) Further exacerbations Persistent symptoms and/or further exacerbations LAMA + LABA +ICS LAMA LAMA + LABA LABA + ICS

Roflumilast (Daliresp) Phosphodiesterase E4 inhibitor Approval: 2011 Indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Dose 500 ug once daily

Recommendations for Use of Roflumilast in Primary Care Clear identification of patients eligible for roflumilast Phenotyping of patients in primary care lung function measurement (FEV1<50%) accurate health status classification At least 1 exacerbation last year Smoking > 20 pk/years recording of chronic cough and regular sputum production Price, D et al. Prim Care Respir J. 2011 Mar;20(1):45.

Additional Concerns with Roflumilast Roflumilast and suicidal thoughts or depression 20% of patients in trial had 5-10% weight loss GI Side effects

A Word About Co-morbidities Cardiovascular disease Systolic or Diastolic HF 20%-70%* PVD 8.8%** Osteoporosis Lung Cancer (Screening) Anxiety and Depression Metabolic Syndrome GERD *Bhatt SP, Dransfield MT. Transl Res 2013; 162(4): 237-51. **Houben-Wilke S, Jorres RA, Bals R, et al. Am J Respir Crit Care Med 2016; EPub 17 Aug 2016

Multifactorial Approach to the COPD Patient Kevin Gruffydd-Jones Primary Care Respiratory Journal (2012) 21, 437 441

An Example of Updated Office Documentation for COPD 1) COPD FEV1 = 40% predicted, GOLD Spirometry Class 3, CAT Score = 8, Type C, BODE 5 (0+2+2+1). a) Currently on LABA and LAMA. b) Completed pulmonary rehab (Or needs) c) Not LVRS candidate. (If FEV 1 25-40%) d) Currently with adequate oxygenation at rest, sleep and ambulation. (Or needs testing) e) Assessed cardiac, malignancy risks (Needs )

Miscellaneous Topics in Management

Non-Pharmacologic Treatments for COPD Smoking Cessation Pulmonary Rehabilitation Oxygen Therapy Ventilatory Support Lung Volume Reduction Surgery Lung Transplantation Vaccination From: Global Strategy for Diagnosis, Management and Prevention of COPD. GOLD Slideset 2015

USPSTF Low Dose Lung Cancer Screening Recommendation Annual screening until: a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery Aged 55 to 80 years 30 pack-year smoking history Currently smoke or have quit within the past 15 years.

Exacerbation Care Exacerbation Acute Care Acute steroids < 30 days Acute Pulmonary Rehab <4 weeks Discuss treatment regimen Assess oxygen needs 1-4 Week Follow Up Evaluate ability to cope and perform ADLs Review Treatment Plan Reassess inhaler techniques Reassess Oxygen needs Reassess Comorbidity Sttus 12-16 Week Follow Up All 1-4 Week Perform FEV 1 Chronic Care A,B,C,D Risk Stratification and Treatment Assess CAT, mmrc All 1-4 week assessments

Summary

Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD When assessing risk, choose the highest risk according to GOLD grade or exacerbation history. One or more hospitalizations for COPD exacerbations should be considered high risk.) Patient Characteristic Spirometric Classification Exacerbations per year CAT mmrc A B C Low Risk Less Symptoms Low Risk More Symptoms High Risk Less Symptoms GOLD 1-2 1 < 10 0-1 GOLD 1-2 1 > 10 > 2 GOLD 3-4 > 2 < 10 0-1 D High Risk More Symptoms GOLD 3-4 > 2 > 10 > 2 2014 Global Initiative for Chronic Obstructive Lung Disease

Multifactorial Approach to the COPD Patient Kevin Gruffydd-Jones Primary Care Respiratory Journal (2012) 21, 437 441

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Goals of Therapy Relieve symptoms Improve exercise tolerance Improve health status Prevent disease progression Prevent and treat exacerbations Reduce mortality Reduce symptoms Reduce risk 2015 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Key Points Identification and reduction of exposure to risk factors are important steps in prevention and treatment. Individualized assessment of symptoms, airflow limitation, and future risk of exacerbations should be incorporated into the management strategy. All COPD patients benefit from rehabilitation and maintenance of physical activity. Pharmacologic therapy is used to reduce symptoms, reduce frequency and severity of exacerbations, and improve health status and exercise tolerance. 2015 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Key Points Long-acting formulations of beta 2 -agonists and anticholinergics are preferred over short-acting formulations. Based on efficacy and side effects, inhaled bronchodilators are preferred over oral bronchodilators. Long-term treatment with inhaled corticosteroids added to long-acting bronchodilators is recommended for patients with high risk of exacerbations. 2015 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Key Points Long-term monotherapy with oral or inhaled corticosteroids is not recommended in COPD. The phospodiesterase-4 inhibitor roflumilast may be useful to reduce exacerbations for patients with FEV 1 < 50% of predicted, chronic bronchitis, and frequent exacerbations. 2015 Global Initiative for Chronic Obstructive Lung Disease

Q: Does the recent proliferation of new therapeutic agents for really change our treatment of COPD? A: Quite Possibly Q: Should I think about COPD Patients Differently? A: Almost Certainly

Appendix and Supplementary Slides

Benefits of Pulmonary Rehab In Patients with COPD Improve exercise capacity Enhance quality of life (QOL) Decrease exacerbations within 30 days of discharge Impact on Hospitalization and Mortality* *Inconsistently shown

Mortality Benefits of Pulmonary Rehabilitation (N=246) Endpoint (-) Rehab (+) Rehab Hospitial LOS for Respiratory Related Illness 25% 20% Mortality for Respiratory Related Illness 39% 7% BODE Score 4% (worsened) 19% (improved Cote CG, Celli BR Pulmonary rehabilitation and the BODE index in COPD. Eur Respir J. 2005;26(4):630

Surgical Options for Advanced COPD Lung Volume Reduction Surgery Lung Transplantation

Lung Volume Reduction Surgery Only for Select Emphysema Patients Selection Criteria 45% < FEV1 < 25% TLC >100% RV > 150% Post Rehab Exercise Capacity 6MW > 140m CPET with < 40 watts(men), <25 watts(women)

LVRS Results FEV1 = 1.60 L (37%) FEV1 = 2.23 L (52%)

LVRS Results Pulmonary Testing Pre-LVRS Post-LVRS FEV 1 (L/min 1.60 (37%) 2.23 (52%) FVC (L) 4.29 (76%) 4.70 (84%) TLC (L) 9.21 (113%) 7.73 (94%) RV(L) 4.77 (186%) 2.97 (116%)

Lung Volume Reduction Surgery Exclusions BMI, > 31.1 kg/m 2 (men) or > 32.3 kg/m 2 (women) PCO 2, > 60 mm Hg PO 2, < 45 mm Hg on room air Active Smoking or quit < 4 months Alpha 1 Antitrypsin Disease Non-Apical Distribution of Emphysema

Kaplan Meier Estimates of the Probability of Death as a Function of the Number of Months after Randomization (Upper Lobe Disease with Low Exercise Capacity After Rehabilitation N=290) National Emphysema Treatment Trial Research Group, N Engl J Med 2003;348:2059-2073 National Emphysema Treatment Trial Research Group, N Engl J Med 2003;348:2059-2073

Global Strategy for Diagnosis, Management and Prevention of COPD Asthma COPD Overlap Syndrome Characterized by some element of fixed obstruction and multiple features of both COPD and asthma. Suggested to be relatively common Q:Why should we care? May represent a distinct clinical entity / prognosis. May open the door to earlier and more prominent use of inhaled steroids in ACOS or modulation of allergic type pathways. May need to be eliminated from therapeutic trials in COPD. Especially those impacting inflammatory pathways. Recognition may shed light on frequent exacerbators and triggers.

Risk Factors for Asthma and COPD and the Influence of Environment and Aging. Postma DS, Rabe KF. N Engl J Med 2015;373:1241-1249

Features that (when present) favor asthma or COPD Feature Favors asthma Favors COPD Age of onset qbefore age 20 years qafter age 40 years Pattern of respiratory symptoms Lung function Past history or family history Time course GINA 2014, Box 5-2B (3/3) q Symptoms vary overminutes, hours or days q Worse during night or early morning qtriggered by exercise, emotions including laughter, dust, or exposure to allergens qno worseningof symptoms over time. Symptoms vary seasonally, or from year to year qmay improve spontaneously, or respond immediately to BD or to ICS over weeks q Symptoms persist despite treatment qgood and bad days, but always daily symptoms and exertional dyspnea qchronic cough and sputum preceded onset of dyspnea, unrelated to triggers Syndromic diagnosis of airways disease The shaded columns list features that, when present, best distinguish between qrecord of variable airflow limitation asthma and COPD. (spirometry, peak flow) For a patient, qnormal count between the number symptoms of check boxes in each column. If 3 or qmore Previous boxes doctor are diagnosis checked of for asthma either asthma or COPD, that diagnosis is suggested. qfamily history of asthma, and other allergic If there conditions are similar (allergic numbers rhinitis of or checked eczema) boxes in each column, the diagnosis of ACOS should be considered. qrecord of persistent airflow limitation (post-bd FEV 1 /FVC <0.7) q Abnormal between symptoms qprevious doctor diagnosis of COPD, chronic bronchitis or emphysema qheavy exposure to a risk factor: tobacco smoke, biomass fuels qsymptomsslowly worsening over time (progressive course over years) qrapid-acting bronchodilator treatment provides only limited relief Chest X-ray q Normal q Severe hyperinflation Global Initiative for Asthma

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy OTHER POSSIBLE TREATMENTS C D GOLD 4 GOLD 3 GOLD 2 GOLD 1 A SABA and/or SAMA Theophylline Theophylline Carbocysteine N-acetylcysteine SABA and/or SAMA Theophylline B SABA and/or SAMA Theophylline 2 or more or > 1 leading to hospital admission 1 (not leading to hospital admission) 0 Exacerbations per year CAT < 10 mmrc 0-1 CAT > 10 mmrc > 2 2015 Global Initiative for Chronic Obstructive Lung Disease