Therapeutic equivalence of inhaled beclomethasone dipropionate with CFC and non-CFC (HFA 134a) propellants both delivered via the Easibreathe inhaler for the treatment of paediatric asthma.

Chlorofluorocarbon (CFC)-containing inhalers for use in the treatment of asthma are to be phased out under the terms of the Montreal Protocol (1). In this multi-centre, randomized, double-blind study, the therapeutic equivalence of two formulations of beclomethasone dipropionate (BDP) containing CFC or non-CFC (HFA134a) propellant, both delivered via the Easibreathe (Norton Healthcare Ltd, London, U.K.) inhaler, was determined in 229 asthmatic children. Each child received 100 microg doses of BDP (containing either CFC or HFA propellant) twice daily for 12 weeks. Both CFC and HFA formulations produced statistically and clinically significant improvements in patient's lung function and symptom scores when administered via the Easibreathe inhaler. The improvements in mean morning peak expiratory flow (PEF) were 41 l min(-1) and 34 l min(-1) for the BDP-HFA and BDP-CFC products respectively (P<0.001) and for mean evening PEF the improvements were 38 l min(-1) and 38 l min(-1), respectively (P<0.001). Similar findings were demonstrated for the other efficacy parameters. The two formulations were statistically equivalent with respect to efficacy. For mean morning PEF the estimated treatment difference (BDP-CFC/BDP-HFA ratio) was 102.6% (95% CI 99.1, 106.2). Similar equivalence was shown for the other efficacy parameters. Both products were well tolerated, with no difference in the adverse event profiles, effects on 24 h urinary cortisol or Candida colonisation. This study demonstrates that the new formulation of BDP with HFA-134a propellant is equivalent to and directly substitutable for BDP with the older CFC propellant in a dose for dose manner. This should enable a seamless transition from one product to the other when CFC containing products are eventually phased out. In addition this study has also shown that the Easibreathe inhaler is an effective delivery system for use with inhaled products for the treatment of asthma in children.

The energetics of Escherichia coli during aerobic growth in continuous culture.

1. The energetics of Escherichia coli W growing aerobically in continuous culture have been investigated. Conditions were chosen such that growth was limited by the availability of carbon or oxygen (energy-limited cultures), or of ammonium of sulphate ions (excess energy cultures). 2. Under glycerol-limited conditions YmaxO2 (true molar growth yield with respect to oxygen) and YmaxATP (true molar growth yield with respect to ATP equivalents) were 50.9 g cells-mol O-02(-1) and 12.7 g cells-mol ATP equivalents-1 respectively; these values were not substantially altered during growth limited by oxygen, ammonium or sulphate. In contrast, M (the energy requirement for maintenance purposes) increased from approximately 2 mmol ATP equivalents-h-1-g cells-1 during energy-limited growth to 16.8 and 30.8 mmole ATP equivalents-h-1-g cells-1 when growth was limited by ammonium and sulphate ions respectively. 3. Replacement of glycerol by other limiting carbon sources caused YmaxATP to alter within the range 13.9 (glucose) to 7.1 (acetate) g cells-mol ATP equivalents-1 in the order glucose greater than galactose greather than arabinose greater than fructose greater than glycerol greater than fumarate greater than lactate greater than pyruvate greater than acetate. In each case the experimental value of YmaxATP was less than or equal to 55% of the theoretical value calculated from the known energy requirements for the biosynthesis of cell materials. 4. It is concluded from these results that neither M nor Ymax ATP are constant values for E. coli. M varies with the energy supply, being highest under excess energy growth conditions where it may reflect energy wastage by the cell. On the other hand, YmaxATP varies with the nature of the growth substrate and thus reflects the different energy requirements for the synthesis of cell material from different carbon sources.