PFT Refresher and Modern Inhaler Strategy for COPD

1. PFT Refresher and Modern Inhaler Strategy for COPD Todd C. Hoopman, MD North Idaho Lung, Asthma and Critical Care Coeur d’Alene, ID

2. Pulmonary Function Testing • Indications: • Evaluate: Cough, wheeze, breathlessness, crackles • Monitor: COPD, asthma, pulmonary vascular disease • Preoperative evaluation: lung resection, abdominal surgery, cardiovascular surgery • Surveillance for respiratory complications: CTD or neuromuscular disease • Post-lung transplantation • Contraindications: • AMI < 30 days • Unstable angina • Recent eye surgery • Current pneumothorax • Current tracheostomy • Recent thoraco-abdominal surgery

3. Pulmonary Function Testing • Components: • Spirometry (pre and post-bronchodilator) • Lung volumes evaluation • Diffusion capacity • Other tests: • Maximum Voluntary Ventilation • Mean Inspiratory Pressure • Mean Expiratory Pressure

4. Spirometry • Measure volume against time and flow against volume • Most frequently used measure of lung function • FEV1, FVC, FEV1/FVC ratio, FEF25-75%, Bronchodilator response

5. Spirometry - Obstruction • FEV1/FVC ratio < 70% (absolute not predicted)

6. Spirometry - Obstruction • Pathophysiology: • Alveoli and support structures are destroyed (reduced tethering/loss of recoil) • Bronchial passageways are blocked by secretions and inflammation • Airway compression by adjacent over distended lung units 1 www.NEJM.org

7. Spirometry - Restriction • FEV1/FVC ratio > 70% (absolute not predicted) • Reduced FVC (<80% predicted) • Lung volumes needed to confirm (TLC < 80% predicted) • Concurrent reduction of FVC in severe obstruction

8. “Other Obstructions” of the Flow-Volume Loop

9. “Other Obstructions” of the Flow-Volume Loop Tracheomalacia Polychrondritis Tumors of trachea Vocal Cord Paralysis Glottic strictures Tumors/Goiter

10. Flow-Volume Loops

11. Bronchodilator Response • Measure basic spirometry and then administer a bronchodilator • 20% improvement AND200 mL improvement in either FEV1 OR FVC • Evaluate pre-bronchodilator effort carefully • 6 second exhalation

12. Lung Volumes • Measure total lung capacity at maximal inspiration • Measure amount of air left in the lungs after maximal expiration (Residual Volume) • *Body plethysmography • Nitrogen washout • Helium washout • Confirm the degree of restriction seen with spirometry • Determine if a reduced Vital Capacity is due to air trapping or intrinsic lung disease

13. Lung Volumes • Plethysmography can be difficult for some patients: • Morbid obesity • Claustrophobia • Hard of hearing • Mixed disorder • TLC < 80% with with FEV1/FVC < 70% • COPD + IPF • Asthma + Obesity

14. Diffusion Capacity of Lung for Carbon Monoxide • Measure of gas exchange • Effort dependent • Exhale to RV and then inhale to vital capacity using air mixed with CO & Helium • Hold breath for 10 seconds and then exhale QUICKLY • Measure concentrations of CO and Helium as a function of the exhaled volume • Dependent upon the surface area of the alveolar membrane • <80% is considered a reduced value

15. COPD Facts1 • Currently the 4th leading cause of death in the world1 • 2012: 3 million deaths • Projected to be the 3rd leading cause by 2020 • Continued exposure to COPD risk factors and aging of the population • Risk Factors • Exposure to noxious particles or gases • #1: Tobacco • Others: pipe, cigar, water pipe, marijuana • Outdoor, occupational and indoor air pollution (burning of biomass fuels) • Non-smokers: complex interplay of long-term exposures combined with host factors 1 GOLD 2018 Edition

16. COPD Facts1 • Currently the 4th leading cause of death in the world1 • 2012: 3 million deaths • Projected to be the 3rd leading cause by 2020 • Continued exposure to COPD risk factors and aging of the population • Risk Factors • Exposure to noxious particles or gases • #1: Tobacco • Others: pipe, cigar, water pipe, marijuana • Outdoor, occupational and indoor air pollution (burning of biomass fuels) • Non-smokers: complex interplay of long-term exposures combined with host factors 1 GOLD 2018 Edition

17. COPD Facts1 • COPD should be considered in any patient who has dyspnea, chronic cough or sputum production and/or history of exposure to risk factors for the disease • Spirometry is required to make the diagnosis • Post-bronchodilator FEV1/FVC < 0.70 confirms the presence of airflow limitation • Key Indicators: • Progressive dyspnea.: Worse with exercise & Persistent • Chronic cough: May be intermittent and may be non-productive • Chronic sputum production • History of risk factors: tobacco, biomass fuel burning, occupational • Family Hx of COPD and/or childhood factors: low birthweight, childhood resp infxn 1 GOLD 2018 Edition

18. COPD Versus Asthma

19. Pharmacotherapy for COPD • Bronchodilators: increase FEV1 and/or change in spirometry • Beta2 Agonists: Relax airway smooth muscle; antagonize bronchoconstriction • Antimuscarinics: Block the bronchoconstrictor effects of acetylcholine on airway smooth muscle • Methylxanthines: toxicity is dose-related; most benefit occurs at near-toxic doses • Anti-inflammatory agents • Inhaled and oral corticosteroids • Phosphodiesterase-4 inhibitors • Antibiotics • Azithromycin 3x per week (increased bacterial resistance and reduced hearing)

20. Technique is everything • Wide variety of devices available: • Nebulizers • Pressurized metered dose inhalers (pMDI) • Dry powder inhalers (DPI) • Soft mist inhalers (SMI) • Significant patient error with device usage • Meta-analysis: 100% of patients demonstrate at least one error1 • 92% of patients experience critical errors (i.e. impacts effectiveness of the drug) • Right Device for the Right Patient: • Age • Ethnicity • Dexterity • Inspiratory capacity 1 Prim Care Resp Med: 27; 22. 2017

21. Technique is everything

22. Technique is everything 1 Prim Care Resp Med: 27; 22. 2017

23. ABCD Assessment Tool of 2011 • Incorporated patient-reported outcomes and highlighted the importance of exacerbation prevention: • No better than spirometry for mortality prediction • Confusion and concerns by this system • Significant patient error with device usage • Meta-analysis: 100% of patients demonstrate at least one error1 • 92% of patients experience critical errors (i.e. impacts effectiveness of the drug) • Right Device for the Right Patient: • Age • Ethnicity • Dexterity • Inspiratory capacity

26. ABCD Assessment Tool of 2011 • Incorporated patient-reported outcomes and highlighted the importance of exacerbation prevention: • No better than spirometry for mortality prediction • Confusion and concerns by this system • Significant patient error with device usage • Meta-analysis: 100% of patients demonstrate at least one error1 • 92% of patients experience critical errors (i.e. impacts effectiveness of the drug) • Right Device for the Right Patient: • Age • Ethnicity • Dexterity • Inspiratory capacity

27. Severity of COPD (based upon post-bronchodilator FEV1) • Patient with an FEV1/FVC < 0.70: 1 GOLD Guidelines 2018.

28. Long-Acting Muscarinic (LAMA) Therapy for COPD (MOA: Block Acetylcholine interaction with airway smooth muscle to prevent contractions) • Mid 2000s: UPLIFT Trial • 4 year trial with Tiotroprium (Spiriva) vs Placebo • Increased QOL • Reduced exacerbation rate by 14% and reduced time to first exacerbation • No demonstration of reduced rate of decline in FEV1 • Mostly GOLD 2 and 3 (90% of enrolled participants) • 2/3 on inhaled LABA or inhaled steroid or both • Led to GOLD recommendation for LAMA Therapy for GOLD 2 patients as first-line therapy • 3 additional LAMAs: • Aclidimium (Tudorza) • Umeclidinium (Incruse) • Glycopyrrolate (Lonhala)

29. LAMA and LABA combinations1 • 2016: • GOLD Report: LAMA + LABA for Group B (high sx/low risk) if not better with 1 agent • 2017: • GOLD Report: LAMA + LABA for Group B (high sx/low risk) w/ severe breathlessness • NEJM 2016: LAMA + LABA superior to ICS + LABA at preventing COPD exacerbations for patients with one or more COPD exacerbations • GOLD Recommendation for Group D (high symptoms/high risk) • LAMA + LABA > LABA + ICS • Bevespi (Glycopyrrolate/Formoterol) • Anoro (Umeclidinium/Vilanterol) • Stiolto (Olodaterol/Tiotropium) • Utibron (Indacaterol/Glycopyrrolate) 1 NEJM. 2016; 374 (23): 2222-2234.

31. Triple Therapy Combination for COPD • 2018:Trelegy (Fluticasone + Umeclidinium + Vilanterol) • Evidence: • IMPACT Study: NEJM May 20181 • Compared ICS/LAMA/LABA vs. ICS/LABA or LAMA/LABA) • Trelegy v. Breo v. Anoro • Primary endpoint: annual rate of moderate or severe COPD exacerbations • Results: • 34% reduction in COPD hospitalizations vs. Anoro • 13% reduction in COPD hospitalizations vs. Breo (non-significant) • ICS (Trelegy and Breo) had a lower on-treatment risk of mortality vs. Anoro • Higher rate of pneumonia in the ICS groups • GOLD Recommendation: Triple therapy for Group D patients who continue to experience exacerbations despite dual therapy. 1 NEJM. 2018; 378 : 1671-1680.

32. GOLD Recommendations