Nejm 2004;350:2689; 2000;343:276

Cause:Bronchitis/hyperreactive airways from smoking, recurrent infections; cystic fibrosis (Cystic Fibrosis (Mucoviscidosis); ₁-antitrypsin deficiency (₁-ATD) (Nejm 2009;360:2749; 1993;328:1392), autosomal recessive (Nejm 1977;296:1190), and usually combined with smoking in heterozygote (Ann IM 2002;136:270), occurs even w/o smoking in homozygote

Pathophys:

Proteases, esp elastase from polys and macrophages, are balanced by ₁-antitrypsin, the primary antielastase; hence functional deficiencies cause loss of lung elasticity; and smoke both inactivates it (Ann IM 1987;107:761; Nejm 1983;309:694) and increases the polys in the lung capillaries (Nejm 1989;321:924). Thus elasticity is decreased, causing loss of connective tissue support that normally keeps bronchioles open; when expiratory pressure is increased, that loss of elastic support causes bronchiole collapse and resulting “ball valving” entrapment of air and hence emphysema, along with V/Q imbalances, end-stage hypoventilation, and increased pCO₂. Goblet cell hyperplasia may contribute to bronchiolar plugging and initiate more of above. Recurrent infection causes progression (Nejm 2008;359:2355)

Classified now by global obstructive lung disease system (Am J Respir Crit Care Med 2001;163:1256)

Smoker-type onset usually after age 50 yr; males > females; increased prevalence in cold damp climates. Maternal smoking may increase incidence in offspring (Nejm 1983;309:699). ₁-ATD type: gene incidence ~5% in US (Nejm 1969;281:279); onset by age 45 yr

Sx: Dyspnea on exertion of arms more than legs (New Eng J Med 1986;314:1485); chronic productive cough with bronchitis not emphysema

Table 16.2 Symptoms of COPD (J Gen IM 1993;8:63)

Si: Barrel chest. Two extremes: "blue bloater" (CHF, hypoxia, and hypercarbia), to "pink puffer" (weight loss, low pCO₂, moderate decrease in pO₂ at rest and left-sided CHF, which may be occult) (New Eng J Med 1971;285:361)

Forced expiratory time over trachea >6 sec (75% sens/specif—Jama 1993;270:731)

Table 16.3 Signs of COPD (J Gen IM 1993;8:63)

Pink puffer has better prognosis than blue bloater because pulmonary hypertension is less (Nejm 1972;286:912)

Polycythemia; pulmonary hypertension (Pulmonary Hypertension (Primary and Secondary)), peptic ulcer disease (Nejm 1969;281:279), acute respiratory failure; hypophosphatemia, esp on ventilator, <1 mM/L (<1.5 mg %) impairs diaphragmatic contractility, treatable (Nejm 1985;313:420); exacerbations 3-4 ×/yr often caused by a new bacterial pathogen. Pulm embolus present in 25% of those w no obvious exacerbaton cause (Ann IM 2005;144:390)

Lab:

Bact:Chronically infected sputum with bronchitis

Path:Emphysema, centrilobular of secondary and tertiary respiratory bronchioles most commonly; in ₁-ATD, panlobular of primary lobules and PAS-positive staining inclusions in hepatocytes (Nejm 1975;292:176)

PFTs:Diffusion capacity decreased in emphysema, not bronchitis or asthma alone, due to loss of total alveolar/capillary membrane surface area; <55% of predicted correlates with hypoxia on exercise (Nejm 1984;310:1218); increased total lung capacity; decreased FEV₁/FVC; 7-min nitrogen washout with O₂ is prolonged

Serol:in ₁-ATD, SPEP shows decreased ₁ peak <0.2 gm (no false pos—Ann IM 1970;73:9)

Rx: (Guidelines—Ann IM 2007;147:633, 639) Stop smoking (Smoking Cessation) to prevent or stabilize progression, steroid inhalers not much help if don’t (Nejm 1999;340:1948); pulmonary rehab programs (Lancet 1996;348:1115; Ann IM 1995;122:823) improve quality of life and endurance (Chest 1997;111:1077). Cardioselective -blockers safe if needed for ASHD (ACP J Club 2006;144:66; 2001;135:87)

Vaccination vs influenza, pneumococcus, and eventually maybe RSV and para-influenza (Jama 2000;283:499)

O₂: if pO₂ <55 mm Hg, 1-2 L/min nasal prongs or enough to maintain O₂ sats without driving up pCO₂; round the clock O₂ to increase survival (Ann IM 1983;99:519). CHF rx with digoxin, if L- but not if R-sided failure, helps (Ann IM 1981;95:283)

Meds (Nejm 2004;350:2689; Jama 2003;290:2301, 1313):

• 1st: Steroid inhalers prophylaxis and helpful to tx bronchoreactive component (Asthma) (Nejm 1992;327:1413), help sx but don’t slow progression (controversial—ACP J Club 2004;140:57) and incr osteoporosis (Nejm 2000;343:1902)
• 2nd: Rapid-acting catechol bronchodilators (Asthma) w iprotropium, via nebulizers or inhalers for acute asthmatic sx
• or anticholinergics:
• ipratropium (Atrovent) 2-3 puffs qid (Nejm 1988;319:486; Med Let 1987;29:71);
• tiotropium (Spiriva) (Nejm 2011;364:1093) 18 µgm pwdr inhaler qd improves PFTs and quality of life and decr exacerbations but does not reduce rate of FEV₁ decline (Nejm 2008;359:1543), often used w Advair; $120/mo
• or long-acting -agonists only in combination with inhaled corticosteroids (Ann IM 2006;144:904, 936)
• or other options:
• Theophylline preparations; acutely of no benefit (BMJ 2003;327:643) but help ~50% of chronics (Chest 1993;104:1101) via increased diaphragmatic muscle strength and by dampening sense of dyspnea, as can opiates (Nejm 1995;333:1547)
• Antibiotics prophylactically: Tm/S, tetracyclines, or amoxicillin at 1st si of cold, fever, or change in sputum (Jama 1995;273:957; Med Let 1980;22:68)
• Continuous O₂ if resting hypoxia <PaO₂ of 55 mm Hg
• Perhaps ₁-proteinase inhibitor for ₁-antitrypsin deficiency (Med Let 1988;30:29) iv weekly or monthly
• Proteolytics like acetylcysteine po (not inhaled) may work (BMJ 2001;322:1271)
• Surgical resection of bullae and/or severely impaired areas (Nejm 2000;343:239; 1996;334:1095, 1198); can improve diaphragm and accessory muscle effectiveness; may help only pts w low inspiratory resistances (Nejm 1998;338:1181) or those w predominant upper lobe disease AND low exercise capacity (Nejm 2003;348:2055, 2059, 2134, 2092)
• of acute exacerbation (Ann IM 2001;134:595, 600; Nejm 2002;346:988): chest xray then prn O₂, bronchodilators, steroids × 1-2 wk maximum, antibiotics (ampicillin, Tcn, Tm/S) (Nejm 2008;359:2355); no chest PT, mucolytics, or theophyllines