Comparison of the occlusion and inflation techniques for measuring total respiratory compliance in sick, intubated infants.

Respiratory system compliance (Crs) can be used to assess lung stiffness in sick, intubated infants, avoiding the use of an esophageal balloon. Crs was assessed in a group of 15 sick, intubated infants using the occlusion and inflation techniques. The occlusion technique gave satisfactory results in 13 infants. Apneic pauses following occlusion were obtained in infants up to 10 months of age. Satisfactory measurements of Crs were obtained in all 15 infants using the inflation technique, but difficulty was experienced in obtaining data over the tidal volume range in three of them. A close agreement was found between the two methods of measuring Crs in the ten infants in whom a direct comparison was possible.

The accuracy of esophageal pressure measurements in convalescent and sick intubated infants.

Assessment of the esophageal pressure technique for measuring dynamic lung compliance (Cdyn) showed that accurate results were obtained in only 5 of 15 studies of sick intubated infants, whereas they were obtained in 6 of 6 studies of convalescent nonintubated infants. In sick infants, inaccuracy was due to large variations in esophageal pressure change (delta Pes) at different esophageal depths and difficulties validating Pes using the occlusion test. Methods of assessing lung stiffness that depend on the measurement of esophageal pressure are unreliable and should not be used in sick intubated infants.

Branhamella catarrhalis colonization in preschool asthmatics.

Branhamella catarrhalis has been associated with exacerbations of chronic bronchitis and asthma in adults. To investigate the possible role of B. catarrhalis in asthma of early childhood, we took posterior pharyngeal swabs from 24 normal children, 20 well asthmatics, and 20 acutely wheezy asthmatics, all between 1 and 4 years of age. On culture, 33% of the normal children were colonized with B. catarrhalis; colonization rates in the well asthmatics (70%) and in the wheezy asthmatics (75%) were significantly higher than in normals. The nature of this association requires further study.

Growth during one year of treatment with fluticasone propionate or sodium cromoglycate in children with asthma.

The aim of this study was to compare accurately measured growth over 12 months in asthmatic children treated with either fluticasone propionate (FP) 50 micrograms twice daily (b.i.d.) or sodium cromoglycate (SCG) 20 mg four times daily (q.i.d.). After a 2-week run-in, asthmatic children aged 4-10 years from 15 UK centers were randomized in a 3:4 ratio to open-label FP (n = 52) or SCG (n = 70). After 8 weeks, those whose asthma was not adequately controlled were switched from SCG to FP or withdrawn. Standing height was measured (Holtain stadiometry) at baseline, after 8 weeks and at 6 weeks intervals thereafter for 1 year. Morning peak flows (PEFam) were recorded by patients for 2 weeks during baseline, and 1 week before each visit during treatment. Urinary free cortisol (24 h) was measured at baseline, 6 months, and 1 year. After 8 weeks, 22 patients were withdrawn from SCG group (and were switched to FP), and five patients were withdrawn from the FP group due to poor asthma control. A further 21 and 11 patients were withdrawn from the SCG and FP groups, respectively, during the course of the study. There were no significant differences between patients who received FP and SCG for 1 year (n = 34 and n = 26, respectively) in terms of height velocity adjusted for age and gender (HV), or height velocity standard deviation scores adjusted for gender (HVSDS). Mean HV (mean HVSDS) were 6.0 cm/yr (0.1) and 6.5 cm/yr (0.5) for FP and SCG, respectively. There were no treatment differences in mean 24 h urinary free cortisol levels at 6 and 12 months. Mean % predicted PEFam improved over 1 year in both groups but to a greater degree in the FP group. We concluded that growth was normal in mildly asthmatic children receiving FP (50 micrograms bid) for 1 year. There were fewer withdrawals and lung function improved to a greater extent in FP treated patients than in patients receiving SCG.

Methicillin-resistant Staphylococcus aureus in children with cystic fibrosis: An eradication protocol.

A retrospective 12-year study (May 1988-July 2000) was undertaken in children with cystic fibrosis (CF) to evaluate 1) the magnitude of methicillin-resistant Staphylococcus aureus (MRSA) in these children; 2) the clinical impact of MRSA on CF; and 3) the efficacy of an MRSA protocol aimed at the eradication of the carrier state. The study maneuver comprised of 1) surveillance cultures of throat/rectum to detect the MRSA carrier state; 2) life-long cephradine rather than flucloxacillin to lift selection pressure; 3) topical application of oral and nebulized vancomycin for 5 days to clear the carriage of MRSA; and 4) a strict antistaphylococcal hygiene program, including handwashing and device policy. Fifteen children with CF (11 boys, with median age 117 months) positive for MRSA were enrolled. The current prevalence of MRSA among children with CF in our hospital is 6.5%. Of 15 children identified, only 12 (18 episodes of MRSA colonization) were treated according to protocol. Median age of MRSA acquisition was 73 months (interquartile range, 43-134 months). In 7 patients (55%), MRSA was eradicated. Of a total of 18 MRSA episodes, the protocol was successful in 10 episodes. The mean period of MRSA-free status was 12 months (range, 6-36 months). Pulmonary function (measured by FEV(1)) was not affected (68% of predicted before treatment, and 68% of predicted after treatment). All children were oropharyngeal carriers of both MRSA and ceftazidime-resistant P. aeruginosa. We believe that an effort has to be made to limit MRSA in CF clinics for the following reasons: 1) MRSA carriage in any individual is an abnormal condition; 2) limitation of systemic vancomycin use is desirable; 3) MRSA carriage may be a contraindication for lung transplantation; and 4) epidemiologically, a CF unit with a substantial MRSA problem functions as a source of dissemination for other patients.

Selective histamine blockade in childhood asthma; the effect of terfenadine on resting bronchial tone and exercise induced bronchoconstriction.

The orally active histamine H1 blocker terfenadine was investigated for its effect on resting bronchial tone and exercise induced bronchoconstriction in 20 asthmatic children by a double blind placebo controlled study. Terfenadine produced acute broncholidation with an average 32% improvement in FEV1 by 3 h. After exercise challenge terfenadine partially inhibited exercise induced bronchoconstriction. The maximum fall in PEFR after exercise was reduced from 32% after placebo to 21.5% after terfenadine. These results suggest that asthmatic children have background resting 'histamine tone' that is reversible by histamine H1 blockage.

Targeting of dornase alpha therapy in adult cystic fibrosis.

Although dornase alpha (recombinant human DNase) can thin the viscid pulmonary secretions of cystic fibrosis (CF), clinical trials in groups of unselected patients have shown only modest average improvements in pulmonary function. The product is very expensive, so in conjunction with purchasers we designed selection criteria and a protocol for a 2-week trial to target CF individuals who might gain most benefit. Treatment was to be continued in those showing > or = 10% improvement in pulmonary function. Those who had a trial of dornase alpha were followed up for 2 years. Of 25 patients who had a 2-week trial of dornase alpha, 17 met the criteria for continuation (average gain in forced expiratory volume 37%). The 11 of these who were still alive at 2 years had a greater initial average FEV1 improvement than those who had died (45% versus 22%), and still had an average improvement of 31% at 2 years. The 8 patients who did not meet the criteria for continuation were older and had required fewer intravenous antibiotic courses. All these were alive at 2 years with unchanged clinical indices. This method of selection for dornase alpha treatment allows targeting to those who gain most benefit without disadvantaging the remaining patients. Furthermore, production of such guidelines in conjunction with purchasers obviates funding difficulties and allows rational prescribing.

Pulmonary function in children after neonatal meconium aspiration syndrome.

Eighteen children aged 6 to 11 years old who fulfilled criteria for the diagnosis of neonatal meconium aspiration syndrome were investigated to find out the prevalence of previous and current respiratory symptoms, and abnormal pulmonary function tests, chest radiographs, and ventilation scans. Eleven of the 18 had no respiratory symptoms and eight of these had normal pulmonary function on testing. Two had mild limitation of expiratory airflow that did not respond to treatment with bronchodilators, and one had exercise induced bronchospasm that responded to treatment with bronchodilators. Seven of the 18 had recurrent cough and wheezing compatible with a diagnosis of asthma, and five of these had appreciable exercise induced bronchospasm that responded to treatment with bronchodilators. None of the children with symptoms had a personal or family history of atopy or had had acute bronchiolitis. All chest radiographs were normal. We found a much higher prevalence of asthmatic symptoms and abnormal bronchial reactivity among survivors of neonatal meconium aspiration syndrome than in the general childhood population. Aspiration of meconium may have long term consequences for the developing respiratory tract and is associated with abnormal respiratory function in later childhood.

Fluorescein dilaurate test of exocrine pancreatic function in cystic fibrosis.

The fluorescein dilaurate test, a non-invasive test of exocrine pancreatic function, was carried out on 21 children with cystic fibrosis and pancreatic exocrine insufficiency, and 12 healthy siblings. The test clearly discriminated between the patients with cystic fibrosis and severe exocrine pancreatic insufficiency and the normal control subjects.

Long term outcome of ventilated asthmatics.

Over a 25 year period, 31 asthmatic children received artificial ventilation for acute asthma at Alder Hey Children's Hospital on 48 occasions. Altogether 47 episodes occurred from 1971-89, with no decline in the number of episodes per year (mean 2.5) over this period. Eight children died during intermittent positive pressure ventilation (IPPV), and of the 23 survivors, three further children had subsequently died from asthma. Seventeen children were followed up for more than a year after IPPV. Sixteen still had symptoms of asthma and over half had symptoms every day. Ten cooperated with pulmonary function tests: mean forced expiratory volume in one second was 83% of predicted and geometric mean provocative histamine concentration (PC20) was 2.1 mg/ml. Since the follow up study a fourth patient had died from asthma. IPPV continues to be required for a small number of asthmatic children each year. The survivors remain a high risk group with significant continuing morbidity and mortality.

Oro-caecal transit time and intra-luminal pH in cystic fibrosis patients with distal intestinal obstruction syndrome.

Oro-caecal transit time assessed by the lactulose/hydrogen breath test was prolonged in cystic fibrosis patients experiencing distal intestinal obstruction syndrome (DIOS); compared to those without the syndrome, and normal controls. Jejunal intraluminal pH was lower in cystic fibrosis patients compared to controls, but no difference was observed between those patients experiencing DIOS, and those cystic fibrosis patients without the syndrome. The prolonged oro-caecal transit time observed in cystic fibrosis patients with DIOS may contribute to the syndrome, however intraluminal pH is unlikely to be a factor in the aetiology of DIOS.

Accident and emergency department attendance by asthmatic children.

Attendances at the accident and emergency department of a children's hospital for treatment of acute asthma were studied for one year to determine the characteristics of the children attending and their management. Eight hundred and twenty children, median age 5.5 years, made 1389 visits. Records were available from 1046 visits. Clinical information and assessment of the severity of the attack in the department was often inadequate. Peak flow records were available for 366 (35%). Attendances were most frequent in September and during the evening, but there was no significant day to day variation. Eight hundred and three children (78%) were self referred. Before attendance 962 (92%) had used a bronchodilator, including nebulised salbutamol (11%); 2% had taken prednisolone and 21% antibiotics. Five hundred and sixteen visits (49%) led to admission and 19% of those admitted required intravenous treatment. Probably some children who at present attend hospital for treatment of acute asthma could be managed at home, but this cannot be assumed without better understanding of the reasons for hospital attendance. More information is needed.

An unusual manifestation of staphylococcal lung infection.

An infant developed a rapidly progressive respiratory illness with cystic lesions on chest radiography. At thoracotomy there were multiple bullae on the surface of the lung. Staphylococcus aureus, of phage type 71, was isolated from the bullous fluid. We believe the lung disease was caused by an epidermolytic toxin.

In vitro assessment of combined antibiotic and mucolytic treatment for Pseudomonas aeruginosa infection in cystic fibrosis.

The minimal inhibitory concentration of azlocillin for Pseudomonas aeruginosa is appreciably reduced when combined with the mucolytic agent mesna (Mistabron) because of an independent bacteriostatic effect of mesna. Bactericidal activity of azlocillin is unaltered by mesna. Mesna inhalations alone or combined with azlocillin may benefit cystic fibrosis patients with pseudomonas lung infections.

Pathology mimicking distal intestinal obstruction syndrome in cystic fibrosis.

Eight patients with cystic fibrosis had chronic abdominal pain and the other features of distal intestinal obstruction syndrome. Coexistent abdominal pathology was shown in six patients. Two had a small bowel volvulus, and the others had Crohn's disease, a small bowel fistula, appendix abscess, and an ovarian dermoid. Opiate abuse exacerbated symptoms in two other patients.

Recurrent accident and emergency department attendance for acute asthma in children.

Asthmatic children aged over 5 years making repeated visits to the accident and emergency department of a children's hospital were compared prospectively, on the basis of a clinical questionnaire and pulmonary function tests, with a control group of outpatients with asthma to find the reasons for their repeated attendance. Recurrent attenders (n = 145) had more severe asthma than control subjects (n = 118), with greater airway obstruction at rest (FEV1 79% v 85% predicted) and bronchial lability (47% v 38%). Significantly more of the "emergency" group used pressurised aerosols and fewer dry powder inhalers to administer bronchodilators. There were no differences in prophylactic treatment. Seventy one per cent of parents in the emergency group had feared that their child would die during an attack, compared with 56% of control subjects. Eighty one per cent of children were self referred to the accident and emergency department. Most parents had found hospital to be the quickest means of obtaining treatment in an emergency. There were no differences between the two groups in parents' knowledge about asthma, home conditions, or social disadvantage. Although children who repeatedly attend hospital accident and emergency departments for treatment of acute attacks have more severe asthma than controls and show some deficiencies in treatment, the major determinant of attendance appeared to be the parents' conviction that appropriate treatment could not be obtained elsewhere.

Ceftazidime treatment in cystic fibrosis: resistant organisms in sputum and faeces.

Ceftazidime was used as the only intravenous agent for treating lower respiratory tract infections in patients with cystic fibrosis. The risks of inducing beta lactamases and conferring antibiotic resistance are high when monotherapy is used; so the emergence of resistant bacteria was studied prospectively in the sputum of 120 patients. The mean age of patients was 9.0 (range 0.3-25) years and there were equal number of male and female patients. Pseudomonas aeruginosa was the only ceftazidime resistant bacterium to be isolated from the respiratory tract, and was identified only in chronically colonised patients. Ceftazidime resistance occurred in 103 (14%) of 750 P aeruginosa isolates, and in 16 of 36 chronically colonised patients. Ceftazidime resistant organisms were isolated from the faeces of 17 of 64 patients investigated. Eighty two per cent of the resistant faecal organisms were single isolates: the same resistant organism in faeces was isolated from successive samples in only two patients. In no case was the ceftazidime resistant enteric isolate the same as that from sputum. Patients chronically colonised by P aeruginosa did not harbour ceftazidime resistant enteric organisms any more than non-colonised patients. The use of ceftazidime as a single intravenous agent in treating chest exacerbations in cystic fibrosis does not induce a reservoir of ceftazidime resistant bacteria.

Postural effects on gas exchange in infants.

In adults with unilateral lung disease, pulmonary gas exchange is better when the patients is positioned with the good lung dependent. We studied the effects of body position on gas exchange in 10 infants with unilateral lung disease by measuring transcutaneous oxygen and carbon dioxide pressures in the supine and right and left lateral positions. We also performed krypton lung scans and measured changes in thoracic gas volumes in four of the infants. Transcutaneous oxygen pressure (mean +/- S.E.) was greater with the good lung uppermost (82 +/- 7.6 mm Hg) than with the good lung dependent (73 +/- 7 mm Hg) (P less than 0.02) or in the supine position (78 +/- 7 mm Hg). There were no changes in transcutaneous carbon dioxide pressure. The proportion of ventilation to the good lung was greater with the good lung uppermost than with the good lung dependent (P less than 0.01) or in the supine position (P less than 0.02) (64 +/- 3, 46 +/- 6, and 59 +/- 7 per cent, respectively). There were no significant changes with position in functional residual capacity, tidal volume, or dynamic lung compliance. We conclude that oxygenation in infants with unilateral lung disease is best with the good lung uppermost--the reverse of what has been observed in adults.

Changes in pulmonary function during the diuretic phase of respiratory distress syndrome.

To evaluate the relationship between improvement in pulmonary function and spontaneous diuresis in respiratory distress syndrome, nine premature infants requiring mechanical ventilation for RDS were studied at a mean age of 11.9 hours prior to the onset of diuresis, at onset of diuresis, at maximum urine output (mean age 44.9 hours), and at 24 hours after maximum urine output. Prior to diuresis functional residual capacity decreased from mean +/- SEM of 16.2 +/- 2 to 13.3 +/- 1.2 ml/kg, and dynamic lung compliance decreased from 2.5 +/- 0.3 to 1.8 +/- 0.3 ml/cm H2O (P less than 0.05), indicating that the respiratory disease was worsening. There was no significant change in alveolar-arterial oxygen gradient, peak inflating pressure, or rate of intermittent mandatory ventilation over this period. At the time of maximum urine output, however, FRC had increased 36% (P less than 0.05). CL had increased by 60% to 2.8 +/- 0.4 ml/cm H2O (P less than 0.025), AaDO2 had decreased from 246 +/- 27 to 184 +/- 30 torr (P less than 0.005), and PIP had decreased from 14.9 +/- 2.2 to 11.3 +/- 2.1 cm/H2O (P less than 0.05). On follow-up study 24 hours after maximum urine output, there was no further significant improvement in FRC, CL or PIP, but IMV rate and AaDO2 continued to decrease. These data show that the pulmonary function in RDS deteriorates until the onset of diuresis, after which it rapidly improves. This diuresis may represent the removal of excess lung liquid and seems necessary for improvement in RDS.