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 microl vs 402.2 +/- 31.3 microl, p = 0.0002), while BHR(-) subjects did not show this change (387.6 +/- 29.7 microl vs 364.1 +/- 30.1 microl, 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 microM vs 1.5 +/- 0.1 microM, 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.

Outcome evaluation of early discharge after hospitalization for asthma.

PURPOSE OF REVIEW: This review is designed to assess the evidence around the criteria used to decide when it is appropriate for an individual with asthma to be discharged from hospital. RECENT FINDINGS: There has been scanty recent published research on this subject, and no strong evidence-based discharge guidelines exist. The limited data available suggest that clinical outcome in children is similar when the timing of discharge is the need for 3-hourly rather than 4 hourly bronchodilator. In children, the adoption of this policy would shorten the average length of hospital stay by 5-6 h. SUMMARY: The available data for adults with acute asthma on the appropriate end points for discharge from hospital are inadequate to provide firm conclusions. Children with acute asthma should be considered ready for discharge when clinically stable on 3-hourly bronchodilator.

Exhaled breath condensate nitrite/nitrate and pH in relation to pediatric asthma control and exhaled nitric oxide.

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 microM, CI 7.5-9.4) was significantly elevated when compared with normal (4.8 microM, CI 3.4-6.2, P = 0.0007) and atopic children (6.5 microM, CI 4.0-9.1, P = 0.02). The mean level of eNO was significantly higher in those with asthma (43.7 ppb, CI 34.7-51.1, P < 0.001) and atopy (24 ppb, CI 16.7-31.2, P < 0.05) when compared with normal children (11.5 ppb, CI 6.7-16.2). There was a significantly lower pH in those with asthma and a FEV(1) < 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.

Improvement in asthma management practices in child care services: an evaluation of a staff education program.

ISSUES ADDRESSED: The aim of this study was to identify the strengths and weaknesses of asthma management in child care services in the Hunter region and to develop, implement and evaluate a health education program to address the deficiencies. METHODS: A questionnaire was sent to the 190 child care services in the Hunter region in 1997 to assess their asthma management practices. Results of the survey were used to develop a two-hour training workshop for child care staff in the management of asthma. District-based workshops were conducted for 535 child care staff (representing 140 services) over two years. Participants completed pre- and post-workshop knowledge and confidence questionnaires. The survey was repeated in 2000. RESULTS: The baseline survey identified potential for substantial improvement in the management of asthma in child care services and in the training of staff. Training workshops significantly improved asthma knowledge and confidence in managing asthma (p<0.0001). The follow-up survey showed that an additional 50% (p<0.0001) of all child care services had implemented recommended asthma management practices. CONCLUSION: The program was effective in achieving vast improvements in the knowledge and confidence that child care staff require to manage asthma and has led to the broad dissemination and adoption of the appropriate policies and procedures for the management of asthma in child care services.

Mirth-triggered asthma: is laughter really the best medicine?

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.

Randomized controlled trial of a teacher-led asthma education program.

Our objective was to determine whether an asthma education program in schools would have 1) a direct impact on student knowledge and attitudes to asthma and quality of life of the students with asthma, 2) an indirect impact on teacher knowledge and attitudes to asthma and on school policies about asthma, and 3) a sustainable program after the resources to implement the research were withdrawn. Seventeen intervention and 15 control schools participated in a controlled trial. Baseline knowledge and attitudes were measured in year 8 students (ages 13-14 years) and their teachers together with quality of life in the students with asthma. A three-lesson package about asthma was delivered by teachers as part of the Personal Development/Health/Physical Education (PD/H/PE) curriculum. Follow-up questionnaires were administered to students and staff. Efforts to change school policies were documented. Five years after the intervention, PD/H/PE teachers were contacted to determine whether the program was still operating. Main outcome measures included asthma knowledge, attitudes, and quality of life. Questionnaires were returned by 4,161/4,475 of the year 8 students at baseline and by 3,443 at follow-up. In intervention schools, compared with control schools, students showed improved asthma knowledge (P < 0.0001), improvement in tolerance to asthma (P = 0.02), internal control (P = 0.03), and less tendency to believe in the role of chance in asthma control (P = 0.04). Students from intervention but not control schools showed significant improvements in overall quality of life (P = 0.003 vs. P = 0.82, respectively). Teachers from intervention schools showed significant increases in knowledge compared to control schools (P < 0.0001). Intervention schools were more likely to seek further health education about asthma (P < 0.01). Five years after the 35 schools involved in the development of the materials or the trial had been offered the Living With Asthma package, 25 (71%) were still teaching the program to most or all of their students. Fifty-nine of the 61 (97%) high schools in the Hunter Region now have the program. Management and distribution of the Living With Asthma program have been taken over by the Asthma Foundation of New South Wales. The package has been updated and is being offered to all high schools throughout New South Wales as part of the National Asthma-Friendly Schools Project. In conclusion, a teacher-led asthma education program in secondary school had direct and indirect beneficial outcomes and was sustained at a high level for 5 years in most schools in the Hunter Region, despite minimal ongoing maintenance and support from health workers.

Migration to a western country increases asthma symptoms but not eosinophilic airway inflammation.

The prevalence of asthma symptoms varies markedly throughout the world. However, the asthma mechanisms involved are not defined. Studying the effects of migration can help identify the reasons for this geographic variation. The aims of this study were to examine the prevalence of asthma symptoms, airway hyperresponsiveness (AHR), and induced sputum eosinophils in adolescents who migrate to Australia. The study was conducted in Sydney, Australia, where adolescent students completed a video symptom questionnaire, hypertonic saline challenge, sputum induction, and allergy skin testing. The 211 students had widely different cultural backgrounds, including Asian, South Pacific, Middle Eastern, European, and African countries. Among adolescents who were migrants to Australia, the prevalence of asthma symptoms was higher than that reported using a similar methodology in their country of origin. Asthma symptom prevalence was related to residence time in Australia. The prevalence of wheeze was 17.2% in recent arrivals, 20.5% in adolescents living in Australia for >2 years, and 36.3% in those living all their lifetime in Australia (P = 0.013). For every year of residence in Australia, there was an 11% increase in prevalence of current wheeze (odds ratio, 1.11; P = 0.02). This effect was not related to atopy, AHR, or eosinophilic airway inflammation. Sputum neutrophils were elevated in recent arrivals. In conclusion, adolescents who migrate to Australia report increased asthma symptoms, compared to their country of origin, and asthma symptoms are further increased for every additional year of residence in Australia. The development of wheeze after migration to Australia was independent of eosinophilic inflammation and consistent with noneosinophilic asthma mechanisms.

Relationship between sputum inflammatory markers, lung function, and lung pathology on high-resolution computed tomography in children with cystic fibrosis.

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 CF 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 (FEV(1)) 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 CF between March 1998 and April 2000. Mean age was 12.3 years (range, 6-21 years), FEV(1) (% 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. FEV(1) 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 FEV(1) 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 FEV(1) 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.

Self-assembled monolayers of alkylphosphonic acid on GaN substrates.

In this paper we describe the formation and characterization of self-assembled monolayers of octadecylphosphonic acid (ODPA) on epitaxial (0001) GaN films on sapphire. By immersing the substrate in its toluene solution, ODPA strongly adsorbed onto UV/O 3-treated GaN to give a hydrophobic surface. Spectroscopic ellipsometry verified the formation of a well-packed monolayer of ODPA on the GaN substrate. In contrast, adsorption of other primarily substituted hydrocarbons (C n H 2 n+1 X; n = 16-18; X = -COOH, -NH 2, -SH, and -OH) offered less hydrophobic surfaces, reflecting their weaker interaction with the GaN substrate surfaces. A UV/O 3-treated N-polar GaN had a high affinity to the -COOH group in addition to ODPA, possibly reflecting the basic properties of the surface. These observations suggested that the molecular adsorption was primarily based on hydrogen bond interactions between the surface oxide layer on the GaN substrate and the polar functional groups of the molecules. The as-prepared ODPA monolayers were desorbed from the GaN substrates by soaking in an aqueous solution, particularly in a basic solution. However, ODPA monolayers heated at 160 degrees C exhibited suppressed desorption in acidic and neutral aqueous solution maybe due to covalent bond formation between ODPA and the surface. X-ray photoelectron spectroscopy provided insight into the effect of the UV/O 3 treatment on the surface composition of the GaN substrate and also the ODPA monolayer formation. These results demonstrate that the surface of a GaN substrate can be tailored with organic molecules having an alkylphosphonic acid moiety for future sensor and device applications.

Barriers to metered-dose inhaler/spacer use in Canadian pediatric emergency departments: a national survey.

BACKGROUND: Metered-dose inhalers and spacers (MDI+S) are at least as effective as nebulizers for treating children with mild to moderate asthma exacerbations. Despite advantages in terms of efficacy, side effects, and ease of use, MDI+S are not used in many North American pediatric emergency departments (PEDs). OBJECTIVES: To survey emergency physicians, emergency nurses, and respirologists in Canadian pediatric teaching hospitals regarding their practices, beliefs, and barriers to change with respect to bronchodilator delivery. METHODS: This was a cross-sectional, mailed survey of all emergency physicians, all respirologists, and a random sample of emergency nurses at ten Canadian PEDs. RESULTS: A total of 291 of 349 health care professionals (83%) responded. Twenty-one percent of emergency physicians use MDI+S in the PED (largely concentrated at two "user sites"). A majority at nonuser sites, and virtually all professionals at user sites, responded that MDI+S are at least as effective as nebulizers, switching to MDI+S is justified by existing research, patient outcomes would be equal or better, and they have the required knowledge and skills to use MDI+S in the emergency department. The largest perceived barriers to MDI+S implementation include concerns regarding safety and costs, related to feasibility of providing and sterilizing spacers, and parental expectations for nebulizers. Other barriers included staff beliefs regarding the effectiveness of MDI+S, changes in nursing workload, and lack of a physician champion for change. CONCLUSIONS: MDI+S are infrequently used to treat patients with acute asthma in Canadian PEDs, despite the fact that most emergency staff believe they are effective. Important barriers to using MDI+S have been identified in this study and should be used to guide future implementation strategies.

National policy on asthma management for schools.

A previous position paper provided a national policy on asthma management for schools. This updated paper takes into account new medications and devices, changes in approaches to management, national guidelines for cleaning of asthma first aid kits in schools and the National Asthma Friendly Schools Program. School teachers and ancillary staff need to be aware both of asthma symptoms and the general principles of asthma management.

13. Children in Australian society.

Although children in Australia generally have good health, some alarming indicators of poor health and wellbeing exist, which are related to major socioeconomic discrepancies. The pathways connecting socioeconomic disadvantage to child health outcomes are complex and poorly understood. Reducing social disadvantage requires strategies beyond the health arena, involving political, moral, cultural and economic initiatives. Developing "social capital"--cohesion in communities, a sense of belonging and involvement in community affairs--may be a key strategy in improving health indicators. Overseas studies of early intervention and home visiting programs in early childhood have shown improvements in child health and development outcomes. Similar programs have been introduced in Australia and face considerable challenges in their widespread roll-out and evaluation. Health professionals need to develop practical ways to interact with community programs and thus improve social capital.

Antibiotic-related renal failure and cystic fibrosis.

Recently published reports suggest that the combination of aminoglycosides with ceftazidime may increase the risk of renal disease in cystic fibrosis. We describe a case of unusually severe acute tubular necrosis occurring in an adolescent with cystic fibrosis receiving i.v. gentamicin plus ceftazidime and discuss the possible mechanisms.

The relationship of exhaled nitric oxide to airway inflammation and responsiveness in children.

Exhaled nitric oxide (eNO) is a potential tool in epidemiological studies of asthma. It was hypothesized that in a cross-sectional survey of asthma in adolescent children, eNO may contribute to the detection of this disease. A cohort of Australian school children in two educational years (n = 107, aged 14.7 +/- 2.3 years, 42.9% female) were surveyed in terms of exhaled nitric oxide (eNO), which was compared with other indicators of asthma: asthma symptoms, atopy [skin prick tests (SPT)], hypertonic saline bronchial reactivity, sputum inflammatory cells and eosinophilic cationic protein. Significant positive correlations were found with eNO and number of positive skin prick tests (p = 0.001; n = 98), symptoms (p = 0.05; n = 107), sputum eosinophils (p = 0.025; n = 83), and sputum eosinophilic cationic protein (p = 0.009; n = 83). There was no significant relationship with airway hyperresponsiveness (p = 0.3; n = 15). eNO had a negative predictive value for asthma of 83%, and a positive predictive value of 54%, which is comparable with most current tests for diagnosing asthma. eNO appears to be a useful indicator of atopy and airway inflammation, but in this population it was not closely related to airway hyperresponsiveness.

Designing home telecare: a case study in monitoring cystic fibrosis.

The objective of this study was to investigate the feasibility of using home telecare for monitoring cystic fibrosis (CF). Five adolescents were asked to use a home telecare system during a routine hospital visit over one week. Frequency of use was measured from computer logs. Unacceptable measurements were identified by visual inspection. User impressions of home telecare and appropriateness of the system for managing CF was determined from observations of user interaction, survey and qualitative analysis. Patients used the system to record lung function measurements without any supervision and indicated that the system was easy to learn and use. The role of home telecare in supporting collaborative self-management appeared to be well understood. Home telecare was seen as a supplement to standard care that would provide a link to the hospital between clinic visits. Participants indicated that feedback provided by the system and ongoing clinical support would determine long-term use and compliance with the monitoring protocol. Clinicians reported the usefulness of home telecare in maintaining a longitudinal record of their patient's health that would supplement verbal description of symptoms and reduce time to treatment by increasing patient self-awareness of health status. Home telecare may be a feasible intervention for monitoring CF. Feedback provided by the system must be presented in a format that is familiar and easily understood by users. Further system refinement and evaluation is required to determine patient compliance with their customized monitoring protocol prior to assessing impact on clinical outcomes.

Invasive monitoring of airway inflammation.

What we know: Ethical concerns have limited research involving invasive bronchoscopy techniques in young children. No longitudinal studies have been conducted to compare the findings of bronchial biopsy or bronchoalveolar lavage in young children with transient episodic wheeze versus asthma. Children with atopic asthma have more airway eosinophils and mast cells than children with viral-associated wheeze. Both neutrophilic and eosinophilic patterns of inflammation are present in asthma. What we need to know: Can we establish robust normal values for tissue and fluid samples obtained at bronchoscopy or bronchoalveolar lavage? Do biopsy specimens taken at the carina tell us about the pathological processes occurring in asthma? Can we use invasive procedures to predict which children with wheeze will continue to wheeze and develop a classical asthma phenotype? Can we use invasive procedures to guide asthma therapy? Can we expect airway inflammation to resolve with anti-inflammatory medication? Can we correlate invasive with non-invasive measures of inflammation? Can we use our understanding of pro- and anti-inflammatory pathways to develop new therapeutic interventions? Is there a presymptomatic phase of inflammation?

Outcome evaluation of early discharge from hospital with asthma.

OBJECTIVE: The aim of the study was to determine whether it was safe to discharge children with asthma from hospital when stable on 3-hourly rather than 4-hourly doses of salbutamol. METHODOLOGY: A retrospective study of 419 individual admissions of 359 children with asthma was undertaken. We defined a theoretical 'time ready for discharge' (TRD) for asthmatic admissions based on: (i) at least two doses of 3-hourly salbutamol and due for the third dose, (ii) no oxygen supplementation, (iii) no intravenous fluid or therapy, and (iv) time of discharge should be either before 17:30 hours or after 07:30 hours. Each admission was analysed using appropriate parameters to assess for risks and benefits of using this theoretical TRD as a guide for discharging asthmatic children from hospital. RESULTS: A total of 116 (27.7%) children were discharged before our theoretical TRD, including 11 children who received salbutamol no less often than 2-hourly and 37 who had a single dose of 3-hourly salbutamol before discharge. Re-admission to hospital and representation to the Emergency Department without re-admission within 1 week of discharge were less common in the group who were discharged before they had achieved theoretical TRD than in those who were discharged at or after the theoretical TRD, although the numbers were too small to reach statistical significance. Between our theoretical TRD and actual time of discharge two children who received supplemental oxygen and more frequent salbutamol may have required re-admission. CONCLUSIONS: From the medical viewpoint discharge when the child is stable on 3-hourly rather than 4-hourly doses appears safe. This can be expected to shorten length of stay by an average of 5.5 h (P < 0.001).

Inflammation, infection, and pulmonary function in infants and young children with cystic fibrosis.

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.