Effect of transfer from a pediatric to adult cystic fibrosis center on clinical status and hospital attendance.

AIM: Transfer from pediatric to adult services could lead to clinical deterioration, few studies have examined this. We sought to examine the clinical impact of a structured individualized transition and transfer process in patients with cystic fibrosis (CF). METHODS: Medical records of all patients with CF in Western Australia who transferred from a pediatric center (Princess Margaret Hospital for Children) to an adult CF center (Sir Charles Gairdner Hospital) between 2008 and 2012 were reviewed. Data were extracted for 2 years before and after transfer. The number of CF outpatient visits, inpatient days, and home intravenous antibiotic therapy (HIVT) days were recorded at yearly intervals before and after transfer. Sputum culture results at transfer were collected. All respiratory function and anthropometric data over the 4 years were extracted. RESULTS: Forty-two patients with CF were transferred between 2008 and 2012. The mean age at transfer was 18.9 years (range 17-22). Compared to 1-year pre-transfer, the frequency of outpatient visits at 1- and 2-year post-transfer increased. After transfer, there was no change in BMI, HIVT days, or inpatient days, and no acceleration in the expected decline in FEV1. CONCLUSION: This study found that transfer from a pediatric to an adult CF center using a structured, individualized transition and transfer process was not associated with accelerated clinical deterioration.

Epidemiology of paediatric chronic fatigue syndrome in Australia.

OBJECTIVE: To estimate the paediatrician-diagnosed incidence of chronic fatigue syndrome (CFS) in Australia, and describe demographic and clinical features, as well as approaches to diagnosis and management. METHODS: The Australian Paediatric Surveillance Unit facilitates monthly national surveillance of uncommon conditions seen by paediatricians. Data from young people aged <18 years diagnosed with CFS were collected. Incidence was estimated based on new cases reported from April 2015 to April 2016. RESULTS: A total of 164 cases of newly diagnosed CFS in young people aged 4-17 years were identified for inclusion. The estimated national incidence for children aged 4-9 years was 0.25 per 100 000 per annum. In children aged 10-17 years, the estimated incidence of paediatrician-diagnosed cases for Victoria (17.48 per 100 000) was substantially greater than other Australian states (range 1.31-5.51 per 100 000). Most cases were female and Caucasian, most commonly presenting after an infectious illness with symptoms gradual in onset. The majority were diagnosed at least 13 months after symptom onset. Symptoms, associations, investigations and management strategies were highly variable. CONCLUSIONS: Current findings suggest that, consistent with other countries, the Australian incidence of CFS in children aged <10 years is very low. In contrast, the national incidence of CFS in older children and adolescents (aged 10-17 years) is more unclear, with marked variability between geographical regions apparent. This may be due to variation in service accessibility and clinician understanding of CFS. Accordingly, national initiatives to improve equity of care for children with CFS may be required.

Medical needs of adolescent refugees resettling in Western Australia.

OBJECTIVE: To investigate the medical needs and socioeconomic determinants of health among adolescent refugees resettling in Western Australia. DESIGN: Comprehensive medical and socioeconomic health data of resettling adolescent refugees aged 12 years and above attending a Refugee Health Service over a 1-year period were analysed. RESULTS: Medical records of 122 adolescents, median (range) age of 14 (12-17) years, were reviewed. Socioeconomic vulnerabilities included dependence on government financial support (50%), housing issues (27%) and child protection service involvement (11%). Medical concerns included non-communicable disorders (85%), infectious diseases (81%), nutrition/growth (71%) and physical symptoms of non-organic origin (43%). One quarter (27%) of female adolescents had sexual/reproductive health issues. A median (range) of 5 (2-12) health concerns were identified for each adolescent with 49% requiring referral to subspecialty services. CONCLUSION: Resettling adolescent refugees are socioeconomically vulnerable with a range of medical issues that frequently require additional subspecialty health referrals.

Identification of health risk behaviours among adolescent refugees resettling in Western Australia.

OBJECTIVE: Adolescent refugees encounter traumatic stressors and are at risk of developing psychosocial health problems; limited research data exist internationally. This study aims to identify health risk behaviours among adolescent refugees resettling in Western Australia and assess the feasibility of using a standardised adolescent health questionnaire for this purpose. DESIGN: Refugees aged 12 years and above attending a tertiary Refugee Health Service (RHS) were recruited over 12 months. Sociodemographic data were collected. Psychosocial assessments based on the 'Home, Education/Eating, Activities, Drugs, Sexuality, Suicide/mental health' (HEADSS) framework were undertaken utilising interpreters where required. Health concerns identified were managed through the RHS. RESULTS: A total of 122 adolescents (20 ethnicities) participated; 65% required interpreters. Median age (range) was 14 (12-17) years. Most (80%) had nuclear family separation. Almost half (49%) had a deceased/missing family member. A third (37%) had lived in refugee camps and 20% had experienced closed detention. The median time (range) since arrival in Australia was 11 (2-86) months. Every adolescent had at least one health concern identified during the psychosocial assessment. Frequency of health concerns identified in each domain were 87% for home, 66% for education, 23% for eating, 93% for activities, 5% for drugs, 88% for sexuality and 61% for suicide/mental health. Most adolescents (75%) required intervention, consisting of counselling for health risk behaviours and/or referral to health or community services. CONCLUSION: It is feasible to use a standardised adolescent health questionnaire to identify health risk behaviours among a cohort of ethnically diverse adolescent refugees. Use of the questionnaire identified a large burden of psychosocial health issues requiring multidisciplinary intervention.

Development of the bronchial epithelial reticular basement membrane: relationship to epithelial height and age.

BACKGROUND: The bronchial epithelium and underlying reticular basement membrane (RBM) have a close spatial and functional inter-relationship and are considered an epithelial-mesenchymal trophic unit (EMTU). An understanding of RBM development is critical to understanding the extent and time of appearance of its abnormal thickening that is characteristic of asthma. METHODS: RBM thickness and epithelial height were determined in histological sections of cartilaginous bronchi obtained postmortem from 47 preterm babies and infants (median age 40 weeks gestation (22 weeks gestation-8 months)), 40 children (2 years (1 month-17 years)) and 23 adults (44 (17-90) years) who had died from non-respiratory causes, and had no history of asthma. RESULTS: The RBM was visible by light microscopy at 30 weeks gestation. RBM thickness increased in successive age groups in childhood; in infants (r=0.63, p<0.001) and in children between 1 month and 17 years (r=0.82, p<0.001). After 18 years, RBM thickness decreased with increasing age (r=-0.42, p<0.05). Epithelial height showed a similar relationship with age, a positive relationship from preterm to 17 years (r=0.50, p<0.001) and a negative relationship in adulthood (r=-0.84, p<0.0001). There was a direct relationship between epithelial height and RBM thickness (r=0.6, p<0.001). CONCLUSIONS: The RBM in these subjects was microscopically identifiable by 30 weeks gestation. It thickened during childhood and adolescence. In adults, there was either no relationship with age, or a slow reduction in thickness in older age. Developmental changes of RBM thickness were accompanied by similar changes in epithelial height, supporting the close relationship between RBM and epithelium within the EMTU.

Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers.

RATIONALE: It is unclear when the pathologic features of asthma first appear. We hypothesized that eosinophilic airway inflammation and epithelial reticular basement membrane (RBM) thickening, absent in wheezy infants, would be present in preschool children with severe, recurrent wheeze. OBJECTIVES: To compare RBM thickness and inflammation in endobronchial biopsies (EBs) from wheezy preschool children and age-matched control subjects. METHODS: EBs were obtained from wheezy preschool children (aged 3 mo to 5 yr), undergoing a clinically indicated fiberoptic bronchoscopy. Subjects undergoing fiberoptic bronchoscopy to investigate stridor acted as nonasthmatic controls. RBM thickness was measured and the density of subepithelial, immunologically distinct inflammatory cells was determined and expressed as a volume fraction (%). EBs from 16 children (median age, 29 [7-57] mo) with wheeze confirmed by video questionnaire (confirmed wheezers [CWs]), 14 with reported wheeze (reported wheezers [RWs]) (median age, 17 [8-58] mo), and 10 control subjects (median age, 19 [5-42] mo) were assessed. MEASUREMENTS AND MAIN RESULTS: RBM thickness in the three groups was as follows: CWs: median, 4.6 (range, 2.9-8.0) microm; RWs: median, 3.5 (2.1-5.4) microm; control subjects: median, 3.8 (2.5-4.7) microm. RBM was significantly thicker in CWs than in control subjects (P < 0.05). Eosinophil density was as follows: CWs: median, 1.07% (range, 0.0-3.52%); RWs: median, 0.72% (0.0-2.04%); control subjects: median, 0.0% (0.0-1.05%). Eosinophilic inflammation was significantly greater in CWs compared with control subjects (P < 0.05). There were no between-group differences for any other inflammatory cell phenotype. CONCLUSIONS: The characteristic pathologic features of asthma in adults and school-aged children develop in preschool children with confirmed wheeze between the ages of 1 and 3 years, a time when intervention may modify the natural history of asthma.

Does sputum eosinophilia predict the response to systemic corticosteroids in children with difficult asthma?

Little evidence exists to guide the management of children with difficult asthma. The aim of this study was to determine whether children with difficult asthma, associated with sputum eosinophilia, are more likely to benefit from further treatment with high-dose systemic corticosteroids, compared to those without sputum eosinophilia. Induced sputum was obtained from 20 children aged between 8 and 15 years with difficult asthma before and after a systemic corticosteroid trial (prednisolone 40 mg/day for 14 days or a single 80 mg dose of intramuscular triamcinolone). Subjects were defined as "eosinophilic" if the baseline sputum eosinophil percentage was > or = 2.5% or "non-eosinophilic" if < 2.5%. Clinical response to the corticosteroid trial was assessed using spirometry and clinical data and defined by an increase in pre-bronchodilator forced expiratory volume in 1 sec (FEV1) > 9% predicted and/or an overall subjective improvement. Seventeen children had evidence of satisfactory adherence to the systemic corticosteroid treatment; eight of these were "eosinophilic" and nine were "non-eosinophilic" subjects. Following the trial there was a similar clinical improvement in both groups, with FEV1 increasing in both the "eosinophilic" and "non-eosinophilic" groups (median change in FEV1 16 [range 5-54]% vs. 12.5 [1-29]% predicted). Sputum eosinophils fell in the "eosinophilic" group (median 17.5 [range 3-37]% vs. 0 [0-23]%, P = 0.054), with no change in the "non-eosinophilic" group (0 [0-2]% vs. 0 [0-1]%, P = 0.12). Sputum neutrophils did not change in either the "eosinophilic" (22.5 [5-50]% vs. 25 [0-91]%) or the "non-eosinophilic" group (27.5 [0-96] vs. 44 [9-96]%). In conclusion children with difficult asthma may benefit clinically from high-dose systemic corticosteroids even in the absence of sputum eosinophilia.

Airway eosinophilia in children with severe asthma: predictive values of noninvasive tests.

RATIONALE: Children with severe asthma experience persistent symptoms despite maximal conventional treatment. Fraction of exhaled nitric oxide (Fe(NO)) and sputum eosinophils are used as markers of airway inflammation to guide treatment with steroids, but no data are available on how reliable they are in predicting airway eosinophilia assessed bronchoscopically in these children. OBJECTIVES: To determine how Fe(NO) and sputum eosinophils predict airway eosinophilia measured in both bronchoalveolar lavage (BAL) and endobronchial biopsy. METHODS: Twenty-seven children with moderate to severe persistent asthma attempted measurement of Fe(NO) and sputum eosinophils, followed by bronchoscopy, BAL, and endobronchial biopsy within 24 h. MAIN RESULTS: Significant correlations were found between eosinophils in sputum and both BAL eosinophils (n = 20, r = 0.45, p = 0.045) and Fe(NO) (n = 23, r = 0.42, p = 0.049). The relationship between Fe(NO) and BAL eosinophils was also significant with a stronger correlation (n = 24, r = 0.54, p = 0.006). The positive predictive value (PPV) for increased sputum eosinophil percentage (> 2.5%) to detect elevated eosinophils in BAL (> 1.19%) was 75%; the negative predictive value (NPV) was 63%. All patients with both increased sputum eosinophils and an elevated Fe(NO) value (> 23 ppb) had elevated eosinophils in BAL (PPV, 100%); the NPV of these two markers was 65%. Eight of nine patients without any sputum eosinophils had normal subepithelial eosinophil numbers (< 1.2%; NPV, 89%). However, the PPV of any sputum eosinophils for increased subepithelial eosinophilia was only 36.4%. CONCLUSIONS: There was moderate agreement between both Fe(NO) and sputum eosinophils and BAL eosinophils. There was good NPV, but only poor PPV for these markers for mucosal eosinophilia.

Exhaled breath condensate cysteinyl leukotrienes and airway remodeling in childhood asthma: a pilot study.

BACKGROUND: It has been suggested that cysteinyl leukotrienes (cysLTs) play an important role in airway remodeling. Previous reports have indicated that cysLTs augment human airway smooth muscle cell proliferation. Recently, cysLTs have been measured in exhaled breath condensate (EBC). The aim of this study was to evaluate the relationship between cysLTs in EBC and another marker of airway remodeling, reticular basement membrane (RBM) thickening, in endobronchial biopsies in children. METHODS: 29 children, aged 4-15 years, with moderate to severe persistent asthma, who underwent bronchoscopy as part of their clinical assessment, were included. Subjects underwent spirometry and EBC collection for cysLTs analysis, followed by bronchoscopy and endobronchial biopsy within 24 hours. RESULTS: EBC cysLTs were significantly lower in asthmatic children who were treated with montelukast than in those who were not (median (interquartile range) 36.62 (22.60-101.05) versus 249.1 (74.21-526.36) pg/ml, p = 0.004). There was a significant relationship between EBC cysLTs and RBM thickness in the subgroup of children who were not treated with montelukast (n = 13, r = 0.75, p = 0.003). CONCLUSION: EBC cysLTs appear to be associated with RBM thickening in asthma.

Is a two-week trial of oral prednisolone predictive of target lung function in pediatric asthma?

We used a 2-week trial of prednisolone to determine "target" lung function for subsequent asthma therapy. The aim of this study was to evaluate whether some children exceed their "target" forced expired volume in 1 sec (FEV1) on subsequent visits in the following year, and whether this is associated with particular clinical or pathological features. Children (aged 6-16 years) with difficult asthma underwent spirometry and exhaled nitric oxide (FE(NO)) measurements before and after 2 weeks of prednisolone 40 mg/day. At the end of the course, subepithelial eosinophils and reticular basement membrane thickness were assessed. The highest FEV1 obtained in a 1-year follow-up was compared with the poststeroid postbronchodilator ("target") FEV1. Four of 22 children (18%) demonstrated an increase of > 9% above their "target" FEV1 during follow-up. None of these children had been prescribed additional asthma medications. Three of 7 children with persistent airflow limitation (PAL; poststeroid postbronchodilator FEV1 < 80% predicted) recorded an FEV1 > 80% predicted during follow-up. The median (interquartile range) number of subepithelial eosinophils was significantly higher in children who exceeded their target FEV1 than in children who did not (12.4 (8.5-39.9) vs. 1.4 (0.0-4.8) cells/mm2, P = 0.018). In conclusion, a 2-week course of prednisolone is not necessarily predictive of "target" lung function. Definitions such as PAL should be regularly reviewed on individual basis.

Sputum induction in children with difficult asthma: safety, feasibility, and inflammatory cell pattern.

Difficult childhood asthma is defined by persistent symptoms despite maximal conventional therapy. We aimed to establish a safe method of sputum induction for these children and to study cytology and the relationship to exhaled nitric oxide (eNO). Sputum induction was performed in 38/40 children (aged 6-16 years) with difficult asthma, using 3.5% saline for four 5-min periods after bronchodilator pretreatment. Two children were excluded from sputum induction because postbronchodilator forced expired volume in 1 sec (FEV(1)) was <65% predicted. Seven of 38 children had symptoms (dyspnea and wheezing) during induction; of these, 3 experienced a fall in FEV(1) of >20% from postbronchodilator FEV(1), readily reversed with salbutamol. Sputum induction was successful in 28/38 children, with a higher success rate in children >/= 12 years than in younger children (87% vs. 50%, P = 0.02). Only 9/28 had abnormal sputum cytology; of these, 6 had predominant sputum eosinophilia (>2.5% eosinophils, 54% neutrophils). Of 23 children with elevated eNO values, only 6 had sputum eosinophilia. In conclusion, sputum induction can be used to assess airway inflammation in children with difficult asthma, but abnormal sputum cytology is only present in a minority. Raised nitric oxide is only poorly predictive of sputum eosinophilia in these children.

Airway remodeling and inflammation in symptomatic infants with reversible airflow obstruction.

RATIONALE: We hypothesized that the epithelial reticular basement membrane (RBM) thickening and eosinophilic inflammation characteristic of asthma would be present in symptomatic infants with reversible airflow obstruction. METHODS: RBM thickness and numbers of inflammatory cells were determined in ultrathin sections of endobronchial biopsies obtained from 53 infants during clinical bronchoscopy for severe wheeze and/or cough. Group A: 16 infants with a median age of 12 months (range 3.4-26 months), with decreased specific airway conductance (sGaw) and bronchodilator reversibility; Group B: 22 infants with a median age of 12.4 months (5.1-25.9 months), with decreased sGaw but without bronchodilator reversibility; and Group C: 15 infants with a median age of 11.5 months (3.4-24.3 months) with normal sGaw. Additional comparisons were made with the following groups. Group D: 17 children, median age 10.3 years (6-16 years), with difficult asthma; Group E: 10 pediatric control subjects without asthma, median age 10 years (6-16 years); and Group F: nine adult normal, healthy control subjects, median age 27 years (21-42 years). MAIN RESULTS: There were no significant differences in RBM thickness or inflammatory cell number between the infant groups. RBM thickness was similar in the infants and Groups E and F. However, the RBM in all infant groups (Group A: median 4.3 microm [range 2.8-9.2 microm]; Group B: median 4.15 microm [range 2.7-5.8 microm]; Group C: median 3.8 microm [range 2.7-5.5 microm]) was significantly less thick than that in the older children with asthma (Group D: median 8.3 microm [range 5.3-12.7 microm]; p < 0.001). CONCLUSION: RBM thickening and the eosinophilic inflammation characteristic of asthma in older children and adults are not present in symptomatic infants with reversible airflow obstruction, even in the presence of atopy.

Nitric oxide in allergic airway inflammation.

PURPOSE OF REVIEW: Exhaled nitric oxide has been proposed as a useful noninvasive marker of airway inflammation in asthma. Great efforts have been made to standardize the methodology for exhaled nitric oxide measurement in both children and adults. As a consequence there is now an opportunity to establish the precise relationship between exhaled nitric oxide, atopy and airway inflammation, and to investigate whether or not there is a role for the measurement of exhaled nitric oxide in the management of patients with asthma. RECENT FINDINGS: A number of recent studies have investigated the relationship between exhaled nitric oxide and airway inflammation in asthma measured directly, using sputum induction, bronchoalveolar lavage and endobronchial biopsy. These measurements suggest that exhaled nitric oxide reflects eosinophilic airway inflammation in asthma, although there is no evidence for any relationship between exhaled nitric oxide and other airway inflammatory cells. Exhaled nitric oxide levels were found to be higher in atopic compared with nonatopic groups. These levels, however, are further elevated in atopic patients with asthma, suggesting that exhaled nitric oxide is not simply a marker of atopy. Although there is little evidence to support the routine use of measurement of exhaled nitric oxide in the management of patients with asthma, it may prove to be useful in assessing adherence to treatment with inhaled corticosteroids, or in the identification of patients in whom respiratory symptoms are associated with eosinophilic airway inflammation. SUMMARY: There is good evidence that exhaled nitric oxide reflects eosinophilic airway inflammation in asthma. Well designed, long-term studies are needed to evaluate whether the addition of exhaled nitric oxide measurements to clinical and lung function assessment results in improved asthma control.

Early thickening of the reticular basement membrane in children with difficult asthma.

Remodeling of the airway wall occurs in adults with asthma, and reticular basement membrane (RBM) thickening is pathognomonic of the asthma process. To investigate whether RBM thickening is present in children with difficult asthma and comparable to that seen in adults with asthma, we used light microscopy to measure RBM thickness in plastic-embedded endobronchial biopsy sections from 19 children with difficult asthma who were prescribed 1,600 microg/day or more of inhaled steroids (age range, 6-16 years), 10 children without asthma (7-16 years), and three adult groups: 8 healthy control subjects (21-42 years), 10 mild steroid-naive subjects with asthma (18-41 years), and 6 adults (3 steroid naive and 3 on inhaled steroids) intubated after a life-threatening attack of asthma (20-64 years). RBM thickness in the children with asthma was similar to that in adults with either mild or life-threatening asthma (median 8.2 [range 5.4-11.1] versus 8.1 [5.8-10.0] and 7.2 [2.8-10.0] microm, respectively) and greater than either adult or pediatric control subjects (8.2 [5.4-11.1] versus 4.4 [3.2-6.3] microm, p < 0.01, and 4.9 [3.7-8.3] microm, p < 0.01). We conclude that RBM thickening is already present in children with difficult asthma and to a similar extent to that seen in adults with asthma. In addition, we find no association with age, symptom duration, lung function, or concurrent eosinophilic airway inflammation.

Subcutaneous terbutaline in children with chronic severe asthma.

A continuous subcutaneous infusion of terbutaline (CSIT) was used to treat 8 children with chronic severe asthma who continued to experience frequent symptoms, despite treatment with regular oral prednisolone. Five patients experienced a symptomatic improvement from CSIT, leading to a reduction in regular medication. Three patients did not experience any lasting benefit from CSIT. The most common side effects were related to the infusion site (bruising and local infection). CSIT may lead to an improvement in symptoms and a reduction in oral steroid dose in selected children with chronic severe asthma. These initial findings support the need for further controlled studies to evaluate the use of CSIT in severe childhood asthma.