Lower airway responses to nebulised bronchodilators were studied in 18 chronically or recurrently wheezy infants, aged 3-15 months, by means of partial forced expiratory flow-volume manoeuvres performed with an inflatable jacket. Maximum flow at functional residual capacity (FRC) (VmaxFRc) was used as the index of intrathoracic airways function. Peak expiratory flow rate was also measured. Baseline airways resistance and lung volume were determined during quiet breathing in an infant whole body plethysmograph. Measurements were made on separate days before 'and after nebulised salbutamol 25 mg with nebulised saline as control. The results were paradoxical: there was no change in VmaxFRc after saline, but a significant decline in VmaxFRc was found after salbutamol. Peak expiratory flow remained unchanged. These observations suggest that under conditions of forced expiration intrathoracic airways function may be further impaired by nebulised bronchodilator treatment in wheezy infants. When nebulised bronchodilator drugs are used to treat severe airways obstruction in infancy, careful monitoring is essential.It is now widely believed that wheezy infants, in constrast with older children, do not respond to either of the two generally available classes of bronchodilator drugs, P2 selective sympathomimetic agents and anticholinergic, antimuscarinic agents. Most physiological measurements'-' and clinical trials34 have shown no significant effect, although a clinical benefit has been claimed for combination treatment with a 2 sympathomimetic agent and a corticosteroid in acute bronchiolitis.5 The many reasons that have been put forward for the apparent lack of response include inadequate airway smooth muscle, insufficient or ineffective P receptors, and inappropriate airway pathophysiology.6 One additional factor that has not been taken into account is the relative contribution of the upper airways to airways obstruction in wheezy infants. In the past, measurements of airways function in wheezy infants have been made during sleep, when it is reasonable to assume nasal breathing, and have therefore provided an overall value for upper and lower airways combined. Normally the nasal passages

Little is known about airway responsiveness in infancy. The bronchial response to incremental doses of nebulised histamine (to a maximum dose of 8 g/l) was measured in 11 wheezy infants with a mean age of 8-7 months. The study was repeated after a 30-40 minute recovery period in seven infants and again on a separate day in 10. The index of response was the provoking concentration of histamine that produced a 30% fall in the maximum expiratory flow at functional residual capacity (PC30), taken from partial forced expiratory flow-volume curves produced in a pressure jacket. Nine of 11 infants had a PC30 of less than 8 g/l. The response was consistent between tests in both the nine responders and the two who failed to respond at 8 g/l. The PC30 was lower in infants with more severe baseline airway obstruction. Spontaneous recovery after challenge was complete in 30 minutes in seven of eight infants studied. The highest doses of histamine caused changes in the configuration of the flow-volume curves and symptomatic cough and wheeze in addition to a change in forced flow rates. This study provides clear evidence of intrathoracic airway responsiveness to histamine in infancy.The concept of bronchial responsiveness has played an important part in elucidating the pathophysiology of asthma in older children1 2 and adults.34 Very little is known, however, about airway function in wheezy infants. The repeated failure of wheezy infants under 18 months to respond to nebulised sympathomimetic agents,5 in contrast with older subjects, suggests that different mechanisms may operate in the infant airway.Two recent studies have shown that the infant airway can respond to an inhaled bronchoconstrictor agent,6 7 suggesting that wheezy infants may have the capacity to develop bronchoconstriction in a similar way to older children. Unfortunately, both these studies relied on measurements of resistance that included the upper airway (nasal passages and larynx) as well as the intrathoracic airways. As the nasal passages account for about half of the total airway resistance in normal infants,8 an index of responsiveness that includes upper airway changes is likely to be a poor reflection of true bronchial

CVST has non-specific presenting features and a high risk of significant morbidity. CVST is typically found in association with a predisposing condition. Although heparin is the mainstay of treatment, thrombolysis may reverse deterioration as seen in three cases in this series. However, there is insufficient evidence to recommend the routine use of thrombolysis at present.

SUMMARY In the period from September 1983 until June 1986 a prospective study was carried out to determine the incidence and severity of retinopathy of prematurity in inborn infants of less than 1500 g at birth and the risk factors associated with the development of retinopathy of prematurity in infants of less than 31 weeks' gestation. One hundred and forty four infants were eligible for inclusion in the study. Altogether 140 infants of less than 1500 g birth weight were examined, 42 (30%) of whom developed retinopathy of prematurity. Fifteen of these infants had progression to advanced disease (stage III or stage IV).One hundred and seventeen of the infants were of less than 31 weeks' gestation and 34 (29%) of them developed retinopathy of prematurity. Thirty four risk factors shown previously to be associated with the development of the disease were collected prospectively and analysed using multiple logistic regression analysis to determine the independently significant variables. Three risk factors: acidosis, the number of times that the pH was <7-2; hyperoxia, the number of times that arterial oxygen tension was greater than 12 kPa; and gestational age were found to be independently associated with the development of retinopathy of prematurity in these infants. These findings suggest that acidosis may be an important aetiological factor in the pathogenesis of this disease.There is a considerable variation in the reported incidence of retinopathy of prematurity1-6 and the association of risk factors with its development.7-25The most important factor contributing to this variability is likely to be differences in ophthalmic practice in infants in different centres. Thus the selection of infants for examination, the timing of the first retinal examination, and the frequency of follow up examinations will each affect the apparent incidence of the disease. Furthermore the inclusion of retrospective data, and the methods used for statistical treatment of these data may also have important effects. Lastly, differing survival rates of extremely low birthweight infants would be expected to have a profound effect on the observed incidence of retinopathy of prematurity.The present study was designed to determine the incidence and severity of retinopathy of prematurity in all infants born at less than 31 weeks' gestation or less than 1500 g birth weight and to investigate the association between a range of clinical features and the development of retinopathy of prematurity. Only infants born at the Hammersmith Hospital were included in the study so that risk factors were recorded prospectively by a single observer over a continuous 31 month period and non-uniformity in neonatal care was minimised. Infants were examined early and frequently until term. In all infants less than 31 weeks' gestation, 34 risk factors were recorded prospectively and subjected to multiple logistic regression analysis in order to determine which variables were independently associated with the development and progression of retinopathy of mat...

The effect of nebulised salbutamol on the bronchial response to nebulised histamine was studied in five wheezy infants aged 3-12 months. The response to doubling concentrations of up to 8 g/l of histamine was assessed by the change in maximum flow at FRC (VmaxFRc), measured by flow-volume curves produced during forced expiration with a pressure jacket. The concentration of histamine required to provoke a 30% fall in VmaxFRc (PC30) was measured. All of the infants responded to low concentrations of histamine during control tests before and after nebulised saline (mean PC30 1 07 and 0-51 g/l). On a separate day there was a similar response to histamine before salbutamol (PC30 0 57 g/l), but after salbutamol the response was completely abolished up to the maximum concentration of histamine in all subjects (PC30 > 8 g/1). Thus wheezy infants have highly effective P2 adrenoceptors in intrathoracic airways.Wheezing disorders of infancy, although common, are difficult to treat.1 Physiological studies carried out on wheezy infants have failed to show any useful response to nebulised f adrenergic agents in terms of reduction in the overall respiratory resistance or work of breathing.2`Since, however, in infants more than 50% of total airway resistance is contributed by the upper airways, a change in intrathoracic airway calibre may well be masked in this type of study. In a recent study of airway responsiveness to salbutamol in wheezy infants we used a pressure jacket to produce partial expiratory flow-volume (PEFV) curves. From these curves we determined forced expiratory flow at FRC (VmaxFRc) as an index of intrathoracic airway function. In common with others5 -7we found a significant fall in VmaXFRc after nebulised salbutamol. Although negative, this observation supports the concept that ,B receptors are present in the infant airway in sufficient density to be recognisable by gross physiological measurements. A possible explanation for this paradoxical response to a "bronchodilator" drug is that a reduction in smooth muscle tone, without a commensurate fall in airway resistance, renders the airways more compliant and therefore less able to support high flow rates.8