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Chronic Obstructive Pulmonary Disease

J.B. Handler, M.D.Physician Assistant ProgramUniversity of New England

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Abbreviations PO2- partial pressure of

oxygen. PCO2- partial pressure of

carbon dioxide SaO2- arterial oxygen

saturation Sx- symptoms CNS- central nervous

system HTN- hypertension PRN- as necessary

A- alveoli RB- respiratory bronchiole AD- alveolar ducts CHD- coronary heart

disease PVD- peripheral vascular

disease PAP- pulmonary artery

pressure HR- heart rate

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Case 1 A 64 y/o man presents for further evaluation of

progressive dyspnea. Over the last 3 years his dyspnea has progressed to where he is SOB at rest. He has >60 pk/year hx of smoking, and has recently “cut down” to 1 ppd.

PE reveals a thin male, SOB at rest. Percussion: hyperresonance. Auscultation: expiratory phase with breath sounds; no wheezes, crackles or ronchi. PFT’s: marked obstructive pattern.

What is the most likely diagnosis?

Anatomy and Respiratory Disease

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COPD A disease state characterized by

airflow obstruction as a result of chronic bronchitis or emphysema.

Generally progressive over time. Smoking

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Epidemiology 14 million in USA with COPD Dx

Equal number likely undiagnosed COPD: 4th leading cause of death in

U.S. 115,000 annual deaths from COPD Death rate increasing, esp older men

Worldwide incidence increasing smoking in developing countries

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General Considerations Airflow obstruction from bronchitis or

emphysema resulting in resistance to airflow.

Obstruction of conducting airways with airway hyperactivity that may be partially reversible Chronic Bronchitis.

Loss of support structure to terminal respiratory units Emphysema.

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General Considerations Cigarette smoking most important

cause (90% of patients). Involves 15% of all smokers Major factor for other diseases: CHD, PVD,

stroke, lung cancer. Other factors: genetics, pollution, dusts,

chemical irritants, infection. Chronic Bronchitis & Emphysema:

Significant overlap in symptoms, presentation and management.

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General Considerations In evaluating and treating patients, best

to think about COPD as a mixed process containing elements of both bronchitis and emphysema. No major differences in management. Often the bronchitic or emphysematous

picture predominates the clinical presentation. Pathophsiology: We will focus on

bronchitis and emphysema as separate processes.

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Chronic Bronchitis Clinical definition: Productive cough

for 3 months/yr for 2 consecutive years.

Bronchitis clinical presentation more common than emphysema. Often a mixed picture of

bronchitis/emphysema with bronchitic features predominating.

Chronic Bronchitis

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Pathophysiology: Bronchitis Initial insult: inflammation of

conducting airways damages respiratory epithelium; loss of cilia. Columnar cells may be replaced by squamous cells (metaplasia). Metaplasia is a pre-cancerous lesion

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Pathophysiology: Bronchitis Airway narrowing: mucus secretion;

hypertrophy/hyperplasia of glands and smooth muscle hypertrophy; bronchospasm occurs. work of breathing ventilation of distal alveoli (V/Q

mismatch)

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Pathophysiology: Bronchitis Airway hyperresponsiveness. Obstruction in airways during

exhalation; usually present once dyspnea present.

Smokers with early airways disease can alter disease process/ progression with smoking cessation.

Normal Bronchiole

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Chronic Bronchitis

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Chronic Bronchitis Symptoms present by 5th or 6th decade,

sometimes earlier; insidious onset. Excessive cough, sputum production

and SOB (later in course). Sputum: thick, often purulent looking. Symptoms often present for years before

seeking medical attention. Patients often overweight; cyanosis is a

late finding.

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Chronic Bronchitis Dyspnea: Not a factor early; presents

initially with exertionrest. Acute exacerbations from minor

respiratory infections common; often with fever; common in winter months.

Complications: Pneumonia, pulmonary hypertension right sided heart failure (late finding), respiratory failure (end stage).

Cardiac Pressures

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Physical Exam and CxR Tachycardia, tachypnea: work of

breathing, hypoxemia. Use of accessory muscles later stages. Increased expiratory phase. Wheezing and ronchi common;

represents airway obstruction/turbulence. Coarse crackles represent mucus in distal

airways. CxR: may be normal early; hyperinflation,

flattening of diaphragms later.

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PFT’s: Chronic Bronchitis Lung Volumes: RV, FRC, TLC. Spirometry: FVC nl or mildly ; FEV1,

FEV1/FVC; ing FVC indicates more severe disease.

FEV1/FVC <70% confirms obstructive pattern. Some reversibility post bronchodilator. Diffusion capacity (DLCO) normal. ABG: reflects V/Q; PO2 late; PCO2 usually

normal; PCO2 very late- severe disease/bad prognosis.

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Emphysema Pathological definition Abnormal and permanent

enlargement of the air spaces distal to the conducting bronchioles, accompanied by destruction of their walls without obvious fibrosis.

Involves terminal respiratory units.

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Emphysema: Pathology Lung tissue subject to injury from

oxidants: smoking, pollutants, etc; protected by endogenous anti-oxidants.

Locally produced enzymes from neutrophils and macrophages (proteases/elastases) can damage elastic connective tissue supporting terminal respiratory units.

Anti-elastases/proteases in circulation protect lung tissue from proteolytic damage: -1 antitrypsin/antiprotease.

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Emphysema: Pathology Smoking:

Direct oxidant injury: Elastin and collagen fiber damage.

function of protease inhibitors including -1 antitrypsin/antiprotease: Elastin and collagen fiber damage.

Elastic tissue destroyed by imbalance of neutrophil elastase/protease inhibitors.

Result: Connective/elastic tissue damage to terminal respiratory units (RB, AD, A)

Terminal Respiratory Units

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Emphysema: Pathophys Elastic recoil, compliance. Loss of alveolar connective tissue

and lung support; RB, AD, A dilate. Premature collapse of respiratory

bronchioles in expiration results in air trapping; result is “obstructive picture” on PFT’s (see below).

Emphysema

Emphysema

Normal Lung Emphysema

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Emphysema: Pathophys Progressive destruction of

alveoli and vasculature leads to V/Q mismatch with both shunting (V/Q ratio) and increased alveolar dead space.

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-1 Antitrypsin (-1AT) Also called -1 Antitiprotease Acute phase serum protein made in liver Inhibits proteases released from WBC’s

(neutrophil elastase) that destroy elastic tissue in lung parenchyma (terminal respiratory units/alveoli).

Normal: 110-270 mg/dL; risk if<80mg/dL Autosomal co-dominant

-Heterozygous: -1AT by 20-25% -Homozygous: -1AT by 85-90%

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Emphysema: Clinical Presentation Dypnea predominates: Esp with exercise,

later at rest; progressive and irreversible. weight, muscle mass and wasting at end

stage. “Barrel” chest, A-P diameter. Tachypnea and tachycardia. Breath sounds, expiratory phase; +/-

wheezing. heart sounds common. CxR: Hyperinflation, flattening of

diaphragms.

CxR: COPD/Emphysema

Narrow cardiac silhouette and hyperinflationImages.google.com

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Emphysema: PFT,s TLC and lung volumes; RV, FRC FVC, FEV1, FEV1/FVC- obstructive

pattern; FVC reflects alveolar damage. Prolonged FVC DLCO initially normal but ’s in proportion

to extent of emphysema (loss of alveolar surface area).

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Case 1: Diagnosis COPD with features most consistent

with emphysema.

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Dyspnea and COPD Major cause of disability. Occurs relatively late in disease

process. Sense of muscular effort to breath

in relation to ventilation achieved. May or may not be accompanied by

significant hypoxemia (PO2 or SaO2).

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ABG and COPD Early on will be normal As disease progresses: PO2

PCO2 usually normal but as disease progresses, PCO2 may

Some patients will lose PCO2 drive to ventilation and develop drive from PO2.

Important to document and understand if supplemental O2 is to be used.

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Smoking Cessation Smoking cessation is the most

important intervention for COPD treatment/prevention; does not reverse damage but decreases progression. Requires behavioral modification and drugs. Drugs: Nicotine (patch, gum, inhaler); Varenicline (Chantix)-new.

Bupropion: Antidepressant increases brain norepinephrine and dopamine; mimics effects of nicotine.

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Bronchodilators Most important agents in management

of COPD. Improve symptoms. Do not reverse

decline in lung function or alter progression. Improve exercise tolerance and overall health

status. 2 classes: ß2 agonists and anticholinergics,

both delivered by MDI inhaler. Nebulized ß2 agonists likely no better than MDI for COPD (vs asthma).

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Anticholinergics Anticholinegic Rx beneficial because

patients with COPD have airway tone mediated by acetylcholine.

Decrease vagally mediated bronchoconstriction. Improve symptoms in similar fashion to ß2 agonists, less side effects. Short acting: Ipratropium Long acting (new): Tioproprium

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Anticholinergics New data shows mild superiority of

tiotropium vs ipratropium. Improvement in dyspnea & lung

function, exacerbations, improved “quality of life”.

More expensive.

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ß2 Agonists

ß2 agonists: Stimulate ß2 receptors in lungrelax smooth muscle mild bronchodilation. Improve Sx and exercise tolerance. Side effects: tremor, HR.

Albuterol and others: short acting, q6hrs; less expensive than anticholinergics. PRN vs scheduled dosing.

Anticholinergics often combined with ß2 agonists in patients with COPD and for COPD exacerbations.

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Corticosteroids Anti-inflammatory effects Oral or IV (systemic) glucocorticoids:

Acute exacerbations or hospitalized patients only.

Inhaled: Very Limited benefit compared to use in asthma. May improve FEV1 and Sx in minority (10%) patients; May frequency of acute exacerbations. 6 wk trial with pre/post PFT’s looking for 20% improvement in FEV1.

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Oxygen Therapy Increased morbidity and mortality from chronic

hypoxemia in patients with COPD. Symptoms from hypoxemia: Dyspnea, CNS, etc.

Pulmonary hypertension leads to: Cor pulmonale - RVH or Rt sided heart failure

Long term O2 prolongs life, pulm HTN

Indications: PO2 55mmHg, SaO2 88% Measurements: Resting, exercise, sleep Goal: PO2 60-80 mmHg; provide O2 for > 15

hrs/day.

O2-Hemoglobin Dissociation

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Other Measures Education: Effective coughing,

mobilization of secretions. Graded aerobic exercise to improve

conditioning: Pulmonary rehabilitation. 1-AT replacement therapy- IV;

expensive. For severe deficiency.

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Acute Exacerbations Acute flare with worsening

symptoms (cough, sputum, dyspnea, wheezing) functional status, PO2/SaO2. Sometimes accompanied by PCO2 (fatigue).

Precipitants: Infections, sedation, bronchospasm, pollutants.

Often treated as out-patient.

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Acute Exacerbations: Rx Rx: Bronchodilators (dose + combo Rx),

O2 if needed (O2 sat< 90%), antibiotics; oral corticosteroids (prednisone).

Antibiotics- EBM supports use. Organisms: H influenza, M catarrhalis, S pneumococcus, others. Drugs: Doxycycline, Trimethoprim/Sulfa, Flouroquinolones (Levofloxacin et al), Amoxacillin/clavulanate and others.

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Indications for Hospitalization

Rapid increase in severity of symptoms

Advanced age Presence of arrhythmias Poor home support Failure to improve as out-patient Worsening hypoxemia or

presence/worsening of hypercarbia

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Hospitalized patients Rx: Bronchodilators: B2 agonists +

anticholinergics to max doses. IV/PO steroids (methylprednisolone or

prednisone)- superphysiologic dosing. Broad spectrum antibiotics Supplemental O2, goal reduce hypoxemia

(keep O2 sat>89%), PAP Mechanical ventilation for respiratory failure

(oxygenation/ventilation). Hydration, arrhythmias, etc.

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Surgery for COPD Lung transplant: single/double; Of limited

usefulness; indication: end-stage disease. Cost:>$250,000. Benefits: 75% 2-year survival.

Lung volume reduction surgery (emphysema): Bilateral resection of 20-30% lung volumemodest improvement in pulm function, exercise capacity and dyspnea. 5-10% mortality. Bullectomy (emphysema)- removal of large bullae

dead space, improves V/Q mismatch.