RESPIRATORY DISEASES

Health Evidence Bulletins - Wales
Team Leader: Dr Michael Burr Date of completion: 5/3/98

The contents of this bulletin are likely to be valid for approximately one year, by which time significantly new research evidence may become available


1. Cystic Fibrosis

(Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation)

The Statements The Evidence
1a. The gene associated with cystic fibrosis is now known. Antenatal screening allows parents at risk, those with a family history of cystic fibrosis, to consider their options and make appropriate arrangements.
(Health gain notation - 2 "likely to be beneficial")
Neonatal screening allows the identification of affected children early enough to preserve maximum lung function and maintain a good nutritional state.
(Health gain notation -1 "beneficial")
Genetic counselling is an important adjunct to this and in advising patients with cystic fibrosis as they survive unto adulthood and consider producing a family.
(Health gain notation -1 "beneficial")
Total population screening is not considered appropriate at this timei,ii.
(Health gain notation - 4 "unknown")
i. Phelan PD. Neonatal screening for cystic fibrosis. Thorax 1995; 50: 705-706
(Type V evidence - expert opinion);
ii. Porteous DJ, Dorin JR. Cloning the cystic fibrosis gene: implication for diagnosis and treatment. Thorax 1991; 46: 46-55
(Type V evidence - expert opinion)
1b. Continuous treatment in infancy with flucloxacillin up to the age of 2 years reduces the incidence of cough and the risk and duration of admission to hospital (mean days stay = 2.2 0.9 days for the treated group and 6.4 0.9 days for the control group during the 2nd year of treatment, p < 0.01) i.
(Health gain notation - 1 "beneficial")
Further research would be beneficial, particularly in relation to the duration of treatment.
i. Weaver LT, Green MR, Nicholson K et al. Prognosis in cystic fibrosis treated with continuous flucloxacillin from the neonatal period. Archives of Disease in Childhood 1994; 70: 84-89
(Type II evidence - randomised controlled trial)
1c. Patients whose lungs are chronically infected by Pseudomonas aeruginosa improve as measured by lung function (mean change in FEV1 = 8.6 % 95% CI, 4.6-12.6)i and hospital admissions if they receive inhaled antibioticsi,ii. Chronic colonisation can be prevented by treatment with oral and inhaled antibiotics when the organism is first detected iii.

(Health gain notation - 1 "beneficial")

i. Mukhopadhyay S, Singh M, Cater JI, Ogston S, Franklin M, Oliver RE. Nebulised antipseudomonal antibiotic therapy in cystic fibrosis: a meta-analysis of benefits and risks. Thorax 1996; 51: 364-368
(Type I evidence - meta analysis);
ii. Touw DJ, Brimicombe RW, Hodson ME, Heijerman HGM, Bakker W. Inhalation of antibiotics in cystic fibrosis. European Respiratory Journal 1995; 8: 1594-1604
(Type I evidence - systematic review);
iii. Valerius NH, Koch C, H°iby N. Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. Lancet 1991; 338: 725-726
(Type II evidence - randomised controlled trial)

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1d. Dornase alfa slightly reduces the incidence of exacerbations of respiratory symptoms (measured by the need for antibiotics and length of hospital stay) and produces slight improvement in lung function in patients with moderate impairment (FVC>40% predicted)i,ii,iii. An expert team recommends limited use in cystic fibrosis centres within agreed clinical guidelines iii.
(Health gain notation - 2 "likely to be beneficial")
caveat: Unexpected small decreases in lung-function in some patients occurred during one Phase I trial but, overall, adverse effects are generally mild and transientii.
A cost-benefit study of dornase alfa is recommended since it is expensive and has a limited benefit. It is not clear whether dornase alfa has a small effect on a wide range of patients or a larger effect on a subgroup. Such a study could be combined with comparisons with other types of treatment (inhaled antibiotics, high-dose ibuprofen)
i. Cramer GW, Bosso JA. The role of dornase alfa in the treatment of cystic fibrosis. Annals of Pharmacotherapy. 1996; 30: 656-661.
(Type I evidence - systematic review);
ii. Witt DM, Anderson L. Dornase alfa: a new option in the management of cystic fibrosis. Pharmacotherapy 1996; 16: 40-48
(Type II evidence - summary of randomised controlled trials);
iii. Payne JN, Dixon S, Cooper NJ, McCabe J. The use of DNase in cystic fibrosis. Guidance note for purchasers 96/01. Universities of Leicester, Nottingham and Sheffield: Trent Institute for Health Services Research, 1996
(Type V evidence - expert opinion)
1e. There is some evidence that continuous treatment with high doses of a non-steroidal anti-inflammatory drug (ibuprofen) slows the progression of the lung disease as measured by change in weight and FEV1 (annual rate of change = -1.48 0.69% versus -3.57 0.65% in the placebo group, p = 0.03) without serious adverse effects i.
caveat: Dosage must be monitored closely because of the risk of adverse effects.
(Health gain notation - 2 "likely to be beneficial")
i. Konstan MW, Byard PJ, Hoppel CL, Davis PB. Effect of high-dose ibuprofen in patients with cystic fibrosis. New England Journal of Medicine 1995; 332: 848-854
(Type II evidence - randomised controlled trial)

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1f. Physiotherapy assists in sputum expectoration; when it is combined with exercise there is a beneficial effect on lung function (FEV1) not shown by physiotherapy alone i.
(Health gain notation - 1 "beneficial")
i. Thomas J, Cook DJ, Brooks D. Chest physical therapy management of patients with cystic fibrosis: a meta-analysis. American Journal of Respiratory and Critical Care Medicine 1995; 151: 846-850
(Type I evidence - meta-analysis)
1g. Enteric-coated pancreatic enzyme improves fat absorption i. The dose should not  exceed 10000 U of lipase per kg body weight per day and should be adjusted until steatorrhoea is controlledii.
(Health gain notation - 1 "beneficial")
caveat: Use of high dose enzyme has been associated with an increased risk of colonic stricturesiii.
i. Dutta SK, Hubbard VS, Appler M. Critical examination of therapeutic efficacy of a pH-sensitive enteric-coated pancreatic enzyme preparation in treatment of exocrine pancreatic insufficiency secondary to cystic fibrosis. Digestive Diseases and Sciences 1988; 33: 1237-1244
(Type II evidence - randomised controlled trial);
ii. Beker LT, Fink RJ, Shamsa FH et al. Comparison of weight-based dosages of enteric-coated microtablet enzyme preparations in patients with cystic fibrosis. Journal of Paediatric Gastroenterology and Nutrition 1994; 19: 191-197
(Type II evidence - randomised controlled trial);
iii. Smyth RL, van Velzen D, Smyth AR, Lloyd DA, Heaf DP. Strictures of ascending colon in cystic fibrosis and high-strength pancreatic enzymes. Lancet 1994; 343: 85-86
(Type IV evidence - case reports)
1h. Guidelines detailing good practice for the care of patients with cystic fibrosis are availablei. It is recommended that all patients have access to a National Resource Centre or a Major Specialist Centre as an ideal, and to a Local Specialised Centre as a minimum, although this access may be achieved by shared care.
(Health gain notation - 1 "beneficial")
i. Cystic Fibrosis Trust; British Paediatric Association; British Thoracic Society. Clinical guidelines for cystic fibrosis care. Recommendations of a working group. London: Royal College of Physicians,   1996
(Type V evidence - expert opinion)

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Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: weightmanal@cardiff.ac.uk