COPD OTHER THAN ASTHMA

See also "Asthma"

I. Lung volume reduction surgery for emphysema

  1. Usually reserved as last resort for pts with aggressive emphysema (FEV1 20-35% predicted; PaCO2 < 55mm Hg, no severe pulm HTN, previous pleurodesis, or severe comorbidities).
  2. 5-10% perioperative mortality
  3. In a trial of 48 pts with severe emphysema randomized to bilateral LVRS vs. medial tx, mortality at 6mo were not sig. diff, but sig. diff. in improvemenet in median FEV1, quality-of-life scores, and physical endurance (NEJM 343:239, 2000--JW)
  4. In a randomized trial of LVRS in 1,033 pts with advanced emphysema, initial subgroup analysis showed sig. higher 30d total mortality (RR 4.0) with surgery for the subgroup of pts considered "high risk" (FEV1 < 20% predicted and either homogeneously distributed emphysema on CT or DLCO < 20% predicted (National Emphysema Treatment Trial, NEJM 345:1075, 2001--JW)
  5. 1,218 pts with severe emphysema randomized to lung colume-reduction surgery vs. medical treatment; surgical group had sig. higher 90d mortality (7.9%
    vs. 1.3%) but no diff. in mortality after mean 29mo f/u. Surgical pts had sig. higher exercise capacity and health-related quality of life at 24mos.  (National Emphysema Treatment Trial; NEJM 348:2092, 2003--JW)

II. O2 for COPD (NEJM 328:1017, 1993--cited in AFP rvw 5/15/98)

  1. Recommended if PaO2 < 56mm Hg or SaO2 < 90% at rest, with exercise, or during sleep OR PaO2 56-59mm Hg or SaO2 < 91% with pulmonary HTN, cor pulmonale, mental or psychologic impairment, or polycythemia
  2. Medicare reimburses O2 for PaO2 < 56mm Hg or SaO < 89% OR PaO2 56-59mm Hg or SaO2 < 90% with cor pulmonale (as evidenced by "p pulmonale" on EKG, polycythemia, or CHF)
  3. Heliox (Helium-Oxygen mixture) for COPD
    1. Associated with increased exercise tolerance compared with standard air with identical oxygen content (J. Respir. Crit. Care Med. 173:865, 2006--AFP)

III. Chronic bronchitis

  1. Defined as daily productive cough > 3mos' duration during 2 consecutive years, with evidence of airways obstruction
  2. Airways obstruction results from excessive tracheobronchial mucus production and produces decrease in FEV1 and FEV1/FVC on spirometry
  3. 90% of pts have a smoking history
  4. Acute exacerbations of chronic bronchitis
    1. Usually described as increase in dyspnea, sputum volume and/or purulence, and fever in a pt with chronic bronchitis
    2. Commonly precipitated by bacterial infection (pneumococcus, H. flu, Moraxella catarrhalis)--though in > 50% of acute exacerbations, no organisms can be isolated (Am. Rev. Respir. Dis 146:1067, 1992--cited in rvw in AFP 5/15/98)
    3. Meta-analysis of 9 randomized trials of abx vs. placebo in AECB in 839 pts (tetracycline, ampicillin, chloramphenicol, or trimethoprim-sulfamethoxazole) showed evaluating outcomes such as days of illness, sx score, and change in PEFR, showed a very modest "effect size" on these outcomes of 0.22 (95% CI, 0.10 to 0.34), indicating a small benefit (about 0.25 SD) in the antibiotic-treated group (JAMA 273:957, 1995--abst)
    4. Ciprofloxacin for AECB
      1. 307 adults with asthma or other COPD and a new episode of purulent bronchitis randomized to ciprofloxain vs. PO cefuroxime x 14d; no sig. diff. in clinical resolution during f/u period (Clin. Inf. Dis. 27:722, 1998--JW)
      2. 376 adults aith AECB randomized to ciprofloxacin vs. clarithromycin; no sig. diff. in clinical resolution furing f/u period (Clin. Inf. Dis. 27:730, 1998--JW)
  1. Surfactant therapy
    1. 87 pts with chronic bronchitis but no other pulmonary disease including asthma, and FEV1 40-70% predicted randomized to nebulized synthetic surfactant 202.5mg-1215mg per day vs. isotonic saline placebo over 2wks. Sig. increases in FEV1 and FVC lasting at least 1wk after cessation of tx was seen in groups w/doses of 607.5mg/d and greater; no sig. diff. in sx improvement between surfactant and placebo groups (JAMA 278:1426, 1997--AFP)

IV. Inhaled short-acting beta-agonists, e.g. albuterol

  1. Provide symptom relief to the degree that bronchospasm is involved
  2. Regularly scheduled use no better than PRN use in improving quality of life, physical stamina, or exacerbation frequency in a rnadomized trial of 53 pts with COPD and FEV1 of < 70% predicted (Am. J. Resp. Crit. Care Med. 163:85, 2001--JW)
  3. See link above for info on possible cardiovascular adverse effects associated with use of these medications
  4. See below for data on comparisons with inhaled anticholinergics.

V. Inhaled Anticholinergics for symptomatic relief or maintenance

  1. In a systematic review of randomized trials comparing inhaled anticholinergics with inhaled short-acting beta-agonists for COPD, beta-agonist recipients had sig. higher incidence of both moderate (RR 2.02) and severe (RR 1.95) exacerbations; no advantage to combined therapy vs. anticholinergics alone (J. Gen. Int. Med. 21:1011, 2006--AFP)
  2. In a study in 7,400 pts with moderate-to-severe COPD randomized to inhaled tiotropium vs. salmeterol x 1y, tiotropium recipients had sig. lower annual incidence of exacerbations (0.64 vs. 0.72) and hospitalization (0.09 vs. 0.13); difference was present regardless of use of inhaled steroids.  (NEJM 364:1093, 2011-JW)

VI. Systemic Corticosteroids for COPD exacerbations: 2wk course is probably best

  1. 271 pts admitted w/COPD exacerbations randomized to steroids for 2wks vs. 8wks vs. placebo. Steroids consisted of methylprednisolone 125mg IV Q6h then tapering course of oral prednisone. Rate of tx failure (death, intubation, readmission for COPD, or intensified drug therapy) sig. higher w/placebo at 1mo (33% vs. 23%) and 3mos (48% vs. 37%) but not 6mos. No diff. between 2wk and 8wk groups, though 8wk groups DID have sig. increased rate of rehospitalization for secondary infections (NEJM 340:1941, 1999--JW)
  2. 56 pts (mean age 56y) hosp'd with acute exacerbations of non-asthma COPD randomized to prednisolone 30mg PO QD vs. placebo x 2wks; steroid group had greater increases at FEV1 over initial 5d of admission as well as shorter median hospital stay (7d vs. 9d) (Lancet 354:456, 1999--JW)
  3. In a randomized study in pts with COPD exacerbation randomized to methylprednisolone IV x 3d vs.10d (regimen was 0.5mg/kg IV Q6h x 3d then Q12h x 3d then QD x 4d), at 10d the 10d-tx group had sig. greater benefits in FEV1, PaO2, and dyspnea (Chest 119:726, 2001--AFP)
  4. 147 pts > 35yo being discharged after being seen at an emergency department for COPD exacerbation randomized to prednisone 40mg PO QD x 10d vs. placebo; all pts received PO antibiotics and inhaled albuterol & ipratropium.  30d incidence of "relapse" (ED or office visit) was 27% in prednisone vs. 43% in placebo group (sig.). (NEJM 348:2618, 2003--JW)
  5. In a Cochrane review, use of 7 RCTs of systemic corticosteroids for acute exacerbations of COPD concluded that corticosteroids were ass'd with significantly higher FEV1 72h after initiation of tx than placebo (Ann. Emerg. Med. 42:426, 2003--AFP)
  6. In a retrospective study in about 80,000 pts admitted to non-ICU beds with COPD exacerbations, those receiving oral prednisone (median 60mg total for first 2d), after adjustment for multiple potential confounders, had sig. lower incidence (RR 0.84) of incidence of treatment failure (need for mechanical ventilation after first 2d, death, or readmission for COPD within 30d) than those receiving parenteral steroids (median 600mg prednisone-equivalent over first 2d) (JAMA 303:2359, 2010-JW)

VII. Inhaled Steroids for COPD maintenance (click on link for info)--See also data on combination therapy inhaled steroids-salmeterol

VIII. Long-Acting Beta-Adrenergic Agonists for COPD maintenance

  1. Salmeterol inhaled 42mg BID associated with sig. greater improvements in pulmonary function, sx, and quality-of-life ratings c/w ipratropium inhaled 36mg QID or placebo in a randomized trial of pts with COPD and at least a 10-pack-year smoking history (oops, I forgot the reference!)
  2. 1465 pts with COPD (FEV1 25-70% of predicted; non-reversible) randomized to salmeterol 50ug inhaled BID, fluticasone 500ug inhaled BID, both, or double placebo.  At 1y, combination-therapy group had sig. greater increases in mean FEV1 (10%) than the salmeterol-alone or fluticasone-alone groups (2% for both).  Some symptom measures also showed a benefit with combination therapy (Lancet 361:449, 2003--JW)
  3. In a study in > 6,000 pts with COPD, h/o smoking, and FEV1 < 60% predicted randomized to inhaled salmeterol BID + fluticasone BID, either alone, or placebo, at 3y, there were no sig. diffs. in overall mortality among the groups, though combined therapy group had sig. lower incidence of hospitalization than the placebo group; both fluticasone-recipient groups had sig. higher incidence of pneumonia than the non-fluticasone-recipient groups (19% vs. 13%); combined-therapy group had sig. lower incidence of mod-severe COPD exacerbations than any of the other groups ("TORCH" Trial; NEJM 356:775, 2007--JW)

IX. Theophylline in COPD--Some benefit as an adjunct to inhaled long-acting beta agonists

  1. 943 pts with mod-severe COPD randomized to 12wks of inhaled salmeterol BID, oral sustained-release theophylline, or both; combo therapy ass'd with sig. better FEV1 than either tx alone; salmeterol alone better than theo alone; theo ass'd with sig. more GI side f/x than placebo (Chest 119:1661, 2001--JW)

X. Oral Mucolytics (e.g. Acetylcysteine)

  1. A systematic review of 23 randomized trials involving 4143 pts with COPD showed that routine use of oral mucolytics was ass'd with sig. fewer exacerbations c/w placebo (1.9/pt/yr vs. 2.7/pt/yr); also mean days of illness/mo and mean days/mo taking abx were both significantly reduced (BMJ 322:1271, 2001--JW)

XI.Phosphodiesterase-4 inhibitors

  1. Decrease lung inflammation in COPD
  2. Roflumilast (Daliresp)
    1. In a study in 1,400 pts with moderate-to-severe COPD randomized to the phosphodiesterase-4 inhibitor roflumilast 250-500 micrograms/d vs. placebo, after 24wks, roflumilast had sig. greater improvement in both pre- and post-bronchodilator FEV1; also had sig. fewer minor exacerbations (no diff. in moderate or severe exacerbations). Roflumilast was associated with sig. greater incidence of diarrhea than placebo) (Lancet 366:563, 2005--JW)
    2. FDA-approved (as of 2011) for pts with severe COPD associated with chronic bronchitis and h/o exacerbations

XII. N-acetylcysteine

  1. In a study in 523 pts with COPD randomized to n-acetylcysteine 600mg/d vs. placebo, at 3y, there was no sig. diff. in frequency of exacerbations, rate of decline in FEV1 or vital capacity, or quality of life (Lancet 365:1552, 2005--JW)

XIII. Empiric antibiotics for COPE exacerbations

  1. In a retrospective cohort study of 85,000 pts admitted for COPD exacerbation, those who reecived antibiotics had sig. lower incidence of mechanical ventilation (1.1% vs. 1.8%), 30d readmission (7.9% vs.8.8%), and all-cause mortality (1.0% vs. 1.6%) (JAMA 303:2035, 2010-JW)