Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand.

This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi-disciplinary team that included consumers. The main statements are: Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co-existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease). Confirm bronchiectasis with a chest computed-tomography scan, using age-appropriate protocols and criteria in children. Undertake a baseline panel of investigations. Assess baseline severity, and health impact, and develop individualized management plans that include a multi-disciplinary approach and coordinated care between healthcare providers. Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality-of-life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis. Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules. Treat exacerbations with 14-day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs. Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures. Individualize therapy for long-term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents. Ensure ongoing care with 6-monthly monitoring for complications and co-morbidities. Undertake optimal care of under-served peoples, and despite its challenges, delivering best-practice treatment remains the overriding aim.

Cryobiopsy for Identification of Usual Interstitial Pneumonia and Other Interstitial Lung Disease Features. Further Lessons from COLDICE, a Prospective Multicenter Clinical Trial.

Rationale: Transbronchial lung cryobiopsy (TBLC) is an emerging technique for interstitial lung disease diagnosis. Good histopathologic agreement between TBLC and surgical lung biopsy (SLB) was demonstrated in the COLDICE (Cryobiopsy versus Open Lung Biopsy in the Diagnosis of Interstitial Lung Disease Alliance) study; however, diagnostic confidence was frequently lower for TBLC than SLB. Objectives: To characterize specific features of TBLC predictive of usual interstitial pneumonia (UIP) in corresponding SLB and to identify clinical indices predictive of biopsy concordance. Methods: The COLDICE study was a prospective, multicenter study investigating diagnostic agreement between TBLC and SLB. The participants underwent both procedures with blinded pathologist analysis of specimens, applying international guideline criteria. The TBLC features predictive of UIP in the paired SLB and predictive features of overall concordance were analyzed. Measurements and Main Results: A total of 65 patients (66.1 ± 9.3 yr; FVC, 84.7 ± 14.2%; DlCO, 63.4 ± 13.8%) participated in the COLDICE study. UIP was identified in 33/65 (50.8%) SLB, and 81.5% were concordant with corresponding TBLC (κ, 0.61; 95% confidence interval [CI], 0.38-0.77). The UIP guideline criteria of "predominantly subpleural or paraseptal fibrosis" was infrequently reported in TBLC (8/33, 24.2%), whereas "patchy fibrosis," "fibroblast foci," and the "absence of alternative diagnostic features" were frequently observed in TBLC. The combination of these three features strongly predicted UIP in paired SLB (odds ratio [OR], 23.4; 95% CI, 6.36-86.1; P < 0.0001). Increased numbers of TBLC samples predicted histopathologic concordance with SLB (OR, 1.8; 95% CI, 1.08-3.01; P = 0.03). The predictors of discordance included older age, family history, and radiologic asymmetry. Conclusions: Subpleural and/or paraseptal fibrosis were not essential for diagnosing UIP in TBLC, provided that other guideline criteria features were present. The diagnostic accuracy of TBLC was strengthened when increased numbers of samples were taken. Clinical trial registered with www.anzctr.org.au (ACTRN12615000718549).

Otitis media guidelines for Australian Aboriginal and Torres Strait Islander children: summary of recommendations.

INTRODUCTION: The 2001 Recommendations for clinical care guidelines on the management of otitis media in Aboriginal and Torres Islander populations were revised in 2010. This 2020 update by the Centre of Research Excellence in Ear and Hearing Health of Aboriginal and Torres Strait Islander Children used for the first time the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. MAIN RECOMMENDATIONS: We performed systematic reviews of evidence across prevention, diagnosis, prognosis and management. We report ten algorithms to guide diagnosis and clinical management of all forms of otitis media. The guidelines include 14 prevention and 37 treatment strategies addressing 191 questions. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: A GRADE approach is used. Targeted recommendations for both high and low risk children. New tympanostomy tube otorrhoea section. New Priority 5 for health services: annual and catch-up ear health checks for at-risk children. Antibiotics are strongly recommended for persistent otitis media with effusion in high risk children. Azithromycin is strongly recommended for acute otitis media where adherence is difficult or there is no access to refrigeration. Concurrent audiology and surgical referrals are recommended where delays are likely. Surgical referral is recommended for chronic suppurative otitis media at the time of diagnosis. The use of autoinflation devices is recommended for some children with persistent otitis media with effusion. Definitions for mild (21-30 dB) and moderate (> 30 dB) hearing impairment have been updated. New "OMapp" enables free fast access to the guidelines, plus images, animations, and multiple Aboriginal and Torres Strait Islander language audio translations to aid communication with families.

Priorities and expectations of patients attending a multidisciplinary interstitial lung disease clinic.

BACKGROUND AND OBJECTIVE: The significant and progressive morbidity associated with ILD mean that patients often struggle with the impact of this disease on their QOL and independence. To date, no studies have investigated the importance of multidisciplinary care on patient experience in ILD. We aimed to determine the expectations and priorities of patients attending a tertiary referral centre multidisciplinary ILD clinic. In particular, we sought to learn how important the multidisciplinary element of the clinic was to patients and which aspects of the clinic were most valued. METHODS: An 18-item patient questionnaire was developed in conjunction with expert physicians and specialist nurses involved in the ILD clinic and sent to all patients on the centre's ILD registry at the time of the study (n = 240). Patients rated the importance of different aspects of their experience of attending the clinic. Data collected were analysed using descriptive statistics. Comparisons across disease severity were made using two-sided Z-tests for independent proportions. RESULTS: A total of 100 respondents comprised the study group. Almost all respondents valued the multidisciplinary aspect of the clinic. Obtaining an accurate diagnosis and improving their disease understanding was most important to respondents. The importance of the ILD specialist nurse for both education and support increased with worsening disease severity. CONCLUSION: Our results suggest that a multidisciplinary approach to the management of ILD with additional focus on patient education, as well as tailoring care to disease severity, is a plausible pathway to improving the patient experience with ILD.

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.

Nocturnal hypoxaemia is associated with adverse outcomes in interstitial lung disease.

BACKGROUND AND OBJECTIVE: Sleep-disordered breathing (SDB) has been reported as highly prevalent in idiopathic pulmonary fibrosis (IPF) and other interstitial lung disease (ILD) populations. Nocturnal oxygen desaturation (NOD), or the total sleep time spent with SpoO2 < 90% (TST < 90), can occur both with and without associated apnoeas, and is common in ILD. This study aimed to characterize abnormal SDB and extent of TST < 90 in ILD patients and evaluate relationships between TST < 90 and markers of disease severity, development of pulmonary hypertension (PH) and mortality. METHODS: Consecutive, newly referred ILD patients attending a specialist clinic underwent polysomnography (PSG). Serial lung function tests, echocardiography and other clinical variables were recorded. Predictors of PH and mortality were evaluated using logistic regression and Cox proportional hazards regression analyses. RESULTS: A total of 92 ILD patients (including 44 with IPF) underwent PSG. At least mild obstructive sleep apnoea (OSA) was observed in 65.2%, with rapid eye movement (REM)-related events occurring frequently. At least 10% TST < 90 (designated 'significant NOD') was present in 35.9% of patients, and was associated with PH at baseline echocardiography. Multiple indices of hypoxaemia during sleep, including significant NOD, predicted the development of new or worsening PH. TST < 90 predicted overall and progression-free survival. CONCLUSION: Nocturnal oxygen saturation is associated with poorer prognosis in ILD patients and may contribute towards the pathogenesis of pulmonary vascular disease.

Bacteria and viruses in the nasopharynx immediately prior to onset of acute lower respiratory infections in Indigenous Australian children.

Acute lower respiratory infection (ALRI) is a major cause of hospitalization for Indigenous children in remote regions of Australia. The associated microbiology remains unclear. Our aim was to determine whether the microbes present in the nasopharynx before an ALRI were associated with its onset. A retrospective case-control/crossover study among Indigenous children aged up to 2 years. ALRI cases identified by medical note review were eligible where nasopharyngeal swabs were available: (1) 0-21 days before ALRI onset (case); (2) 90-180 days before ALRI onset (same child controls); and (3) from time and age-matched children without ALRI (different child controls). PCR assays determined the presence and/or load of selected respiratory pathogens. Among 104 children (182 recorded ALRI episodes), 120 case-same child control and 170 case-different child control swab pairs were identified. Human adenoviruses (HAdV) were more prevalent in cases compared to same child controls (18 vs 7%; OR = 3.08, 95% CI 1.22-7.76, p = 0.017), but this association was not significant in cases versus different child controls (15 vs 10%; OR = 1.93, 95% CI 0.97-3.87 (p = 0.063). No other microbes were more prevalent in cases compared to controls. Streptococcus pneumoniae (74%), Haemophilus influenzae (75%) and Moraxella catarrhalis (88%) were commonly identified across all swabs. In a pediatric population with a high detection rate of nasopharyngeal microbes, HAdV was the only pathogen detected in the period before illness presentation that was significantly associated with ALRI onset. Detection of other potential ALRI pathogens was similar between cases and controls.

The Utility of Cardiac Magnetic Resonance Imaging in the Diagnosis of Cardiac Sarcoidosis.

BACKGROUND: Autopsy reports suggest that cardiac sarcoidosis occurs in 20 to 25% of patients with pulmonary sarcoidosis, yet the clinical ante-mortem diagnosis is made in only 5% of cases. Current diagnostic algorithms are complex and lack sensitivity. Cardiac Magnetic Resonance imaging (CMR) provides an opportunity to detect myocardial involvement in sarcoidosis. The aim of this study is to determine the prevalence and clinical significance of late gadolinium enhancement (LGE) on CMR in patients with sarcoidosis. METHODS: Consecutive patients with biopsy-proven sarcoidosis undergoing CMR were retrospectively evaluated for cardiac sarcoidosis. Medical records were correlated with CMR. RESULTS: Forty-six patients were evaluated. Late gadolinium enhancement was present in 22%, indicating myocardial involvement, and 70% had corresponding hyper-intense T2 signal indicating active inflammation. Late gadolinium enhancement was 18%+/-9.7% of overall left ventricular (LV) mass and most commonly located in the basal to mid septum. There was no association between LGE and cardiovascular symptoms or pulmonary stage. Eighty per cent of patients with LGE did not fulfill conventional diagnostic criteria for cardiac sarcoidosis. However, LGE was associated with clinically significant arrhythmia (p<0.01) and a lower LVEF (p=0.04). CONCLUSIONS: Using CMR, we identified a higher prevalence of cardiac sarcoidosis than previously reported clinical studies, a prevalence which is more consistent with autopsy data. The presence of LGE was highly correlated with clinically significant arrhythmias and lower LVEF.

Clinical impact of the interstitial lung disease multidisciplinary service.

BACKGROUND AND OBJECTIVE: Multidisciplinary discussions (MDDs) have been shown to improve diagnostic accuracy in interstitial lung disease (ILD) diagnosis. However, their clinical impact on patient care has never been clearly demonstrated. We describe the effect that an ILD multidisciplinary service has upon the diagnosis and management of patients with suspected ILD. METHODS: Patients at two specialized centres with suspected ILD underwent ILD multidisciplinary team review (ILD-MDT) (standard ILD clinic visit and diagnostic review at ILD-MDD). We compared changes in ILD diagnosis and management at referral to those following the ILD-MDT. RESULTS: Ninety patients, 60% males (54/90), aged 67.3 years (SD = 11.4) were reviewed for suspected ILD. Overall, the ILD-MDT resulted in a change in specific ILD diagnosis in 48/90 (53%) patients. Of the 27 patients referred with a diagnosis of idiopathic pulmonary fibrosis (IPF), the diagnosis was changed at MDD in 10 patients. In contrast, seven patients had their diagnosis changed to IPF. There was also a significant reduction in 'unclassifiable' diseases and disease behaviour classifications provided additional information beyond ILD diagnosis. CONCLUSION: Dedicated tertiary ILD-MDT service has an important clinical impact on the care of the ILD patient, with frequent changes in ILD diagnosis and subsequent management. Further research to investigate long-term clinical outcomes of ILD-MDT is required.

Dobutamine stress for evaluation of right ventricular reserve in pulmonary arterial hypertension.

Right ventricular contractile response to pharmacological stress in pulmonary arterial hypertension (PAH) has not been characterised. We evaluated right ventricular contractile reserve in adults with PAH using dobutamine stress echocardiography. 16 PAH patients and 18 age-matched controls underwent low-dose dobutamine stress echocardiography. Contractile reserve was assessed by the change (Δ; peak stress minus rest value) in tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (S'). A subgroup of 13 PAH patients underwent treadmill cardiopulmonary exercise testing for peak oxygen uptake (V'O2peak). At rest, TAPSE and S' were reduced in the PAH group compared with controls (1.7 ± 0.4 versus 2.4 ± 0.2 cm and 9.7 ± 2.6 versus 12.5 ± 1.2 cm · s(-1), respectively; p<0.05). Contractile reserve was markedly attenuated in PAH compared to controls (ΔTAPSE 0.1 ± 0.2 versus 0.6 ± 0.3 cm and ΔS' 4.6 ± 2.8 versus 11.2 ± 3.6 cm · s(-1); p<0.0001). In the sub-group of PAH patients with preserved right ventricular systolic function at rest, contractile reserve remained depressed compared to controls. V'O2peak was significantly correlated with ΔS' (r=0.87, p=0.0003) and change in stroke volume (r=0.59, p=0.03). Dobutamine stress can reveal sub-clinical reduction in right ventricular contractile reserve in patients with PAH. A correlation with exercise capacity suggests potential clinical value beyond resting measurements.

Chronic respiratory disease in Indigenous peoples: a framework to address inequity and strengthen respiratory health and health care globally.

Indigenous peoples around the world bear a disproportionate burden of chronic respiratory diseases, which are associated with increased risks of morbidity and mortality. Despite the imperative to address global inequity, research focused on strengthening respiratory health in Indigenous peoples is lacking, particularly in low-income and middle-income countries. Drivers of the increased rates and severity of chronic respiratory diseases in Indigenous peoples include a high prevalence of risk factors (eg, prematurity, low birthweight, poor nutrition, air pollution, high burden of infections, and poverty) and poor access to appropriate diagnosis and care, which might be linked to colonisation and historical and current systemic racism. Efforts to tackle this disproportionate burden of chronic respiratory diseases must include both global approaches to address contributing factors, including decolonisation of health care and research, and local approaches, co-designed with Indigenous people, to ensure the provision of culturally strengthened care with more equitable prioritisation of resources. Here, we review evidence on the burden of chronic respiratory diseases in Indigenous peoples globally, summarise factors that underlie health disparities between Indigenous and non-Indigenous people, propose a framework of approaches to improve the respiratory health of Indigenous peoples, and outline future directions for clinical care and research.

Twenty-four Month Outcomes of Extended- Versus Standard-course Antibiotic Therapy in Children Hospitalized With Pneumonia in High-Risk Settings: A Randomized Controlled Trial.

BACKGROUND: Pediatric community-acquired pneumonia (CAP) can lead to long-term respiratory sequelae, including bronchiectasis. We determined if an extended (13-14 days) versus standard (5-6 days) antibiotic course improves long-term outcomes in children hospitalized with CAP from populations at high risk of chronic respiratory disease. METHODS: We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals. Children aged 3 months to ≤5 years hospitalized with radiographic-confirmed CAP who received 1-3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, were randomized to either extended-course (8-day oral amoxicillin-clavulanate) or standard-course (8-day oral placebo) arms. Children were reviewed at 12 and 24 months. The primary outcome was children with the composite endpoint of chronic respiratory symptoms/signs (chronic cough at 12 and 24 months; ≥1 subsequent hospitalized acute lower respiratory infection by 24 months; or persistent and/or new chest radiographic signs at 12-months) at 24-months postdischarge, analyzed by intention-to-treat, where children with incomplete follow-up were assumed to have chronic respiratory symptoms/signs ("worst-case" scenario). RESULTS: A total of 324 children were randomized [extended-course (n = 163), standard-course (n = 161)]. For our primary outcome, chronic respiratory symptoms/signs occurred in 97/163 (60%) and 94/161 (58%) children in the extended-courses and standard-courses, respectively [relative risk (RR) = 1.02, 95% confidence interval (CI): 0.85-1.22]. Among children where all sub-composite outcomes were known, chronic respiratory symptoms/signs between groups, RR = 1.10, 95% CI: 0.69-1.76 [extended-course = 27/93 (29%) and standard-course = 24/91 (26%)]. Additional sensitivity analyses also revealed no between-group differences. CONCLUSION: Among children from high-risk populations hospitalized with CAP, 13-14 days of antibiotics (versus 5-6 days), did not improve long-term respiratory outcomes.

Erdosteine in children and adults with bronchiectasis (BETTER trial): study protocol for a multicentre, double-blind, randomised controlled trial.

INTRODUCTION: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function. ETHICS AND DISSEMINATION: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations. TRIAL REGISTRATION NUMBER: ACTRN12621000315819.

Mailed versus frozen transport of nasal swabs for surveillance of respiratory bacteria in remote Indigenous communities in Australia.

BACKGROUND: Surveillance programs and research for acute respiratory infections in remote Australian communities are complicated by difficulties in the storage and transport of frozen samples to urban laboratories for testing. This study assessed the sensitivity of a simple method for transporting nasal swabs from a remote setting for bacterial polymerase chain reaction (PCR) testing. METHODS: We sampled every individual who presented to a remote community clinic over a three week period in August at a time of low influenza and no respiratory syncytial virus activity. Two anterior nasal swabs were collected from each participant. The left nare specimen was mailed to the laboratory via routine postal services. The right nare specimen was transported frozen. Testing for six bacterial species was undertaken using real-time PCR. RESULTS: One hundred and forty participants were enrolled who contributed 150 study visits and paired specimens for testing. Respiratory illnesses accounted for 10% of the reasons for presentation. Bacteria were identified in 117 (78%) presentations for 110 (79.4%) individuals; Streptococcus pneumoniae and Haemophilus influenzae were the most common (each identified in 58% of episodes). The overall sensitivity for any bacterium detected in mailed specimens was 82.2% (95% CI 73.6, 88.1) compared to 94.8% (95% CI 89.4, 98.1) for frozen specimens. The sensitivity of the two methods varied by species identified. CONCLUSION: The mailing of unfrozen nasal specimens from remote communities appears to influence the utility of the specimen for bacterial studies, with a loss in sensitivity for the detection of any species overall. Further studies are needed to confirm our finding and to investigate the possible mechanisms of effect. CLINICAL TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry Number: ACTRN12609001006235.

Azithromycin for Indigenous children with bronchiectasis: study protocol for a multi-centre randomized controlled trial.

BACKGROUND: The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis. METHODS/DESIGN: We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12-24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV(1); for children ≥6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4 months for up to 24 months from study entry are recorded on standardised forms. DISCUSSION: Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations, it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12610000383066.

Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial.

BACKGROUND: High-level evidence is limited for antibiotic duration in children hospitalized with community-acquired pneumonia (CAP) from First Nations and other at-risk populations of chronic respiratory disorders. As part of a larger study, we determined whether an extended antibiotic course is superior to a standard course for achieving clinical cure at 4 weeks in children 3 months to ≤5 years old hospitalized with CAP. METHODS: In our multinational (Australia, New Zealand, Malaysia), double-blind, superiority randomized controlled trial, children hospitalized with uncomplicated, radiographic-confirmed, CAP received 1-3 days of intravenous antibiotics followed by 3 days of oral amoxicillin-clavulanate (80 mg/kg, amoxicillin component, divided twice daily) and then randomized to extended (13-14 days duration) or standard (5-6 days) antibiotics. The primary outcome was clinical cure (complete resolution of respiratory symptoms/signs) 4 weeks postenrollment. Secondary outcomes included adverse events, nasopharyngeal bacterial pathogens and antimicrobial resistance at 4 weeks. RESULTS: Of 372 children enrolled, 324 fulfilled the inclusion criteria and were randomized. Using intention-to-treat analysis, between-group clinical cure rates were similar (extended course: n = 127/163, 77.9%; standard course: n = 131/161, 81.3%; relative risk = 0.96, 95% confidence interval = 0.86-1.07). There were no significant between-group differences for adverse events (extended course: n = 43/163, 26.4%; standard course, n = 32/161, 19.9%) or nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus or antimicrobial resistance. CONCLUSIONS: Among children hospitalized with pneumonia and at-risk of chronic respiratory illnesses, an extended antibiotic course was not superior to a standard course at achieving clinical cure at 4 weeks. Additional research will identify if an extended course provides longer-term benefits.

Successful application of a simple specimen transport method for the conduct of respiratory virus surveillance in remote Indigenous communities in Australia.

OBJECTIVE: Surveillance programs and research for acute respiratory infections in remote Aboriginal communities are complicated by difficulties in the storage and transport of frozen samples to urban laboratories for testing. This study assessed the sensitivity of a simple method for transporting respiratory samples from a remote setting for viral PCR compared with frozen specimens. METHODS: We sampled every individual who presented to a remote Aboriginal community clinic in a non-epidemic respiratory season. Two anterior nasal swabs were collected from each participant. The left nare specimen was mailed to the laboratory via routine postal services. The right nare specimen was transported frozen. Testing for 16 viruses was undertaken using real-time multiplex PCR. RESULTS: A total of 140 participants were enrolled who contributed 150 study visits. Respiratory illnesses accounted for 10% of the reasons for presentation. Sixty-one viruses were identified in 50 (33.3%) presentations for 40 (28.6%) individuals; bocavirus and rhinovirus were the most common viruses identified (14.0% and 12.6% of episodes respectively). The sensitivity for any virus detected in mailed specimens was 67.2% (95%CI 55.4, 78.9) compared to 65.6% (95%CI 53.7, 77.5) for frozen specimens. CONCLUSION: The mailing of unfrozen nasal specimens from remote communities does not compromise the viability of the specimen for viral studies.

Pregnancy outcomes in the current era of cystic fibrosis care: a 15-year experience.

BACKGROUND: With improvement in clinical care and longer survival of patients with cystic fibrosis (CF), pregnancy has become commonplace. However, the impact of pregnancy on maternal health and fetal outcomes requires ongoing review. METHODS: A retrospective study of 20 pregnancies from 18 women with CF during the period 1995-2009 was performed. Changes in lung function, body mass index (BMI) and development of gestational diabetes were recorded. Fetal outcomes and maternal survival were examined, and the influence of pre-pregnancy parameters on outcomes was evaluated. RESULTS: Mean maternal age at pregnancy was 29±5 years with a mean pre-pregnancy forced expiratory volume in 1 s (FEV1) of 65.6±20.8% predicted. Eleven of 20 pregnancies had a pre-pregnancy FEV1 <60% predicted. During pregnancy, FEV1% predicted fell by 4.8% (CI 1.6-7.9), but recovered to baseline within 6 months post-partum. Mothers gained a mean weight of 7.6±3.2 kg, and gestational diabetes developed in 43% of women. All women delivered live births apart from one therapeutic abortion. Five infants were preterm, and two mature infants had low birth weight. Three mothers either died or required lung transplantation after pregnancy (range 2.5-8.0 years). FEV1 <60% predicted and BMI <20 kg/m(2) were significant predictors of fetal complications. CONCLUSION: Most women tolerated pregnancy well without major complications despite many having at least moderate lung function impairment. Pre-pregnancy FEV1 and BMI were important predictors of outcomes.

Long-term outcomes of adults with acute respiratory failure treated with veno-venous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation is increasingly used for severe but potentially reversible acute respiratory failure in adults; however, there are limited data regarding long-term morbidity. At our institution, most patients requiring veno-venous extracorporeal membrane oxygenation have been followed up by a single physician. Our primary aim was to describe the serial long-term morbidity for respiratory, musculoskeletal and psychological functioning.A retrospective audit of inpatient and outpatient medical records was conducted. A total of 125 patients treated with veno-venous extracorporeal membrane oxygenation for primary respiratory failure were included. The patients were young (mean (standard deviation) age 43.7 (4.1) years), obese (mean (standard deviation) body mass index 30.8 (10.4) kg/m2), and mostly were male (59%). Most patients (60%) had no comorbidities.The survival rate to discharge was 70%, with body mass index and the number of comorbidities being independent predictors of survival on multiple logistic regression analysis. Over half (57%) of the Australian survivors had regular outpatient follow-up. They had a median of three reviews (range 1-9) over a median of 11.8 months (range 1.5-79) months. Breathlessness and weakness resolved in most within six months, with lung function abnormalities taking longer to resolve. Over half (60%) returned to employment within six months of discharge. Over a quarter (29%) displayed symptoms of anxiety, depression or post-traumatic stress disorder.