The Nutritional Status of Chronic Obstructive Pulmonary Disease Exacerbators

Introduction Malnutrition is underdiagnosed in chronic obstructive pulmonary disease. Objectives This study aimed to evaluate the nutritional status of COPD patients and the link between dyspnea and nutritional status. Methods This longitudinal observational study included patients hospitalized with exacerbated COPD. Nutritional status was assessed using Nutrition Risk Screening 2002, anthropometric, and biochemical assessments, in the first 48 hours of hospitalization. Results Thirty patients were evaluated. According to the Nutrition Risk Screening 2002, half of the patients were at increased risk of malnutrition. 36.7% were classified as malnourished if we only considered the body mass index. From the evaluation of the tricipital skin fold, 69.0% were classified as malnourished, with 48.3% having severe malnutrition. According to the serum albumin level, 29.6% had malnutrition criteria. A significant association between dyspnea and increasing age (p=0.037) was found. There was a strong association between the fold classification and the degrees of severity of dyspnea (Fisher exact test: 13.60, p=0.001, V Cramer = 0.826). Most patients were malnourished and had higher grades of dyspnea. Tricipital skinfold reflects subcutaneous adipose tissue; this anthropometric measurement seems to be a good method to classify the nutritional status of COPD patients. It classified the biggest portion of patients as malnourished. Conclusion The number of patients classified as malnourished changed with the method under analysis. The tricipital skin fold parameter was strongly associated with the dyspnea score. Most patients had adipose tissue and muscular mass depletion.


Introduction
Chronic obstructive pulmonary disease (COPD) is a prevalent and progressive disease with systemic involvement. Chronic inflammation is associated with lesions of the respiratory system.
In COPD, systemic inflammation is an important player in nutritional abnormalities and muscle dysfunction. Malnutrition is a serious problem in COPD patients. However, it is an underdiagnosed problem. Malnutrition impairs normal skeletal muscle functioning, with reduced muscle mass and decreased strength and endurance of respiratory muscles. Respiratory failure, then, becomes common as weight loss increases [4]. Malnutrition is associated with the severity of the disease, is related to more exacerbations, and increases hospital stays. Patients with advanced COPD are often seen with low body weight, and this has been recognized as a poor prognostic factor. e negative effect of malnutrition in COPD patients compromises health and quality of life. us, recognizing and treating malnutrition is crucial for overall patient management and optimizing outcomes [4][5][6]. ere is no universal method for the diagnosis of malnutrition, but anthropometry measures and biochemical assessments may be helpful. Different studies use distinct methods, which makes it difficult to compare results.

Study Design and Population.
e authors conducted a longitudinal observational study with hospitalized exacerbated COPD patients from September 2019 to February 2020 in a Portuguese tertiary hospital.
Exacerbation was defined, according to GOLD, as an acute worsening of respiratory symptoms that needs additional therapy. All the included patients had severe exacerbations requiring hospitalization.
All the participants signed a written informed consent at the time of inclusion in the study. Assessments were made in the first 48 hours of hospitalization. All the anthropometric measurements were performed by the same trained dietitian.

Statistical Analysis.
Statistical analyses were performed using SPPS software (version 23.0). Continuous variables are presented as mean ± standard deviation or median and respective interquartile range, depending on the normality underlying the data. For categorical variables, the respective absolute and relative frequencies are presented. e normality underlying the data was assessed using the Shapiro-Wilk test. e comparison of continuous variables that followed a normal distribution was performed using Student's t-test. For variables that have not followed a normal distribution the nonparametric Mann-Whitney test was used. Pearson's linear correlation coefficient was used as a measure of association between two continuous variables.
e significance value was taken as p < 0.05.

Results
A total of 30 patients were included in the study. Most of the patients were male 76.7% (n � 23), and 23.3% (n � 7) were female. e median age was 68 years, and the median BMI was 23.3 kg/m 2 . Information on smoking habits was also collected, and it was found that 53.3% (n � 16) of the individuals were exsmokers, and 43.3% (n � 13) were currently smoking. Only 3.3% (n � 1) were nonsmokers.
About 90% (n � 27) of our patients had three or more comorbidities. Older patients had more comorbidities (r � 0.424, p � 0.020). According to GOLD criteria, about 43.3% (n � 13) of the patients had severe obstruction and 20% (n � 6) had a very severe obstruction. Most patients were medicated with triple bronchodilator therapy with a long-acting muscarinic antagonist, long-acting beta2-agonist, and inhaled corticosteroids. 66.7% (n � 20) had home oxygen therapy, and 40% (n � 12) patients had home noninvasive ventilation support. e demographic and clinical characteristics of COPD patients are presented in Table 1.
For these individuals, the number of exacerbations in the last year was recorded. 66.7% (n � 20) had two or more exacerbations without hospitalization, and 40% (n � 12) had at least one exacerbation with hospitalization. For 60% (n � 18) of the patients, this was their first severe exacerbation, with hospitalization.
At admission to the emergency department, half (n � 15) of the patients had global respiratory insufficiency, and 16.7% (n � 5) had respiratory acidemia. 40.0% (n � 12) were submitted to noninvasive ventilation support during hospitalization.
Regarding the application of the Modified Medical Research Council (mMRC) scale for dyspnea, the following results were observed: 6.7% (n � 2) classified as grade 1; 3.3% (n � 1) classified as grade 2; 43.3% (n � 13) as grade 3, and 30.0% (n � 9) as grade 4. No records were obtained for 16.7% (n � 5) of the individuals. e authors found a significant association between dyspnea and increasing age (p � 0.037).
Additionally, the authors proceeded to the evaluation of the nutrition status of individuals, taking into account different variables. e majority of patients (65%) had weight loss in the last 12 months. Half of COPD patients (n � 15) were at increased nutritional risk according to NSR-2002, and 36.7% (n � 11) were classified as malnourished according to BMI. From the evaluation of the TSF, 69.0% (n � 20) were classified as malnourished, with 48.3% (n � 14) having severe malnutrition. e midupper arm circumference (MUAC) classified 64% of the patients with malnutrition. According to the serum albumin level, 29.6% (n � 8) had malnutrition criteria. ere was no association between the severity degrees of dyspnea and malnutrition (χ 2 � 1.264, gl � 2, p � 0.796). It was found that almost all patients had vitamin D deficiency (n � 28, 93.3%).
We also detected a strong association between skin fold and dyspnea (Fisher exact test 13.60; p � 0.001, V Cramer 0.826).
None of the patients needed to be transferred to the intensive care unit, and none died during hospitalization. e median hospital stay was 12 days (IQR 9.75). We observed that the time of hospitalization increases in patients with lower serum albumin levels (r � −0.491, p � 0.015) and with lower BMI (r � −0.421, p � 0.045).

Discussion
Assessing malnutrition and acting to promote an adequate nutritional status is crucial to the management of patients with COPD [5]. ere is no gold standard method to assess the nutritional status of patients with COPD. BMI is a simple method for assessing nutritional status, and a low BMI is associated with a worse prognosis [7]. However, BMI may not accurately reflect the nutritional status of COPD patients [8]. Our results show that only a part of the patients was classified as malnourished if we used this measure. e NSR-2002 was developed by the European Society for Clinical Nutrition and Metabolism and is widely used to assess nutritional status [7,9].
In addition to BMI and NRS-2002, serum albumin is considered a good biomarker to evaluate nutritional status. In our study, this biomarker classified as malnourished only a small portion of our patients. Nutritional evaluation of COPD patients should not be limited to BMI or albumin level. e body mass is divided into two parts: fat-free mass (FFM) and fat mass (FM). Fat mass is an energy store. FM and FFM decreases are important prognostic factors in COPD [4,8,10,11].
portion of patients as malnourished (69% vs. 64%). FM and FFM depletion was present in the biggest portion of our patients. ese two parameters seem to be useful to classify COPD exacerbators on their nutritional status. TST and MUAC were associated with the dyspnea score, reflecting the advanced stage of the disease. We also found that older patients had more comorbidities and more dyspnea.
Exacerbations are associated with an increased inflammation status, anorexia, and increased work of breathing.
is has a direct impact on muscle dysfunction, causing an increased risk of hospitalization due to exacerbations. e loss of muscle mass compromises the work of the respiratory muscles, leading to a negative functional impact in these patients [12]. Showing that acute exacerbations have a negative impact on nutritional status and muscle function. Our patients were frequent exacerbators, and they had a significant loss of adipose tissue as well.
Cachexia is a complex metabolic syndrome characterized by involuntary and progressive loss of skeletal muscle mass with variable loss of fat mass. Adipose tissue in cachexia plays an important role in disease progression [13,14]. e advanced disease has a more gradual loss of muscle and fat mass, as seen in our patients. e occurrence of multiple exacerbations leads to disease progression and depletion of adipose reserves. According to previous studies, the loss of muscle mass as well as of fat mass might be related to specific effects of hypoxia on energy balance [13].
We identified that COPD patients with lower levels of albumin, or lower BMI had prolonged hospitalization.
Anthropometric measures seem to be a poorly sensitive marker of mild-to-moderate nutritional abnormalities [12,13]. is shows that our patients are at high nutritional risk, with severe nutritional abnormalities.
Several studies report that vitamin D deficiency contributes to severe COPD by magnifying inflammation. Vitamin D supplementation may have an effect in reducing exacerbations and is also important to comorbidities associated with COPD as osteoporosis [15][16][17]. Our results reflect that almost all of the COPD exacerbators had a Vitamin D deficiency.
More nutritional studies should be done assessing the different stages of COPD disease. May adipose tissue depletion be a therapeutic target?

Conclusion
Most of the patients had significant complaints of dyspnea in a stable phase of the disease. Dyspnea was higher in older patients. e number of patients classified as malnourished changed with the method under analysis. Nutrition screening in COPD exacerbators, only with BMI, leads to under diagnosis of malnutrition. e TST and MUAC assessment tools encompassed more patients in the undernutrition category and were strongly associated with the dyspnea score. ese anthropometric measurement methods seem to be the best to stratify the nutritional status of COPD patients compared with the other methods under analysis, they allowed classifying a higher number of patients as malnourished. Vitamin D deficiency was prevalent in COPD exacerbators' patients. e majority of COPD exacerbators had adipose tissue and muscular mass depletion.
Nutritional status evaluation is an important parameter in COPD exacerbators. Once, by identifying the existence of malnutrition, we can treat it.

Data Availability
e data used to support the findings of this study are available from the corresponding author upon request.
Ethical Approval e present study was conducted following ethical and legal principles. e study protocol was approved by the hospital's Ethics Committee.

Consent
All patients signed the informed consent form.

Conflicts of Interest
e authors declare that they have no conflicts of interest.

Authors' Contributions
CRS conceptualized the study, developed the methodology, analyzed the results, and drafted and reviewed the manuscript. TDD developed the methodology, analyzed the results, and reviewed the manuscript. LM reviewed the manuscript. MC collected the data and drafted and reviewed the manuscript. AN collected the data and reviewed the manuscript. RC collected the data and drafted and reviewed the manuscript. TSS conceptualized the study, collected data, assessed the patient, and reviewed the manuscript. TF conceptualized the study and drafted and reviewed the manuscript. AD conceptualized the study and drafted and reviewed the manuscript.