Diagnosis and Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease | EB Medicine

Diagnosis and Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

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Table of Contents
About This Issue

As more and more patients present to the ED with symptoms that suggest an acute exacerbation of COPD –worsening dyspnea, cough and sputum production  – emergency clinicians can improve patient comfort and possibly mitigate morbidity and mortality with the right testing and treatment interventions:

COPD is a clinical diagnosis, but some tests can exclude comorbid conditions

When to give antibiotics and when to culture

The SpO2 range to aim for

ECG findings typical of COPD

The role of ultrasound

Oxygen, bronchodilators, corticosteroids, and antibiotics: which ones, and how much?

Reviewing noninvasive ventilation and intubation options

Table of Contents
  1. Abstract
  2. Case Presentations
  3. Introduction
  4. Selected Abbreviations
  5. Critical Appraisal of the Literature
  6. Definition
  7. Epidemiology, Etiology, and Pathophysiology
    1. Epidemiology of COPD
    2. Etiology of Acute Exacerbation of COPD
    3. Pathophysiology of COPD
  8. Differential Diagnosis
  9. Prehospital Care
  10. Emergency Department Evaluation
    1. History
    2. Physical Examination
  11. Diagnostic Studies
    1. Laboratory Testing and Arterial Blood Gas Sampling
    2. Chest Imaging
    3. Electrocardiogram
    4. Serum Cardiac Biomarkers
    5. Microbiologic Evaluation
    6. Point-of-Care Ultrasound
    7. Other Tests
  12. Treatment
    1. Supplemental Oxygen
    2. Bronchodilators
    3. Corticosteroids
    4. Antibiotics
    5. Magnesium Sulfate
    6. Methylxanthines
    7. Noninvasive Positive-Pressure Ventilation
    8. Mechanical Ventilation
    9. High-Flow Nasal Cannula
  13. Controversies and Cutting Edge
    1. Biomarkers
    2. Heliox
    3. Capnography
  14. Disposition
    1. Outpatient Versus Inpatient Care
    2. Management for Patients Going Home
  15. Summary
  16. Risk Management Pitfalls in Managing Acute Exacerbation of COPD
  17. Time- and Cost-Effective Strategies
  18. Case Conclusions
  19. Clinical Pathways
    1. Clinical Pathway For Diagnostic Evaluation of Acute Exacerbation of COPD
    2. Clinical Pathway For Management of Acute Exacerbation of COPD
  20. Tables and Figures
    1. Table 1. Model of Symptom Risk Evaluation of COPD
    2. Table 2. Differential Diagnosis of Acute Exacerbation of COPD
    3. Table 3. Summary of Diagnostic Testing in Patients With Acute Exacerbation of COPD
    4. Table 4. Arrhythmias Related to COPD
    5. Table 5. Electrocardiogram Abnormalities Related to COPD
    6. Table 6. Antibiotics to Consider for the Treatment of Acute Exacerbation of COPD
    7. Table 7. Exclusion Criteria for Noninvasive Positive-Pressure Ventilation and Indications for Intubation
    8. Table 8. Ventilator Setting Recommendations Post Intubation
    9. Table 9. Factors Associated With Risk of Death From COPD Exacerbation
    10. Table 10. Indications for Hospital Admission
    11. Figure 1. Saber-Sheath Trachea on Computed Tomography
    12. Figure 2. Electrocardiogram of Multifocal Atrial Tachycardia
    13. Figure 3. Electrocardiogram of Right Ventricular Hypertrophy
    14. Figure 4. End-Tidal Capnography Tracings
  21. References


Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a clinical diagnosis that is based on changes in dyspnea, cough, and/or sputum production in a COPD patient; however, patients presenting with an acute exacerbation may be undiagnosed or have a variety of comorbid conditions that can complicate diagnosis. This issue presents strategies and algorithms for the early use of evidence-based interventions, including appropriate use of antibiotics, bronchodilators, and corticosteroids, along with noninvasive ventilation with capnography, to minimize morbidity and mortality associated with this disease.

Case Presentation

It is change of shift, and you receive sign-out on a 67-year-old gentleman with a history of COPD presenting with 5 days of worsening productive cough, wheezing, and increased albuterol use despite outpatient treatment with prednisone and doxycycline. His oxygen saturation was 86% on arrival, and the nurse placed him on oxygen therapy at 6 L/min via nasal cannula shortly before you arrived. You find the patient sitting on the edge of his bed, tachypneic, with increased work of breathing and audible wheezing on auscultation. He is alert and acknowledges your presence but does not speak. You wonder why he continues to be hypoxic and if there is any other intervention that is indicated . . .

Your next patient is a 57-year-old woman with a history of smoking 2 packs of cigarettes per day. Her husband called 911 because she was having increased difficulty with breathing and productive cough for the previous week. She has no documented pulmonary history. Upon arrival, EMS noted that she could not speak in full sentences, her oxygen saturation was 81% on room air, and she had diffuse end-expiratory wheezing on auscultation. IV access was obtained. She was given continuous albuterol nebulization without relief and started on supplemental oxygen. The chest x-ray does not demonstrate a focal infiltrate; however, her lungs appear hyperinflated, with flattened diaphragms and a small cardiac silhouette. You wonder if she has COPD with an acute exacerbation and whether prednisone and antibiotics are indicated . . .


Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. From a financial perspective, COPD exacted a net $36 billion toll in 2010 in the United States, and its costs are expected to continue to rise.1 Despite decreasing tobacco use nationally, emergency department (ED) visits for COPD-related problems continue to climb, with over 1.7 million in 2011 alone. Moreover, about one-fifth of COPD patients presenting to the ED required hospitalization.2

COPD is characterized by a persistent airflow limitation, after administration of bronchodilators, that can be identified on spirometry as a ratio of forced expired volume in 1 second (FEV1) to forced vital capacity (FVC) that is < 70%. Although COPD is a treatable disease, the airflow limitation is not fully reversible. Previous definitions of COPD have included the terms emphysema and chronic bronchitis; however, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines do not, and they clarify the distinction: Emphysema is a pathological term that refers to the destruction of alveoli, which can be present but is not inherent in patients with COPD. Chronic bronchitis is an independent clinical entity characterized by cough and sputum production for at least 3 months in each of 2 consecutive years and can occur without the development of airflow limitation. Guidelines define acute exacerbation of COPD (AECOPD) as an event characterized by a worsening of the patient’s respiratory symptoms (dyspnea, cough, and/or sputum production) that is beyond normal day-to-day variations, and that leads to a change in medication.3,4

Patients with COPD often have comorbid conditions that may have either resulted from COPD, (eg, pulmonary hypertension or malnutrition) or are simply associated with it (eg, anxiety, cardiovascular disease, sleep apnea, and venous thromboembolism).5 Because of the myriad presenting features of COPD and/or these comorbidities, diagnostic challenges exist when these patients present to the ED in extremis. This issue of Emergency Medicine Practice reviews the most recent evidence-based recommendations for the diagnosis and management of AECOPD, with a focus on tailoring management to the underlying pathophysiology of the disease state.

Selected Abbreviations

AECOPD Acute exacerbation of COPD
ATS American Thoracic Society
BLUE Bedside lung ultrasound in emergency
CAT COPD Assessment Test
CI Confidence interval
COPD Chronic obstructive pulmonary disease
ERS European Respiratory Society
FEV1 Forced expired volume in 1 second
FVC Forced vital capacity
GOLD Global Initiative for Chronic Obstructive Lung Disease
IPAP Inspiratory positive airway pressure
mMRC Modified Medical Research Council scale
NIPPV Noninvasive positive-pressure ventilation
PaCO2 Arterial partial pressure of carbon dioxide
PvCO2 Venous partial pressure of carbon dioxide
REDUCE Reduction in the Use of Corticosteroids in Exacerbated COPD Trial
RR Relative risk
SpO2 Oxygen saturation measured by pulse oximetry

Critical Appraisal of the Literature

A literature search was performed in PubMed, with the search terms COPDchronic obstructive pulmonary disease, and acute COPD exacerbation. The search was limited to articles published within the last 10 years, and studies relating specifically to acute COPD exacerbation (as opposed to stable COPD) were reviewed. In addition, references were appraised for additional relevant articles. A total of 127 articles have been included in this review.

The Cochrane Library was searched for systematic reviews using the key term acute COPD exacerbation, which identified 25 articles. In addition, guidelines from the GOLD, American Thoracic Society (ATS), European Respiratory Society (ERS), American College of Chest Physicians (ACCP), and National Institute for Health and Care Excellence (NICE) were reviewed.

COPD is a composite of heterogenous etiologies that contribute to variations in the presentation in patient populations. For example, it has been increasingly recognized that exposures to substances other than cigarette smoke contribute to the pathophysiology of disease. The asthma-COPD overlap syndrome is a newly identified condition, with varied acceptance in the community, but it illustrates that a history of asthma does not exclude coexisting COPD. Cohorts included in studies are similarly diverse, making the generalizability of results challenging. Clinically, the varied presentation of COPD makes detecting previously undiagnosed patients more difficult; however, these patients may well be the ones seeking care in the ED.

The current state of the literature remains limited mainly by the retrospective observational nature of most studies. There are few randomized controlled trials to direct management of acute COPD exacerbations. Furthermore, existing studies have wide-ranging outcome measures, such as pulmonary function, symptom scores, rate of exacerbation, and short-term mortality. In the absence of high-quality data, some interventions should be directed by prior individual patient response.

Risk Management Pitfalls in Managing Acute Exacerbation of COPD

1. “But the patient said he has asthma.”

Not all wheezing is asthma, and not all patient-reported histories of asthma are actually asthma. Ensure that the patient’s risk factors and history align with the diagnosis.

2. “I know she has COPD, but I doubt that’s what’s causing her respiratory distress.”

Inadequately assessing triggers for AECOPD may lead you down an expensive and ultimately fruitless diagnostic path. A good history can increase efficiency, decrease costs, and most importantly, improve clinical outcomes.

3. “This COPD patient’s respiratory and hemodynamic statuses are simply not improving, despite doing everything by the book. What’s going on?”

Largely due to the high systemic inflammatory state in individuals with COPD, patients presenting with an AECOPD have a surprisingly high incidence of pulmonary embolism. Be vigilant to ensure that the patient does not have a pulmonary embolism when he fails to respond as expected to the standard interventions for an AECOPD.

4. “COPD is not possible - I don’t hear any wheezing.”

Although wheezing is often considered a hallmark of COPD, a lack of wheezing can actually signify a loss of effective airflow and can indicate imminent clinical deterioration.

5. “His COPD exacerbation wasn’t that bad - I didn’t need to actually measure anything.”

Much of the physical examination is inherently subjective, which may cause an underappreciation of the severity of a patient’s AECOPD. A focused diagnostic assessment can identity poor prognostic markers.

6. “We need to keep the oxygen saturation as high as possible to make sure that oxygenation remains stable.”

Not only is there no benefit to maintaining an oxygen saturation in the high 90s in a patient with COPD, it may actually be harmful. Recent guidelines agree on an arterial saturation target of 88% to 92%.

7. “She looks really sick; let’s intubate to assist her breathing now.”

Many patients can avoid endotracheal intubation with early implementation of NIPPV with bilevel positive airway pressure. Taking into account the absolute contraindications for NIPPV, consider a trial to assist breathing.

8. “We need to provide high tidal volumes on the ventilator to blow down the CO2!”

Despite a desire to increase minute ventilation to remove CO2 in a COPD patient, excessive tidal volumes on the ventilator may actually injure the lungs.

9. “I don’t need to give any oral or IV corticosteroids because the patient is already on inhaled ones.”

Although some systemic absorption of inhaled steroids can occur, it is insufficient to suppress the inflammatory process in the airways during an AECOPD. Therefore, oral or IV steroids are necessary for these circumstances.

10. “There’s no need to tell the patient to stop smoking because it’s so obvious and, plus, there’s nothing I can do to change that.”

Smoking cessation can normalize the natural rate of decline in a person’s lung function, even in a long-term smoker, and brief clinician advice about the need to stop smoking

Tables and Figures

Table 1. Model of Symptom Risk Evaluation of COPD



Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.

  1. Ford ES, Murphy LB, Khavjou O, et al. Total and state-specific medical and absenteeism costs of COPD among adults aged = 18 years in the United States for 2010 and projections through 2020. Chest. 2015;147(1):31-45. (Retrospective observational study)
  2. Ford ES. Hospital discharges, readmissions, and ED visits for COPD or bronchiectasis among US adults: findings from the nationwide inpatient sample 2001-2012 and Nationwide Emergency Department Sample 2006-2011. Chest. 2015;147(4):989-998. (Retrospective observational study)
  3. * Celli BR, MacNee W, Agusti A, et al. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004;23(6):932-946. (Systematic review; consensus guidelines)
  4. * Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016. http://goldcopd.org/. Accessed September 10, 2017. (Systematic review; consensus guidelines)
  5. Cavailles A, Brinchault-Rabin G, Dixmier A, et al. Comorbidities of COPD. Eur Respir Rev. 2013;22(130):454-475. (Review article)
  6. Mannino D, Watt G, Hole D, et al. The natural history of chronic obstructive pulmonary disease. Eur Respir J. 2006;27(3):627-643. (Review article)
  7. Heron M. Deaths: leading causes for 2014. Natl Vital Stat Rep. 2016;65(5):1-96. (Retrospective observational study)
  8. Mathers C, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLOS Medicine. 2006;3(11):e442. (Retrospective epidemiologic study)
  9. Yeatts KB, Lippmann SJ, Waller AE, et al. Population-based burden of COPD-related visits in the ED. Chest. 2013;144(3):784-793. (Retrospective observational study; 97,511 patients)
  10. Mannino DM, Higuchi K, Tzy-Chyi Y, et al. Economic burden of COPD in the presence of comorbidities. Chest. 2015;148(1):138-150. (Retrospective observational study; 183,681 patients)
  11. Suissa S, Dell’Anioello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67(11):957-963. (Prospective observational study; 73,106 patients)
  12. Seemungal T, Harper-Owen R, Bhowmik A, et al. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;164(9):1618-1623. (Prospective observational study; 83 patients)
  13. Querol-Ribelles J, Molina J, Naberan K, et al. Discrepency between antibiotics administered in acute exacerbations of chronic bronchitis and susceptibility of isolated pathogens in respiratory samples: multicentre study in primary care setting. Int J Antimicrob Ag. 2006;28(5):472-476. (Prospective observational study; 1537 patients)
  14. Monso E, Ruiz J, Manterola J, et al. Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Care Med. 1995;152(4):1316-1320. (Prospective observational study; 69 patients)
  15. Ko F, Ip M, Chan PK, et al. A 1-year prospective study of the infectious etiology in patients hospitalized with acute exacerbations of COPD. Chest. 2007;131(1):44-52. (Prospective, observational study; 373 patients)
  16. Atkinson RW, Anderson HR, Sunyer J, et al. Acute effects of particulate air pollution on respiratory admissions. Am J Respir Crit Care Med. 2001;164(10):1860-1866. (Retrospective observational study; 79,008 patients)
  17. Peacock JL, Anderson HR, Bremner SA, et al. Outdoor air pollution and respiratory health in patients with COPD. Thorax. 2011;66(7):591-596. (Prospective observational study; 94 patients)
  18. Schikowski T, Mills IC, Anderson HR, et al. Ambient air pollution: a cause of COPD? Eur Respir J. 2014(43):250-263. (Systematic review; 14 studies)
  19. Macklem PT. Therapeutic implications of the pathophysiology of COPD. Eur Respir J. 2010;35:676-680. (Review article)
  20. Cameron L, Pilcher J, Weatherall M, et al. The risk of serious adverse outcomes associated with hypoxaemia and hyperoxaemia in acute exacerbations of COPD. Postgrad Med J. 2012;88(1046):684-689. (Retrospective observational study; 680 patients)
  21. Ringbaek TJ, Terkelsen J, Lange P. Outcomes of acute exacerbations in COPD in relation to pre-hospital oxygen therapy. Eur Clin Respir J. 2015;2:10.3402/ecrj.v2.27283. eCollection 2015. (Retrospective observational study; 405 patients)
  22. Denniston AK, O’Brien C, Stableforth D. The use of oxygen in acute exacerbations of chronic obstructive pulmonary disease: a prospective audit of pre-hospital and hospital emergency management. Clin Med (Lond). 2002;2(5):449-451. (Prospective observational study; 97 patients)
  23. Mal S, McLeod S, Iansavichene A, et al. Effect of out-of-hospital noninvasive positive-pressure support ventilation in adult patients with severe respiratory distress: a systematic review and meta-analysis. Ann Emerg Med. 2014;63(5):600-607. (Systematic review; 7 studies, 632 patients)
  24. US Preventive Services Task Force (USPSTF), Siu AL, Bibbins-Domingo K, et al. Screening for chronic obstructive pulmonary disease: US Preventive Services Task Force recommendation statement. JAMA. 2016;315(13):1372-1377. (Systematic review; consensus guidelines)
  25. Straus SE, McAlister FA, Sackett DL, et al. The accuracy of patient history, wheezing, and laryngeal measurements in diagnosing obstructive airway disease. CARE-COAD1 Group. Clinical assessment of the reliability of the examination-chronic obstructive airways disease. JAMA. 2000;283(14):1853-1857. (Prospective observational study; 309 patients)
  26. Soler N, Agusti C, Angrill J, et al. Bronchoscopic validation of the significance of sputum purulence in severe exacerbations of chronic obstructive pulmonary disease. Thorax. 2007;62(1):29-35. (Prospective observational study; 40 patients)
  27. Seemungal TA, Donaldson GC, Bhowmik A, et al. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161(5):1608-1613. (Prospective observational study; 101 patients)
  28. Austin MA, Wills KE, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:c5462. (Randomized controlled trial; 405 patients)
  29. Gunen H, Hacievliyagil SS, Kosar F, et al. Factors affecting survival of hospitalised patients with COPD. Eur Respir J. 2005;26(2):234-241. (Prospective observational study; 205 patients)
  30. Mattos WL, Signori LG, Borges FK, et al. Accuracy of clinical examination findings in the diagnosis of COPD. J Bras Pneumol. 2009;35(5):404-408. (Prospective case-control study; 98 patients)
  31. Bohadana AB, Mohankumar T. Symptoms and signs in the assessment of chronic airflow obstruction. Indian J Chest Dis Allied Sci. 1982;24(2-3):133-142. (Review)
  32. Fletcher CM. The clinical diagnosis of pulmonary emphysema; an experimental study. Proc R Soc Med. 1952;45(9):577-584. (Retrospective observational study)
  33. Holleman DR Jr, Simel DL, Goldberg JS. Diagnosis of obstructive airways disease from the clinical examination. J Gen Intern Med. 1993;8(2):63-68. (Prospective observational study)
  34. Schapira RM, Schapira MM, Funahashi A, et al. The value of the forced expiratory time in the physical diagnosis of obstructive airways disease. JAMA. 1993;270(6):731-736. (Cross-sectional study; 500 patients)
  35. Marini JJ, Pierson DJ, Hudson LD, et al. The significance of wheezing in chronic airflow obstruction. Am Rev Respir Dis. 1979;120(5):1069-1072. (Prospective observational study; 83 patients)
  36. Straus SE, McAlister FA, Sackett DL, et al. Clinical assessment of the reliability of the examination-chronic obstructive airways disease. Accuracy of history, wheezing, and forced expiratory time in the diagnosis of chronic obstructive pulmonary disease. J Gen Intern Med. 2002;17(9):684-688. (Prospective observational study; 161 patients)
  37. Tokuda Y, Miyagi S. Physical diagnosis of chronic obstructive pulmonary disease. Intern Med. 2007;46(23):1885-1891. (Review article)
  38. McKeever TM, Hearson G, Housley G, et al. Using venous blood gas analysis in the assessment of COPD exacerbations: a prospective cohort study. Thorax. 2016;71(3):210-215. (Prospective observational study; 234 patients)
  39. Kelly AM, Kerr D, Middleton P. Validation of venous pCO2 to screen for arterial hypercarbia in patients with chronic obstructive airways disease. J Emerg Med. 2005;28(4):377-379. (Prospective observational study; 112 patients)
  40. Asiimwe AC, Brims FJ, Andrews NP, et al. Routine laboratory tests can predict in-hospital mortality in acute exacerbations of COPD. Lung. 2011;189(3):225-232. (Retrospective, observational study; 5985 patients)
  41. Webb WR. Radiology of obstructive pulmonary disease. AJR Am J Roentgenol. 1997;169(3):637-647. (Review article)
  42. Emerman CL, Cydulka RK. Evaluation of high-yield criteria for chest radiography in acute exacerbation of chronic obstructive pulmonary disease. Ann Emerg Med. 1993;22(4):680-684. (Retrospective observational study; 742 patients)
  43. Sherman S, Skoney JA, Ravikrishnan KP. Routine chest radiographs in exacerbations of chronic obstructive pulmonary disease. Diagnostic value. Arch Intern Med. 1989;149(11):2493-2496. (Retrospective observational study; 242 patients)
  44. Tsai TW, Gallagher EJ, Lombardi G, et al. Guidelines for the selective ordering of admission chest radiography in adult obstructive airway disease. Ann Emerg Med. 1993;22(12):1854-1858. (Prospective observational study; 128 patients)
  45. MacDonald MI, Shafuddin E, King PT, et al. Cardiac dysfunction during exacerbations of chronic obstructive pulmonary disease. Lancet Respir Med. 2016;4(2):138-148. (Review article)
  46. McCord J, Barzak S. Multifocal atrial tachycardia. Chest. 1998;113(1):202-209. (Review article)
  47. Goudis CA, Konstantinidis AK, Ntalas IV, et al. Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease. Int J Cardiol. 2015;199:264-273. (Review article)
  48. Vanfleteren LE, Franssen FM, Uszko-Lencer NH, et al. Frequency and relevance of ischemic electrocardiographic findings in patients with chronic obstructive pulmonary disease. Am J Cardiol. 2011;108(11):1669-1674. (Retrospective observational study; 543 patients)
  49. Lazovic B, Svenda MZ, Mazic S, et al. Analysis of electrocardiogram in chronic obstructive pulmonary disease patients. Med Pregl. 2013;66(3-4):126-129. (Retrospective observational study; 110 patients)
  50. Pavasini R, d’Ascenzo F, Campo G, et al. Cardiac troponin elevation predicts all-cause mortality in patients with acute exacerbation of chronic obstructive pulmonary disease: systematic review and meta-analysis. Int J Cardiol. 2015;191:187-193. (Systematic review, 10 studies; meta-analysis, 8 studies)
  51. Buchan A, Bennett R, Coad A, et al. The role of cardiac biomarkers for predicting left ventricular dysfunction and cardiovascular mortality in acute exacerbations of COPD. Open Heart. 2015;2(1):e000052. (Systematic review; 14 studies)
  52. Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359(22):2355-2365. (Review article)
  53. Sykes A, Mallia P, Johnston SL. Diagnosis of pathogens in exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2007;4(8):642-646. (Review article)
  54. Boixeda R, Almagro P, Diez-Manglano J, et al. Bacterial flora in the sputum and comorbidity in patients with acute exacerbations of COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:2581-2591. (Retrospective observational study; 536 patients)
  55. Larsen MV, Janner JH, Nielsen SD, et al. Bacteriology in acute exacerbation of chronic obstructive pulmonary disease in patients admitted to hospital. Scand J Infect Dis. 2009;41(1):26-32. (Retrospective observational study; 118 patients)
  56. Wu X, Chen D, Gu X, et al. Prevalence and risk of viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease: a meta-analysis. Mol Biol Rep. 2014;41(7):4743-4751. (Systematic review and meta-analysis; 17 studies)
  57. Zwaans WA, Mallia P, van Winden ME, et al. The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease-a systematic review. J Clin Virol. 2014;61(2):181-188. (Systematic review; 19 studies, 1728 patients)
  58. Akhtar S, Theodoro D, Gaspari R, et al. Resident training in emergency ultrasound: consensus recommendations from the 2008 Council of Emergency Medicine Residency Directors Conference. Acad Emerg Med. 2009;16 Suppl 2:S32-S36. (Consensus statement)
  59. Lichtenstein DA, Meziere GA. Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol. Chest. 2008;134(1):117-125. (Prospective observational study; 260 patients)
  60. Gallard E, Redonnet JP, Bourcier JE, et al. Diagnostic performance of cardiopulmonary ultrasound performed by the emergency physician in the management of acute dyspnea. Am J Emerg Med. 2015;33(3):352-358. (Prospective observational study; 147 patients)
  61. Laursen CB, Sloth E, Lambrechtsen J, et al. Focused sonography of the heart, lungs, and deep veins identifies missed life-threatening conditions in admitted patients with acute respiratory symptoms. Chest. 2013;144(6):1868-1875. (Prospective observational study; 139 patients)
  62. Laursen CB, Sloth E, Lassen AT, et al. Point-of-care ultrasonography in patients admitted with respiratory symptoms: a single-blind, randomised controlled trial. Lancet Respir Med. 2014;2(8):638-646. (Prospective randomized trial; 320 patients)
  63. Stolz LA, Stolz U, Fields JM, et al. Emergency medicine resident assessment of the emergency ultrasound milestones and current training recommendations. Acad Emerg Med. 2017;24(3):353-361. (Prospective observational study; 539 patients)
  64. Pothirat C, Chaiwong W, Phetsuk N, et al. Peak expiratory flow rate as a surrogate for forced expiratory volume in 1 second in COPD severity classification in Thailand. Int J Chron Obstruct Pulmon Dis. 2015;10:1213-1218. (Prospective observational study; 300 patients)
  65. Emerman CL, Cydulka RK. Use of peak expiratory flow rate in emergency department evaluation of acute exacerbation of chronic obstructive pulmonary disease. Ann Emerg Med. 1996;27(2):159-163. (Prospective observational study; 199 patients)
  66. Rizkallah J, Man SF, Sin DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009;135(3):786-793. (Systematic review and meta-analysis; 5 studies, 550 patients)
  67. Aleva FE, Voets LW, Simons SO, et al. Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD: a systematic review and meta-analysis. Chest. 2017;151(3):544-554. (Systematic review; 7 studies)
  68. * Vestbo J, Hurd SS, Agusti AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187(4):347-365. (Consensus statement; guidelines)
  69. Robinson TD, Freiberg DB, Regnis JA, et al. The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161(5):1524-1529. (Prospective observational study; 22 patients)
  70. Schreck D. Asthma pathophysiology and evidence-based treatment of severe exacerbations. Am J Health Syst Pharm. 2006;63(3). (Review article)
  71. Karpel JP, Pesin J, Greenberg D, et al. A comparison of the effects of ipratropium bromide and metaproterenol sulfate in acute exacerbations of COPD. Chest. 1990;98(4):835-839. (Prospective randomized trial; 32 patients)
  72. Gruber P, Swadron S. The acute presentation of chronic obstructive pulmonary disease in the emergency department: a challenging oxymoron. Emerg Med Pract. 2008;10(11):1-28. (Review article)
  73. McCrory DC, Brown CD. Anticholinergic bronchodilators versus beta2-symathomimetic agents for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2002(4):CD003900. (Systematic review; 4 trials)
  74. Turner MO, Patel A, Ginsburg S, et al. Bronchodilator delivery in acute airflow obstruction. A meta-analysis. Arch Intern Med. 1997;157(15):1736-1744. (Systematic review and meta-analysis; 12 studies, 507 patients)
  75. Turner JR, Corkery KJ, Eckman D, et al. Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction. Chest 1988;93(3):476-481. (Randomized controlled trial; 75 patients)
  76. Summer W, Elston R, Tharpe L, et al. Aerosol bronchodilator delivery methods. Arch Intern Med. 1989;149(3):618-623. (Randomized controlled trial; 36 patients)
  77. Keatings VM, Jatakanon A, Worsdell YM, et al. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997;155(2):542-548. (Prospective crossover study; 15 patients)
  78. Culpitt SV, Maziak W, Loukidis S, et al. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1635-1639. (Randomized controlled trial; 25 patients)
  79. Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet. 1999;354(9177):456-460. (Randomized controlled trial; 56 patients)
  80. Thompson WH, Nielson CP, Carvalho P, et al. Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. Am J Respir Crit Care Med. 1996;154(2 Pt 1):407-412. (Randomized controlled trial; 27 patients)
  81. Aaron SD, Vandemheen KL, Hebert P, et al. Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med. 2003;348(26):2618-2625. (Randomized controlled trial; 147 patients)
  82. Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med. 1999;340(25):1941-1947. (Randomized controlled trial; 271 patients)
  83. Schacke H, Docke W, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002;96(2):23-43. (Review article)
  84. de Jong YP, Uil SM, Grotjohan HP, et al. Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Chest. 2007;132(6):1741-1747. (Randomized controlled trial; 435 patients)
  85. * Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309(21):2223-2231. (Randomized controlled trial; 314 patients)
  86. National Institute for Health and Care Excellence (NICE). Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Clinical guideline [CG101]. June 2010. Available at: https://www.nice.org.uk/guidance/cg101. Accessed September 10, 2017. (Consensus statement; guidelines)
  87. Nseir S, Di Pompeo C, Cavestri B, et al. Multiple-drug-resistant bacteria in patients with severe acute exacerbation of chronic obstructive pulmonary disease: prevalence, risk factors, and outcome. Crit Care Med. 2006;34(12):2959-2966. (Prospective observational study; 857 patients)
  88. Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: a systematic review and meta-analysis. Chest. 2008;133(3):756-766. (Systematic review, meta-analysis; 35 trials, 2958 patients)
  89. * Vollenweider DJ, Jarrett H, Steurer-Stey CA, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;12:CD010257. (Systematic review and meta-analysis; 16 trials, 2068 patients)
  90. Stefan MS, Rothberg MB, Shieh MS, et al. Association between antibiotic treatment and outcomes in patients hospitalized with acute exacerbation of COPD treated with systemic steroids. Chest. 2013;143(1):82-90. (Retrospective observational study; 53,900 patients)
  91. Gonzalez JA, Garcia CH, Gonzalez PA, et al. Effect of intravenous magnesium sulfate on chronic obstructive pulmonary disease exacerbations requiring hospitalization: a randomized placebo-controlled trial. Archivos de Bronconeumologia. 2006;42(8):384-387. (Randomized controlled trial; 24 patients)
  92. Edwards L, Shirtcliffe P, Wadsworth K, et al. Use of nebulised magnesium sulphate as an adjuvant in the treatment of acute exacerbations of COPD in adults: a randomised double-blind placebo-controlled trial. Thorax. 2013;68(4):338-343. (Randomized controlled trial; 161 patients)
  93. * Ram FS, Picot J, Lightowler J, et al. Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2004;(3)(3):CD004104. (Systematic review and meta-analysis; 14 studies)
  94. Merlani PG, Pasquina P, Granier JM, et al. Factors associated with failure of noninvasive positive pressure ventilation in the emergency department. Acad Emerg Med. 2005;12(12):1206-1215. (Retrospective observational study; 104 patients)
  95. Allen JY, Macias CG. The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Ann Emerg Med. 2005;46(1):43-50. (Randomized controlled trial; 68 patients)
  96. Hirota K, Lambert D. Ketamine: its mechanism(s) of action and unusual clinical use. Br J Anaesth. 1996;77(4):441-444. (Review article)
  97. Sato T, Hirota K, Matsuki A, et al. The relaxant effect of ketamine on guinea pig airway smooth muscle is epithelium-independent. Anesthesiol Analges. 1997;84:641-647. (Animal study)
  98. Howton JC, Rose J, Duffy S, et al. Randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma. Ann Emerg Med. 1996;27(2):170-175. (Randomized controlled trial; 53 patients)
  99. Parrilla FJ, Moran I, Roche-Campo F, et al. Ventilatory strategies in obstructive lung disease. Semin Respir Crit Care Med. 2014;35(4):431-440. (Review article)
  100. Bonin F, Sommerwerck U, Lund LW, et al. Avoidance of intubation during acute exacerbation of chronic obstructive pulmonary disease for a lung transplant candidate using extracorporeal carbon dioxide removal with the Hemolung. J Thorac Cardiovasc Surg. 2013;145(5):e43-e44. (Case report)
  101. Pazarli AC, Koseoglu HI, Doruk S, et al. Procalcitonin: is it a predictor of noninvasive positive pressure ventilation necessity in acute chronic obstructive pulmonary disease exacerbation? J Res Med Sci. 2012;17(11):1047-1051. (Cross-sectional study; 118 patients)
  102. Hashemian SM, Fallahian F. The use of heliox in critical care. Int J Crit Illn Inj Sci. 2014;4(2):138-142. (Review article)
  103. Hunt T, Williams MT, Frith P, et al. Heliox, dyspnoea and exercise in COPD. Eur Respir Rev. 2010;19(115):30-38. (Systematic review; 8 studies)
  104. Jolliet P, Ouanes-Besbes L, Abroug F, et al. A multicenter randomized trial assessing the efficacy of helium/oxygen in severe exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2016. (Randomized controlled trial; 445 patients)
  105. Maggiore SM, Richard JC, Abroug F, et al. A multicenter, randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease. Crit Care Med. 2010;38(1):145-151. (Randomized controlled trial; 204 patients)
  106. Mieloszyk RJ, Verghese GC, Deitch K, et al. Automated quantitative analysis of capnogram shape for COPD-normal and COPD-CHF classification. IEEE Trans Biomed Eng. 2014;61(12):2882-2890. (Prospective observational trial; 139 patients)
  107. Roche N, Rabbat A, Zureik M, et al. Chronic obstructive pulmonary disease exacerbations in emergency departments: predictors of outcome. Curr Opin Pulm Med. 2010;16(2):112-117. (Review article)
  108. Bustamante-Fermosel A, De Miguel-Yanes JM, Duffort-Falco M, et al. Mortality-related factors after hospitalization for acute exacerbation of chronic obstructive pulmonary disease: the burden of clinical features. Am J Emerg Med. 2007;25(5):515-522. (Retrospective observational study; 763 patients)
  109. Quintana JM, Esteban C, Unzurrunzaga A, et al. Predictive score for mortality in patients with COPD exacerbations attending hospital emergency departments. BMC Medicine. 2014;12(1):66. (Prospective observational study; 2487 patients)
  110. Roche N, Zureik M, Soussan D, et al. Predictors of outcomes in COPD exacerbation cases presenting to the emergency department. Eur Respir J. 2008;32(4):953-961. (Prospective, observational study; 794 patients)
  111. Singanayagam A, Schembri S, Chalmers JD. Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2013;10(2):81-89. (Systematic review; 37 studies, 189,772 subjects)
  112. Hu G, Zhou Y, Wu Y, et al. The pneumonia severity index as a predictor of in-hospital mortality in acute exacerbation of chronic obstructive pulmonary disease. PLoS One. 2015;10(7):e0133160. (Prospective observational study; 752 patients)
  113. Chang CL, Sullivan GD, Karalus NC, et al. Predicting early mortality in acute exacerbation of chronic obstructive pulmonary disease using the CURB65 score. Respirology. 2011;16(1):146-151. (Prospective observational study; 252 patients)
  114. Xiao K, Guo C, Su L, et al. Prognostic value of different scoring models in patients with multiple organ dysfunction syndrome associated with acute COPD exacerbation. J Thorac Dis. 2015;7(3):329-336. (Retrospective observational study; 153 patients)
  115. Steer J, Gibson J, Bourke SC. The DECAF Score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease. Thorax. 2012;67(11):970-976. (Prospective observational study; 920 patients)
  116. Echevarria C, Steer J, Heslop-Marshall K, et al. Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD. Thorax. 2016;71(2):133-140. (Prospective observational study; 1725 patients)
  117. Steer J, Norman EM, Afolabi OA, et al. Dyspnoea severity and pneumonia as predictors of in-hospital mortality and early readmission in acute exacerbations of COPD. Thorax. 2012;67(2):117-121. (Prospective observational study; 920 patients)
  118. Shorr AF, Sun X, Johannes RS, et al. Validation of a novel risk score for severity of illness in acute exacerbations of COPD. Chest. 2011;140(5):1177-1183. (Retrospective observational study; 34,669 patients)
  119. Esteban C, Arostegui I, Garcia-Gutierrez S, et al. A decision tree to assess short-term mortality after an emergency department visit for an exacerbation of COPD: a cohort study. Respir Res. 2015;16:151. (Prospective observational study; 2487 patients)
  120. Criner GJ, Bourbeau J, Diekemper RL, et al. Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest. 2015;147(4):894-942. (Consensus statement; guidelines)
  121. Schembri S, Morant S, Winter JH, et al. Influenza but not pneumococcal vaccination protects against all-cause mortality in patients with COPD. Thorax. 2009;64(7):567-572. (Retrospective observational study; 177,120 patients)
  122. Tomczyk S, Bennett NM, Stoecker C, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged = 65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2014;63(37):822-825. (Consensus statement)
  123. Kraicer-Melamed H, O’Donnell S, Quach C. The effectiveness of pneumococcal polysaccharide vaccine 23 (PPV23) in the general population of 50 years of age and older: a systematic review and meta-analysis. Vaccine. 2016;34(13):1540-1550. (Systematic review, meta-analysis)
  124. Lee TA, Weaver FM, Weiss KB. Impact of pneumococcal vaccination on pneumonia rates in patients with COPD and asthma. J Gen Intern Med. 2007;22(1):62-67. (Retrospective observational study; 34,193 patients)
  125. Lodewijckx C, Sermeus W, Vanhaecht K, et al. Inhospital management of COPD exacerbations: a systematic review of the literature with regard to adherence to international guidelines. J Eval Clin Pract. 2009;15(6):1101-1110. (Systematic review; 7 studies)
  126. Sandhu SK, Chu J, Yurkovich M, et al. Variations in the management of acute exacerbations of chronic obstructive pulmonary disease. Can Respir J. 2013;20(3):175-179. (Retrospective observational study; 293 patients)
  127. Tsai CL, Ginde AA, Blanc PG, et al. Improved care of acute exacerbation of chronic obstructive pulmonary disease in two academic emergency departments. Int J Emerg Med. 2009;2(2):111-116. (Retrospective observational study; 272 patients)
Publication Information

Van Holden, MD; Donald Slack, III, MD; Michael T. McCurdy, MD, FCCM, FCCP, FAAEM; Nirav G. Shah, MD, FCCP

Publication Date

October 1, 2017

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