COPD: One Patient’s Journey Ralph J. Panos, MD Cincinnati VAMC Pulmonary, Critical Care, and Sleep Division University of Cincinnati College of Medicine

She smoked about half a pack for less than 10 years during her 20’s Cathy’s COPD Journey: Chapter 1 67yoF for her initial evaluation. Worked in a retail store for 40 years. She has HTN treated w/ diuretic and has “pre-DM”. Her weight has been inc’ing since retirement, she is relatively inactive . She has noted mild breathlessness on climbing up a flight of steps. PE: BP 154/92; P 86; RR 14 weight 182 pounds; height 63 inches She has Grade 1 hypertensive retinopathy on funduscopic examination. Cardiac RRR, 2/6 systolic flow murmur. The chest is resonant with symmetric air movement and no wheezes. Abdomen NML. There is no clubbing, cyanosis, or edema. Neuro NML. Under what circumstances would you order spirometry for this patient? FamHx lung disease She smoked about half a pack for less than 10 years during her 20’s She is unable to walk with her peers due to breathlessness A cardiac evaluation reveals no evidence of CAD Chest imaging shows radiographic evidence of emphysema C - She is unable to walk with her peers due to breathlessness

1. When to Perform Spirometry 2. COPD Respiratory Symptoms Answer: C. She is unable to walk with her peers due to breathlessness Objectives: 1. When to Perform Spirometry 2. COPD Respiratory Symptoms 3. Gender differences in COPD susceptibility and presentation

Indications for Spirometry Role of screening spirometry is controversial and is not recommended for asymptomatic individuals Indications for Spirometry 1. Significant risk factors > 20 pack years of smoking Exposure to chemicals, dusts, fumes 2. Respiratory Symptoms or Recurrent Chest Infections Shortness of Breath Cough Phlegm Production Wheezing and Chest Tightness

Patients under-report and providers under-detect respiratory symptoms Screening Questionnaires for the recognition of respiratory symptoms Veterans Airflow Obstruction Screening Questionnaire (VAFOSQ) COPD Population Screener 11-Q COPD Screening Questionnaire Lung Function Questionnaire Personal Level Screener for COPD Screening Questionnaire Variables: Age Dyspnea Cough Smoking Activity limitation Other: Veterans Airflow Obstruction Screening Questionnaire Personal Level Screener 11-Q COPD Screening Questionnaire COPD Population Screener Lung Function Questionnaire LLN Specificity 44% 67% 9% 45% 13% Sensitivity 72% 53% 97% 73% 95% LR+ 1.27 1.61 1.07 1.34 1.09 LR- 0.65 0.70 0.32 0.59 0.40 PPV 32% 37% 28% 33% NPV 81% 80% 89% 82% 87% FR 43% 69% 46% 14% 66% 50% 94% 1.17 1.03 1.29 1.11 0.78 0.73 0.67 0.33 51% 42% 47% 68% LLN n ROC AUC Confidence Limits   VAFOSQ 376 0.604 (0.542,0.666) PLS 336 0.600 (0.540,0.660) 11-Q 255 0.629 (0.553,0.705) COPD-PS 362 0.621 (0.556,0.686) LFQ 0.661 (0.597,0.725) FR 0.575 (0.516,0.633) 0.594 (0.541,0.648) 0.612 (0.542,0.683) 0.623 (0.565,0.681) 0.655 (0.599,0.712)

Gender Differences in COPD Susceptibility and Presentation In contrast to previous studies that reported M>F COPD prevalence and mortality, more recent data from developed countries show M=F 2000 more women than men died from COPD 2011 women twice as likely to be diagnosed with chronic bronchitis: 56.7 vs. 29.6 per 1000 2011 women more likely to be diagnosed with emphysema: 21.4 vs 19.0 per 1000 M=F in recent studies

Airway Cross Sectional Area (mm2) Gender Differences in COPD Susceptibility and Presentation Women may be more susceptible to the effects of tobacco smoke than men Develop greater airflow limitation at younger ages and with less tobacco smoke exposure Experience a faster rate of lung function decline than men Higher risk for hospitalization for COPD exacerbations Dysanapsis: airway size disproportionate to lung size Elevated susceptibility to inflammation and mucus hypersecretion Different effects of hormones Differences in pulmonary particle deposition Greater and longer tobacco smoke inhalation by women compared to men Airway Cross Sectional Area (mm2) Matched For Lung Size Airway Men Women % Difference Trachea 296 238 19.5% RMB 193 147 23.8% LMB 124 102 18.1%

Presence of persistent respiratory symptoms Cathy’s COPD Journey: Chapter 2 Cathy says that she may have underestimated her smoking hx and thinks that she smoked 30 years intermittently up to 1.5 packs per day and quit 5 years ago but still smokes an occasional cigarette. She does have a minimal morning cough but does not produce any phlegm. She is breathless upon walking >4 blocks on the level and going up any incline. Spirometry is obtained and the results are: FEV1/FVC <70% is obstructive D – All three You consider the diagnosis of COPD based upon these criteria: Presence of persistent respiratory symptoms Exposure to noxious particles or gases. Airflow limitation quantified by spirometry Presence of persistent respiratory symptoms, exposure to noxious particles or gases, and airflow limitation.

1. GOLD Definition of COPD 2. Review Interpretation of Spirometry Answer: D. Presence of persistent respiratory symptoms, exposure to noxious particles or gases, and airflow limitation Objectives: 1. GOLD Definition of COPD 2. Review Interpretation of Spirometry 3. Definition and Classification of Airflow Obstruction

COPD: sx’s, exposure, spirometry

Definition of COPD FEV1/FVC Age 0.7 LLN Underdiagnosed Overdiagnosed 2017 GOLD COPD definition: COPD is a common, preventable and treatable dz characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abNMLties usually caused by significant exposure to noxious particles or gases. Spirometry Definition of airflow limitation FEV1/FVC ratio Different thresholds and their advantages and disadvantages FEV1/FVC < 0.7 or LLN (lower limit of normal) FEV1/FVC Age 0.7 LLN Underdiagnosed Overdiagnosed

Albuterol metered dose inhaler PRN Cathy’s COPD Journey: Chapter 3 She has never required healthcare for breathing problems. Her breathlessness and cough are unchanged and her PE reveals no new findings. You review the results of the spirometry with them. What pharmacologic treatment would you initiate at this time? Albuterol metered dose inhaler PRN Albuterol PRN and long acting antimuscarinic agent (LAMA) Albuterol PRN and a LABA/ICS combo Albuterol PRN and an ICS B - Albuterol PRN and long acting antimuscarinic agent (LAMA)

1. Present 2016 GOLD staging of COPD: Spirometry Symptoms and risk Answer: B. Albuterol prn and long acting antimuscarinic agent Objectives: 1. Present 2016 GOLD staging of COPD: Spirometry Symptoms and risk 2. Discuss 2016 GOLD COPD Management Guidelines Pharmacologic Treatments

COPD: Management Objectives Prevent dz progression Relieve sx’s Improve exercise tolerance Improve health status Prevent and treat exacerbations and complications Reduce mortality Minimize side effects from tx

COPD: Management Objectives Reduce Risk Factors Reduce total personal exposure to prevent progression Tobacco smoke Occupational dusts and chemicals Indoor and outdoor air pollutants Smoking cessation Single most effective and cost-effective intervention to reduce the risk of developing COPD and slow its progression.

GOLD 2016 COPD Management Guidelines Symptoms Exacerbation Risk (Exacerbations in past year) 0-1 mMRC >2 <10 CAT >10 0-1 Outpatient > 2 Outpatient > 1 Hospitalization Less Symptoms High Risk C Lower Risk A More Symptoms B D GOLD 2016 COPD Management Guidelines High risk of exacerbation is class C&D More symptoms is class B or D

GOLD 2016 COPD Management Guidelines Symptoms Exacerbation Risk (Exacerbations in past year) 0-1 mMRC >2 <10 CAT >10 0-1 Outpatient > 2 Outpatient > 1 Hospitalization LAMA or LAMA+ICS or LAMA+LABA C Bronchodilator A Long Acting LAMA or LABA or LABA+LAMA B LAMA+LABA+ICS ? Roflumilast ? Macrolide D GOLD 2016 COPD Management Guidelines

COPD is treatable but no interventions prolong life. Cathy’s COPD Journey: Chapter 4 You discuss COPD and its px & tx with the patient and her daughter. In addition to low dose screening chest CT, you suggest influenza and pneumococcal vaccinations and pulmonary rehabilitation. The patient and her daughter are very concerned about this new diagnosis and what her future will be. During your discussion with Cathy and her daughter, you explain: COPD is treatable but no interventions prolong life. She should seek lung transplantation evaluation. Spirometry can be used to predict the course and duration of illness. Now is a good time to begin advanced care planning discussions. Start supplemental O2 because it is the only tx for COPD that prolongs life. D - Now is a good time to begin advanced care planning discussions.

1. COPD Disease Trajectory is Poorly Predictable Answer: D. Now is a good time to begin advanced care planning discussions. Objectives: 1. COPD Disease Trajectory is Poorly Predictable 2. Discuss COPD Management Goals 2. Advanced Care Planning should begin at COPD Diagnosis

COPD Disease Trajectory Diagnosis Intermittent Acute Management Death Health Symptomatic Pre-Diagnosis Chronic Disease Management Advanced Care Planning Palliative Care Hospice End of Life Care Bereavement COPD Disease Trajectory

Evidence-Based Interventions that Reduce Mortality in COPD Smoking Cessation Oxygen for Patients with Resting Hypoxemia Vaccination Noninvasive Ventilation for Exacerbations Lung Volume Reduction Surgery Pulmonary Rehabilitation/Exercise Tiotropium

Azithromycin and prednisone Clarithromycin and fluticasone Cathy’s COPD Journey: Chapter 5 She completes pulmonary rehabilitation, completely stops smoking, and establishes a regular exercise program. In pulmonary rehabilitation, she learns how to use her inhalers correctly and she is religiously adherent with them. Her low dose chest CT revealed no abnormalities and she receives a yearly influenza vaccination. She develops a severe cough productive of yellow to greenish phlegm, fevers, increased breathlessness that is not relieved with her albuterol and she is having difficulty sleeping at night due to dyspnea. She presents to the ED. Her medications are HCTZ, albuterol MDI, and tiotroprium. PE: temperature is 102.4, BP 176/94, P 110, RR 28 SpO2 88% RA. Tachycardia; breath sounds are reduced and there are diffuse inspiratory and expiratory wheezes. After an albuterol nebulizer treatment and breathing 2 LPM supplemental oxygen by nasal cannula, her SpO2 is 92%; she remains tachypneic and exam reveals persistent diffuse wheezes. In addition to continuing her SABA and supplemental oxygen, you initiate treatment with: Azithromycin and prednisone Clarithromycin and fluticasone Intravenous corticosteroids and cetriaxone Doxycycline and salmeterol/fluticasone Erythromycin and roflumilast A - Azithromycin and prednisone Inc’d exacerbation risk, now class C&D. But this is an exacerbation.

1. Recognition of COPD Exacerbation Answer: A. Azithromycin and prednisone Objectives: 1. Recognition of COPD Exacerbation 2. Assessment and Treatment of COPD Exacerbations

COPD Exacerbations: acute worsening of respiratory symptoms that necessitates additional therapy COPD Exacerbation Classification: Mild: short acting bronchodilators: SABA and or SAMA Moderate: short acting bronchodilators and antibiotics and/or oral corticosteroids Severe: emergency department visit or hospitalization Worsens Lung Fx + Sx’s Reduces Quality of Life Inc’s Cost COPD Exacerbation Augments Mortality Quickens Lung Fx Decline

Supplemental oxygen 2 LPM continuously. Cathy’s COPD Journey: Chapter 6 Three months after her hospitalization for her COPD exacerbation, presents for f/u. She has returned to regular exercise and only has her usual early morning cough and no phlegm production. She is short of breath walking up a slight incline or when hurrying. She continues to use tiotroprium daily and albuterol 2-4 puffs daily. PE: temperature 98.6, BP 154/82, P 82, RR 12 SpO2 91% while breathing room air. Heart and lung examinations RRR, 2/6 flow murmur, hyperresonance, prolonged expiration with diminished breath sounds and no wheezing. Your nursing assistant walks the patient in the hallway for 5 minutes and her SpO2 drops from 91% to a nadir of 86% and returns to 92% upon resting. Based upon recent events, these findings, and to improve her quality of life and reduce respiratory complications, you order: Supplemental oxygen 2 LPM continuously. Supplemental oxygen 2 LPM with exertion. Supplemental oxygen 2 LPM with exertion and at night. A long-acting beta agonist. Theophylline SR 300 mg BID. D - A long-acting beta agonist.

1. Review the use of supplemental oxygen in COPD MRC/NOTT LOTT Answer: D. A long acting beta agonist Objectives: 1. Review the use of supplemental oxygen in COPD MRC/NOTT LOTT

Oxygen Therapy in Patients with COPD and Resting Severe Hypoxemia NOTT 1980 203 of 1,043 screened patients in 6 centers; PaO2 < 59 Not blinded, treated with NOT or COT at 1-4 lpm 12 months: mortality tx:control 0.53 [0.25-1.11] 24 months: mortality tx: control 0.45 [0.25-0.81] MRC 1981 87 patients randomized to O2 or no O2; not blinded; PaO2 40-60 Treated with oxygen at a minimum flow rate of 2 lpm First 500 days: men no difference in mortality; women improved mortality 5 years: 0.42 [0.18-0.98] MRC Study: Control risk of death: 0.67 O2 TX RR: 0.45 Absolute risk reduction: 0.22 NNT: 5 patients with severe hypoxemic COPD with supplemental oxygen saved one life over the 5 year study period.

738 patients with: moderate resting hypoxemia (SpO2 89-93%) or exercise desaturation (SpO2 >80% for 5 min and <90% for > 10 sec) during 6MW Treated with supplement oxygen or no oxygen No change in Mortality First hospitalization Quality of life Lung function 6MW Distance

Supplemental Oxygen Reduces mortality in individuals with COPD and resting hypoxemia: PaO2 < 55 torr or 88% PaO2 55-59 torr with edema No effect on mortality, exacerbations, or quality of life for those with mild resting hypoxemia or exertional desaturation

Cathy’s COPD Journey: Epilogue Cathy’s respiratory symptoms inc’d to breathlessness with daily activities and her respiratory medications were increased to LAMA+LABA+ICS with PRN SABA. Despite maximal pharmacologic tx, her resting SpO2 declined to 86-87% at age 74 and she started continuous supplemental oxygen. She continues with maintenance pulmonary rehabilitation. At age 77, she attended her grandson’s college graduation. COPD is a preventable, incurable chronic disorder that is eminently treatable- Best practice management can and does improve quality of life, reduce complications and exacerbations, and prolongs life