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. (C) 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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.

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%FEV(1)) 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%FEV(1) 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.

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.

Back ground. 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 mu l vs 402.2 +/- 31.3 mu l, p =0.0002), while BHR(-) Subjects did not show this change (387.6 +/- 29.7 mu l vs 364.1 +/- 30.1 mu l, 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 mu M vs 1.5 +/- 0.1 mu M, 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.

Background: Combining exhaled breath condensate (EBC) and exhaled nitric oxide (eNO) may be a useful, non-invasive method to assess airway inflammation in pediatric asthma. This cross-sectional study evaluated the relationship of both EBC nitrite/nitrate (NOx) and EBC pH with asthma control and eNO in asthmatic, normal, and atopic children.Methods: A total of 92 children were recruited, comprising 62 with asthma, 14 with atopy only, and 16 who were normal and non-atopic. All completed a questionnaire for asthma symptoms and control. Variables measured were spirometry, EBC NOx, pH, and eNO.Results: EBC NOx in those with asthma (mean 8.4 mu M, Cl 7.5-9.4) was significantly elevated when compared with normal (4.8 mu M, Cl 3.4-6.2, P= 0.0007) and atopic children (6.5 mu M, Cl 4.0-9.1, P=0.02). The mean level of eNO was significantly higher in those with asthma (43.7 ppb, Cl 34.7-51.1, P< 0.001) and atopy (24 ppb, Cl 16.7-31.2, P< 0.05) when compared with normal children (11.5 ppb, Cl 6.7-16.2). There was a significantly lower pH in those with asthma and a FEV1, < 80% predicted (P= 0.03), but no significant overall differences in EBC pH between the three groups of children. There was a significant correlation between eNO and EBC NOx in the group as a whole, but not between eNO and EBC pH.Conclusions: Mean EBC NOx levels differ between children with asthma, atopy, and those who are normal, but it is not interchangeable with eNO. EBC pH may be an additional marker of asthma control.

An admission to an intensive care unit (ICU) with asthma is a marker of asthma severity and may be a precursor of asthma death. The aim of this study was to investigate risk factors for acute severe asthma needing an ICU admission. We hypothesized that children admitted to the ICU represent a severe phenotype with identifiable premorbid clinical features. The study was case-control in design. One hundred and forty-one children were studied. Seventy children admitted to the ICU and 71 children admitted to the general medical ward served as cases and controls, respectively. Children were aged between 1-16 years. They underwent skin prick allergy testing, and had a nasopharyngeal aspirate and serology performed to screen for respiratory pathogens. Their parents completed an asthma and allergy symptom questionnaire and the Newcastle Asthma Knowledge Questionnaire (NAKQ). On univariate analysis, an admission to the ICU was more likely in children with 1) "frequent episodic" or "persistent" background asthma; 2) three or more previous admissions for asthma; 3) one or more asthma admissions in the previous 12 months; 4) three or more presentations to the Emergency Department (ED) in the preceding 12 months; 5) three or more positive responses on skin prick allergy testing; 6) an elevated IgE level; 7) oxygen saturation on presentation < or =91%; 8) longer duration of asthma; 9) lower level of maternal education; 10) an admission during autumn; 11) three or more siblings; and 12) being prescribed antibiotics. Risk factors that remained significant on multivariate analysis were three or more presentations to the ED in the preceding 12 months (P=0.003), an elevated IgE level (P=0.01), oxygen saturation on presentation < or =91% (P=0.003), and longer asthma duration (P=0.02). ICU patients took longer to see a doctor and to commence oral steroids. No differences were found between cases and controls in the proportion taking preventer therapy (58% vs. 52%), provided with a written asthma action plan (32% vs. 25%), or in whom spirometry or peak flow was measured (28% vs. 42%). However, rates were low in both groups. Parental asthma knowledge was generally poor. This study identified risk factors for an ICU admission in children with asthma. A potentially preventable risk factor is a history of multiple ED presentations in the past year. Specialist referral of children with multiple ED presentations may improve asthma control and reduce the risk of an ICU admission. Background asthma management remains suboptimal in children needing hospitalization.

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.

Mirthful emotions such as laughter and excitement are unrecognized but perhaps important triggers of asthma. Our study aimed to explore the prevalence, mechanisms, and associations of mirth-triggered asthma (MTA) in children. Our MTA prevalence questionnaire was given to 285 children who presented to the Emergency Department of Sydney Children's Hospital (SCH) with an acute episode of asthma. Our MTA profile questionnaire study was a cross-sectional study of 541 children with asthma. The parents completed a questionnaire regarding their child's asthma. In our laughter diary study, diary cards were given to the parents of 21 children with asthma. The diary required details regarding the mirthful stimulus, symptoms of asthma, and recording of peak expiratory flow (PEF) measurements. Of the selected cohort, 31.9% had mirth-triggered asthma. In the cross-sectional study, mirth-triggered asthma was more common: with increasing age (P = 0.02); in those who in the last 3 months had taken more doses of salbutamol (P = 0.005), and who had more wheeze, nocturnal symptoms, and early morning symptoms (P < 0.0005); and in those who reported exercise-induced asthma (P < 0.0005). Laughter was more commonly reported as a trigger than excitement; cough was the most prominent symptom; and symptoms mostly occurred within 2 min of the mirthful stimulus. In the laughter diary study, 59 of 130 recorded events described symptoms of asthma. Mirth while watching a film led to PEF of 73% of baseline, compared with 81% for mirth with exertional play, and 95% for mirth with nonexertional play (P = 0.01). Mirth-triggered asthma is common, and is an indicator of suboptimal asthma control.

Our aim was to study the effect of lower airway infection on clinical parameters, pulmonary function tests, and inflammation in clinically stable infants and young children with cystic fibrosis (CF). To accomplish this goal, a prospective cohort of screened CF patients under 4 years of age were studied, using elective anesthesia and intubation for: passive respiratory mechanics (single breath occlusion passive deflation) and lung volumes (nitrogen washout), under neuromuscular blockade; and bronchoalveolar lavage (BAL) of 3 main bronchi for cytology, cytokine interleukin (IL)-8, and quantitative microbiology. There were 22 children studied, with a mean age of 23.2 months (6.7-44 months). A greater relative risk of lower airway pathogens was associated with prior respiratory admission (3.60, 95% confidence interval [CI] 2.87-4.51), history of asthma (1.75, 95% CI 1.52-2.03), and chronic symptoms (1.50, 95% CI 1.23-1.83), especially wheeze (1.88, 95% CI 1.61-2.19). Lower respiratory pathogens (> or = 10 cfu/ml BAL) were found in 14 out of 22, and greater than 10(5) cfu/ml in 8 out of 22 subjects. The level of pathogens in BAL (log10 cfu/ml) explained 78% of the variability in percent neutrophils and 34% of the variability in IL-8 levels. Pathogen level also correlated with pulmonary function tests of specific respiratory system compliance (r -0.49, p = 0.02) and functional residual capacity over total lung capacity (r 0.49, p = 0.03). We conclude that the presence of pathogens in the lower airways correlated with levels of inflammation, respiratory system compliance, and degree of air trapping.

High-resolution computed tomography (HRCT) is a sensitive technique for early visualisation and location of cystic fibrosis (CF) bronchopathology, and has been shown to detect acute reversible and chronic changes. It would be expected to correlate with markers of the underlying pathological processes, such as sputum cytokines and cytology, as well as with pulmonary function tests (PFTs). Our aim was to study the relationship between PFTs, sputum cytology, and sputum cytokine interleukin-8 (IL-8) and HRCT in CIF patients. Prospective standardized collection of sputum samples was performed at the time of routine annual high-resolution CT scans. Forced expired volume in 1 sec (FEV1) and forced vital capacity (FVC) were recorded. Sputum processing was selective, with dispersal by the three-enzyme technique. IL-8 measurements were by kit assay. HRCT scans were scored by a pediatric radiologist, blinded to clinical condition, using a modified Bhalla score.Forty-three CT scans were performed on 34 children with CIF between March 1998 and April 2000. Mean age was 12.3 years (range, 6-21 years), FEV1 (% predicted) was 67% (range, 23-120%), and mean modified Bhalla score was 11.2 (range, 0-22). Sputum IL-8 concentration (mean, 86; range, 4-150 ng/mL) and total cell count (mean, 31.9 x 10(6)/mL; range, 21.8-42.0 x 10(6)/mL) were high. FEV1 and FVC correlated with modified Bhalla score (r = -0.66, P < 0.0001 for both), and most individual components of the score, especially mosaic perfusion (r = -0.64, r = -0.61 respectively, P < 0.0001) and extent of bronchiectasis (r = -0.61, P < 0.0001 for both). The combination of these two predicted 58% of the variability in FEV1 on analysis of variance (P < 0.0001). Sputum total cell count correlated weakly with modified Bhalla score (r = 0.38, P < 0.05) and with FEV1 and FVC (r = -0.36, P < 0.05; and r= -0.46, P < 0.01). Differential cell counts, cell viability, and IL-8 did not correlate with modified Bhalla scores, or with reversible components such as mucus plugging, centrilobular nodules, or peribronchial thickening.In conclusion, pathological changes on HRCT correlated with lung function but not with sputum markers of inflammation. (C) 2002 Wiley-Liss, Inc.

Despite the importance of pulmonary exacerbations in CF in both clinical and research settings, both published evidence and consensus are lacking concerning the criteria used to define an exacerbation. The use of hospitalization as a surrogate measure presupposes uniformity among clinicians in diagnosis and treatment of exacerbations. Our aims were to evaluate consensus among clinicians about the variables considered helpful in diagnosing an exacerbation requiring treatment. A comprehensive list of symptoms, signs, and investigations used to define exacerbations was compiled from published trials. A written self-administered questionnaire included the list in age-appropriate groups to survey opinion about the helpfulness of each item, and the estimated proportion of patients admitted within a month of diagnosis of an exacerbation. This was sent to all clinicians managing CF patients in Australia. There were replies from 59/91 clinicians (65%), 41/60 (68%) from those managing children and 18/31 (58%) from those managing adults. Responses of those managing children and adults differed for 7/32 variables (Mann-Whitney test, P < 0.05). Clinic grouping did not show greater consensus among responses of pediatricians (Kruskal-Wallis test, P = 0.362). Consensus, >74% or <26% of respondents rating a variable helpful/very helpful, was found in only 50% of variables listed. Estimated admission rate within a month of diagnosis was 61% (30-100%) for those managing adults and 48% %5-100%) for pediatricians. A lack of consensus was found among clinicians managing CF about the variables considered in diagnosing an exacerbation. The estimated proportion admitted within a month of diagnosis was very variable. This demonstrated inhomogeneity in approach to diagnosis and management of an exacerbation suggests a significant heterogeneity of clinical care.

Australian and New Zealand Journal of MedicineVolume 16, Issue 6 p. 812-812 CYSTIC FIBROSIS. MANUAL OF DIAGNOSIS AND MANAGEMENT. Second Edition. By Mary C. Goodchild and John A. Dodge John Morton, John Morton Prince of Wales Children's Hospital, NSWSearch for more papers by this author John Morton, John Morton Prince of Wales Children's Hospital, NSWSearch for more papers by this author First published: December 1986 https://doi.org/10.1111/j.1445-5994.1986.tb00047.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume16, Issue6December 1986Pages 812-812 RelatedInformation

To the Editor: In response to Dr. Driver’s concern with regard to our documentation of malnutrition in this girl, I would like to submit the following documentation. It was our feeling that this young girl was suffering from anorexia nervosa. She had had a weight loss of 14 kg during the eight months prior to her first hospital admission and a further loss of 9 kg during her initial hospitalization in Denver. When we first saw her, her weight was 30 kg which is well below the third percentile and her height 154 cm, which is just on the 10th percentile. Mid-arm circumference and triceps skin fold thickness were not measured. Serum albumen levels initially 5 mg% on her initial admission fell progressively to 2.6 mg%. Her total lymphocyte count, initially 33% of 12,550, had fallen to 9% of 11,000 at the time of her admission in Boston and before the commencement of antifungal therapy. There was no question in our minds clinically that this girl was indeed grossly malnourished.

An adolescent developed invasive pulmonary aspergillosis in the limited form of a lung abscess. She had a weak immunologic response to the infection. Her depressed immunity was the result of prolonged corticosteroid therapy, compounded by malnutrition. In spite of this and other complications of corticosteroids, she made a full recovery from the fungal infection following treatment with amphotericin B and surgical excision of the lung abscess.