Chronic Obstructive Pulmonary Disease and Protein Consumption: What is the Connection?

Keywords

Pulmonary Disease; Exercise; Sarcopenia; Whey Protein.

Abbreviations

COPD: Chronic Obstructive Pulmonary Disease; WP: Whey Protein.

Introduction

Chronic obstructive pulmonary disease (COPD) is characterized physiologically by obstruction to pulmonary airflow and clinically by dyspnea [1]. The disease arises from exposure to harmful gases and particles that lead to oxidative stress in the lungs along with an exaggerated inflammatory response, which results in destruction of the elastin present in the pulmonary alveoli [2, 3]. Smoking is a major cause of COPD [4], but other risk factors are also associated, such as exposure to dust, chemicals, wood smoke, severe respiratory infections in childhood, old age, socioeconomic status and individual factors [5, 6].

COPD is increasingly present in the adult population, in both sexes, especially after 40 years [7]. Data from two large multicenter studies, PLATINO [8] and BOLD [5], show that the prevalence is close to 10%, reaching almost 20% in some regions. In addition to being prevalent, it is an important cause of morbidity and mortality worldwide, estimated by the WHO as the fifth cause of death in 2002 and possibly characterized as the third cause in 2030 [9].

Cough and dyspnoea are the most common symptoms, which can occur daily or intermittently [10]. Exacerbations, also present in these patients, are characterized by a greater amplification of the inflammatory response in the respiratory tract, being able to be triggered by bacterial or viral infections, or by environmental pollutants. During this process, there is an increase in pulmonary hyperinflation and airway obstruction, with reduced expiratory flow, representing a significant increase in shortness of breath [11]. The chronicity of the disease generates limitations due to the symptomatology and worsening of the quality of life of the affected individuals, besides many expenses to the health system due to hospitalizations, medications and exams [12].

The gold standard in the diagnosis of COPD is spirometry. The post bronchodilator fixed ratio between forced expiratory volume in the first second and forced vital capacity of 0.7 is used to define the presence of airflow limitation [13]. The main goals in relation to the disease and treatment are to determine the severity, impact on the patient's daily life and risk of new events (exacerbations, hospitalizations, death). For this, it is necessary to know separately each of the following aspects: level of current symptoms, results of spirometry, risk of exacerbation and presence of comorbidities [11].

In addition to respiratory compromise, COPD has systemic manifestations, such as increased oxidative stress, inflammatory cell activation, nutritional and body composition alterations, osteoarticular, cardiovascular and nervous system involvement [14]. Likewise, exercise limitation is not only conditioned by respiratory changes, but also by skeletal muscle dysfunction, often involving sarcopenia [15-17]. Worsening of the prognosis of these patients is related to sedentarism, tissue hypoxia, chronic use of corticosteroids, nutritional depletion and, mainly, systemic inflammation [18, 19]. Many of these symptoms, such as increased muscle catabolism, low physical activity and insufficient protein intake may be further aggravated, since the population suffering from COPD is mainly composed of elderly individuals. In this population there is a physiological tendency for this to occur even without the disease [20-22].

Nutritional depletion characterized by weight loss and/or muscle mass in patients with COPD may be the result of imbalance caused by insufficient dietary intake and an increased energy and protein requirement [23]. Decreased protein intake, especially during the first few days of acute exacerbation, decreases protein synthesis and increases protein turnover [23]. In addition, the exaggerated systemic inflammatory response characteristic of this disease has been described as a possible cause of this protein imbalance due to the marked catabolism that is inherent to this process [24]. Adding to this is the tendency to reduce the level of physical activity due to an intolerance to exercise, which is associated with sedentary lifestyle, depletion or peripheral muscular dysfunction, and respiratory restrictions such as exertional dyspnea [25]. Physical inactivity results in greater deconditioning and impairment of skeletal muscle function, leading to sarcopenia [26], and the loss of lean body mass in patients with COPD can occur in those with normal weight, overweight and obesity, it is not restricted to patients with low weight [27, 28].

In general, the rate of absorption and availability of amino acids in plasma (protein kinetics) depends on several factors, such as: mode of administration, quality and quantity of protein ingested, which in turn will directly influence muscle protein synthesis [29, 30]. Several studies have shown that elderly people have a higher leucine threshold, the amino acid with greater potential for protein synthesis [31] and therefore may require higher levels of protein, both at rest and at concomitant physical exercise, than young people [31-34]. Another consideration in the recommendations of protein consumption is its quality, since the elderly population may present low energy and protein consumption, together with reduced appetite and levels of physical activity [34-36]. Higher quality proteins may be advantageous since they do not require an intake as high as low biological value protein to reach the leucine thresholds [37-39].

Whey Protein (WP), are currently considered the best type of protein to be ingested because of its high biological value, related to the profile of essential amino acids it possesses, especially leucine, in addition to fast and easy digestion and absorption [40, 41]. Thus, WP is essentially used because of the role it plays in the synthesis of muscle protein [42]. Numerous studies have demonstrated the effects of WP on protein synthesis and hypertrophy in different situations involving diseases such as cancer, rheumatoid arthritis, neurodegenerative diseases and in patients with human immunodeficiency virus [43-45]. However, its use in COPD patients still has controversial results in the literature [40, 46-49].

According to nutrient recommendations from the Dietary Reference Intakes [50] based on analyzes of nitrogen balance studies in humans, the recommended dietary intake of high biological value protein for healthy subjects of both sexes is 0.8g/kg body weight per day. However, a recent review in 2016 established recommendations for the elderly population of 0.4g/kg body weight per main meal: breakfast, lunch and dinner, in order to provide the amount of protein required for optimum synthesis of muscle protein and at the same time limit and treat age-related declines in muscle mass, strength and function [51], suggesting that this amount of protein is more important than 0.8g/kg/day.

Conclusion

The population with COPD is mostly composed of elderly individuals, who often present with nutritional depletion, loss of lean mass and exercise intolerance.Highlight that the normalization of protein intake in order to reach the goal of 0.4g/kg body weight per main meal could minimize synergistic sarcopenic effects of age and disease.

1. Karel DJ. Respiratory Conditions Update: Chronic Obstructive Pulmonary Disease. FP Essent. 2016 Sep;448:20-8. PubMed PMID: 27576232.
2. Białas AJ, Sitarek P, Miłkowska-Dymanowska J, Piotrowski WJ, Górski P. The role of mitochondria and oxidative/antioxidative imbalance in pathobiology of chronic obstructive pulmonary disease. Oxid Med Cell Longev. 2016;2016:7808576. doi: 10.1155/2016/7808576. PubMed PMID: 28105251.
3. Stewart JI, Criner GJ. The small airways in chronic obstructive pulmonary disease: pathology and effects on disease progression and survival. Curr Opin Pulm Med. 2013 Mar;19(2):109-15. doi: 10.1097/MCP.0b013e32835ceefc. PubMed PMID: 23325030.
4. Atsou K, Chouaid C, Hejblum G. Variability of the chronic obstructive pulmonary disease key epidemiological data in Europe: systematic review. BMC Med. 2011 Jan 18;9:7. doi: 10.1186/1741-7015-9-7. PubMed PMID: 21244657.
5. Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM, et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet. 2007 Sep 1;370(9589):741-50. PubMed PMID: 17765523.
6. Kant S, Gupta B. Role of lifestyle in the development of chronic obstructive pulmonary disease: a review. Lung India. 2008 Apr;25(2):95-101. doi: 10.4103/0970-2113.59591. PubMed PMID: 20165658.
7. Casey G. COPD: obstructed lungs. Nurs N Z. 2016 Jun;22(5):20-4. PubMed PMID: 27514228.
8. Menezes AM, Perez-Padilla R, Jardim JB, Muiño A, Lopez MV, Valdivia G, et al. Chronic obstructive pulmonary disease in five Latin American cities (the PLATINO study): a prevalence study. Lancet. 2005 Nov 26;366(9500):1875-81. PubMed PMID: 16310554.
9. World Health Organization. Chronic Respiratory Disease.
10. Marcos PJ, de Molina RM, Casamor R. Risk stratification for COPD diagnosis through an active search strategy in primary care. Int J Chron Obstruct Pulmon Dis. 2016 Mar 1;11:431-7. doi: 10.2147/COPD.S98659. PubMed PMID: 27042035.
11. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD).
12. Kawada T. Approaches to daily body condition management in patients with stable chronic obstructive pulmonary disease. J Clin Nurs. 2016 Nov;25(21- 22):3279-3290. doi: 10.1111/jocn.13370. PubMed PMID: 27545279.
13. Global Initiative for Chronic Obstructive Lung Disease. Spirometry for health care providers. 2010;1-14.
14. Gea J, Pascual S, Casadevall C, Orozco-Levi M, Barreiro E. Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings. J Thorac Dis. 2015 Oct;7(10):E418-38. doi: 10.3978/j. issn.2072-1439.2015.08.04. PubMed PMID: 26623119.
15. Hudson AL, Gandevia SC, Butler JE. The effect of lung volume on the coordinated recruitment of scalene and sternomastoid muscles in humans. J Physiol. 2007 Oct 1;584(Pt 1):261-70. PubMed PMID: 17690147.
16. McKenzie DK, Butler JE, Gandevia SC. Respiratory muscle function and activation in chronic obstructive pulmonary disease. J Appl Physiol (1985). 2009 Aug;107(2):621-9. doi: 10.1152/japplphysiol.00163.2009. PubMed PMID: 19390004.
17. Loring SH, Garcia-Jacques M, Malhotra A. Pulmonary characteristics in COPD and mechanisms of increased work of breathing. J Appl Physiol (1985). 2009 Jul;107(1):309-14. doi: 10.1152/japplphysiol.00008.2009. PubMed PMID: 19359620.
18. Brinchault G, Diot P, Dixmier A, Goupil F, Guillais P, Gut-Gobert C, et al. Comorbidities of COPD. Rev Pneumol Clin. 2015 Dec;71(6):342-9. doi: 10.1016/j.pneumo.2015.09.009. PubMed PMID: 26585876.
19. Tödt K, Skargren E, Jakobsson P, Theander K, Unosson M. Factors associated with low physical activity in patients with chronic obstructive pulmonary disease: a cross‐sectional study. Scand J Caring Sci. 2015 Dec;29(4):697-707. doi: 10.1111/scs.12200. PubMed PMID: 25653122.
20. Fried TR, Fragoso CA, Rabow MW. Caring for the older person with chronic obstructive pulmonary disease. JAMA. 2012 Sep 26;308(12):1254-63. PubMed PMID: 23011715.
21. Ribeiro SM, Kehayias JJ. Sarcopenia and the analysis of body composition. Adv Nutr. 2014 May 14;5(3):260-7. doi: 10.3945/an.113.005256. PubMed PMID: 24829472.
22. Miljkovic N, Lim JY, Miljkovic I, Frontera WR. Aging of skeletal muscle fibers. Ann Rehabil Med. 2015 Apr;39(2):155-62. doi: 10.5535/ arm.2015.39.2.155. PubMed PMID: 25932410.
23. Sugawara K, Takahashi H, Kasai C, Kiyokawa N, Watanabe T, Fujii S, et al. Effects of nutritional supplementation combined with low-intensity exercise in malnourished patients with COPD. Respir Med. 2010 Dec;104(12):1883-9. doi: 10.1016/j.rmed.2010.05.008. PubMed PMID: 20627502.
24. Bachini FI, Bassini A, Cameron LC. Hypermetabolism and muscle changes during chronic obstructive pulmonary disease. Fisiot Brasil. 2010;11(6):462- 8.
25. Eisner MD, Blanc PD, Sidney S, Yelin EH, Lathon PV, Katz PP, et al. Body composition and functional limitation in COPD. Respir Res. 2007 Jan 29;8:7. PubMed PMID: 17261190.
26. Byun MK, Cho EN, Chang J, Ahn CM, Kim HJ. Sarcopenia correlates with systemic inflammation in COPD. Int J Chron Obstruct Pulmon Dis. 2017 Feb 20;12:669-675. doi: 10.2147/COPD.S130790. PubMed PMID: 28255238.
27. van de Bool C, Rutten EP, Franssen FM, Wouters EF, Schols AM. Antagonistic implications of sarcopenia and abdominal obesity on physical performance in COPD. Eur Respir J. 2015 Aug;46(2):336-45. doi: 10.1183/09031936.00197314. PubMed PMID: 25882802.
28. Joppa P, Tkacova R, Franssen FM, Hanson C, Rennard SI, Silverman EK, et al. Sarcopenic obesity, functional outcomes, and systemic inflammation in patients with chronic obstructive pulmonary disease. J Am Med Dir Assoc. 2016 Aug 1;17(8):712-8. doi: 10.1016/j.jamda.2016.03.020. PubMed PMID: 27161848.
29. Pasiakos SM. Exercise and amino acid anabolic cell signaling and the regulation of skeletal muscle mass. Nutrients. 2012 Jul;4(7):740-58. doi: 10.3390/nu4070740. PubMed PMID: 22852061.
30. Jonker R, Deutz NE, Erbland ML, Anderson PJ, Engelen MP. Hydrolyzed casein and whey protein meals comparably stimulate net whole-body protein synthesis in COPD patients with nutritional depletion without an additional effect of leucine co-ingestion. Clin Nutr. 2014 Apr;33(2):211-20. doi: 10.1016/j.clnu.2013.06.014. PubMed PMID: 23886411.
31. Wall BT, Hamer HM, de Lange A, Kiskini A, Groen BB, Senden JM, et al. Leucine co-ingestion improves post-prandial muscle protein accretion in elderly men. Clin Nutr. 2013 Jun;32(3):412-9. doi: 10.1016/j.clnu.2012.09.002. PubMed PMID: 23043721.
32. Cermak NM, de Groot LC, Saris WH, van Loon LJ. Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis. Am J Clin Nutr. 2012 Dec;96(6):1454-64. doi: 10.3945/ajcn.112.037556. PubMed PMID: 23134885.
33. Yang Y, Churchward-Venne TA, Burd NA, Breen L, Tarnopolsky MA, Phillips SM. Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men. Nutr Metab (Lond). 2012 Jun 14;9(1):57. doi: 10.1186/1743-7075-9-57. PubMed PMID: 22698458.
34. Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, et al. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2015 Sep 1;16(9):740-7. doi: 10.1016/j.jamda.2015.05.021. PubMed PMID: 26170041.
35. Phillips SM, Fulgoni III VL, Heaney RP, Nicklas TA, Slavin JL, Weaver CM. Commonly consumed protein foods contribute to nutrient intake, diet quality, and nutrient adequacy. Am J Clin Nutr. 2015 Jun;101(6):1346S-1352S. PubMed PMID: 25926509.
36. Phillips SM. Nutritional supplements in support of resistance exercise to counter age-related sarcopenia. Adv Nutr. 2015 Jul 15;6(4):452-60. doi: 10.3945/an.115.008367. PubMed PMID: 26178029.
37. Katsanos CS, Chinkes DL, Paddon-Jones D, Zhang XJ, Aarsland A, Wolfe RR. Whey protein ingestion in elderly persons results in greater muscle protein accrual than ingestion of its constituent essential amino acid content. Nutr Res. 2008 Oct;28(10):651-8. doi: 10.1016/j.nutres.2008.06.007. PubMed PMID: 19083472.
38. Bauer J, Biolo G, Cederholm T, Cesari M, Cruz-Jentoft AJ, Morley JE, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013 Aug;14(8):542-59. doi: 10.1016/j.jamda.2013.05.021. PubMed PMID: 23867520.
39. Deutz NE, Bauer JM, Barazzoni R, Biolo G, Boirie Y, Bosy-Westphal A, et al. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clin Nutr. 2014 Dec;33(6):929-36. doi: 10.1016/j.clnu.2014.04.007. PubMed PMID: 24814383.
40. Laviolette L, Lands LC, Dauletbaev N, Saey D, Milot J, Provencher S, et al. Combined effect of dietary supplementation with pressurized whey and exercise training in chronic obstructive pulmonary disease: a randomized, controlled, double-blind pilot study. J Med Food. 2010 Jun;13(3):589-98.doi: 10.1089/jmf.2009.0142. PubMed PMID: 20521985.
41. Chen WC, Huang WC, Chiu CC, Chang YK, Huang CC. Whey protein improves exercise performance and biochemical profiles in trained mice. Med Sci Sports Exerc. 2014 Aug;46(8):1517-24. doi: 10.1249/MSS.0000000000000272. PubMed PMID: 24504433.
42. Farnfield M, Carey K, Gran P, Trenerry M, Cameron-Smith D. Whey protein ingestion activates mTOR-dependent signalling after resistance exercise in young men: a double-blinded randomized controlled trial. Nutrients. 2009 Feb;1(2):263-75. doi: 10.3390/nu1020263. PubMed PMID: 22253983.
43. Franceschelli A, Cappello A, Cappello G. Retrospective study on the effects of a whey protein concentrate on body composition in 262 sarcopenic tube fed patients. Minerva Med. 2013 Feb;104(1):103-12. PubMed PMID: 23392543.
44. Olsen MF, Abdissa A, Kæstel P, Tesfaye M, Yilma D, Girma T, et al. Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia. BMJ. 2014 May 15;348:g3187. doi: 10.1136/bmj.g3187. PubMed PMID: 25134117.
45. Mikkelsen UR, Dideriksen K, Andersen MB, Boesen A, Malmgaard-Clausen NM, Sørensen IJ, et al. Preserved skeletal muscle protein anabolic response to acute exercise and protein intake in well-treated rheumatoid arthritis patients. Arthritis Res Ther. 2015 Sep 25;17:271. doi: 10.1186/s13075-015-0758-3. PubMed PMID: 26407995.
46. Sugawara K, Takahashi H, Kashiwagura T, Yamada K, Yanagida S, Homma M, et al. Effect of anti-inflammatory supplementation with whey peptide and exercise therapy in patients with COPD. Respir Med. 2012 Nov;106(11):1526-34. doi: 10.1016/j.rmed.2012.07.001. PubMed PMID: 22857881.
47. Engelen MP, De Castro CL, Rutten EP, Wouters EF, Schols AM, Deutz NE. Enhanced anabolic response to milk protein sip feeding in elderly subjects with COPD is associated with a reduced splanchnic extraction of multiple amino acids. Clin Nutr. 2012 Oct;31(5):616-24. doi: 10.1016/j.clnu.2012.04.006. PubMed PMID: 22682082.
48. Engelen MP, Rutten EP, De Castro CL, Wouters EF, Schols AM, Deutz NE. Casein protein results in higher prandial and exercise induced whole body protein anabolism than whey protein in chronic obstructive pulmonary disease. Metabolism. 2012 Sep;61(9):1289-300. doi: 10.1016/j.metabol. 2012.03.001. PubMed PMID: 22512824.
49. Ahnfeldt-Mollerup P, Hey H, Johansen C, Kristensen S, Brix Lindskov J, Jensahnfeldt-Mollerupen C. The effect of protein supplementation on quality of life, physical function, and muscle strength in patients with chronic obstructive pulmonary disease. Eur J Phys Rehabil Med. 2015 Aug;51(4):447-56. PubMed PMID: 25426541.
50. Dietary Reference Intakes. Dietary guidance: Food and Nutrition information center. Washington: USDA; 2006.
51. Murphy CH, Oikawa SY, Phillips SM. Dietary protein to maintain muscle mass in aging: a case for per-meal protein recommendations. J Frailty Aging. 2016;5(1):49-58. doi: 10.14283/jfa.2016.80. PubMed PMID: 26980369.