Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management

Abstract

Chronic obstructive pulmonary disease (COPD) is a common, complex and heterogeneous condition which is responsible for considerable and growing morbidity, mortality and healthcare expense worldwide. In order to decipher the complexity of COPD, it is imperative that we identify groups of patients with similar clinical characteristics, prognosis and/or therapeutic needs, so called clinical phenotypes. This strategy is logical for research but it may be of limited clinical value because clinical phenotypes may overlap in the same patient and the same clinical phenotype could result from different biological mechanisms. With the goal of matching assessment to treatment choices, the most recent iteration of GOLD reorganized treatment objectives into two categories (improving symptoms, i.e., dyspnoea and health status, and decreasing future risk, as predicted by FEV1 level and exacerbations history), thus moving closer to individualized medicine using currently available bronchodilators and anti-inflammatory medications. Yet, future therapeutic options are likely to include targeting endotypes which reflect subtypes of patients defined by a distinct pathophysiological mechanism. Specific biomarkers of these endotypes would be particularly useful for clinical practice, especially when clinical phenotype alone is insufficient to identify the underlying endotype. Currently, a limited series of potential COPD endotypes and biomarkers have been suggested. We will gain empiric knowledge from proof of concept trials in COPD with emerging drugs that target specific inflammatory pathways. In each instance, specific endotyping and biomarker efforts will likely be required for success of these trials, since the pathways are likely to be operative in only a subset of patients. Network analysis of human diseases offers the possibility of a better understanding of disease patho-biologic complexity while facilitating the development of new therapeutic alternatives and, importantly, a reclassification of complex diseases. All these development should pave the way towards personalized treatment of COPD in the clinic.

Treatable traits: toward precision medicine of chronic airway diseases

“…Both are ideally suited for precision medicine because they likely represent a continuum of different diseases that may share biological mechanisms (often referred to as "endotypes") and present similar clinical features (often referred to as "phenotypes") that require "individualised" treatment [1, [10][11][12]. For the discussion that follows, it is important to define precisely these two terms.…”

“…Hence, just considering molecular measurements does not address endotypes, unless the critical causal role of the molecular pathway has been established [14]. According to this latter definition, so far only few (if any) endotypes have been identified in airway disease that have therapeutic implications [11,14]. In this setting, phenotypes can be used for hypothesis generation and probabilistic prediction of treatment outcomes, whereas endotypes are the result of hypothesis testing, being of course also highly suitable for treatment choices.…”

Patient Heterogeneity in Health Economic Decision Models for Chronic Obstructive Pulmonary Disease: Are Current Models Suitable to Evaluate Personalized Medicine?

“…Although this new classification is a step forward to personalized treatment for COPD, proposed treatment guidelines for the subgroups of patients still need to be validated [7]. Manufacturers of drugs and devices focus are increasingly focused on specific phenotypes of patients, such as the patients with frequent exacerbations, a rapid decline in lung function, persistent systemic inflammation, raised eosinophil concentrations, bacterial colonization etc [8,9]. In addition, caregivers providing multidisciplinary integrated care programs develop different treatment modules for subgroups of patients who need physical reactivation, 5 smoking cessation support, nutritional interventions, treatment of depression etc.…”

Metabolomics of Exhaled Breath Condensate: A Means for Phenotyping Respiratory Diseases?

“…A phenotype is operationally defined as ''a cluster of features that leads to the separation of a specific group at a given time" [3]. Therefore, what is required is the identification of specific phenotypes, which recognize groups of patients with similar characteristics, prognosis or treatment needs, paving the path to p ersonalized r espiratory medicine [4].…”