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  • A 29-year-old man presents to the emergency department with severe pleuritic chest pain. He tells the resident that he is worried he might have another collapsed lung. His temperature is 98.7°F (37.1°C), blood pressure is 118/78 mmHg, pulse is 119/min, respirations are 31/min, and oxygen saturation is 85% on room air. On examination, he appears cachectic. A chest radiograph is obtained. 
Introduction
  • Clinical definition
    • chronic obstructive pulmonary disease (COPD) is defined as persistent airflow limitation due to mixture of small airway disease and parenchymal destruction
      • early classifications distinguished emphysema and chronic bronchitis
      • no longer distinguished but helpful to separate for pathophysiologic understanding and clinical management
    • emphysema is defined by alveolar wall destruction and dilation that presents in 2 forms
      • centrilobular
        • almost always due to smoking
      • panlobular/panacinar
        • rare and caused by alpha-1-antitrypsin deficiency
          • misfolded alpha-1-antitrypsin (AAT), which normally inhibits elastase
          • without AAT, elastase is over active and destroys elastic tissues
          • can accumulate in hepatocytes and cause cirrhosis
  • Epidemiology
    • demographics
      • males > females
      • 4th most common cause of death globally
    • risk factors
      • tobacco use (most common)
      • air pollution
      • occupational exposure
      • AAT deficiency
  • Pathogenesis
    • damage to airways distal to terminal bronchiole (i.e., acinus)
    • abnormal dilation of airspaces and destruction of alveoli walls due to proteinases (i.e., elastase)
    • decreased alveolar and capillary surface area, which decreases gas exchange
Presentation
  • Symptoms 
    • dyspnea
    • mild cough
    • fatigue
    • hyperventilation
  • Physical exam
    • "pink puffers"
      • non-cyanotic
      • cachectic
      • pursed-lip breathing
    • accessory muscle use
    • hypoxia
    • barrel chest
    • decreased breath sounds
    • end-expiratory wheezing and/or prolonged expiration
    • signs of cirrhosis if associated with AAT deficiency
Studies
  • Diagnostic testing
    • imaging
      • chest radiograph
        • not required for routine diagnosis
        • hyperinflation/flattened diaphragm
        • bullae and/or blebs
        • may have decreased lung markings
      • computed tomography
        • not necessary for management but can determine classification of emphysema (centrilobular or panacinar)
    • studies
      • pulmonary function tests (PFTs) 
        • best initial test
        • decreased FEV1 / FVC (< 0.7) that is incompletely reversible
          • obstructive pattern
          • diagnostic
          • FEV1 = forced expiratory volume
          • FVC = forced vital capacity
        • decreased % FEV1
          • used to categorize severity based on Global initiative for chronic Obstructive Lung Disease (GOLD)
            • mild: > 80%
            • moderate: 50-79%
            • severe: 30-49%
            • very severe: < 30%
        • normal or decreased FVC
        • increased total lung capacity (TLC)
          • more than with chronic bronchitis
        • decreased DLCO (vs. normal in chronic bronchitis)
          • DLCO = diffusing capacity of the lungs for carbon monoxide
      • arterial blood gas (ABG)
        • indicated for O2 saturation < 92%, altered mental status, or acute exacerbation
        • hypoxemia
          • decreased PO2
          • may cause increased hemoglobin/polycythemia
        • acute or chronic respiratory acidosis
          • increased PCO2 (hypercapnia) due to retention
Differential
  • Asthma 
    • distinguishing factor
      • obstructive pattern on PFTs are reversible after administration of inhaled bronchodilator
  • Bronchiectasis 
    • distinguishing factor
      • computed tomography (CT) is gold standard for diagnosis
        • large internal bronchial diameter, thickened bronchial wall, and altered airway geometry
        • "tram-track" and "signet-ring" signs
  • Interstitial lung disease (ILD) 
    • distinguishing factor
      • restrictive lung pattern on PFTs

 

Treatment
  • First-line
    • conservative
      • smoking cessation
        • greatest impact on mortality
      • home O2
        • indicated if resting PaO2 < 55 mmHg or SaO2 <89%
      • flu and pneumococcal vaccines
    • pharmacological 
      • step-wise depending on GOLD classification of disease severity
        • mild
          • short-acting inhaled bronchodilators
          • short-acting inhaled beta-agonist (e.g., albuterol) as needed
          • short-acting inhaled anticholinergic (e.g., ipratropium) as needed
          • most patients will present in more advanced stages
        • moderate
          • long-acting inhaled bronchodilator
          • long-acting beta-agonist (e.g., salmeterol or formoterol)
          • long-acting anticholinergic (e.g., tiotropium)
          • can be used in combination
        • severe
          • inhaled corticosteroid (e.g., budesonide or fluticasone) + long-acting bronchodilator
        • very severe
          • triple therapy
            • inhaled corticosteroid + long-acting anticholinergic + long-acting beta-agonist
          • may require roflumilast
            • phosphodiesterase (PDE)-4 inhibitor
          • theophylline
            • PDE inhibitor and adenosine receptor blocker
            • indicated for severe and refractory disease
            • low therapeutic index
        • AAT deficiency
          • IV pooled AAT
  • Second-line
    • lung resection or transplantation
      • may be beneficial in severe cases refractory to medical management

 

Complications
  • Acute exacerbation   
  • Pneumothorax 
    • caused by rupture of bullae

 

 

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Questions (3)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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Topic COMMENTS (4)
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