The emergence of new biological drugs for treatment of the obstructive lung diseases, asthma and COPD, are paving the way for personalized and improved treatment of large patient groups. However, choosing which patients will benefit from the treatments is a major challenge. By this study we aim to characterize a real-life population of patients with asthma, COPD and in-between conditions, to define and validate distinct biomarkers that reflect the disease state. The biomarkers can be used as outcome predictors for use in the clinical setting to facilitate stratification of patients to the right treatment for the benefit of both patients and the society.
The real-life population will be recruited from primary, secondary and tertiary health care centers with all patients included being referred from primary care physicians. These will constitute a population of patients that is expected to benefit from the new available treatments, regardless of their disease progression.
All data and physical samples obtained from the patients will be included in a database and a biobank. The information and material from these platforms can be used to further characterize patients with obstructive airway disease in a real-life setting, providing comparable information on COPD and asthma patients with mild, moderate and severe disease. This offers unique and valuable information that is not routinely obtained from clinical studies; often, patients with mild and moderate disease are omitted from clinical studies, which then only reflect the effect of the different interventions in a population with severe disease and not the entire patient group.
Using the material in the biobank and the database, we wish to define the value of biomarkers at various degrees of disease severity and we have chosen to define biomarkers as a parameter objectively measuring any biological response to a change in a condition (i.e. disease severity, disease progression, response to treatment etc.), whether this is a molecular, physiological, microbial or symptomatical response.
With the aid from the unique personal identification numbers provided at birth or immigration to all citizens in Denmark and Sweden, we also have the possibility of correlating the diagnosis of obstructive lung disease to personal data such as socio-economic status, education, job profile, co-morbidities and long-term work disability (sickness absences or disability pensions) to better characterize the disease burden in the population. Furthermore, the Nordic countries also have the possibility to analyze the use of medication, the specific type of medication including inhaled and systemic therapy, as well as the level of well-treated disease as measured by a low use of CS and short-acting β2-agonists. Lastly, the prescription list can also provide an indirect measure of adherence through the frequency of drug bought over a period of 12 months.
Personalized Treatment and Biological Drugs
Targeted treatment of eosinophilic asthma using antibody-based therapies has proven very successful, and underlines the importance of finding biomarkers for optimizing diagnosis and treatment of obstructive lung disease. The antibody-based treatments target different components downstream of the Th2-mediated inflammation, such as IL4, IL5 and IL13 and ongoing studies are examining the effects of targeting the upstream components of Th2-inflammation such as anti-TSLP treatment, a cytokine central to the eosinophilic response in atopic asthma (Ito, Liu, and Arima 2012).
The antibody-based treatments have primarily been tested in selected individuals diagnosed with severe asthma and often with high eosinophilic cell counts and high level of other biomarkers such as periostin, FENO or atopy (Parulekar, Atik, and Hanania 2014). However, some COPD patients may also benefit from antibody-based treatment, i.e. COPD with an eosinophilic phenotype. Few, if any, studies with targeted therapies have been directed towards the non-eosinophilic (Th2-low) asthma. Yet, the medical need for this large asthma category may be particularly high due to a reduced response to CS treatment (Mike Berry et al. 2007). The development and evaluation of new treatment for non-eosinophilic (Th2-low) asthma is further complicated by lack of knowledge regarding the involved inflammatory mechanisms and even though non-eosinohilic (Th2-low) asthma may have a pauci-granulocytic, or sometimes neutrophilic, signature (Bergqvist et al. 2013), the nature of the inflammation needs to be further defined. At the moment, there are no targeted therapies for the non-eosinophilic asthma/COPD, and in light of the positive response to targeted therapies in patients with eosinophilic disease, the urgent need for a better characterization of non-eosinophilic inflammatory disease is further emphasized (Chung 2015).
In conclusion, the inflammatory, cellular and physiological phenotypes of asthma and COPD are only partly described with differences and similarities between the two obstructive diseases. Nothing is known about differences between specific phenotypes and the use of Medicare, the development of disability or the treatment possibilities towards the basic airway pathology. Moreover, the prevalence of co-morbidities such as rhinosinusitis, nasal polyps and dysfunctional breathing in asthma and COPD is not well characterized, which poses major challenges to disease-control and new knowledge is urgently needed to improve response to treatment in asthma and COPD patients.
Responsible for research project:
Vibeke Backer, MD, DMSci, Professor, Chief Respiratory Physician, Bispebjerg Hospital; Celeste Porsbjerg, MD, PhD, Associate Professor, Chief Respiratory Physician, Bispebjerg Hospital; Uffe Bødtger, MD, PhD, Chief Respiratory Physician, Næstved Sygehus; Leif Bjermer, MD, DMSci, Professor, Chief Respiratory Physician, Skåne University Hospital; Kerstin Romberg, MD, PhD, Specialist in general medicine, Skanör, Höllviken, Sweden; Jonas Erjefält, MSc, PhD, Professor, Dept. Exp. Medical Sciences, Lund University; Karsten Kristiansen, MSc, DMSci, Professor, Department of Biology, University of Copenhagen.