Anthony D. Milner

Bilirubin and ascorbate antioxidant activity in neonatal plasma

Extremely low birth weight premature infants have been known for many years to have limited antioxidant protective capacity, especially with reference to those antioxidant components which do not cross the placenta until the third trimester of gestation. In this study the total antioxidant activity and the concentrations of individual antioxidants in plasma from premature neonates (27 ± 2 weeks gestation) compared to term babies (38–41 weeks gestation) have been examined. The results show elevated levels of ascorbate at birth in the plasma of premature neonates compared with those of term babies, but the total plasma antioxidant status of the premature babies is significantly lower than that of term babies. At 5 days post‐partum the ascorbate levels are within the normal adult range and plasma bilirubin levels are considerably enhanced in both groups, while the total plasma antioxidant status of the premature neonates has increased. Analysis of the relationship between the total plasma antioxidant activity and the bilirubin concentration show a direct, highly significant correlation for the term group, r 2 = 0.774, consistent with significance of bilirubin as a plasma antioxidant.

Drug delivery from jet nebulisers.

Maximising the rate of drug delivered in particles small enough to reach the lower respiratory tract from jet nebulisers may allow treatment times to be reduced and thus improve the acceptability of this form of treatment, particularly in very young patients. The role of various technical factors such as driving gas flow (DGF) in determining the rate of drug delivery was studied by constructing a model to simulate the respiratory pattern of individuals with different tidal volumes using a Starling ventilator and filter. Sodium cromoglycate was nebulised under a variety of operating conditions and the dose deposited on the filter was assayed. Tidal volumes of 50 and 400 ml were used at a frequency of 32 breaths per minute. Increasing the DGF from 4 to 8 l/minute produced a 264% increase in the rate of drug output but only a 32% increase in aerosol concentration. The mass of drug contained within droplets less than 5 microns increased from 26.8% to 70.8% of the total. The resultant increase in rate of drug delivery to the filter was 34% for a tidal volume of 50 ml and 79% for a tidal volume of 400 ml though the dose contained within droplets less than 5 microns increased by 4-fold at 50 ml tidal volume and by more than 5-fold at the higher tidal volume. Halving the solution concentration halved the rate of drug delivery. Increasing the tidal volume 8-fold from 50 to 400 ml resulted in an increase in the rate of drug deposition upon the filter of only 2.2 to 3-fold depending upon the DGF so that substantially more drug per ml inhaled was delivered at the lower tidal volume. These results are explained by considering factors that influence the rate of drug delivery. At low tidal volumes the rate of drug delivery at a given respiratory rate is dependent on the tidal volume and aerosol concentration. At high tidal volumes it is dependent upon aerosol concentration and volume of available aerosol and is essentially independent of tidal volume.

Drug delivery from holding chambers with attached facemask.

There is much interest in the use of holding chambers with an attached facemask to deliver aerosols from metered dose inhalers to infants. In order to study the influence of various design factors on the dose inhaled at different tidal volumes, a model was constructed in which a Starling ventilator was used to generate an inspiratory/expiratory cycle across a filter. Sodium cromoglycate was administered via a Nebuhaler and mask, Aerochamber and mask, and a coffee cup using tidal volumes of 25, 50, and 150 ml and the dose deposited upon the filter after six breaths was assayed using an ultraviolet spectrophotometric method. At the lowest tidal volume the high aerosol concentration in the smaller chamber enhanced drug delivery while at the highest tidal volume delivery was greatest from the larger chamber reflecting the larger dose available. Multiple breaths ensured that the dose inhaled per kilogram from each chamber was relatively large and also permitted significant drug delivery despite the introduction of a relatively large dead space between valve and filter. The dose delivered was increased by increasing the dose introduced into the chamber though not proportionately. These devices appear likely to deliver significant quantities of aerosol to infants, though drug delivery may be enhanced by the use of an appropriate valve.

Effects of smoking in pregnancy on neonatal lung function

AIMS To assess the effects of smoking during pregnancy on lung mechanics and lung volumes in the immediate neonatal period, before infants are exposed to passive smoking. METHODS Lung function tests were carried out within 72 hours of delivery in infants born to 100 non-smoking and 189 smoking mothers. Lung growth was assessed by plethysmography and lung mechanics using the single breath occlusion technique and oesophageal balloon/ pneumotachography. Antenatal maternal serum cotinine values were obtained from 133 mothers. RESULTS Smoking was associated with a significant reduction in birthweight (mean 256 g, 95% CI 0.164 to 0.392), and length (mean 1.26 cm, 95% CI 0.48 to 2.00). Lung volume was not reduced when related to weight. Smoking was associated with a highly significant reduction in static compliance (Crs). This effect remained significant after relating Crs to weight and lung volume. Regression analyses showed that the Crs association was limited to the boys. Smoking was associated with a small but significant reduction in respiratory system conductance (Grs) (single breath occlusion technique) and total pulmonary conductance (Gp). These associations were limited to girls. CONCLUSIONS Smoking in pregnancy reduces static compliance in boys and conductance in girls. There was no evidence that maternal smoking adversely affected fetal lung growth. Key messages • Smoking during pregnancy has an adverse effect on birthweight, length, head and chest circumference • The lungs of boys but not girls infants born to smoking mothers have reduced compliance • The lungs of girls but not boys born to smoking mothers have increased airways resistance, possibly due to the growth suppression effect • Pulmonary hypoplasia is not responsible for the increase in respiratory symptoms associated with antenatal smoking

Randomised controlled trial of budesonide for the prevention of post-bronchiolitis wheezing

BACKGROUND Previous studies suggest that recurrent episodes of coughing and wheezing occur in up to 75% of infants after acute viral bronchiolitis. AIM To assess the efficacy of budesonide given by means of a metered dose inhaler, spacer, and face mask in reducing the incidence of coughing and wheezing episodes up to 12 months after acute viral bronchiolitis. METHODS Children under the age of 12 months admitted to hospital with acute viral bronchiolitis were randomised to receive either budesonide or placebo (200 μg or one puff twice daily) for the next eight weeks. Parents kept a diary card record of all episodes of coughing and wheezing over the next 12 months. RESULTS Full follow up data were collected for 49 infants. There were no significant differences between the two study groups for the number of infants with symptom episodes up to six months after hospital discharge. At 12 months, 21 infants in the budesonide group had symptom episodes compared with 12 of 24 in the placebo group. The median number of symptom episodes was 2 (range, 0–13) in those who received budesonide and 1 (range, 0–11) in those who received placebo. Because there is no pharmacological explanation for these results, they are likely to be caused by a type 1 error, possibly exacerbated by there being more boys in the treatment group. CONCLUSION Routine administration of budesonide by means of a metered dose inhaler, spacer, and face mask system immediately after acute viral bronchiolitis cannot be recommended.

Adrenal function in asthma.

A dose dependent suppression of daily cortisol excretion was shown in 25 children with asthma being treated with beclomethasone dipropionate. Cortisol metabolites tended to occur below the normal range when doses of beclomethasone of more than 400 micrograms/m2/day were given. Androgen excretion below the normal range was apparent in asthmatic children aged 8-13 years regardless of whether they were receiving inhaled steroids. This may be the reason for growth delay often seen in asthmatic children. These side effects of beclomethasone are not enough reason to discourage its prescription for the treatment of asthma, but endocrine assessment is desirable when the dose exceeds 400 micrograms/m2/day.

A simple method of face mask resuscitation at birth.

Twenty two infants were resuscitated at birth using a face mask connected to an oxygen supply from a conventional resuscitaire. Intermittent finger occlusion provided the positive pressure within the mask. This method was apparently at least as effective as the best bag and mask systems and was convenient to use.

Treatment of recurrent acute wheezing episodes in infancy with oral salbutamol and prednisolone

The aim of this study was to investigate the role of oral salbutamol and prednisolone in the treatment of acute episodes of wheezing in infants under 15 months of age. Sixty-two acute episodes of wheezing were studied in 59 babies (age range 3–14 months; mean 7 months), who had all suffered at least one previous wheezy episode. Patients were randomised to receive either salbutamol and prednisolone, salbutamol and placebo or double placebo. Parents were requested to keep a diary card record of twice daily scoring of their babys symptoms over the next 14 days. A significantly greater number of treatment failures occurred in the placebo group compared to babies treated with oral salbutamol (relative risk 2.51; 95% confidence intervals for relative risk 1.09–5.79). There was no difference in the number of treatment failures between babies treated with a combination of salbutamol and placebo and those treated with salbutamol and prednisolone (relative risk 0.71; 95% confidence intervals for relative risk 0.18–2.80).ConclusionThis study demonstrates that oral salbutamol is beneficial in the treatment of acute episodes of wheezing in infancy. A combination of oral salbutamol and oral prednisolone appeared to have no additional benefit over treatment with oral salbutamol alone.

Adrenal function and high dose inhaled corticosteroids for asthma

OBJECTIVE To investigate effects on adrenal function of fluticasone, a recently released inhaled steroid preparation with lower systemic bioavailability than beclomethasone dipropionate. METHODS 34 children on high doses (400-909 μg/m2/d) of inhaled beclomethasone dipropionate or budesonide were recruited into a double blind, crossover study investigating the effects on adrenal function of beclomethasone and fluticasone propionate, given using a standard spacer (Volumatic). The 24 hour excretion rates of total cortisol and cortisol metabolites were determined at baseline (after a two week run in), after six weeks treatment with an equal dose of beclomethasone, and after six weeks of treatment with half the dose of fluticasone, both given through a spacer device. RESULTS The comparison of effects between fluticasone and beclomethasone during treatment periods, although favouring fluticasone in all measured variables, reached significance only after correction for urinary creatinine excretion (tetrahydrocortisol and 5α-tetrahydrocortisol geometric means: 424 v 341 μg/m2/d). The baseline data showed adrenal suppression in the children taking beclomethasone (total cortisol geometric means: 975 v 1542 μg/d) and a dose related suppression in the children taking budesonide. Suppressed adrenal function in the children who were taking beclomethasone at baseline subsequently improved with fluticasone and beclomethasone during treatment periods. CONCLUSIONS Fluticasone is less likely to suppress adrenal function than beclomethasone at therapeutically equivalent doses. The baseline data also support the claim that spacer devices should be used for the administration of high doses of inhaled topical steroids.

Estimation of fetal lung volume using enhanced 3-dimensional ultrasound: a new method and first result

Objective To measure fetal lung volume using a computer based, enhanced, 3‐dimensional ultrasound imaging system.