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1.
Pediatr Infect Dis J ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830139

ABSTRACT

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.

2.
Eur Respir Rev ; 33(172)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38599675

ABSTRACT

Respiratory symptoms are ubiquitous in children and, even though they may be the harbinger of poor long-term outcomes, are often trivialised. Adverse exposures pre-conception, antenatally and in early childhood have lifetime impacts on respiratory health. For the most part, lung function tracks from the pre-school years at least into late middle age, and airflow obstruction is associated not merely with poor respiratory outcomes but also early all-cause morbidity and mortality. Much would be preventable if social determinants of adverse outcomes were to be addressed. This review presents the perspectives of paediatricians from many different contexts, both high and low income, including Europe, the Americas, Australasia, India, Africa and China. It should be noted that there are islands of poverty within even the highest income settings and, conversely, opulent areas in even the most deprived countries. The heaviest burden of any adverse effects falls on those of the lowest socioeconomic status. Themes include passive exposure to tobacco smoke and indoor and outdoor pollution, across the entire developmental course, and lack of access even to simple affordable medications, let alone the new biologicals. Commonly, disease outcomes are worse in resource-poor areas. Both within and between countries there are avoidable gross disparities in outcomes. Climate change is also bearing down hardest on the poorest children. This review highlights the need for vigorous advocacy for children to improve lifelong health. It also highlights that there are ongoing culturally sensitive interventions to address social determinants of disease which are already benefiting children.


Subject(s)
Respiration Disorders , Social Determinants of Health , Child , Child, Preschool , Humans , China , Europe , Morbidity , Poverty , Female , Pregnancy , Infant, Newborn , Infant , Prenatal Exposure Delayed Effects
3.
ERJ Open Res ; 10(2)2024 Mar.
Article in English | MEDLINE | ID: mdl-38590934

ABSTRACT

Background: Asthma is the most common chronic childhood respiratory condition globally. Inhaled corticosteroid (ICS)-formoterol reliever-based regimens reduce the risk of asthma exacerbations compared with conventional short-acting ß2-agonist (SABA) reliever-based regimens in adults and adolescents. The current limited evidence for anti-inflammatory reliever therapy in children means it is unknown whether these findings are also applicable to children. High-quality randomised controlled trials (RCTs) are needed. Objective: The study aim is to determine the efficacy and safety of budesonide-formoterol reliever alone or maintenance and reliever therapy (MART) compared with standard therapy: budesonide or budesonide-formoterol maintenance, both with terbutaline reliever, in children aged 5 to 11 years with mild, moderate and severe asthma. Methods: A 52-week, multicentre, open-label, parallel group, phase III, two-sided superiority RCT will recruit 400 children aged 5 to 11 years with asthma. Participants will be randomised 1:1 to either budesonide-formoterol 100/6 µg Turbuhaler reliever alone or MART; or budesonide or budesonide-formoterol Turbuhaler maintenance, with terbutaline Turbuhaler reliever. The primary outcome is moderate and severe asthma exacerbations as rate per participant per year. Secondary outcomes are asthma control, lung function, exhaled nitric oxide and treatment step change. Assessment of Turbuhaler technique and cost-effectiveness analysis are also planned. Conclusion: This will be the first RCT to compare the efficacy and safety of a step-wise budesonide-formoterol reliever alone or MART regimen with conventional inhaled ICS or ICS-long-acting ß-agonist maintenance plus SABA reliever in children. The results will provide a much-needed evidence base for the treatment of asthma in children.

5.
Chest ; 164(6): 1378-1386, 2023 12.
Article in English | MEDLINE | ID: mdl-37437879

ABSTRACT

BACKGROUND: Respiratory exacerbations in children and adolescents with bronchiectasis are treated with antibiotics. However, antibiotics can have variable interindividual effects when treating exacerbations. RESEARCH QUESTION: Can phenotypic features associated with symptom resolution after a 14-day course of oral antibiotics for a nonsevere exacerbation of bronchiectasis be identified? STUDY DESIGN AND METHODS: Combining data from two multicenter randomized controlled trials, we identified 217 children with bronchiectasis assigned to at least 14 days of oral antibiotics to treat nonsevere (nonhospitalized) exacerbations. Univariable and then multivariable logistic regression were used to identify factors associated with symptom resolution within 14 days of commencing antibiotics. Identified associations were re-evaluated by mediation analysis. RESULTS: Of the 217 study participants (52% male patients), 41% were Indigenous (Australian First Nations, New Zealand Maori, or Pacific Islander). The median age was 6.6 years (interquartile range, 4.0-10.1 years). By day 14, symptoms had resolved in 130 children (responders), but persisted in the remaining 87 children (nonresponders). Multivariable analysis found those who were Indigenous (adjusted OR [AOR], 3.59; 95% CI, 1.35-9.54) or showed new abnormal auscultatory findings (AOR, 3.85; 95% CI, 1.56-9.52) were more likely to be responders, whereas those with multiple bronchiectatic lobes at diagnosis (AOR, 0.66; 95% CI, 0.46-0.95) or higher cough scores when starting exacerbation treatment (AOR, 0.55; 95% CI, 0.34-0.90) were more likely to be nonresponders. Detecting a respiratory virus at the beginning of an exacerbation was not associated with antibiotic failure at 14 days. INTERPRETATION: Children with Indigenous ethnicity, milder bronchiectasis, mild exacerbations (low reported cough scores), or new abnormal auscultatory signs are more likely to respond to appropriate oral antibiotics than those without these features. These patient and exacerbation phenotypes may assist clinical management and development of biomarkers to identify those whose symptoms are more likely to resolve after 14 days of oral antibiotics. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry; Nos.: ACTRN12612000011886 and ACTRN12612000010897; URL: https://www.anzctr.org.au.


Subject(s)
Anti-Bacterial Agents , Bronchiectasis , Adolescent , Child , Female , Humans , Male , Anti-Bacterial Agents/therapeutic use , Australia , Bronchiectasis/diagnosis , Bronchiectasis/drug therapy , Cough/drug therapy , Disease Progression , Phenotype
6.
Respirology ; 28(4): 339-349, 2023 04.
Article in English | MEDLINE | ID: mdl-36863703

ABSTRACT

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.


Subject(s)
Bronchiectasis , Lung Diseases , Child , Humans , Adult , Adolescent , New Zealand , Australia , Bronchiectasis/therapy , Bronchiectasis/drug therapy , Lung Diseases/drug therapy , Anti-Bacterial Agents/therapeutic use
7.
J Child Health Care ; 27(4): 587-598, 2023 12.
Article in English | MEDLINE | ID: mdl-35379016

ABSTRACT

This qualitative study was conducted to explore the experiences of youth living with bronchiectasis in New Zealand (NZ). Semi-structured interviews were conducted with youth with bronchiectasis. Key themes were identified using an inductive approach through constant comparative analysis and guided by Thorne's interpretive description (ID). Fifteen young people of mixed ethnicity (nine females and six males) aged between 13 and 23 years participated. Three key themes 'sore and tired', 'life interrupted and 'looking after self' were identified. This paper will focus on 'sore and tired' and its three subthemes which describe the participants symptom experience. While there was variability in physical symptom patterns, cough, soreness and fatigue were prominent features impacting physical, emotional and social aspects of day-to-day life. All identified pervasive and profound fatigue as significant. The identification of prodromal symptoms provides opportunity for greater appreciation of the varied and personal symptom experience of young people with bronchiectasis. Early identification of these symptoms and inclusion within management plans for escalating treatment has the potential to improve outcomes, reducing delays in seeking additional medical management and preventing further exacerbation.


Subject(s)
Bronchiectasis , Quality of Life , Male , Female , Humans , Adolescent , Young Adult , Adult , Quality of Life/psychology , Pain , Bronchiectasis/therapy , Qualitative Research , Fatigue/etiology
8.
Chest ; 163(1): 52-63, 2023 01.
Article in English | MEDLINE | ID: mdl-36030839

ABSTRACT

BACKGROUND: Following evidence from randomized controlled trials, patients with bronchiectasis unrelated to cystic fibrosis receive long-term azithromycin to reduce acute respiratory exacerbations. However, the period when azithromycin is effective and which patients are likely to most benefit remain unknown. RESEARCH QUESTIONS: (i) What is the period after its commencement when azithromycin is most effective? and (ii) Which factors may modify azithromycin effects? STUDY DESIGN AND METHODS: A secondary analysis was conducted of our previous randomized controlled trial involving 89 indigenous children with bronchiectasis unrelated to cystic fibrosis. Semi-parametric Poisson regression identified the azithromycin efficacy period. Multivariable Poisson regression identified factors that modify azithromycin effect. RESULTS: Azithromycin was associated with fewer exacerbations per child-week during weeks 4 through 96, with the most effective period observed between weeks 17 and 62. Eleven factors were associated with different azithromycin effects; four were significant at the P < .05 level. Compared with their counterparts, higher reduction in exacerbations was observed in children with nasopharyngeal carriage of bacterial pathogens (incidence rate ratio [IRR] = 0.81 [95% CI, 0.57-1.14] vs 0.29 [0.20-0.44]; P < .001); New Zealand children (IRR = 0.73 [0.51-1.03] vs 0.39 [0.28-0.55]; P = .012); and those with higher weight-for-height z scores (interaction IRR = 0.82 [0.67-0.99]; P = .044). Compared with their counterparts, lower reduction was observed in those born preterm (IRR = 0.41 [0.30-0.55] vs 0.74 [0.49-1.10]; P = .012). INTERPRETATION: Regular azithromycin is best used for at least 17 weeks and up to 62 weeks, as these periods provide maximum benefit for indigenous children with bronchiectasis unrelated to cystic fibrosis. Several factors modified azithromycin benefits; however, these traits need confirmation in larger studies before being adopted into clinical practice. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry; ACTRN12610000383066.


Subject(s)
Bronchiectasis , Cystic Fibrosis , Humans , Infant, Newborn , Anti-Bacterial Agents/therapeutic use , Australia/epidemiology , Azithromycin/therapeutic use , Bronchiectasis/drug therapy , Bronchiectasis/complications , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Double-Blind Method
9.
Lancet Respir Med ; 10(8): 776-784, 2022 08.
Article in English | MEDLINE | ID: mdl-35662406

ABSTRACT

BACKGROUND: Structural lung disease and neutrophil-dominated airway inflammation is present from 3 months of age in children diagnosed with cystic fibrosis after newborn screening. We hypothesised that azithromycin, given three times weekly to infants with cystic fibrosis from diagnosis until age 36 months, would reduce the extent of structural lung disease as captured on chest CT scans. METHODS: A phase three, randomised, double-blind, placebo-controlled trial was done at eight paediatric cystic fibrosis centres in Australia and New Zealand. Infants (aged 3-6 months) diagnosed with cystic fibrosis following newborn screening were eligible. Exclusion criteria included prolonged mechanical ventilation in the first 3 months of life, clinically significant medical disease or comorbidities other than cystic fibrosis, or macrolide hypersensitivity. Participants were randomly assigned (1:1) to receive either azithromycin (10 mg/kg bodyweight orally three times per week) or matched placebo until age 36 months. Randomisation was done with a permuted block strategy and an interactive web-based response system, stratified by study site. Unblinding was done once all participants completed the trial. The two primary outcomes were the proportion of children with radiologically defined bronchiectasis, and the percentage of total lung volume affected by disease. Secondary outcomes included clinical outcomes and exploratory outcomes were inflammatory markers. Analyses were done with the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT01270074). FINDINGS: Between June 15, 2012, and July 10, 2017, 281 patients were screened, of whom 130 were enrolled, randomly assigned, and received first study dose. 68 participants received azithromycin and 62 received placebo. At 36 months, 88% (n=50) of the azithromycin group and 94% (n=44) of the placebo group had bronchiectasis (odds ratio 0·49, 95% CI 0·12 to 2·00; p=0·32), and total airways disease did not differ between groups (median difference -0·02%, 95% CI -0·59 to 0·56; p=0·96). Secondary outcome results included fewer days in hospital for pulmonary exacerbations (mean difference -6·3, 95% CI -10·5 to -2·1; p=0·0037) and fewer courses of inhaled or oral antibiotics (incidence rate ratio 0·88, 95% CI 0·81 to 0·97; p=0·0088) for those in the azithromycin group. For the preplanned, exploratory analysis, concentrations of airway inflammation were lower for participants receiving azithromycin, including interleukin-8 (median difference -1·2 pg/mL, 95% CI -1·9 to -0·5; p=0·0012) and neutrophil elastase activity (-0·6 µg/mL, -1·1 to -0·2; p=0·0087) at age 36 months, although no difference was noted between the groups for interleukin-8 or neutrophil elastase activity at 12 months. There was no effect of azithromycin on body-mass index at age 36 months (mean difference 0·4, 95% CI -0·1 to 0·9; p=0·12), nor any evidence of pathogen emergence with the use of azithromycin. There were few adverse outcomes with no differences between the treatment groups. INTERPRETATION: Azithromycin treatment from diagnosis of cystic fibrosis did not reduce the extent of structural lung disease at 36 months of age; however, it did reduce airway inflammation, morbidity including pulmonary exacerbations in the first year of life and hospitalisations, and improved some clinical outcomes associated with cystic fibrosis lung disease. Therefore we suggest thrice-weekly azithromycin is a strategy that could be considered for the routine early management of paediatric patients with cystic fibrosis. FUNDING: Cystic Fibrosis Foundation.


Subject(s)
Bronchiectasis , Cystic Fibrosis , Anti-Bacterial Agents , Azithromycin , Bronchiectasis/drug therapy , Child , Child, Preschool , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Double-Blind Method , Humans , Infant , Infant, Newborn , Inflammation/drug therapy , Interleukin-8 , Leukocyte Elastase/therapeutic use
10.
J Cyst Fibros ; 21(4): e221-e231, 2022 07.
Article in English | MEDLINE | ID: mdl-35753987

ABSTRACT

BACKGROUND: This international study aimed to characterise the impact of acute SARS-CoV-2 infection in people with cystic fibrosis and investigate factors associated with severe outcomes. Methods Data from 22 countries prior to 13th December 2020 and the introduction of vaccines were included. It was de-identified and included patient demographics, clinical characteristics, treatments, outcomes and sequalae following SARS-CoV-2 infection. Multivariable logistic regression was used to investigate factors associated with clinical progression to severe COVID-19, using the primary outcome of hospitalisation with supplemental oxygen. RESULTS: SARS-CoV-2 was reported in 1555 people with CF, 1452 were included in the analysis. One third were aged <18 years, and 9.4% were solid-organ transplant recipients. 74.5% were symptomatic and 22% were admitted to hospital. In the non-transplanted cohort, 39.5% of patients with ppFEV1<40% were hospitalised with oxygen verses 3.2% with ppFEV >70%: a 17-fold increase in odds. Worse outcomes were independently associated with older age, non-white race, underweight body mass index, and CF-related diabetes. Prescription of highly effective CFTR modulator therapies was associated with a significantly reduced odds of being hospitalised with oxygen (AOR 0.43 95%CI 0.31-0.60 p<0.001). Transplanted patients were hospitalised with supplemental oxygen therapy (21.9%) more often than non-transplanted (8.8%) and was independently associated with the primary outcome (Adjusted OR 2.45 95%CI 1.27-4.71 p=0.007). CONCLUSIONS: This is the first study to show that there is a protective effect from the use of CFTR modulator therapy and that people with CF from an ethnic minority are at more risk of severe infection with SARS-CoV-2.


Subject(s)
COVID-19 , Cystic Fibrosis , COVID-19/epidemiology , COVID-19/therapy , Cystic Fibrosis/complications , Cystic Fibrosis/epidemiology , Cystic Fibrosis/therapy , Cystic Fibrosis Transmembrane Conductance Regulator , Ethnicity , Humans , Minority Groups , Oxygen , SARS-CoV-2
11.
Pediatr Infect Dis J ; 41(7): 549-555, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35476706

ABSTRACT

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.


Subject(s)
Community-Acquired Infections , Pneumonia , Amoxicillin/therapeutic use , Amoxicillin-Potassium Clavulanate Combination/adverse effects , Anti-Bacterial Agents , Child , Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiology , Double-Blind Method , Humans , Infant , Pneumonia/drug therapy
12.
J Cyst Fibros ; 21(6): 977-983, 2022 11.
Article in English | MEDLINE | ID: mdl-35341694

ABSTRACT

BACKGROUND: Despite improvements in general health and life expectancy in people with cystic fibrosis (CF), lung function decline continues unabated during adolescence and early adult life. METHODS: We examined factors present at age 5-years that predicted lung function decline from childhood to adolescence in a longitudinal study of Australasian children with CF followed from 1999 to 2017. RESULTS: Lung function trajectories were calculated for 119 children with CF from childhood (median 5.0 [25%-75%=5.0-5.1]) years) to early adolescence (median 12.5 [25%-75%=11.4-13.8] years). Lung function fell progressively, with mean (standard deviation) annual change -0.105 (0.049) for forced vital capacity (FVC) Z-score (p<0.001), -0.135 (0.048) for forced expiratory volume in 1-second (FEV1) Z-score (p<0.001), -1.277 (0.221) for FEV1/FVC% (p<0.001), and -0.136 (0.052) for forced expiratory flow between 25% and 75% of FVC Z-score (p<0.001). Factors present in childhood predicting lung function decline to adolescence, in multivariable analyses, were hospitalisation for respiratory exacerbations in the first 5-years of life (FEV1/FVC p = 0.001, FEF25-75p = 0.01) and bronchoalveolar lavage neutrophil elastase activity (FEV1/FVC% p = 0.001, FEV1p = 0.05, FEF25-75p = 0.02). No examined factor predicted a decline in the FVC Z-score. CONCLUSIONS: Action in the first 5-years of life to prevent and/or treat respiratory exacerbations and counteract neutrophilic inflammation in the lower airways may reduce lung function decline in children with CF, and these should be targets of future research.


Subject(s)
Cystic Fibrosis , Child , Adult , Adolescent , Humans , Child, Preschool , Cystic Fibrosis/complications , Longitudinal Studies , Lung , Vital Capacity , Forced Expiratory Volume , Spirometry
13.
J Paediatr Child Health ; 58(6): 1039-1045, 2022 06.
Article in English | MEDLINE | ID: mdl-35170144

ABSTRACT

AIM: Following trials of inhaled antibiotics in adults, this study investigates the efficacy of nebulised gentamicin to improve respiratory function in children with bronchiectasis. METHODS: This is a randomised, double-blind, placebo-controlled, crossover trial of 12-week nebulised placebo/gentamicin, 6-week washout, 12-week gentamicin/placebo. Participants were children (5-15 years) with bronchiectasis, chronic infection (any pathogen), and able to perform spirometry from a hospital bronchiectasis clinic. Primary outcomes were change in forced expiratory volume in 1 s (FEV1 ) and hospitalisation days. Secondary outcomes included sputum bacterial density, sputum inflammatory markers, additional antibiotics and symptom severity. Analyses were on an intention-to-treat basis. RESULTS: Fifteen children (mean 11.7-years-old) completed the study. There was no significant change in mean FEV1 (56%/55%, P = 0.38) or annual rate of hospital admissions (1.1/0, P = 0.12) between gentamicin and placebo, respectively. However, Haemophilus influenzae sputum growth (27% vs. 80%, P = 0.002) and bacterial density (2.4 log10 cfu/mL lower P < 0.001) improved with gentamicin. Sputum inflammatory markers interleukin-1ß (P < 0.001), interleukin-8 (P < 0.001) and tumour necrosis factor-α (P = 0.003) were lower with gentamicin. Poor recruitment limited study power and treatment adherence was challenging for this cohort. CONCLUSIONS: In this crossover study of nebulised gentamicin in children with bronchiectasis, there was a reduction in sputum bacterial density and inflammation. However, there were no major improvements in clinical outcomes and adherence was a challenge.


Subject(s)
Bronchiectasis , Gentamicins , Anti-Bacterial Agents/therapeutic use , Bronchiectasis/drug therapy , Bronchiectasis/microbiology , Child , Cross-Over Studies , Double-Blind Method , Gentamicins/therapeutic use , Haemophilus influenzae , Humans , Sputum
14.
ERJ Open Res ; 7(4)2021 Oct.
Article in English | MEDLINE | ID: mdl-34853785

ABSTRACT

BACKGROUND: Asthma is the most common chronic disease in children, many of whom are managed solely with a short-acting ß2-agonist (SABA). In adults, the evidence that budesonide-formoterol as sole reliever therapy markedly reduces the risk of severe exacerbations compared with SABA alone has contributed to the Global Initiative for Asthma recommending against SABA monotherapy in this population. The current lack of evidence in children means it is unknown whether these findings are also relevant to this demographic. High-quality randomised controlled trials (RCTs) are needed. OBJECTIVE: The aim of this study is to determine the efficacy and safety of as-needed budesonide-formoterol therapy compared with as-needed salbutamol in children aged 5 to 15 years with mild asthma, who only use a SABA. METHODS: A 52-week, open-label, parallel group, phase III RCT will recruit 380 children aged 5 to 15 years with mild asthma. Participants will be randomised 1:1 to either budesonide-formoterol (Symbicort Rapihaler®) 50/3 µg, two actuations as needed, or salbutamol (Ventolin®) 100  µg, two actuations as needed. The primary outcome is asthma attacks as rate per participant per year. Secondary outcomes assess asthma control, lung function, exhaled nitric oxide and treatment step change. A cost-effectiveness analysis is also planned. CONCLUSION: This is the first RCT to assess the safety and efficacy of as-needed budesonide-formoterol in children with mild asthma. The results will provide a much-needed evidence base for the treatment of mild asthma in children.

15.
Int J Qual Stud Health Well-being ; 16(1): 2003520, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34793292

ABSTRACT

PURPOSE: Bronchiectasis is a chronic respiratory disease that impacts significantly on quality of life for those who have it. There is a paucity of literature exploring the perspectives of children and young people. The aim of this study was to examine the day-to-day life experience of a group of young people with bronchiectasis. METHOD: A qualitative study using semi-structured interviews explored fifteen young people's perspectives of life with bronchiectasis. Key themes were identified using an inductive iterative approach through constant comparative analysis guided by Thorne's interpretive description. RESULTS: Life with bronchiectasis was conceptualized by participants as "Pretty Normal". This consisted of two co-existing life views which represented how young people balanced the ups and downs of adolescence while learning to accommodate the demands of living with bronchiectasis. Three key thematic elements "sore and tired", 'life interrupted and "looking after self", influenced and challenged these two views of life. CONCLUSIONS: Young people with bronchiectasis portray life as being the same as their peers. Despite this, they recognized that the symptoms, interruptions, and self-management responsibilities led them to find ways of coping and integrating their experience into a new and modified view of normal.


Subject(s)
Bronchiectasis , Self-Management , Adaptation, Psychological , Adolescent , Child , Humans , Qualitative Research , Quality of Life
16.
Pediatr Pulmonol ; 56(9): 2949-2957, 2021 09.
Article in English | MEDLINE | ID: mdl-34232567

ABSTRACT

AIM: The incidence of childhood empyema has been increasing in some developed countries despite the introduction of pneumococcal vaccination. This study aimed to document the incidence, bacterial pathogens, and morbidity/mortality of parapneumonic effusion/empyema in New Zealand. METHODS: A prospective study of 102 children <15 years of age requiring hospitalization with parapneumonic effusion/empyema between May 1, 2014 and May 31, 2016 notified via the New Zealand Paediatric Surveillance Unit. Parapneumonic effusion/empyema was defined as pneumonia and pleural effusion persisting ≥7 days, and/or any pneumonia, and pleural effusion necessitating drainage. Notifying pediatricians completed standardized questionnaires. RESULTS: Annual pediatric parapneumonic effusion/empyema incidence was 5.6/100,000 (95% confidence interval [CI]: 4.7-6.9). Most children (80%) required surgical intervention and 31% required intensive care. A causative organism was identified in 71/102 (70%) cases. Although Staphylococcus aureus (25%) and Streptococcus pneumoniae (25%) infection rates were equal, prolonged hospitalization and intensive care admission were more common in children with S. aureus PPE/E. Maori and Pasifika children were over-represented at 2.2 and 3.5 times, their representation in the New Zealand pediatric population. Pneumococcal vaccination was incomplete, with only 61% fully immunized and 30% unimmunized. Haemophilus influenzae type b vaccine uptake was near complete at 89/94 (95%), with influenza immunization only 3/78 (4%). CONCLUSIONS: New Zealand has a high incidence of pediatric complicated parapneumonic effusion/empyema with significant morbidity. S. aureus was a significant cause of severe empyema in New Zealand, particularly for Maori and Pasifika children. Improvements in vaccine coverage are needed along with strategies to reduce S. aureus disease morbidity.


Subject(s)
Empyema, Pleural , Empyema , Pleural Effusion , Child , Empyema, Pleural/epidemiology , Humans , Infant , New Zealand/epidemiology , Pleural Effusion/epidemiology , Prospective Studies , Staphylococcus aureus
19.
Eur J Pediatr ; 180(10): 3171-3179, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33909156

ABSTRACT

Non-cystic fibrosis bronchiectasis is increasingly described in the paediatric population. While diagnosis is by high-resolution chest computed tomography (CT), chest X-rays (CXRs) remain a first-line investigation. CXRs are currently insensitive in their detection of bronchiectasis. We aim to determine if quantitative digital analysis allows CT features of bronchiectasis to be detected in contemporaneously taken CXRs. Regions of radiologically (A) normal, (B) severe bronchiectasis, (C) mild airway dilation and (D) other parenchymal abnormalities were identified in CT and mapped to corresponding CXR. An artificial neural network (ANN) algorithm was used to characterise regions of classes A, B, C and D. The algorithm was then tested in 13 subjects and compared to CT scan features. Structural changes in CT were reflected in CXR, including mild airway dilation. The areas under the receiver operator curve for ANN feature detection were 0.74 (class A), 0.71 (class B), 0.76 (class C) and 0.86 (class D). CXR analysis identified CT measures of abnormality with a better correlation than standard radiological scoring at the 99% confidence level.Conclusion: Regional abnormalities can be detected by digital analysis of CXR, which may provide a low-cost and readily available tool to indicate the need for diagnostic CT and for ongoing disease monitoring. What is Known: • Bronchiectasis is a severe chronic respiratory disorder increasingly recognised in paediatric populations. • Diagnostic computed tomography imaging is often requested only after several chest X-ray investigations. What is New: • We show that a digital analysis of chest X-ray could provide more accurate identification of bronchiectasis features.


Subject(s)
Bronchiectasis , Algorithms , Bronchiectasis/diagnostic imaging , Child , Humans , Thorax , Tomography, X-Ray Computed , X-Rays
20.
Emerg Infect Dis ; 27(2): 641-643, 2021 02.
Article in English | MEDLINE | ID: mdl-33263515

ABSTRACT

In March 2020, a national elimination strategy for coronavirus disease was introduced in New Zealand. Since then, hospitalizations for lower respiratory tract infection among infants <2 years of age and cases of respiratory syncytial or influenza virus infection have dramatically decreased. These findings indicate additional benefits of coronavirus disease control strategies.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Influenza, Human/epidemiology , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Tract Infections/epidemiology , COVID-19/virology , Female , Humans , Incidence , Infant , Infant, Newborn , Influenza, Human/virology , Male , New Zealand/epidemiology , Orthomyxoviridae , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus, Human , Respiratory Tract Infections/virology , SARS-CoV-2 , Seasons
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