Introduction
Cystic Fibrosis (CF) is a life-threatening, autosomal recessive disorder caused by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutation. The mutation causes the absence or dysfunction of the CFTR protein that controls the movement of essential ions—mainly chloride, sodium, and bicarbonate—through the apical membrane in select epithelial cells1. The alteration of this protein impairs many organs, including the lungs, sinuses, pancreas, liver, and gastrointestinal tract.
While pulmonary insufficiency is the cause of death for most cystic fibrosis patients, many suffer from malnutrition1. This complication of CF is a multifactorial process. There is pancreatic insufficiency which can start as early as in fetal stages2, severely impairing fat absorption3. Other nutrients such as carbohydrates, proteins, and fat-soluble vitamins A, D, E, and K are underutilized. Additionally, CF patients frequently have gastrointestinal problems, including cramping, bloating, and gastroesophageal reflux disease, making the consumption of extra calories painful and difficult4.
CF patients have a higher resting energy expenditure than the non-CF population; this is more prominent in patients with advanced lung disease who consume more energy to maintain respiratory demands5. The combination of inadequate nutrient absorption and calorie consumption and a higher resting energy expenditure create the persistent condition of negative energy balance and subsequent malnutrition and weight loss.
Nutritional status is assessed in many ways. In clinical practice, body mass index (BMI) strongly correlates with disease progression, as low body weight and BMI are consistently associated with increased risk of mortality and severity of pulmonary disease6. CF patients who maintain a high-fat diet and higher body weight have improved long-term survival7. Malnourished CF patients usually increase lung function–clinically monitored through the amount of forced expiratory volume in one second (FEV1)–when they gain weight and increase their BMI8. Also, there is a correlation between a higher BMI and increased bone mineral density in adult CF patients; this risk factor is an important finding, as adequate nutrition and the corresponding increase in body weight could help prevent osteopenia and osteoporosis9.
Maintaining an adequate body weight in CF patients has been traditionally difficult. The current Cystic Fibrosis Foundation (CFF) guidelines recommend that the nutrition and growth of CF patients are monitored very closely. CFF care teams keep track of nutrition in their patients by recording weight, height, and BMI quarterly. Patients 20 years and older have a BMI goal of 22 kg/m2 for females and 23 kg/m2 for males10. CF pediatric patients two years and older should remain above or equal to the 50th percentile in BMI using the CDC growth charts11. A multi-disciplinary team consisting of a pulmonologist, dietician, gastroenterologist, endocrinologist, social worker, and psychologist ensures that each patient receives assistance for every aspect of their nutritional needs. This means actively addressing malnutrition complications, including pulmonary and GI issues, inadequate food intake, impaired glucose tolerance, and depression/anxiety. CF care teams emphasize nutrition and adequate body weight in their plan of care to preserve lung function and decrease the risk of mortality in their patients.
In recent years, the treatment of CF has focused on using CFTR modulators to restore function to the CFTR protein. Currently, there are four modulators on the market, but only two are considered highly effective modulator therapies: ivacaftor and the recently approved elexacaftor/tezacaftor/ivacaftor triple combination therapy (TCT)12. While increased weight gain happens with all the modulators, the extent to which the patient sees benefit is related directly to the mutation-specific modulator. Studies consistently report improved body weight and BMI in patients on ivacaftor, less significant weight gain on lumacaftor/ivacaftor, and only a modest weight promotion in patients on tezacaftor/ivacaftor. The only widely known information on the correlation of weight gain with TCT is based on two preliminary clinical trials that were relatively short-term—only 4 and 24 weeks long. The subjects enrolled in these clinical trials did see an improvement in their body weight and BMI13. However, long-term data are lacking.
The introduction of CFTR modulators has led to improved weight gain in CF patients, which has led to an increased opportunity for excess weight and obesity in some patients. In 2014, one CF center found that 15% of their patient population was overweight, with another 8% meeting the criteria for obesity14. Theoretically, the initiation of even more efficacious modulators could increase that prevalence by further improving the mechanisms of benefit. Ivacaftor has possibly induced weight gain by increasing the amount of sodium bicarbonate in the gut, which helps improve intraluminal adhesions and causes positive changes in gut flora15. Patients reported increased digestion and food consumption while on ivacaftor; this improvement would help patients gain weight by allowing an enhanced ability to consume more calories16. Lastly, other studies have shown that ivacaftor improved weight gain by decreasing resting energy expenditure and gut inflammation while increasing fat absorption17.
The nutritional health of CF patients is a delicate balance between malnutrition and excess weight, with unique health risks presented with each situation. The introduction of the highly effective TCT modulator presents the possibility of weight gain; it is essential to be aware of these weight changes so that clinical care can be modified if needed. Our study aimed to identify the weight changes in CF patients receiving care at our CF center, after a year of taking TCT.