Growth failure in cystic fibrosis

OBJECTIVE: The aim of this study was to describe and compare the nutritional status of children aged 0-18 years attending the cystic fibrosis (CF) clinic at the Royal Children's Hospital, Brisbane, Australia, as outpatients in 1986 and 1996. METHODOLOGY: The heights, weights and pulmonary function of children attending the CF clinic as outpatients in 1986 (n = 97) and 1996 (n = 227) were retrospectively analysed using a computerized database maintained by the CF clinic. The heights and weights were analysed in terms of z scores for height for age (HAZ), weight for age (WAZ) and weight for height (WHZ). Pulmonary function data is not available for all children. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and forced mid expiratory flows (FEF) were expressed as a percentage of predicted and are presented here. RESULTS: The 1986 sample consisted of 41 males (age range 0.18-14.59 years, mean age 6.52 (4.33)) and 56 females (age range 0.15-14.97 years, mean age 7.75 (3.70)). The 1996 sample consisted of 111 males (age range 0.09-17.97 years, mean age 8.80 (5.49)) and 114 females (age range 0.12-17.98 years, mean age 8.49 (5.26)). In 1986, males were shorter than females (P = 0.0096) and females had a lower mean FVC than males (P = 0.0438). In 1996, males were shorter, lighter and more wasted than females (P = 0.0357, P = 0.0034 and P = 0.0273, respectively) and females had a lower mean FEV1 and mean FVC than males (P = 0.0176 and P = 0.0079, respectively). Males in 1996 were lighter and more wasted than males in 1986 (P = 0.0023 and P = 0.0139, respectively) and had a lower mean FEV1, mean FVC and mean FEF (P < 0.0001, P = 0.0012 and P = 0.0069, respectively). Females in 1996 were shorter and lighter than females in 1986 (P = 0.0273 and P = 0.0405, respectively) and had a lower mean FEV1, mean FVC and mean FEF (P < 0.0001, P < 0.0001 and P < 0.0001, respectively). When subjects were classified according to FEV1 (FEV1 > or = 75% or FEV1 < 75%), there were no significant differences in z scores between the 1986 group and 1996 group. Similarly, when the 1986 group were matched for gender and FEV1 with the 1996 group, there were no significant differences in z scores for males or females. CONCLUSIONS: It is suggested that the apparent worsening of nutritional status among the 1996 group of CF patients is in fact due to an effect of increased survival of patients with more severe clinical symptoms. The findings from this study highlight the continuing, and in fact, worsening problem of growth failure in children with CF.     

Growth hormone treatment in children with cystic fibrosis

Children with cystic fibrosis (CF) have problems with poor linear growth and inadequate weight gain. Nutritional augmentation has been the mainstay of therapy for improving both weight and height in CF; however inadequate growth continues to be a problem. Furthermore, protein catabolism has been documented even in non-acutely ill adults and children with CF, and could adversely affect longitudinal growth. Human recombinant growth hormone (GH) has positive effects on nitrogen balance, and multiple studies have demonstrated improved height and weight in children treated with GH. The purpose of this article is to summarize studies evaluating GH use in children with CF.     

Growth hormone normalizes pubertal onset in children with cystic fibrosis

Children with cystic fibrosis (CF) have a high incidence of delayed puberty and poor growth. We retrospectively reviewed pubertal maturation data from 105 children with CF who had participated in studies on growth hormone (GH). As part of the GH study, participants were randomized into two cohorts, one of which was treated with GH for 1 year, and then followed off GH, and the other group was first followed off GH, and then treated with GH for 1 year. Pubertal staging was obtained throughout these studies and we have retrospectively analyzed the data. RESULTS: In prepubertal females, GH treatment resulted in a normalized onset of breast development as compared to delayed onset in non-treated females. Females treated during puberty had a normal tempo of breast development. In prepubertal males, GH treatment resulted in a normalized onset of testicular volume compared to non-treated males. Testicular size progression was not accelerated in pubertal boys treated with GH. CONCLUSION: GH treatment normalizes pubertal onset in prepubertal children with CF.     

Growth hormone improves bone mineral content in children with cystic fibrosis

AIM: Osteoporosis and osteopenia have been reported as common complications of cystic fibrosis (CF); however, little is known about accrual of bone mineral in CF. The goal of our study was to measure bone mineral content (BMC) in non-acutely-ill, but poorly growing children with CF, and to determine the relationship between height, lean body mass and BMC. Our second aim was to evaluate the effect of one year of treatment with human recombinant growth hormone (GH) on total body BMC. METHODS: We measured total-body BMC using dual energy X-ray absorptiometry in 32 poorly growing (height < or =10th percentile for age) prepubertal Caucasian children (ages 7 years 6 months-12 years 9 months, 17 M and 15, F) with CF. BMC and lean tissue mass (LTM) were measured at baseline, at 6 months and one year. One half of the children were randomly assigned to receive treatment with GH (GHTX). Results were compared to reference data maintained for healthy children matched for age and ethnicity. Sex steroid and IGF-I levels were also measured. RESULTS: Children with CF exhibited lower total body BMC and LTM than age-, ethnicity- and gender-matched controls. This was still apparent when the data were matched for height and bone age. BMC correlated with height, LTM, and IGF-I levels. Although at baseline the groups were similar, the GHTX group demonstrated significantly greater increase in height, weight, LTM and BMC than the NonTX group. These differences remained despite correction for increase in height CONCLUSION: Our study is the first to evaluate BMC in children with CF and suggests that poor accumulation of bone mineral is a problem. We have further demonstrated that GH treatment improves accumulation of bone mineral.     

Growth problems and growth hormone treatment in children with cystic fibrosis

Children with cystic fibrosis (CF) typically demonstrate poor linear growth and, despite aggressive nutritional supplementation, suboptimal weight gain. Growth velocity may be particularly blunted during puberty, a finding that occurs independently of clinical status or sex steroid levels. Several studies indicate that growth hormone (GH) treatment may be associated with significant improvement in both height velocity and weight gain in children with CF. These findings may translate into improvements in clinical status. In our experience, improved growth and weight status have been associated with fewer hospitalizations, fewer antibiotic courses, and improved pulmonary function. A large multicenter trial is currently underway to assess the effect of long-term therapy with GH on the quality of life and pulmonary status.     

Glucose intolerance in children with cystic fibrosis

OBJECTIVE: To evaluate the relations among glucose intolerance, genotype, and exocrine pancreatic status in patients with cystic fibrosis (CF). STUDY DESIGN: Data on 335 patients <18 years of age were from the Toronto CF database. A modified oral glucose tolerance test was given to 94 patients 10 to 18 years of age without recognized CF-related diabetes. CF transmembrane conductance regulator mutations and exocrine pancreatic status were determined for all patients. RESULTS: CF-related diabetes was clinically recognized in 9 of 335 (2.7%) patients <18 years of age, all of whom were pancreatic insufficient, and 8 of 9 had severe (classes I through III) mutations on both alleles. The ninth patient had unidentified mutations. Although all patients given the oral glucose tolerance test were asymptomatic and had normal fasting blood glucose, 16 of 94 (17%) had impaired glucose tolerance and 4 of 94 (4.3%) had CF-related diabetes without fasting hyperglycemia. Abnormal glucose tolerance was associated exclusively with severe mutations and exocrine pancreatic insufficiency. Glycosylated hemoglobin (HbA(1)C) levels did not correlate with glucose tolerance results. CONCLUSIONS: Screening of pancreatic-insufficient, adolescent patients with CF identified more with abnormal oral glucose tolerance than was suspected clinically and is recommended as a routine practice. HbA(1)C was not useful in screening for CF-related glucose intolerance.     

Thyroid function in children with cystic fibrosis

Serum concentrations of T4, T3, reverse T3 (rT3), TSH, Thyroxine binding globulin (TBG) and Thyroxine binding prealbumin (TBPA) were measured and a TRH-stimulation test was performed in 10 iodide untreated children affected by cystic fibrosis (CF) and in 84 controls.As compared to the controls, CF patients had lower T4 and rT3, similar T3 and TBG and increased T3:T4 ratios. They also had lower TBPA, but this could not account for the low T4. Finally they had higher basal and TRH-stimulated TSH. Our results indicate subclinical hypothyroidism in CF. The mechanisms responsible for this situation are not elucidated by our data.Presented in part at the 41st Meeting of the Italian Society of Pediatrics, October, 22–25, 1981, Bologna, Italy     

Aminoglycoside-associated hypomagnesaemia in children with cystic fibrosis

Hypomagnesaemia in children with cystic fibrosis (CF) is under-recognized. We report a child with CF who developed significant hypomagnesaemia following intravenous (i.v.) treatment with aminoglycosides for exacerbations of Pseudomonas aeruginosa infection. Three additional cases have also been observed. Investigations in two patients have revealed excessive renal loss of magnesium. It is postulated that renal tubular damage secondary to the cumulative effects of repeated courses of aminoglycosides resulted in hypomagnesaemia, and we suggest screening for this problem by monitoring serum magnesium regularly in all patients with CF receiving multiple courses of aminoglycosides.     

Psychosocial problems in children with cystic fibrosis

AIM: To compare the well-being of children (7-14 years) with cystic fibrosis (CF) (n = 43) with the well-being of healthy controls (n = 1121). METHODS: The self-report questionnaire Beck Youth Inventories (BYI) was used to study depression, anxiety, anger, disruptive behaviour and self-concept in children with CF. A measure of social desirability was included as well as body mass index (BMI) and percentage of predicted forced expiratory volume in one second (FEV(1)) as measures of health status. RESULTS: The children with CF did not differ from the norm group concerning depression, disruptive behaviour and self-concept. Young children with CF (7-10 years) and boys with CF scored significantly higher on anxiety. Girls with CF scored significantly lower on anger than controls. BMI was not associated with any of the BYI subscales. In patients aged 11-14 years, there was a significant correlation between FEV(1) and self-concept as well as a significant inverse correlation between FEV(1) and anxiety. CONCLUSIONS: Younger children with CF and boys with CF were more anxious than the healthy controls, and girls with CF expressed less anger than their healthy peers. Effects sizes however were small. Low FEV(1) was associated with low self-concept and high anxiety in adolescent patients.     

Liver disease in children with cystic fibrosis

Identification, evaluation and treatment of liver disease are increasingly important challenges in children with cystic fibrosis (CF). Liver disease usually presents at puberty and is receiving more attention with improved life expectancy. The abnormal CF transmembrane regulator protein in the apical surface of the biliary epithelium causes the disease. Hyperviscous bile accumulates in the biliary tree causing cholangiocyte and hepatocyte injury, stimulating focal fibrosis. Fibrosis is thought to lead on to cirrhosis over a period of years, a process which is usually asymptomatic. Steatosis and biliary tree anomalies including cholecystitis also occur. Clinical signs of liver disease appear late, by which time cirrhosis may be established. Early diagnosis would allow interventions to be evaluated but there is no gold standard for screening. Currently, regular clinical assessment, measurement of liver enzymes, ultrasound and liver biopsy are all used to evaluate liver disease in CF. Bile acid therapy reverses many markers of the disease but there is no good evidence that progression to cirrhosis can be prevented. A few children with cirrhosis decompensate (demonstrated by falling plasma albumin or coagulopathy) but they do well with liver transplantation. Children with portal hypertension as the sole manifestation of CF liver disease can be effectively managed with a programme of variceal obliteration or porto-systemic shunts.     

Growth hormone therapy improves growth in children with cystic fibrosis related liver disease

Growth impairment in cystic fibrosis (CF) is worsened by liver disease. Children with CF have serum levels of insulin-like growth factor-I (IGF-I) that are lower than expected for their normal growth hormone (GH) production. In children with CF-related liver disease (CFLD), response to endogenous GH is further reduced. We present our experience with two young children with CFLD given recombinant human GH (rhGH). The first patient was a 5 year-old female with CFLD and poor growth who responded well for 1 1/2 years to rhGH therapy during her initial course and without a significant increase in serum IGF-I, but with a substantial increase in IGF-I concentration when the GH dose was increased. The second patient was a 5 month-old male with advanced liver disease who had transient improved growth and liver function following rhGH. These patients suggest that rhGH is safe and may be effective in children with CFLD.     

Growth dynamics in cystic fibrosis

The growth profiles of 28 cystic fibrosis patients, followed for at least three years, were analysed in order to study the dynamics of growth and to verify if any correlation with clinical events exists. Heights and weights were recorded at three-month intervals, and the patterns did not appear stable or linear, although a graphical smoothing might depict a linear pattern. Height and weight velocity profiles were plotted and all cases showed regular pulsatile patterns of height and weight velocity. By taking measurements at three-month intervals, the pulsatile rhythm was found to be associated with a circannual rhythm. When the appearance of clinical events was related to growth velocity profiles for each individual, the majority (71–82%) occurred during the descending phase of the growth velocity. An understanding of the individual pulsatile pattern of growth may actually increase the sensitivity of surveillance, and checks might be programmed according to the individual pattern, since the risk of developing an adverse clinical event is significantly greater during the slowing phase of the growth velocity.     

Physiotherapy for children with cystic fibrosis

Physiotherapy is an important part of the daily routine of patients with cystic fibrosis. It is one of a number of treatments used to help improve the quality of life. Airway clearance techniques aim to relieve respiratory symptoms by physical means, helping removal of tracheobronchial secretions, and thereby preventing or slowing deterioration in respiratory function. Exercise is used to monitor patient progress, maintain thoracic mobility, and improve well being and morale. Cystic fibrosis patients require ongoing assessment throughout life; physiotherapists can help to minimize the effect of the treatment burden by being as flexible as possible with regard to where, when and how they assess and plan treatments with their patients.