A.O.B. Redmond

Evaluation of the PEP mask in cystic fibrosis

ABSTRACT. Twenty‐eight patients suffering from cystic fibrosis, with an age range of 8‐21 years entered a randomised cross‐over trial to study the efficacy of the Positive Expiratory Pressure (PEP) mask as a method of chest physiotherapy, both on its own and in conjunction with other physiotherapy techniques. Twenty‐four of these patients completed the trial consisting of 4 treatment programmes each lasting one month and with no wash‐out period between them. Five of these patients went on to a fifth programme of Forced Expiratory Technique (FET) alone. At the end of the trial, no significant difference was found between the programmes as regards growth, Shwachman score, Chrispin—Norman score or pulmonary function tests. Twenty‐three patients chose to continue using the PEP mask in conjunction with FET long‐term as their chest physiotherapy programme as they felt it was an effective treatment allowing increased independence, with postural drainage being kept to a minimum.

Clinical Features Associated with a Delayed Diagnosis of Cystic Fibrosis

Background: The majority of patients with cystic fibrosis (CF) are diagnosed in the first decade of life. In a small number of patients, the diagnosis is not made until later. Objective: In this study, the clinical and genetic features of patients diagnosed after the age of 10 were examined. Methods: All living patients in Northern Ireland diagnosed prior to 1983, when neonatal screening was introduced, were studied. A total of 103 patients were identified of whom 18 were diagnosed after the age of 10. The relationships between late diagnosis and clinical presentation, sputum microbiology, pancreatic sufficiency, nutritional status, genotype and distance from the regional CF centres was determined by multiple regression analysis. Results: All 18 late-diagnosed patients had a sweat (chloride >70 mmol/l). Late diagnosis was significantly related to carriage of the R117H mutation (r2 = 0.45) and pancreatic sufficiency (r2 = 0.37). There was a weak relationship with pulmonary function (r2 = 0.09). Conclusions: In Northern Ireland, late diagnosis in mainly associated with pancreatic function and carriage of the R117H mutation.

Clinical outcome after acquisition of Burkholderia cepacia in patients with cystic fibrosis.

BackgroundRespiratory disease is the major cause of morbidity and mortality in cystic fibrosis (CF). The significance ofBurkholderia cepacia (B. cepacia) in the pathogenesis of lung disease in CF is debated, but its exact role remains unclear.AimTo assess the impact of respiratory tract colonisation withB. cepacia in patients with CF by measuring changes in pulmonary function and body mass index (BMI).MethodsThree groups of patients were defined based on sputum culture isolates: Group 1 wereB. cepacia andPseudomonas aeruginosa (P. aeruginosa) positive patients; Group 2 wereP. aeruginosa positive; and Group 3 were colonised with neither organism. Forced expiratory volume (FEV1) and BMI were measured annually from 1987 to 1995 and the year of acquisition ofP. aeruginosa orB. cepacia was recorded.ResultsThe mean annual decrease in FEV1 was significantly different in all three groups: Group 1, −5.4 (5.1)%; Group 2, −3.9 (6.5)%; and Group 3, −1.6 (1.0)%, (p<0.05). The mean percentage decrease in FEV1 of a sub-group of Group 1 patients where theB. cepacia acquisition date was known was 6.1% per year versus 1.55% in Group 2 patients (p<0.05).ConclusionsAcquisition ofB. cepacia may be a cause of, rather than a marker for, a decrease in pulmonary function.

Mutation characterization of CFTR gene in 206 Northern Irish CF families: Thirty mutations, including two novel, account for ∼94% of CF chromosomes

A variety of mutation detection techniques, including restriction endonuclease digestion, allele specific oligonucleotides, and automated fluorescent sequencing, were used in the identification of 15 CFTR mutations representing 86.7% of CF chromosomes in 206 Northern Irish cystic fibrosis (CF) families. A systematic analysis of the 27 exons and intron/exon boundaries of the CFTR gene was performed using denaturing gradient gel electrophoresis (DGGE) in an attempt to characterise the 55 unknown CF mutations in 51 patients. Twenty different mutations were detected by DGGE on 30 chromosomes accounting for a further 7.3% of CF alleles. Fifteen of these mutations had not previously been found in Northern Ireland, and two are novel, M1I(G>T) and V562L. In total, 30 CFTR mutations account for 93.9% of the 412 Northern Irish CF chromosomes tested. The three major CF mutations in Northern Ireland are ▵F508, G551D, and R117H with respective frequencies of 68.0%, 5.1%, and 4.1%. The efficacy of the DGGE technique was proven by the detection of 77 out of 77 control variants from all the CFTR exons. DGGE is a highly efficient and sensitive method for mutation screening especially in large genes where the mutation spectrum is known to be heterogeneous.

INSULIN AND GLUCAGON RESPONSE TO ARGININE INFUSION IN CYSTIC FIBROSIS

Abstract Redmond, A. O. B., Buchanan, K. D. and Trimble, E. R. (The Royal Belfast Hospital for Sick Children, Belfast, and The Department of Medicine, Queens University, Belfast). Insulin and glucagon response to arginine infusion in cystic fibrosis. Acta Paediatr Scand, 66:199, 1977.—The glucagon and insulin responses to intravenous arginine were studied in 17 children with cystic fibrosis and in 9 control children. It was found that the overall secretion of insulin was diminished; however, four of the CF children did have a normal output. The glucagon responses did not parallel those of insulin. The glucagon output varied in the CF children—seven had normal, four excessively high and six low output. Three of the four children with extremely high output had more severe disease and were below the third centile on the weight chart. These four had a fasting hypoglycaemia and also a very low glucose and insulin response. We have confirmed diminished insulin secretion in cystic fibrosis, but diminished glucagon secretion was only noted when some insulin secretion was preserved. The high levels of glucagon seen in the most insulin deficient subjects may be derived from extrapancreatic sources, or may be associated with ‘stress‘ reaction in these patients who also had most severe pulmonary involvement. The data would be consistent with diminished glucagon and insulin secretion from the pancreas but as the disease progresses an excessive secretion of extra pancreatic glucagon results.

Detection of cystic fibrosis homozygotes and heterozygotes by serum isoelectrofocusing

SummaryIt is suggested that the majority of individuals with the cystic fibrosis (CF) gene have a unique serum protein (CFP) which can be demonstrated by means of isoelectrofocusing (IEF) in thin layer polyacrylamide gels. We have found the CFP in 90% of patients with cystic fibrosis, in approximately 80% of individuals heterozygous for the CF gene, and in 8% of normal control individuals. We conclude that CFP is a useful marker for the CF gene.

Comparison between a standard pancreatic supplement and a high enzyme preparation in cystic fibrosis

This study compared the relative effectiveness of a standard pancreatic enzyme supplement (‘Creon’, Duphar) and a new preparation (‘Pancrease HL’, Cilag) containing about 3 times the lipase and more than 5 times the protease activity. Capsule dosage was adjusted to a ratio of approximately 3:1. Fat balances showed that absorption of fat did not change significantly on conversion to the new high‐lipase product, and the coefficient of absorption of total energy was similarly maintained. The coefficient of protein absorption was significantly enhanced with the high enzyme preparation (P < 0.01), which may explain the reported subjective improvement in stool odour. No adverse effects were recorded. Patient acceptability of the new compound was high; the great reduction in the number of capsules required at each meal was cited by all patients as the reason for their preference.

A review of cystic fibrosis children born to single mothers

The purpose of this study was to examine the relationship between single parents and the health of their children with cystic fibrosis. Seventy‐five children aged between 0.8 and 6.0 y were identified from our patient register; 20 of these children came from single parent families. Socioeconomic profiles were collated for each family. Retrospective medical data including, gene mutation analysis, were recorded from the hospital notes of all 75 patients. Maternal health was assessed by means of the General Health Questionnaire (28‐item version). The results show that maternal age of ≤19y and lone parenthood were associated with higher morbidity in CF patients <6y of age. Predicted values of the Shwachman score being lower by 4.1 and 4.3 points, respectively. A declining Shwachman score of 1.1 points/y was associated with increasing patients age. In addition, analysis showed that the CF children of teenage mothers were 16 times more likely to have admission rates of ≥1/y. Single mothers experienced more stress‐related symptoms than those from the married group. We concluded that the young CF children of single or teenage mothers have a significantly worse clinical progress and consequently have a higher demand for hospital services. Clearly this population requires extra clinical vigilance and social support.

Fluorescent multiplex microsatellites used to identify haplotype associations with 15 CFTR mutations in 124 Northern Irish CF families

The cystic fibrosis transmembrane conductance regulator gene contains three highly informative microsatellites; IVS8CA, IVS17BTA and IVS17BCA. Fluorescent multiplexes of these microsatellites were assayed in 124 CF families carrying 15 different CFTR mutations, from N. Ireland.

Pancreatic enzyme supplements in cystic fibrosis

Approximately 95% of patients in Northern Europe are pancreatic insufficient due to an inadequacy of their own pancreatic enzyme secretions (Littlewood et al, 2006). These patients need to take pancreatic enzyme replacement therapy (PERT) in order to prevent the symptoms of fat malabsorption. These symptoms include frequent pale, oily and offensive stools, abdominal pain, poor growth and deficiencies of fat soluble vitamins and essential fatty acids.