Analysing weaknesses in undernutrition management in COPD patients: an excursus from the screening to the treatment.

Chronic obstructive pulmonary disease (COPD) is a common, complex and heterogeneous disease characterized by a persistent airflow limitation. Whilst the negative impact of lung function impairment on patients’ survival and symptom burden has been widely clarified, body weight and body composition abnormalities in COPD have attracted fewer attention, considered for years a consequence rather than an independent determinant of patients’ survival. Nowadays, evidence about the negative influence of undernutrition on the clinical disease course are increasing and it has been demonstrated that it is associated with worse quality of life, increased healthcare use and costs. Undernutrition is primarily caused by an altered energy balance characterized by an insufficient intake of energy and nutrients therefore, the quantification of the balance of energy intake and expenditure should be warranted especially in COPD patients who have an increased resting energy expenditure (REE). The clinical gold standard for the estimation of REE is the indirect calorimetry (IC) however, due to high cost and time requested for the exam, dieticians and pneumologists usually use predictive formulas, even though not validated in a COPD population. This contributes to underestimate undernutrition in COPD patients. Given that, it can be useful to identify clinical predictors of undernutrition collected during routine respiratory assessment in order to immediately recognize patients at risk of undernutrition that need to undergo full nutritional evaluation. The management of undernutrition is a pathway that first forecasts dietary advices to ensure the correct intake of energy and macro and micronutrients and, for high risk individuals, they should be used alongside oral nutritional supplementation (ONS). Despite guidelines strongly recommend ONS, evidence on this topic remains still controversial and no study evaluated ONS efficacy stratifying according to type of supplementation (macro or microsupplementation). It is clear that, although the negative role of undernutrition in COPD patients is well established, it continues to be underestimated and under-recognized among healthcare professionals. The aim of this thesis is to go through the management of undernutrition in COPD patients, highlighting weaknesses and pitfalls from the screening to the treatment, paying particular attention to:  The accuracy of predictive formulas for the estimation of resting energy expenditure (chapter 2)  The identification of clinical predictors for undernutrition (chapter 3)  The role of nutritional supplements in improving pulmonary function, nutritional status, and quality of life (chapter 4). The primary end-point was to evaluate the reliability of predicting formulas used for REE and to investigate to which extent the errors of REE predicting formulas affect the identification of an energy unbalance in COPD patients. Although indirect calorimetry (IC) represents the gold standard for its measurement, its cost and the need of qualified technicians limit its use in the daily clinical practice, compelling clinicians to use predictive equations not validated in COPD, like the Harris-Benedict (HB) or Moore-Angelillo (MA) [3,4]. In line with the previous literature [4], in Chapter 2 it has been demonstrated that predictive formulas are unable to capture more than 50% of negatively unbalanced patients, therefore they should be discouraged in clinical practice especially in patients with an overt malnutrition. In case of need or if IC is unavailable, the use of MA formula should be preferred to HB because of its tendency of overestimating rather than underestimating. Given that the formulas lack for sensitivity in diagnosing undernutrition and being this latter highly prevalent in COPD patients, it would be of auspicial to identify predictive factors in the clinical setting of patients at risk of undernutrition. Therefore, in Chapter 3 the potential role of clinical predictors and instrumental variables collected during a routine respiratory assessment associate with undernutrition were investigated. Previous studies have shown that the incidence of undernutrition increased as the disease severity of the patients increased [5], hence in our study patients underwent a multidimensional assessment including the use of Cumulative Illness Rating Scale (CIRS) to quantify the burden of chronic diseases [6] in addition to the evaluation of pulmonary function and nutritional status. Our results show that clinical evaluation and pulmonary function tests are unable to reliably predict undernutrition in COPD patients, nevertheless they confirm that the severity, rather than the number of comorbidities, increases the risk of undernutrition by reducing the energy intake and increasing the REE. Thus, as suggested by NICE guidelines [7], validated nutritional screening (e.g. Malnutrition Universal Screening Tool) should always be forecast in this population based on an accurate evaluation of energy intake and expenditure and body composition, but it is highly recommended in COPD patients with a CIRS severity index ≥ 0.45. The previous steps of this thesis work aimed at identifying those COPD patients affected by undernutrion. Successively, it was investigated how undernutrition should be managed. The current available guidelines indicate to supplement patients with a low BMI (<20 kg/m2) or in case of unintentional weight loss (>10% of body weight over 3-6 months), however the evidence on this topic is controversial, probably due to heterogeneity in the tested interventions. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effect of macro or micronutrients supplementation on nutritional status, physical functional capacity and quality of life in patients with COPD. The results, that confirm the results reported by the latest meta-analysis available in literature [8], suggest that the use of macronutrients supplementation in COPD patients improves BMI, FFMI, exercise tolerance and quality of life, while it does not ameliorate respiratory function. Micronutrients supplementation alone did not improve any of the considered outcomes. We can speculate that the reason for a poor response on respiratory function is due to an increased energy expenditure not correctly evaluated, as shown in Chapter 2, therefore not properly balanced by an adequate overall dietary intake. Thus, the nutritional intervention itself was not of sufficient magnitude to produce a positive effect. In fact, the multifactorial mechanism of respiratory disease in COPD prevented the supplementation from achieving positive effect on respiratory function since the obstructive alterations occurred overtime can not be modified by nutrition. In general, macronutrients supplementation should be offered to COPD patients even if well-nourished, in order to avoid further weight loss, improve anthropometric parameters, quality of life, and exercise tolerance and prevent undernutrition. In conclusion, undernutrition affects a high proportion of COPD patients and its association with increased exacerbation rates, hospital admission and costs and mortality requires that healthcare professionals include nutritional screening into the daily clinical practice. Dietary advices and nutritional education can be of beneficial in the short term, providing for improved energy intake and correct balance of micro and macronutrients, however a more robust and patient's tailored nutritional assessment is desirable to constantly monitor the nutritional status and promptly adapt it to the variable COPD patient's phases.