The progress of nutritional support for chronic obstructive pulmonary disease

Jiao-Jiao Wang, Mei Tang, Yun-Xian Ma, Peng-Cheng Zhou

1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan province, China.

2＊Correspondence to:Peng-Cheng Zhou, Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu,610072, Sichuan Province, China.

Abstract The patients with chronic obstructive pulmonary disease (COPD)often occur weight loss and reduced muscle mass, which leads to decreased exercise capacity and vital capacity. The nutritional status is closely related to the prognosis of patients with COPD and nutritional support has played an important role in the treatment of COPD. In order to provide proper nutritional support, this article reviews the progress of nutritional support in COPD from the causes of malnutrition, energy demand assessment, assessment of nutritional risk and nutritional support methods. Moreover, this review specially reviewed the application of traditional Chinese medicine diet.

Key words: Chronic obstructive pulmonary disease, Nutritional factors, Nutritional support methods, Traditional Chinese medicine

Introduction

Chronic obstructive pulmonary disease (COPD) is a chronic progressive disease characterized with shortness of breath, chronic cough, and poor exercise tolerance. A prospective analysis shows that the prevalence of malnutrition was 24.6% in patients with COPD and malnutrition was closely related to the increased mortality risk and prognosis of the disease [1]. Nutritional status also has been recognized as an independent risk factor for prognosis in patients with COPD. Evidence-based medicine has proved that nutritional supplements can improve lung function and exercise tolerance in patients with COPD [2]. Malnutrition is associated with impaired lung function, muscle weakness, decreased exercise tolerance,and increased mortality rate in patients with COPD [3-5].Therefore, nutritional support plays an important role in the comprehensive treatment of chronic obstructive pulmonary disease.

Abbreviations

COPD= chronic obstructive pulmonary disease AECOPD =acute exacerbation of chronic obstructive pulmonary disease FEV1= expiratory volume in 1s EN= enteral nutrition PN= parental nutrition MV= mechanical ventilation BMI=Body mass index FFMI= Fat-free mass index ONS=oral nutritional supplements HGS= handgrip strength REE=resting energy expenditure ETF=enteral tube feeding

The intake of nutrients such as fat, carbohydrates, protein, vitamins, minerals and dietary fiber, is closely related to the nutritional status of patients with COPD. The nutrient requirements of patients with COPD in different stages are different [3]. At present, the nutritional methods for patients with COPD mainly include dietary advice, oral nutritional supplements (ONS), enteral nutrition (EN) and parenteral nutrition (PN). we need to select the fit nutritional methods for patients with COPD according to the condition. This article reviews the progress of nutritional support in COPD, it may offer suggestion on the preparation of an optional enteral diet formulation and the selection of nutritional methods. The information obtained may also be used to enhance nutritional support strategies for the patients with COPD.

1 Causes of malnutrition in patients with COPD

Due to the decreasing heart and lung function, the lower tolerance of daily activities, mechanical ventilation (MV),and comorbidity disease, the patients with COPD have insuき cient intake of nutrients. Laudisio et al. [4] found that energy intake and micronutrients were lower than recommended in patients with COPD. The increased airway resistance, increased respiratory work and increased oxygen consumption in patients with COPD lead to a higher basal metabolic rate and active energy expenditure than healthy people [5]. Moreover, chronic respiratory failure and pulmonary heart disease often occur in the progress of the disease, resulting in gastrointestinal congestion. Long-term use of broad-spectrum antibiotics, oral or intravenous glucocorticoid also can cause gastric mucosa damage, intestinal f lora imbalance, f lora shift, which can aff ect the digestion and absorption of nutrients, and result in malnutrition.It has been proved that tumor necrosis factor-alpha (TNF-α)is one of the causes of malnutrition in patients with COPD.TNF-α can reduce muscle energy eき ciency, muscle atrophy, increase protein and fat catabolism, and cause energy deficiency and body weight loss in patients with COPD.A lot of research showed that levels of interleukin-6 (IL-6), leptin, and myostatin are also closely related to malnutrition in COPD [6]. Zhang et al. [7] observed that serum leptin levels were negatively correlated with nutritional status in patients with COPD. (Figure 1)

Figure 1: The causes of malnutrition in patients with COPD.

2 Energy needs of patients with COPD

Huang [8] have shown that when the total energy supplied per day is higher than 30% of the basic needs of the human body, it is most benef icial to the body. According to the characteristics of patients with COPD, energy should be given in fractions of the day to avoid loss of appetite and increased ventilation due to high caloric load. There were many measures used to assess the energy expenditure in patients with COPD. The standard method for determining energy demand and consumption clinically is indirect calorimetry (IC). The IC measures respiratory oxygen consumption and carbon dioxide production to calculate resting energy expenditure (REE) [9]. Due to the expensive costs of the IC apparatus, REE formulas were often used in clinical practice, such as Harris & Benedict (HB),which takes the age, weight and height of individuals into account:

For male: REE=66.437 +(5.0033× height [cm])+(13.7516×weight [kg]) -(6.755 ×age [years])

For female: REE=655.0955+ (1.8496 ×height [cm]) +(9.5634 ×weight [kg]) -(4.6756×age [years])

3 Assessment of nutritional risk in patients with COPD

The European Society for Clinical Nutrition and Metabolism (ESPEN) states that we can use nutritional screening tools to identify malnourished individuals. Malnutrition can be diagnosed when patients with COPD meet the following conditions: 1) BMI ＜ 18.5 kg/m2and/or; 2) In the absence of a clear time period, the body weight is reduced by ＞ 10%, or the weight loss is ＞ 5% within 3 months; on this basis, satisfying one of the following two points can be diagnosed. ①BMI ＜ 20 kg/m2(age ＜ 70 years old) or BMI ＜ 22 kg/m2(age ≥ 70 years old); ②FFMI ＜ 15 kg/m2(female) or FFMI ＜ 17 kg/m2(male) [10]. The tool for nutritional risk assessment in patients with COPD including the following:

3.1 The Nutritional Risk Screening 2002 (NRS 2002)

NRS 2002 content includes three aspects:① Nutritional status impairment score (0 to 3 points); ② Disease severity score (0 to 3 points); ③ Age score: based on the above scores, age ≥ 70 years old plus 1 point. The total score is 0 to 7 points, and patients with a total score ≥ 3 have nutritional risk [11].

3.2 Mini-Nutritional Assessment Short Form (MNASF)

MNA-SF consists of 6 parts including diet, weight loss,activity ability, presence or absence of psychological trauma or acute disease, mental health, body mass index and calf leg circumference. Patients have the risk of malnutrition between 8 and 11 points, and patients who are between 0 and 7 points are in malnutrition [12].

4 The role of nutritional support in COPD

Nutritional depletion leads to widespread fiber atrophy,especially the reduction of the cross-sectional area of type II muscle fibers, altered levels of glycolysis and oxidase enzymes, and depletion of energy-rich substrates such as phosphocreatine and glycogen [13]. Nutritional consumption leads to increase respiratory fatigue, decrease respiratory muscle strength and endurance. Nutritional support can increase body mass, enhance respiratory muscle capacity, improve lung function, strengthen muscles,and increase serum albumin. Moreover, it can increase the number of T lymphocyte subsets, improve cellular immune function, shorten the duration of stay and improve the quality of life of patients [14]. A prospective, single-center,randomized, open, and controlled studies were conducted in Lima (Peru), includes 99 outpatients diagnosed with COPD between 18 and 80 years of age, observed that there are a significantly increase in BMI, FFMI, quality of life (QoL) and the handgrip strength (HGS) through three months of oral supplementation [15]. Another systematic review and meta-analysis conducted by Coollins et al. showed that nutritional supplements significantly improved respiratory function, respiratory muscle strength,HGS, and exercise performance [1]. Grigorakos et al. [16]reported that the combination of EN and PN accelerates the weaning from MV and shortens the duration of stay of patients with COPD under MV.

5 Application of different nutritional factors in COPD

5.1 Fats and Carbohydrates

Studies have shown that patients with COPD can benefit from a high-fat diet. Compared to carbohydrates, fat produces less metabolic CO2and has a lower respiratory quotient (RQ). Patients with COPD with low CHO had a significant decrease in CO2levels in the arterial blood gas and had a significant increase of FEV1 about 22% in the lung function. Xu et al. [17] found that the lung function of patients with COPD and respiratory failure has improved significantly after low-glucose high-fat nutritional support.Meng-jar Hsieh et al. [18] reported that when patients with COPD receive a medium fat or high fat enteral formula,gastric emptying is significantly delayed in patients given a high fat diet. The severity of patients with COPD should be considered when using a high-fat compound formulation. Omega-3 fatty acids are one of polyunsaturated fatty acid, which promotes anti-inflammatory activity and is a protective factor against the tumor necrosis factor [19].

5.2 Dietary fiber

Dietary fiber helps maintain intestinal function, promote digestion and improve breathing. The daily recommended intake of dietary fiber is 20 to 35 g per day [9], and patients should ensure adequate fluid intake when increasing dietary fiber provision to avoid constipation [20].

5.3 Protein and amino acids

Accelerated loss of FFM often occurs in patients with COPD , there is a direct correlation between low plasma concentrations of branched-chain amino acid (BCAA) and low FFM [18]. The dietary supplementation of protein in patients with COPD should be at least 1.5 g/kg per day [13].Glutamate is a non-essential amino acid that plays an important role in the metabolic pathways of skeletal muscle.Glutamate is an indispensable component in the synthesis of glutathione (an important antioxidant in muscle). It has been reported that the concentration of muscle glutamate in COPD is significantly reduced. Li [21] observed that exogenous glutamine significantly increases T cell (CD3,CD4, CD8) and IgG levels in lymphocytes of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and improves lung ventilation.

5.4 Vitamins and minerals

Due to long-term use of hormones, reduction of outdoor activities, and lack of vitamin D intake, patients with COPD often have vitamin D deficiency. Vitamin D deficiency can lead to impaired lung function, osteoporosis,immune dysfunction and muscle weakness [22]. Vitamin D status is assessed by the serum levels of 25-hydroxyvitamin D (25-(OH) D), (25-(OH)D) is the main storage form of vitamin D in the body [23]. Hsieh et al. [18] showed that long-term supplementation of vitamin E can reduce the risk of COPD. Some studies have shown that minerals such as selenium, calcium, and iron are associated with FEV1 levels. Therefore, additional supplement of vitamins and minerals is beneficial to the prognosis of patients with COPD.

6 Nutritional support methods

6.1 Selection of nutritional support methods in the stable phase of COPD

Dietary advise and EN are widely used in the stable phase of COPD. It is beneficial for patients with COPD to eat less and increase the frequency of meals throughout the day. This way can avoid overly full and causing shortness of breath [19]. Farooqi et al. [24] observed that BWI, HGS and exercise performance significantly improved after receiving the dietary advice for 1 year in patients with COPD. A meta-analysis conducted by Zheng et al. [25] showed that healthy/prudent dietary pattern is associated with a decreased risk of COPD, the unhealthy/ western-style dietary pattern is related to an increased risk of COPD. Except the dietary advise, EN is an important nutritional intervention for patients with COPD who have poor gastrointestinal tolerance or even cannot eat.At present, the enteral nutrition formula for COPD mainly includes NovaSource Pulmonary, Nutren Pulmonary, Pulmocare, and Respalor. In the nutritional formula of Nova-Source Pulmonary, omega-3 fatty acids are the main lipids source. NovaSource Pulmonary is the only enteral nutrient containing fiber (8 g/L), which is specifically for patients with lung disorders such as COPD [19]. Zhao et al. [25]observed that patients with COPD in the stable phase complicated with chronic respiratory failure were treated with enteral nutrition suspension support and non-invasive ventilation at home, after one year, the arterial blood gas index and nutritional index of the experimental group improved more significantly than that of the control group, and the number of readmissions decreased significantly. A systematic review and meta-analysis of randomized, controlled trials (RCT) investigated the eきcacy of nutritional support of food strategy such as dietary advise, ONS and enteral tube feeding (ETF) in the patients with COPD, found that malnourished patients receiving ONS have significant functional improvements compared with dietary advice and ETF [1].

6.2 Selection of nutritional support methods for acute exacerbation of COPD

Due to loss of appetite, breathlessness or other treatments such as noninvasive ventilation during acute exacerbation,energy intake reduced significantly. Thus nutrition support is crucial for the therapy, EN and PN are recommended as the nutritional support methods. Zhang et al. [26] studied 60 elderly patients with acute exacerbation of COPD and found that nutrition support can improve their nutritional status, correct hypoproteinemia, reduce inflammation, and improve immune function. Liu et al. [27] observed that a short-term, partial parenteral nutrition support can shorten the length of hospital stay of patients with AECOPD and respiratory failure using non-invasive ventilation. Grigorakos et al. [16] found that the combination of EN and PN accelerates the weaning from MV and shortens the duration of stay of patients with COPD under mechanical ventilation. Iovinelli et al. [28] observed that patients with AECOPD under mechanical ventilation receiving medium chain triglycerides (MCT)/long chain triglycerides (LCT)emulsion (1:1) have a considerably shorter period of weaning compared with patients receiving LCT alone. Ge et al. [29] found that PN support combined with omega-3 fish oil, fat emulsion, and alanine-glutamine can reduce the intensive care unit (ICU) stay, mechanical ventilation time, and the incidence of ventilator-associated pneumonia. The gastrointestinal mucosa damaging and intestinal flora imbalance usually occurs in the acute exacerbation of COPD. Dai et al. [30] found that EN combined with microecological preparations can reduce the incidence of gastric retention, bloating, and diarrhea in patients with AECOPD mechanical ventilation. It is recommended to use EN combined with PN early in the hospital and then gradually transition to full EN according to the patient's gastrointestinal tolerance [31], Early EN is more effective in improving the nutritional status of patients with COPD,reducing complications and mortality. Compared with PN,EN has advantages in preventing intestinal mucosal atrophy, maintaining immune activity, normal intestinal flora,and reducing stress ulceration during acute exacerbation[32].

7 Application of traditional Chinese medicine diet in COPD

Traditional Chinese medicine diet has a long history in the prevention and treatment of respiratory disease. Food and traditional Chinese medicine also have four qi and f ive f lavors. The four qi is “cold, hot, warm, cool,” and it is called f latness when it is not warm or cold. Traditional Chinese medicine diet is guided by the theory of traditional Chinese medicine. It has the characteristics of color, aroma, taste, and shape of the traditional diet, and can achieve health care, disease prevention and treatment. China has had the theory of homology of medicine and food since ancient times. Compared with the poor tolerance of traditional Chinese medicine decoctions, traditional Chinese medicine diet is more easily accepted by patients [33]. Traditional Chinese medicine diets can regulate the function of lung, spleen, and kidney and should be applied according to pattern identif ication and treatment. Patients with Qi def iciency can eat Shan Yao (Rhizoma Dioscoreae), Dang Shen (Radix Codonopsis), Ren Shen (Radix Ginseng),etc. Patients with Yang def iciency can eat Lu Rong (Cornu Cervi Pantotrichum), Yang Rou (Musculus Ovis), etc.Patients with Yin def iciency can eat Xi Yang Shen (Radix Panacis Quinquefoli), Yin Er (Tremella Fuciformis), Sha Shen (Radix Adenophorae Strictae), Yu Zhu (Rhizoma Polygonati Odorati). Patients with dampness can eat Chen Pi(Pericarpium Citri Reticulatae), radish, lentils, Sheng Jiang(Rhizoma Zingiberis Recens). Patients with hemiplegia can eat Yi Yi Ren (Semen Coicis), Fu Ling (Poria), Chi Xiao Dou (Semen Vignae Umbellatae). Moreover, chicken,young pigeon and lean can be used to tonify the spleen and kidney, and the pig lung and pig heart have the effect of nourishing the heart and lung. Zhao et al. [34] summarized the food diet experiences of Professor Su in the treatment of COPD. It showed that patients with lung Qi def iciency can use Sheng Jiang sirloin rice, patients with lung and spleen Qi def iciency can use Dang Shen soup, and Wu Wei Zi (Fructus Schisandrae Chinensis) soup, lung and kidney Yin def iciency can choose Shi Hu (Herba Dendrobii) Bai He (Bulbus Lilii Viriduli) stewed terrapin, When phlegm is obvious, Huang Qi (Radix Astragali Mongolici) Ban Xia(Rhizoma Pinelliae) Ren Shen porridge can be used. Zhou et al. [35] studied the effect of traditional Chinese medicine diet on the malnutrition caused by COPD disease with spleen-lung deficiency. In the diet treatment plan, Shan Yao, Lian Zi (Semen Nelumbinis), Yi Yi Ren and Yan Mai(Fructus Avenae Sativae) are separately boiled with jujube to make porridge; Fish, quail eggs, duck, chicken, and lean are stewed with Ren Shen, Huang Qi. Ren Shen, Huang Qi, and jujube are made tea for drinking; After 8 weeks of intervention, the lung function and exercise tolerance,nutritional status, and quality of life of the experimental group were improved. (Figure 2)

Figure 2: The nutritional support methods in COPD

8 Discussion

Regardless of the acute exacerbation or stable phase of COPD, the proportion and content of various nutrients should be fully considered when selecting different nutritional methods. Nutritional factors play an important role in the nutritional support treatment of COPD, especially the supplementation of omega-3 fatty acid, glutamine,and vitamin D. A randomized, controlled trial conducted by Calder et al. [36] showed that targeted medical supplements containing large doses of omega-3 fatty acids,vitamin D and high quality protein have a positive effect on dyspnea. De Benedetto et al. [37] observed that dietary supplementation of coenzyme Q10 (CoQ10) and Creatine improves daily activity, BMI and dyspnea in patients with COPD. Because the respiratory quotient of fat is lower,numerous studies have shown that the intake of high-fat content is more beneficial for patients with COPD, but high-fat enteral nutrition may increase the time of gastric emptying in patients and affecting the respiratory movement, the ratio of fat to carbohydrate should be adjusted according to the patient's condition.

In the stable phase of COPD, ONS is the best nutritional support methods for patients with COPD. ONS can achieve targeted nutrition and patient acceptance and compliance are better, patients can benefit more from ONS.Moreover, ONS can maintain intestinal biological environment and promote gastrointestinal motility and absorb nutrients more adequately, For the patients with COPD who cannot eat, we can choose ETF as the main nutritional support methods, and combined with PN if necessary. When choosing enteral formulation for patients with COPD,we must consider not only how to achieve the nutritional goals, but also the proportion of various nutrients [19].

In the acute exacerbation of COPD, EN and PN are recommended as the nutritional support methods. However, for those who do not need mechanical ventilation,ONS and EN can be adapted to maintain the nutritional support. When patients with acute exacerbation of COPD undergo MV treatment, early EN combined with PN may be the most appropriate nutritional support method. At the same time, we can add some microecological preparations on the basis. Microecological preparations can improve immune function, reduce inflammation, reduce complications, and improve patient prognosis. Adversely, long-term PN may cause intestinal microbial disorders and decline in gastrointestinal motility. It is recommended to use EN combined with PN early. However, when we can give EN,the conclusion is inconsistent. Some scholars believed that EN can be given within 24-48 hours after admission.On the one hand, some scholars thought that it should be given about 1 week after admission, considering that most patients have obvious gastrointestinal congestion and mucosal damage at admission. In summary, we can decide the time to give EN and according to the patient's gastrointestinal tolerance [38].

In aspect of diagnosing and assessing the risk of malnutrition in COPD, MNA-SF has a more comprehensive predictive value for both nutritional risk and mortality compared with NRS-2002 [12]. In addition, FFMI has significant value for the diagnosis of malnutrition in patients with COPD [10].

Traditional Chinese medicine diet has great research value in chronic obstructive pulmonary disease, but there are few related clinical studies, especially multi-center, large sample research. In the future, we need to conduct an indepth study on the value of Chinese medicine diet in the treatment of COPD malnutrition.

To conclude, this study shows the importance of nutrition supports in COPD patients, the measures to assess nutritional risk, and nutritional support methods. In order to improve the prognosis for hospitalized COPD patients,identifying and providing proper nutrition supports is a way forward.