Chronic respiratory disease is a collective term for diseases affecting the airways and other structures of the lungs. These diseases are major contributors to global mortality and the overall burden on health. Some of the most common types are chronic obstructive pulmonary disease (COPD), asthma, and pulmonary hypertension, diseases which all exhibits various subtypes. Characteristics of these diseases are the changes to the lung tissue and the inflammatory microenvironment, leading to both lung tissue destruction and the deposition of excess proteins in the wrong location (Figure 1).
Nordic Bioscience develop non-invasive blood-based biomarkers which can be used as tools to quantify these key pathological changes in the lung. These biomarkers can help us understand the complex molecular pathways that lead to chronic respiratory disease and promote personalized treatment options.
Chronic respiratory diseases such as COPD are highly heterogeneous and the traditional “one size fits all” treatment approach has largely failed. However, by stratifying patients based on subtypes using biomarkers, there is a potential to enhance the success rate in clinical trials by recruiting patients with the greatest likelihood of treatment response. Subtyping can be based on the identification of relevant molecular pathways that may be suitable for specific treatment modalities, or by predicting disease progression that may accelerate the initiation of appropriate treatment options. An example of the latter is shown in Figure 2. |  Figure 2. Subtyping chronic respiratory diseases |
COPD is the third leading cause of death worldwide with a growing healthcare burden due to the aging population and continued exposure to risk factors. Currently, there are no treatments available to modify the lung tissue changes and halt the decline in lung function for COPD patients. Recent advances in drug development can be attributed to the inclusion of specific patient subsets in clinical trials, enabling the demonstration of treatment efficacy in individuals with shared molecular pathways that drive the disease. This highlights the importance of identifying clinically treatable COPD endotypes to bring novel treatment options to patients.
At Nordic Bioscience, we aim to characterize COPD better and use data-driven approaches to identify novel treatable endotypes. This has the potential of improving the efficacy of clinical trials and aid in the discovery of targeted treatments. We take advantage of our access to large, well-characterized cohorts and our unique biomarkers that are non-invasive tools for investigating causal molecular pathways leading to lung tissue destruction.
Nordic ProteinFingerPrint Technology™ biomarkers for COPD reflect lung tissue destruction, elastin degradation, inflammatory cell profile, blood clotting, and small airway fibrosis. We have demonstrated three key features of these biomarkers in COPD patients:
- Biomarkers can differentiate the mechanisms that lead to airflow limitation. In Figure 3A we show that COPD patients with emphysema have the highest levels of the biomarker EL-NE which quantifies neutrophil elastase-mediated elastin degradation[1].
- Biomarkers are directly associated with disease activity. In Figure 3B we show an example of a biomarker of basement membrane destruction, C4M, that rise significantly during an acute exacerbation of COPD. When the patients are clinically stable again at follow-up, the biomarker levels drop to the original baseline value[2].
- Biomarkers are prognostic for mortality outcome. In Figure 3C, COPD patients with high baseline levels of the tissue formation biomarker PRO-C6 (Q4) have a higher risk of mortality compared to those with lower levels (Q1-Q3)[3].
Figure 3A, B, C. Nordic Bioscience biomarkers' key features in COPD
Asthma is characterized by airway constriction, chronic inflammation, and extracellular matrix remodeling. It is common practice in the asthma field to treat patients based on their underlying molecular features such as asthma driven by type 2 inflammation. Chronic inflammation results in the destruction of the lung tissue and the asthma severity may be monitored by biomarkers (Figure 4A)[4].
Changes to the basement membrane are a well-known characteristic of the asthmatic lung. The C4Ma3 biomarker quantifies the degradation of the alveolar basement membrane and has been shown to be a valuable biomarker for asthma. For example, C4Ma3 is associated with eosinophilic inflammation (Figure 4B) and high baseline levels of C4Ma3 predicted response to an anti-IgE treatment in patients with allergic asthma (Figure 4C)[5].
Figure 4A, B, C. Nordic Bioscience biomarkers measure inflammation in the lungs
COPD stands for Chronic Obstructive Pulmonary Disease and is a chronic inflammatory lung disease characterized by restricted airflow that mainly affects middle-aged or elderly adults who smoke. Chronic obstructive pulmonary disease is a progressive disease that results in symptoms such as shortness of breath, coughing, and mucus production. Restricted airflow is caused by a mixture of obstructive bronchitis and fibrosis in the small airways and the destruction of the lung parenchyma, leading to emphysema.
How many people have COPD?
COPD is an underdiagnosed disease with a prevalence of 251 million cases worldwide. With 3.2 million deaths in 2015, chronic obstructive pulmonary disease caused 5% of all deaths worldwide, making it the third leading cause of death. Tobacco smoke is the main cause of COPD, but other important risk factors include indoor and outdoor air pollution and workplace dust or fumes.
How is COPD treated?
There is no cure for COPD, but bronchodilators are the most common type of treatment to improve lung function and relieve symptoms temporarily. The treatment regimen is based on symptoms, lung function and risk of exacerbations.
How is COPD diagnosed?
Current diagnosis is based on spirometry with a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) value below 0.7 after bronchodilation. This confirms persistent airflow limitation and, together with symptoms, leads to a diagnosis.
Asthma is a chronic inflammatory disease of the respiratory tract. Chronic inflammation causes the airways to swell, making them highly sensitive and narrowed. The swelling can occur randomly or after triggers such as allergies, smoke, air pollution, and exercise. The main symptoms are wheezing, shortness of breath, and coughing, which may temporarily worsen and lead to asthma attacks.
How many people have asthma?
Asthma is one of the most common chronic diseases, affecting more than 300 million people worldwide. Asthma affects people of all ages and often begins in childhood, although it can also first appear in adults.
How is asthma treated?
The symptoms of asthma can usually be controlled by treatment with inhalers for relief or prevention. However, patients with severe asthma may have persistent problems and difficulty controlling their asthma symptoms with treatment, which increases the risk of asthma attacks.
How is asthma diagnosed?
The current diagnosis of asthma is based on variable expiratory limitation measured by forced expiratory volume in 1 second (FEV1), family history, and symptoms.
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