Pneumothorax from subpleural blebs-a new association of sotos syndrome?

We describe two unrelated patients with molecularly confirmed Sotos syndrome with multiple subpleural blebs and pneumothorax. We propose this as a new association. Patient 1 is a 3-year-old boy with a 1.9 Mb interstitial deletion of the long arm of chromosome 5, with breakpoints at q35.2 and q35.3, encompassing NSD1 and Patient 2 is a 9-year-old girl with a de novo truncating mutation within NSD1. Both patients presented with sudden onset dyspnea due to a unilateral pneumothorax: Patient 1 at the age of 18 months and Patient 2 at 9 years. In both, the pneumothorax recurred following removal of the chest drain and, on further investigations, multiple subpleural blebs were identified necessitating a pleurodesis and tissue resection. This is the first report of multiple subpleural blebs leading to pneumothorax in association with Sotos syndrome. Given the similar and unusual presentation in the two affected patients, we suggest that this may be a real association, albeit a rare one. While screening would not be advocated for such a rare association, we recommend that clinicians consider pneumothorax in patients with Sotos syndrome and sudden onset of dyspnea and are aware that it may be refractory to first line treatment.

Serum vitamin D levels in children with cystic fibrosis.

Osteopenia is increasingly recognized in adults with cystic fibrosis (CF), and is potentially related to vitamin D deficiency in both adulthood and childhood. Vitamin D supplements are recommended and prescribed to all pancreatic-insufficient patients. We aimed to ascertain whether vitamin D deficiency in children with CF was prevalent. 25-hydroxyvitamin D (25-OHD) was measured in 290 children attending a specialist pediatric CF clinic for annual assessment. 25-OHD levels were compared with reference values and to other biochemical markers, lung function, and growth. Levels were also analyzed by pancreatic status and by the presence of CF-related liver disease. Median 25-OHD was 65 (range, 9-190) nmol/l. One percent had levels below 15 nmol/l, and 6% had levels less than 25 nmol/l. Levels were lower in adolescents (P < 0.001) and during the "winter" months (P < 0.001). No relationship was found with pancreatic status or liver disease. In conclusion, the majority of children had normal 25-OHD levels. Interpretation is difficult due to a lack of knowledge of optimal levels of 25-OHD required for healthy bone accretion. Lower levels in adolescents may be a precursor to low levels in adulthood, and did not seem to be simply related to poor compliance with supplementation. This may reflect normal physiology.

Changes in lung function between age 8 and 14 years in children with birth weight of less than 1,501 g.

We set out to determine whether lung function of children with a birth weight of <1,501 g changed relative to expectations between the ages of 8 and 14 years. We hypothesized that changes in lung function may differ between those of birth weight above and below 1,000 g. The subjects of this study were born in the Royal Women's Hospital, Melbourne. There were 86 consecutive survivors with birth weights <1,000 g born between January 1, 1977 and March 31, 1982, and 124 consecutive survivors with birth weights 1,000-1,500 g born between October 1, 1980 and March 31, 1982. Lung function was measured at both age 8 and 14 years, corrected for prematurity in 78% (67/86) of those with birth weight <1,000 g, and in 69% (86/124) of those with birth weight 1,000-1,500 g. Overall, lung function was similar to predicted values at both 8 and 14 years of age [e.g., (forced expired volume in 1 s, FEV1% predicted) at age 8 years mean 88.5% (SD 14.7) and at age 14 years, mean 94.9% (SD 13.8)]. There were significant changes, mostly improvements, in lung function between age 8-14 years relative to predicted values: FEV1 (% predicted) increased between 8-14 years of age by a mean of 6.4 (95% confidence interval, 4.4-8.3). The improvements in some lung function variables were significantly greater in those of birth weight <1,000 g compared with those of birth weight 1,000-1,500 g: improvement in FEV1 (% predicted) between age 8-14 years in infants with birth weight <1,000 g had a mean of 10.3 (SD 13.1), and in those with birthweight 1,000-1,500 g a mean of 3.3 (SD 10.1). We conclude that lung function improved significantly relative to predicted values in children of birth weight <1,501 g between age 8-14 years. The improvements were greatest in those of birth weight <1,000 g.

The neorule: a new instrument to measure linear growth in preterm infants.

OBJECTIVES: To compare measurements of crown-heel length (CHL) made with the neorule with CHL measurements made with a stadiometer in term infants. To examine safety and reproducibility of CHL measurements in infants < 32 weeks gestational age (GA) using the neorule. METHODS: Three measurements of CHL were made by three teams during the first 2 days of life in healthy term infants. One team used the stadiometer and two the neorule. Two different teams made three measurements of CHL on four occasions at two week intervals in infants less than 32 weeks GA. Infants were continuously monitored, and any adverse event was recorded. RESULTS: Fifty term infants were studied, median (range) birth weight 3440 (2020-5010) g. The mean (SD, 95% confidence interval) difference between values obtained with the stadiometer and neorule was 0.08 (6.22, -1.69 to +1.85) mm and between the two neorule teams was 0.8 (4.48, -0.47 to +2.08) mm. Twenty preterm infants were studied, GA median (range) 29 (25(+0)-31(+6)) weeks, median (range) CHL 397 (339-475) mm. There were no adverse events. The difference (SD, 95%CI) between teams in the mean CHL measurement was 0.18 (4.79, -1.02 to +1.38) mm, with interobserver limit of agreement -9.2 to +9.6 mm and coefficient of variation 1.2%. There were no significant differences between measurements made by single observers; the F ratio was 0.449 (df = 61, p = 0.6). CONCLUSION: The neorule is a safe and accurate way to measure CHL in newborn infants.

Short acting beta agonists for recurrent wheeze in children under 2 years of age.

BACKGROUND: Wheeze is a common symptom in infancy and is a common cause for both primary care consultations and hospital admission. Beta2-adrenoceptor agonists (b2-agonists) are the most frequently used as bronchodilator but their efficacy is questionable. OBJECTIVES: To determine the effectiveness of b2-agonist for the treatment of infants with recurrent and persistent wheeze. SEARCH STRATEGY: Relevant trials were identified using the Cochrane Airways Group database (CENTRAL), Medline and Pubmed. The database search used the following terms: Wheeze or asthma and Infant or Child and Short acting beta-agonist or Salbutamol (variants), Albuterol, Terbutaline (variants), Orciprenaline, Fenoterol SELECTION CRITERIA: Randomised controlled trials comparing the effect of b2-agonist against placebo in children under 2 years of age who had had two or more previous episodes of wheeze, not related to another form of chronic lung disease. DATA COLLECTION AND ANALYSIS: Eight studies met the criteria for inclusion in this meta-analysis. The studies investigated patients in three settings: at home (3 studies), in hospital (2 studies) and in the pulmonary function laboratory (3 studies). The main outcome measure was change in respiratory rate except for community based studies where symptom scores were used. MAIN RESULTS: The studies were markedly heterogeneous and between study comparisons were limited. Improvement in respiratory rate, symptom score and oxygen saturation were noted in one study in the emergency department following two salbutamol nebulisers but this had no impact on hospital admission. There was a reduction in bronchial reactivity following salbutamol. There was no significant benefit from taking regular inhaled salbutamol on symptom scores recorded at home. REVIEWER'S CONCLUSIONS: There is no clear benefit of using b2-agonists in the management of recurrent wheeze in the first two years of life although there is conflicting evidence. At present, further studies should only be performed if the patient group can be clearly defined and there is a suitable outcome parameter capable of measuring a response.

Diagnosis of cystic fibrosis in London and South East England before and after the introduction of newborn screening.

INTRODUCTION: Newborn screening (NBS) for cystic fibrosis (CF) was introduced to London and South East England in 2007. We wished to assess the details of missed cases, and to compare the age at diagnosis and other clinical parameters, prescreening and postscreening. METHODS: Retrospective and prospective case notes and database review of all newly diagnosed CF patients in our 7 CF centres, for 18 months before and 4 years after NBS started. RESULTS: 347 patients were diagnosed with CF. 126 patients were not screened (born before or abroad), and had a median age at diagnosis of 2.4 years, excluding those with meconium ileus (MI). Their median time to diagnosis from initial symptoms was 1 year, and in 10% it was >6 years. After NBS started, 170 were diagnosed by NBS (48% were already symptomatic); 7 moved into the region after NBS elsewhere; 34 presented with MI (6 were negative on NBS); and 10 screened children were missed (false negative cases). Median age of diagnosis was 3 weeks. Prevalence was 1 in 3991 live births. By 2 years of age (with data on 104 patients), 49 children (47%) had their first isolation of Pseudomonas aeruginosa, while 37 (36%) had their first growth of Staphylococcus aureus from respiratory cultures. CONCLUSIONS: NBS has significantly reduced the age of diagnosis, although many were symptomatic even at 3 weeks of age. A small number of patients with CF can still be missed by the screening programme, and the diagnosis should be considered even with a negative screen result.

Comparison of resistance measured by the interrupter technique and by passive mechanics in sedated infants.

Airways resistance measured by the interrupter technique (Rint) requires little patient cooperation and has been successfully used in young children, but little studied in infants. The authors aimed to evaluate the measurement of Rint in infants, using a commercially available device (the MicroRint), by comparing it with an established technique to measure respiratory resistance: the single breath occlusion technique (SBT); and a measure of airflow obstruction during forced expiration. Infants <18 months old with a history of wheeze, sedated with triclofos for pulmonary function testing, had measurements taken and compared to Rint (using the MicroRint), respiratory system resistance (Rrs) by SBT, and to maximal flow at functional residual capacity (V'maxFRC). Paired data from 25 of 37 infants studied was obtained. There was a significant difference between Rint (mean 2.94+/-0.68) and Rrs (4.02+/-0.87), but the two measures were strongly correlated (r=0.7). Rint was negatively correlated with V'maxFRC (r=-0.63). Smaller infants failed to trigger the MicroRint. Interrupter resistance values in infants are significantly lower than values of respiratory system resistance obtained by passive mechanics. However, there is a strong correlation between the two measurements, as well as between resistance measured using the interrupter technique and maximal flow at functional residual capacity, which indicates that resistance measured using the interrupter technique may be a useful marker of airway obstruction in infants. There remain a number of theoretical and technical problems which require further exploration.

How do we treat wheezing infants? Evidence or anecdote.

Consultant paediatricians were questioned about their management of wheezing disorders in infants. Salbutamol was the preferred bronchodilator for recurrent wheeze, whereas ipratropium was preferred in viral bronchiolitis. Doses of both medications varied widely. Both inhaled and oral corticosteroids were considered by most respondents. Practice does not clearly follow guidelines or evidence and presumably continues to be based on anecdote.

Persistent wheezing in infants with an atopic tendency responds to inhaled fluticasone.

BACKGROUND: The role of inhaled corticosteroids for the treatment of wheeze in infancy remains unclear. AIM: To investigate the effect of inhaled fluticasone on symptoms in a group of wheezy infants who had a high risk of progressing to childhood asthma. METHODS: A total of 52 infants, under 1 year of age, with a history of wheeze or cough and a history (personal or first degree relative) of atopy were prescribed either 150 microg fluticasone twice daily (group F) or placebo (group P), via metered dose inhaler, for 12 weeks following a two week run in period. Symptoms were scored in a parent held diary and the mean daily symptom score (MDS) and symptom free days (SFD) calculated for each two week period. RESULTS: Thirty seven infants completed the study. Both MDS and SFD improved significantly between the run in and final two week period in group F, but not group P, with a mean difference in change (95% CI) between groups of 1.12 (0.05 to 2.18) for MDS and median difference of 3.0 (0.002 to 8.0) for SFD. CONCLUSION: Improvement of clinical symptoms in response to fluticasone can be shown in this high risk group of infants. In the absence of effective alternatives inhaled corticosteroids should be considered in this patient group.

To clip or not to clip? Noseclips for spirometry.

The use of noseclips for open-circuit spirometry is sporadic, despite guidelines encouraging their use. The authors aimed to evaluate whether noseclips significantly affected measurements of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in children attending a tertiary, paediatric respiratory centre. Children attending the asthma and cystic fibrosis (CF) clinics were asked to perform two sets of spirometry, one with and one without noseclips in random order, 20-min apart. Paired data was obtained on 62 patients (32 asthma, 30 CF) with a median age of 11.4 yrs (range 7.2-17.2 yrs). There were no systematic differences in FEV1 or FVC measured with and without noseclips, although seven children (11%) had clinically significant differences in FEV1 of >190 mL. There is no clear advantage to wearing noseclips when performing open-circuit spirometry. Individuals should be assessed to ascertain their optimal technique, which should then be used consistently in clinical practice. Noseclips should probably be retained for research protocols.

Inhaled salbutamol for wheezy infants: a randomised controlled trial.

BACKGROUND: Salbutamol is frequently used as a bronchodilator for infants who wheeze. Many single dose studies have questioned its effectiveness. AIMS: To investigate the response of wheezy infants to salbutamol over an extended time period in order to elucidate either symptomatic relief or a protective effect. METHODS: Eighty infants under 1 year, with persistent or recurrent wheeze and a personal or family history of atopy, were recruited to a randomised, double blind, cross over, placebo controlled trial. Salbutamol (200 microg three times daily) or placebo were administered regularly over two consecutive treatment periods of four weeks via a spacer and mask. Symptoms of wheeze and cough were recorded in a diary. At the end of the study pulmonary function tests were performed before and after salbutamol (400 microg). RESULTS: Forty eight infants completed the diary study; 40 infants underwent pulmonary function testing. No difference in mean daily symptom score was observed between the salbutamol and placebo periods. There was no difference in the number of symptom free days. Compliance and forced expiratory flows remained unchanged and resistance increased following salbutamol. There was no relation between the response measured by symptom score or pulmonary function in individual patients. CONCLUSION: In wheezy infants with an atopic background, there was no significant beneficial effect of salbutamol on either clinical symptoms or pulmonary function. Clinical effects could not be predicted from pulmonary function tests. Salbutamol cannot be recommended as the bronchodilator of choice in this age group.

Partial liquid ventilation compared with conventional mechanical ventilation in an experimental model of acute lung injury.

OBJECTIVE: To compare the effects of partial liquid ventilation with conventional mechanical ventilation on oxygenation and pulmonary mechanics in saline lavaged rabbits. METHODS: Following acute lung injury (saline-lavage), rabbits were assigned to continue conventional mechanical ventilation (n = 6) or commence partial liquid ventilation (n = 6). In both groups the inspired oxygen concentration was 100% throughout the study. The target PaCO2 of 40-60 mmHg was accomplished by keeping the tidal volume between 7 and 10 mL/kg. During the study the peak inspiratory pressure was adjusted to maintain the target PaCO2. Arterial blood gases were taken pre-lavage, immediately post-lavage (time = 0) and then hourly for 5 hours. Pulmonary mechanics were estimated by measuring compliance and resistance. Pulmonary function was measured pre-lavage, immediately post-lavage and at 1 and 5 hours. At 5 hours the rabbits were killed and the lungs were removed for histological examination. RESULTS: Baseline PaO2, compliance and resistance were not significantly different between groups. The partial liquid ventilation group had a higher PaO2 and a significantly better oxygenation index one hour after commencing partial liquid ventilation and a significantly higher PaO2 averaged over the three hours post-treatment. There were no significant differences in compliance, resistance or lung damage scores. CONCLUSIONS: In this experimental model of acute lung injury, partial liquid ventilation resulted in immediate and sustained increase in PaO2 over 3 hours without significant change in lung mechanics or histological lung damage.

Partial liquid ventilation and nitric oxide in experimental acute lung injury.

OBJECTIVE: To investigate the effects of inhaled nitric oxide (iNO) and partial liquid ventilation (PLV) on oxygenation and pulmonary haemodynamics in acute lung injury (ALI), and to assess their effects on lung function, systemic haemodynamics and lung injury. METHODS: Using saline lung lavage, ALI was induced in 18 piglets. A control group was ventilated with conventional mechanical ventilation (CMV) for 2 h. An iNO-first group received iNO for the first hour and then iNO with PLV. A PLV-first group received PLV for the first hour and then PLV with iNO. Variables were measured at baseline, 5 min postlavage, and at 1 h and 2 h postlavage. RESULTS: During the first hour, both treatment groups showed improvement in oxygenation index (OI). At 2 h, the dif-ferences in OI were statistically significant (P = 0.037), with a mean +/- SD of 23.8 +/- 20.7 in the control group, 4.4 +/- 0.9 in the PLV-first group and 6.5 +/- 3.1 in the iNO-first group. The OI was similar in both treatment groups (P = 0.178). At 2 h, the pulmonary artery pressure (PAP) was significantly different (P = 0.04) between groups, with a mean +/- SD PAP of 36.3 +/- 7.2 mmHg in the control group, 27.4 +/- 4.0 mmHg in the PLV-first group and 30.0 +/- 4.1 mmHg in the iNO-first group. The PAP was similar in both treatment groups (P = 0.319). CONCLUSION: In ALI, oxygenation and pulmonary hypertension are improved with PLV and iNO given together, regardless of the order in which they are commenced.

Oxygenation is not improved by partial liquid high frequency ventilation using a high lung volume strategy. An experimental study.

OBJECTIVE: To investigate the effect on oxygenation and lung damage of partial perfluorocarbon liquid high frequency oscillatory ventilation (PL-HFOV) versus high frequency oscillatory ventilation (HFOV) alone, in rabbits with acute lung injury, using high lung volume strategy HFOV. METHODS: Twelve adult New Zealand white rabbits were initially ventilated with HFOV after anaesthesia, sedation and paralysis. After induction of lung injury with saline lavage, all animals received a single sigh breath of 30 cmH(2)O for 30 seconds. They were then allocated to receive either HFOV alone (n = 6) or PL-HFOV (n = 6). Arterial blood gases were taken pre- and post-lavage and then hourly for 5 hours. The oxygenation index (OI, in cmH(2)O/mmHg) was calculated using the formula: OI = (MAP x F(I)O(2) x 100) / PaO(2). The lungs were then removed for histological examination to score lung injury. RESULTS: Two rabbits died in the PL-HFOV group and none in the HFOV group, p = 0.45 (Fisher's exact test). At one hour the oxygenation index (OI) was 4.5 in the HFOV group and 6.6 in the PL-HFOV group, p = 0.49 and the PaO(2) was 374 mmHg in the HFOV group and 311 mmHg in the PL-HFOV group, p = 0.39. Average OI over the first three hours was 3.6 in the HFOV group and 5.0 in the PL-HFOV group, p = 0.27 and the PaO(2) was 404 mmHg in the HFOV group and 337 mmHg in the PL-HFOV group, p = 0.12. The lung histology damage score was 2.33 in the HFOV group and 2.50 in the PL-HFOV group, p = 0.83. CONCLUSIONS: In this model of acute lung injury, using a high volume HFOV strategy to optimise lung recruitment, PL-HFOV did not result in any further improvement in oxygenation when compared with HFOV alone. The question of safety with PL-HFOV remains.