The impact of early cystic fibrosis diagnosis on pulmonary function in children

OBJECTIVE: To investigate the impact of early diagnosis on pulmonary function in a large cohort of children with cystic fibrosis (CF). STUDY DESIGN: CF cases identified from the CF Foundation National Patient Registry and diagnosed between 1982 and 1990 were categorized as: early asymptomatic diagnosis (EAD; n = 157), early symptomatic diagnosis (ESD; n = 227), later asymptomatic diagnosis (LAD; n = 161), and later symptomatic diagnosis (LSD; n = 3080). Early CF diagnosis was diagnosis before 6 weeks of age; later diagnosis was diagnosis at 6 weeks to 36 months of age, inclusive. Asymptomatic diagnosis included diagnosis by either family history, genotype, prenatally, or neonatally. Pulmonary function was measured as percentage of predicted forced expiratory volume in one second (FEV(1)). RESULTS: There were no overall differences in pulmonary function among the 4 diagnostic groups. However, EAD cases born more recently (1987 or later) had a higher mean FEV(1) throughout the study, compared with the remaining diagnostic groups. For this later birth cohort, Cox regression analysis for those diagnosed later and/or symptomatically, demonstrated a 2-fold increase in risk (P =.06) for having moderate-to-severe pulmonary function (FEV(1) <70%) at ages 6 to 10 years, compared with EAD cases. CONCLUSIONS: Children diagnosed with CF early, asymptomatically and more recently may have better pulmonary function throughout early childhood, probably as a result of improved CF treatments in recent years.     

Growth and lung function in Asian patients with cystic fibrosis

Background: The incidence of cystic fibrosis (CF) in Asians is rare. How these patients fare in terms of morbidity and mortality in the UK compared to their non-Asian peers is not well documented. Aims: To retrospectively study annual reviews of 31 Asian CF patients from three London paediatric CF centres. Methods: Disease severity was assessed by lung function, age at first infection with Pseudomonas aeruginosa, and body mass index (BMI). The Asian children were compared with 143 matched non-Asian patients with CF. Matching criteria used were same sex and treatment centre as the Asian index patient. In addition, the controls were matched so that their date of birth, date of diagnosis, and date at annual review were within 12 months of the index patient. Results: There was no significant difference in age at diagnosis or age at annual review between the Asian and non-Asian children. Mean Z-scores for FEV₁ and FVC were significantly lower for the Asian girls. There was no significant difference in Z-scores for BMI between the Asian children and their controls. Age at first isolation of Pseudomonas aeruginosa in Asian girls was significantly later than for their controls (8.3 years compared to 5.6 years for non-Asian girls). Conclusions: While the Asian boys'' lung function seems comparable with that of their non-Asian peers, the Asian girls emerge as a potentially vulnerable group and more work is required to discover why this is the case.     

Growth and lung function in Asian patients with cystic fibrosis.

BACKGROUND: The incidence of cystic fibrosis (CF) in Asians is rare. How these patients fare in terms of morbidity and mortality in the UK compared to their non-Asian peers is not well documented. AIMS: To retrospectively study annual reviews of 31 Asian CF patients from three London paediatric CF centres. METHODS: Disease severity was assessed by lung function, age at first infection with Pseudomonas aeruginosa, and body mass index (BMI). The Asian children were compared with 143 matched non-Asian patients with CF. Matching criteria used were same sex and treatment centre as the Asian index patient. In addition, the controls were matched so that their date of birth, date of diagnosis, and date at annual review were within 12 months of the index patient. RESULTS: There was no significant difference in age at diagnosis or age at annual review between the Asian and non-Asian children. Mean Z-scores for FEV1 and FVC were significantly lower for the Asian girls. There was no significant difference in Z-scores for BMI between the Asian children and their controls. Age at first isolation of Pseudomonas aeruginosa in Asian girls was significantly later than for their controls (8.3 years compared to 5.6 years for non-Asian girls). CONCLUSIONS: While the Asian boys' lung function seems comparable with that of their non-Asian peers, the Asian girls emerge as a potentially vulnerable group and more work is required to discover why this is the case.     

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.     

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.     

Renal function in cystic fibrosis

The effect of saline extracellular volume expansion (4 ml/min/10 kg b.w. X 60 min) on renal function has been studied in patients with cystic fibrosis (CF) and in normal age-matched controls. Basal values for glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium and chloride (Na, Cl) handling were similar in both groups. Saline expansion resulted in an increase in GFR and RPF in the CF patients: 127 +/- 18 ml/min/1.73 sqm BSA to 166 +/- 5; p less than 0.001, but not in the control group: 112 +/- 10 to 120 +/- 20. These hemodynamic changes were associated with increased proximal tubular reabsorption of NaCl in the CF patients whereas controls had reduced NaCl reabsorption. Renin and aldosterone levels suggested that increased NaCl reabsorption in CF patients was not secondary to chronic extracellular volume contraction or salt loss. These results support the hypothesis that the renal tubule is involved in the generalised electrolyte transport disorder exhibited in other epithelial structures. This study also indicated that the regulation of renal hemodynamics is altered in CF. The relationship between the disorder of proximal tubular salt handling and changes in renal hemodynamics is not known, but the observed changes imply a tubulo-glomerular feedback mechanism.     

Relationships between pulmonary function and plasma fatty acid levels in cystic fibrosis patients

Nineteen patients with cystic fibrosis (CF) were studied to determine whether plasma fatty acids correlated with severity of their lung disease as assessed by pulmonary function testing. Results were compared with 19 normal subjects of similar age and sex. Linoleic acid content of all lipid fractions was significantly lower in CF patients than controls including cholesterol ester fraction (CF 31%, control 50%, p less than 0.001), triglyceride fraction (7.6 to 16.6%, p less than 0.001), and phospholipid fraction (13.9 to 21.7%, p less than 0.001). Mean 20:3 omega 9/20:4 omega 6 ratio for CF patients was higher in all lipid classes and was suggestive of essential fatty acid deficiency. Correlations were found to exist between most pulmonary function parameters and fatty acids of plasma phospholipids but not any other lipid class. Positive correlations were found between all ventilatory tests and total omega 3 polyunsaturated fatty acids and also 22:5 omega 3 and 22:6 omega 3. There was no correlation between total saturated fatty acids, total monounsaturates, total omega 6 fatty acids, or triene/tetraene ratios and pulmonary function. Positive correlations were found between pulmonary function parameters and certain omega 6 polyunsaturates including 20:4 and 22:4 but not 18:2.     

Relation between dietary intake and nutritional status in cystic fibrosis

This study evaluated adherence to current dietary recommendations of children with cystic fibrosis and mild lung disease and their siblings by comparing energy intake. Fifty children (25 with cystic fibrosis) aged between 7 and 12 years completed the study. Energy intake was assessed by weighed dietary intake, resting energy expenditure was used to calculate recommended daily intakes. The children with cystic fibrosis had significant deficits in Z scores for both height and weight compared with their siblings, but there was no difference in percentage of ideal weight for height. The cystic fibrosis group had a significantly higher energy intake per kilogram body weight per day but there was no difference in the percentage of energy derived from fat, protein or carbohydrate. Energy intake (per kg/day) and fat intake (g/kg) were both significant predictors of weight for height in the cystic fibrosis group. Targets for dietary management in cystic fibrosis should perhaps be related to fat intake per kilogram body weight.     

Long-term effects of physical exercise on working capacity and pulmonary function in cystic fibrosis

Seven patients with cystic fibrosis aged 6 to 20 were enrolled for 30 months in a daily exercise program. After 12 months conventional chest physiotherapy was withdrawn. Patients with low initial Shwachman scores improved as regards maximal working capacity. Spirometric data and volume of trapped gas indicated opening of closed airways. We suggest that physical exercise in general should be the basis of pulmonary therapy in cystic fibrosis. Other forms of physiotherapy are advisable when hard physical exercise is not feasible.     

Pancreatic endocrine function in cystic fibrosis

To characterize pancreatic endocrine secretion and to examine interrelationships among alterations in alpha, beta, and pancreatic polypeptide cell function in patients with cystic fibrosis (CF), we studied 19 patients with exocrine insufficiency (EXO), including 9 receiving insulin therapy (EXO-IT); 10 patients with no exocrine insufficiency (NEXO); and 10 normal control subjects. First-phase C-peptide response to intravenously administered glucose was significantly impaired in CF patients with exocrine insufficiency (EXO-IT = 0.02 +/- 0.01; EXO = 0.11 +/- 0.02; NEXO = 0.25 +/- 0.05; control subjects = 0.30 +/- 0.04 nmol/L). Lowering fasting glucose levels with exogenous insulin administration in EXO-IT did not improve beta cell responsivity to glucose. The C-peptide response to arginine was less impaired (EXO-IT = 0.12 +/- 0.02; EXO = 0.15 +/- 0.02; NEXO = 0.23 +/- 0.06; control subjects = 0.28 +/- 0.04 nmol/L). Alpha cell function, measured as peak glucagon secretion in response to hypoglycemia, was diminished in EXO but not NEXO (EXO-IT = 21 +/- 10; EXO = 62 +/- 19; NEXO = 123 +/- 29; control subjects = 109 +/- 12 ng/L). Despite diminished glucagon response, EXO patients recovered normally from hypoglycemia. Peak pancreatic polypeptide response to hypoglycemia distinguished CF patients with exocrine insufficiency from those without exocrine insufficiency (EXO-IT = 3 +/- 2; EXO = 3 +/- 1; NEXO = 226 +/- 68; control subjects = 273 +/- 100 pmol/L). Thus CF patients with exocrine disease have less alpha, beta, and pancreatic polypeptide cell function than CF patients without exocrine disease. These data suggest either that exocrine disease causes endocrine dysfunction in CF or that a common pathogenic process simultaneously and independently impairs exocrine and endocrine function.     

Defining a pulmonary exacerbation in cystic fibrosis

OBJECTIVES: Despite the central importance of pulmonary exacerbations (PExs) as an outcome measure in cystic fibrosis clinical trials, no standardized definition of PEx exists. We conducted a prospective, multicenter study to establish a standardized PEx definition and score for use in clinical trials, based on clinical status rather than on treatment decisions. STUDY DESIGN: Subjects were 246 patients enrolled in the placebo arm of a randomized, controlled trial of tobramycin for inhalation. Physician-investigators completed PEx questionnaires on all subjects at scheduled intervals during the 6-month study, indicating new or worsening symptoms, physical examination findings, and impression of PEx status (presence or absence and severity). Logistic regression was used to assess the relative importance of each of the characteristics in predicting a PEx. RESULTS: We developed 2 PEx scores that use easily ascertained symptoms and chest examination findings; one also includes change in forced expiratory volume in 1 second over the preceding month. Both scores were sensitive and specific for predicting the presence of a PEx (sensitivity, 86%; specificity, 86%). The scores were validated in subjects in the intervention arm of the trial. CONCLUSION: We hope that the proposed PEx score might serve as a standardized outcome measure for future clinical trials in cystic fibrosis, allowing meaningful comparisons of study results.