Unravelling the mechanisms driving multimorbidity in COPD to develop holistic approaches to patient-centred care

Abstract

COPD is a major cause of morbidity and mortality worldwide. Multimorbidity is common in COPD patients and a key modifiable factor, which requires timely identification and targeted holistic management strategies to improve outcomes and reduce the burden of disease.We discuss the use of integrative approaches, such as cluster analysis and network-based theory, to understand the common and novel pathobiological mechanisms underlying COPD and comorbid disease, which are likely to be key to informing new management strategies.Furthermore, we discuss the current understanding of mechanistic drivers to multimorbidity in COPD, including hypotheses such as multimorbidity as a result of shared common exposure to noxious stimuli (e.g. tobacco smoke), or as a consequence of loss of function following the development of pulmonary disease. In addition, we explore the links to pulmonary disease processes such as systemic overspill of pulmonary inflammation, immune cell priming within the inflamed COPD lung and targeted messengers such as extracellular vesicles as a result of local damage as a cause for multimorbidity in COPD.Finally, we focus on current and new management strategies which may target these underlying mechanisms, with the aim of holistic, patient-centred treatment rather than single disease management.

The Role of Extracellular Vesicles as a Shared Disease Mechanism Contributing to Multimorbidity in Patients With COPD

“…The occurrence of multiple chronic conditions termed “comorbidities” or “multimorbidities” are common in patients with COPD ( 14 , 15 ) ( Figure 1 ). Other conditions commonly observed in conjunction with COPD include cardiovascular disease (CVD), diabetes, osteoporosis and gastro-oesophageal reflux disease ( 15 ).…”

“…The occurrence of multiple chronic conditions termed “comorbidities” or “multimorbidities” are common in patients with COPD ( 14 , 15 ) ( Figure 1 ). Other conditions commonly observed in conjunction with COPD include cardiovascular disease (CVD), diabetes, osteoporosis and gastro-oesophageal reflux disease ( 15 ). While the term ‘‘comorbidity’’ refers to the combined effects of additional conditions in reference to an index chronic condition, “multimorbidity” indicates that no single condition holds priority over any of the co-occurring conditions ( 16 ).…”

“…Our current understanding of the mechanistic drivers for multimorbidity in COPD, including the role of shared risk factors were recently reviewed in detail by Burke and Wilkinson ( 15 ). These authors suggested that disease co-occurrence may not be by chance but as a result of shared genetic predisposition and responses to biological and environmental stressors ( 15 ). They also highlighted current and novel management strategies that target these underlying mechanisms.…”

“…In addition, there is accumulating evidence that exposure to shared risk factors including inhalation of noxious stimuli and accelerated ageing may act as a central mechanism contributing to the development of multiple chronic diseases ( 18 , 19 ). Furthermore, Burke and Wilkinson introduced the concept that extracellular vesicles (EVs) may contribute to dissemination of inflammation and therefore multimorbidity in COPD patients ( 15 ).…”

“…Recently EVs have been reported as local and systemic immune and inflammatory mediators that may act to spread or alleviate disease ( 15 , 20 – 22 ). During acute and chronic inflammation, vascular permeability is dramatically increased and the alveolar-capillary barrier is reduced allowing lung inflammatory mediators such as proteins and EVs to reach the systemic circulation and potentially distant organs ( 21 , 23 ).…”