Many cystic fibrosis (CF) patients have increased circulating levels of oxidation products and/or decreased antioxidant status. This study investigated whether treatment of pulmonary exacerbations decreased oxidative stress in CF patients.Seventeen adult patients were studied at the beginning and end of treatment with intravenous antibiotics. Plasma concentrations of the antioxidants ascorbic acid, atocopherol, uric acid and total reduced thiols, together with plasma retinol, lipid hydroperoxides, malondialdehyde and protein carbonyl levels were determined. Median (interquartile range) pretreatment and post-treatment levels were compared using the Wilcoxon signed rank test.Clinical resolution was reflected by improved spirometry. Significant increases were observed in plasma ascorbic acid (pre 30.4 (15.7±38.6) mM, post 35.2 (27.3±49.6) mM), a-tocopherol (pre 19.7 (13.6±25.2) mM, post 25.2 (19.3±31.6) mM) and retinol (pre 1.9 (1.5±2.5) mM, post 2.7 (1.7±3.5) mM). No change in plasma total reduced thiols occurred following treatment (pre 409 (366±420) mM, post 392 (366±423) mM), whereas uric acid fell with treatment (pre 307 (274±394) mM, post 260 (216±317) mM). This study demonstrated that treatment of infective exacerbations resulted in increased plasma levels of some antioxidant vitamins. No immediate change in plasma protein oxidation was observed, but lipid oxidation was decreased. Eur Respir J 1999; 13: 560±564.

Refractoriness to indirect bronchoconstrictor stimuli, is a feature of asthma but the mechanism is poorly understood. This study tested the hypothesis that endogenous nitric oxide (NO) produced during a first bronchoconstrictor challenge protects against subsequent challenge and therefore has a role in the refractory process.The effect of an NO synthase inhibitor, N G -mono-methyl-L-arginine (L-NMMA), on refractoriness to sodium metabisulphite (MBS) was investigated in 20 subjects with mild asthma. On visit one, the dose of MBS which caused a 20% fall in forced expiratory volume in one second (FEV1) (PD20) was determined. On visit two, the refractory index (RI) to MBS was determined by challenging the subjects twice with their PD20 of MBS, the second challenge proceeding after recovery from the first. Those showing a refractory index of~30% (10 subjects) inhaled either L-NMMA or placebo followed 5 min later by two challenges with their PD20 of MBS in a doubleblind cross over study at two further visits.The dose of L-NMMA used was shown to reduce exhaled NO for a duration sufficient to cover the second MBS challenge However, no significant difference was found between L-NMMA and placebo in maximum fall in FEV1% and area under the curve (AUC) during first or second MBS challenges or in RI on the two study days.It is concluded that subjects with mild asthma show refractoriness to sodium metabisulphite, but that endogenous nitric oxide is unlikely to be involved either in the refractory process or in the response to sodium metabisulphite per se. Eur Respir J 1999; 14: 702±705. Refractoriness, a reduced response to a second bronchoconstrictor challenge after recovery from the first, is well recognized with several indirect bronchoconstrictor challenges [1±3]. This may be an important physiological protective mechanism. However, the mechanisms involved in refractoriness are poorly understood. It has previously been shown that inhibitory prostaglandins may be responsible for part but not all of the refractoriness to challenges such as sodium metabisulphite (MBS) and exercise [1,3], but other factors are clearly important.Nitric oxide (NO) is a potential candidate for a bronchoprotective role in the refractory process as endogenous NO acts as a bronchodilator and neurotransmitter of inhibitory nonadrenergic noncholinergic (iNANC) nerves [4]. This might be particularly important with MBS since it is thought to cause bronchoconstriction via a neural mechanism, possibly NANC, which would be expected to cause NO release. It was hypothesized that endogenous NO produced during a first indirect bronchoconstrictor challenge might protect against subsequent challenge. If endogenous NO is involved in refractoriness then pretreatment with an inhibitor of NO production during a first challenge would prevent refractoriness induced by subsequent challenge. The authors therefore determined whether inhaled N G -mono-methyl-L-NMMA (L-NMMA) given immediately prior to an MBS challenge would prevent refractoriness in subjects wit...

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Background: ADEKs® is a new multivitamin preparation formulated specifically for cystic fibrosis (CF) patients, containing all four fat‐soluble vitamins. There is no data currently available on its use in CF. Method: We carried out a retrospective study to evaluate ADEKs® in 54 CF patients attending the specialist CF Unit at Nottingham City Hospital. Plasma vitamin A and E levels were collected from annual review reports when taking ADEKs® and a year previously when using other vitamin preparations. Dietary assessment data was available for 24 of these patients (11 children, 13 adults). Results: ADEKs® was taken for a median of 9.5 months by 19 children (mean age 11.3 years; range 7–15 years) and for 4 months by 35 adults (mean age 24 years; range 17–36 years). Median plasma vitamin A levels were significantly higher ( P<0.05) for all age groups (27% increase for 7–10 year olds, 48% increase for 11–15 year olds, 100% increase for 16+ year olds) following the change from other vitamin supplements to ADEKs®. Median plasma vitamin E levels were also significantly higher (59% increase for 7–10 year olds; 16% increase for 11–15 year olds; 26% increase for 16+ year olds). Fifteen (28%) and 9 (17%) patients went from below to within the normal plasma reference range for vitamins A and E, respectively, when changed onto ADEKs®. Four (7%) and 11 (20%) patients had values above the normal plasma range for vitamins A and E, respectively, whilst on ADEKs®. Conclusion: This study suggests that ADEKs® tablets are useful for CF patients aged over 10 years as plasma vitamin A and E levels were improved. The use of a single vitamin preparation such as ADEKs® is likely to improve compliance. We have reservations over its use amongst the 7–10 year olds because of high plasma vitamin A (3/9) and E (7/9) levels, although further research may ultimately endorse its future use within this group.