Late presentation of upper airway obstruction in Pierre Robin sequence.

A retrospective review was carried out of 11 consecutive patients with the Pierre Robin sequence referred to a tertiary paediatric referral centre over a five year period from 1993 to 1998. Ten patients were diagnosed with significant upper airway obstruction; seven of these presented late at between 24 and 51 days of age. Failure to thrive occurred in six of these seven infants at the time of presentation, and was a strong indicator of the severity of upper airway obstruction. Growth normalised on treatment of the upper airway obstruction with nasopharyngeal tube placement. All children had been reviewed by either an experienced general paediatrician or a neonatologist in the first week of life, suggesting that clinical signs alone are insufficient to alert the physician to the degree of upper airway obstruction or that obstruction developed gradually after discharge home. The use of polysomnography greatly improved the diagnostic accuracy in assessing the severity of upper airway obstruction and monitoring the response to treatment. This report highlights the prevalence of late presentation of upper airway obstruction in the Pierre Robin sequence and emphasises the need for close prospective respiratory monitoring in this condition. Objective measures such as polysomnography should be used, as clinical signs alone may be an inadequate guide to the degree of upper airway obstruction.

Effects of birthweight and oxygen supplementation on lung function in late childhood in children of very low birth weight.

Impaired respiratory function has been found frequently in ex-premature children, but it is unclear which specific factors influence this impairment the most. The aim of this study was to determine the importance of the contributions of birth weight, gestational age, neonatal respiratory disease, and its treatment on subsequent childhood lung function at age 11 years in a cohort of children of very low birth weight (VLBW; 2,000 g) of similar age. VLBW children were shorter and lighter than controls (P < 0.0001) at 11 years of age, and had reduced expiratory flows (P < 0.00001) and forced vital capacities (P < 0.001). The residual volume to total lung capacity ratio (RV/TLC ratio) was increased (P < 0.00001), while total lung capacity (TLC) remained unchanged. Those with bronchopulmonary dysplasia (BPD) had the lowest mean expiratory flows. Males had lower expiratory flows than females. On univariate analysis, gestational age by itself accounted for 8.8% of the explained variance in FEV(1) at 11 years of age, but birth weight accounted for 16% on its own; both together accounted for a further 0.2% (16.2%), suggesting that the latter was the dominant factor. On multivariate analysis, the contribution of birth weight and gestational age was small, and the best predictors at 11 years of age, which together explained 43.4% of the total variance in FEV(1), were log days of supplemental oxygen (9.6%) and a reported history of asthma (10.8%). For FEF(25-75), these predictors explained 7.2% and 13.4%, respectively, of the total explained variance of 40.6%. The relation between neonatal oxygen supplementation and childhood FEV(1) was such that up to 20 days of supplemental oxygen had little effect on subsequent FEV(1) at 11 years of age, but each additional week of supplemental oxygen after that time was associated with a progressive reduction in FEV(1) of 3%. These data confirm the significant role of supplemental oxygen in the neonatal period and a history of asthma on the subsequent reduction of expiratory flows in VLBW children. Birth weight was a more important prenatal factor than gestational age, but both were of lesser predictive significance than either supplemental oxygen or a reported history of asthma.

Trends in hospital readmission for asthma: has the Australian National Asthma Campaign had an effect?

OBJECTIVES: To describe patterns of hospital readmission for asthma in South Australia from 1989 to 1996, in relation to implementation of the National Asthma Campaign. DESIGN AND SETTING: A comparison of hospital admissions in South Australia of patients aged between one year and 49 years for three conditions: asthma (or respiratory failure with asthma as an underlying condition) and two control conditions--diabetes and epilepsy. Individuals were identified by Medicare number and date of birth. OUTCOME MEASURES: Hospital readmission within 28 days and within one year. RESULTS: Overall, by 1996, there was a statistically significant decline in the risk of readmission for asthma within 28 days of 18% and within one year of 17% compared with 1989 readmission rates. There were no reductions in the risk of readmission for diabetes or epilepsy, suggesting that the decline in risk of readmission for asthma was greater than the underlying effects of general changes in hospital casemix. CONCLUSIONS: The decline in risk of readmission may reflect changes in asthma severity or improved management practices. However, hospital readmission rates still remain high, and to further reduce readmissions for asthma there is a need to identify factors related to presentation for asthma at accident and emergency departments.

Repeated dose inhaled budesonide versus placebo in the treatment of croup.

OBJECTIVE: To investigate the efficacy and tolerance of 12-hourly dosing with 2 mg 4 mL-1 of inhaled budesonide versus placebo in patients admitted to hospital with moderate/severe croup. METHOD: Eighty-two children hospitalised with croup received either 2 mg 4 mL-1 of budesonide or placebo 12 hourly (maximum four doses) via Ventstream nebuliser in a randomised, double-blind manner. Croup scores were performed at 0, 2, 6, 12, 24, 36 and 48 h from initial nebulisation whilst the patient remained hospitalised. Follow-up assessments were made 1 and 3 days after discharge. RESULTS: Improvement was observed in the budesonide group over the 12-h dosing interval when compared to placebo (P = 0.04). Time to attain a significant clinical improvement was superior in the budesonide group (P = 0.01). Three days after discharge seven of 32 placebo-treated patients and one of 34 budesonide-treated patients had sought further medical follow-up (P = 0.02). CONCLUSION: Twelve-hourly dosing with inhaled budesonide significantly improved symptoms of croup as well as decreased relapse rates when compared with placebo.

Fetal lung compliance in premature and term lambs after two methods of in utero repair of diaphragmatic hernia.

BACKGROUND: In utero surgery was used to correct a surgically induced model of congenital diaphragmatic hernia (CDH) in premature and term lambs, resulting in an improvement in lung mechanics at birth. METHODS: The differences between the in utero "patch" repair method and the "silo" repair method were assessed in 55 lambs by measuring the static respiratory system compliance (CST,RS) at birth in term (approximately 145 day) and in premature (128 day) animals. RESULTS: Both methods resulted in similar improvements in CST,RS in term lambs, but in premature lambs only the silo method produced an increase in compliance. Comparisons of specific compliance related to length or birth weight did not alter these findings; however, corrections related to lung weight or a measure of lung volume showed there was no difference between any experimental groups in either term or premature lambs. CONCLUSIONS: These findings suggest that there was no difference in the intrinsic compliance of the lung tissue between normal, unrepaired and repaired animals, and that the differences in respiratory system compliance measured at birth may be due primarily to differences in lung size. The silo repair method appears to provide an earlier improvement in CST,RS than the patch repair method.

Coagulopathy with piperacillin administration in cystic fibrosis: two case reports.

Two cases are reported of coagulopathy in association with the administration of piperacillin to patients with cystic fibrosis. In both cases the coagulopathy was associated with the development of a serum sickness-like illness with fever, rash and abnormal liver function tests occurring on day 12 and day 16 of treatment, respectively. On withdrawal of the piperacillin, both the serum sickness and the coagulopathy resolved rapidly, without sequelae.

Peripheral intravenous line survival and phlebitis prevention in patients receiving intravenous antibiotics: heparin/hydrocortisone versus in-line filters.

OBJECTIVE: To compare the use of in-line filtration with the addition of heparin/hydrocortisone (hep/hc) to the infusate for both phlebitis prevention and intravenous (i.v.) line survival in peripheral i.v. catheters. This study was specific for a patient group receiving prolonged courses of i.v. antibiotics. Analysis of the two endpoints for conventional short i.v. catheters (short lines) versus long (30 cm) i.v. catheters (long lines) was also performed. METHODS: Patients with cystic fibrosis receiving intermittent i.v. antibiotics were randomly allocated to receive their drugs either through an in-line filter using a drug-free infusate or with no filter and an infusate containing heparin 500 units and hydrocortisone 10 mg/L. Infusion sites were assessed daily. RESULTS: Both the hep/hc and filter groups were similar in terms of phlebitis incidence and i.v. line survival when analyzed separately for both short and long lines. Long lines displayed markedly prolonged survival times and reduced phlebitis compared with short lines. CONCLUSIONS: The effectiveness of i.v. filters in excluding the large particle load introduced by i.v. antibiotics and hence in reducing the subsequent phlebitis makes them a useful alternative to the use of hep/hc. The use of filters in this patient group may offer advantages in terms of ease of use and a possible decrease in hep/hc-related problems. Long lines offer practical advantages over short lines for patients requiring longer term i.v. access.

Induction of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by Pseudomonas aeruginosa and exotoxin A-induced suppression of lymphoproliferation and TNF, lymphotoxin, gamma interferon, and IL-1 production in human leukocytes.

Pseudomonas aeruginosa is a dominant pathogen in infection in cystic fibrosis. This bacterium is thought to play a major role in the chronic bronchial infection-induced pathophysiology. Our data showed that whole formalin-fixed heat-killed P. aeruginosa was mitogenic for human lymphocytes and induced production of substantial amounts of tumor necrosis factor alpha (TNF) in peripheral blood mononuclear leukocytes in cultures. Significant amounts of TNF were produced at 10(3) bacteria per 2 x 10(5) mononuclear leukocytes. Treatment of P. aeruginosa with polymixin B did not affect its ability to stimulate TNF production, suggesting that bacterial lipopolysaccharide is not involved. P. aeruginosa, however, did not stimulate production of the T-cell lymphokine lymphotoxin (TNF beta). Exotoxin A, considered to be an important virulence factor produced by P. aeruginosa, did not stimulate either lymphoproliferation or production of TNF. In fact, this toxin, at nontoxic concentrations, was found to depress lymphoproliferation induced by phytohemagglutinin and Staphylococcus aureus and decreased production of TNF, lymphotoxin, and gamma interferon in either lymphocytes or macrophages. This toxin similarly inhibited the production of interleukin-1 beta (IL-1 beta) and IL-1 alpha, but for the inhibition of the latter, 25-fold-less toxin was required than for inhibition of the former. Inhibition of production of TNF was as sensitive as the IL-1 alpha to exotoxin A. The effects of exotoxin A on lymphoproliferation and cytokine production could be neutralized by the addition of anti-exotoxin A antibodies. These results suggest that two mechanisms by which P. aeruginosa could contribute to the chronic bronchial infection-induced pathophysiology are the nonspecific stimulation of TNF and IL-1 and the release of exotoxin A, a toxin which depresses immune responses.

Production of tumor necrosis factors alpha and beta by human mononuclear leukocytes stimulated with mitogens, bacteria, and malarial parasites.

Tumor necrosis factors alpha and beta (TNF-alpha and TNF-beta) are multifaceted polypeptide cytokines which may mediate some of the significant changes in cellular homeostasis which accompany the invasion of the mammalian host by viruses, bacteria, and parasites. Although it is well established that bacterial lipopolysaccharide is a potent inducer of TNF-alpha, there is still very little known of the types of agents which can trigger the production of TNFs in mononuclear leukocytes. Using an enzyme-linked immunosorbent assay for measuring TNF-alpha and TNF-beta, we examined the capacity of various T-lymphocyte and beta-lymphocyte mitogens as well as microbial components to stimulate production of these cytokines in culture. The mitogens phytohemagglutinin, concanavalin A, and pokeweed mitogen induced production of both TNF-alpha and TNF-beta, while whole-killed Staphylococcus aureus and Bordetella pertussis, like lipopolysaccharide, were potent inducers of TNF-alpha but failed to stimulate TNF-beta production. TNF-alpha production was detectable within 1 h after stimulation, while TNF-beta production was not detected until after 8 h of culture. The bacterial products tetanus toxoid, purified protein derivative, pertussis filamentous hemagglutinin, and pertussis toxin were all able to induce TNF-alpha and TNF-beta production. Disrupted (frozen-thawed) Plasmodium falciparum-infected erythrocytes were also potent inducers of TNF-alpha and TNF-beta. The results demonstrated that a wide variety of microbial components are inducers of TNF-alpha. Some may not only be more effective than lipopolysaccharide but can also induce TNF-beta production. Furthermore, evidence is presented showing that TNF-beta but not TNF-alpha production correlates with lymphoproliferation.