Lung transplantation (LTx) is an accepted treatment option for patients with end-stage lung disease who do not respond to non-transplant treatments. Lung transplantation (LTx) is an accepted treatment option for patients with end-stage lung disease who do not respond to non-transplant treatments. It is important to optimize the nutritional status of patients during the waiting period before transplantation, to positively improve their vital functions such as exercise capacity, to get up as soon as possible after transplantation, to shorten the hospitalization process and to support survival. Pulmonary rehabilitation (PR) aims to prevent further progression of respiratory disease and improve the physical and mental health of patients, as well as helping patients to adopt healthy behavior habits. PR before transplantation helps individuals maintain or optimize their functional status before surgery. PR before transplantation helps individuals maintain or optimize their functional status before surgery. Beta-hydroxy-beta-methylbutyrate (HMB) is an active metabolite of the branched-chain essential amino acid leucine. Several studies have shown HMB supplements to be beneficial, either alone or in combination with other amino acids and exercise training, for maintaining and restoring lean body mass, muscle strength and function in older adults. HMB provides a decrease in muscle protein breakdown along with an increase in muscle protein synthesis. In addition, it stimulates muscle protein synthesis by activating the mechanical target of the mammals are the target of rapamycin (mTOR) system and growth hormone/insulin-like growth hormone. Given the very low amounts of HMB and the low conversion rate of leucine to HMB (5-10%), the optimal dose requirement of HMB cannot be met with a standard diet. Therefore, oral supplementation of HMB is seen as an alternative to alleviate adult metabolic diseases, muscle wasting and functional loss. In lung transplant candidates, it is important to optimize nutrition and health conditions during the listing period, to get up as soon as possible after transplantation, to shorten the hospitalization process and to support survival. The study aimed to investigate the positive/negative effects of pulmonary rehabilitation and HMB supplementation, which supports muscle mass and protein production, on patients compared to pulmonary rehabilitation alone in lung transplant candidates.
Lung transplantation (LTx) is an accepted treatment option for patients with end-stage lung disease who do not respond to non-transplant treatments. Lung transplantation (LTx) is an accepted treatment option for patients with end-stage lung disease who do not respond to non-transplant treatments. Primary indications for lung transplantation in the world are; 34% chronic obstructive pulmonary disease (COPD), 24% idiopathic pulmonary fibrosis (IPF), 17% cystic fibrosis (CF), 6% alpha-1-antitrypsin deficiency, 3% idiopathic pulmonary arterial hypertension (IPAH), 4% pulmonary fibrous (non-IPF), 3% bronchiectasis, 2.6% re transplantation and 2.5% of them are classified as sarcoidosis. Absolute contraindications for lung transplantation are; active malignancy, coronary artery disease without revascularization ability, significant extrapulmonary organ dysfunction, active tobacco or bad substance use, the presence of extremely serious active infections such as tuberculosis, morbid obesity and lack of psychosocial support. Absolute contraindications for lung transplantation are; active malignancy, coronary artery disease without revascularization ability, significant extrapulmonary organ dysfunction, active tobacco or bad substance use, the presence of extremely serious active infections such as tuberculosis, morbid obesity and lack of psychosocial support. Some relative contraindications are critical illness, mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) support, each transplant center has a different attitude. The upper age limit for lung transplantation varies according to each center, but is generally accepted as between 70 and 75 years of age. Beta-hydroxy-beta-methylbutyrate (HMB) is an active metabolite of the branched-chain essential amino acid leucine.roxy-beta-methylbutyrate (HMB) is an active metabolite of the branched-chain essential amino acid leucine. HMB is found in very small amounts in some foods such as avocados, citrus fruits, caulidroxy-beta-methylbutyrate (HMB) is an active metabolite of the branched-chain essential amino acid leucine. HMB is found in very small amounts in some foods such as avocados, citrus fruits, cauliflower and catfish. Leucine has a specific role in the regulation and control of protein synthesis in muscle cells. About 5% of leucine in the body is converted into HMB. Many studies have shown that HMB supplements alone or in combination with other amino acids and in combination with exercise training are beneficial for maintaining and restoring lean body mass, muscle strength and function in older adults. Many studies have shown that HMB supplements alone or in combination with other amino acids and in combination with exercise training are beneficial for maintaining and restoring lean body mass, muscle strength and function in older adults. Leucine is the most effective branched chain amino acid in important cellular processes such as protein synthesis and energy metabolism. The first step in leucine metabolism in the body is the reversible transamination that occurs in skeletal muscles to form α-ketoisocaproate with simultaneous production of glutarate from α-ketoglutarate. The first step in leucine metabolism in the body is the reversible transamination that occurs in skeletal muscles to form α-ketoisocaproate with simultaneous production of glutarate from α-ketoglutarate. The second stage is the irreversible oxidative decarboxylation of α-ketoisocaproate by branched-chain α-keto acid dehydrogenase (BCKD) and α-ketoisocaproate dehydrogenase (KICD) enzymes. In liver mitochondria, 90% of the α-ketoisocaproate produced causes the formation of acetoacetate and acetyl CoA, while in liver cytosol, the remaining 5-10% α-ketoisocaproate is oxidized to HMB by the enzyme KICD. Liver mitochondria, 90% of the α-ketoisocaproate produced causes the formation of acetoacetate and acetyl CoA, while in liver cytosol, the remaining 5-10% α-ketoisocaproate is oxidized to HMB by the enzyme KICD. HMB provides a decrease in muscle protein breakdown along with an increase in muscle protein synthesis. In addition, it stimulates muscle protein synthesis by activating the mechanical target of the rapamyc November (mTOR) system and growth hormone/insulin-like growth hormone. HMB has also been shown to be associated with a decrease in muscle proteolysis by inhibiting the ubiquitin-proteasome and autophagy-lysosome systems. Given the very low amounts of HMB present in foods and the low conversion rate of leucine to HMB (5-10%), optimal HMB dose requirements cannot be met with a standard diet. Therefore, oral HMB supplementation is considered an alternative to alleviate adult metabolic diseases, muscle wasting, and functional loss. Pulmonary rehabilitation (PR) aims to prevent further progression of respiratory disease and improve patients' physical and mental health, while also encouraging patients to adopt healthy behavioral habits. The European Respiratory Society and the American Thoracic Society define PR as "patient-specific treatments, including but not limited to exercise training and behavior modification, designed to improve the physical and psychological well-being of individuals with chronic respiratory diseases and to promote long-term health-promoting behaviors." PR, which includes exercise training, is a powerful intervention designed to improve exercise tolerance, skeletal and respiratory muscle function, movement efficiency, symptoms of dyspnea and fatigue, and health-related quality of life. PR aims to stabilize or reverse the pathophysiological and psychopathological symptoms of the disease and strives to restore the patient to the highest possible functional capacity. The optimal exercise type, duration, intensity, and frequency for PR have not yet been determined. A minimum of eight weeks is generally recommended for PR programs to provide lasting benefits to the patient. Exercise sessions are generally scheduled 3-5 times a week, each session lasting 20-45 minutes. It is suggested that the improvement mechanism of exercise training is related to increasing aerobic capacity and peripheral muscle performance in patients. Exercise intolerance and decreased quality of life often persist after transplantation. Physiological changes associated with severe chronic lung disease, extremity muscle dysfunction, inactivity/deconditioning, and nutritional deficiencies can affect exercise capacity and physical functioning in lung transplant candidates. Prolonged post-transplant hospital and intensive care unit stays, prolonged immobilization, immunosuppressant medications, and organ rejection can all impact lung recipients' recovery in terms of exercise tolerance and quality of life. Decreases in muscle mass and quadriceps strength are frequently observed in the pre-transplant period and have been reported to persist for up to 3 years post-transplant. Pre-transplant PR helps individuals maintain or optimize their pre-operative functional status. The nutritional status of patients on the waiting list is associated with post-transplant survival. Studies have identified obesity, low body mass index, and low serum albumin concentration as significant risk factors for increased mortality after lung transplantation. Nutritional status in lung transplant candidates is associated with post-transplant survival. Obesity, as well as pre-transplant malnutrition, is considered a contraindication and appears to increase the risk of post-transplant mortality independently of other risk factors. Lean body mass (FFM) is an important indicator of nutritional status. It is associated with muscle mass, muscle function, lung function, and quality of life. A decrease in FFM is significantly associated with increased mortality while waiting for transplantation and prolonged intensive care unit stay after transplantation. Body mass index (BMI) is a parameter used to assess nutritional status, calculated by dividing body mass by the square of height in meters. The resulting BMI is evaluated according to the World Health Organization (WHO) classification. A BMI above 30 kg/m² or below 18.5 kg/m² has been shown to increase post-transplant mortality and primary graft dysfunction. Furthermore, low albumin levels have frequently been associated with adverse post-transplant outcomes. In patients with end-stage lung disease, significant loss of lung function, respiratory failure, recurrent infections, decreased appetite caused by hypoxia and depression, and gastrointestinal dysfunction all contribute to inadequate energy intake and, consequently, malnutrition and even cachexia. The various complications associated with malnutrition lead to increased frequency and duration of hospitalization and shortened survival after transplantation. Therefore, it is crucial to assess the nutritional status of lung transplant candidates before transplantation, identify any risks of malnutrition in a timely manner, and provide an individualized nutrition program tailored to each patient. Optimizing nutrition and health status in lung transplant candidates during the listing period is crucial for achieving recovery as quickly as possible after transplantation, shortening hospital stays, and promoting survival. The study aimed to investigate the positive/negative effects of pulmonary rehabilitation and HMB supplementation, which supports muscle mass and protein synthesis, compared to pulmonary rehabilitation alone in lung transplant candidates.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
30
Participants of half will be given hydroxymethylbutyrate for 2 months.
Koşuyolu Yüksek Ihtisas Eğitim Ve Araştırma Hastanesi
Istanbul, Kartal, Turkey (Türkiye)
Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy, and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.
Participants' biochemical measurements fasting glucose was evaluated at the beginning of the study and at the end of the 8-week study. The samples were evaluated in the laboratory of Koşuyolu High Specialization Training and Research Hospital. Fasting blood sugar is usually measured after 8-10 hours of fasting, and the normal range is 70-99 mg/dL.
Time frame: From the registration stage to the end of the 8-week follow-up period.
Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.
Participiants' 6-minute walk test was evaluated at the begining of the study and at the end of the 8-week study. The 6-minute walk test was performed by a physiotherapist from the lung transplant team. The normal distance for a 6-minute walking test is between 400-700m.
Time frame: From the registration stage to the end of the 8-week follow-up period.
Comporasion of lung transplant candidates who received pulmonary rehabilitation, dietary therapy abd hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.
Participants' respiratory function tests (FEV1, FVC AND FEV1/FVC) was evaluated at the begining of the study and at the end of the 8-week study. A pulmonary function test was performed by a nurse working at Koşuyolu High Specialization Training and Research Hospital. FEV1 and FVC values of 80% or higher are considered normal. The FEV1/FVC ratio is normally between 70% and 80%.
Time frame: From the registration stage to the end of the 8-week follow-up period.
Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.
Participants' body composition (weight (kilograms), height (meters), BMI (kg/m2)) was assessed at the beginning of the study and at the end of the 8-week study using a BC-420MA body analyzer and measuring tape. BMI is by dividing weight (kilograms) by the square of height (meters). Individuals with a BMI between 25.0 and 29.9kg/m2 were accepted.
Time frame: From the registration stage to the end of the 8-week follow-up period.
Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.
Participants' short form -36 (SF-36) quality of life scale was evaluated at the beginning of the study and at the end of the 8-week study. SF-36 quality of life scale scores were evaluated and compared at the beginning and end of the study. Higher scores on the SF-36 scale indicate a better quality of life. The score ranges from a minimum of zero to a maximum of one hundred points.
Time frame: From the registration stage to the end of the 8-week follow-up period.
Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy, and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.
Participants' biochemical measurements (total protein, prealbumin, albumin) was evaluated at the beginning of the study and at the end of the 8-week study. The samples were evaluated in the laboratory of Koşuyolu High Specialization Training and Research Hospital. The normal range for total serum protein is 6.0 to 8.3 g/dl. The normal range for prealbumin is 15-36 mg/dl. The normal range for serum albumin is 34-54 mg/dl.
Time frame: From the registration stage to the end of the 8-week follow-up period.
Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy, and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy
Participants' biochemical measurements (urea, creatinine) was evaluated at the beginning of the study and at the end of the 8-week study. The samples were evaluated in the laboratory of Koşuyolu High Specialization Training and Research Hospital. The normal range for serum urea is 10-50 mg/dl. The normal serum creatinine range is 0.5-1.1 mg/dl for women and 0.6-1.2 mg/dl for men.
Time frame: From the registration stage to the end of the 8-week follow-up period.
Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy, and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.
Participants' biochemical measurements (total cholesterol, triglyceride) was evaluated at the beginning of the study and at the end of the 8-week study. The samples were evaluated in the laboratory of Koşuyolu High Specialization Training and Research Hospital. The normal value for serum total cholesterol should be below 200 mg/dl. The normal value for serum total triglycerides should be below 150 mg/dl.
Time frame: From the registration stage to the end of the 8-week follow-up period.
Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.
Participants' body composition (lean body mass (FFM), body fat percentage, body muscle mass, body fat mass) was assessed at the beginning of the study and at the end of the 8-week study using a BC-420MA body analyzer and measuring tape. The normal FFM value should be 75-85% for women and 80-90% for men. The normal range for body fat percentage is 25-31% for women and 18-24% for men.
Time frame: From the registration stage to the end of the 8-week follow-up period.
Comparison of lung transplant candidates who received pulmonary rehabilitation, dietary therapy and hydroxymethylbutyrate for 8 weeks with those who received only pulmonary rehabilitation and dietary therapy.
Participants' body composition (waistcircumference, hip circumference, waist-to-hip ratio, upper mid-arm circumference, calf circumference) was assessed at the beginning of the study and at the end of the 8-week study using a measuring tape. Waist circumference should be below 80cm for women and 94cm for men. A waist-to-hip ratio of 0.85 or less is considered normal for women, and 0.90 or less for men. An upper mid-arm circumference of 22cm or more is considered normal for women, and 23cm or more for men. A calf circumference of 31-36 cm is considered normal for women, and 35-38 cm for men.
Time frame: From the registration stage to the end of the 8-week follow-up period.
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