COPD. Stan Kellar, MD. Physiology 11/4/2014. Chief of Clinical Affairs, BH NLR Pulmonary Medicine Sleep Medicine

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Stan Kellar, MD Chief of Clinical Affairs, BH NLR Pulmonary Medicine Sleep Medicine COPD Physiology The lungs are filters Filter in oxygen Filter out carbon dioxide (Vascular filter, not part of this discussion) 1

Physiology Ventilation Perfusion Diffusion Anatomy Inspiration/Expiration 2

INSPIRATION Passive Expiration Forced Expiration 3

Respiratory bronchiole Tethering 4

Normal Conducting System Alveoli Surface area equivalent to that of a tennis court. Very thin. Alveolar and capillary surface 5

Perfusion Low pressure bed, PA pressure 30/10. Approximately 6 billion capillaries in human lung, or about 2000 per alveolus. Under normal (resting) conditions there is little or no flow to the apices, a waterfall effect. Ventilation/Perfusion Under normal circumstances the V/Q (ventilation to perfusion) ratio is 1. This is altered with decreased perfusion (PE) or decreased ventilation (obstructive lung disease or infiltrative diseases). Transportation O2 Primarily by hemoglobulin. Very little dissolved in plasma. 6

Transportation of CO2 10% dissolved in plasma. 20 % carried by Hemoglobin. 70% in form of bicarbonate. CO2 dissociation curve linear. COPD Chronic airflow limitation Airway inflammation Affects more than 6% of the population Third leading cause of death in US Preventable Treatable COPD Chronic bronchitis chronic productive cough for three months in two successive years Emphysema permanent enlargement of airspaces distal to the terminal bronchioles, loss of alveolar walls Asthma Reversible airflow limitation 7

Emphysema Causes Smoking Duration and Amount. PACK YEARS Threshold? About 25 pack years Smoking Smoking Biomass fuel in developing countries Incidence Overall 6.3% USA Higher in men, lower education level and socioeconomic groups Incidence increases with increasing age 3 rd to 6 th leading cause of death 8

RISK BY AGE Pathology Airway limitation inflammation Goblet cell hyperplasia Mucus plugging Loss of airway tethering Loss of airway rigidity Bronchospasm Normal Airway 9

Airway narrowing Symptoms Shortness of breath Cough, with or without sputum Wheezing Chest tightness Dyspnea Lung disease Heart disease Circulatory problems Neuromuscular diseases Therefore not all dyspnea is due to lung diseases 10

Wild Cards ACID REFLUX 25% of patients with significant reflux have no reflux symptoms Another 25% underestimate the degree of reflux Patients with symptoms have 2x rate of exacerbations Deconditioning Physical Findings Wheezing Decreased breath sounds Crackles in bases Diminished heart sounds Barrel shaped chest Tobacco stained finger tips Clubbing is rare Chest X ray Normal Hyperinflation Bullae Flattened hemi diaphragms Basilar scarring Unexpected disease pneumothorax, lung cancer 11

Hyperinflation Pneumothorax Spirometry FEV1 effort dependent FVC effort and time dependent, more than 6 seconds FEV1/FVC ratio less than 70% Peak flow useful for trends, very effort dependent 12

Global initiative on chronic Obstructive Lung Disease GOLD 1: Mild (FEV1 >80% Pred.) GOLD 2: Moderate (FEV1 50 80% Pred.) GOLD 3: Severe (FEV1 30 50% Pred.) GOLD 4: Very severe (FEV1 < 30% Pred.) COPD Assessment Test OK < 10 Modified Medical Research Council Guide Please Check Line That Applies to You Grade 0: I only get short of breath with strenuous exercise. Grade 1: Short of breath hurrying or up slight incline. Grade 2: I walk slower on level ground as similar aged individuals or I stop to rest when walking on my own. Grade 3: I stop for breath when walking 100 meters or after a few minutes. Grade 4: I am too breathless to leave the house or I am breathless dressing or undressing. 13

RISK Related to history of exacerbations Group A: Low risk, less symptoms GOLD 1 2 and 0 1 exacerbations Group B: Low risk, More symptoms GOLD 1 2 and 0 1 exacerbations Group C: High risk, Less symptoms GOLD 3 4 and > 2 exacerbations Group D: High risk, More symptoms GOLD 3 4 and > 2 exacerbations Exacerbations Increased dyspnea Increased cough Sputum production +/ fever +/ chest pain chest tightness Exacerbation Treatment Steroids, oral or IV Antibiotics, oral or IV Additional bronchodialators Hospitalization Non invasive ventilation Ventilation Over 7% do not return to baseline 14

Smoking Cessation Without help/nicotine replacement 10% With help/nicotine replacement 50 60% ASK ADVISE ASSESS ASSIST ARRANGE Chantix Nicotine, Give enough Too much nicotine causes nausea Decreased airflow + smoking Progressive lung disease 25 times normal risk for heart attack or stroke 8 times risk for lung, laryngeal, esophageal, stomach, kidney, bladder, oral and pancreatic cancer Cessation rapidly reduces the risk of cardiovascular complications 15

Medications: Short acting Rescue Beta agonists, MDI or nebulizer (albuterol) Techniques Spacers Cost Intended for rescue Primary side effects cardiac arrhythmia (tachycardia) and tremor Medications: Short acting Rescue Anticholinergics, MDI or nebulizer (Atrovent) Short acting Rescue Costs Adverse effects rare, dryness Medications: Long acting Beta agonists, MDI and nebulizer Foradil and Serevent are the primary single agents with MDI Perforomist and Brovana are the nebulized forms Almost never used alone Increased risk of death in asthma patients when use alone (Black Box Warning) 16

Medications: Long acting Anticholinergics, MDI Spiriva and Tudorza Cost Medications: Inhaled Steroids MDI and nebulizer Controversy Single agents, Flovent, Asmanex, Qvar, Pulmicort Anti inflammatory Adverse effects oral thrush, hoarseness, possible osteoporosis, increased risk of pneumonia Medications: Steroids/Beta agonists MDIs Advair Discus and MDI Symbicort Dulera Breo, new, fluticasone and vilanterol 17

Medication: LABA + LA Anticholinergic Anoro, new Medications: Steroids Anti inflammatory Oral prednisone or Medrol Dose and length of treatment controversial IV for hospitalized patients, dose and length of treatment controversial Adverse effects Hyperglycemia, thrush, increased risk of infection, osteoporosis, weight gain, myopathy Medications: Phosphodiesterase 4 Inhibitors Daliresp anti inflammatory Frequent side effects with nausea, vomiting, diarrhea, generalized aches, loss of appetite 18

Medication: Theophyllins Moderate bronchodialator Toxicity is dose related Adverse effects nausea, vomiting, headaches, seizures Blood levels altered by other medications, both up and down Special Consideration Alpha 1 Antrypsin Deficiency Earlier emphysema with a basilar predominance Replacement available Testing is free Vaccinations Yearly flu immunization Pneumococcal vaccine for patients 65 years and older 19

Oxygen Improve mortality Improve dyspnea Improve quality of life Improve cognition Cost over $500/mo., 1 million patients in USA at a cost of over 2 billion dollars Oxygen PaO2, 55 mmhg or saturation, 89% at rest PaO2, 60 with cor pulmonale, right heart failure or HCT > 55 O2 saturation less than 89 % for more than 5 minutes with sleep (Look for OSA) Pao2 < 55 or saturation <88 with exercise In COPD patients check ABGs on O2 to check PaCO2 ANN Internal Med 1980; 93:391 20

Lancett 11981; 1:681 Oxygen No benefit for saturations > 92% Increase in PaCO2 (Hypoventilation) Absorptive atelectasis Hyper oxemia can result in decreased free water clearance Facial burns especially in patients with facial hair Fall risk with the tubing NO SMOKING RISK Related to history of exacerbations Group A: Low risk, less symptoms GOLD 1 2 and 0 1 exacerbations Group B: Low risk, More symptoms GOLD 1 2 and 0 1 exacerbations Group C: High risk, Less symptoms GOLD 3 4 and > 2 exacerbations Group D: High risk, More symptoms GOLD 3 4 and > 2 exacerbations 21

Treatment Recommendations GOLD Group A Group B Group C Group D Group A Group B Group C Group D S A Beta agonist or anticholinergic L A Beta agonist or anticholinergic ICS + LA Beta or LA anticholinergic ICS + LA Beta +/or LA anticholinergic ALTRERNATIVE LA Beta or LA anticholinergic or SA Beta with SA anticholinergic LA Beta with LA anticholinergic LA Beta + LA anticholinergic or LA Beta + PD4 Inh or LA anticholinergic + PD4 Inh ICS + LA Beta + LA Antichol. Or ICS + LA Beta + PD4 Inh, or LA Beta + LA antichol, LA antichol + PD4 inh Exercise Mucolytics Antidepressants Other Considerations Comorbidities Coronary artery disease Osteoporosis Peripheral vascular disease Cancer Heart failure Atrial fibrilation Interstitial lung diseases 22

Referrences Global Initiative for Chronic Obstructive lung Disease Lancet 370; 2007, p741, International variation Lancet 378; 2011, p991, Lifetime risk MMWR 61, 2012, p938, COPD among adults UpToDate Chest 130; 2006, p1096, Role of gastroesophageal Am J Crit Care Med 180; 2009, p3, The Natural History NEJM 365: 2011, p1184, Changes in Forced Pulmonary Physiology in Clinical Medicine, Tisi Am J Respir Crit Care Med 161; 2000, p 1608, Time course and recovery BMJ 1; 1977, p1645, The natural history Am J Respir Crit Care Med178; 2008, p332, Effect of pharmacotherapy JAMA 309;2013, p2223, Short term vsconventional 23