The PROTECCT-M study: a cohort study investigating associations between novel specific biomarkers, patient-related, healthcare system markers and the trajectory of COPD patients treated in primary care

Chronic obstructive pulmonary disease (COPD) is a common chronic, often life-threatening disease characterised by a permanent and progressive airway obstruction. COPD is clinically defined as having irreversibly reduced airway function of an obstructive type (FEV₁/FVC <70%) [1‐3]. According to the World Health Organisation 80 million people suffer from moderate to severe COPD worldwide, and it is expected that this will increase to become the third most important cause of death. It is estimated that in the population of 5.5 million inhabitants in Denmark, 430 000 people suffer from COPD, 230 000 of these from moderate COPD and 40 000 from severe COPD [4]. Denmark has one of the highest prevalences and mortality rates of COPD, probably primarily due to frequent tobacco use. Hospital visits for this group of patients are common and account for a substantial part of healthcare costs as a whole [5, 6]. Some 85% of patients with COPD are or have been smokers, and it is estimated that 35-40% of smokers develop the disease [7]. COPD is associated with a low socioeconomic status, markedly reduced quality of life, large use of prescribed drugs and frequent contacts with the healthcare system [2, 6, 8]. COPD is a progressive disease developing over decades, but if the degree of disease progression among COPD patients is not stopped, in 10-15 years there will be an even greater need for hospital beds, medical treatment and rehabilitation at huge expenditure.

In Denmark 98% of the population is listed with a GP who provides primary care for a defined part of the population. A large part of the population consults their GP several times during a year. Most COPD patients are diagnosed by their GP, typically after a long period of productive cough and reduced function in daily life with dyspnoea. The maximum prevalence is reached at about the age of 80 years. Today much of a patient´s lung function is already lost at the time of diagnosis. Despite massive preventive measures COPD is a major and rising problem in Denmark [9]. The diagnosis is made by investigation of lung function (spirometry), which can be performed by the GP, but it takes time and requires skill and is therefore not always performed [10, 11]. The measurement of lung function can, however, neither in light or moderate COPD predict the development of the disease, as it only reflects loss of lung capacity and not disease activity. Exacerbations are associated with significant mortality, loss in lung function and deterioration in quality of life [12‐14]. Apart from previous exacerbation history, we currently have no good tools to identify frequent exacerbators. Use of biomarkers for detection of early COPD could be a possible new way [15, 16] of predicting prognosis to aid both the GP and his/her patients, but until now no biomarkers of disease activity have been shown to predict a COPD trajectory. However, through an ongoing collaboration [17] we have established a working relationship with specialists in molecular medicine. Two molecules have especially been in focus for their studies: surfactant protein D (SP-D) [18, 19] and microfibrillar-associated protein 4 (MFAP4). Lack of either SP-D or MFAP4 leads to development of emphysema in mice and could thus be involved in the heterogeneity in disease development and progression of COPD. Both molecules are primarily expressed in the lungs, and both molecules are present in humans. In the ECLIPSE cohort SP-D has been shown to be associated with exacerbations, but not with the severity of COPD [18].

COPD is a common disease in the population, which is often diagnosed and followed in primary care in the early phases. COPD is a complex disease with both pulmonary and extrapulmonary manifestations. Some patients deteriorate quickly, while others remain stable for a long period. More accurate tools/markers, which can predict prognosis and thus identify groups of patients in need of specific therapies or rehabilitation are needed. COPD can be a challenge to the GP since there are few tools to elucidate the prognosis of the individual patient. For such tools to be of “clinical utility” [34] it is of importance that the evidence is generated in general practice under conditions that resemble normal clinical practice as closely as possible, which we believe that data collection through data capture offers. It is thus of importance that GPs are interested in participating in studies such as the present study aiming at creating more personalised medicine for COPD patients treated in primary care. The aim was to study factors determining frequency of exacerbations and to investigate if the biomarkers SP-D and MFAP4 have such a role in COPD patients treated in primary care.