Chronic Obstructive Pulmonary Disease Exacerbation: When it isn’t just your classic exacerbation…

Authors: Sarah Iosifescu, MD (EM Resident Physician, St. Luke’s-Mount Sinai West) and Jennifer Beck-Esmay, MD (EM Attending Physician/Assistant Residency Director, St. Luke’s-Mount Sinai West) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Clinical Case #1:  

An 82-year-old male with a history of ACS, DVT, HTN, CHF, and COPD not on home O2 presents to the ED with worsening shortness of breath. He states that he has been completely compliant with all of his medications and diet. He was last discharged from the ED for COPD exacerbation one week ago. He is here almost weekly for CHF or COPD exacerbations. EMS brought him in and states that they heard he was wheezing so started him on albuterol and ipratropium. He states the shortness of breath came on this morning with no real chest tightness. He can’t describe it well, and it does feel similar to his other exacerbations but at the same time it feels different.  He denies any fever and change in his baseline cough or sputum production. Your intern states it’s clearly his COPD exacerbation and puts him in for steroids, more duonebs, an x-ray, and labs.

Vitals signs show RR 24, HR 96, BP 135/80, SpO2 92% on RA, T 98.6. His exam is completely normal. Labs including a troponin, and x-ray look normal, but he’s not responding to his nebulizers. His EKG shows a new RBBB. What do you do next?

Clinical Case #2:

A 75-year-old female with a history of recently diagnosed CHF and a long list of primary care active issues in the EMR presents with shortness of breath for the past three days. She lives at home and has a visiting home health aide four hours a day. She is compliant with her medications and denies any recent travel, surgeries, fever, chest pain, or lower leg swelling. She was started on a few new medications by her cardiologist for her heart failure. She was a smoker most of her life but had never been diagnosed with asthma or COPD.

Vital signs show RR 20, HR 88, BP 154/76, SPO2 94% on room air, T 98.6. Her exam is positive for expiratory wheezing and tachypnea (you realize the RR on her vitals is completely inaccurate).


Chronic Obstructive Pulmonary Disease (COPD) is a group of respiratory conditions characterized by airflow limitation. Prevalence of COPD varies nationally by state, from 4% – 9% [1] of the population. In addition, it is the third leading cause of death in the United States. While smoking remains the primary cause for development of COPD, there are also genetic and environmental factors that contribute to the disease. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines COPD as a common, chronic, treatable, and preventable disease characterized by, “persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.” [2]

Per the GOLD report, COPD exacerbations are defined as worsening of known COPD patients’ respiratory symptoms beyond normal variations, ultimately leading to a change in medications. Exacerbations are most frequently caused by medication noncompliance and infectious causes, resulting in lower airway inflammation and leading to anti-inflammatory defenses and tissue damage. The biggest risk factor for COPD exacerbations is a prior history of exacerbations [3, 4], and frequent exacerbations are associated with increased morbidity and mortality, rapidly increasing decline in lung function, and overall poorer health status. Identifying key triggers to prevent exacerbation is an area of increased interest. However, one third of COPD exacerbations have no identified cause.[5]   Other medical conditions including CHF and pneumonia can present similar to a COPD exacerbation.  Identifying risk factors for exacerbation can help to prevent patients with COPD from having more frequent exacerbations and ideally result in decreased morbidity and mortality. In addition, keeping a broad differential in what appears to be a COPD exacerbation is important, given many of these patients have numerous other co-morbidities and can present with another condition that appears similar to an exacerbation. Here we will discuss some other causes and mimics of COPD exacerbations that are important to consider.


Sneaky COPD Triggers

The Question of PE

The diagnosis of pulmonary embolism (PE) in COPD exacerbation has been controversial. The overlap in symptoms between an acute PE and COPD exacerbation pose a challenge to the emergency physician given the predominant clinical sign of both COPD exacerbation and PE is dyspnea. Does this then warrant working up every COPD exacerbation for PE? A 2009 systemic review and meta-analysis published in CHEST found that one of four COPD patients who required hospitalization for an acute COPD exacerbation may have a pulmonary embolus.[6] In a 2006 study published in Annals of Internal Medicine [7], 197 patients who were specifically categorized as having COPD exacerbation of unknown origin were assessed for possible PE. They defined COPD exacerbation with unknown origin as “without purulence of sputum, history of a cold or sore throat, pneumothorax, or iatrogenic intervention, or when there was a discrepancy between the clinical and radiologic features and hypoxemia severity.” They used the Geneva Score and determined that while 60% of the patients in their study had a low probability of PE according to the Geneva score, 9% of those had confirmed PE; 46% who had an intermediate probability had PE, and 100% of patients with high probability had confirmed PE. In total, 25% of the 197 patients with COPD and severe exacerbation with unknown origin had PE.

This data should be interpreted cautiously, as determining when a COPD exacerbation is triggered by an ‘unknown cause’ generally relies on clinical judgement; there is no standard assessment. However, as evidence has demonstrated, in patients who have increasing dyspnea with no significant changes in sputum, cough, infectious etiology, or who are not responsive to COPD exacerbation therapy, PE should be considered.

Cold Weather

Do you feel like you see way more COPD in the cold weather? A Taiwanese case-crossover study investigated 16,254 patients greater than 40 years old with a COPD exacerbation diagnosis by ICD-9 codes in association to air temperature. Their findings showed that a 5-degree Celsius decrease in temperature was significantly correlated with increased numbers of COPD exacerbations (OR, 1.039, 95% CI 1.007-1.071, p=0.015). This increase was more significant in the elderly and those who hadn’t taken inhaled medication in the past month. [8]


Epidemiologic research has identified increased frequency of COPD exacerbations during periods of elevated pollution. Increases in the amount of sulfur dioxide (SO2), ozone (O3), black smoke particulate matter, and nitrogen dioxide (NO2) are associated with increases in pulmonary symptoms, COPD exacerbations, and mortality. [9, 10]

In “Reassessment of the Lethal Fog of 1952: Novel Indicators of Acute and Chronic Consequences of Acute Exposure to Air Pollution” researchers compared insurance claims, hospital admission rates, mortality records for cardiac, and respiratory disease during the 1952 London smog epidemic and compared it to the previous years. Admissions for respiratory disease during the fog jumped to 41% from 23% prior to the episode. Respiratory deaths and illness during the time of the fog more highly correlated with pollution level averages from the week prior to admission, suggesting that there may be a cumulative effect of exposure to increase pollution. [9]

In a 1997 study published in European Respiratory Journal, scientists conducted a prospective standardized study analyzing air pollution and daily admissions for COPD in six different European cities. Findings showed that relative risks of admissions were significantly increased for numerous pollutants, most consistently ozone, SO2, and NO2. [11]


Secondary spontaneous pneumothorax is defined as pneumothorax from underlying disease. The two most common conditions associated with secondary spontaneous pneumothorax are COPD and PCP pneumonia related to HIV. [12] Secondary pneumothorax generally occurs in older populations consistent with increasing development of chronic lung disease in older populations. The incidence of secondary spontaneous pneumothorax in patients with COPD is approximately 26 per 100,000 patients with COPD disease per year. [12] The physiology for pneumothorax in COPD includes increasing alveolar pressure exceeding interstitial pressure after coughing, resulting in rupture of the alveoli and air moving through the interstitial to the hilum of the lung. Another mechanism for secondary pneumothorax includes air moving from a ruptured alveolus directly into the pleural space as a result of lung necrosis. Patients will often complain of ipsilateral chest pain, and symptoms do not typically resolve with standard treatment. [12] Physical findings are often subtle and difficult to assess, especially in patients with chronic lung disease.

Beta Blockers

COPD and Congestive Heart Failure (CHF) are two disease processes that frequently occur together. The prevalence of COPD amongst CHF patients approaches 20%. Randomized controlled trials have demonstrated improved survival in patients with CHF taking beta-blockers. However, there has been ongoing controversy about prescribing beta blockers in patients with both CHF and COPD due to possible adverse respiratory effects of non-selective beta blockers. As a review, beta-1 receptors are located primary on the heart and kidneys and beta-2 receptors on the lungs, gastrointestinal tract, liver, vascular smooth muscle, and skeletal muscle. [13] In COPD exacerbations, we normally treat with a beta -2 agonist to increase bronchial dilation.  Non-selective beta blockers have similar effect on beta -1 and beta -2 receptors, whereas selective beta blockers have greater affinity for beta -1 receptors, avoiding blocking the beta -2 receptors on the lung and causing bronchial constriction. [14]

The extent of the effect of non-selective beta blockers on lung function can be seen even while using non selective beta blocker eye drops for increased ocular pressures. In a 2016 meta-analysis, authors found that using non-selective beta blocker eye drops on patients with asthma caused mean falls in FEV1 of 10.9% (95% CI -14.9 to – 6.9) as compared to falls in selective beta blockers of 6.3% (95% CI – 11.7 to -0.8). [13] A randomized crossover trial published in 2010 studied the effects of switching between selective b-1 blockers and a non-selective beta blocker and vice versa in patients with both CHF and COPD. The study found that FEV1 function was significantly higher in patients treated with bisoprolol, a beta-1 selective drug, versus carvedilol, a non-selective beta blocker. Authors state that, “despite this, no excess intolerance was observed changing from bisoprolol to carvedilol.” At the same time, patients switched from bisoprolol to carvedilol had short term reductions in NT-proBNP, which is a prognostic marker in CHF. [15] A Cochrane review in 2005 confirmed that cardio selective beta blockers did not produce adverse effects in patients with underlying COPD. The review looked at trials studying cardioselective b-1 blockers including atenolol, metoprolol, bisoprolol, practolol, celiprolol, and acebutolol. The general consensus of these discussions has been that it is safe to place patients with CHF and COPD on cardioselective beta blockers. [16] However, if you find you have a patient with undiagnosed or poorly managed COPD on a non-selective beta blocker, or perhaps recently started on a new beta blocker, it is worth considering if this is contributing to their COPD exacerbation.


The exact numbers vary, but it is believed that over 50% of COPD exacerbations are caused by infections.  Bacterial species account for 40-60% of infections, viruses 30%, and atypical bacteria 5-10%. The most common bacteria implicated are Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis. [15]

Literature suggests changes in sputum color or increased sputum purulence are markers of bacterial infection. [18] A 2012 Cochrane review looked at 16 trials with 2068 participants and concluded that there were differences in treatment of infectious triggers of COPD depending on level of COPD exacerbation. In exacerbations managed in an outpatient setting (considered mild to moderate exacerbations), there was low quality evidence that antibiotics had a statistically significant reduction in reducing treatment failure in a period between 7 days and 1 month following the exacerbation (RR 0.80; 95% CI 0.63 to 1.01) when restricted to currently available drugs. In severe exacerbations and ICU admissions for COPD exacerbations, there was high quality evidence of antibiotic use in reducing treatment failure: RR 0.77 (95% CI 0.65 to 0.91) and RR 0.19 (95% CI 0.08 to 0.45), respectively.  There was low quality evidence on inpatient mortality effect but statistically significant effect of mortality on ICU patients when using antibiotics. [19] A 2018 Cochrane review suggests similar results. [20]

Key Points

  • Do not assume that all patients with COPD that present with dyspnea have a clear-cut infectious or medicine non-compliant COPD exacerbation. Keep a lookout for abnormal lab results or lack of responsiveness to standard treatment in COPD exacerbations in case there are other underlying causes.
  • There is mixed data on PE as a trigger for a COPD exacerbation, but the evidence so far suggests it may be real. It doesn’t mean that you need to evaluate every COPD patient for PE with CT, but it should be on your mind.
  • COPD patients are more sensitive to environmental and weather triggers and are more likely to have exacerbations in cold weather and when exposed to higher air concentration of pollutants.
  • Non-selective beta blockers can decrease lung function in COPD patients; use beta blockers with caution in COPD patients.
  • Infections are likely the most common cause of COPD exacerbation, with bacteria the most common species. Antibiotics are associated with improved outcomes, especially in severe exacerbations.

Case conclusion #1

You order a d-dimer which is elevated and obtain a CT pulmonary study which shows pulmonary embolus.  Given he has RBBB changes but no hypotension, you categorize him as submassive PE. As you and your resident are discussing the case, you are alerted that his blood pressure has dropped to 85/50, and he is starting to feel worse. You decide it is time for thrombolytics. The patient is admitted to the ICU where he does well, is eventually moved to the floor, and discharged five days later. You and your intern have an extensive discussion about the importance of keeping a broad differential in patients with shortness of breath and what you think about PE as a possible underlying cause for COPD exacerbation.

Case Conclusion #2

You call the patients cardiologist and realize she was started on carvedilol. She has never seen a pulmonologist and has never been diagnosed with asthma or COPD. Given her smoking history, you have a feeling the carvedilol tipped her over, and she likely has underlying respiratory dysfunction. You coordinate with the cardiologist to switch her to a cardio-selective beta blocker and arrange for her to have an appointment with the pulmonologist. She improves with duonebs and wants to go home. You discharge her with follow up with her cardiologist the following day and a pulmonologist appointment next week, along with prescribing her a short acting beta agonist inhaler, a steroid inhaler, and a prednisone taper.

From Dr. Katy Hanson at Hanson’s Anatomy:

References/Further Reading

  1. COPD Death Rates in the United States. Accessed September 25, 2018.
  2. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of chronic obstructive pulmonary disease: 2018 Report.
  3. Qureshi, H., A. Sharafkhaneh, N. A. Hanania. 2014. Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications. Ther. Adv. Chronic Dis. 5: 212–227.
  4. Hurst J, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, et al. Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010; 363:1128–38.
  5. Brulotte CA, Lang ES. Acute exacerbations of chronic obstructive pulmonary disease in the emergency department. Emerg Med Clin North Am 2012;30:223-47.
  6. Rizkallah J, Man SF, Sin DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: A systematic review and metaanalysis. Chest 2009;135:786-93.
  7. Tillie-Leblond I, Marquette CH, Perez T, Scherpereel A, Zanetti C, Tonnel AB, et al. Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: Prevalence and risk factors. Ann Intern Med 2006;144:390-6.
  8. Tseng, C., Chen, Y., et al. The Effect of Cold Temperature on Increased Exacerbation of Chronic Obstructive Pulmonary Disease: A Nationwide Study
  9. Ministry of Health. Mortality and morbidity during the London fog of December 1952, Report No 95 on Public Health and Medical Subjects. London: Ministry of Health, 1954.
  10. World Health Organisation. Acute effects on health of smog episodes. Copenhagen: World Health Organisation.
  11. AndersonHR, Spix C, Medina S, et al. Air pollution and daily admissions for chronic obstructive pulmonary disease in 6 European cities: results from the APHEA project. Eur Respir J. 1997;10(5):1064–1071.
  12. Sahn, S. and Heffner, J. (2000). Spontaneous Pneumothorax. New England Journal of Medicine, 342(12):868-874.
  13. Morales DR, Dreischulte T, Lipworth BJ, Donnan PT, Jackson C, Guthrie B. Respiratory effect of beta-blocker eye drops in asthma: population-based study and meta-analysis of clinical trials. British Journal of Clinical Pharmacology. 2016;82(3):814-822.
  14. McCorry LK. Physiology of the Autonomic Nervous System. American Journal of Pharmaceutical Education. 2007;71(4):78.
  15. Jabbour A, Macdonald PS, Keogh AM, et al. Differences Between Beta-Blockers in Patients With Chronic Heart Failure and Chronic Obstructive Pulmonary Disease: A Randomized Crossover Trial. J Am Coll Cardiol. 2010 Apr 27;55(17):1780-7.
  16. Salpeter S, Ormiston T, Salpeter E, Poole P, Cates C. Cardioselective beta-blockers for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2002.
  17. Sethi S, Murphy TF. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev. 2001;14:336–363.
  18. Miravitlles M, Anzueto A. Antibiotics for acute and chronic respiratory infection in patients with chronic obstructive pulmonary disease. Am Respir J Crit Care Med. 2013;188(9):1052–7.
  19. Vollenweider, DJ, Jarrett, H, Steurer-Stey, CA, Garcia-Aymerich, J, Puhan, MA. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;12:CD010257.
  20. Vollenweider DJ, Frei A, Steurer-Stey CA, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018;10:CD010257.

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