Contents

Search

chronic obstructive pulmonary disease (COPD)

Patients with COPD often fall into 1 of 2 classes: Emphysema (pink puffers) or chronic bronchitis (blue bloaters). [64] Classification: - Global Initiative for Chronic Obstructive Lung Disease - GOLD1 (mild) FEV1 >= 80% of predicted - GOLD2 (moderate) FEV1 50-80% of predicted - GOLD3 (severe) FEV1 30-50% of predicted - GOLD4 (very severe) FEV1 < 30% of predicted - disease severity (ACP) [3] - symptoms - airflow obstruction on spirometry - acute COPD exacerbations - comorbidities - heterogeneity - emphysema - chronic bronchitis - obliterative bronchiolitis - asthmatic bronchitis Etiology: 1) chronic exposure to airway irritants a) smoking (cigarette smoke is the most important risk factor [3]) b) environmental/occupational exposures [101] - publishing - mining - office & administrative support - transportation & material moving jobs (for women) - biomass fuels (developing coutries, Haiti) - air pollution [121] 2) acute exacerbations (see COPD exacerbation) * a healthy diet appears to mitigate risk of COPD [56] Epidemiology: - onset in midlife - 12% of never-smokers > 40 years of age - 4th leading cause of death in older patients [44] - allelic variation at the Arg16Gly locus of the ADRB2 gene (beta2-adrenergic receptor) in blacks do not seem to affect response to long-acting beta agonists (LABA) [60] - 62% false positive diagnosis; post-bronchodilator FEV1/FVC not < 70% [104] Pathology: 1) obstruction to airflow 2) airway collapse during expiration a) increased intrathoracic airway pressure during expiration b) loss of elastic recoil of lungs c) leads to air trapping & hyperinflation 3) bronchospasm a) increased bronchomotor tone in smooth muscles of airway b) mediators: vagus nerve, extrinsic allergens, cytokine release, external & physical chemical injury, airway hypothermia 4) mucosal inflammation & edema - neutrophil & CD8-mediated inflammation [79] 5) mucus gland hypertrophy & mucus plugging Clinical manifestations: 1) dyspnea [16] a) persistent & progressive b) generally worse with exercise c) described by patient 'increased effort to breathe' 'heaviness' 'air hunger' 'gasping' d) respiratory failure may occur 2) fatigue 3) chronic bronchitis a) chronic cough - may be intermittent & non-productive [44] b) chronic sputum production [16] - sputum may be increased with exacerbations 4) purse-lip breathing & other manifestations of emphysema 5) does not fluctuate much over a period of several months* 6) weight loss, muscle atrophy & weakness are common with severe COPD [3] - patients with COPD are hypermetabolic likely due to increased work of breathing [130] 7) smokers over 40 years of age may initially present with lower-respiratory tract symptoms [43] 8) 15% of COPD patients have asthma overlap syndrome [65] 9) wheezing * distinguishing feature from asthma Laboratory: 1) arterial blood gas (ABG) if FEV1 < 50% predicted a) hypercarbia over baseline b) pH < 7.30 c) carboxyhemoglobin level to identify continued smoking 2) serum alpha-1 antitrypsin all patients [3] a) caucasian & < 45 years of age [16] b) absence of risk factors (smoking, occupational dust) c) basilar lung predominance of emphysema 3) eosinophil count [111] Special laboratory: 1) spirometry confirms diagnosis (NEJM) [128] a) obstructive pattern - FEV1, FEV1/FVC & FEF[25-75], measures of expiratory airflow are diminished - post bronchodilator FEV1/FVC < 70% of predicted for diagnosis (ACP) [3,103] - when FEV1/FVC is 65-70% of predicted, a single spirometry may not be enough for diagnosis [85] - in these patients diagnostic reversal within 5 years in up to 27% with smoking cessation [85] - post bronchodilator FEV1 < 80% of predicted (GOLD) - when the FEV1 falls below 1 liter, 5 year survival is 50% b) response to bronchodilators is generally poor (in contrast to asthma) c) spirometry to confirm airway obstruction prior to treatment with bronchodilator [57] d) repeat spirometry to evaluate change in condition - annual spirometry can provide objective measure of change in pulmonary function [3] e) USPSTF recommends against screening for COPD with spirometry 2) complete pulmonary function testing a) indications - evaluation for lung reduction surgery - evaluation for lung transplantation - otherwise not cost effective & does not change management [3] b) increased total lung capacity suggests emphysema c) diminished DLCO suggests lung parenchymal changes consistent with emphysema 3) echocardiogram: {pulmonary hypertension & cor pulmonale} 4) COPD assessment test or 5) Modified Medical Research Council Dyspnea Scale 6) 6-minute walk [111] Radiology: - chest X-ray (r/o heart failure, tuberculosis ...) [16] - computed tomography (CT) of thorax - emphysema-like findings on CT associated with increased mortality, even in asymptomatic patients [55] - not routinely recommended to monitor COPD [3] - low dose lung CT for adults aged 55-80 with a 30-pack-year smoking history who currently smoke or have quit within the past 15 years [3] - persistent COPD exacerbations [121] - symptoms out of proportion to airflow obstruction - evidence of air trapping/hyperinflation [121] - pulmonary CT angiography for pulmonary embolism if acute dyspnea, cardiac disease & infection unlikely/ruled out regardless of Wells score - radionuclide ventriculography {pulmonary hypertension} Staging: see stages of COPD Complications: - COPD exacerbation - gabapentinoid use increases risk for severe COPD exacerbation [126] - increased risk of mild cognitive impairment (MCI) [46] - RR = 1.86 for non-amnestic MCI [46] - comorbidities are commn - cardiovascular disease, sarcopenia, osteopenia [3] - depression (screen for depression) - also see common comorbidities in patients with COPD - increased postoperative complications - 30 day mortality 6.7% vs 1.4% - 30 day morbidity 25.8% vs 10.2% with increased risk for - postoperative pneumonia, respiratory failure, MI, cardiac arrest, sepsis, & renal failure [74] - increased risk of lung cancer even in never smokers (RR=2.5) [107] - risk higher in smokers (RR=6) Differential diagnosis: (other obstructive pulmonary diseases) 1) asthma (fluctuating course) 2) cystic fibrosis (early age of onset) - bronchiectasis - pulmonary &/or GI symptoms most common presentations in adults - recurrent respiratory tract infections - infertility [3] 3) bronchiolitis obliterans - current or former smokers - may be associated with rheumatoid arthritis - poorly responsive to bronchodilators - may respond to smoking cessation & glucocorticoids [3] 4) bronchiectasis - may be associated with childhood pneumonia, foreign body, cystic fibrosis, immobile ciliary syndrome, allergic bronchopulmonary aspergillosis - large volume of sputum, purulent exacerbations, hemoptysis - lung CT: airway diameter > accompanying blood vessel - lack of distal airway tapering [3] 5) tuberculosis [16] 6) congestive heart failure [16] 7) upper airway obstruction 8) alpha-1 antitrypsin deficiency Management: 1) manage acute exacerbations: (see COPD exacerbation) 2) treatment determined by: [121] a) degree of airflow obstruction b) current symptoms c) history of moderate & severe exacerbations d) comorbidities [121] === long-term management of COPD === 1) smoking cessation* can slow decline in FEV1 [3] - nicotine patch, varenicline or bupropion 2) stepwise approach [3,10] - ensure patient receives training on proper inhaler technique [3] - cognitive testing may be necessary to determine whether patient is able to maintain proper inhaler technique [122] - LABA or LAMA 1st line, followed by LABA/LAMA combination if - >= 2 COPD exacerbations or 1 hospitalization due to COPD exacerbation - addition of inhaled glucocorticoid if eosinophil count > 300/uL (GOLD) [90] - LABA/LAMA glucocorticoid combination 3) bronchodilators are 1st line a) short-acting bronchodilator in symptomatic patients with FEV1 60-80% of predicted (stage 1) [3,27,44] b) long-acting bronchodilator indicated for moderate to severe COPD - FEV1 < 60% of predicted [3,31] - >= 2 COPD exacerbations per year LABA/LAMA combination [44] 4) bronchodilators act by different mechanisms a) short-acting beta2-adrenergic agonist as needed - albuterol MDI PRN b) long-acting inhaled beta2 agonist MDI (LABA) 1] formoterol, salmeterol) if using albuterol on a regular basis [3] 2] long-acting beta2-adrenergic agonist may offer survival advantage in elderly [24] 3] increased cardiovascular risk in the elderly - highest risk 2-3 weeks after starting treatment [39] c) ipratropium (Atrovent) MDI, short-acting muscarininc antagonist - muscarinic antagonists may increase risk of urinary retention in elderly men d) long-acting muscarininc antagonists MDI (LAMA) 1] LAMA preferred vs LABA in patients with frequent exacerbations [88] 2] tiotropium (Spiriva) MDI long-acting a] attenuates symptoms in moderate COPD but does not slow progression b] effective in early-moderate COPD [17,86] c] tiotropium superior to salmeterol [22] d] initial use of tiotropium vs salmeterol results in higher mortality (14%) [26] e] increased cardiovascular risk in the elderly; highest risk 2-3 weeks after starting treatment [39] f] aclidinium does not worsen cardiovascular outcomes in COPD 3] do not use long-acting & short-acting anticholinergic agents (ipratropium & tiotropium) in combination [3] 4] glycopyrrolate, long-acting e) LABA & LAMA with similar cardiovascular risk in elderly [82] - risk of pneumonia may be lower with LAMA [82] - LAMA preferred for patients with frequent exacerbations [83] - new initiation of LABAs or LAMAs in patients with COPD is associated ~1.5-fold increased cardiovascular risk [89] f) LABA/LAMA combination treatment of choice regardless of cardiovascular risk - prolonged QTc interval not a contraindication [120] g) all patients using long-acting bronchodilator should have short-acting bronchodilator as rescue medication [3] h) theophylline - no benefit for preventing exacerbations [95] - may be of benefit for nighttime symptoms - do not use (MKSAP19) [3] 5) glucocorticoids, inhaled steroids (MDI) a) not useful as monotherapy [3] - LABA + LAMA + budesonide is triple therapy - predominantly benefits patients with elevated blood eosinophil count (> 300 x 10E6/L) [111, 121] b) add at stage 3, see stages of COPD) [16] c) decrease in exacerbations offset by increase risk of pneumonia [11,110] d) patients with eosinophilia, chronic bronchitis or asthma/COPD overlap, seem to benefit most [90,121] e) patients with emphysema may not benefit [90] f) discontinuing inhaled glucocorticoids in patients with COPD lowers relative risk for pneumonia (37%) [62] g) glucocorticoids may increase risk of bone fractures [28,91] h) high-dose Advair may diminish exacerbation [11] i) Advair might improve survival relative to tiopropium, but no difference in exacerbations, & more pneumonia [11] j) use of fluticasone may increase mortality, - budesonide may not increase mortality due to shorter 1/2life [16] - budesonide 320 ug (high-dose) added to formoterol + glycopyrrolate (Breztri Aerosphere) may diminish mortality (1.3% vs 2.3%) with severe COPD [110] - fluticasone contraindicated in combination with strong CYP3A4 inhibitors i.e. HIV1 protease inhibitors such as ritonavir, use budesonide instead (see drug interactions) k) fluticasone may be withdrawn safely in patients also taking tiotropium & salmeterol [51] - in patients with < 2 COPD exacerbations in the past year without eosinophilia or comorbid asthma, inhaled glucocorticoid may be withdrawn from LABA/LAMA combination [93] l) avoid oral glucocorticoid except in case of COPD exacerbation [3] 6) combination therapies a) combined use of LABA (formoterol) + LAMA (tiotropium) - 1st line GOLD group E (2 COPD exacerbations or 1 requiring hospitalization) - better than either agent alone [3,10] - combination better than monotherapy in improving lung function & dyspnea & preventing COPD exacerbations [49,120] - LABA + LAMA better than LABA + inhaled glucocorticoid [102,123] - LABA + LAMA with improved symptom control & fewer adverse effects than LABA + LAMA + inhaled glucocorticoid (triple therapy) [117] - umeclidinium/vilanterol (Anoro Ellipta) is once a day - glycopyrrolate/indacaterol better than fluticasone/salmeterol for preventing COPD exacerbation [73] - LABA/LAMA combination treatment of choice regardless of cardiovascular risk - prolonged QTc interval not a contraindication [120] b) triple combination therapy reduces COPD exacerbations, hospital admissions & mortality in patients with moderate-severe COPD [32,84,87,115] 1] inhaled glucocorticoid 2] inhaled long-acting beta2 agonist 3] inhaled anticholinergic agent 4] no survival benefit relative to LABA/LAMA [96] 5] may benefit patients with eosinphilia or COPD/asthma [108] 6] increased risk for pneumonia relative to LABA/LAMA [96,108] 7] withdraw glucocorticoid after 1 year with no COPD exacerbations [109] 8] fluticasone/umeclidinium/vilanterol (Trelegy Ellipta) is once a day 9] budesonide/formoterol/glycopyrrolate is twice a day c) combined long-acting beta2 agonist (LABA) + inhaled glucocorticoid - recommended for COPD-asthma overlap syndrome - fluticasone + salmeterol is better than either agent alone [3,6] at cost of increased risk of pneumonia [18] - combination associated with better outcomes than LABA alone in older adults [50] a] 5 year mortality or hospitalization 58% vs 61% b] outcomes better in patients with cormorbid asthma c] outcomes better in patients not taking inhaled anticholinergic agent [50] d] blacks using fluticasone + salmeterol are more likely than whites to suffer asthma-related deaths [61] e] fluticasone/vilanterol (Breo Ellipta) reduces risk of COPD exacerbations [78] - budesonide 200 ug + formoterol 6 ug BID with additional budesonide 400 ug + formoterol 12 ug BID for 10 days at 1st sign of cold symptoms reduces risk of hospitalization for COPD exacerbation [92] d) combined tiotropium (LAMA) + inhaled glucocorticoid not inferior to combined LABA + inhaled glucocorticoids in blacks [60] e) insufficient evidence to recommend when combination therapy should be chosen over monotherapy [27] f) continue albuterol inhaler for rescue with combination therapies 7) ensure proper use of MDI before changing medications [3,37,47] 8) oxygen* a) severe hypoxemia at rest [27] (stage 3 or 4) b) room air SaO2 <= 88% or pO2 <= 55 mm Hg [3,38,94,114] c) pO2 55-60 mm Hg with signs of tissue hypoxia 1] polycythemia 2] pulmonary hypertension 3] right heart failure (cor pulmonale) d) nocturnal SaO2 <= 88% (overnight pulse oximetry) e) exercise pO2 <= 55 mm Hg or SaO2 <= 88% [3,38] (6 minute walk) - ambulatory oxygen therapy if exertional hypoxemia [114] - portable liquid oxygen is best f) O2 reduces mortality in COPD patients with pO2 <= 55 mm Hg or SaO2 <= 88% [31] g) no mortality benefit or reduction in hospitalization for supplemental oxygen if SaO2 > 88% [80,119] h) no mortality benefit if oxygen desaturation with exercise between 80-89% [31] i) supplemental oxygen of no benefit for isolated nocturnal desaturation [113] 9) room air (2 L/min by nasal cannula) or presumably blown on face via a fan relieves dyspnea in normoxemic patients with COPD [30] 10) roflumilast (PDE-4 inhibitor, FDA-approved) - add on therapy for severe COPD associated with chronic bronchitis with recurrent COPD exacerbations [3,111,121] - reduces frequency of COPD exacerbations in patients on optimal therapy - not useful for emphysema [3] - not useful for acute bronchospasm [3] 11) long-term azithromycin 250 mg/day may reduce risk of COPD exacerbation [29,77] - indicated for non-smokers with severe COPD & frequent COPD exacerbations [3,121] 12) N-acetylcysteine 600 mg PO BID improves airway reactivity & airway resistance - 600 mg QD is not effective [40] 13) mepolizumab (Nucala) may benefit COPD patients with peripheral eosinophilia [88] 14) dupilumab injections every 2 weeks for patients with eosinophil count > 300/uL - reduces COPD exacerbations, improves lung function, improves symptoms [124] 15) doxycycline 100 mg QD may benefit patients with severe COPD or those with blood eosinophil counts of < 300/uL [125] 16) beta-blockers not contradindicated (see comorbidities below) - beta-blocker associated with reduced risk for hospitalization [97] - metoprolol does not lower risk for COPD exacerbation without other indication for beta-blocker [105] - cardioselective beta-blocker bisoprolol neither beneficial nor harmful [129] 17) regular use of antitussives contraindicated in stable COPD [16] 18) interventional bronchoscopy [83] 19) surgery a) lung volume reduction (upper lobe emphysema) - not indicated if FEV1 or DLCO < 20% of predicted [3] b) surgery for GERD c) lung transplantation 20) acupuncture may improve dyspnea on exertion [34] === other considerations for patients with COPD === 1) pulmonary hypertension & cor pulmonale a) optimize bronchodilators b) provide oxygen therapy c) phlebotomy when hematocrit > 50% despite oxygen therapy in presence of CNS compromise d) diuretics are contraindicated; may preciptitate metabolic alkalosis 5e) vasodilators: not indicated 2) rehabilitation a) exercise program, nutritional counseling b) pulmonary rehabilitation - recommended for symptomatic patients with COPD & FEV1 < 50% of predicted & for patients hospitalized with COPD exacerbation [3,121] - improves quality of life, but not survival [3] - improves 1 year survival [31,116] - consider for symptomatic, exercise-limited patients regardless of FEV1 [27] 3) CPAP for COPD patients with chronic hypercapnia or sleep apnea 4) vaccination a) yearly influenza vaccination reduces mortality [31] b) pneumococcal vaccine - if >= 65 years of age or FEV1 < 40% predicted [16] - all COPD patients [3] - only PPSV23 recommended if patient < 65 years of age [3] 5) psychoactive drugs a) buspirone (anxiolytic usually well tolerated, but with delayed (several weeks) onset of action) b) doxepin 25-100 mg/day agent of choice for agitated depression (may have mild bronchodilator effect) c) protriptyline 20 mg QHS, non-sedating tricyclic antidepressant improves diurnal & nocturnal hypoxemia in patients with COPD 6) alpha-1 antitrypsin inhibitor in patients with documented alpha-1 antitrypsin deficiency (< 11 um/L) FEV1 (30-60% of normal) - non-smoking. Prolastin 60 mg/kg IV weekly 7) treatments found to be of no benefit a) N-acetylcysteine 600 mg QD of no benefit (see BRONCUS study) b) self-management [33] 8) comorbidities: (see common comorbidities in patients with COPD) - depression (screen for depression) - beta-blockers may reduce mortality & COPD exacerbations in patients with with COPD & cardiovascular disease [19,25] 9) end stage disease: - FEV1 < 30% of predicted, oxygen dependence, multiple hospitalizations for COPD exacerbations, comorbidities, weight loss, cachexia, decreased functional status, & increased dependence on others should trigger end-of-life discussions & referral to hospice as indicated [3] - home non-invasive positive pressure ventilation (NPPV) may benefit COPD patients with hypercarbia [106] - a face mask may exacerbate distress, interfere with communication - low-dose opiates reduce breathlessness & alleviate distress [42,63,112] - oral morphine (nebulized morphine of no benefit) [3] - 10 mg morphine SR PO BID reduces dyspnea [112] - low-dose, extended-release morphine does not reduce breathlessness among persons with COPD & severe chronic breathlessness [118] - codeine 30-60 mg every 6 hours [2] - handheld fan can reduce dyspnea [3] 10) prognosis for COPD: - risk factors for recurrent COPD exacerbations - >= 2 COPD exacerbations in the past year - ever been hospitalized for COPD exacerbation - FEV1 < 50% of predicted - see BODE index 11) patients with COPD are hypermetabolic & spend more calories than other elderly likely due to increased work of breathing [130] - recommend dietary changes: increased calories with decreased carbohydrates - nutritionist support helpful 12) referral to pulmonologist [3] - diagnosis of COPD <= 40 years of age - >= 2 exacerbations/year despite adequate treatment - rapid disease progression - decline in FEV1, progressive dyspnea - FEV1 < 50% of predicted despite optimal treatment - need for oxygen therapy - onset of comorbidity, especially cardiovascular event - diagnostic uncertainty (COPD vs or +/- asthma) - symptoms disproportinate to FEV1 - confirmed or suspected alpha-1 antitrypsin deficiency - patient request for a 2nd opinion - potential candidate for lung volume reduction surgery or lung transplantation - severe COPD in a patient who requires elective surgery that may impair respiratory function 13) patient education - action plan consisting of - patients receiving prescriptions for short courses of - prednisone - antibiotics - patient taught to recognize symptoms that should prompt initiation of prednisone & antibiotics - action plans can cut hospitalization in 1/2 [21] - health coaching can reduce hospital readmission [81] - self-management plan offers no benefit over usual care [36] - telemonitoring offers no benefit over usual care [41] 14) screening for COPD in asymptomatic persons not recommended (USPSTF) [3] - see screening for COPD * smoking cessation & oxygen have been shown to increase survival; triple combination therapy may also reduce mortality

Interactions

disease interactions

Related

BODE index & prognosis for COPD common comorbidities in patients with COPD features of chronic bronchitis vs pulmonary emphysema Global Initiative for Chronic Obstructive Lung Disease (GOLD) risk factors for COPD screening for chronic obstructive pulmonary disease (COPD) stages of COPD

Specific

chronic bronchitis COPD exacerbation pulmonary emphysema

General

obstructive lung disease bronchospastic pulmonary disease chronic lung disease

Figures/Diagrams

EKG: pulmonary disease pattern

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 242
  2. Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Prescriber's Letter 8(5):25 2001
  5. Journal Watch 23(6):50, 2003 Lightowler JV et al Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ 326:185, 2003 PMID: 12543832 http://bmj.com/cgi/content/full/326/7382/185 - Babu KS & Chauhan AL Non-invasive ventilation in chronic obstructive pulmonary disease. BMJ 326:177, 2003 PMID: 12543819 http://bmj.com/cgi/content/full/326/7382/177
  6. Journal Watch 23(8):61-62, 2003 Calverley P et al Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 361:449, 2003 PMID: 12583942 Rennard SI COPD: treatments benefit patients. Lancet 361:444, 2003 PMID: 12583937
  7. Journal Watch 23(14):113, 2003 Keenan SP et al Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation? A systematic review of the literature. Ann Intern Med 138:861, 2003 PMID: 12779296
  8. Journal Watch 25(2):19, 2005 Man WD, Polkey MI, Donaldson N, Gray BJ, Moxham J. Community pulmonary rehabilitation after hospitalisation for acute exacerbations of chronic obstructive pulmonary disease: randomised controlled study. BMJ. 2004 Nov 20;329(7476):1209. Epub 2004 Oct 25. PMID: 15504763 http://bmj.bmjjournals.com/cgi/content/full/329/7476/1209
  9. Journal Watch 25(13):101, 2005 Decramer M, Rutten-van Molken M, Dekhuijzen PN, Troosters T, van Herwaarden C, Pellegrino R, van Schayck CP, Olivieri D, Del Donno M, De Backer W, Lankhorst I, Ardia A. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet. 2005 Apr 30;365(9470):1552-60. PMID: 15866309
  10. van Noord JA et al, Effects of tiotropium with and without formoterol on airflow obstruction and resting hyperinflation in patients with COPD Chest 2006; 129:509 PMID: 16537846
  11. Prescriber's Letter 14(4): 2007 High-dose Advair for COPD Detail-Document#: 230414 (subscription needed) http://www.prescribersletter.com - Prescriber's Letter 15(3): 2008 Advair (Salmeterol/Fluticasone) vs Spiriva (Tiotropium) for COPD Detail-Document#: 240308 (subscription needed) http://www.prescribersletter.com
  12. Rabe KF et al, Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Car Med 2007, 176:532 PMID: 17507545
  13. Part I: Diagnosis and Management of Stable COPD http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart1_3.inc Part II: Diagnosis and Management of Acute Exacerbations http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart2_3.inc - Updated Guideline Syntheses on COPD Part I http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart1_5.inc Part II http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart2_5.inc (Finnish Medical Society)
  14. Qaseem A, Snow V, Shekelle P, Sherif K, Wilt TJ, Weinberger S, Owens DK; for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians*. Diagnosis and Management of Stable Chronic Obstructive Pulmonary Disease: A Clinical Practice Guideline from the American College of Physicians. Ann Intern Med. 2007 Nov 6;147(9):633-638. PMID: 17975186 corresponding NGC guideline withdrawn Nov 2016
  15. US Preventive Services Task Force Screening for Chronic Obstructive Pulmonary Disease using spirometry: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2008 Apr 1;148(7):529-34. Epub 2008 Mar 3. PMID: 18316747 http://www.annals.org/content/148/7/529.full - Lin K et al, Screening for Chronic Obstructive Pulmonary Disease using spirometry: Summary of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2008 Apr 1;148(7):535-43. Epub 2008 Mar 3. PMID: 18316746 http://www.annals.org/content/148/7/535.full (corresponding NGC guideline withdrawn Jan 2014)
  16. Sin DD et al Budesonide and the risk of pneumonia: A meta-analysis of individual patient data. Lancet 2009 Aug 29; 374:712 PMID: 19716963 - Welte T. Inhaled corticosteroids in COPD and the risk of pneumonia. Lancet 2009 Aug 29; 374:668. PMID: 19716946
  17. Decramer M et al. Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): A prespecified subgroup analysis of a randomised controlled trial. Lancet 2009 Oct 3; 374:1171. PMID: 19716598 - Davies L and Calverley PMA. UPLIFTing care for chronic obstructive pulmonary disease. Lancet 2009 Oct 3; 374:1129. PMID: 19716599
  18. Rodrigo GJ et al. Safety and efficacy of combined long-acting beta-agonists and inhaled corticosteroids vs long-acting beta-agonists monotherapy for stable COPD: A systematic review. Chest 2009 Oct; 136:1029. PMID: 19633090
  19. Rutten FH et al beta-Blockers May Reduce Mortality and Risk of Exacerbations in Patients With Chronic Obstructive Pulmonary Disease Arch Intern Med. 2010;170(10):880-887. PMID: 20498416 http://archinte.ama-assn.org/cgi/content/short/170/10/880 - Sin DD and Man SF A Curious Case of beta-Blockers in Chronic Obstructive Pulmonary Disease Arch Intern Med. 2010;170(10):849-850. PMID: 20498410 http://archinte.ama-assn.org/cgi/content/short/170/10/849 - Prescriber's Letter 17(7): 2010 Beta-Blockers and Chronic Obstructive Pulmonary Disease (COPD) Detail-Document#: 260702 (subscription needed) http://www.prescribersletter.com
  20. National Heart, Lung, and Blood Institute (NHLBI) COPD (Chronic Obstructive Pulmonary Disease): https://www.nhlbi.nih.gov/health-topics/copd - Chronic Obstructive Pulmonary Disease (COPD) VA/DoD Clinical Practice Guidelines http://www.oqp.med.va.gov/cpg/COPD/COPD_base.htm
  21. Rice KL et al. Disease management program for chronic obstructive pulmonary disease: A randomized controlled trial. Am J Respir Crit Care Med 2010 Oct 1; 182:890 PMID: 20075385
  22. Vogelmeier C et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med 2011 Mar 24; 364:1093 PMID: 21428765 - Wedzicha JA. Choice of bronchodilator therapy for patients with COPD. N Engl J Med 2011 Mar 24; 364:1167. PMID: 21428773
  23. Lamprecht B et al. COPD in never smokers: Results from the population-based Burden of Obstructive Lung Disease Study. Chest 2011 Apr; 139:752. PMID: 20884729
  24. Gershon A et al Comparison of Inhaled Long-Acting beta-Agonist and Anticholinergic Effectiveness in Older Patients With Chronic Obstructive Pulmonary Disease: A Cohort Study Ann Intern Med. 2011 May 3;154(9):583-92. PMID: 21536937
  25. Short PM et al Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study BMJ 2011; 342:d2549 PMID: 21558357 http://www.bmj.com/content/342/bmj.d2549.full
  26. Gershon A et al. Comparison of inhaled long-acting beta-agonist and anticholinergic effectiveness in older patients with chronic obstructive pulmonary disease: A cohort study. Ann Intern Med 2011 May 3; 154:583 PMID: 21536937
  27. Qaseem A et al Diagnosis and Management of Stable Chronic Obstructive Pulmonary Disease: A Clinical Practice Guideline Update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society Annals 0f Internal Medicine 2011 155(3):179-191 PMID: 21810710 http://www.annals.org/content/155/3/179.abstract corresponding NGC guideline withdrawn Nov 2016
  28. Prescriber's Letter 18(8): 2011 Spiriva (Tiotropium) vs Long-Acting Beta-2 Agonists for COPD Detail-Document#: 270807 (subscription needed) http://www.prescribersletter.com
  29. Prescriber's Letter 18(10): 2011 Azithromycin to Prevent COPD Exacerbations Detail-Document#: 271004 (subscription needed) http://www.prescribersletter.com
  30. Abernethy AP, McDonald CF, Frith PA, et al. Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial. Lancet 2010; 37(9743):784-793. PMID: 20816546
  31. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010 - Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  32. Short PM et al. The impact of tiotropium on mortality and exacerbations when added to inhaled corticosteroids and long-acting beta-agonist therapy in COPD. Chest 2012 Jan; 141:81. PMID: 21799028
  33. Bucknall CE et al. Glasgow supported self-management trial (GSuST) for patients with moderate to severe COPD: Randomised controlled trial. BMJ 2012 Mar 6; 344:e1060. PMID: 22395923
  34. Suzuki M et al. A randomized, placebo-controlled trial of acupuncture in patients with chronic obstructive pulmonary disease (COPD): The COPD-Acupuncture Trial (CAT). Arch Intern Med 2012 May 14 PMID: 22905352 http://archinte.jamanetwork.com/article.aspx?doi=10.1001/archinternmed.2012.1233
  35. Vestbo J et al. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2012 Aug 9 PMID: 22878278 http://ajrccm.atsjournals.org/content/early/2012/07/25/rccm.201204-0596PP
  36. Bischoff E WMA et al Comprehensive self management and routine monitoring in chronic obstructive pulmonary disease patients in general practice: randomised controlled trial BMJ 2012;345:e7642 PMID: 23190905 http://www.bmj.com/content/345/bmj.e7642
  37. Fromer L, Goodwin E, Walsh J. Customizing inhaled therapy to meet the needs of COPD patients. Postgrad Med. 2010 Mar;122(2):83-93 PMID: 20203459
  38. Stoller JK, Panos RJ, Krachman S et al Oxygen therapy for patients with COPD: current evidence and the long-term oxygen treatment trial. Chest. 2010 Jul;138(1):179-87 PMID: 20605816
  39. Gershon A et al Cardiovascular Safety of Inhaled Long-Acting Bronchodilators in Individuals With Chronic Obstructive Pulmonary Disease. JAMA Intern Med. 2013;():1-9. PMID: 21536937 http://archinte.jamanetwork.com/article.aspx?articleid=1689974
  40. Tse HN et al. High-dose N-acetylcysteine in stable COPD: The 1-year, double- blind, randomized, placebo-controlled HIACE study. Chest 2013 Jul; 144:106 PMID: 23348146
  41. Pinnock H et al Effectiveness of telemonitoring integrated into existing clinical services on hospital admission for exacerbation of chronic obstructive pulmonary disease: researcher blind, multicentre, randomised controlled trial. BMJ 2013;347:f6070 PMID: 24136634 http://www.bmj.com/content/347/bmj.f6070 - Jordan R et al Telemonitoring for patients with COPD BMJ 2013;347:f5932 PMID: 24136632 http://www.bmj.com/content/347/bmj.f5932
  42. Ekstrom MP et al Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study. BMJ 2014;348:g445 PMID: 24482539 http://www.bmj.com/content/348/bmj.g445
  43. Jones RC et al Opportunities to diagnose chronic obstructive pulmonary disease in routine care in the UK: a retrospective study of a clinical cohort. Lancet Respir Med, 13 February 2014 PMID: 24717623 http://www.thelancet.com/journals/lanres/article/PIIS2213-2600%2814%2970008-6/abstract
  44. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, - Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
  45. Hanania NA, Sharma G, Sharafkhaneh A. COPD in the elderly patient. Semin Respir Crit Care Med. 2010 Oct;31(5):596-606 PMID: 20941660
  46. Singh B et al. A prospective study of chronic obstructive pulmonary disease and the risk for mild cognitive impairment. JAMA Neurol 2014 Mar 17 PMID: 24637951 http://archneur.jamanetwork.com/article.aspx?articleid=1846749
  47. Prescriber's Letter 21(4): 2014 Inhalers for COPD Detail-Document#: 300403 (subscription needed) http://www.prescribersletter.com
  48. Gooneratne NS, Patel NP, Corcoran A. Chronic obstructive pulmonary disease diagnosis and management in older adults. J Am Geriatr Soc. 2010 Jun;58(6):1153-62. Review. PMID: 20936735
  49. Celli B et al. Once-daily umeclidinium/vilanterol 125/25 ug therapy in COPD: A randomized, controlled study. Chest 2014 May; 145:981 PMID: 24385182 http://journal.publications.chestnet.org/article.aspx?articleid=1809987
  50. Gershon AS et al Combination Long-Acting beta-Agonists and Inhaled Corticosteroids Compared With Long-Acting beta-Agonists Alone in Older Adults With Chronic Obstructive Pulmonary Disease. JAMA. 2014;312(11):1114-1121 PMID: 25226477 http://jama.jamanetwork.com/article.aspx?articleid=1904829 - Calverley PMA Treating COPD in the Real World JAMA. 2014;312(11):1101-1102 PMID: 25226474 http://jama.jamanetwork.com/article.aspx?articleid=1904812
  51. Magnussen H, Disse B, Rodriguez-Roisin R et al Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med 2014 Sep 8 PMID: 25196117 http://www.nejm.org/doi/full/10.1056/NEJMoa1407154
  52. Tashkin DP et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008 Oct 7; 359:1543 PMID: 18836213
  53. Karner C and Cates CJ. Long-acting beta(2)-agonist in addition to tiotropium versus either tiotropium or long-acting beta(2)-agonist alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012 Apr 20; 4:CD008989 PMID: 22513969
  54. Spencer S, Karner C, Cates CJ, Evans DJ. Inhaled corticosteroids versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD007033. PMID: 22161409
  55. Oelsner EC et al Association Between Emphysema-like Lung on Cardiac Computed Tomography and Mortality in Persons Without Airflow Obstruction: A Cohort Study Ann Intern Med. 2014;161(12):863-873 PMID: 25506855 http://annals.org/article.aspx?articleid=2023010
  56. Varraso R et al Alternate Healthy Eating Index 2010 and risk of chronic obstructive pulmonary disease among US women and men: prospective study. BMJ 2015;350:h286 PMID: 25649042 http://www.bmj.com/content/350/bmj.h286
  57. Collins BF et al. Factors predictive of airflow obstruction among veterans with presumed empirical diagnosis and treatment of COPD. Chest 2015 Feb; 147:369 PMID: 25079684
  58. Barnes PJ Chronic obstructive pulmonary disease. N Engl J Med. 2000 Jul 27;343(4):269-80 PMID: 10911010
  59. Rennard S, Decramer M, Calverley PM et al Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey. Eur Respir J. 2002 Oct;20(4):799-805. PMID: 12412667
  60. Wechsler ME et al. Anticholinergic vs long-acting beta-agonist in combination with inhaled corticosteroids in black adults with asthma: The BELT randomized clinical trial. JAMA 2015 Oct 27; 314:1720 PMID: 26505596
  61. Nelson HS et al, The salmeterol multicenter asthma research trial: A comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol Chest 2006, 129:15 PMID: 16424409 - O'Byrne PM, Adelroth E. Beta2 deje vu. Chest. 2006 Jan;129(1):3-5. PMID: 16424402
  62. Suissa S et al. Discontinuation of inhaled corticosteroids in COPD and the risk reduction of pneumonia. Chest 2015 Nov; 148:1177 PMID: 26110239 http://journal.publications.chestnet.org/article.aspx?articleid=2363032
  63. Ekstrom MP, Abernethy AP, Currow DC. The management of chronic breathlessness in patients with advanced and terminal illness. BMJ. 2015. 349:g7617 PMID: 25556037
  64. Shem S House of God. ISBN: 0-440-13368-8 (1978)
  65. Cosio BG et al. Defining the asthma-COPD overlap syndrome in a COPD cohort. Chest 2016 Jan PMID: 26291753
  66. Barreiro E, Criner GJ. Update in chronic obstructive pulmonary disease 2013. Am J Respir Crit Care Med. 2014 Jun 1;189(11):1337-44. PMID: 24881938
  67. Lee SD, Huang MS, Kang J et al The COPD assessment test (CAT) assists prediction of COPD exacerbations in high-risk patients. Respir Med. 2014 Apr;108(4):600-8. PMID: 24456695 Free Article
  68. Martinez-Garcia MA, de la Rosa Carrillo D, Soler-Cataluna JJ et al Prognostic value of bronchiectasis in patients with moderate- to-severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013 Apr 15;187(8):823-31 PMID: 23392438
  69. Sharif R, Cuevas CR, Wang Y, Arora M, Sharma G Guideline adherence in management of stable chronic obstructive pulmonary disease. Respir Med. 2013 Jul;107(7):1046-52. PMID: 23639271 Free Article
  70. Vestbo J, Agusti A, Wouters EF et al Should we view chronic obstructive pulmonary disease differently after ECLIPSE? A clinical perspective from the study team. Am J Respir Crit Care Med. 2014 May 1;189(9):1022-30. PMID: 24552242
  71. Wedzicha JA, Rabe KF, Martinez FJ et al Efficacy of roflumilast in the COPD frequent exacerbator phenotype. Chest. 2013 May;143(5):1302-11 PMID: 23117188
  72. Curtis JR Palliative and end-of-life care for patients with severe COPD. Eur Respir J. 2008 Sep;32(3):796-803. Epub 2007 Nov 7. PMID: 17989116
  73. Wedzicha JA et al Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. N Engl J Med. May 15, 2016 PMID: 27181606 http://www.nejm.org/doi/full/10.1056/NEJMoa1516385 - Donohue JF Another Choice for Prevention of COPD Exacerbations. N Engl J Med. May 15, 2016 PMID: 27181835 http://www.nejm.org/doi/full/10.1056/NEJMe1604444
  74. Gupta H, Ramanan B, Gupta PK et al Impact of COPD on postoperative outcomes: results from a national database. Chest. 2013 Jun;143(6):1599-606. PMID: 23287892
  75. Ameer F, Carson KV, Usmani ZA, Smith BJ. Ambulatory oxygen for people with chronic obstructive pulmonary disease who are not hypoxaemic at rest. Cochrane Database Syst Rev. 2014 Jun 24;(6):CD000238. Review. PMID: 24957353
  76. Calverley PM, Anderson JA, Celli B et al Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007 Feb 22;356(8):775-89. PMID: 17314337 Free Article
  77. Herath SC, Poole P. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2013 Nov 28;(11):CD009764. Review. PMID: 24288145
  78. Vestbo J, Leather D, Diar Bakerly N, et al Effectiveness of Fluticasone Furoate-Vilanterol for COPD in Clinical Practice. N Engl J Med. Sept 4, 2016 PMID: 27593504 Free Article http://www.nejm.org/doi/full/10.1056/NEJMoa1608033
  79. Martinez FD Early-Life Origins of Chronic Obstructive Pulmonary Disease. N Engl J Med 2016; 375:871-878. September 1, 2016 PMID: 27579637 http://www.nejm.org/doi/full/10.1056/NEJMra1603287
  80. Long-Term Oxygen Treatment Trial Research Group A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation. N Engl J Med 2016; 375:1617-1627. October 27, 2016 PMID: 27783918 http://www.nejm.org/doi/full/10.1056/NEJMoa1604344?query=pfw&jwd=000000793830&jspc=FPG - Ekstrom M Clinical Usefulness of Long-Term Oxygen Therapy in Adults. N Engl J Med 2016; 375:1683-1684. October 27, 2016 PMID: 27783914 http://www.nejm.org/doi/full/10.1056/NEJMe1611742?query=pfw&jwd=000000793830&jspc=FPG
  81. Benzo R, Vickers K, Novotny PJ et al. Health coaching and chronic obstructive pulmonary disease rehospitalization: A randomized study. Am J Respir Crit Care Med 2016 Sep 15; 194:672 PMID: 26953637
  82. Suissa S, Dell'Aniello S, Ernst P. Long-acting bronchodilator initiation in COPD and the risk of adverse cardiopulmonary events: A population-based comparative safety study. Chest 2017 Jan; 151:60 PMID: 27554300 http://www.sciencedirect.com/science/article/pii/S0012369216561625
  83. Vogelmeier CF, Criner GJ, Martinez FJ et al Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary . Am J Respir Crit Care Med. 2017 Mar 1;195(5):557-582 PMID: 28128970 http://www.atsjournals.org/doi/abs/10.1164/rccm.201701-0218PP
  84. Vestbo J, Papi A, Corradi M et al. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): A double-blind, parallel group, randomised controlled trial. Lancet 2017 Apr 3; PMID: 28385353 - Fabbri LM, Roversi S, Beghe B. Triple therapy for symptomatic patients with COPD. Lancet 2017 PMID: 28385354
  85. Aaron SD, Tan WC, Bourbeau J et al. Diagnostic instability and reversals of chronic obstructive pulmonary disease diagnosis in individuals with mild to moderate airflow obstruction. Am J Respir Crit Care Med 2017 Aug 1; 196:306. PubMed: 28267373 http://www.atsjournals.org/doi/10.1164/rccm.201612-2531OC
  86. Zhou Y, Zhong NS, Li X et al Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease. N Engl J Med 2017; 377:923-935. September 7, 2017 PMID: 28877027 http://www.nejm.org/doi/full/10.1056/NEJMoa1700228 - Ko FWS, Wong GWK. Drug treatment for early-stage COPD. N Engl J Med 2017 Sep 7; 377:988. PMID: 28877018
  87. Lipson DA, Barnacle H, Birk R et al. FULFIL Trial: Once-daily triple therapy for patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2017 Aug 15; 196:438. PMID: 28375647 - Lipson DA, Barnhart F, Brealey N et al Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. April 18, 2018 PMID: 29668352 http://www.nejm.org/doi/full/10.1056/NEJMoa1713901 - Suissa S, Drazen JM. Making Sense of Triple Inhaled Therapy for COPD. N Engl J Med. April 18, 2018 PMID: 29669218 http://www.nejm.org/doi/full/10.1056/NEJMe1716802 - Lipson DA et al. Reduction in all-cause mortality with fluticasone furoate/umeclidinium/vilanterol in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2020 Jun 15; 201:1508 PMID: 32162970 Free PMC article https://www.atsjournals.org/doi/10.1164/rccm.201911-2207OC - Vestbo J. Fixed triple therapy in chronic obstructive pulmonary disease and survival: Living better, longer, or both? Am J Respir Crit Care Med 2020 Jun 15; 201:1463 PMID: 32212973 Free PMC article https://www.atsjournals.org/doi/10.1164/rccm.202003-0622ED
  88. Pavord ID, Chanez P, Criner GJ et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med 2017 Sep 11 PMID: 28893134 Free Article
  89. Wang MT, Liou JT, Lin CW et al Association of Cardiovascular Risk With Inhaled Long-Acting Bronchodilators in Patients With Chronic Obstructive Pulmonary Disease. A Nested Case-Control Study. JAMA Intern Med. Published online January 2, 2018 PMID: 29297057 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2666790
  90. Papi A Vestbo J, Fabbri L et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): A double-blind, parallel group, randomised controlled trial. Lancet 2018 Feb 8; PMID: 29429593 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30206-X/fulltext - Agusti A. Filling the gaps in COPD: The TRIBUTE study. Lancet 2018 Feb 8 PMID: 29429594 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30252-6/fulltext
  91. Gonzalez AV, Coulombe J, Ernst P, Suissa S et al. Long-term use of inhaled corticosteroids in COPD and the risk of fracture. Chest 2018 Feb; 153:321. PMID: 28716642 http://journal.chestnet.org/article/S0012-3692(17)31243-6/fulltext - Cho YJ, Sin DD. Inhaled corticosteroids and fractures in COPD: Can we finally put this to bed? Chest 2018 Feb; 153:293. PMID: 29406210 http://journal.chestnet.org/article/S0012-3692(17)31481-2/fulltext
  92. Stolz D et al. Intensified therapy with inhaled corticosteroids and long-acting beta2-agonists at the onset of upper respiratory tract infection to prevent chronic obstructive pulmonary disease exacerbations. A multicenter, randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med 2018 May 1; 197:1136. PMID: 29266965 https://www.atsjournals.org/doi/10.1164/rccm.201709-1807OC - Wedzicha JA, Martinez FJ. Intensifying long-acting beta-agonist/corticosteroid therapy at acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2018 May 1; 197:1096. PMID: 29451809 https://www.atsjournals.org/doi/10.1164/rccm.201801-0202ED
  93. Chapman KR, Hurst JR, Frent SM et al. Long-term triple therapy de-escalation to indacaterol/ glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET): A randomized, double-blind, triple-dummy clinical trial. Am J Respir Crit Care Med 2018 Aug 1; 198:32 PMID: 29779416 Free Article https://www.atsjournals.org/doi/10.1164/rccm.201803-0405OC
  94. NEJM Knowledge+ Question of the Week. Nov 17, 2020 https://knowledgeplus.nejm.org/question-of-week/229/ - Niewoehner DE. Clinical practice. Outpatient management of severe COPD. N Engl J Med 2010 Apr 16; 362:1407. PMID: 20393177 https://www.nejm.org/doi/full/10.1056/NEJMcp0912556
  95. Devereux G et al. Effect of theophylline as adjunct to inhaled corticosteroids on exacerbations in patients with COPD: A randomized clinical trial. JAMA 2018 Oct 16; 320:1548. PMID: 30326124 https://jamanetwork.com/journals/jama/fullarticle/2707459 - Criner GJ, Celli BR. Failure of low-dose theophylline to prevent exacerbations in patients with COPD. JAMA 2018 Oct 16; 320:1541. PMID: 30326108 https://jamanetwork.com/journals/jama/fullarticle/2707440
  96. Zheng Y, Zhu J, Liu Y et al Triple therapy in the management of chronic obstructive pulmonary disease: systematic review and meta-analysis. BMJ 2018;363:k4388 PMID: 30401700 Free PMC Article https://www.bmj.com/content/363/bmj.k4388
  97. Nielsen AO, Pedersen L, Sode BF, Dahl M beta-Blocker Therapy and Risk of Chronic Obstructive Pulmonary Disease- A Danish Nationwide Study of 1.3 Million Individuals. EClinicalMedicine Open Access. Jan 28, 2019 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30004-5/fulltext
  98. Riley CM, Sciurba FC. Diagnosis and Outpatient Management of Chronic Obstructive Pulmonary Disease. A Review. JAMA. 2019;321(8):786-797. PMID: 30806700 https://jamanetwork.com/journals/jama/fullarticle/2725693
  99. Chong J, Leung B, Poole P. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017 Sep 19;9:CD002309. Review. PMID: 28922692
  100. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med. 1980 Sep;93(3):391-8. PMID: 6776858
  101. Syamlal G, Doney B, Mazurek JM. Chronic Obstructive Pulmonary Disease Prevalence Among Adults Who Have Never Smoked, by Industry and Occupation - United States, 2013-2017. MMWR Morb Mortal Wkly Rep 2019;68:303-307 https://www.cdc.gov/mmwr/volumes/68/wr/mm6813a2.htm
  102. Suissa S et al. Comparative effectiveness and safety of LABA-LAMA vs LABA-ICS treatment of COPD in real-world clinical practice. Chest 2019 Jun; 155:1158. PMID: 30922950
  103. Bhatt SP, Balte PP, Schwartz JE et al. Discriminative accuracy of FEV1:FVC thresholds for COPD-related hospitalization and mortality. JAMA 2019 Jun 25; 321:2438-2447. PMID: 31237643 https://jamanetwork.com/journals/jama/fullarticle/2736562 - Vestbo J, Lange P. Accuracy of airflow obstruction thresholds for predicting COPD-related hospitalization and mortality: Can simple diagnostic thresholds be used for a complex disease? JAMA 2019 Jun 25; 321:2412-2413 PMID: 31237620 https://jamanetwork.com/journals/jama/fullarticle/2736536
  104. Sator L, Horner A, Studnicka M, et al. Overdiagnosis of COPD in subjects with unobstructed spirometry: A BOLD analysis. Chest 2019 Aug; 156:277-288. PMID: 30711480 - Vanfleteren LEGW, Andersson AE, Fabbri LM. COPD: What's in a name? Mismatch of diagnostic labels and required physiologic features. Chest 2019 Aug; 156:195-196 PMID: 31395252
  105. Dransfield MT, Voelker H, Bhatt SP et al Metoprolol for the Prevention of Acute Exacerbations of COPD. N Engl J Med, October 20, 2019 PMID: 31633896 https://www.nejm.org/doi/full/10.1056/NEJMoa1908142 - MacNee W Beta-Blockers in COPD - A Controversy Resolved? N Engl J Med, October 20, 2019 PMID: 31633892 https://www.nejm.org/doi/full/10.1056/NEJMe1912664
  106. Wilson ME, Dobler CC, Morrow AS et al. Association of home noninvasive positive pressure ventilation with clinical outcomes in chronic obstructive pulmonary disease: A systematic review and meta-analysis. JAMA 2020 Feb 4; 323:455. PMID: 32016309 https://jamanetwork.com/journals/jama/fullarticle/2760390
  107. Park HY, Kang D, Shin SH et al Chronic obstructive pulmonary disease and lung cancer incidence in never smokers: a cohort study Thorax. April 2, 2020 PMID: 32241883 Free Article https://thorax.bmj.com/content/early/2020/03/10/thoraxjnl-2019-213732.full
  108. Suissa S, Dell'Aniello S, Ernst P. Comparative effects of LAMA-LABA-ICS vs LAMA-LABA for COPD: Cohort study in real-world clinical practice. Chest 2020 Apr; 157:846 PMID: 31759966 https://journal.chestnet.org/article/S0012-3692(19)34225-4/pdf
  109. Nici L, Mammen MJ, Charbek E et al Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Apr 13 PMID: 32283960 https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0625ST
  110. Rabe KF, Martinez FJ, Ferguson GT et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N Engl J Med 2020 Jul 2; 383:35. PMID: 32579807 https://www.nejm.org/doi/10.1056/NEJMoa1916046
  111. Labaki WW, Rosenberg SR. Chronic obstructive pulmonary disease. Ann Intern Med 2020 Aug 4; 173:ITC17 PMID: 32745458 https://www.acpjournals.org/doi/10.7326/AITC202008040
  112. Verberkt CA et al. Effect of sustained-release morphine for refractory breathlessness in chronic obstructive pulmonary disease on health status: A randomized clinical trial. JAMA Intern Med 2020 Aug 17; [e-pub] PMID: 32804188 - Widera EW. The role of opioids in patients with chronic obstructive pulmonary disease and chronic breathlessness. JAMA Intern Med 2020 Aug 17; [e-pub]. PMID: 32804196
  113. Lacasse Y et al. Randomized trial of nocturnal oxygen in chronic obstructive pulmonary disease. N Engl J Med 2020 Sep 17; 383:1129 PMID: 32937046 https://www.nejm.org/doi/10.1056/NEJMoa2013219
  114. Jacobs SS, Krishnan JA, Lederer DJ, et al. Home Oxygen Therapy for Adults with Chronic Lung Disease. An Official American Thoracic Society Clinical Practice Guideline Am J Respir Crit Care Med. 2020 Nov 15;202(10):e121-e141 PMID: 33185464 https://www.atsjournals.org/doi/full/10.1164/rccm.202009-3608ST - Ekstrom M et al. Long-term oxygen therapy for 24 or 15 hours per day in severe hypoxemia. N Engl J Med 2024 Sep 19; 391:977. PMID: 39254466 https://www.nejm.org/doi/10.1056/NEJMoa2402638
  115. Boyles S Triple Treatment Reduces COPD Exacerbations. Also a suggestion of reduced mortality with one dose level, large multicenter ETHOS trial finds. MedPage Today June 25, 2021 https://www.medpagetoday.com/meetingcoverage/ats/87261 - Rabe KF, Martinez FJ, Ferguson GT et al Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N Engl J Med 2020; 383:35-48 PMID: 32579807 https://www.nejm.org/doi/full/10.1056/NEJMoa1916046
  116. Lindenauer PK, Stefan MS, Pekow PS et al. Association between initiation of pulmonary rehabilitation after hospitalization for COPD and 1-year survival among Medicare beneficiaries. JAMA. 2020;323(18):1813-1823 PMID: 32396181 PMCID: PMC7218499 Free PMC article https://jamanetwork.com/journals/jama/fullarticle/2765730
  117. Gever J Triple Therapy for COPD: One Drug Too Many, Too Often? Dropping the inhaled steroid seems to help many patients in real-world study. MedPage Today May 19, 2022 https://www.medpagetoday.com/meetingcoverage/ats/98804
  118. Ekstrom M, Ferreira D, Chang S et al Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease. The BEAMS Randomized Clinical Trial. JAMA. 2022;328(20):2022-2032. November 22/29 PMID: 36413230 https://jamanetwork.com/journals/jama/fullarticle/2798741
  119. Lacasse Y et al. Home oxygen for moderate hypoxaemia in chronic obstructive pulmonary disease: A systematic review and meta-analysis. Lancet Respir Med 2022 Nov; 10:1029. PMID: 35817074 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00179-5/fulltext
  120. NEJM Knowledge+ - Oba Y, Keeney E, Ghatehorde N, Dias S. Dual combination therapy versus long-acting bronchodilators alone for chronic obstructive pulmonary disease (COPD): a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2018 Dec 3;12(12):CD012620. PMID: 30521694 PMCID: PMC6517098 Free PMC article
  121. Agusti A, Celli BR, Criner GJ et al. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD executive summary. Am J Respir Crit Care Med. 2023 Apr 1;207(7):819-837. PMID: 36856433 PMCID: PMC10111975 Free PMC article https://www.atsjournals.org/doi/10.1164/rccm.202301-0106PP
  122. Short E Cognitive Testing Flags COPD Patients Unable to Maintain Proper Inhaler Technique. Lower MoCA scores associated with improper inhaler use despite face-to-face training. MedPage Today April 28, 2023 https://www.medpagetoday.com/pulmonology/smokingcopd/104266 - Iamthanaporn C, Wisitsartkul A, Chuaychoo B. Cognitive impairment according to Montreal Cognitive Assessment independently predicts the ability of chronic obstructive pulmonary disease patients to maintain proper inhaler technique. BMC Pulm Med, 2023 23:144. April 26. PMID: 37101175 PMCID: PMC10131352 Free PMC article https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-023-02448-x
  123. Feldman WB et al. Chronic obstructive pulmonary disease exacerbations and pneumonia hospitalizations among new users of combination maintenance inhalers. JAMA Intern Med 2023 May 22; [e-pub]. PMID: 37213116 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2804685
  124. Bhatt SP et al. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. N Engl J Med 2023 May 21; [e-pub] PMID: 37272521 https://www.nejm.org/doi/10.1056/NEJMoa2303951
  125. Allinson JP, Vlies BH, Brill SE et al A Double-Blind, Randomised, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable COPD. Am J Respir Crit Care Med. 2023 Jul 14. Online ahead of print. PMID: 37450935
  126. Rahman AA, Dell'Aniello S, Moodie EEM et al Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease. A Population-Based Cohort Study Ann Intern Med 2024. Jan 16 PMID: 38224592 https://www.acpjournals.org/doi/10.7326/M23-0849
  127. Gooneratne NS, Patel NP, Corcoran A. Chronic obstructive pulmonary disease diagnosis and management in older adults. J Am Geriatr Soc. 2010 Jun;58(6):1153-62. . PMID: 20936735 Review. https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/j.1532-5415.2010.02875.x - Cortopassi F, Gurung P, Pinto-Plata V. Chronic Obstructive Pulmonary Disease in Elderly Patients. Clin Geriatr Med. 2017 Nov;33(4):539-552. PMID: 28991649 Review.
  128. NEJM Knowledge+
  129. Devereux G et al. Bisoprolol in patients with chronic obstructive pulmonary disease at high risk of exacerbation: The BICS randomized clinical trial. JAMA 2024 May 19; [e-pub]. PMID: 38762800 https://jamanetwork.com/journals/jama/fullarticle/2819083 - Han MK, Dransfield MT. beta-Blockers in chronic obstructive pulmonary disease - Walking the tightrope. JAMA 2024 May 19; [e-pub] PMID: 38762796 https://jamanetwork.com/journals/jama/fullarticle/2819086
  130. King DA, Cordova F, Scharf SM. Nutritional aspects of chronic obstructive pulmonary disease Proc Am Thorac Soc. 2008 May 1;5(4):519-23 PMID: 18453365 PMCID: PMC2645329 Free PMC article. Review.
  131. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for Diagnosis, Management and Prevention of COPD. February 2015. http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html - Global Initiative for Chronic Obstructive Lung Disease (GOLD) http://www.goldcopd.com/GuidelinesResources.asp?l1=2&l2=0 - Updated guideline synthesis: COPD Part I. Diagnosis and Management http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart1_4.inc http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart1_6.inc http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart1_7.inc includes updated GOLD recommendations. - Updated guideline synthesis: COPD Part II. Diagnosis and Management of Acute Exacerbations to include the updated GOLD recommendations. http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart2_4.inc http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart2_7.inc) http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart2_8.inc - PART III. PULMONARY REHABILITATION http://www.guideline.gov/Compare/comparison.aspx?file=COPDPart3_2.inc - CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): PULMONARY REHABILITATION http://www.guideline.gov/Compare/comparison.aspx?file=COPD_Pulmonary_Rehab5.inc - DIAGNOSIS AND MANAGEMENT OF STABLE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) http://www.guideline.gov/Compare/comparison.aspx?file=COPD_STABLE9.inc - Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2023 GOLD Report. https://goldcopd.org/2023-gold-report-2/. - Pocket Guide to COPD Diagnosis, Management, and Prevention Global Initiative for Chronic Obstructive Lung Disease (GOLD) http://www.goldcopd.org/guidelines-pocket-guide-to-copd-diagnosis.html - Pocket Guide to COPD Diagnosis, Management and Prevention. A Guide for Healthcare Professionals. Updated 2013 http://www.goldcopd.org/uploads/users/files/GOLD_Pocket_2013_Mar27.pdf
  132. DIAGNOSIS AND MANAGEMENT OF STABLE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). GUIDELINES COMPARED American College of Physicians (ACP) Global Initiative for Chronic Obstructive Lung Disease (GOLD) Singapore Ministry of Health (SMOH). Chronic obstructive http://www.guideline.gov/Compare/comparison.aspx?file=COPD_STABLE8.inc - CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): DIAGNOSIS AND MANAGEMENT OF ACUTE EXACERBATIONS Global Initiative for Chronic Obstructive Lung Disease (GOLD) Singapore Ministry of Health (SMOH) Department of Veterans Affairs, Department of Defense (VA/DoD) http://www.guideline.gov/Compare/comparison.aspx?file=COPD_ACUTE10.inc