Personalized medicine for patients with COPD: where are we?

Chronic airflow limitation is the common denominator of patients with chronic obstructive pulmonary disease (COPD). However, it is not possible to predict morbidity and mortality of individual patients based on the degree of lung function impairment, nor does the degree of airflow limitation allow guidance regarding therapies. Over the last decades, understanding of the factors contributing to the heterogeneity of disease trajectories, clinical presentation, and response to existing therapies has greatly advanced. Indeed, diagnostic assessment and treatment algorithms for COPD have become more personalized. In addition to the pulmonary abnormalities and inhaler therapies, extra-pulmonary features and comorbidities have been studied and are considered essential components of comprehensive disease management, including lifestyle interventions. Despite these advances, predicting and/or modifying the course of the disease remains currently impossible, and selection of patients with a beneficial response to specific interventions is unsatisfactory. Consequently, non-response to pharmacologic and non-pharmacologic treatments is common, and many patients have refractory symptoms. Thus, there is an ongoing urgency for a more targeted and holistic management of the disease, incorporating the basic principles of P4 medicine (predictive, preventive, personalized, and participatory). This review describes the current status and unmet needs regarding personalized medicine for patients with COPD. Also, it proposes a systems medicine approach, integrating genetic, environmental, (micro)biological, and clinical factors in experimental and computational models in order to decipher the multilevel complexity of COPD. Ultimately, the acquired insights will enable the development of clinical decision support systems and advance personalized medicine for patients with COPD.

Copper-Heparin Inhalation Therapy To Repair Emphysema: A Scientific Rationale.

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration.

Should vitamin K be supplemented instead of antagonised in patients with idiopathic pulmonary fibrosis?

INTRODUCTION: There is an ongoing need for additional interventions in idiopathic pulmonary fibrosis (IPF) as antifibrotic drugs currently available only inhibit and do not stall disease progression. Vitamin K is a co-factor for the activation of coagulation factors. However, it is also required to activate proteins with functions outside of the coagulation cascade, such as matrix Gla protein (MGP), a defender against soft tissue calcification. Vitamin K antagonists are anticoagulants that are, for unknown reasons, associated with increased mortality in IPF. Areas covered: We advance the hypothesis that modulation of vitamin K-dependent MGP activation in IPF patients by either vitamin K antagonism or administration may result in acceleration and deceleration of fibrosis progression, respectively. Furthermore, shortfall in vitamin K could be suspected in IPF based on the high prevalence of certain co-morbidities, such as vascular calcification and lung cancer. Expert commentary: We hypothesize that vitamin K status is reduced in IPF patients. This, in combination with studies suggesting that vitamin K may play a role in lung fibrosis pathogenesis, would provide a rationale for conducting a clinical trial assessing the potential mitigating effects of vitamin K administration on progression of lung fibrosis, prevention of co-morbidities and mortality in IPF.

The patient with a complex chronic respiratory disease: a specialist of his own life?

INTRODUCTION: The independent and central role of the patient with a complex chronic respiratory disease in targeted, personalized disease management strategies is becoming increasingly important. Patients are the ones living with the disease and are finally responsible for their lives underlining their role as essential members of the interdisciplinary treatment team. Areas covered: The present paper narratively reviews existing research and discusses the special, as well as specialized, role of the patient with a complex chronic respiratory disease in the healthcare system and highlights fundamental elements of the (future) relationship between patient and healthcare professionals. Expert commentary: Since the chronic respiratory disease at hand is part of the patient's entire life, we need holistic, personalized approaches optimizing patients' quality of life by not only treating the disease but considering the patients' whole environment and where healthcare professionals and patients are co-creating value care.

COPD care delivery pathways in five European Union countries: mapping and health care professionals' perceptions.

BACKGROUND: COPD is among the leading causes of chronic morbidity and mortality in the European Union with an estimated annual economic burden of €25.1 billion. Various care pathways for COPD exist across Europe leading to different responses to similar problems. Determining these differences and the similarities may improve health and the functioning of health services. OBJECTIVE: The aim of this study was to compare COPD patients' care pathway in five European Union countries including England, Ireland, the Netherlands, Greece, and Germany and to explore health care professionals' (HCPs) perceptions about the current pathways. METHODS: HCPs were interviewed in two stages using a qualitative, semistructured email interview and a face-to-face semistructured interview. RESULTS: Lack of communication among different health care providers managing COPD and comorbidities was a common feature of the studied care pathways. General practitioners/family doctors are responsible for liaising between different teams/services, except in Greece where this is done through pulmonologists. Ireland and the UK are the only countries with services for patients at home to shorten unnecessary hospital stay. HCPs emphasized lack of communication, limited resources, and poor patient engagement as issues in the current pathways. Furthermore, no specified role exists for pharmacists and informal carers. CONCLUSION: Service and professional integration between care settings using a unified system targeting COPD and comorbidities is a priority. Better communication between health care providers, establishing a clear role for informal carers, and enhancing patients' engagement could optimize current care pathways resulting in a better integrated system.