Improvement of nebulised antibiotic delivery in cystic fibrosis.

AIM: To investigate deposition patterns and to assess the delivery rate of two nebuliser systems in children with cystic fibrosis (CF). METHODS: Thirty three children with CF on regular treatment with nebulised antibiotics had radioisotope scans performed using technetium-99m labelled aerosol antibiotic generated by a Ventstream nebuliser (median mass diameter (MMD), 3.3 microm; delivery rate, 0. 075 ml/min) under conditions similar to their routine home practice. The inhomogeneity of the images was scored on a 1-10 rating scale (a low score indicating even distribution of the antibiotic), and stomach deposition was measured as a percentage of overall deposition. Twenty patients had a repeat scan using an Optimist nebuliser (MMD, 1.8 microm; delivery rate, 0.02 ml/min). RESULTS: The mean inhomogeneity scores were 5.4 in the Ventstream group and 3. 5 in the Optimist group. Mean stomach deposition was 17.3% in the 33 patients using the Ventstream nebuliser. There was an inverse relation between height and stomach deposition (r = 0.69). In the 20 patients who had both nebulisers, the mean percentages of stomach deposition for the Ventstream and Optimist nebulisers were 11.8% and 1.6%, respectively. The Ventstream nebuliser delivered antibiotic at an average 2.8 times faster rate than the Optimist nebuliser. IMPLICATIONS: A smaller particle size results in a more homogenous distribution of the antibiotic in the lungs with decreased stomach deposition. This should not be seen as a recommendation to use the Optimist nebuliser because more antibiotic was delivered to most parts of the lung with the Ventstream because of its increased delivery rate.     

Methicillin resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis

BACKGROUND—Methicillin resistant Staphylococcus aureus (MRSA) infection is increasingly found in patients with cystic fibrosis (CF).
AIMS—To determine whether MRSA infection has a deleterious effect on the clinical status of children with CF.
METHODS—Children with MRSA in respiratory cultures during a seven year period were identified and compared with controls matched for age, sex, and respiratory function. Respiratory function tests, anthropometric data, Shwachman-Kulczycki score, Northern chest x ray score, intravenous and nebulised antibiotic therapy, and steroid therapy were compared one year before and one year after MRSA infection.
RESULTS—From a clinic population of 300, 10 children had positive sputum or cough swab cultures for MRSA. Prevalence rose from 0 in 1992-1994 to 7 in 1998. Eighteen controls were identified. Children with MRSA showed significant worsening of height standard deviation scores and required twice as many courses of intravenous antibiotics as controls after one year. They had significantly worse chest x ray scores at the time of the first MRSA isolate and one year later, but showed no increase in the rate of decline in chest x ray appearance. There was a trend towards lower FEV₁ and FEF_25-75 in children with MRSA. There were no significant differences between the two groups with respect to change in weight, body mass index, or Shwachman score. There was no significant difference in prior use of steroids or nebulised antibiotics.
CONCLUSION—MRSA infection in children with CF does not significantly affect respiratory function, but may have an adverse effect on growth. Children with MRSA require significantly more courses of intravenous antibiotics and have a worse chest x ray appearance than controls.

     

Concentrations of antimony in infants dying from SIDS and infants dying from other causes

BACKGROUND—A patient with cystic fibrosis (CF) and repeated calcium oxalate renal stones prompted us to investigate other children for risk factors for this recognised complication of CF.
METHODS—Twenty four hour urinary excretion of calcium, oxalate, and glycolate was measured in children with CF and no symptoms of renal tract stones. Normal diet and treatments were continued.
RESULTS—In 26 children (aged 5-15.9 years) oxalate excretion was correlated with age; 14 of 26 children had oxalate excretion above an age appropriate normal range. There was a positive correlation between oxalate excretion and glycolate excretion. Mean calcium excretion was 0.06 mmol/kg/24 h with 21 of 24 children having calcium excretion below the normal range.
CONCLUSIONS—Hyperoxaluria may reflect malabsorption although correlation between excretion of oxalate and glycolate suggests a portion of the excess oxalate is derived from metabolic processes. The hypocalciuria observed here may protect children with CF from renal stones.

     

Correlates of prepubertal bone mineral density in cystic fibrosis

AIM—To examine early factors in bone mineral accretion in cystic fibrosis (CF).
METHODS—In 22 prepubertal children with CF and mild lung disease, the relation between total body bone mineral density (BMD) and measures of body composition, biochemistry, lung function, and physical activity was studied.
RESULTS—There was a non-significant mild reduction in mean total body BMD. No relation was found between BMD and anthropometric indices, fat free soft tissue, degree of lung disease, degree of fat malabsorption, dietary energy intake, or level of physical activity. Significant impairments in physical growth were apparent in this population and were found to correlate with degree of lung disease.
CONCLUSION—A CF specific factor appears unlikely to be associated with the osteopenia commonly found in CF. Careful attention to general aspects of lifestyle and nutrition is recommended to maximise bone mineral accretion in this population.

     

Faecal candida and diarrhoea

BACKGROUND—Candida species are frequently isolated from stools of children with diarrhoea but are not proven enteropathogens. It is hypothesised that faecal candida causes diarrhoea.
AIMS—To determine the prevalence of faecal candida in childhood diarrhoea and the relation between faecal yeasts and diarrhoea.
METHODS—Comparison of clinical and laboratory data, including quantitative stool culture for yeasts from 107 children hospitalised with diarrhoea and 67 age matched controls without diarrhoea.
RESULTS—Yeast species, predominantly candida, were identified in the stools of 43 children (39%) with diarrhoea and 26 (36%) without diarrhoea. The concentration of candida was positively associated with recent antibiotic use (p = 0.03) and with the presence of another enteric pathogen (p < 0.005), but not with patient age, nutritional status, or duration of diarrhoea.
CONCLUSION—Candida species do not cause childhood diarrhoea in well nourished children.

     

Social disadvantage, family composition, and diabetes mellitus: prevalence and outcome

OBJECTIVE—To present self reports by children and reports by parents on behalf of their children relating to general health, current conditions, and recent symptoms.
DESIGN—Questionnaires completed by children and parents as part of the longitudinal "West of Scotland 11 to 16 study: teenage health."
SETTING—135 primary schools in Central Clydeside.
SUBJECTS—2586 children aged 11 years, surveyed from October 1994 to March 1995 (response rate 93%). Questionnaires also completed by parents of 86% of the sample.
MAIN OUTCOME MEASURES—Ratings of health over the past 12 months, presence of (limiting) longstanding illness, nine current conditions, and 11 recent symptoms.
RESULTS—Only 47% of children described their health as "good" in the previous year. Around 20% reported a longstanding illness and 8% a limiting illness; 20% reported migraine or headaches, 13% reported asthma. Recent stomach aches or sickness, colds or flu, and headaches were each reported by around 60%. "Malaise" (emotional) symptoms were common. Parents reported similar levels of (limiting) longstanding illness, but rates of conditions and symptoms reported by parents were lower than reported by their children. Parent-child agreement was greatest for the presence of longstanding illness and the conditions of asthma, diabetes, and skin problems. It was lower for recent symptoms, particularly those categorised as reflecting malaise.
CONCLUSIONS—These results challenge assumptions of good health and wellbeing at this age. Illness reporting depends on various factors, including saliency, social desirability, and definitions of normality. Parent-child discrepancies may reflect different definitions of illness or symptoms; they do not mean that one should be dismissed as "wrong."

     

A randomised controlled trial of short term growth and collagen turnover in asthmatics treated with inhaled formoterol and budesonide

AIMS—To determine effects on short term growth and collagen turnover of adding formoterol (Eformoterol) to half the glucocorticoid dose in children with asthma, treated with inhaled budesonide (Pulmicort Turbuhaler).
DESIGN—A randomised double blind, placebo controlled crossover study with two six-week periods.
SETTING—Outpatient clinic in secondary referral centre.
SUBJECTS—A total of 27 prepubertal children aged 6-13 years.
INTERVENTIONS—Formoterol 12 µg and dry powder budesonide 100 µg twice daily in one period; placebo and dry powder budesonide 200 µg twice daily in the other.
OUTCOME MEASURES—Primary outcome measures were lower leg growth rate, and serum and urine markers of type I and type III collagen turnover. Secondary outcome measures were inflammation markers in serum, and parameters of asthma control.
RESULTS—During budesonide 200 µg twice daily treatment, mean lower leg growth rate was 0.14 mm/week (p = 0.02) lower than during the formoterol and budesonide period. Similar statistically significant effects on markers of collagen turnover were found, whereas inflammation markers and asthma control did not vary statistically significantly between the two periods.
CONCLUSIONS—In children treated with inhaled glucocorticoids, halving the dose and adding formoterol is associated with faster short term growth and an increase in markers of collagen turnover, with no loss of asthma control.

     

Living at high altitude and risk of sudden infant death syndrome

OBJECTIVE—To investigate the association between altitude of residence and risk of sudden infant death syndrome (SIDS).
METHODS—A retrospective, case control study in the Tyrol, Austria enrolled 99 infants with SIDS occurring between 1984 and 1994, and 136 randomly selected control cases. Data on pregnancy, delivery, child care practice, and sociodemographic characteristics including altitude of residence were collected with a standardised questionnaire.
RESULTS—The risk of SIDS increased gradually with increasing altitude of residence. This relation remained independently significant when the analysis was adjusted for gestational age, birth weight, prenatal care, mother''s age at delivery, educational level of parents, and cigarette smoking during pregnancy. The prone sleeping position emerged as an obligatory cofactor in this association. In the whole of Austria, a similar trend of association emerged between the average altitudes in the 99 political counties and the rates of SIDS.
CONCLUSIONS—This study identified altitude of residence as a significant risk predictor of SIDS, primarily in combination with the prone sleeping position. Respiratory disturbances, reduced oxygen saturation, and lower temperatures at high altitude might explain this association.

     

Systemic availability and pharmacokinetics of nebulised budesonide in preschool children

AIM—To evaluate the systemic availability and basic pharmacokinetic parameters of budesonide after nebulisation and intravenous administration in preschool children with chronic asthma.
METHODS—Plasma concentrations of budesonide were measured for three hours after an intravenous infusion of 125 µg budesonide. The children then inhaled a nominal dose of 1 mg budesonide through the mouthpiece of a Pari LC Jet Plus nebuliser connected to a Pari Master compressor, and the plasma concentrations of budesonide were measured for another six hours. The amount of budesonide inhaled by the patient ("dose to subject") was determined by subtracting from the amount of budesonide put into the nebuliser, the amount remaining in the nebuliser after nebulisation, the amount emitted to the ambient air (filter), and the amount found in the mouth rinsing water.
RESULTS—Ten patients aged 3 to 6 years completed both the intravenous and the inhaled treatment. The mean dose to subject was 23% of the nominal dose. The systemic availability of budesonide was estimated to be 6.1% of the nominal dose (95% confidence intervals (CI), 4.6% to 8.1%) or 26.3% of the dose to subject (95% CI, 20.3% to 34.1%). Budesonide clearance was 0.54 l/min (95% CI, 0.46 to 0.62), steady state volume of distribution 55 litres (95% CI, 45 to 68), and the terminal half life was 2.3 hours (95% CI, 2.0to 2.6).
CONCLUSIONS—Approximately 6% of the nominal dose (26% of the dose to subject) reached the systemic circulation of young children after inhalation of nebulised budesonide. This is about half the systemic availability found in healthy adults using the same nebuliser.

     

Randomised controlled study of clinical efficacy of spacer therapy in asthma with regard to electrostatic charge

BACKGROUND—Inhalation therapy using a pressured metered dose inhaler (pMDI) and a spacer is frequently used in the treatment of airway disease in children. Several laboratory studies found a clear negative influence of electrostatic charge (ESC) on plastic spacers on the delivery of aerosol.
AIMS—To investigate whether ESC on plastic spacers could diminish bronchodilating responses to salbutamol.
METHODS—Ninety asthmatic children (aged 4-8 years) were randomised into three groups: metal Nebuchamber, plastic Volumatic, and plastic Aerochamber. The bronchodilating response was measured by the change in peak expiratory flow rate (PEF) after 100 µg and 400µg salbutamol. Within the Volumatic and Aerochamber groups, a crossover comparison was made between electrostatic and non-electrostatic spacers.
RESULTS—We found no significant effect of ESC on the bronchodilating response to salbutamol with any of the doses in the Aerochamber and Volumatic groups. For the plastic spacers, the mean difference of the change in PEF after 100 µg salbutamol between non-electrostatic and electrostatic spacers was only +1.7% (95% CI −1.3% to 4.7%). After 400 µg salbutamol this was +1.9% (95% CI −1.4% to 5.1%). A comparable efficacy was found for the Nebuchamber, the Aerochamber, and Volumatic with respect to the change in PEF after 100 and 400 µg salbutamol.
CONCLUSION—This study showed no negative influence of ESC on plastic spacers with regard to clinical efficacy of a β₂ agonist (salbutamol) in children with asthma. The metal Nebuchamber, plastic Aerochamber, and plastic Volumatic were equally effective.

     

Reliability of percentage ideal weight for height

AIMS—To assess the reliability of percentage ideal weight for height (%WFH) as a measure in children.
METHODS—Forty two dietitians calculated %WFH of six children. Eleven of the 42 repeated the calculations.
RESULTS—Interexaminer estimates varied by 16.5 to 40 percentage points (mean 27.8). Intraexaminer variability was also large.
CONCLUSIONS—%WFH is an unreliable measure of nutritional status.

     

Incidence and cause of fractures in European districts

AIMS—To compare fracture rates in European districts.
SETTING—Geographically defined areas of Wales (Swansea and Neath Port Talbot), Norway (Harstad, Trondheim, Stavanger, and Drammen), Sweden (Jamtlands), and Finland (Porvoo).
METHODS—Surveillance of fractures at emergency departments and hospitals and linkage with population data. Comparison of age adjusted and crude rates. Calculation of confidence intervals for ratios.
RESULTS—A total of 4113 fractures occurred in 167 560 children during 1996. Fracture rates in south Wales (36 per 1000) were substantially higher than in Scandinavian districts (which were similar). Limiting analysis to the most severe injuries to correct for the possibility of ascertainment bias reduced some of the excess rate in Wales: the Welsh:Scandinavian fracture ratio was 1.82 (95% confidence interval: 1.64 to 2.03).
CONCLUSIONS—Fracture rates in Welsh children are substantially higher than in Scandinavian children.

     

Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa

BACKGROUND—Bacteriological confirmation of pulmonary tuberculosis is difficult in infants and young children. In adults and older children, sputum induction has been successfully used; this technique has not been tested in younger children.
AIMS—To investigate whether sputum induction can be successfully performed in infants and young children and to determine the utility of induced sputum compared to gastric lavage (GL) for the diagnosis of pulmonary tuberculosis in HIV infected and uninfected children.
SUBJECTS AND METHODS—149 children (median age 9 months) admitted to hospital with acute pneumonia who were known to be HIV infected, suspected to have HIV infection, or required intensive care unit support. Sputum induction was performed on enrolment. Early morning GL was performed after a minimum four hour fast. Induced sputum and stomach contents were stained for acid fast bacilli and cultured for Mycobacterium tuberculosis.
RESULTS—Sputum induction was successfully performed in 142 of 149 children. M tuberculosis, cultured in 16 children, grew from induced sputum in 15. GL, performed in 142 children, was positive in nine; in eight of these M tuberculosis also grew from induced sputum. The difference between yields from induced sputum compared to GL was 4.3% (p = 0.08). M tuberculosis was cultured in 10 of 100HIV infected children compared to six of 42 HIV uninfected children (p = 0.46).
CONCLUSION—Sputum induction can be safely and effectively performed in infants and young children. Induced sputum provides a satisfactory and more convenient specimen for bacteriological confirmation of pulmonary tuberculosis in HIV infected and uninfected children.

     

Height and weight reference curves for homozygous sickle cell disease

OBJECTIVE—To derive height and weight growth reference curves for children with homozygous sickle cell disease.
STUDY DESIGN—Subjects (n = 315) were participants in a population based, longitudinal cohort study of sickle cell disease in Kingston, Jamaica. Regular measurements of height and weight were made from enrollment into the study at birth up to 22 years of age.
RESULTS—Sex specific growth reference curves for height for age and weight for age covering the age range 0-18 years are presented.
CONCLUSION—These growth reference curves are suitable for identifying coincidental growth problems in children with homozygous sickle cell disease.

     

Inconsistencies in sweat testing in UK laboratories

BACKGROUND—Sweat testing procedures are perceived to vary widely.
AIM—To evaluate variability in sweat collection, analysis, and interpretation.
METHODS—Questionnaire responses from 30 self selected centres: 15 paediatric centres, and 15 district general hospitals.
RESULTS—Centres carried out 30-400 tests per year (median 100), with a diagnostic rate of 1:5-152 (median 1:30). Staff performed 5-268 tests per year. Minimum test age varied from 24 hours to four months. All stimulated sweating by pilocarpine iontophoresis using varying currents and times. Twenty six had observed urticaria or skin reddening, and nine blistering or burns. Sweat was collected for 10-60 minutes onto filter paper or into Macroduct coils. Between 2% and 25% of tests were considered insufficient. Twenty eight measured sodium, 24 chloride, and one osmolality and conductivity. Fifteen used literature and five in house reference ranges. Eleven would not test severely eczematous children.
CONCLUSIONS—Local audit is required to improve performance, as well as a national guideline to standardise collection, and external quality assessment to provide analytical feedback.

     

Maimonides (1135-1204) and his philosophy of medicine

AIM—To quantify the exposure of very low birthweight neonates to ionising radiation from diagnostic x-rays.
METHODS—Retrospective analysis was made of all radiographs performed over 18 months in an integrated special care baby unit and regional neonatal surgical unit in a large teaching hospital of surviving inborn babies of very low birthweight (<1500 g) admitted to the unit.
RESULTS—Fifty five VLBW neonates were treated for a total of 3296 days and received 498 radiographs (median 5 per infant). The mean effective radiation dose was 0.04 mSv and the maximum for one infant was 0.54mSv.
CONCLUSIONS—The radiation burden in this group of neonates is low and the benefits of diagnostic radiographs far outweigh any potential radiation risks.

     

Re-vaccination of 421 children with a past history of an adverse vaccine reaction in a special immunisation service

BACKGROUND—In Australia an adverse event following immunisation (AEFI), with the exception of anaphylaxis and encephalopathy, is no longer considered an absolute contraindication to continuing vaccination with the suspect vaccine. Despite these recommendations there is a paucity of information on the re-vaccination of such children.
AIMS—To describe the re-vaccination of a large number of children with a past history of an AEFI.
METHODS—A review of children attending special immunisation services in three Australian tertiary care paediatric centres.
RESULTS—During the review 970 children attended of whom 469 had experienced a past AEFI. Of these, 293 had experienced minor while 176 children had experienced significant neurological or allergic reactions. The majority (421/469) were re-vaccinated, with only one child having a significant neurological event; this was transient and resolved spontaneously.
CONCLUSIONS—Re-vaccination of children who have a past history of an AEFI appears safe. A special immunisation service should be part of a comprehensive immunisation programme.

     

Cerebral blood flow during vasovagal syncope induced by active standing or head up tilt

BACKGROUND—Vasovagal syncope is usually associated with a sudden drop of blood pressure and/or heart rate. However, occasionally the symptoms of syncope induced by orthostatic stress testing are not associated with obvious haemodynamic changes. The mechanisms of syncope in these patients are not clear.
AIM—To evaluate changes in cerebral blood flow velocities during orthostatic stress testing in children and adolescents with vasovagal syncope.
METHODS—Electrocardiogram, instantaneous arterial blood pressure, and right middle cerebral artery blood flow velocity were recorded at rest, during active standing, and 80° head up tilt. 32 children and adolescents aged between 7 and 18 years with a history of repeated vasovagal syncope and 23 healthy control subjects were studied.
RESULTS—Presyncope occurred in 10 patients during standing, and 13 patients during head up tilt. None of the controls had symptoms during the test. The transcranial Doppler study showed that the symptoms were associated with significant decreases of diastolic cerebral blood flow velocity and an increase of pulsatility. There was no significant change of the systolic cerebral blood flow velocity. The changes of cerebral blood flow velocities occurred in all episodes of presyncope, including those not associated with severe drop of blood pressure or heart rate.
CONCLUSIONS—Diastolic cerebral blood flow velocity decreased significantly during episodes of presyncope induced by orthostatic stress. Impairment of autoregulation of cerebral blood flow might play an important role in the pathophysiology of syncope.

     

Unsuspected Pneumocystis carinii pneumonia at presentation of severe primary immunodeficiency

BACKGROUND—Pneumocystis carinii is an important pathogen in immunodeficiency but may be an unrecognised cause of respiratory compromise.
OBJECTIVES—To ascertain the incidence of P carinii pneumonia (PCP) at presentation of severe combined immunodeficiency (SCID), whether it had been diagnosed, and the effect of treatment on outcome.
SETTING—The supraregional paediatric bone marrow transplant unit for primary immunodeficiencies at Newcastle General Hospital.
METHODS—Retrospective case note review of infants referred with a diagnosis of SCID from 1992 to 1998.
RESULTS—Ten of 50 infants had PCP at presentation; only one was diagnosed before transfer. Eight were diagnosed by bronchoalveolar lavage and two by lung biopsy. In only one was P carinii identified in nasopharyngeal secretions. Five required ventilation for respiratory failure but all were successfully treated with co-trimoxazole and methylprednisolone with or without nebulised budesonide. Nine survived to bone marrow transplantation and four are long term survivors after bone marrow transplantation; no deaths were related to PCP.
CONCLUSIONS—PCP is a common presenting feature of SCID but is rarely recognised. Bronchoalveolar lavage or lung biopsy are needed for diagnosis. Treatment with co-trimoxazole is highly successful.