John Morton

Asthma Exacerbations in Children Associated with Rhinovirus but not Human Metapneumovirus Infection

Children with asthma were studied during the Southern hemisphere winter and summer of 2001-2002. Human rhinovirus (hRV) was significantly associated (P=.0001) with asthma exacerbations in winter and spring/summer, but not in intervening asymptomatic periods. Although hRV was also found in children with upper respiratory tract infection (URTI) who underwent sampling at the same time, it was present in significantly higher numbers of children with symptomatic asthma (P<.0001). Human metapneumovirus was also found in small numbers of children with URTI, but significantly less frequently in children with asthma.

Lung Growth and Airway Function after Lobectomy in Infancy for Congenital Lobar Emphysema

To characterize the outcome of lobectomy in infancy and the low expiratory flows which persist after lobectomy for congenital lobar emphysema, 15 subjects with this history were studied at age 8-30 yr. Total lung capacity was normal in all, but higher values (P < 0.05) were observed in nine subjects with upper lobectomy than in five subjects with right middle lobectomy. Ratio of residual volume to total lung capacity was correlated (P < 0.05) with the amount of lung missing as estimated from normal relative weights of the respective lobes. Xe(133) radiospirometry in eight subjects showed that the operated and unoperated sides had nearly equal volumes at total lung capacity, but that the operated side was larger than the unoperated side at residual volume. Perfusion was equally distributed between the two sides. Similar findings were detected radiographically in four other subjects. Forced expiratory volume in 1 s and maximal midexpiratory flow rate averaged 72 and 45% of predicted, respectively. Low values of specific airway conductance and normal density dependence of maximal flows in 12 subjects suggested that obstruction was not limited to peripheral airways. Pathologic observations at the time of surgery and morphometry of the resected lobes were not correlated with any test of pulmonary function. These data show that lung volume can be completely recovered after lobectomy for congenital lobar emphysema in infancy. The volume increase occurs on the operated side, and probably represents tissue growth rather than simple distension. The response to resection is influenced by the particular lobe resected and may be associated with decreased lung recoil near residual volume. Low expiratory flows in these subjects could be explained by several mechanisms, among which a disproportion between airway and parenchymal growth in infancy (dysanaptic growth) is most compatible with our data.

Early Cystic Fibrosis Lung Disease Detected by Bronchoalveolar Lavage and Lung Clearance Index

RATIONALE Unrecognized airway infection and inflammation in young children with cystic fibrosis (CF) may lead to irreversible lung disease; therefore early detection and treatment is highly desirable. OBJECTIVES To determine whether the lung clearance index (LCI) is a sensitive and repeatable noninvasive measure of airway infection and inflammation in newborn-screened children with CF. METHODS Forty-seven well children with CF (mean age, 1.55 yr) and 25 healthy children (mean age, 1.26 yr) underwent multiple-breath washout testing. LCI within and between-test variability was assessed. Children with CF also had surveillance bronchoalveolar lavage performed. MEASUREMENTS AND MAIN RESULTS The mean (SD) LCI in healthy children was 6.45 (0.49). The LCI was higher in children with CF (7.21 [0.81]; P < 0.001). The upper limit of normal for the LCI was 7.41. Fifteen (32%) children with CF had an elevated LCI. LCI measurements were repeatable and reproducible. Airway infection was present in 17 (36%) children with CF, including 7 (15%) with Pseudomonas aeruginosa. Polymicrobial growth was associated with worse inflammation. The LCI was higher in children with Pseudomonas (7.92 [1.16]) than in children without Pseudomonas (7.02 [0.56]) (P = 0.038). The LCI correlated with bronchoalveolar lavage IL-8 (R(2) = 0.20, P = 0.004) and neutrophil count (R(2) = 0.21, P = 0.001). An LCI below the upper limit of normality had a high negative predictive value (93%) in excluding Pseudomonas. CONCLUSIONS The LCI is elevated early in CF, especially in the presence of Pseudomonas and airway inflammation. The LCI is a feasible, repeatable, and sensitive noninvasive marker of lung disease in young children with CF.

Early Glucose Abnormalities in Cystic Fibrosis Are Preceded by Poor Weight Gain

OBJECTIVE Progressive β-cell loss causes catabolism in cystic fibrosis. Existing diagnostic criteria for diabetes were based on microvascular complications rather than on cystic fibrosis–specific outcomes. We aimed to relate glycemic status in cystic fibrosis to weight and lung function changes. RESEARCH DESIGN AND METHODS We determined peak blood glucose (BGmax) during oral glucose tolerance tests (OGTTs) with samples every 30 min for 33 consecutive children (aged 10.2–18 years). Twenty-five also agreed to undergo continuous glucose monitoring (CGM) (Medtronic). Outcome measures were change in weight standard deviation score (wtSDS), percent forced expiratory volume in 1 s (%FEV1), and percent forced vital capacity (%FVC) in the year preceding the OGTT. RESULTS Declining wtSDS and %FVC were associated with higher BGmax (both P = 0.02) and with CGM time >7.8 mmol/l (P = 0.006 and P = 0.02, respectively) but not with BG120 min. A decline in %FEV1 was related to CGM time >7.8 mmol/l (P = 0.02). Using receiver operating characteristic (ROC) analysis to determine optimal glycemic cutoffs, CGM time above 7.8 mmol/l ≥4.5% detected declining wtSDS with 89% sensitivity and 86% specificity (area under the ROC curve 0.89, P = 0.003). BGmax ≥8.2 mmol/l gave 87% sensitivity and 70% specificity (0.76, P = 0.02). BG120 min did not detect declining wtSDS (0.59, P = 0.41). After exclusion of two patients with BG120 min ≥11.1 mmol/l, the decline in wtSDS was worse if BGmax was ≥8.2 mmol/l (−0.3 ± 0.4 vs. 0.0 ± 0.4 for BGmax <8.2 mmol/l, P = 0.04) or if CGM time above 7.8 mmol/l was ≥4.5% (−0.3 ± 0.4 vs. 0.1 ± 0.2 for time <4.5%, P = 0.01). CONCLUSIONS BGmax ≥8.2 mmol/l on an OGTT and CGM time above 7.8 mmol/l ≥4.5% are associated with declining wtSDS and lung function in the preceding 12 months.

Bone mineral density in prepubertal asthmatics receiving corticosteroid treatment

Objective: To examine whether bone mass is reduced in prepubertal, asthmatics receiving high doses of inhaled corticosteroids.

Once daily insulin detemir in cystic fibrosis with insulin deficiency

The aim of this study was to determine if once daily insulin detemir reverses decline in weight and lung function in patients with cystic fibrosis (CF). 12 patients with early insulin deficiency and six with CF related diabetes (aged 7.2–18.1 years) were treated for a median of 0.8 years. Changes in weight and lung function following treatment were compared to pretreatment changes. Before treatment, the change in weight SD score (ΔWtSDS), percentage of predicted forced expiratory volume in 1 s (Δ%FEV1) and percentage of predicted forced vital capacity (Δ%FVC) declined in the whole study population (−0.45±0.38, −7.9±12.8%, −5.8±14.3%) and in the subgroup with early insulin deficiency (−0.41±0.43, −9.8±9.3%, −6.8±10.3%). Following treatment with insulin ΔWtSDS, Δ%FEV1 and Δ%FVC significantly improved in the whole study population (+0.18±0.29 SDS, p=0.0001; +3.7±10.6%, p=0.007; +5.2±12.7%, p=0.013) and in patients with early insulin deficiency (+0.22±0.31 SDS, p=0.003; +5.3±11.5%, p=0.004; +5.8±13.4%, p=0.024). Randomised controlled trials are now needed.

Cantú Syndrome: Report of Nine New Cases and Expansion of the Clinical Phenotype

Cantú syndrome, a rare disorder of congenital hypertrichosis, characteristic facial anomalies, cardiomegaly, and osteochondrodysplasia was first described in 1982 by Cantú. Twenty‐three cases of Cantú syndrome have been reported to date. The pathogenesis of this rare autosomal dominant condition is unknown. We describe 10 patients with Cantú syndrome (9 new cases and the long‐term follow‐up of a 10th case reported by Robertson in 1999) comparing the phenotype with that of the previously reported cases. We describe how the distinctive facial appearance evolves with time and report several new findings including recurrent infections with low immunoglobulin levels and gastric bleeding in some of our patients. The cardiac manifestations include patent ductus arteriosus, septal hypertrophy, pulmonary hypertension, and pericardial effusions. They may follow a benign course, but of the 10 cases we report, 4 patients required surgical closure of the patent ductus arteriosus and 1 patient a pericardectomy. Long‐term follow‐up of these patients has shown reassuring neuro‐developmental outcome and the emergence of a behavior phenotype including obsessive traits and anxiety.

Single high-dose oral vitamin D3 (stoss) therapy — A solution to vitamin D deficiency in children with cystic fibrosis?

OBJECTIVES To determine the safety and efficacy of stoss therapy on vitamin D levels over a 12 month period in children with cystic fibrosis and vitamin D deficiency (<75 nmol/L). STUDY DESIGN Retrospective chart review of 142 paediatric CF patients from 2007 till 2011. RESULTS Thirty eight children received stoss therapy and 37 children with vitamin D deficiency were not treated and served as a control group. The stoss treated group had a significant and sustained increase in 25-hydroxyvitamin D levels measured at 1, 3, 6 and 12 months post treatment compared to controls (94.82 ± 41.0 nmol/L, p=0.001; 81.54 ± 24.6 nmol/L, p=0.001; 92.18 ± 36.5 nmol/L, p=0.008 and 64.6 ± 20.0 nmol/L, p=0.006 respectively). At 12 months post intervention, the mean difference in vitamin D levels from baseline between the stoss treated group and controls was significant at 15 nmol/L compared to 5 nmol/L (p=0.038). CONCLUSION Stoss therapy effectively achieves and maintains levels of 25-hydroxyvitamin D greater than 75 nmol/L over 12 months.

A quality assurance review of outpatient care of children with life‐threatening asthma exacerbations

Objectives: A hospital admission for asthma represents an opportunity to address and improve asthma control. The aims of this study were to compare the ambulatory care of children admitted to the intensive care unit (ICU) following a life‐threatening asthma exacerbation with published guidelines of asthma management and to identify areas that could be targeted for change.

Mediators in Exhaled Breath Condensate after Hypertonic Saline Challenge

Background. Airway narrowing after hypertonic saline challenge (HSC) is postulated to be mediated by bronchoconstrictors and inflammatory mediators. Objective. To study the mechanism of this challenge by using exhaled breath condensate (EBC). Methods. Fifty-six subjects (9 to 72 years of age) performed an HSC, with EBC collection and exhaled nitric oxide (FENO) measurements before and after the challenge. Bronchial hyper-reactivity (BHR) was defined if forced expiratory volume in 1 second (FEV1) decreased by 10% compared with baseline (PD10). EBC volume was recorded and was analyzed for mucin, histamine, nitrite/nitrate, and pH. Results. Those with BHR had a significant rise in EBC volume/5-minute collection period after challenge (286.3 ± 25.6 μl vs 402.2 ± 31.3 μl, p = 0.0002), while BHR(−) subjects did not show this change (387.6 ± 29.7 μl vs 364.1 ± 30.1 μl, p = 0.55). FENO showed a significant decrease in both BHR(+) and BHR(−) groups after challenge (p = < 0.0001). In BHR(+) subjects histamine increased significantly (1.3 ± 0.1 μM vs 1.5 ± 0.1 μM, p = 0.006) compared with baseline, while EBC pH and mucin increased significantly after HSC in both groups. EBC nitrite did not change in either group. Conclusion. EBC analysis suggests that HSC causes an increase in pH and mucin in both groups, but EBC volume and histamine only increased in the BHR(+) group. This suggests that mast cells are activated and fluid flux is associated with the positive response, while mucin release is independent of BHR in HSC.