Pulmonary Pitfalls: The Case of the “Frequent Exacerbator” Patient With COPD
1University of California, Davis, Department of Respiratory Care
2University of California Davis Health, Division of Internal Medicine
3University of California, Davis, Division of Pulmonary and Critical Care Medicine
Craddock KM, Gupta R, Louie S, Kuhn BT. Pulmonary pitfalls: The case of the "frequent exacerbator" patient with COPD. Consultant. 2023;63(1):20-25. doi:10.25270/con.2022.11.000013
Received October 19, 2022. Accepted November 7, 2022. Published online December 27, 2022.
The authors of this manuscript have no financial or other conflicts of interest that are relevant to the topic of COPD diagnosis.
Samuel Louie MD, University of California, Davis, Division of Pulmonary and Critical Care Medicine, 4150 V St #3400, Sacramento, CA 95817 (email@example.com)
Chronic obstructive pulmonary disease (COPD) is not a single disease, but a syndrome with a range of clinical phenotypes. Indeed, there are several different types of patients to treat: those with alpha-1 antitrypsin deficiency, the frequent exacerbator, the patient with chronic bronchitis without frequent exacerbations, asthma-COPD overlap syndrome (ACOS), bronchiectasis-COPD overlap syndrome (BCOS), and overlap with obstructive sleep apnea, to mention a few. The following case illustrates, what we believe to be, an unrecognized COPD phenotype.
Patient history. A 56-year-old woman with a diagnosis of COPD presented to the pulmonary clinic after hospital discharge for a severe exacerbation of COPD. In the last 12 months, she has presented to the hospital three times for exacerbations, which clinicians treated with non-invasive positive pressure ventilation, systemic corticosteroids, and antibiotics. Her past medical history includes coronary artery disease, heart failure, morbid obesity, and 20 years smoking history, although she quit 10 years prior.
She was diagnosed with COPD by a physician more than 20 years ago, but experienced dyspnea with exertion since childhood. Although she reported being mostly asymptomatic, exacerbations interrupted her life approximately three to four times per year. In those instances, she would be treated with a short course of prednisone and antibiotics.
Physical examination. Her physical examination is notable for obesity with a BMI of 30.9, distant breath sounds without wheeze or prolonged exhalation, and bilateral lower extremity edema in the ankles. Prior arterial blood gas tests showed acute chronic hypercapnia, and computed tomography (CT) of the chest did not show signs of emphysema, bronchitis, or mosaic attenuation. Pulmonary function testing (PFT) was ordered after the clinic visit and revealed a mild restrictive pattern, no evidence of chronic obstructive disease (FEV1/FVC), and reduced expiratory reserve volume (ERV) (Figures 1 and 2).
Figure 1. Spirometry and lung volumes from patient case. No post-bronchodilator values given normal spirometry.
Figure 2. Flow volume loop from patient case demonstrating restrictive disease, not chronic obstructive disease.
Diagnosis. Our case report shows that patients may repeatedly receive hospital care for severe COPD exacerbations when the underlying diagnosis of COPD is incorrect. We diagnosed our patient with obesity hypoventilation syndrome acutely worsened by exacerbations of heart failure after years of carrying an incorrect COPD diagnosis and receiving COPD treatments. She did not have COPD by all known clinical and radiographic criteria. In fact, the patient shared that she not only failed to feel better with inhaled bronchodilators, but that clinicians never asked about how she felt after using the COPD treatments. Antibiotics and prednisone did not improve her symptoms during exacerbation either. Once again, no one asked her or listened to her story until the consultation in pulmonary clinic. We believe the unrecognized COPD phenotype here is pseudo-COPD.
Discussion. COPD should be considered for any patient with symptoms of dyspnea on exertion, chronic cough, sputum production, chest tightness, and/or a history of risk factors, such as tobacco or smoke exposure. It is estimated that only 10% to 15% of smokers develop COPD, however.1 It is important to note that the symptoms linked to COPD are non-specific in real-world practice and occur in other diseases with similar risk factors, like asthma, heart failure, coronary artery disease, and obesity-hypoventilation (Table 1).2
Table 1. Common causes of symptoms in misdiagnosed COPD.
Clinical COPD phenotypes are generally less well known than in asthma, where phenotypes like allergic, non-allergic, late-onset, asthma associated with obesity, asthma associated with fixed airways obstruction, eosinophilic, or non-eosinophilic can overlap with each other. COPD phenotypes such as the frequent exacerbator in our case report is less defined. Common and proposed clinical phenotypes of COPD include:
- Frequent Exacerbator
- Infrequent Exacerbator
- Alpha 1 anti-trypsin deficiency
- Asthma COPD Overlap Syndrome (ACOS)
- Bronchiectasis COPD Overlap Syndrome (BCOS)
- Obstructive Sleep Apnea-COPD Overlap syndrome
- Eosinophilic COPD
- Non-eosinophilic COPD
How many moderate exacerbations are required annually to fulfill the frequent exacerbator criteria remains a controversial issue. Is one moderate exacerbation one too many? A moderate exacerbation of COPD often requires an escalation, such as the use of short-acting bronchodilators together with antibiotics and/or a short course of oral corticosteroids. In this scenario, the patient typically remains at home. Severe exacerbation requires the same initial treatments as in moderate cases, but patients are hospitalized and may die from acute respiratory failure or cardiovascular complications such as myocardial infarction or stroke.
Do we let patients with COPD experience two moderate exacerbations annually before taking a more aggressive approach to COPD care and treatment? Are two moderate exacerbations equivalent to one severe exacerbation of COPD as far as danger to the patient’s health and safety?
Despite the availability of international COPD guidelines and best practice approaches, in our experience, there is an unspoken general apathy concerning the care and treatment of patients who live with COPD. The new iteration of the Global Strategy for Prevention, Diagnosis and Management of COPD (GOLD) strategy for 2023 will likely include clinical trial data that shows the potential for reduced all-cause mortality among patients with COPD. It could not have come at a better time. COPD is the third leading cause of death worldwide, according to GOLD2 and was the sixth leading cause of death in the United States in 2020, according to the CDC.3 COPD exacerbations led to 7 million COPD-related medical events with $5 billion in medical expenditures in 20174 and $49 billion in 2020.5
Slowing the disease progression and frequency of COPD exacerbations, as well as its associated patient and health system costs (regardless of phenotype) can only be achieved by confirming the diagnosis of COPD first. Although there is no cure, COPD symptoms are reversible and treatable, and exacerbations are preventable. In the Global Burden of Obstructive Lung Disease (BOLD) study, patients received spirometry, and of those with a clinical diagnosis of COPD, no obstruction was identified in 61.9% of patients using the lower limit of normal criteria (55.3% using fixed ratio).5 This issue is not simply one of documentation. Up to one-third of hospitalized patients diagnosed and treated for COPD may be inaccurately diagnosed (often patients with obesity, which account for 70.5% of COPD misdiagnoses) based on confirmed spirometry testing.6-8
Spirometry is necessary in both diagnosing and staging severity of COPD in patients1; however, the use of spirometry in real-world clinical practice remains disappointing.6 When looking back at chest X-rays and chest CT scans obtained in patients admitted to our hospital for severe COPD, there were original diagnoses of COPD that we considered questionable, based on our expertise and experience. (Figure 3 and Figure 4)
Figure 3. Chest x-rays of patients admitted for COPD exacerbation. (A) shows classic findings of COPD with hyperinflation and hypolucency of the lung. (B) shows diffuse alveolar filling from an atypical bacterial infection. (C) shows elevation of the right hemidiaphragm. (D) shows suggestion of heart disease: marked cardiomegaly, defibrillator, and sternotomy wires. (E) does show hyperinflation, but also diffuse bronchiectasis with mucous plugging.