The Case of the “Frequent Exacerbator” Patient With COPD

AFFILIATIONS:

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

CITATION:

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.

DISCLOSURES:

The authors of this manuscript have no financial or other conflicts of interest that are relevant to the topic of COPD diagnosis.

CORRESPONDENCE:

Samuel Louie MD, University of California, Davis, Division of Pulmonary and Critical Care Medicine, 4150 V St #3400, Sacramento, CA 95817 (sylouie@ucdavis.edu)

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
• Pseudo-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.  Figure 4. CT chest of two patients admitted for COPD exacerbation. (A) shows no emphysema, but potential alternative causes (obesity and bilateral pleural effusions and cardiomegaly consistent with heart failure).  (B) demonstrates diffuse centrilobular emphysema appearing as moth-eaten areas of hyperlucency.  

The risk of overdiagnosis of COPD is well known because the FEV1/FVC ratio decreases with age in otherwise healthy adults.² Inadequate diagnosis (diagnosis of COPD without the necessary confirmatory evidence) and misdiagnosis of COPD (diagnosis of COPD despite contradictory evidence) may be commonplace but unrecognized in both outpatient and inpatient settings.^6-8  We should clarify that the term “misdiagnosis” here should not be confused with “missed diagnosis,” which is the failure to diagnose. Many patients receive costly COPD treatments for years from inadequate diagnosis or misdiagnosis, as in our case report.²  As many as 35% of patients receiving inhaled drugs for respiratory symptoms are incorrectly diagnosed as having COPD.^8,9  This is a comparable diagnostic error rate to asthma, which has a prevalence of 33%.¹⁰

Both inadequate or misdiagnosis of COPD raises patient safety concerns and are apt targets for systematic identification and intervention to improve quality and safety of care. This diagnosis dilemma and subsequent unnecessary treatment is more prevalent in higher income countries, like the United States.⁶ (Table 2). COPD claims-based data, whether firmly diagnosed or otherwise, has demonstrated medical and pharmaceutical costs estimating at $6,246 per year and higher with those who had ≥1 COPD exacerbation claim at an average of $11,395 per year.⁹

Additionally, the Institute of Medicine's (IOM) report demonstrated a total of $75.7 billion to $101.2 billion as waste from overtreatment or low-value care, with an estimated savings amount of $12.8 billion to $28.6 billion annually with successful interventions.¹⁰

Table 2. Types of Errors Categorized by the IOM Report, Improving Diagnosis in Health Care.¹¹

Why you may think the patient has COPD without spirometry

One of the factors that may hinder clinicians from obtaining spirometry is immediacy bias. Indeed, clinicians commonly assess and treat patients empirically during acute exacerbations, during which therapy of respiratory distress is prioritized over diagnostic testing. The consequences could be that these patients are prescribed expensive and potentially dangerous drugs that lack therapeutic benefit. This is akin to the similar challenge of antibiotics inappropriately prescribed to patients without true bacterial infection.

Numerous factors impede clinicians from obtaining spirometry in the evaluation of these patients. Spirometry is time-consuming, requires specific devices and resources, and is not recommended when patients are in acute respiratory distress making use during inpatient admission difficult. Even when performed, many clinicians are not comfortable with interpretation.

In the inpatient setting, many institutions do not routinely perform bedside spirometry.⁷ Referrals for outpatient pulmonary function tests are inconsistently performed due to insurance, social support, access, and fragmented care across health care systems. Patients with COPD also are susceptible to gaps during transitions of care, making management and even obtaining basic and necessary diagnostic tests such as spirometry challenging.

Why spirometry is necessary in the diagnosis of COPD

Spirometry is required to confirm the diagnosis of COPD since 2001.² Failure to prove airflow limitation defined by a FEV1/FVC < 0.70, and instead diagnose solely based on symptoms and tobacco exposure risks misdiagnosis. In addition to improving diagnosis, another key patient safety opportunity is reducing overtreatment of COPD through accurate staging.² It is estimated that more than 50% of the current financial burden of inhaled medications is due to overdiagnosis and overtreatment.¹² This begs the question, are we missing opportunities to improve patient safety and quality care by not performing spirometry in clinic or in the hospital to confirm the COPD diagnosis in a patient first?

In a random sample of 2,871 European adults aged 70 years and older, approximately 35% of these healthy, elderly patients who have never smoked had an FEV1/FVC% of < 0.70 and would be classified as having at least a Stage or Grade 1 COPD. This percentage increased with age and in those aged more than 80 years, greater than 50% would be classified as having COPD and approximately one-third would have an FEV1 of greater than 80% predicted (Stage or Grade 2 COPD).¹³ The current GOLD criteria can lead to a significant degree of overdiagnosis of COPD in those aged greater than 70 years old. Age-specific criteria should be developed to define the various stages of COPD.

To address overuse (and misuse) of FDA-approved COPD treatments in clinical practice, we need to balance unintended consequences, such as clinician bias, and provide an expedient way of performing spirometry. Spirometry is under-utilized in general, but especially among patients of lower socioeconomic status and historically marginalized populations.¹⁴ Low socioeconomic status is associated with more exacerbations, less access to care, worse symptom burden, and lower FEV1 at diagnosis, especially among women and Black patients.¹⁴

Interpretation of spirometry is equally important in appropriately diagnosing COPD, a disease that suffers from diagnostic bias and unevenly distributed care.¹⁵ Result analysis requires a keen eye to take a race-conscious approach when interpreting of falsely high predicted values of our non-White patients.¹⁵ During early efforts to define population variance in lung function as defined by spirometry, researchers observed vital capacity was lower in non-White patients compared with White patients. Spirometry “normal ranges” were then adjusted for ethnicity and a narrative of innate differences developed.¹⁶ The consequences of embedding race in the interpretation of spirometry ranges resulted in fewer non-White patients diagnosed with obstruction.¹⁷ Subsequent epidemiology studies demonstrated the differences in race/ethnicity are not apparent after adjustment for environmental factors (smoke and air pollution exposure).¹⁸ And while the creation of "normal ranges" occurred with a focus on race rather than other Influences such as environment and socioeconomic status, spirometry as a tool remains vital to the diagnosis of obstruction.

Pitfalls to avoid

It is a major pitfall not to confirm the diagnosis of COPD in every patient with a post-bronchodilator FEV1/FVC < 0.70. Before initiating targeted therapy, clinicians should pause to confirm if the patient indeed meets criteria for diagnosis: exposure, symptoms, structural damage, and—perhaps most importantly—obstruction on spirometry.¹  Clinicians or support teams should confirm spirometry has been performed for all patients with a chart diagnosis of COPD. Every opportunity to obtain spirometry should be taken, including point-of-care spirometry during hospitalization and clinic visits.

Other pitfalls evident from our case include diagnosing COPD based on tobacco smoking history alone and omitting spirometry in favor of prescribing inhaled medications based on clinical impression alone.

Health systems can also support a team-based, care management approach for patients with COPD to help complete spirometry, reduce pressure on visit times, and improve care coordination for high-risk patients. Opportunities for improving care management include using patient registries to proactively identify patients at high risk of hospitalization and who lack diagnostic spirometry, medication management, and patient navigation and transitional care programs across health care settings.¹⁷

Conclusion

Error or delay in correct COPD diagnosis, or failure to obtain spirometry, and failure to act on the evidence or failure to assess and monitor for response to treatment poses short-term and long-term patient safety concerns. The diagnosis of COPD needs to be challenged more often, and most importantly with spirometry. Unintended consequences to the patient’s care and treatment abound with inadequate diagnoses and misdiagnosis. The veritable underlying cause of dyspnea (i.e., obesity hypoventilation, heart failure, and aspiration in our case) in pseudo-COPD will continue to deteriorate the individual patient’s health and safety as well as risk and incur unwarranted health care costs, including inappropriate treatments and hospitalization. Population-health strategies can aid care teams in assuring spirometry has been performed and provide potential waste and cost reduction. Our experience at UC Davis convinces us that one of our greatest responsibilities is to be aware of misdiagnosed patients with COPD and to refocus their care and treatments appropriately.