Clinical Implementation and Outcomes Evaluation of Blood-Based Biomarkers for Chronic Obstructive Pulmonary Disease Management

An acute exacerbation of COPD (AECOPD) is defined as an acute event characterized by a worsening of the patient's respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication (in most cases to antibiotics and/or oral corticosteroids). In most cases of AECOPD, patients experience a gradual crescendo-like increase in shortness of breath, cough and purulent sputum production over days to weeks. At their peak, patients may experience extreme shortness of breath (sometimes described as "breathless paralysis") and uncontrollable paroxysms of cough and purulent sputum production. AECOPDs are complex physiological events. In 70-80% of cases, AECOPDs are precipitated by bacterial or viral respiratory tract infections. However, most patients who develop acute symptoms (e.g., runny nose, cough or fever) do not progress to AECOPDs and experience spontaneous resolution of their symptoms. Furthermore, many patients with COPD who do harbour pathogenic organisms in their airways do not develop AECOPD symptoms. Thus, other factors, including the host inflammatory response, likely play a role in the pathogenesis of AECOPDs. Prompt recognition and treatment of AECOPD during this prodromal period can abrogate full blown attacks. Thus by identifying and treating AECOPDs early on (in physicians' offices), emergency visits, hospitalizations, and even deaths can be significantly reduced. However, this is not easy as symptoms of AECOPD (especially early in their course) are non-specific and can easily be confused with other ailments such as heart failure, allergies, or even upper respiratory tract infections. Since there are no biochemical tests that clinicians can order to objectively confirm AECOPD, AECOPD can be missed entirely or misdiagnosed, leading to delayed treatments or in some cases to the wrong treatment, which may result in devastating consequences including respiratory failure, hospitalizations or even death. Once patients are in the full blown attack stage of AECOPD, treatments are only modestly helpful in relieving symptoms and hospitalization is often required to resolve them. The median duration of hospitalization for AECOPD in Canada is 10 days, followed by an average of 3 months of convalescence. Unfortunately, in most cases, full recovery is never achieved and patients continue to experience rapid decline in lung and physical function (compared to patients not hospitalized for AECOPD). The 3 year mortality rate following hospitalization is 50%, and hospitalizations and emergency visits are avoidable with earlier detection, diagnosis and treatment of AECOPD. Indeed, COPD is the leading cause of preventable hospitalization in Canada. However, without a simple blood test that primary care physicians (PCPs) can order in their offices, earlier diagnosis will not be feasible.

The primary objective of this study is to identify blood biomarkers that can diagnose AECOPD.

Following informed consent, blood samples will be collected from patients who are admitted for an exacerbation at day 1, 3 and 7 of their hospitalization and then at 30 days and 90 days post-hospitalization. Sputum samples will also be collected on the day of admission for AECOPD etiologic phenotyping. All patients receive standard anti-exacerbation care in hospital, including systemic corticosteroids and antibiotics and are followed both in and out of hospital by a transition team consisting of a nurse, physiotherapist and respiratory therapist with special expertise in COPD care.

Following informed consent of non-exacerbating patients, a blood sample will be collected which will be used as a comparison to the exacerbating patient samples.