PFT Refresher and Modern Inhaler Strategy for COPD

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

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

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

Spirometry ▸ Measure volume against time and flow against volume ▸ Most frequently used measure of lung function ▸ FEV 1, FVC, FEV 1/FVC ratio, FEF 25 -75%, Bronchodilator response

Spirometry - Obstruction ▸ FEV 1/FVC ratio < 70% (absolute not predicted) FEV 1 % predicted > 80% 50 – 79% 30 – 49% < 30% Stage Mild Moderate Severe Very Severe

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

Spirometry - Restriction ▸ FEV 1/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 Pulmonary IPF and ILD Asbestosis Sarcoidosis Lung resection Extrapulmonary: Pleural Cavity Effusion Pneumothorax Neuromuscular Diaphragm paralysis Neuromuscular disease (ALS, MD) Chest Wall Obesity Kyphoscoliosis Chest trauma Abdominal mass (pregnancy, ascites)

“Other Obstructions” of the Flow-Volume Loop

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

Flow-Volume Loops

Bronchodilator Response ▸ Measure basic spirometry and then administer a bronchodilator ▸ 20% improvement AND 200 m. L improvement in either FEV 1 OR FVC ▸ Evaluate pre-bronchodilator effort carefully ▸ 6 second exhalation

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

Lung Volumes ▸ Plethysmography can be difficult for some patients: ▸ Morbid obesity ▸ Claustrophobia ▸ Hard of hearing ▸ Mixed disorder ▸ TLC < 80% with FEV 1/FVC < 70% ▸ COPD + IPF ▸ Asthma + Obesity

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 Reduced Pulmonary fibrosis COPD Pulmonary emboli Anemia CHF/Pulm Edema Collagen Vascular Disease (SLE) Increased Obesity (Incr blood volume) Polycythemia Intra-alveolar hemorrhage Left-to-Right intracardiac shunts

COPD Facts 1 ▸ Currently the 4 th leading cause of death in the world 1 ▸ 2012: 3 million deaths ▸ Projected to be the 3 rd 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

COPD Facts 1 ▸ Currently the 4 th leading cause of death in the world 1 ▸ 2012: 3 million deaths ▸ Projected to be the 3 rd 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

COPD Facts 1 ▸ 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 FEV 1/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

COPD Versus Asthma COPD • Onset in mid-life • Symptoms slowly progressive • History of tobacco smoking or exposure to other types of smoke • Non-reversible / Constant Asthma • Onset early in life (often childhood) • Symptoms vary widely from day to day • Symptoms worse at night/early morning • Allergy, rhinitis and/or eczema also present • Family history of asthma • Obesity coexistence • Periods of “normalcy”

Pharmacotherapy for COPD ▸ Bronchodilators: increase FEV 1 and/or change in spirometry ▸ Beta 2 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 3 x per week (increased bacterial resistance and reduced hearing)

Technique is everything ▸ Wide variety of devices available: ▸ ▸ Nebulizers Pressurized metered dose inhalers (p. MDI) Dry powder inhalers (DPI) Soft mist inhalers (SMI) ▸ Significant patient error with device usage ▸ Meta-analysis: 100% of patients demonstrate at least one error 1 ▸ 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

Technique is everything 1. Established and familiar 2. Better for patients with very low inspiratory flows 1. Requires coordination 2. High deposition in mouth/oropharynx DPI 1. Breath-actuated 2. No propellants 1. Requires a minimum inspiratory effort SMI 1. Lower dependency on inspiratory flow 2. High lung deposition with lower mouth/oropharynx deposition 1. Not breath-actuated 2. Only one device currently available 1. Good for any age 2. Can be utilized when acutely ill 3. No specific inhalation technique required 1. Noisy 2. Time-consuming 1. Less dependent on inspiratory effort 2. Easier to coordinate 3. Higher lung deposition than p. MDI alone 4. Reduced mouth/oropharynx deposition 1. Less portable than p. MDI 2. Electrostatic charge 3. Requires regular cleaning p. MDI Nebulizers p. MDI with Spacer

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

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 error 1 ▸ 92% of patients experience critical errors (i. e. impacts effectiveness of the drug) ▸ Right Device for the Right Patient: ▸ ▸ Age Ethnicity Dexterity Inspiratory capacity

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 error 1 ▸ 92% of patients experience critical errors (i. e. impacts effectiveness of the drug) ▸ Right Device for the Right Patient: ▸ ▸ Age Ethnicity Dexterity Inspiratory capacity

Severity of COPD (based upon post-bronchodilator FEV 1) ▸ Patient with an FEV 1/FVC < 0. 70: GOLD 1 Mild FEV 1 > 80% predicted GOLD 2 Moderate GOLD 3 Severe 50% < FEV 1 < 80% predicted 30% < FEV 1 < 50% predicted GOLD 4 Very Severe FEV 1 > 30% predicted 1 GOLD Guidelines 2018.

Long-Acting Muscarinic (LAMA) Therapy for COPD (MOA: Block Acetylcholine interaction with airway smooth muscle to prevent contractions) ▸ Mid 2000 s: 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 FEV 1 ▸ 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: 1. 2. 3. Aclidimium (Tudorza) Umeclidinium (Incruse) Glycopyrrolate (Lonhala)

LAMA and LABA combinations 1 ▸ 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.

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.

GOLD Recommendations