Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in children with bronchiectasis (BEST-2): a multicentre, double-blind, non-inferiority, randomised controlled trial.

BACKGROUND: Although amoxicillin-clavulanate is the recommended first-line empirical oral antibiotic treatment for non-severe exacerbations in children with bronchiectasis, azithromycin is also often prescribed for its convenient once-daily dosing. No randomised controlled trials involving acute exacerbations in children with bronchiectasis have been published to our knowledge. We hypothesised that azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with bronchiectasis. METHODS: We did this parallel-group, double-dummy, double-blind, non-inferiority randomised controlled trial in three Australian and one New Zealand hospital between April, 2012, and August, 2016. We enrolled children aged 1-19 years with radiographically proven bronchiectasis unrelated to cystic fibrosis. At the start of an exacerbation, children were randomly assigned to oral suspensions of either amoxicillin-clavulanate (22·5 mg/kg, twice daily) and placebo or azithromycin (5 mg/kg per day) and placebo for 21 days. We used permuted block randomisation (stratified by age, site, and cause) with concealed allocation. The primary outcome was resolution of exacerbation (defined as a return to baseline) by 21 days in the per-protocol population, with a non-inferiority margin of -20%. We assessed several secondary outcomes including duration of exacerbation, time to next exacerbation, laboratory, respiratory, and quality-of-life measurements, and microbiology. This trial was registered with the Australian/New Zealand Registry (ACTRN12612000010897). FINDINGS: We screened 604 children and enrolled 236. 179 children had an exacerbation and were assigned to treatment: 97 to amoxicillin-clavulanate, 82 to azithromycin). By day 21, 61 (84%) of 73 exacerbations had resolved in the azithromycin group versus 73 (84%) of 87 in the amoxicillin-clavulanate group. The risk difference showed non-inferiority (-0·3%, 95% CI -11·8 to 11·1). Exacerbations were significantly shorter in the amoxicillin-clavulanate group than in the azithromycin group (median 10 days [IQR 6-15] vs 14 days [8-16]; p=0·014). Adverse events were attributed to the trial medication in 17 (21%) of 82 children in the azithromycin group versus 23 (24%) of 97 in the amoxicillin-clavulanate group (relative risk 0·9, 95% CI 0·5 to 1·5). INTERPRETATION: By 21 days of treatment, azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with non-severe bronchiectasis. In some patients, such as those with penicillin hypersensitivity or those likely to have poor adherence, azithromycin provides another option for treating exacerbations, but must be balanced with risk of treatment failure (within a 20% margin), longer exacerbation duration, and the risk of inducing macrolide resistance. FUNDING: Australian National Health and Medical Research Council.

Presence of atopy increases the risk of asthma relapse.

OBJECTIVES: To describe the point prevalence of respiratory viruses/atypical bacteria using PCR and evaluate the impact of respiratory viruses/atypical bacteria and atopy on acute severity and clinical recovery in children with hospitalised and non-hospitalised asthma exacerbations. DESIGN: This was a prospective study performed during 2009-2011. SETTING: The study was performed in the emergency departments of two hospitals. PATIENTS: 244 children aged 2-16 years presenting with acute asthma to the emergency departments were recruited. A nasopharyngeal aspirate and allergen skin prick test were performed. MAIN OUTCOME MEASURES: The outcomes were divided into (1) acute severity outcomes (Australian National Asthma Council assessment, hospitalisation, Functional Severity Scale, Acute Asthma Score, asthma quality of life questionnaires for parents (PACQLQ) on presentation, asthma diary scores (ADS) on presentation and length of hospitalisation) and (2) recovery outcomes (PACQLQ for 21 days, ADS for 14 days and representation for asthma for 21 days). RESULTS: PCR for viruses/atypical bacteria was positive in 81.7% of children (75.1% human rhinovirus, codetection in 14.2%). Mycoplasma pneumoniae and Chlamydophila pneumoniae were rarely detected. The presence of micro-organisms had little impact on acute asthma or recovery outcomes. Children with atopy were significantly more likely to relapse and represent for medical care by day 14 (OR 1.11, 95% CI 1.00 to 1.23). CONCLUSIONS: The presence of any viruses is associated with asthma exacerbations but does not appear to influence asthma recovery. In contrast, atopy is associated with asthma relapse. M. pneumoniae and C. pneumoniae are rare triggers of acute asthma in young children.

A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy.

BACKGROUND: Epidemiologic evidence suggests delayed introduction of egg might not protect against egg allergy in infants at risk of allergic disease. OBJECTIVE: We sought to assess whether dietary introduction of egg between 4 and 6 months in infants at risk of allergy would reduce sensitization to egg. METHODS: We conducted a randomized controlled trial in infants with at least 1 first-degree relative with allergic disease. Infants with a skin prick test (SPT) response to egg white (EW) of less than 2 mm were randomized at age 4 months to receive whole-egg powder or placebo (rice powder) until 8 months of age, with all other dietary egg excluded. Diets were liberalized at 8 months in both groups. The primary outcome was an EW SPT response of 3 mm or greater at age 12 months. RESULTS: Three hundred nineteen infants were randomized: 165 to egg and 154 to placebo. Fourteen infants reacted to egg within 1 week of introduction (despite an EW SPT response <2 mm at entry) and were unsuitable for intervention. Two hundred fifty-four (83%) infants were assessed at 12 months of age. Loss to follow-up was similar between groups. Sensitization to EW at 12 months was 20% and 11% in infants randomized to placebo and egg, respectively (odds ratio, 0.46; 95% CI, 0.22-0.95; P = .03, χ2 test). The absolute risk reduction was 9.8% (95% CI, 8.2% to 18.9%), with a number needed to treat of 11 (95% CI, 6-122). Levels of IgG4 to egg proteins and IgG4/IgE ratios were higher in those randomized to egg (P < .0001 for each) at 12 months. There was no effect on the proportion of children with probable egg allergy (placebo, 13; egg, 8). CONCLUSIONS: Introduction of whole-egg powder into the diets of high-risk infants reduced sensitization to EW and induced egg-specific IgG4 levels. However, 8.5% of infants randomized to egg were not amenable to this primary prevention.

Respiratory manifestations and management in children with Common Variable Immunodeficiency.

Common variable immunodeficiency is an antibody deficiency that usually presents in childhood with recurrent sino-pulmonary infections. Diagnostic delay is frequent and thus respiratory morbidity is common, ranging from recurrent suppurative bronchitis to bronchiectasis. Immunoglobulin replacement therapy is the mainstay of treatment, whilst prophylactic antibiotic therapy and muco-ciliary clearance are additional treatment options. This review examines the diagnosis and management of respiratory issues in children with CVID.

Children with chronic cough: when is watchful waiting appropriate? development of likelihood ratios for assessing children with chronic cough.

BACKGROUND: Chronic cough is associated with poor quality of life and may signify a serious underlying disease. Differentiating nonspecific cough (when watchful waiting can be safely undertaken) from specific cough (treatment and further investigations are beneficial) would be clinically useful. In 326 children, we aimed to (1) determine how well cough pointers (used in guidelines) differentiate specific from nonspecific cough and (2) describe the clinical profile of children whose cough resolved without medications (spontaneous resolution). METHODS: A dataset from a multicenter study involving children newly referred for chronic cough (median duration, 3-4 months) was used to determine the sensitivity, specificity, predictive values, and likelihood ratios (LRs) of cough pointers (symptoms, signs, and simple investigations [chest radiography, spirometry]) recommended in guidelines. RESULTS: The pretest probability of specific cough was 88%. The absence of false-positive results meant that most pointers had strongly positive LRs. The most sensitive pointer (wet cough) had a positive LR of 26.2 (95% CI, 3.8-181.5). Although the absence of other individual pointers did not change the pretest probability much (negative LR close to 1), the absence of all pointers had a strongly negative LR of 0 (95% CI, 0-0.03). Children in the resolved spontaneously group were significantly more likely to be older, to be non-Indigenous, and to have a dry cough and a normal chest radiograph. CONCLUSIONS: Children with chronic dry cough without any cough pointers can be safely managed using the watchful waiting approach. The high pretest probability and high positive LRs of cough pointers support the use of individual cough pointers to identify high risk of specific cough in pediatric chronic cough guidelines. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry; No.: 12607000526471; URL: www.anzctr.org.au.

Increased day-to-day variability of forced oscillatory resistance in poorly controlled or persistent pediatric asthma.

BACKGROUND: Pediatric asthma lacks sensitive objective measures for asthma monitoring. The forced oscillation technique (FOT) offers strong feasibility across the pediatric age range, but relationships between FOT parameter day-to-day variability and pediatric asthma severity and control are unknown. METHODS: Day-to-day variability in FOT respiratory system resistance (Rrs) and respiratory system reactance (Xrs) compared with peak expiratory flow (PEF) were defined in 22 children with asthma (mean ± SD age, 10.4 ± 1.1 years) during a 5-day asthma camp. FOT was performed at 6 Hz in triplicate on each test occasion. Relationships between day-to-day FOT variability (expressed as within-subject SD [SDW] and asthma control and severity (defined according to GINA [Global Initiative for Asthma] recommendations) were explored. For comparison, normal baseline FOT values and variability, measured on two occasions, were defined in a separate cohort of 38 healthy children (age, 9.5 ± 1.0 years). RESULTS: Day-to-day Rrs variability was greater in persistent (n = 16) vs intermittent (n = 6) asthma (mean SDW, 0.69 cm H2O/L/s vs 0.39 cm H2O/L/s; P ≤ .01). Day-to-day Rrs variability was increased in uncontrolled (n = 13) vs partly controlled asthma (n = 9) (mean SDW, 0.75 cm H2O/L/s vs 0.42 cm H2O/L/s; P ≤ .05). PEF variability did not differentiate the groups. Day-to-day variability of Rrs and Xrs but not baseline values were increased in children with asthma vs control children (Rrs mean SDW, 0.61 cm H2O/L/s vs 0.33 cm H2O/L/s [P ≤ .05]; Xrs mean SDW, 0.24 cm H2O/L/s vs 0.15 cm H2O/L/s [P ≤ .05]). CONCLUSIONS: Increased day-to-day FOT variability exists in school-aged children with asthma. Day-to-day Rrs variability was associated with asthma severity and asthma control. FOT may be a useful objective monitoring tool in pediatric asthma and warrants further study. TRIAL REGISTRY: Australian and New Zealand Clinical Trials Registry; No.: ACTRN12614000885695; URL: www.anzctr.org.au.

Childhood interstitial lung disease due to surfactant protein C deficiency: frequent use and costs of hospital services for a single case in Australia.

BACKGROUND: Rare chronic diseases of childhood are often complex and associated with multiple health issues. Such conditions present significant demands on health services, but the degree of these demands is seldom reported. This study details the utilisation of hospital services and associated costs in a single case of surfactant protein C deficiency, an example of childhood interstitial lung disease. METHODS: Hospital records and case notes for a single patient were reviewed. Costs associated with inpatient services were extracted from a paediatric hospital database. Actual costs were compared to cost estimates based on both disease/procedure-related cost averages for inpatient hospital episodes and a recently implemented Australian hospital funding algorithm (activity-based funding). RESULTS: To age 8 years and 10 months the child was a hospital inpatient for 443 days over 32 admissions. A total of 298 days were spent in paediatric intensive care. Investigations included 58 chest x-rays, 9 bronchoscopies, 10 lung function tests and 11 sleep studies. Comprehensive disease management failed to prevent respiratory decline and a lung transplant was required. Costs of inpatient care at three tertiary hospitals totalled $966,531 (Australian dollars). Disease- and procedure-related cost averages underestimated costs of paediatric inpatient services for this patient by 68%. An activity-based funding algorithm that is currently being adopted in Australia estimated the cost of hospital health service provision with more accuracy. CONCLUSIONS: Health service usage and inpatient costs for this case of rare chronic childhood respiratory disease were substantial. This case study demonstrates that disease- and procedure-related cost averages are insufficient to estimate costs associated with rare chronic diseases that require complex management. This indicates that the health service use for similar episodes of hospital care is greater for children with rare diseases than other children. The impacts of rare chronic childhood diseases should be considered when planning resources for paediatric health services.

Effect of general anesthesia on pulmonary function and clinical status on children with cystic fibrosis.

INTRODUCTION: Children with cystic fibrosis (CF) receive general anesthesia (GA) for a variety of different procedures. Historical studies assessing risk of GA report a high risk of morbidity. There is a paucity of data evaluating the risk of currently available anesthetic agents. The aim of this study was to assess the effect of GA on clinical status and lung function on children with CF. METHODS: Children with CF aged 8-18 years admitted for IV antibiotic treatment for a pulmonary exacerbation were invited to participate. Spirometry, forced oscillation technique (FOT), and CF clinical score (CFCS) were measured pre-GA, at 24 and 48 h post-GA. The nature and duration of the GA were recorded. RESULTS: Twenty two patients were recruited of which 19 patients (mean age 11.4 years, range 8-18 years, 12 male) required GA. Typically, either propofol or sevoflurane was used as induction agent and maintenance of anesthesia was with sevoflurane. A laryngeal mask was used in most cases. FEV1 mean (±SD) pre-GA was 75.1% (±23.46) which decreased at 24 h to 74.8 (±23.0) and at 48 h to 74.3 (±20.5). FOT resistance and reactance decreased at 24 and 48 h from baseline. Changes in spirometry and CFCS were not statistically significant. Two adverse events were observed in this cohort. CONCLUSION: The results suggest that children with mild to moderate CF lung disease do not experience significant deterioration in central or peripheral airway function following GA. The low rate of complications suggests an improved level of safety for children with CF with modern anesthesia compared with historical published data.

Intrapleural urokinase versus surgical management of childhood empyema.

AIM: Empyema can be managed conservatively with intravenous antibiotics or invasively with a drain inserted under image guidance or via surgical evacuation. Both approaches are successful but comparisons of the method of drainage are few. This study compared clinical outcomes for empyema in previously well children from a single centre over a 12 year period. METHODS: A retrospective analysis of cases over 12 years from the Children's Hospital at Westmead in Sydney was undertaken. Ethics committee approval was obtained. RESULTS: Seventy two cases were identified from medical records, 12 cases were excluded and 60 cases remained. The mean age was 4.7±4.3 years and there was a slight male preponderance. Treatment was divided into surgical management with a large bore drain alone [n=25] and minimally invasive management with the use of a "pigtail catheter" and intrapleural fibrinolytic ["Urkoinase"][n=35]. At presentation the mean heart rate and respiratory rate were not statistically different. The median (range) number of doses of urokinase was 5.66 doses (1-12). More fluid was drained with the use of urokinase [594 ml (25-4575 ml) vs. 195 ml (10-1426 ml); p=0.006], but this did not influence the rate of resolution of fever or the length of hospital stay. A pathogen was isolated in 42.9% of the urokinase group and 68% of the surgical group which approached statistical significance [p=0.054]. CONCLUSIONS: Both large bore surgical drains and "pigtail catheter" drains with the instillation of urokinase lead to similarly favourable treatment outcomes. Either treatment could be recommended depending on local expertise and preferences.

Exercise-induced respiratory symptoms not due to asthma.

This manuscript describes two interesting patients who had exercise-induced symptoms that unmasked an alternative underlying diagnosis. The first is an 8-year-old boy who was treated for asthma all his life but really had exercise-induced stridor (labelled as wheeze) causing significant exercise limitation, which was due to a double aortic arch with the right arch compressing the trachea. The second case describes the diagnosis of vocal cord dysfunction in a 13-year-old anxious high achiever. He also initially had exercise-induced symptoms treated as exercise-induced wheeze but again had a stridor due to vocal cord dysfunction. Both these cases demonstrate the importance of detailed history including during exercise, which can unmask alternative diagnosis. Another important message is that if there is no response to bronchodilator treatment with absence of typical signs and symptoms of asthma, alternative diagnosis should be considered.

Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised controlled trial.

BACKGROUND: Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. METHODS: A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged ≥6 years; and vaccine safety. DISCUSSION: As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ANZCTR) number: ACTRN12612000034831.

Newer treatments in the management of pediatric asthma.

Asthma control remains a significant challenge in the pediatric age range in which ongoing loss of lung function in children with persistent asthma has been reported, despite the use of regular preventer therapy. This has important implications for observed mortality and morbidity during adulthood. Over the past decade, there has been an emergence of other treatment adjuncts, such as anti-Immunoglobulin E (IgE)-directed therapy, low dose theophylline, and the use of macrolide antibiotics, yet their exact role in asthma management remains unclear, despite omalizumab now being incorporated into several international asthma guidelines. As with many aspects of pediatric care, this is driven by a lack of appropriately designed pediatric trials. Extrapolation of data reported in adult studies may be appropriate for adolescent asthma, but is not for younger age groups, in which important pathophysiological differences exist. Novel drugs under development offer potential for benefit in the future, but to date existing data are in most cases limited to adults. Pediatric asthma also offers unique potential to prevent or modify the underlying pathophysiology. Although attempts to do so have been unsuccessful to date, advances may yet come from this approach, as our understanding about the interaction between genetics, environmental factors, and viral illness improve. This review provides an overview of the newer treatment options available for management of pediatric asthma and discusses the merits of other novel therapies in development, as we search to optimize management and improve future outcomes.

A cough algorithm for chronic cough in children: a multicenter, randomized controlled study.

OBJECTIVES: The goals of this study were to: (1) determine if management according to a standardized clinical management pathway/algorithm (compared with usual treatment) improves clinical outcomes by 6 weeks; and (2) assess the reliability and validity of a standardized clinical management pathway for chronic cough in children. METHODS: A total of 272 children (mean ± SD age: 4.5 ± 3.7 years) were enrolled in a pragmatic, multicenter, randomized controlled trial in 5 Australian centers. Children were randomly allocated to 1 of 2 arms: (1) early review and use of cough algorithm ("early-arm"); or (2) usual care until review and use of cough algorithm ("delayed-arm"). The primary outcomes were proportion of children whose cough resolved and cough-specific quality of life scores at week 6. Secondary measures included cough duration postrandomization and the algorithm's reliability, validity, and feasibility. RESULTS: Cough resolution (at week 6) was significantly more likely in the early-arm group compared with the delayed-arm group (absolute risk reduction: 24.7% [95% confidence interval: 13-35]). The difference between cough-specific quality of life scores at week 6 compared with baseline was significantly better in the early-arm group (mean difference between groups: 0.6 [95% confidence interval: 0.29-1.0]). Duration of cough postrandomization was significantly shorter in the early-arm group than in the delayed-arm group (P = .001). The cough algorithm was reliable (κ = 1 in key steps). Feasibility was demonstrated by the algorithm's validity (93%-100%) and efficacy (99.6%). Eighty-five percent of children had etiologies easily diagnosed in primary care. CONCLUSIONS: Management of children with chronic cough, in accordance with a standardized algorithm, improves clinical outcomes irrespective of when it is implemented. Further testing of this standardized clinical algorithm in different settings is recommended.

Medication use in Indian children with asthma: the user's perspective.

BACKGROUND AND OBJECTIVE: Despite the high prevalence of asthma in children, there has been limited research into patient perception of medication use, particularly in the developing world. This study therefore aimed to carry out an in-depth exploration of the views of carers and children with asthma on asthma medication use. METHODS: Grounded theory approach was used to conduct semistructured qualitative interviews in a purposive convenience sample of parents and children with asthma. The participants were recruited from two specialty hospitals in New Delhi, India. Interviews were tape-recorded, transcribed verbatim and thematically analysed. RESULTS: Twenty children (7-12 years old) with asthma and their parent or carer were interviewed in July 2011. Major reported issues included poor parent and child understanding of disease and medications. Fears, misinformed beliefs and lack of self-management skills were apparent. Child self-image, resistance to medication use and lack of responsibility in medication taking were themes that emerged from child interviews. CONCLUSIONS: This is one of the first research studies exploring the viewpoint of children with asthma about their medications. Resource constraints dictate a pragmatic paternalistic approach by physicians which, in contrast to patients in westernized nations, seems to be acceptable and satisfactory to Indian patients (carers).

Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial.

BACKGROUND: Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. METHODS: This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. DISCUSSION: Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879.

Medication use in Australian children with asthma: user's perspective.

BACKGROUND AND OBJECTIVES: Medication use-related issues remain problematic in childhood asthma despite effective treatment strategies and public investment into improved asthma management strategies in industrialized countries. This study aimed to carry out an in-depth exploration of the views of parents/carers and children with asthma on medication use. METHODS: Semi-structured qualitative interviews were conducted with a purposive convenience sample of children with asthma and their parents recruited from general practices in Sydney. Interviews were tape-recorded, transcribed verbatim, and thematically analyzed. RESULTS: A total of 52 interviews (26 parents/carers and 26 children with asthma) were conducted. Major themes which emerged from the children's interviews included issues such as self-image, resistance to medication use, and lack of responsibility in medication taking. Parental or carer issues included lack of clear understanding of how medications worked, as well as administration difficulties, cost constraints, and beliefs about medications contrary to quality use. DISCUSSION: This is one of the few research studies exploring the viewpoint of children with asthma about their medications in Australia. Despite investment in dissemination of professional, targeted evidence-based asthma management strategies in healthcare, there seems to be a lack of depth in terms of what parents understand about their child's asthma. Effective communication about medication usage, especially the inclusion of the child in the consultation to empower them to be involved in their own asthma care, may be the answer.