COPD- pulmonary hyperinflation- the diaphragms are at the level of the eleventh posterior ribs and appear flat.

COPD

COPD Hallmark symptom - Dyspnea Chronic productive cough Minor hemoptysis pink puffer blue bloater

COPD- pulmonary hyperinflation- the diaphragms are at the level of the eleventh posterior ribs and appear flat.

COPD - Physical Findings Tachypnea Accessory respiratory muscle use Pursed lip exhalation Weight loss due to poor dietary intake and excessive caloric expenditure for work of breathing

Dominant Clinical Forms of COPD Pulmonary y emphysema Chronic bronchitis Most patients exhibit a mixture of symptoms and signs

COPD - Advanced Dx secondary yp polycythemia y cyanosis tremor somnolence and confusion due to hypercarbia Secondary pulmonary HTN w or w/o cor pulmonale l

COPD Treatment Strategy Elimination of extrinsic irritants bronchodilator h t & glucocorticoid id therapy Antibiotics Mobilization of secretions respiratory vaccines Oxygen therapy - if oxygen saturation <90 90% at rest on room air

Spirometry

A-a gradient A-a gradient = predicted po 2 observed PO 2 PAO 2 = (FIO 2 X 713) (PaCO 2 /0.8) at sealevel PAO 2 = 150-(PaCO 2 /0.8) at sealevel on room air Normal range 10-15mm > 30 years of age Normal range 8mm < 30 years of age Increased A-aDO 2 =diffusion defect Right to left shunt V/Q mismatch

Examples A doubel overdose brings two 30 yr old patients to the ED. Both have ingested substantial amounts of barbiturates and diazepam. Blood gases drawn on room air revealed these values: patient 1- ph =7.18 18, PCO 2 = 70mmHg, PO 2 =50mmHg, HCO 3 =24mEq/L; patient2- ph =7.31 31, PCO 2 =50mmHg, PO 2 =50 50mmHg, HCO 3 =25 25mEq/L

Comment The A-a gradient calculation for patient 1 is as follows: A-a ado 2 = PAO 2 PaO 2 PAO 2 = 150 (1.25x PCO 2 ) PAO 2 = 150 (1.25x 70) PAO 2 = 62 A-a =62 50 A-a = 12

Comment The calculation reveals a normal gradient, indicating that the etiology for hypoxemia and hypoventilation is extrinsic to the lung itself.

Comment The A-a gradient calculation for patient 2 is as follows: PAO 2 = 150 (1.25 xpco) 2 PAO = 150 (1.25 x 50) 2 PAO 2 = 150 63 PAO 2 = 87 Therefore,, A-a = 87 50 =37 (an abnormally increased gradient)

Comment We can be reasonably confident that patient 1 suffered hypoventilation due to the effect of the ingested drugs on the brain stem. Temporary mechanical ventilation restored this patient s gas exchange.

Comment Patient 2, on the other hand, had an increased A-a gradient, indicating a lung problem in addition to any central cause for hypoventilation. The chest x-ray film revealed that this patient s t overdose was complicated by aspiration pneumonitis and that the patient required treatment with antibiotics in addition to mechanical ca ventilation.

COPD (Chronic Obstructive Pulmonary Disease) Chronic Bronchitis Emphysema

Definition A A disease state characterized by airflow limitation that is not fully reversible Conditions include: Emphysema: (anatomically defined condition characterized by destruction and enlargement of the lung alveoli) Chronic bronchitis: clinically defined condition with chronic cough and phlegm Small-airways airways disease: condition in which small bronchioles are narrowed

Epidemiology Fourth leading cause of death in the U.S. Affects > 16 million persons in the U.S. Global l Initiative for Chronic Obstructive ti Lung Disease (GOLD) estimates suggest that chronic obstructive lung disease (COLD) will increase from the sixth to the third most common cause of death worldwide by 2020.

Epidemiology >70 70% of COLD-related health care expenditures go to emergency department visits and hospital care (>$10 billion annually in the U.S.).

Epidemiology Sex Higher prevalence in men, probably secondary to smoking Prevalence of COLD among women is increasing as the gender gap in smoking rates has diminished.

Epidemiology i Age Higher prevalence with increasing age Dose response relationship between cigarette smoking intensity and decreased pulmonary function

Risk Factors 1. Cigarette smoking is a major risk factor. 2. Cigar and pipe smoking 3. Passive (secondhand) smoking Associated with reductions in pulmonary function Its status as a risk factor for COLD remains uncertain

Occupational exposures to dust and fumes (e.g., cadmium) Likely risk factors The magnitude of these effects appears substantially less important than the effect of cigarette smoking. Ambient t air pollution The relationship of air pollution to COLD remains unproven.

Genetic factors α1 antitrypsin (α1at) deficiency Common M allele: normal levels S allele: slightly reduced levels Z allele: markedly reduced levels Null allele: e absence of α1at (rare) (ae) Lowest levels of α1at are associated with incidence of COLD; α1at deficiency interacts with cigarette smoking to increase risk.

Distributions of forced expiratory volume in 1 s (FEV1)values in a general population p sample, stratified by yp pack-years of smoking

Etiology COLD Causal relationship between cigarette smoking and development of COLD has been proven: however, the response varies considerably among individuals.

COLD exacerbation Bacterial infections Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis Mycoplasma pneumoniae or Chlamydia pneumoniae (5 10% of exacerbations) Viral infections (one-third) No specific precipitant identified (20 35%)

Symptoms & Signs 3 most common: Cough Sputum production Exertional dyspnea, frequently of long duration

signs and symptoms Dyspnea at rest Prolonged expiratory phase and/or expiratory wheezing on lung examination Decreased breath sounds Barrel chest Large lung volumes and poor diaphragmatic excursion, as assessed by percussion Use of accessory muscles of respiration Pursed lip breathing (predominantly emphysema) Characteristic "tripod" sitting position to facilitate the actions of the sternocleidomastoid, scalene, and intercostal muscles Cyanosis, visible in lips and nail beds

Systemic wasting Significant weight loss Bitemporal wasting Diffuse loss of subcutaneous adipose tissue Paradoxical respiration Inward movement of the rib cage with inspiration (Hoover's sign) in some patients "Pink puffers" are patients with predominant emphysema no cyanosis or edema, with decreased breath sounds. "Blue bloaters" are patients with predominant bronchitis cyanosis cyanosis and edema. Most patients have elements of each.

Advanced disease: signs of cor pulmonale Elevated jugular venous distention Right ventricular heave Third heart sound Hepatic congestion Ascites Peripheral edema

Differential Diagnosis 1. Congestive heart failure 2. Asthma 3. Bronchiectasis 4. Obliterative bronchiolitis 5. Pneumonia 6. Tuberculosis 7. Atelectasis 8. Pneumothorax 9. Pulmonary embolism

Considerations 1. COLD is present only if chronic airflow obstruction occurs. Chronic bronchitis without chronic airflow obstruction is not COLD. 2. Asthma Reduced forced expiratory volume in 1 second (FEV1) in COLD seldom shows large responses (>30%) to inhaled bronchodilators, although improvements up to 15% are common. Asthma patients can also develop chronic (not fully reversible) airflow obstruction.

Considerations 3. Problems other than COLD should be suspected when hypoxemia is difficult to correct with modest levels of supplemental oxygen. 4. Lung cancer Clubbing of the digits it is not a sign of COLD.In patients with COLD, development of lung cancer is the most likely explanation for newly developed clubbing.

Chronic Bronchitis Chronic lower airway inflammation Increased bronchial mucus production Productive cough Urban male smokers > 30 years old

Chronic Bronchitis Mucus, swelling interfere with ventilation Increased CO 2, decreased 0 2 Cyanosis occurs early in disease Lung disease overworks right ventricle Right heart failure occurs RHF produces peripheral edema Blue Bloater

Emphysema Loss of elasticity in small airways Destruction of alveolar walls Ub Urban male smokers >40 40-50 years old

Emphysema Lungs lose elastic recoil Retain CO 2, maintain near normal O 2 Cyanosis occurs late in disease Barrel chest (increased AP diameter) Thin, wasted Prolonged exhalation through pursed lips Pink Puffer

COPD Management Oxygen Monitor carefully Some COPD patients may experience respiratory depression on high concentration oxygen Assist ventilations as needed

Diagnostic Approach Initial assessment 1. History and physical examination (Signs & Symptoms) 2. Pulmonary function testing to assess airflow obstruction 3. Radiographic studies

Assessment of exacerbation 1. History Fever Change in quantity and character of sputum ill contacts Associated symptoms Frequency and severity of prior exacerbations

Assessment of exacerbation 2. Physical examination Tachycardia Tachypnea Chest examination Focal findings Air movement Symmetry Presence or absence of wheezing Paradoxical movement of abdominal wall Use of accessory muscles Perioral or peripheral cyanosis Ability to speak in complete sentences Mental status

3. Radiographic studies Chest radiography focal findings (pneumonia, atelectasis) t 4. Arterial blood gases Hypoxemia Hypercapnia p 5. Hospitalization recommended for: Respiratory acidosis and hypercarbia Significant hypoxemia Severe underlying disease Living situation not conducive to careful observation and delivery of prescribed treatment

ABG and oximetry Although not sensitive, they may demonstrate resting or exertional hypoxemia. Blood gases provide additional information about alveolar ventilation and acid base status by measuring arterial PCO 2 and ph. Change in ph with PCO 2 is 0.0808 units/10 mmhg acutely and 0.0303 units/10 mmhg in the chronic state.

Laboratory Tests 1. Elevated hematocrit suggests chronic hypoxemia. 2. Serum level of α1at should be measured in some patients. o Presenting at 50 years of age o Strong family history o Predominant basilar disease o Minimal smoking history o Definitive diagnosis of α1at deficiency requires PI type determination. Typically performed by isoelectric focusing of serum, which reflects the genotype at the PI locus for the common alleles and many of the rare PI alleles Molecular genotyping can be performed for the common PI alleles (M, S, and Z). 3. Sputum gram stain and culture (for COLD exacerbation)

Imaging Chest radiography Emphysema: obvious bullae, paucity of parenchymal markings, or hyperlucency Hyperinflation: increased lung volumes, flattening of diaphragm Chest CT Does not indicate chronicity of changes Definitive test for establishing the diagnosis of emphysema, but not necessary to make the diagnosis

Pulmonary function tests/spirometry Diagnostic Procedures Chronically reduced ratio of FEV1 to forced vital capacity (FVC) In contrast to asthma, the reduced FEV1 in COLD seldom shows large responses (>30%) to inhaled bronchodilators, although improvements up to 15% are common. Reduction in forced expiratory flow rates Increases in residual volume Increases in ratio of residual volume to total lung capacity Increased total lung capacity (late in the disease) Diffusion capacity may be decreased in patients with emphysema. Electrocardiography d t t i f t i l h t h

Classification GOLD stage Classification based on pathologic type

GOLD stage 0 I II III IV Severity: at risk Symptoms: chronic cough, sputum production Spirometry: normal Severity: mild Symptoms: with or without chronic cough or sputum production Spirometry: FEV1:FVC < 0.7 and FEV1 80% predicted Severity: moderate Symptoms: with or without chronic cough or sputum production Spirometry: FEV1:FVC < 0.7 and FEV1 50 80 80% predicted Severity: severe Symptoms: with or without chronic cough or sputum production Spirometry: FEV1:FVC < 0.7 and FEV1 30 50 50% predicted Severity: very severe Symptoms: with or without chronic cough or sputum production Spirometry: FEV1:FVC < 0.7 and FEV1 < 30% predicted or FEV1 < 50% predicted with respiratory failure or signs of right heart failure

Treatment Approach General Only 2 interventions ti have been demonstrated t d to influence the natural history. Smoking cessation Oxygen therapy in chronically hypoxemic patients All other current therapies are directed at improving symptoms and decreasing frequency and severity of exacerbations. Therapeutic response should determine continuation of treatment.

Specific Treatments Stable-phase COLD, pharmacotherapy Bronchodilators Used to treat symptoms The inhaled route is preferred. Side effects are less than with parenteral delivery. Theophyllline: various dosages and preparations; p typical dose 300 600 mg/d, adjusted based on levels

Specific Treatments Stable-phase COLD, pharmacotherapy Anticholinergic agents Trial of inhaled anticholinergics is recommended in symptomatic patients. Side effects are minor. Improve symptoms and produce acute improvement in FEV Do not influence rate of decline in lung function Ipratropium bromide (short-acting anticholinergic) (Atrovent) Inhaled: 30-min onset of action; 4-h duration Atrovent: metered-dose dose inhaler; 18 μg per i h l ti 1 2 i h l ti id

Specific Treatments Stable-phase COLD, pharmacotherapy Tiotropium op u (long-acting g anticholinergic) c) (Spiriva) Spiriva: powder via handihaler; 18 μg per inhalation; 1 inhalation qd Symptomatic benefit Long Long-acting inhaled β-agonists, such as salmeterol, have benefits similar to ipratropium bromide. More convenient than short-acting

Specific Treatments Stable-phase COLD, pharmacotherapy Addition of a β-agonist to inhaled anticholinergic therapy provides incremental benefit. Side effects Tremor Tachycardia Salmetrol l (Serevent): Powder via diskus; 50-μg inhalation every 12 h Formoterol (Foradil): Powder via aerolizer; 12 μg inhalation every 12

Specific Treatments Stable-phase COLD, pharmacotherapy Albuterol (short-acting β-agonist) (Proventil HFA, Ventolin HFA, Ventolin, Proventil) Metered-dose dose inhaler (or in nebulizer solution); 180-μg inhalation every 4 6 h as needed Combined β-agonist/anticholinergic: albuterol/ipratropium (Combivent) Metered-dose dose inhaler (also available in nebulizer solution); 120 mcg/21 μg

Specific Treatments Stable-phase COLD, pharmacotherapy Inhaled glucocorticoids Reduce frequency of exacerbations by 25 30% No evidence of a beneficial effect for the regular use of inhaled glucocorticoids on the rate of decline of lung function, as assessed by FEV1 Consider a trial in patients with frequent exacerbations ( 2 per year) and those who demonstrate a significant amount of acute reversibility in response to inhaled bronchodilators.

Specific Treatments Stable-phase COLD, pharmacotherapy Beclomethasone (QVAR): Metered-dose dose inhaler; 40 80 μg/spray; 40 160 μg bid Budesonide (Pulmicort): Powder via Turbuhaler; 200 μg/spray; 200 μg inhaled bid Fluticasone (Flovent): Metered-dose dose inhaler; 44, 110 or 220 μg/spray; 88 440 μg inhaled bid Ti i l (A t)

Oxygen 1. Supplemental l O2 is the only therapy demonstrated to decrease mortality 2. In resting hypoxemia (resting O2 saturation < 88% or < 90% with signs of pulmonary hypertension or right heart failure), the use of O2 has been demonstrated to significantly affect mortality. 3. Supplemental O2 is commonly prescribed for patients with exertional hypoxemia or nocturnal hypoxemia. The rationale for supplemental O2 in these settings is physiologically sound, but benefits are not well substantiated.

Beclomethasone (QVAR): Metered-dose dose inhaler; 40 80 μg/spray; 40 160 μg bid Budesonide (Pulmicort): Powder via Turbuhaler; 200 μg/spray; 200 μg inhaled bid Fluticasone (Flovent): Metered-dose dose inhaler; 44, 110 or 220 μg/spray; 88 440 μg inhaled bid Triamcinolone (Azmacort) Metered-dose dose inhaler via built-in in spacer; 100 μg/spray; / 100 400 μg inhaled bid

Parenteral corticosteroids Long-term use of oral glucocorticoids id is not recommended. Side effects Osteoporosis, fracture Weight gain Cataracts Glucose intolerance Increased risk of infection Patients tapered off long-term low-dose prednisone (~10 mg/d) did not experience any adverse effect on the frequency of exacerbations, quality of life, or lung function. On average, patients lost ~4.5 kg (~10 lb) when steroids were withdrawn.

Theophylline Produces modest improvements in expiratory flow rates and vital capacity and a slight improvement in arterial oxygen and carbon dioxide levels in moderate to severe COPD Side effects Nausea (common) Tachycardia Tremor

Specific Treatments Stable-phase COLD, pharmacotherapy Oh Other agents 1. N-acetyl cysteine Used for its mucolytic and antioxidant (current clinical trials) properties 2. Intravenous α1at augmentation therapy for patients with severe α1at deficiency 3. Antibiotics Long-term suppressive or "rotating" ti " antibiotics are not beneficial

Specific Treatments Stable-phase COLD, nonpharmacologic therapies Smoking cessation All patients with COLD should be strongly urged to quit and educated about the benefit of cessation and risks of continuation. Combining gp pharmacotherapy py with traditional supportive approaches considerably enhances the chances of successful smoking cessation. Bupropion Nicotine replacement (gum, transdermal, inhaler, nasal spray) The U.S. Surgeon General recommendation is for all smokers considering quitting to be offered pharmacotherapy in the absence of any contraindication.

Specific Treatments Stable-phase COLD, nonpharmacologic therapies General medical care 1. Annual influenza vaccine 2. Polyvalent pneumococcal vaccine is recommended, although proof of efficacy in COLD patients is not definitive.

Specific Treatments Stable-phase COLD, nonpharmacologic therapies Pulmonary rehabilitation Improves health-related quality of life, dyspnea, and exercise capacity Rates of hospitalization are reduced over 6 to 12 months.

Specific Treatments Stable-phase COLD, nonpharmacologic therapies Lung volume reduction surgery Produces symptomatic and functional benefit in selected patients Emphysema Predominant upper lobe involvement Contraindications Significant pleural disease (pulmonary artery systolic pressure >45 mm Hg) Extreme deconditioning Congestive heart failure Other severe comorbid conditions FEV1 < 20% of predicted and diffusely distributed emphysema on CT or diffusing capacity for CO <20%

Specific Treatments Stable-phase COLD, nonpharmacologic therapies Lung transplantation COLD is the leading indication. Candidates 65 years Severe disability despite maximal medical therapy No comorbid conditions, such as liver, renal, or cardiac disease Anatomic distribution tion of emphysema and presence of pulmonary hypertension are not contraindications

exacerbation of COPD The goals of emergency therapy correct tissue oxygenation alleviate reversible bronchospasm treat the underlying etiology of the exacerbation

Administer controlled oxygen therapy correct or prevent life-threatening hypoxemia, PaO2 greater than 60 mm Hg or an SaO2 greater than 90 percent Improvement after administration of supplemental l oxygen may take 20 to 30 min to achieve a steady state

B 2-Agonists and anticholinergic agents are first-line therapies in the management of acute, severe COPD

CORTICOSTEROIDS short course (7 to 14 days) of systemic steroids appears more effective than placebo in improving FEV1 in acute severe exacerbations of COPD, role in mild-to to-moderate exacerbations Hyperglycemia is the most common adverse effect

ANTIBIOTICS All current guidelines recommend antibiotics if there is evidence of infection, change in volume of sputum and increased purulence of sputum benefits are more apparent in more severe exacerbations Antibiotic choices should be directed at the most common pathogens known to be associated with COPD exacerbation Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis duration of treatment;(3 to 14 days )

METHYLXANTHINES theophylline and aminophylline severe exacerbation when other therapy has failed or in patients already using methylxanthines who have subtherapeutic drug levels The bronchodilation effect of aminophylline is limited, therapeutic range is narrow

IV loading dose 5 to 6 mg/kg usually required to obtain an initial serum concentration of 8 to 12 macg/ml In patients who regularly use theophylline, a mini-loading dose should be administered: (target concentration currently currently assayed concentration) x volume of distribution (i.e., 0.5 times ideal body weight in liters) target concentration should be between 10 and 15 macg/ml. IV maintenance infusion rate is 0.2 to 0.8 mg/kg g ideal body weight per h. lower maintenance rates (congestive heart failure or hepatic insufficiency ) raise maintenance rates in patients with higher clearance rates, such as smokers

Summary for ED Management Assess severity of symptom Administer controlled oxygen therapy Perform arterial blood gas measurement after 20 30 min if SaO2 remains <90% or if concerned about symptomatic hypercapnia

Administer bronchodilators B2-agonists and/or anticholinergic i agents by nebulization or MDI with spacer Consider adding intravenous methylxanthine, if needed Add corticosteroids ( Oral or intravenous) Consider antibiotics If increased sputum volume, change in sputum color, fever, or suspicion of infectious etiology of exacerbation

Laboratory y evaluation Chest x-ray CBC with differential Electrolytes Arterial blood gases ECG as needed

At all times Monitor fluid balance Consider subcutaneous heparin (venous thrombosis prophylaxis) Identify and treat associated conditions (e.g., heart failure, arrhythmias) Closely monitor condition of the patient

Indications for Invasive Mechanical Ventilation Severe dyspnea with use of accessory muscles and paradoxical abdominal motion Respiratory frequency >35 breaths per min Life-threatening hypoxemia: PaO2 <50 mm Hg (<5.3 kpa) or PaO2/FIO /FIO2 <200 mm Hg Severe acidosis (ph <7.25 25) and hypercapnia (PaCO2 >60 mm Hg or >8.0 kpa) Respiratory arrest Somnolence, impaired mental status Cardiovascular complications (hypotension, shock, heart failure) NIPPV failure

Indications for ICU Severe dyspnea that responds inadequately to initial emergency therapy Confusion, lethargy, coma Persistent or worsening hypoxemia: PaO2 <50 mm Hg (<6.7 kpa) Severe or worsening hypercapnia: PaCO2 >70 mm Hg (>9.3 kpa) Severe or worsening respiratory acidosis (ph <7.30) despite supplemental oxygen and NIPPV

Indications for Hospital Admission Marked increase in intensity of symptoms, such as sudden development of resting dyspnea Severe background of COPD Onset of new physical signs (e.g., cyanosis, peripheral edema) Failure of exacerbation to respond to initial medical management Significant comorbidities Newly occurring arrhythmias Diagnostic uncertainty Older age Insufficient home support

discharge to home (1) adequate supply of home oxygen, if needed (2) adequate and appropriate bronchodilator treatment (3) short course of oral corticosteroids (4) a follow-up with their physician

Spacer Devices for Metered Dose Inhalers Spacer devices have a chamber that receives the aerosol before it is inhaled. They serve two functions: a) to overcome e difficulties in coordinating the timing of the inhaler actuation and inhalation, b) to slow down the speed of delivery of the aerosol into the mouth so that less of the drug impacts in the throat.

Prevention Smoking prevention or cessation Prevention of exacerbations Long-term suppressive antibiotics are not beneficial. Inhalation glucocorticoids id should be considered in patients with frequent exacerbations or in patients with an asthmatic component. Vaccination against influenza and pneumococcal infection