Hospital Pharmacist
Vol 9 No 4 p114
April 2002

Improving the management of cystic fibrosis

Seventy years ago, 70 per cent of babies born with cystic fibrosis (CF) died within the first year of their lives, and even just 40 years ago, half of all patients failed to reach age two.

Advances in the treatment of CF mean that children born in the 1990s can expect to live to an age of 40. Although this is a major improvement, it is also an indication that a great deal of further research and work needs to take place.

The audience of CF consultants, pharmacists, physiotherapists, dietitians and nurses at last month's Midlands cystic fibrosis spring symposium heard about some of the latest research on CF, which is the most common fatal genetic disease in Caucasians. The symposium, chaired by Professor Alan Knox of Nottingham City Hospital and Dr Peter Weller of Birmingham Children's Hospital, looked at the importance of good bone health, avoiding pseudomonas infection where possible, and optimising treatment.

Dr Steve Conway, consultant paediatrician at St James's Hospital, Leeds, began the symposium with an overview of osteoporosis in CF patients. Reduced bone mineral density (BMD) in adults and children with CF was first documented nearly 25 years ago, and during the past decade it has become, increasingly, a key issue in patient care.

Research shows that many factors may contribute to the risk of CF patients developing osteopenia, a reduction in bone mineral density which can progress to osteoporosis. These include malabsorption and poor nutrition associated with CF, low body mass and low levels of fat-soluble vitamins.

"By altering the chest wall structure, a vertebral or rib fracture may impact the way that CF patients can breathe, as well as the way their lungs function," explained Dr Conway. "Coughing and physiotherapy become painful. Mucociliary clearance is reduced, and infection gains an advantage."

It has been shown that patients with end-stage lung disease have a significant reduction in BMD, and two studies of large unselected adults with CF found osteopenia in over 40 per cent, and osteoporosis in one third (Thorax 1999;54:961–7; Thorax 2000;55:798–804).

Dr Conway demonstrated that a number of studies have shown normal bone mineral density among children — but he cautioned against drawing this conclusion.

"Our own more recent work, among many children with CF, indicates important differences in BMD compared with controls, in today's children. I would suggest in all but very young children, BMD should be monitored. Nutrition should be optimised and other possible causes of low BMD should be treated, such as hypogonadism and thyroid problems," advised Dr Conway.

Dr Conway concluded by reviewing the key measures for preventing osteoporosis, such as vitamin D and K supplementation, weight-bearing exercise where bone health allows and adequate calcium intake.

Pseudomonas infection

The most common bacterium to infect the CF lung is Pseudomonas aeruginosa, a micro-organism with a propensity to live in warm, wet environments. Most patients with CF suffer from recurrent and chronic PA infections, but it is possible to prevent or delay the onset of these infections.

"The management of early PA infection is important for a variety of reasons," explained Professor Kevin Webb, Cardiothoracic Medicine, Wythenshawe Hospital. "Once patients are infected with PA they require more treatment. In terms of health, quality of life and cost effectiveness, it's much better to remain without pseudomonas."

Guidelines for the prevention and control of PA, issued by the Cystic Fibrosis Trust, highlight three main factors: microbiological surveillance, hygiene and segregation. "The more controversial issue is segregation," commented Professor Webb. "We now segregate our PA-negative patients in six or seven different ways, and our PA-positive patients do not object." [Segregation of patients can be organised for both inpatients and outpatients. For example, inpatients should use separate bathrooms and toilets; clinics for outpatients with and without infection should be held at different times.]

There are still a number of question marks over how best to treat initial colonisation with PA. A study by Ratjen et al, (The Lancet 2001;358:983) reveals that in 14 of 15 patients with CF who had been colonised with PA, inhaled tobramycin, administered twice daily for 12 months, successfully eradicated the organism. The therapy regimen maintained pulmonary function at high levels.

"There is currently no 'best' treatment, and we need comparative studies of what is available. Should we be going straight into IV antibiotics, and if so, what is the correct dosage? It is definitely important to aggressively treat first colonisation of PA, but exactly how we should be going forward is less clear," Professor Webb concluded.

Latest advances

Currently, the main treatments for CF include physiotherapy to reduce airway obstruction, antibiotics, nebulisers, nutritional supplements, pancreatic enzyme supplements and the newer dornase alfa, (brand name Pulmozyme), the first treatment that specifically improves lung function in CF patients. Dornase alfa works by liquefying the DNA in the mucus that collects in the lungs. One question for clinicians is whether to add dornase alfa to existing CF therapy in patients with mild to moderate disease.

Presenting the results of a recent study, the Pulmozyme early intervention trial (PEIT), internationally renowned CF expert Dr Harm Tiddens, lead investigator of the study and chairman of the Sophia Children's Hospital CF team at the Erasmus Medical Centre in Rotterdam, The Netherlands, showed that dornase alfa treatment can significantly reduce infections in six to 10-year-old CF patients with mild lung function abnormalities. "The PEIT data confirms that dornase alfa reduces respiratory tract infections by 34 per cent and maintains lung function,"said Dr Tiddens.

Findings from the two-year, randomised 474-patient 49-centre study, published last December (The Journal of Pediatrics 2001;139:813–20), show that dornase alfa has a beneficial effect on the peripheral airways, where the disease is most active in the early stages. The effect on the forced expiratory flow_25-75 (forced expiratory time to exhale middle range volume) was particularly marked, with a 7.9 per cent difference in favour of dornase alfa.

"Young patients with good lung health are going to lose their lung function — and this is what we need to prevent," said Dr Tiddens.

Ms O'Connell is a freelance journalist