We measured gastric lipase activity and lipolysis in postprandial gastric samples from 10 adults with steatorrhoea due to cystic fibrosis (CF) and from 10 healthy volunteers of similar age and sex. Gastric samples were aspirated for 2 h following a meal consisting of emulsified long-chain triglyceride. Mean acid-resistant lipase activity was twice as high in CF patients as in controls (596 vs. 299 nmol/ml/min fatty acid released; p = 0.028 for area under the curve). Lipolysis rose from 5 to 10% during the postprandial period in CF patients, compared with a constant 5% in controls (p = 0.036 for area under the curve). We conclude that, in healthy adults, lipolysis of long-chain triglyceride starts in the stomach, while in adults with pancreatic steatorrhoea due to CF, gastric lipase activity and intragastric lipolysis are increased, perhaps in compensation for pancreatic insufficiency.

Following our previous report that thrombocytosis and platelet hyperaggregability (as tested in platelet rich plasma) occur in patients with cystic fibrosis (CF), we have now examined whether this thrombocytosis is related to leukocytosis, and whether platelet hyperaggregability can be documented in whole blood using impedance aggregometry. Our observations show that platelet counts are related to white cell counts (r = 0.34; p = 0.001) and that therefore thrombocytosis may be part of a secondary response to bronchopulmonary infection, which is characteristic of these patients. Platelet counts were, however, not related to serum iron concentration despite the finding of varying degrees of iron deficiency in approximately 50% of patients with cystic fibrosis. Whole blood aggregometry demonstrated platelet hyperaggregability in patients with cystic fibrosis independently of platelet counts. Platelet aggregation (in platelet rich plasma and in whole blood) was normal in obligate heterozygotes, thus suggesting that platelet hyperaggregability in CF is not a consequence of abnormal genetic information.

Vitamin D and parathyroid hormone concentrations were assessed in 31 adults with cystic fibrosis (mean age 24, range 17-52 years), in 28 of whom the bone mineral index in the forearm was also determined. Serum 25-hydroxyvitamin D was subnormal in eight patients, of whom five were receiving vitamin D supplements in standard doses. 1,25-dihydroxyvitamin D and parathyroid hormone concentrations showed no consistent abnormalities. The bone mineral index was lower in patients with cystic fibrosis (p less than 0.02) than in controls. Five patients with unequivocally reduced bone mineral index had a subnormal mean serum 25-hydroxyvitamin D and significantly worse lung function than the other patients. There was a positive correlation between age and bone mineral index (r = 0.68, p less than 0.001). Thus a significant proportion of patients with cystic fibrosis living in a temperate climate are at risk of vitamin D deficiency. Osteopenia is common and is probably related to a combination of hypovitaminosis D, delay in puberty, hypo-oestrogenism in women, and reduced physical activity, rather than to secondary hyperparathyroidism. Since most patients with deficiency of 25-hydroxyvitamin D were receiving oral supplements, parenteral vitamin D supplementation may be appropriate for selected patients who are unable to maintain adequate 25-hydroxyvitamin D concentrations despite oral vitamin D supplements.

Musculoskeletal symptoms are frequent in cystic fibrosis (CF). Here the clinical features of 29 patients with CF who had significant arthropathy are described. Twelve had episodic arthritis (EA) characterised by repeated short attacks of severe, incapacitating polyarthritis, which in seven was associated with fever and erythema nodosum. Ten patients had hypertrophic pulmonary osteoarthropathy (HPOA). The onset of symptoms in the group with HPOA was usually later (mean age 20 years v 16 years for EA) and was associated with significantly worse lung function than in patients with CF, either without arthropathy or with EA. Seven patients had arthropathies which could not be classified as EA or HPOA.

Levels of serum immunoglobulins and immunoglobulin G subclasses were measured in 32 cystic fibrosis (CF) patients, 30 asthmatics and 27 controls. When compared with the asthmatic patients and controls, the CF patients had raised levels of all IgG subclasses as well as total IgG, IgM and IgA, but there was not a statistically significant increase in IgE. The levels of immunoglobulins in the CF patients were examined in relation to the clinical features of the disease. Raised levels of IgG4 were related to levels of IgE, but these raised levels of IgG4 appeared to be part of a general increase in total IgG and not an isolated feature. There was a significant correlation between the total IgG level and its subclasses, IgG1, IgG2, IgG3, IgG4 and IgA. IgG1 was significantly correlated with IgG2 and IgG4; IgG2 with IgG4; and IgG4 with IgE. Total IgG was the immunoglobulin most closely correlated with poor lung function. Serum IgA was higher in patients with positive immediate skin prick reactions to pollens (p less than 0.005) and death within two years of the study was related to high levels of total IgG (p less than 0.01), IgG3 (p less than 0.001), IgA (p less than 0.001), and IgE (p less than 0.005).

Platelet function was investigated in 15 patients with cycstic fibrosis (CF) and in ten age-matched controls. Marked hyperaggregability of platelets to adrenaline, collagen and arachidonic acid was observed in platelet rich plasma (PRP) prepared from patients with cystic fibrosis. Thromboxane A2 (TXA2) release from these platelets was also markedly enhanced. Hyperaggregability and increased TXA2 release observed in patients with CF was not due to the higher platelet counts in these patients since hyperaggregability was observed even in those patients whise platelet counts were similar to those in controls. Platelet hyperaggregability and increased thromboxane release in these patients were also independent of their body weight and occurred despite supplementation with vitamin E. Hyperaggregability of platelets in CF may be clinically relevant since it may contribute to the pathogensis of bronchoconstriction through the release of TXA2 and other bronchoconstrictor platelet products such as serotonin.

In an open, randomised crossover study enteric coated microspheres of pancreatin were compared with a standard preparation of enteric coated pancreatin over two consecutive 28 day treatment periods in 23 adults with steatorrhoea due to cystic fibrosis. Lipase intake was equal to the patients' previous requirements and was the same during the two months. Patients performed 72 hour faecal collections at the end of each month and completed diary cards daily throughout. Comparison of the month of treatment with enteric coated microspheres with the month of standard enteric coated tablets showed a significant increase in body weight on microsphere capsules (p less than 0.02). There was also a reduced frequency of bowel actions (p less than 0.001) and abdominal pain (p less than 0.05), and improvement in stool character (p less than 0.001) on microsphere capsules. Faecal fat excretion was reduced by 44% with the microsphere capsules (p less than 0.01), and 86% of patients showed an increased coefficient of fat absorption (mean increase 13%, 95% confidence limits 6.5-19.1%; p less than 0.001). Eighty one per cent of patients preferred microsphere capsules of the two treatments. Thus enteric coated microsphere capsules are more effective in treating steatorrhoea in cystic fibrosis than standard enteric coated tablets.

A randomized cross-over study was undertaken to compare nebulized (1) ceftazidime with (2) a combination of gentamicin and carbenicillin, and (3) saline, each given for 4 months, in patients with cystic fibrosis infected with Pseudomonas aeruginosa. Mean peak expiratory flow on ceftazidime, 299 litres/min, and on gentamicin and carbenicillin, 297 litres/min, were greater than on saline, 278 litres/min (P<0.02 and P<0.05 respectively). Similarly, mean forced expiratory volume in 1 second on ceftazidime, 1.70 litres, and on gentamicin and carbenicillin, 1.70 litres, were greater than on saline, 1.48 litres (P<0.02 and P<0.01 respectively). Mean forced vital capacity on gentamicin and carbenicillin, 2.93 litres, was also greater than on saline (P<0.05). We were unable to demonstrate any difference in efficacy between the antibiotic regimens. The patients were admitted to hospital less frequently during the study year compared with the previous year (P<0.05). Sixty-nine per cent of patients had a clinically significant (20%) increase in forced expiratory volume in 1 second on an antibiotic regimen compared with that on entry to study, but a minority of patients appear not to respond to this form of treatment.

Circulating lymphocytes subpopulations and their function have been studied in 25 young adults with cystic fibrosis (CF) and 25 normal controls. Mean absolute numbers of all lymphocyte subsets in the CF group were not significantly different from the controls. Antibody-dependent cell cytotoxicity was significantly higher in the CF patients who had Pseudomonas aeruginosa in their sputum compared with those who had not and compared with the normal controls. Within the CF group the numbers of B cells, total T cells and OKT4+ helper cells fell as percent predicted peak expiratory flow (PEF) declined and similar significant positive correlations were found between lymphocyte subsets and percent predicted body weight. Serum albumin levels also showed a positive correlation with total T lymphocyte numbers (p less than 0.05). In vitro lymphocyte proliferative responses to mitogen were not significantly different from the control group, but again correlated positively with body weight in the CF patients. This provides further evidence that immune function in CF patients may become impaired as pulmonary disease and nutritional status deteriorate.

40 adult patients with cystic fibrosis (CF) were admitted to hospital with acute exacerbations of infection associated with isolation of Pseudomonas aeruginosa from sputum. The patients were randomly allocated (20 per group) to receive intravenous azlocillin 5 g and gentamicin 80 mg, or oral ciprofloxacin 500 mg. Both treatments were given three times a day for 10 days. The patients were assessed on days 1 and 10, and at 6 weeks. There was a significant improvement in lung function between days 1 and 10 in both groups (p< 0·001). Significant improvement was maintained at 6 weeks after ciprofloxacin but not in the intravenous group. Improvement after ciprofloxacin was superior at day 10. Sputum weight decreased in both groups (p < 0·001). Patient-recorded symptoms also improved in both groups. There was no serious toxicity or side-effects. Drug resistant organisms were isolated no more frequently after ciprofloxacin than after intravenous therapy. 17 of the ciprofloxacin-treated patients said they preferred oral treatment to intravenous therapy. Oral ciprofloxacin is a useful short-term treatment for patients with CF who are infected with Ps aeruginosa.

The pharmacokinetics of the commonly used contraceptive steroids ethinyloestradiol and levonorgestrel were investigated after oral and intravenous administration in six women with cystic fibrosis. The results were compared with data obtained from healthy women of similar age. The total body clearance of ethinyloestradiol was significantly higher in the patients with cystic fibrosis (0.61 (SD 0.19) l/h/kg) than in control women (0.32 (0.16) l/h/kg; p less than 0.02). In addition, the oral bioavailability of ethinyloestradiol was greater in women with cystic fibrosis than in controls (76.9% (11.7%) compared with 47.3% (7.5%); p less than 0.001). As a result of these two changes, the area under the plasma concentration--time curve after an oral dose of ethinyloestradiol was similar in patients and controls. The pharmacokinetics of levonorgestrel did not differ significantly between patients with cystic fibrosis and healthy women. The data suggest that women with cystic fibrosis will receive similar contraceptive protection from these steroids as do healthy women.The pharmacokinetics of the contraceptive steroids ethinyl estradiol and levonorgestrel following oral an intravenous administration were investigated in 6 women with cystic fibrosis. The results were compared with data from healthy controls of similar ages. The bioavailability of ethinyl estradiol was significantly greater in women with cystic fibrosis (76.9%) than in controls (47.3%), but the area under curve after oral administration was similar in both groups. There was a significantly greater total body clearance in women with cystic fibrosis (0.61 1/hr/kg) than in controls (0.32 1/hr/kg). The volume of distribution was not significantly different in patients and controls; thus there was a tendency (nonsignificant) for the elimination half-life and area under curve after the intravenous dose to be less in the women with cystic fibrosis. In terms of levonorgestrel, there were no significant differences between subjects and controls in any of the pharmacokinetic variables studied. These results suggest that the absorption of ethinyl estradiol and levonorgestrel is not impaired by cystic fibrosis. Women with this disease will achieve plasma concentrations of these steroids after an oral dose of a combined oral contraceptive similar to those obtained in healthy women. However, patients with cystic fibrosis should be monitored closely while taking the pill to ensure that vaginal blood loss is regular with no evidence of breakthrough bleeding.

Patients with cystic fibrosis tend to have reduced serum concentrations of vitamin E and are therefore at risk of developing the neurological complications associated with vitamin E deficiency. Improved survival in cystic fibrosis has resulted in an increasing number of older patients who may develop hepatobiliary complications which may further impair the absorption of vitamin E. In this study the vitamin E status and results of supplementation with oral vitamin E were compared in adult patients with and without evidence of liver involvement as assessed by routine liver function tests. The serum vitamin E concentrations were reduced below normal in 24 of 25 patients. The mean serum vitamin E concentration was significantly lower (p less than 0.05) in those patients with abnormal liver function. When vitamin E status was assessed as the serum vitamin E/cholesterol ratio, however, there was no significant difference between those patients with normal and abnormal liver function. After supplementation with oral vitamin E, either 10 mg/kg/day for one month or 200 mg/day (equivalent to 3.4 to 4.4 mg/kg/day) for up to three months, there was no significant difference in the vitamin E status between the two groups. The results of this study indicate that in general, patients with cystic fibrosis and abnormal liver function do not require increased supplements of vitamin E compared with those with normal liver function.