Management of chronic obstructive pulmonary disease beyond the lungs

Summary

Chronic obstructive pulmonary disease (COPD) is an umbrella term that covers many clinical subtypes with clearly different pulmonary and extra-pulmonary characteristics, but with persistent airflow limitation in common. This insight has led to the development of a more personalised approach in bronchodilator therapy, prevention of exacerbations, and advanced treatments (such as non-invasive ventilation and lung volume reduction techniques). However, systemic manifestations and comorbidities of COPD also contribute to different clinical phenotypes and warrant an individualised approach as part of integrated disease management. Alterations in bodyweight and composition, from cachexia to obesity, demand specific management. Psychological symptoms are highly prevalent, and thorough diagnosis and treatment are necessary. Moreover, prevention of exacerbations requires interventions beyond the lungs, including treatment of gastro-oesophageal reflux disease, reduction of cardiovascular risks, and management of dyspnoea and anxiety. In this Review, we discuss the management of COPD beyond the respiratory system and propose treatment strategies on the basis of the latest research and best practices.

Introduction

Although chronic obstructive pulmonary disease (COPD) is defined by the presence of chronic airflow limitation, it is considered a complex, heterogeneous, and multicomponent disease in which comorbidities and extra-pulmonary manifestations have important contributions to disease expression, disease burden, and survival. Thus, a COPD phenotype is not limited to the expression of the pulmonary disease itself. Because different groups of patients with different health status can be identified on the basis of their comorbidity profile¹ and specific treatment of comorbidities can alter the clinical course,² we can rightfully consider these non-pulmonary issues in the phenotypic complexity of patients with COPD.³ The presence of co-occurring chronic non-communicable diseases and other physical and psychological manifestations needs to be recognised in our approach to characterise and manage individual patients with COPD. Although management of comorbidities is now incorporated in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy document,⁴ a COPD-specific approach needs to be considered. The complex and multiple dimensions of COPD demand a drug regimen that includes not only inhaler therapy but also systemic treatments, which have potential pharmacological cross-effects between the respiratory system and other systemic compartments. Indeed, coexisting diseases are interlinked beyond simple coincidence, and perturbation of the network of comorbidities could possibly be achieved by selecting and treating highly connected comorbidities.⁵ Therefore, in-depth knowledge of the underlying biology of these connected comorbidities is necessary.⁶ At the same time, we should also be mindful of the notion of “primum non nocere” (first do no harm) and recommend therapies that have strong proven effectiveness and that have clear benefits over harm. Here, we review published work on the management of COPD beyond the lungs, taking into account the most important COPD-related systemic manifestations and comorbidities (figure 1), and provide recommendations and expert opinion.