Study explores the challenges of the clinical diagnoses of acute exacerbation of chronic obstructive pulmonary disease

By Dr. Priyom Bose, Ph.D.Aug 16 2023Reviewed by Sophia Coveney

A recent BMC Pulmonary Medicine study evaluated the clinical, laboratory, and radiographic characteristics of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). It aimed to distinguish them from other diseases in patients with a history of chronic obstructive pulmonary disease (COPD).

Background

AECOPD is associated with a significant worsening of respiratory symptoms that requires additional therapy. Several studies have indicated that AECOPD increases mortality, morbidity, and overall healthcare cost.

Exacerbations linked to AECOPD have multiple underlying etiologies and clinicopathological processes, which cause similar syndromic phenotypes. Each of these symptoms responds to therapy differentially and has a varied clinical prognosis.

Typically, a clinical diagnosis of AECOPD is based on subjective symptoms and non-specific clinical features. However, these characteristic features could be confounded by multiple comorbidities that are commonly found in the COPD population. Many times, COPD patients with dyspnea were diagnosed with AECOPD. Such misdiagnosis often subjects patients to unnecessary treatment regimens.

About the study

This retrospective cohort study has selected participants from a prospective pilot randomized controlled trial (IPRAC), which investigated the efficacy of intravenous immunoglobulin infusions to prevent recurrent AECOPD in hospitalized patients.

The current study only recruited patients above 40 years of age who were hospitalized due to clinical diagnosis of AECOPD.

Patients with clear alternative diagnoses, such as malignancy, were excluded from this study. Electronic medical records of the patients were reviewed in a systematic manner.

The final diagnosis of the patients was documented based on the discharge diagnosis, which was supported by symptoms, imaging, and laboratory findings. Here, patients were categorized based on the final diagnosis, i.e., AECOPD alone, AECOPD with other conditions, and no AECOPD.

Patients under the ‘AECOPD alone’ category did not present any evidence of other comorbid or acute conditions that could interfere with the diagnosis. Following Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, patients with influenza were put under the AECOPD alone group.

AECOPD patients with dyspnea and wheezes, along with other identifiable etiologies, such as pulmonary embolism, pulmonary edema, or evidence of pneumonia, were categorized under the ‘AECOPD with other conditions’ group. Patients with clear evidence of bacterial pneumonia were groups under ‘no AECOPD.’

Study findings

A total of 395 hospitalized patients with a diagnosis of AECOPD were part of the IPRAC trial. Considering the eligibility criteria, a total of 315 patients were considered in the current study.

This study underscores the challenges associated with the clinical diagnosis of AECOPD. Clinical and/or laboratory findings exhibited limitations in distinguishing classical AECOPD from AECOPD associated with other illnesses.

Although three clinical symptoms, i.e., pneumonia, congestive heart failure, and pulmonary embolism, were associated with AECOPD in univariate analysis, none of the symptoms were able to differentiate AECOPD alone from AECOPD with other acute processes.

An increased venous pCO₂ was linked to the diagnosis of AECOPD. Consistent with previous studies, the current study indicated that radiographic evidence of pleural effusion implies against AECOPD. Additionally, the radiographic data of pneumonia or pulmonary edema indicate against AECOPD-only diagnosis.

Imaging data indicated the possibility of the AECOPD being related to lower respiratory tract infection. Based on this observation, 12% of the patients were wrongly diagnosed with AECOPD. This finding indicates the complexity of AECOPD diagnosis.

At present, not many studies regarding the misdiagnosis of exacerbation are available. The prevalence of higher COPD misdiagnosis in the general population contributes to the challenge of AECOPD diagnosis.

Previous studies have indicated that one-third of patients diagnosed with COPD in the primary care setting may have been misdiagnosed. In Ontario, only one-third of patients diagnosed with COPD undergo a spirometry test that confirms the diagnosis.

One-third of patients considered in the current study were diagnosed with COPD without receiving a spirometry test. Interestingly, many of the patients received a diagnosis of AECOPD and were treated accordingly.

The prevalence of misdiagnosis of AECOPD in hospitalized patients and the general population increase the challenge of determining unique features of the disease, which prevents the distinguishing of AECOPD from other underlying etiologies.

Due to the lack of a reference standard in this field, patients with AECOPD accompanied by other conditions could not be determined suitably. The current GOLD recommendations suggest the exclusion of differential diagnoses before confirming AECOPD; however, this is unreasonable because many times AECOPD are present concurrently with other etiologies.

Notably, elevated sputum purulence was found to be associated with AECOPD with co-existing other conditions but not with AECOPD-only patients. 

Conclusions

The current study has some limitations that include the small sample size. The limited sample size limited inclusion of many variables in the multivariate analysis. Due to inconsistencies in measurement protocols, laboratory parameters, such as procalcitonin, D-dimer, and C-reactive protein, were not considered to distinguish AECOPD from AECOPD with other acute illnesses.

Despite the limitations, this study underscored the complexity of AECOPD diagnosis. The importance of sputum purulence and venous pCO₂ in AECOPD diagnosis was also indicated in this study.