Nutritional phenotyping in COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is a collective term for a condition associated with irreversible airways obstruction causing breathlessness and risk of recurring chest infections, termed exacerbations. Malnutrition has been shown to play an important role in many chronic diseases, but in COPD the extent that differences in nutritional wellbeing determine the patient’s risk of exacerbation, resilience to infection or response to treatment, has not been adequately addressed and so nutritional aspects of care have not been considered primary concerns in the management of the disease. COPD exacerbations are assumed a major driver for the progression of COPD and of healthcare utilisation. Current respiratory variables measured in routine clinical practice are insufficient to identify patients at risk of exacerbation in the short- to medium-term and hence interventions to ameliorate exacerbation risk are limited. There is a real need to explore other non-respiratory markers for risk assessment in COPD patients. Whilst nutritional assessment has been established as an important tool in understanding risk of long-term outcomes, especially mortality, its role in assessing patient’s risk of and response to exacerbations is less well understood. This thesis sought to explore the nutritional status in COPD patients with different disease presentations and clinical outcomes, in order to identify nutritional markers of exacerbation risk. Analysis focused on exploring the relative importance of disease history on nutritional status at baseline (how does previous disease impact on nutritional status), associations between disease status and nutritional status in stable COPD and relationship between nutritional status and clinical outcomes like time to first exacerbation (TTFE) and exacerbation rate over 12 month. Systematic review of the literature demonstrated variability in methods used to assess structural and functional markers of lean mass of COPD patients, which limited the conclusions that could be made. To address this a comparison of methods used in COPD patients was devised and conducted, showing comparability of the results of these methods. To explore the relationship between the nutritional status and clinical outcomes in COPD, a longitudinal, 12 months prospective cohort study, comprised of 127 COPD patients with a previous history of exacerbations was carried out. Nutritional status was assessed using markers of body composition, appetite and functional capacity (grip strength, grip endurance, walk test) at baseline and quarterly basis. These nutritional markers were used to explore their relationship with past medical history, baseline disease markers (spirometry, inflammation) and clinical outcomes, with further assessment of their predictive value for clinical outcomes measured as TTFE. In the studied cohort, 7 to 25% men and approximately 33% women had lean depletion (depending on applied criteria), and unexpectedly, low lean mass was not associated with a shorter time to first exacerbation. Those who had poor appetite were at higher risk of exacerbation in the following month (HR 1.6, p=0.023), which was independent of the exacerbations history and disease severity. Functional limitations including stopping during the 6- minute walk test (HR 1.90, p=0.001) and distance of less than 350m (HR 1.95, p=0.002) were related to TTFE. As none of the domains was sufficient to independently identify patients at high risk of exacerbation with sufficient accuracy in the next month, a multicomponent approach was taken by combining appetite score, body composition and walk test. Poor nutritional status marked by two or more components showed a higher risk of exacerbation, compared with those identified by any single component (HR 3.47 p<0.001). Use of history of exacerbation as additional component did not improve relevance to clinical outcomes and appetite score appeared to be of the greatest relevance to time to first exacerbation. In summary, the findings of this thesis demonstrate that nutritional status is not determined by the history of exacerbations, yet relates to markers of disease status in stable COPD and clinical outcomes in the future. Multicomponent nutritional assessment showed potential to identify patients with high risk of exacerbation in the near future, which was not possible when using standard respiratory measures alone. This thesis emphasises the role of assessing nutritional status in COPD patients and the relevance and need for recognizing different nutritional phenotypes in the disease management.

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