Cystic fibrosis.

There are now more adult than paediatric cystic fibrosis (CF) patients and their life expectancy continues to improve. This means that CF patients will be more commonly encountered in a variety of hospital settings including fertility services, gastrointestinal (GI) clinics, diabetes clinics, surgical wards, and acute admissions. Cystic fibrosis units welcome early contact when patients are admitted to other units and it is important to have a structured approach to their assessment and management.

What defines a pulmonary exacerbation? The perceptions of adults with cystic fibrosis.

BACKGROUND: There is no standardised definition of a pulmonary exacerbation in cystic fibrosis (CF). In attempting to achieve standardised criteria it is important to identify patient-reported indicators. METHODS: Interviews were undertaken with 47 adults with CF. Participants were asked to report symptoms experienced during a pulmonary exacerbation in two ways: the first symptoms they become aware of, and how they subsequently recognised when they were improving. RESULTS: A range of systemic and respiratory symptoms were reported. Their relative importance varied by severity of disease. The severity and subsequent improvement of an exacerbation was often described as limitations on their activities. CONCLUSION: These preliminary data suggest that patient-reported indicators of a pulmonary exacerbation may not be the same for all adults with CF. Whether different indicators are associated with specific demographic or clinical variables remains to be evaluated.

Pharmacological treatment of the biochemical defect in cystic fibrosis airways.

The understanding of the biochemical defect in cystic fibrosis (CF) has advanced considerably since discovery of the CF gene in 1989 and characterization of its product. Studies showing that the abnormality in chloride flux could be corrected by transfection of wild-type cystic fibrosis transmembrane conductance regulator (CFTR) complimentary deoxyribonucleic acid (cDNA) have led to gene therapy trials on both sides of the Atlantic. However, gene therapy as a treatment for CF has yet to be realized. Pharmacological manipulation of the biochemical defect may provide an alternative or complementary approach to treatment. This review will discuss pharmacological agents in development which could correct the abnormal ion movement. The mechanisms of action of these pharmacological agents can be divided broadly into drugs which affect the most common CF mutation, deltaF508, which increase trafficking of the mutant CF protein to the apical membrane; drugs which increase chloride secretion; and drugs which reduce sodium reabsorption across the apical membrane. Treatment options for cystic fibrosis have developed rapidly since discovery of the cystic fibrosis gene over a decade ago. The targeting of specific therapies for particular cystic fibrosis genotypes and the use of combination treatments of chloride channel openers with sodium channel blockers are likely to be key advances in the next decade.

Questionnaire survey of male infertility in cystic fibrosis.

Most male cystic fibrosis (CF) patients are infertile due to obstructive azospermia but little is known about the best time to counsel patients on infertility. All male patients attending the Adult Nottingham CF unit were invited to complete an anonymous questionnaire on infertility. The response rate was 60%. The median age that the patients first became aware of male infertility was 17 years (range 13-24) but the preferred age of receiving this information was 14 years (range 8-16). Patients first learnt about male infertility from the CF team (six patients), parents (five), from written information (two) or unexpectedly (five). Five out of 18 patients had undergone seminal analysis at a median age of 26 years but 17/18 patients felt that this should be offered routinely. Our survey has shown that patients would like infertility discussions at a younger age and routine seminal analysis.

Successful pregnancy and birth after IVF in a woman with cystic fibrosis.

As survival increases, patients with cystic fibrosis (CF) are often confronted with reproductive issues. Initial reports gave conflicting advice regarding the outcome of pregnancy in CF. However a recent large longitudinal study of pregnancies in CF women suggested that pregnancy has little impact on morbidity or mortality. Reduced fertility in CF women has been described, possibly due to thickened cervical mucus, and intrauterine insemination (IUI) has been used to overcome this. We report the first woman with CF, to our knowledge, to be successfully treated with IVF after repeated failed attempts at IUI.

The effect of topical benzamil and amiloride on nasal potential difference in cystic fibrosis.

The electrochemical defect in the bronchial epithelium in cystic fibrosis (CF) consists of defective chloride secretion and excessive sodium reabsorption. The sodium channel blocker, amiloride, has been shown to reversibly correct the sodium reabsorption in CF subjects, but long term studies of amiloride have been disappointing due to its short duration of action. Benzamil, a benzyl substituted amiloride analogue, has a longer duration of action than amiloride in cultured human nasal epithelium. The results of the first randomized, placebo controlled, double blind, crossover study are reported here comparing the effects of benzamil and amiloride on nasal potential difference (nasal PD) in CF. Ten adults with CF attended on three occasions. At each visit baseline nasal PD was recorded, the drug (amiloride 1 x 10(-3) M, benzamil 1.7 x 10(-3) M, or 0.9% sodium chloride) was administered topically via a nasal spray, and nasal PD was measured at 15, 30 min, 1, 2, 4 and 8 h. Results were expressed as maximum change in nasal PD from baseline (PDmax), time for PDmax to return to 50% of baseline (t0.5), and the area under the curve (AUC). PDmax values for benzamil (20.6+/-0.9 mV) and amiloride (20.3+/-1.6 mV), were similar. The duration of effect was much longer for benzamil as measured as either AUC or t0.5 AUC values were 11.8+/-1.6 mV for benzamil, 2.8+/-0.4 mV for amiloride and 0.6+/-0.4 mV for placebo. The AUC value for benzamil was significantly greater than amiloride (95% confidence interval (CI) for the difference 5.3-12.7 mV, p<0.0001). t0.5 values were 4.3+/-0.7 h for benzamil and 0.6+/-0.1 h for amiloride (95% CI for the difference 2.0-5.3 h, p<0.001). It is concluded that benzamil has a similar maximal effect to amiloride but a more prolonged duration of action on nasal potential difference in cystic fibrosis. Benzamil may be a useful sodium channel blocker for the long-term treatment of the biochemical defect in the lungs of patients with cystic fibrosis.

Totally implantable venous access devices in cystic fibrosis: complications and patients' opinions.

The introduction of totally implantable venous access devices (TIVAD) has provided a solution to difficult venous access in patients with cystic fibrosis. Early reports have, however, recognized a number of complications with their use. We report our experience with five devices used over 8 yrs with regard to complications and patient attitudes. Patients' notes were reviewed to record the details of TIVAD insertion, duration of function, and complications. In January 1996 the surviving 30 patients were surveyed on their attitudes to TIVAD and complications by written questionnaire. Sixty one ports were implanted in 42 patients (aged 16-47 yrs) between June 1988 and January 1996, giving a total of 1,510 patient-months' experience. The duration of function ranged from 2 weeks to 6 yrs. Survival analysis showed that the median survival of ports was 53 months, 42 out of 61 (69%) had not failed in service at the end of follow-up or patient death. Twenty-three complications occurred in 19 patients. These included: line occlusion (10 patients), venous thrombosis (4), difficult access (3), infection (2), cellulitis (1), inversion of port chamber (2) and pneumothorax (1). The questionnaire showed that patients had strong views on the positioning of their port. Lifestyle issues included interference with seatbelts (8 patients), sport (4), clothing (2), sexual relations (2) and cosmetic appearance (15). Complication rates were similar to those in other studies, although infection rates and salvage of an occluded port were lower. The survey highlighted a number of lifestyle issues, with cosmetic appearance deemed unsatisfactory by half of the patients. However, the majority (28 out of 30) believed their totally implantable venous access devices to be a better alternative to cannulae or long lines.