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.