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PULMONARYQ

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Definition and epidemiology (NEJM 2004;350:26)

•  Progressive airflow limitation caused by airway and parenchymal inflammation

Pathogenesis (Lancet 2003;362:1053)

•  Cigarette smoke (centrilobular emphysema, affects 15–20% of smokers)

•  Recurrent airway infections

•  ɑ1-antitrypsin defic.: early-onset panacinar emphysema, 1–3% of COPD cases. Suspect if age <45, lower lungs affected, extrathoracic manifestations (liver disease [not if MZ subtype], FMD, pancreatitis). ✓ serum AAT level (nb, acute phase reactant).

Clinical manifestations

•  Chronic cough, sputum production, dyspnea; later stages → freq exac., a.m. HA, wt loss

•  Exacerbation triggers: infxn, other cardiopulmonary disease, incl. PE (Annals 2006;144:390)

Infxn: overt tracheobronchitis/pneumonia from viruses, S. pneumoniaeH. influenzaeM. catarrhalis or triggered by changes in strain of colonizers (NEJM 2008;359:2355)

•  Physical exam: ↑ AP diameter of chest (“barrel-chest”), hyperresonance, ↓ diaphragmatic excursion, ↓ breath sounds, ↑ expiratory phase, rhonchi, wheezes during exacerbation: tachypnea, accessory muscle use, pulsus paradoxus, cyanosis

Diagnostic studies

•  CXR (see Radiology inserts): hyperinflation, flat diaphragms, ± interstitial markings & bullae

•  PFTs: Obstruction: ↓↓ FEV1, ↓ FVC, FEV1/FVC <0.7 (no sig Δ post bronchodilator), expiratory scooping of flow-volume loop; Hyperinflation: ↑↑ RV, ↑ TLC, ↑ RV/TLC;

Abnormal gas exchange: ↓ DLCO (in emphysema)

•  ABG: ↓ PaO2, ± ↑ PaCO2 (in chronic bronchitis, usually only if FEV1 <1.5 L) and ↓ pH

•  ECG: PRWP, S1S2S3, R-sided strain, RVH, ↑ P waves in lead II (“P pulmonale”)

Chronic treatment (NEJM 2010;362:1407; Lancet 2012;379:1341)

•  Bronchodilators (first-line therapy): anticholinergics, β2-agonists (BA), theophylline

Long-acting (LA) anticholinergic (LAA, tiotropium): ↓ exac., ↓ admit, ↓ resp failure (NEJM 2008;359:1543), better than ipratropium or LABA as mono Rx (NEJM 2011;364:1093)

LABA: ~15% ↓ in exacerbations, ↓ FEV1 decline, trend toward ↓ mort. (NEJM 2007;356:775)

LABA + inh steroid: ? ↓ mort. (NEJM 2007;356:775; AJRCCM 2008;177:19)

LAA + LABA + inh steroid: ↑ FEV1, ↓ COPD admits (Annals 2007;146:545)

•  Corticosteroids (inhaled, ICS): ~20% ↓ in exacerb if FEV1 <2.0 L (Chest 2009;136:1029) may slow ↓ FEV1, but more so in combo with LABA (NEJM 2007;356:775); ↑ in PNA (not seen w/ budesonide; Lancet 2009;374:712); no Δ in mort. w/ ICS alone (NEJM 2007;356:775)

•  Antibiotics: daily azithro ↓ exacerb, but not yet routine (NEJM 2011;365:689 & 2012;367:340)

•  Mucolytics: no Δ FEV1, but ? ↓ exacerbation rate (Lancet 2008;371:2013)

•  Oxygen: if PaO2 ≤55 mmHg or SaO2 ≤89% (during rest, exercise or sleep) to prevent cor pulmonale; only Rx proven to ↓ mortality (Annals 1980;93:391; Lancet 1981;i:681)

•  Prevention: Flu/Pneumovax; smoking cessation (eg, varenicline, bupropion) → 50% ↓ in lung function decline (AJRCCM 2002;166:675) and ↓ long-term mortality (Annals 2005;142:223)

•  Rehabilitation: ↓ dyspnea and fatigue, ↑ exercise tolerance, ↓ QoL (NEJM 2009;360:1329)

•  Experimental

Lung volume reduction surgery: ↑ exer. capacity, ↓ mort. if FEV1 >20%, upper-lobe, low exer. capacity (NEJM 2003;348:2059); bronchoscopic w/ endobronchial valves w/ mixed benefits: ↑ lung fxn but ↑ PNA, exacerb, hemoptysis (NEJM 2010;363:1233)

Roflumilast (PDE-4 inhibitor): ↑ FEV1 when added to standard Rx (Lancet 2009;374:685&695)

Nocturnal BiPAP: may improve survival, ? decrease QoL (Thorax 2009;64:561)

•  Lung transplant: ↑ QoL and ↓ sx (Lancet 1998;351:24), ? survival benefit (Am J Transplant 2009;9:1640)

Staging and prognosis

•  FEV1: 50–80% predicted → 3-y mort. ~11%; 30–50% → ~15%; <30% → ~24%

•  BODE 10-pt scale (Lancet 2009;374:704); HR 1.62 for resp mort., 1.34 mort. for each 1-pt ↑ BMI: ≤21 (+1)

Obstruction (FEV1): 50–64% (+1), 36–49% (+2), ≤35% (+3)

Dyspnea (MMRC scale): walking level (+1), after 100 yd (+2), with ADL (+3)

Exs capacity (6-min walk): 250–349 m (+1), 150–249 (+2), ≤149 (+3)

superior to FEV1 (NEJM 2004;350:1005); can predict survival from LVRS (Chest 2006;129:873)

•  mMRC score: ≥2 defined as walking slowly b/c breathlessness or having to stop to catch breath walking level

•  Ratio of diam PA/aorta >1 associated with ~3× ↑ risk of exacerbations (NEJM 2012;367:913)

EXACERBATION