Understanding the Gaps in the Reporting of COPD Exacerbations by Patients: A Review

Abstract

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with loss of lung function, poor quality of life, loss of exercise capacity, risk of serious cardiovascular events, hospitalization, and death. However, patients underreport exacerbations, and evidence suggests that unreported exacerbations have similar negative health implications for patients as those that are reported. Whilst there is guidance for physicians to identify patients who are at risk of exacerbations, they do not help patients recognise and report them. Newly developed tools, such as the COPD Exacerbation Recognition Tool (CERT) have been designed to achieve this objective. This review focuses on the underreporting of COPD exacerbations by patients, the factors associated with this, the consequences of underreporting, and potential solutions.

Keywords:

• COPD
• exacerbations
• underreporting

Introduction

Exacerbations are a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). They cause impaired health status and loss of exercise capacity [1,2]. Repeated exacerbations are associated with accelerated lung function and health status decline, and the number and severity of events are associated with increased all-cause mortality [3,4]. In 2018, Rothnie et al. showed that even a single exacerbation over a 10-year period was associated with an increased risk of death [5].

Apart from the clinical burden, COPD exacerbations also increase the healthcare related costs. In the US and Canada, approximately 70–90% of COPD-related healthcare costs are attributable to COPD-related hospitalization [6,7]. The mean annual costs per exacerbation vary across countries (for example, from €1,197–9,545 across Poland, Italy, Greece, the UK, Turkey, Belgium, and the US), but in all countries, they impose a heavy economic burden [8–14].

Increased symptoms such as dyspnea, sputum volume, sputum purulence, increased airway inflammation, and gas trapping are considered the cardinal features of an exacer­bation [15,16]. Anthonisen et al. classified exacerbations based on the presence of three cardinal symptoms (increased sputum volume, increased sputum purulence and increased dyspnea) into type 1 (presence of all three symptoms), type 2 (presence of two symptoms) and type 3 (presence of one symptom with at least one other symptom such as presence of infection, fever, etc) [17]. However, two recent studies have shown that disturbance of activity is a key feature of exacerbation onset [18,19]. Clinically, exacerbations are categorized as mild (treatable with short-acting bronchodilators), moderate (addition of antibiotics and/or corticosteroids), or severe (addition of antibiotics and/or corticosteroids following an emergency room attendance or hospital admission) [20]. Symptoms of mild or moderate exacerbations can be associated with the common cold; therefore, patients and healthcare providers may miss them [15,16]. Recently, a more objective approach to the diagnosis and assessment of exacerbations has been proposed, but it will be difficult to implement outside an acute care setting [21]. However, clinical diagnosis is outside the scope of the present review.

A large proportion of exacerbations experienced by patients are not reported to healthcare professionals, but such events have a similar negative impact on the health status of patients with COPD to those that are reported [22–25]. Furthermore, early identification and initiation of treatment for exacerbations can result in quicker recovery [26], improving patient outcomes and reducing healthcare costs [27].

The aim of this article is to explore the current challenges in reporting COPD exacerbations by patients, possible factors associated with this underreporting, and potential solutions.

Methodology

A comprehensive literature search was conducted on the PubMed database to identify relevant studies between January 2000 and March 2023. Search terms included COPD-specific terms, along with exacerbation-specific terms. These terms were used to search titles, abstracts, and keywords. Additional searches were conducted in Google Scholar and from other review article reference lists through cross-referenced articles. The search was restricted to data published in the English language. Titles and abstracts were scanned, and duplicate records were reconciled and removed. Full text articles were scanned for outcome, population, and relevance of the article for the purpose of this review (Figure 1).

Figure 1. PRISMA flow depicting studies selected through targeted literature review.

Scale of underreporting

Lack of adequate reporting has been highlighted in multiple studies. Most patients with COPD do not report exacerbations often enough [18,22,23]. In a patient survey conducted across 14 countries, approximately 40% of the patients took a “wait and see” approach, while the remaining 60% either took action (56%) or did nothing (4%). In the same survey, ∼25% preferred self-medication over contacting their physician when experiencing an exacerbation [28]. In another study in the UK, only 60% of exacerbation events were reported to the physician, while the remaining 40% were identified by reviewing the patient’s daily diary cards [26]. It is estimated that the number of underreported exacerbations may be 2 to 5 time more than that of reported ones [18,23].

In a study in Canada, more than half of all exacerbations were unreported. It also reported worsening health-related quality of life (HRQoL) at 1 year in patients in whom more than 1 exacerbation was unreported [25]. In a recent Delphi survey among respiratory experts in 10 countries in Asia and Latin America, only 29% experts agreed that patients with COPD identify and timely report exacerbations to healthcare professionals [29].

Geographic variability in reporting of COPD exacerbations

The frequency of reported exacerbations within a COPD population varies among studies. In Spain, Soler-Cataluna et al. reported that a patient with COPD experiences between 1 and 4 exacerbations per year [30]. In a database study in the UK, Whittaker et al. showed that 30–50% of patients with COPD were treated for at least 1 exacerbation per year [4]. In patients with COPD who were using continuous supplemental oxygen, had received systemic corticosteroids, visited the emergency room, or had been hospitalized for a COPD exacerbation in the previous year in the US and Canada, the average rate of treated exacerbations was 1.53 episodes/year (range: 0.47–4.22). This estimate reflected only reported COPD exacerbations, largely ignoring those that were unreported [31].

A significant geographic variation has been observed in the ratio of reported moderate to severe COPD exacerbations, even in clinical trials. These differences were not explained by demographic features, study protocol, investigators participating in the study, or exacerbation history reported at the time of enrollment [20]. Table 1 provides an overview of exacerbation reporting across the world.

Table 1. Overview of exacerbation reporting in different parts of the world.

Publication	Country™	Number of participants (n)	Number or percentage of participants (n) reporting exacerbations across different studies
Chandra et al. 2009 [27]	North America	396	30% of patients reported the exacerbation immediately, while 70% of patients had a delay in reporting.
Hernandez et al. 2013 [32]	Canada	640	10% reported exacerbations.
Wilkinson et al. 2004 [26]	UK (East London)	128	1,099 exacerbations were recorded by the patients, of which 658 were reported to a physician (60%).
Trappenburg, 2011 [33]	Netherlands	141	17.3% contacted their primary physician after an exacerbation.
Xu et al. 2010 [24]	China	450	A total of 466 unreported (53%) and 410 reported exacerbations were recorded (47%).
Langsetmo et al. 2008 [25]	Canada	421	Less than one-third of exacerbations were reported.

Impact of unreported exacerbations

Studies that have compared reported and unreported exacerbations showed no significant difference in terms of symptom severity, peak expiratory flow (PEF), or forced expiratory volume in 1 s (FEV₁) [34,35]. Calderazzo et al. analyzed clinical data and inflammatory markers in 40 patients with COPD (52% with unreported exacerbations). In this study, no difference in symptoms, recovery from exacerbation in terms of symptoms, lung function, and inflammatory markers at 2- and 6-week time points, Anthonisen type, FEV₁ during an exacerbation, or worsening of a range of inflammatory markers between reported and unreported exacerbations was reported [36]. Other studies have shown that following an unreported exacerbation, symptoms do not recover to baseline in the same way as those that are reported and timely treated [37]. Delayed or missed treatment has been reported to be related to a shorter time to the next exacerbation, whereas earlier reporting and treatment were significantly associated with faster recovery, with each day of delay associated with ‘an increase in recovery time by 0.42 days’ [26]. Consistent with this, in a study in North American emergency departments (EDs), 70% of patients with a COPD exacerbation presented to the ED more than 24 h after symptom onset, and of those, approximately 61% required hospitalization. A delay of more than 24 h in presentation was related to a 2-fold increase in the odds of admission [27].

Another consequence of unreported exacerbations is that the patients may be denied effective post-exacerbation treatment, such as early pulmonary rehabilitation. The benefits of early pulmonary rehabilitation after exacerbation include reductions in mortality, hospital stay and readmissions, and improvements in HRQoL and exercise capacity [38]. A recently published modeling study suggested that earlier pharmacotherapy in patients with exacerbations could slow the decline of lung function and delay the progression to GOLD Grade 4 by up to 3.66 years [39].

While a study in Canada showed similar worsening of health status over 3 months among patients with reported and unreported exacerbations, a study in China reported clinically significant worsening of health status in unreported cases [24,25]. In the ATTAIN study, conducted in 819 patients with COPD in 6 countries, a comparable difference in health status change over 6 months measured using the St. George’s Respiratory Questionnaire (SGRQ) was seen in both reported and unreported exacerbations, compared with patients who did not exacerbate [22].

In conclusion, unreported exacerbations lead to undertreatment, which results in slower recovery, poorer outcomes, and a greater decline in quality of life. Also, underreporting can lead to an underestimation of the patient’s risk of future exacerbations. Whilst there are multiple risk factors for future exacerbations, exacerbation history appears to be the strongest [40]. Underreporting of exacerbations may significantly reduce the patient’s estimated risk, so they may not be given effective preventative therapy.

Factors affecting the rate of reporting of COPD exacerbation events

Typically, patients with less disease severity and lower symptoms tend to underreport their COPD exacerbations [37], but there are several other factors that may affect the reporting of acute events, as illustrated in Figure 2, and described further below [32,41–45].

Figure 2. Factors responsible for underreporting of COPD exacerbations by patients.

Patient understanding of COPD exacerbation

One of the most important factors may be the patient’s lack of understanding of the disease and the importance of worsening symptoms. In an interview-based study conducted by Kessler et al. in France, Germany, Spain, Sweden, and the UK (n = 125), only 2 patients with COPD understood the term exacerbation, and they rather preferred using simpler terms, such as chest infection (16.0%) or crisis (16.0%) [55]. Another study conducted in the UK by Williams et al. also showed that patients do not understand the term “exacerbation” but rather use “flare-ups” to identify changing symptoms [41]. Furthermore, a survey of 428 patients with COPD and 401 physicians who managed patients with COPD reported that, although approximately 71% of the patients understood that disease flare-ups are attributable to their COPD, only 37% understood the difference between a COPD exacerbation and the common cold/flu or bronchitis [42]. A study conducted on 316 well-informed patients with alpha-1 antitrypsin deficiency reported that patients do not always recognize changes in pulmonary symptoms as an exacerbation event. Typically, whilst worsening of sputum volume and color was associated with an exacerbation, worsening of dyspnea was not [43]. In a patient interview study (n = 11) by Machado et al. patients often thought that some symptoms, such as shortness of breath and tiredness or cough and sputum, were related to each other and fluctuated through the day, being worse in the morning and at night, or when they had to exert an effort, making it difficult for them to distinguish between acute exacerbations of COPD and worsening disease [56].

Approach of patients toward their COPD management

The approach of patients toward managing their COPD may also impact the rate of reporting exacerbations to the physicians. This may encompass factors such as attitude toward health and well-being, tendency to self-medicate, subjective assessment of symptom severity, fear of hospitalization, and concerns about adding new medications to their regimen. The patient’s attitude toward their disease and seeking care may be a particularly important factor, as it has been observed that there is a trend for reporting an exacerbation to the physician only when it becomes unmanageable by self-medication. In a global survey of 2,000 patients with COPD from 14 countries, approximately 39% were reported to have taken a “wait and see” approach to exacerbations [28]. In an interview-based qualitative survey of 44 patients in the UK, patients indicated that they preferred to self-medicate as an initial treatment approach and only visited healthcare professionals when they felt no longer able to self-manage their symptoms [41]. Another observational study reported that 70% of patients with COPD experiencing exacerbations opted for self-medication, including rest and increased use of bronchodilators; only 17% opted to visit a healthcare provider. The patients who did visit a healthcare provider had severe airflow obstruction and a higher number of hospital admission days in the previous year. It was also noted that patients who self-medicated had a significantly longer duration of their exacerbations [33]. Further qualitative studies of patients in the UK, Denmark, and the Netherlands found that reluctance to see the doctor, not wanting to disturb the doctor, inadequate continuity of care, inadequate communication, and restrictions in traveling to the clinic all act as barriers to seeking care for an exacerbation [44]. Similar observations were reported from a 2020 COPD Foundation survey report which showed that approximately 60% of patients who followed a “wait and see” approach did not feel that their symptoms were bad enough to be reported, while 36% of the total participants responded that they feared that reporting an exacerbation may lead to hospitalization. Furthermore, 1 out of 3 patients were concerned that “admitting they are having an exacerbation means their COPD is getting worse,” and 10% were concerned that they would need to take additional medication to control the worsening symptoms [42].

Demographic factors related to reporting COPD exacerbations

Demographic characteristics such as age, sex, race, socioeconomic status, education levels, and smoking history may influence the understanding of COPD and exacerbations by patients. A study by Jiang et al. demonstrated that pa­tients with COPD showed low awareness of exacerbations, particularly patients with low income or low education levels [45]. Langsetmo et al. showed that older patients were less likely to report an exacerbation, which may be attributable to feelings of helplessness, frustration, or futility [25]. However, sex was not among the factors that influenced reporting [25].

In the TORCH study, however, reporting of exacerbations was higher in women, and they are typically exhibited more severe disease than men [46].

Reporting of exacerbations is also affected by race. In a study conducted in the US, African American patients were nearly 4 times more prone to experience exacerbation and were more likely to report exacerbations that required hospitalization and impacted their quality of life (QoL) [47].

A study conducted in elderly patients reported that patients with higher income were less likely to report exacerbations than those with lower income [48]. Similarly, Galiatsatos et al. reported that patients living in more disadvantaged areas in the US had higher odds of reporting COPD exacerbations requiring antibiotics or steroids [49]. This indicates a possible link between socio-economic status and reporting of exacerbations, that could be related to factors such as malnutrition and access to healthcare, among others.

Smoking status may impact exacerbation reporting, but evidence on this is unclear. Based on survey data from the UK, Williams et al. reported that approximately 62% of the participants reporting frequent (≥2/year) exacerbations were smokers [41]. However, in another study conducted in Canada, smoking was not listed as a factor [25].

Comorbid conditions and prior medical history

The presence of a large number of comorbidities in elderly patients is a factor affecting prognosis and, at the same time, may lead to difficulties in diagnosis [57]. However, there are no data about the influence of comorbidities on exacerbation reporting. Certain comorbidities, such as pulmonary embolism, heart failure, pneumonia, and myocardial infarction, can be mistaken for COPD exacerbations, or the exacerbation may be mistaken for one of these conditions, leading to a missed or underreporting of a true exacerbation event [15].

Lack of tools/questionnaires for patients to facilitate early reporting

There are no self-administered, easy-to-use questionnaires for routine use by COPD patients to help them identify the onset of an exacerbation. The EXACT® (exacerbations of chronic pulmonary disease tool) is a 14-item patient reported daily symptom diary that was developed specifically to detect exacerbations for use clinical studies and not for routine use [18,58]. Whilst EXACT can detect unreported exacerbations, this is done through a complex retrospective analysis of the diary data, which is not appropriate for a routine clinical setting [22].

How can the barriers to reporting of COPD exacerbations by patients be overcome?

Identifying patients at high risk of exacerbations

Identification of patients who are at risk of exacerbations can potentially focus the healthcare providers’ attention toward educating them and closely following up with them for the early reporting of exacerbations [59]. However, accurate prediction of patients at high risk of exacerbations requires multiple factors to be taken into consideration, which increases the complexity of risk prediction for individual patients in a routine clinical setting. Hurst et al. analyzed data from the ECLIPSE study and reported that an exacerbation during the previous year, lower FEV₁, worse health status, history of gastrointestinal reflux/heartburn, and increased white blood cell count were all significant independent predictors of the risk of exacerbations [40]. Other risk factors that have been reported to be associated with COPD exacerbations include a high COPD Assessment Test (CAT) score, lower body mass index, presence of chronic bronchitis, and fibrinogen levels [60–64]. Assessment of complex risk factors like these requires algorithms and tools and cannot be done easily with the patient sitting in a busy clinic.

Since history of exacerbations appears to be the best predictor of exacerbations, a focus on encouraging patients to report exacerbations to healthcare providers may be the single most effective intervention to reduce the short- and medium-term effects of exacerbations. Patients need to understand the importance of reporting their symptoms/exacerbations, and it is important to create awareness among them, their families, and caregivers. Clinicians should also be able to communicate and inform their patients about the importance of this during patient visits.

Patient education

Education may improve patients’ awareness and ability to identify COPD exacerbations and eventually enable the timely initiation of treatment [65]. A study by Rice et al. indicated that hospitalization and emergency department visits are reduced if patients receive an education session during their course of treatment [66]. Similarly, the REDUX study showed that a nurse-led intervention for enabling patient self-management of COPD exacerbations reduce the time between the onset of symptoms of exacerbations and patient presentation [67].

A Cochrane review concluded that the use of COPD exacerbation action plans that used a single short educational component along with ongoing support directed at the use of the action plan, but without a comprehensive self-management program, reduced in-hospital healthcare utilization and increased access to treatment [68]. A structured education program specially designed for patients with COPD and behavior modification may achieve a substantial decrease in morbidity [69]. Reviewing the evidence overall, it is reasonable to conclude that patient education may guide patients on how to recognize exacerbations earlier and when to reach out to their healthcare provider.

Tools that detect early symptom worsening and improve reporting of exacerbations

In the absence of suitable education material, a five-item COPD Exacerbation Recognition Tool (CERT) was developed to help with the effective identification and reporting of exacerbations by patients (Figure 3). Two separate development programs were run in China (CERT) and Japan (CERT-J) using the same methodology but otherwise independent. The content of both is very similar, the key difference being the inclusion of color of the sputum in CERT-J at the request of the expert panel (although it was ranked sixth in importance by the patients). When tested in the populations in which they were created (the learning sets) the final version of the CERT had a sensitivity of 91.8% predicted and specificity of 100% [18]. With CERT-J sensitivity was 91.8%, and specificity was 56.3% [19]. Further tests of sensitivity and specificity in new study populations (test sets) are planned. One of the key strengths of the CERT is the use of simple descriptions of the symptoms related to exacerbations that can easily be understood by patients. It also has a simple pictogram for each item to aid patient understanding as illustrated in Figure 3. Once the patient answers the questions, the tool guides the patient for next action; for example, to visit the doctor if they have ticks two or more items in red.

Figure 3. Presentation of CERT but note that the CERT can be presented in any way that is culturally appropriate, including colors, and ideograms.

With the CERT, there was low degree of association between symptom severity score and demographics of the participating patients, specifically age and educational status of the patients. In both CERT and CERT-J, patients characterized their exacerbation more through breathlessness and limitation in activity, rather than through increased cough and sputum. This should give confidence in the generalizability of the CERT across other languages and cultures, but like all patient-centred tools, it will need translation with linguistic and cultural validation for use in other languages. It should also be recognized that CERT is not a diagnostic tool and does not pre-set criteria for diagnosis of exacerbations [18,19]. Although more validation is required, the CERT appears to be a tool that can reduce under-reporting of exacerbations.

Use of technology – telemedicine and others

Emerging technologies in telemedicine and remote patient monitoring (RPM) offer possibilities for the proactive management of patients at risk of COPD exacerbation [70]. The value of regular patient monitoring has been reported by several studies [71,72]. Yañez et al. monitored the respiratory frequency in 89 patients with COPD and showed that the breathing rate increased significantly several days before the patients experienced an exacerbation that required hospitalization. They concluded that regular monitoring of several parameters may allow early identification of COPD exacerbations [71]. Bowler et al. also concluded that the interaction and relevance of personal real-time monitoring of respiratory symptoms, physical activity, rescue medication through rescue inhaler sensors, electronic symptom questionnaires, and physical activity monitors in patients with COPD may provide meaningful information to caregivers. Furthermore, visual displays of longitudinal data are thought to be helpful in driving conversations between patients and caregivers for risk-based monitoring [72].

Telemedicine may potentially play a significant role by applying information and communication technology to enable the monitoring of a patient’s vital signs or biological health data (e.g. oxygen saturation), symptoms, medication, or other non-biologic endpoints (e.g. exercise adherence). Such technology can also help to establish a communication link between the patient and care provider, which may facilitate the early reporting of exacerbations [73,74]. A study by Rassouli et al. compared the standard of care with telehealth care and showed that a higher number of moderate exacerbations were detected with telehealth care than usual care. They also reported that telehealth care reduced the rate of worsening of the CAT score over time by 50% [75].

A Cochrane review demonstrated that interventions aimed at facilitating self-management in people with COPD delivered via smart technology significantly improved HRQoL and levels of activity up to 6 months, compared with interventions given through face-to-face/digital and/or written support. No firm conclusions were drawn from this analysis. However, this may be a useful avenue to explore with the aim of improving the reporting of exacerbations [76].

Conclusions and future outlook

Despite the importance of exacerbations, whether reported or unreported, the underreporting of exacerbations is common and due to multiple underlying factors. Being aware of these factors can help the healthcare provider form an effective plan for exacerbation prevention and may enable greater and earlier reporting of exacerbations. Some factors, such as patient attitude and knowledge, will require active intervention from the healthcare providers, whereas the development, validation, and dissemination of user-friendly tools such as CERT are promising but would necessitate the involvement of healthcare organizations. Technology is another aspect that could be integrated with patient edu­cation and other tools. It is clear that the challenge of underreporting and delayed reporting of exacerbations is multifactorial and will necessitate a multipronged approach for the solution.

Authors’ contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Acknowledgment

EVERSANA provided medical writing and editorial support and was funded by GSK.

Disclosure statement

Paul Jones is a contractor to GSK and owns GSK stocks and shares.

Ashraf Alzaabi is an employee of UAE University and Zayed Military Hospital and reports no conflict of interest.

Alejandro Casas Herrera has received support for the support meeting from GSK; has received honoraria for lectures and attending meetings from GSK (Colombia, Chile, and Global) and Sanofi (Colombia); and has received honoraria for lectures from AstraZeneca (Colombia and LATAM) and Boehringer Ingelheim (Colombia and Ecuador).

Mehmet Polatli is an employee of the Aydin Adnan Menderes University in Turkey and reports no conflicts of interest in this work.

Marcelo Fouad Rabahi is an employee of the Federal University of Goias in Brazil and reports no conflicts of interest in this work.

Arturo Cortes-Telles has received honoraria for lectures from GSK and Johnson & Johnson; received honoraria for lectures and manuscript writing from AstraZeneca and Chiesi; and has received support for attending meetings from AstraZeneca and Chiesi.

Bhumika Aggarwal is an employee of GSK and holds shares in GSK.

Sudeep Acharya is an employee of GSK and holds shares in GSK.

Abdelkader El Hasnaoui is an employee of GSK and holds shares in GSK.

Chris Compton is an employee of GSK and holds shares in GSK.

Additional information

Funding

GSK funded the medical writing and journal submission for this review article.