6Dominant Clinical Forms of COPD Pulmonary emphysemaChronic bronchitisMost patients exhibit a mixture of symptoms and signs
7COPD - Advanced Dx secondary polycythemia cyanosis tremor somnolence and confusion due to hypercarbiaSecondary pulmonary HTN w or w/o cor pulmonale
8COPD Treatment Strategy Elimination of extrinsic irritantsbronchodilator & glucocorticoid therapyAntibioticsMobilization of secretions“respiratory vaccines”Oxygen therapy - if oxygen saturation <90% at rest on room air
11A-a gradient A-a gradient = predicted pO2 – observed PO2 PAO2 = (FIO2 X 713) – (PaCO2/0.8) at sealevelPAO2 = 150-(PaCO2/0.8) at sealevel on room airNormal range 10-15mm > 30 years of ageNormal range 8mm < 30 years of ageIncreased A-aDO2=diffusion defectRight to left shuntV/Q mismatch
12ExamplesA 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, PCO2 = 70mmHg, PO2=50mmHg, HCO3=24mEq/L;patient2- pH =7.31, PCO2=50mmHg, PO2=50mmHg, HCO3=25mEq/L
13Comment The A-a gradient calculation for patient 1 is as follows: A-a DO2 = PAO2 – PaO2PAO2 = 150 – (1.25x PCO2)PAO2 = 150 – (1.25x 70)PAO2 = 62A-a =62 – 50A-a = 12
14CommentThe calculation reveals a normal gradient, indicating that the etiology for hypoxemia and hypoventilation is extrinsic to the lung itself.
15Comment The A-a gradient calculation for patient 2 is as follows: PAO2 = 150 – (1.25 x PCO2)PAO2 = 150 – (1.25 x 50)PAO2 = 150 – 63PAO2 = 87Therefore, A-a = 87 – 50 =37 (an abnormally increased gradient)
16CommentWe 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.
17CommentPatient 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 overdose was complicated by aspiration pneumonitis and that the patient required treatment with antibiotics in addition to mechanical ventilation.
19DefinitionA disease state characterized by airflow limitation that is not fully reversibleConditions include:Emphysema:(anatomically defined condition characterized by destruction and enlargement of the lung alveoli)Chronic bronchitis:clinically defined condition with chronic cough and phlegmSmall-airways disease:condition in which small bronchioles are narrowed
20Epidemiology • Affects > 16 million persons in the U.S. • Fourth leading cause of death in the U.S.• Affects > 16 million persons in the U.S.• Global Initiative for Chronic Obstructive 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.
21Epidemiology>70% of COLD-related health care expenditures go to emergency department visits and hospital care (>$10 billion annually in the U.S.).
22EpidemiologySexHigher prevalence in men, probably secondary to smokingPrevalence of COLD among women is increasing as the gender gap in smoking rates has diminished.
23Epidemiology Age Higher prevalence with increasing age Dose–response relationship between cigarette smoking intensity and decreased pulmonary function
24Risk Factors Cigarette smoking is a major risk factor. Cigar and pipe smokingPassive (secondhand) smoking Associated with reductions in pulmonary function Its status as a risk factor for COLD remains uncertain
25Occupational exposures to dust and fumes (e.g., cadmium) Likely risk factorsThe magnitude of these effects appears substantially less important than the effect of cigarette smoking.Ambient air pollutionThe relationship of air pollution to COLD remains unproven.
26Genetic factors α1 antitrypsin (α1AT) deficiency Common M allele: normal levelsS allele: slightly reduced levelsZ allele: markedly reduced levelsNull allele: absence of α1AT (rare)Lowest levels of α1AT are associated with incidence of COLD; α1AT deficiency interacts with cigarette smoking to increase risk.
27Distributions of forced expiratory volume in 1 s (FEV1)values in a general population sample, stratified by pack-years of smoking
28Etiology COLDCausal relationship between cigarette smoking and development of COLD has been proven: however, the response varies considerably among individuals.
29COLD exacerbation Bacterial infections Viral infections (one-third) 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%)
30Symptoms & Signs • 3 most common: Cough Sputum production Exertional dyspnea, frequently of long duration
31signs and symptoms Dyspnea at rest Prolonged expiratory phase and/or expiratory wheezing on lung examinationDecreased breath soundsBarrel chestLarge lung volumes and poor diaphragmatic excursion, as assessed by percussionUse of accessory muscles of respirationPursed lip breathing (predominantly emphysema)Characteristic "tripod" sitting position to facilitate the actions of the sternocleidomastoid, scalene, and intercostal musclesCyanosis, visible in lips and nail beds
32Paradoxical respiration Systemic wasting Significant weight loss Bitemporal wasting Diffuse loss of subcutaneous adipose tissueParadoxical 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 and edema. Most patients have elements of each.
33Advanced disease: signs of cor pulmonale Elevated jugular venous distention Right ventricular heave Third heart sound Hepatic congestion Ascites Peripheral edema
35ConsiderationsCOLD is present only if chronic airflow obstruction occurs. Chronic bronchitis without chronic airflow obstruction is not COLD.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.
36ConsiderationsProblems other than COLD should be suspected when hypoxemia is difficult to correct with modest levels of supplemental oxygen.Lung cancer Clubbing of the digits is not a sign of COLD.In patients with COLD, development of lung cancer is the most likely explanation for newly developed clubbing.
37Chronic Bronchitis Chronic lower airway inflammation Increased bronchial mucus productionProductive coughUrban male smokers > 30 years old
38Chronic Bronchitis Blue Bloater Mucus, swelling interfere with ventilationIncreased CO2, decreased 02Cyanosis occurs early in diseaseLung disease overworks right ventricleRight heart failure occursRHF produces peripheral edemaBlue Bloater
39Emphysema Loss of elasticity in small airways Destruction of alveolar wallsUrban male smokers > years old
40Emphysema Pink Puffer Lungs lose elastic recoil Retain CO2, maintain near normal O2Cyanosis occurs late in diseaseBarrel chest (increased AP diameter)Thin, wastedProlonged exhalation through pursed lipsPink Puffer
41COPD Management Oxygen Assist ventilations as needed Monitor carefully Some COPD patients may experience respiratory depression on high concentration oxygenAssist ventilations as needed
42Diagnostic Approach Initial assessment History and physical examination (Signs & Symptoms)Pulmonary function testing to assess airflow obstructionRadiographic studies
43Assessment of exacerbation History Fever Change in quantity and character of sputum ill contacts Associated symptoms Frequency and severity of prior exacerbations
44Assessment of exacerbation 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
45Hospitalization recommended for: Radiographic studies Chest radiography focal findings (pneumonia, atelectasis)Arterial blood gases Hypoxemia HypercapniaHospitalization recommended for: Respiratory acidosis and hypercarbia Significant hypoxemia Severe underlying disease Living situation not conducive to careful observation and delivery of prescribed treatment
46ABG and oximetryAlthough 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 0.08 units/10 mmHg acutely and 0.03 units/10 mmHg in the chronic state.
47Laboratory Tests Elevated hematocrit suggests chronic hypoxemia. Serum level of α1AT should be measured in some patients.o Presenting at ≤ 50 years of ageo Strong family historyo Predominant basilar diseaseo Minimal smoking historyo Definitive diagnosis of α1AT deficiency requires PI type determination. Typically performed by isoelectric focusing of serum, which reflects thegenotype at the PI locus for the common alleles and many of the rare PIalleles Molecular genotyping can be performed for the common PI alleles (M, S,and Z).Sputum gram stain and culture (for COLD exacerbation)
48Imaging • Chest radiography • Chest CT Emphysema: obvious bullae, paucity of parenchymal markings, or hyperlucencyHyperinflation: increased lung volumes, flattening of diaphragmDoes not indicate chronicity of changes• Chest CTDefinitive test for establishing the diagnosis of emphysema, but not necessary to make the diagnosis
49Diagnostic Procedures Pulmonary function tests/spirometryChronically 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 ratesIncreases in residual volumeIncreases in ratio of residual volume to total lung capacityIncreased total lung capacity (late in the disease)Diffusion capacity may be decreased in patients with emphysema.Electrocardiographymay detect signs of ventricular hypertroph
50ClassificationGOLD stageClassification based on pathologic type
51GOLD stage I II III IV Severity: at risk Severity: at risk Symptoms: chronic cough, sputum production Spirometry: normalI Severity: mild Symptoms: with or without chronic cough or sputum production Spirometry: FEV1:FVC < 0.7 and FEV1 ≥ 80% predictedII Severity: moderate Spirometry: FEV1:FVC < 0.7 and FEV1 50–80% predictedIII Severity: severe Spirometry: FEV1:FVC < 0.7 and FEV1 30–50% predictedIV Severity: very severe Spirometry:FEV1:FVC < 0.7 and FEV1 < 30% predicted orFEV1 < 50% predicted with respiratory failure or signs of right heart failure
52Treatment Approach General Only 2 interventions have been demonstrated to influence the natural history. Smoking cessation Oxygen therapy in chronically hypoxemic patientsAll other current therapies are directed at improving symptoms and decreasing frequency and severity of exacerbations.Therapeutic response should determine continuation of treatment.
53Specific Treatments Stable-phase COLD, pharmacotherapy BronchodilatorsUsed to treat symptomsThe inhaled route is preferred.Side effects are less than with parenteral delivery.Theophyllline: various dosages and preparations; typical dose 300–600 mg/d, adjusted based on levels
54Specific Treatments Stable-phase COLD, pharmacotherapy Anticholinergic agentsTrial of inhaled anticholinergics is recommended in symptomatic patients.Side effects are minor.Improve symptoms and produce acute improvement in FEVDo not influence rate of decline in lung functionIpratropium bromide (short-acting anticholinergic) (Atrovent) Inhaled: 30-min onset of action; 4-h duration Atrovent: metered-dose inhaler; 18 μg per inhalation; 1–2 inhalations qid
55Specific Treatments Stable-phase COLD, pharmacotherapy Tiotropium (long-acting anticholinergic) (Spiriva) Spiriva: powder via handihaler; 18 μg per inhalation; 1 inhalation qdSymptomatic benefitLong-acting inhaled β-agonists, such as salmeterol, have benefits similar to ipratropium bromide. More convenient than short-acting agents
56Specific Treatments Stable-phase COLD, pharmacotherapy Addition of a β-agonist to inhaled anticholinergic therapy provides incremental benefit.Side effects Tremor TachycardiaSalmetrol (Serevent): Powder via diskus; 50-μg inhalation every 12 hFormoterol (Foradil): Powder via aerolizer; 12-μg inhalation every 12 h
57Specific Treatments Stable-phase COLD, pharmacotherapy Albuterol (short-acting β-agonist) (Proventil HFA, Ventolin HFA, Ventolin, Proventil) Metered-dose inhaler (or in nebulizer solution); 180-μg inhalation every 4–6 h as neededCombined β-agonist/anticholinergic: albuterol/ipratropium (Combivent) Metered-dose inhaler (also available in nebulizer solution); 120 mcg/21 μg per inhalation 1–2 inhalations qid
58Inhaled glucocorticoids Specific Treatments Stable-phase COLD, pharmacotherapyInhaled glucocorticoidsReduce 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 FEV1Consider 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.Side effects Increased rate of oropharyngeal candidiasis Increased rate of loss of bone density
60Supplemental O2 is the only therapy demonstrated to decrease mortality OxygenSupplemental O2 is the only therapy demonstrated to decrease mortalityIn 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.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.
62Parenteral corticosteroids Long-term use of oral glucocorticoids is not recommended.Side effects Osteoporosis, fracture Weight gain Cataracts Glucose intolerance Increased risk of infectionPatients 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.
63TheophyllineProduces modest improvements in expiratory flow rates and vital capacity and a slight improvement in arterial oxygen and carbon dioxide levels in moderate to severe COPDSide effects Nausea (common) Tachycardia Tremor
64Specific Treatments Stable-phase COLD, pharmacotherapy Other agentsN-acetyl cysteine Used for its mucolytic and antioxidant (current clinical trials) propertiesIntravenous α1AT augmentation therapy for patients with severe α1AT deficiencyAntibiotics Long-term suppressive or "rotating" antibiotics are not beneficial
65Specific Treatments Stable-phase COLD, nonpharmacologic therapies Smoking cessationAll patients with COLD should be strongly urged to quit and educated about the benefit of cessation and risks of continuation.Combining pharmacotherapy 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.
66Specific Treatments Stable-phase COLD, nonpharmacologic therapies General medical careAnnual influenza vaccinePolyvalent pneumococcal vaccine is recommended, although proof of efficacy in COLD patients is not definitive.
67Specific Treatments Stable-phase COLD, nonpharmacologic therapies Pulmonary rehabilitationImproves health-related quality of life, dyspnea, and exercise capacityRates of hospitalization are reduced over 6 to 12 months.
68Specific Treatments Stable-phase COLD, nonpharmacologic therapies Lung volume reduction surgeryProduces symptomatic and functional benefit in selected patients Emphysema Predominant upper lobe involvementContraindications 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% of predicted (due to increased mortality)
69Specific Treatments Stable-phase COLD, nonpharmacologic therapies Lung transplantationCOLD 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 of emphysema and presence of pulmonary hypertension are not contraindications.Unresolved issues include whether single- or double-lung transplantation is preferred.
70exacerbation of COPD The goals of emergency therapy correct tissue oxygenationalleviate reversible bronchospasmtreat the underlying etiology of the exacerbation
71Administer controlled oxygen therapy correct or prevent life-threatening hypoxemia, PaO2 greater than 60 mm Hg or an SaO2 greater than 90 percentImprovement after administration of supplemental oxygen may take 20 to 30 min to achieve a steady state
72B 2-Agonists and anticholinergic agents are first-line therapies in the management of acute, severe COPD
73CORTICOSTEROIDSshort 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-moderate exacerbationsHyperglycemia is the most common adverse effect
74ANTIBIOTICSAll current guidelines recommend antibiotics if there is evidence of infection,change in volume of sputum and increased purulence of sputumbenefits are more apparent in more severe exacerbationsAntibiotic choices should be directed at the most common pathogens known to be associated with COPD exacerbationStreptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalisduration of treatment;(3 to 14 days )
75METHYLXANTHINES theophylline and aminophylline severe exacerbation when other therapy has failed or in patients already using methylxanthines who have subtherapeutic drug levelsThe bronchodilation effect of aminophylline is limited,therapeutic range is narrow
76In patients who regularly use theophylline, IV loading dose 5 to 6 mg/kg usually required to obtain an initial serum concentration of 8 to 12 macg/mLIn patients who regularly use theophylline,a mini-loading dose should be administered:(target concentration–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 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
77Summary for ED Management Assess severity of symptom Administer controlled oxygen therapy Perform arterial blood gasmeasurement after 20–30 min if SaO2 remains <90% or if concerned about symptomatic hypercapnia
78Administer bronchodilators B2-agonists and/or anticholinergic agents by nebulization or MDI with spacer Consider adding intravenous methylxanthine, if neededAdd corticosteroids ( Oral or intravenous)Consider antibiotics If increased sputum volume, change in sputum color, fever, or suspicion of infectious etiology of exacerbation
79Laboratory evaluation Chest x-ray CBC with differential Electrolytes Arterial blood gases ECG as needed
80At 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
81Indications for Invasive Mechanical Ventilation Severe dyspnea with use of accessory muscles and paradoxical abdominal motionRespiratory frequency >35 breaths per minLife-threatening hypoxemia: PaO2 <50 mm Hg (<5.3 kPa) or PaO2/FIO2 <200 mm Hg Severe acidosis (pH <7.25) and hypercapnia (PaCO2 >60 mm Hg or >8.0 kPa)Respiratory arrestSomnolence, impaired mental statusCardiovascular complications (hypotension, shock, heart failure)NIPPV failure
82Indications for ICUSevere dyspnea that responds inadequately to initial emergency therapyConfusion, lethargy, comaPersistent 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
83Indications for Hospital Admission Marked increase in intensity of symptoms, such as sudden development of resting dyspneaSevere background of COPDOnset of new physical signs (e.g., cyanosis, peripheral edema)Failure of exacerbation to respond to initial medical managementSignificant comorbiditiesNewly occurring arrhythmiasDiagnostic uncertaintyOlder ageInsufficient home support
84discharge to home adequate supply of home oxygen, if needed adequate and appropriate bronchodilator treatmentshort course of oral corticosteroidsa follow-up with their physician
85Spacer 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 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.
86Prevention • Smoking prevention or cessation • Prevention of exacerbationsLong-term suppressive antibiotics are not beneficial.Inhalation glucocorticoids should be considered in patients with frequent exacerbations or in patients with an asthmatic component.• Vaccination against influenza and pneumococcal infection