RESUMO
BACKGROUND: Long-term effects of early, recurrent human exposure to general anaesthesia remain unknown. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial provided an opportunity to examine this issue in children randomly assigned in infancy to either repeated bronchoalveolar-lavage (BAL)-directed therapy with general anaesthesia or standard care with no planned lavages up to 5 years of age when all children received BAL-directed therapy under general anaesthesia. METHODS: This multicentre, randomised, open-label phase 4 trial (CF-GAIN) used the original ACFBAL trial randomisation at 3·6 months (SD 1·6) to BAL-directed therapy or standard-care groups to assess the impact of general anaesthesia exposures over early childhood. Children who completed the ACFBAL trial, with a mean age of 5·1 (SD 0·18) years, received standardised neurobehavioural and health-related-quality-of-life assessment and brain MRI scans between Oct 8, 2013, and June 30, 2017, at a mean age of 12·8 (SD 1·7) years at three hospitals in Australia and one hospital in New Zealand. The primary outcome was a composite score of performance on a standardised, computer-based assessment of child attention, processing speed, and response inhibition skills (Conners Continuous Performance test, second edition). Secondary outcomes included intellectual function, other neurobehavioural measures, and brain imaging as an exploratory outcome. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12613000057785) and is completed. FINDINGS: At 2 years, the BAL-directed therapy group (n=52) and standard-care group (n=45) had a median of 2·0 (IQR 1·0-3·0) and 0·0 (0·0-0·0) exposures, respectively. At completion of the ACFBAL trial, the BAL-directed therapy group had a median of 6·0 (4·0-9·5) exposures and the standard-care group 2·0 (1·0-4·0) exposures. At CF-GAIN completion, the BAL-directed therapy group had a median of 10·0 (IQR 6·5-14·5) exposures and the standard-care group 4·0 (3·0-7·0) exposures. Cumulative general anaesthesia exposure time was not prospectively collected but, for those with complete cumulative exposure time data to the end of the ACFBAL trial, the median cumulative exposure time for the BAL-directed therapy group (n=29) was 180 (IQR 140-285) min and for the standard-care group (n=32) was 48 (30-122) min. The mean Conners Continuous Performance test, second edition composite score was 51 (SD 8·1) in BAL-directed therapy group and 53 (8·8) in the standard-care group; difference -1·7 (95% CI -5·2 to 1·7; p=0·32) with similar performance on other neurobehavioural measures, including measures of executive function, intellectual quotient scores, and brain imaging. INTERPRETATION: Our findings suggest that repeated general anaesthesia exposure in young children with cystic fibrosis is not related to functional impairment in attention, intellectual quotient, executive function, or brain structure compared with a group with fewer and shorter cumulative anaesthesia durations. FUNDING: National Health and Medical Research Council Australia, Queensland Government Health Service and Clinical Innovation Fellowship, and the Children's Hospital Foundation Queensland.
Assuntos
Anestesia Geral , Fibrose Cística , Humanos , Fibrose Cística/terapia , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Feminino , Masculino , Pré-Escolar , Criança , Lavagem Broncoalveolar/métodos , Qualidade de Vida , Lactente , Austrália , Resultado do Tratamento , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: There is no data exclusively on the relationship between health-related quality-of-life (HRQOL) and lung disease severity in early school-aged children with cystic fibrosis (CF). Using data from the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) we assessed the relationships between HRQOL, lung function and structure. METHODS: 125 children aged 6.5-10 years enrolled in the AREST CF program were included from CF clinics at Royal Children's Hospital (RCH), Melbourne (n = 66) and Perth Children's Hospital (PCH), Perth (n = 59), Australia. Demographics, HRQOL measured by Cystic Fibrosis Questionnaire-Revised (CFQ-R), spirometry, multiple-breath washout (MBW) and chest CT were collected across two years. Correlation between CFQ-R scores and lung structure/function parameters and agreement between parent-proxy and child-reported HRQOL were evaluated. RESULTS: No correlation was observed between most CFQ-R domain scores and FEV1 z-scores, excepting weak-positive correlation with parent CFQ-R Physical (rho = 0.21, CI 0.02-0.37), and Weight (rho = 0.21, CI 0.03-0.38) domain and child Body domain (rho = 0.26, CI 0.00-0.48). No correlation between most CFQ-R domain scores and LCI values was noted excepting weak-negative correlation with parent Respiratory (rho = -0.23, CI -0.41--0.05), Emotional (rho = -0.24, CI -0.43--0.04), and Physical (-0.21, CI -0.39--0.02) domains. Furthermore, structural lung disease on CT data demonstrated little to no association with CFQ-R parent and child domain scores. Additionally, no agreement between child self-report and parent-proxy CFQ-R scores was observed across the majority of domains and visits. CONCLUSION: HRQOL correlated poorly with lung function and structure in early school-aged children with CF, hence clinical trials should consider these outcomes independently when determining study end-points.
Assuntos
Fibrose Cística , Qualidade de Vida , Austrália/epidemiologia , Criança , Nível de Saúde , Humanos , Pulmão/diagnóstico por imagem , Índice de Gravidade de DoençaRESUMO
BACKGROUND: For Australians living with cystic fibrosis (CF), increased longevity means greater consideration needs to be given to long-term endocrine sequelae such as CF-related bone disease. Deficits in bone mass accrual are most likely to occur during childhood and adolescence. Current guidelines in Australia suggest repeat dual-energy X-ray absorptiometry (DXA) scans every 2 years. This study aims to stratify clinical factors that determine future bone health in the Australian CF population and use this to guide a more streamlined approach to bone health screening. METHODS: This study was a retrospective audit of all patients diagnosed with CF who were treated at the Royal Children's Hospital Melbourne, Australia from 2000 to 2016 (n = 453). Two hundred and two patients had a DXA scan in the study period (191 with height-adjusted data) and 111 patients had more than one scan (108 with height-adjusted data). An investigation into the associations between bone mineral density (BMD) Z score and potential risk factors was conducted using DXA and historical data. RESULTS: The main predictor of future BMD was the previous BMD Z score (p < .001). Other factors found to be determinants of BMD included nutritional status, lung function (FEV1 ), age, history of previous fracture, oral corticosteroid use, and the number of hospital admissions. However, after adjusting for previous BMD, evidence of an association remained only with nutritional status, FEV1 , and number of hospital admissions. CONCLUSION: Second yearly scans may be unnecessary in children with an adequate DXA score on the initial scan who remain clinically stable. However, clinical deterioration in those whose BMD was previously normal, may require closer monitoring of bone health. We propose a guideline for the frequency of DXA monitoring in relation to clinical risk factors.
Assuntos
Densidade Óssea , Fibrose Cística , Absorciometria de Fóton , Adolescente , Austrália/epidemiologia , Criança , Fibrose Cística/complicações , Fibrose Cística/diagnóstico por imagem , Fibrose Cística/epidemiologia , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: The impact of early cystic fibrosis (CF) on health-related quality-of-life (HRQOL) in preschool children is poorly characterised, and data on relationships between HRQOL and health outcomes in young children with CF are limited. We aimed to characterise and compare parent-proxy and child-reported HRQOL and evaluate relationships with clinical outcomes at age 5-years. METHODS: Subjects were participating in the multi-centre Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial investigating BAL-directed versus standard CF therapy. Children aged 5-years and their parents rated HRQOL using the Pediatric Quality of Life Inventory (PedsQL™) and Cystic Fibrosis Questionnaire-Revised (CFQ-R) questionnaires. RESULTS: PedsQL and CFQ-R questionnaires were completed by 141 primary caregivers and 135 and 130 children, respectively. There were no differences in HRQOL between children randomised to BAL-directed versus standard CF therapy. Children with CF rated worse HRQOL than healthy children and there was poor parent-child concordance across HRQOL domains. Nutritional status, CF-CT scan score, forced expiratory volume in 1-second (FEV1), and pulmonary exacerbations correlated with HRQOL at age 5-years. FEV1 z-scores positively correlated with parent-proxy HRQOL in CFQ-R Respiratory (p = 0.018), Physical (<0.001), Emotional (p = 0.007) subscales and PedsQL Total-score (p = 0.021), Physical (p = 0.019) domains. Pulmonary exacerbation rates were inversely associated with parent-proxy CFQ-R Respiratory (p = 0.004), Physical (p = 0.022), PedsQL Total (p = 0.009) and Physical (p = 0.009) scores. CONCLUSION: Parent-reported HRQOL is a meaningful clinical endpoint to evaluate interventions in young children. Parent and child HRQOL reports provide different, complementary information. A preschool version of the CFQ-R is needed to assess relationships between HRQOL and clinical outcomes in young children.
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Fibrose Cística/psicologia , Gerenciamento Clínico , Nível de Saúde , Pais/psicologia , Qualidade de Vida , Pré-Escolar , Fibrose Cística/fisiopatologia , Fibrose Cística/terapia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Estado Nutricional , Psicologia da Criança/métodos , Testes de Função Respiratória/estatística & dados numéricos , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB).Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study.99 out of 157 ACFBAL children (mean±sd age 13±1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4-22; p≤ 0.001), bronchoalveolar lavage (BAL) log2 interleukin (IL)-8 (OR 1.2, 95% CI 1.05-1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24-1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2 IL-8 (coefficient 1.3, 95% CI 0.57-2.1; p<0.001) at age 5 years.The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.
Assuntos
Fibrose Cística , Adolescente , Austrália , Criança , Pré-Escolar , Progressão da Doença , Seguimentos , Humanos , Pulmão/diagnóstico por imagem , Nova ZelândiaRESUMO
BACKGROUND: Both infection and inflammation are critical to the progression of cystic fibrosis (CF) lung disease. Potential anatomical differences in lower airway infection, inflammation and bronchiectasis in young children with CF raise questions regarding the pathogenesis of early structural lung disease. METHODS: A longitudinal multi-centre birth cohort study of infants newly diagnosed with CF was conducted. Paired bronchoalveolar lavage (BAL) samples were obtained from the right middle lobe (RML) and lingula bronchi. Chest computed tomography (CT) was performed biennially and analysed using the modified CF-CT scoring system. RESULTS: One hundred and twenty-four children (0.11 - 7.0 years) contributed 527 BAL samples and underwent 388 CT chest scans. Pro-inflammatory microbes were detected in 279 BAL samples (53%), either in both lingula and RML samples (69%), in the lingula alone (24%), or in the RML alone in only 7% of samples. Overall, the prevalence of structural lung disease was greater in the setting of pro-inflammatory microbes. Although infection was less commonly isolated in the right lung, bronchiectasis was more commonly detected in the right lung compared with the left. No anatomical differences in the presence of air trapping were detected. CONCLUSION: Overall, the detection of pro-inflammatory microbes in the lower airways was associated with increased risk of both air trapping and bronchiectasis. However, the apparent discordance between commonest sites of isolation of pro-inflammatory microbes and the anatomical site of early bronchiectasis warrants further exploration.
Assuntos
Bronquiectasia/microbiologia , Fibrose Cística/fisiopatologia , Infecções Respiratórias/complicações , Lavagem Broncoalveolar , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Inflamação/microbiologia , Estudos Longitudinais , Masculino , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Serum Glycoprotein A (GlycA) levels are increased in a variety of inflammatory disease states. However, GlycA has not been previously evaluated in children with cystic fibrosis (CF). We assessed the relationship between GlycA and pulmonary infection, inflammation, bronchial wall thickening (BWT) and bronchiectasis in young children with CF. METHODS: From 95 patients, we obtained 311 paired serum and bronchoalveolar lavage (BAL) samples at multiple timepoints, with concurrent chest computed tomography on 168 occasions. Quantitative GlycA was determined using high-throughput nuclear magnetic resonance metabolomic testing. Participants were considered to be infected if ≥1 significant proinflammatory organism was isolated from their BAL. The presence of free neutrophil elastase (NE) above the limit of detection was considered evidence of inflammation. The relationships between GlycA levels and infection state, inflammation, and bronchiectasis were examined using a generalized estimating equation approach. RESULTS: There was a positive relationship between GlycA (mean 1.01 mmol/L, range 0.68-1.92 mmol/L) and being infected with one or more proinflammatory organisms, even after adjusting for age and gender (odds ratio [OR], 1.2 per 0.1 mmol/L, 95% confidence interval [CI], 1.02, 1.4, P = .03). There was also a positive relationship between GlycA and NE (unadjusted OR, 1.2 95% CI, 1.01, 1.4, P = .04), not significant after adjustment. GlycA concentration was associated with BWT but not bronchiectasis. CONCLUSIONS: Although GlycA levels were higher on average in those who had an infection or neutrophilic inflammation, there was also considerable variability, limiting the clinical utility of this biomarker alone in determining early disease status in CF.
Assuntos
Fibrose Cística/sangue , Glicoproteínas/sangue , Biomarcadores/sangue , Bronquiectasia/sangue , Lavagem Broncoalveolar , Pré-Escolar , Feminino , Humanos , Lactente , Inflamação/sangue , Elastase de Leucócito/sangue , Masculino , Infecções Respiratórias/complicaçõesRESUMO
OBJECTIVES: To determine the association between residence and climate with risk of Pseudomonas aeruginosa (Pa) and other respiratory outcomes. METHODS: We performed regular bronchoalveolar lavage and upper airway cultures in young children with CF to identify Pa infection. Children were classified for residence as regional or metropolitan. Bronchiectasis was detected on periodic chest computed tomography scans. Multilocus sequence typing determined Pa genotype. Lung function was assessed using Multiple Breath Washout. RESULTS: Of infants diagnosed with CF between 2006 and 2017, 129 were included in the study. Seven patients moved between metropolitan and regional Victoria and were excluded from analysis. Of the remaining 122 subjects, seventy-four (61%) children resided in metropolitan areas and over half (54%) were male. There were 83â¯Pa episodes in the 122 children who lived consistently in a geographical location. The incidence rate was 0.15 episodes per person-years. We found weak evidence of a 15% increase in the rate of Pa episodes with increasing average annual maximum temperature (95%CI (0.98, 1.36); pâ¯=â¯.086), while the rate of Pa acquision decreased with average annual 3â¯pm humidity (IRRâ¯=â¯0.96; 95%CI(0.92, 1.0008); pâ¯=â¯.054). The rate of Pa episodes was 2.1 times higher in regional participants (95%CI (1.4, 3.1); pâ¯=â¯.001) and risk of second episode was more than five times greater (HR 5.7; 95%CI 1.9, 17); pâ¯=â¯.002). No difference between regions in lung clearance index and presence of bronchiectasis was detected. CONCLUSION: Regional residence is associated with risk of acquiring recurrent infection with Pseudomonas aeruginosa in young children with CF.
Assuntos
Clima , Fibrose Cística , Infecções por Pseudomonas , Pseudomonas aeruginosa/isolamento & purificação , Características de Residência/estatística & dados numéricos , Medição de Risco/métodos , Antibacterianos/uso terapêutico , Austrália/epidemiologia , Bronquiectasia/diagnóstico , Bronquiectasia/etiologia , Lavagem Broncoalveolar/métodos , Pré-Escolar , Fibrose Cística/epidemiologia , Fibrose Cística/fisiopatologia , Fibrose Cística/terapia , Feminino , Humanos , Lactente , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Masculino , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/fisiopatologia , Infecções por Pseudomonas/terapia , Recidiva , Testes de Função Respiratória/métodos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND/AIM: International criteria currently suggest orchidopexy at 6-12months for congenital undescended testis (UDT). Some children require repeat orchidopexy for recurrent UDT. This study aimed to assess practice in Australia over a 20-year period. METHODS: We examined 20years of Australian orchidopexy data (1995-2014) from the Department of Human Services to explore the national revision orchidopexy rates over time. RESULTS: The total number of orchidopexy revisions was 890 over 20years compared with 25,984 primary operations. More than 50% of all primary and revision orchidopexies in 0-14year-old boys were performed in major population centers of NSW and Victoria (which hold 52% male population of same age), with a small number of revisions on 15-24year-old males. The incidence of revision orchidopexy significantly decreased over the 20-year period in boys ages 0-14years old, from 276 operations between 1995 and 1999 decreasing to 165 operations between 2010 and 2014 (-53%), compared to a population increase of +15% (p<0.05). CONCLUSION: These data demonstrate a decrease in revision orchidopexy since 1995, which may be related to change in referral practice with more children undergoing orchidopexy (primary and revision) by pediatric surgeons over the 20-year period. LEVEL OF EVIDENCE: Level IV. TYPE OF STUDY: Therapeutic Case Series with no Comparison Group.
Assuntos
Competência Clínica , Criptorquidismo/diagnóstico , Criptorquidismo/terapia , Orquidopexia/normas , Austrália , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Orquidopexia/efeitos adversos , Projetos de Pesquisa , Testículo/cirurgiaRESUMO
BACKGROUND: We describe Pseudomonas aeruginosa acquisitions in children with cystic fibrosis (CF) aged ≤5-years, eradication treatment efficacy, and genotypic relationships between upper and lower airway isolates and strains from non-CF sources. METHODS: Of 168 CF children aged ≤5-years in a bronchoalveolar lavage (BAL)-directed therapy trial, 155 had detailed microbiological results. Overall, 201/271 (74%) P. aeruginosa isolates from BAL and oropharyngeal cultures were available for genotyping, including those collected before and after eradication therapy. RESULTS: Eighty-two (53%) subjects acquired P. aeruginosa, of which most were unique strains. Initial eradication success rate was 90%, but 36 (44%) reacquired P. aeruginosa, with genotypic substitutions more common in BAL (12/14) than oropharyngeal (3/11) cultures. Moreover, oropharyngeal cultures did not predict BAL genotypes reliably. CONCLUSIONS: CF children acquire environmental P. aeruginosa strains frequently. However, discordance between BAL and oropharyngeal strains raises questions over upper airway reservoirs and how to best determine eradication in non-expectorating children.
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Antibacterianos/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Fibrose Cística/microbiologia , DNA Bacteriano/genética , Orofaringe/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Pré-Escolar , Fibrose Cística/complicações , Feminino , Seguimentos , Genótipo , Humanos , Lactente , Masculino , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/isolamento & purificação , Estudos RetrospectivosRESUMO
OBJECTIVES: To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis (CF), rather than standard therapy, was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions. STUDY DESIGN: Costs were assessed in a randomized controlled trial conducted in Australia and New Zealand on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or standard therapy until they reached 5 years of age. A health care funder perspective was adopted. Resource use measurement was based on standardized data collection forms administered for patients across all sites. Unit costs were obtained primarily from government schedules. RESULTS: Mean costs per child during the study period were Australian dollars (AUD)92â860 in BAL-directed therapy group and AUD90â958 in standard therapy group (mean difference AUD1902, 95% CI AUD-27â782 to 31â586, P = .90). Mean hospital costs per child during the study period were AUD57â302 in the BAL-directed therapy group and AUD66â590 in the standard therapy group (mean difference AUD-9288; 95% CI AUD-35â252 to 16â676, P = .48). CONCLUSIONS: BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a standard protocol based upon clinical features and oropharyngeal culture results alone. Following on our previous findings that BAL-directed treatment offers no clinical advantage over standard therapy at age 5 years, flexible bronchoscopy with BAL cannot be recommended for the routine management of preschool children with CF on the basis of overall cost savings.
Assuntos
Lavagem Broncoalveolar/economia , Fibrose Cística/economia , Fibrose Cística/terapia , Pré-Escolar , Custos e Análise de Custo , Humanos , Lactente , Admissão do Paciente/economia , Admissão do Paciente/estatística & dados numéricosRESUMO
BACKGROUND: In 1964, The Melbourne Asthma Study was established to describe the spectrum and natural history of childhood asthma. OBJECTIVE: To describe the clinical and lung function outcome of childhood asthma to the age of 50 years. METHOD: Subjects were invited to complete an interviewer-administered questionnaire, skin prick testing, and measurement of lung function from the age of 7 years to the age of 50 years at 7-year intervals. RESULTS: Of 458 survivors (from the original 484 subjects at recruitment), 346 subjects (76%) participated, of whom, 197 completed lung function measurement. Asthma remission at the age of 50 years was 64% in those with wheezy bronchitis, 47% for those with persistent asthma, and 15% for those with severe asthma in childhood. Multivariable analysis identified severe asthma in childhood (odds ratio [OR] 11.9 [95% CI, 3.4-41.8]), female sex (OR 2.0 [95% CI, 1.1-3.6]), and childhood hay fever (OR 2.0 [95% CI, 1.0-4.0]) as risk factors for "current asthma" at age 50 years. There was no evidence of a difference in the rate of decline in FEV1 (mL/y, 95% CI) between the severe asthma group (15 mL/y [95% CI, 9-22 mL/y]) and all the other recruitment groups: control (16 mL/y [95% CI, 12-20 mL/y]), mild wheezy bronchitis (14 mL/y [95% CI, 8-19 mL/y]), wheezy bronchitis (16 mL/y [95% CI, 11-20 mL/y]), and persistent asthma (19 mL/y [95% CI, 13-24 mL/y]). CONCLUSION: The clinical and lung function outcome in adult life is strongly determined by asthma severity in childhood. The reduced lung function seen in adults is established in childhood and does not appear to decline more rapidly in adult years despite continuing symptoms.
Assuntos
Asma/epidemiologia , Adolescente , Adulto , Asma/fisiopatologia , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Testes de Função Respiratória , Testes Cutâneos , Fumar , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Use of inhaled tobramycin therapy for treatment of Pseudomonas aeruginosa infections in young children with cystic fibrosis (CF) is increasing. Safety data for pre-school children are sparse. METHODS: The aim of this study was to assess the safety of tobramycin solution for inhalation (TOBI®-TSI) administered twice daily for 2 months/course concurrently to intravenous (IV) tobramycin during P. aeruginosa eradication therapy in children (0-5 years). Audiological assessment and estimation of glomerular filtration rate (GFR) was measured prior to any exposure and end of the study. RESULTS: Data were available from 142 patients who were either never exposed to aminoglycosides (n=39), exposed to IV aminoglycosides only (n=36) or exposed to IV+TSI (n=67). Median exposure to TSI was 113 days [59, 119]. Comparison of effects on audiometry results and GFR, showed no detectable difference between the groups. CONCLUSIONS: Use of TSI and IV tobramycin in pre-school children with CF was not associated with detectable renal toxicity or ototoxicity.
Assuntos
Fibrose Cística/complicações , Infecções por Pseudomonas/tratamento farmacológico , Tobramicina/administração & dosagem , Administração por Inalação , Administração Intravenosa , Antibacterianos/administração & dosagem , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with growth, lung structure and function at age 5 years. METHODS: Respiratory exacerbations were recorded prospectively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years, when all participants underwent clinical assessment, chest CT scans and spirometry. RESULTS: 168 children (88 boys) experienced 2080 exacerbations, at an average rate of 3.66 exacerbations per person-year; 80.1% were community managed and 19.9% required hospital admission. There was an average increase in exacerbation rate of 9% (95% CI 4% to 14%; p<0.001) per year of age. Exacerbation rate differed by site (p<0.001) and was 26% lower (95% CI 12% to 38%) in children receiving 12 months of prophylactic antibiotics. The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores. Ever having a hospital-managed exacerbation was associated with bronchiectasis (OR 2.67, 95% CI 1.13 to 6.31) in chest CT scans, and lower weight z scores at 5 years of age (coefficient -0.39, 95% CI -0.74 to -0.05). CONCLUSIONS: Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Lavagem Broncoalveolar/métodos , Fibrose Cística/complicações , Hospitalização/tendências , Pneumopatias/epidemiologia , Pulmão/fisiopatologia , Pré-Escolar , Fibrose Cística/diagnóstico , Fibrose Cística/terapia , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Incidência , Lactente , Recém-Nascido , Pulmão/diagnóstico por imagem , Pneumopatias/etiologia , Pneumopatias/prevenção & controle , Masculino , Nova Zelândia/epidemiologia , Prognóstico , Estudos Prospectivos , Radiografia Torácica , Espirometria , Tomografia Computadorizada por Raios XRESUMO
CONTEXT: Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality. Despite wide use of oropharyngeal cultures to identify pulmonary infection, concerns remain over their diagnostic accuracy. While bronchoalveolar lavage (BAL) is an alternative diagnostic tool, evidence for its clinical benefit is lacking. OBJECTIVE: To determine if BAL-directed therapy for pulmonary exacerbations during the first 5 years of life provides better outcomes than current standard practice relying on clinical features and oropharyngeal cultures. DESIGN, SETTING, AND PARTICIPANTS: The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) randomized controlled trial, recruiting infants diagnosed with cystic fibrosis through newborn screening programs in 8 Australasian cystic fibrosis centers. Recruitment occurred between June 1, 1999, and April 30, 2005, with the study ending on December 31, 2009. INTERVENTIONS: BAL-directed (n = 84) or standard (n = 86) therapy until age 5 years. The BAL-directed therapy group underwent BAL before age 6 months when well, when hospitalized for pulmonary exacerbations, if Pseudomonas aeruginosa was detected in oropharyngeal specimens, and after P. aeruginosa eradication therapy. Treatment was prescribed according to BAL or oropharyngeal culture results. MAIN OUTCOME MEASURES: Primary outcomes at age 5 years were prevalence of P. aeruginosa on BAL cultures and total cystic fibrosis computed tomography (CF-CT) score (as a percentage of the maximum score) on high-resolution chest CT scan. RESULTS: Of 267 infants diagnosed with cystic fibrosis following newborn screening, 170 were enrolled and randomized, and 157 completed the study. At age 5 years, 8 of 79 children (10%) in the BAL-directed therapy group and 9 of 76 (12%) in the standard therapy group had P. aeruginosa in final BAL cultures (risk difference, -1.7% [95% confidence interval, -11.6% to 8.1%]; P = .73). Mean total CF-CT scores for the BAL-directed therapy and standard therapy groups were 3.0% and 2.8%, respectively (mean difference, 0.19% [95% confidence interval, -0.94% to 1.33%]; P = .74). CONCLUSION: Among infants diagnosed with cystic fibrosis, BAL-directed therapy did not result in a lower prevalence of P. aeruginosa infection or lower total CF-CT score when compared with standard therapy at age 5 years. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12605000665639.
Assuntos
Antibacterianos/uso terapêutico , Fibrose Cística/complicações , Fibrose Cística/patologia , Lesão Pulmonar/etiologia , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Austrália/epidemiologia , Lavagem Broncoalveolar , Pré-Escolar , Fibrose Cística/diagnóstico por imagem , Hospitalização , Humanos , Lactente , Recém-Nascido , Pulmão/fisiopatologia , Lesão Pulmonar/prevenção & controle , Nova Zelândia/epidemiologia , Prevalência , Infecções por Pseudomonas/epidemiologia , Testes de Função Respiratória , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Exercise echocardiography reveals abnormalities in asymptomatic childhood cancer survivors who previously have been treated with anthracyclines. We determined the added value of monitoring childhood cancer survivors with exercise echocardiography compared to monitoring with resting echocardiography alone to predict anthracycline-induced cardiotoxicity. Secondary aims were to evaluate change in resting cardiac function over 10 years and to determine risk factors for late cardiotoxicity. PROCEDURE: We invited a cohort of 110 originally asymptomatic anthracycline-treated childhood cancer survivors, who had undergone cardiac tests including exercise echocardiography 10.5 years earlier, for new cardiac evaluation. Each subject underwent a resting echocardiogram at both evaluations. At first evaluation a repeat echocardiogram was performed following peak exercise. Resting echocardiographic parameters were converted to z-character. RESULTS: Ninety-two of 110 survivors (mean anthracycline dose 307 mg/m(2), mean follow-up time from start of treatment 8.2 years at first and 18.8 years at second evaluation) were evaluated prospectively. Mean resting fractional shortening z-character (RFSz) decreased from -0.18 to -0.93. Higher cumulative anthracycline dose was a risk factor for a lower RFSz at late follow-up (P = 0.0002). Adding exercise fractional shortening (XFS) to a model containing RFSz did not improve prediction of abnormal RFSz at late follow-up. CONCLUSIONS: Monitoring with exercise echocardiography has no added value to monitoring with resting echocardiography alone in predicting late anthracycline-induced cardiotoxicity in childhood cancer survivors. RFSz deteriorates over time, even in originally asymptomatic patients. Previous treatment with higher cumulative anthracycline dose is the main risk factor for a lower RFSz at late follow-up.
Assuntos
Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Ecocardiografia/métodos , Cardiopatias/diagnóstico , Neoplasias/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Exercício Físico , Feminino , Seguimentos , Cardiopatias/induzido quimicamente , Humanos , Lactente , Masculino , Curva ROC , SobreviventesRESUMO
OBJECTIVE: Our aim was to determine the safety of BAL in young children <6 years with CF. METHODS: As part of a multi-center study of BAL-directed therapy, children with CF < 6 years had one or more BALs between September 1999 and December 2005. Adverse events were recorded intraoperatively and for 24 hr thereafter. Clinical characteristics before BAL, findings at bronchoscopy and BAL results were assessed as risk factors for adverse events. RESULTS: 333 BALs were conducted in 107 (56 males) children, median age 23.5 (range 1.6-67.5) months, including 170 (51%) for pulmonary exacerbation. 29 BALs (8.7%) were followed by fever >or=38.5 degrees C and 10 (3%) had clinically significant episodes (five intraoperative hemoglobin desaturations to <90% requiring intervention, one tachyarrhythmia, two needing post-operative supplemental oxygen, one hospitalization for stridor). Two contaminated bronchoscopes were detected. 180 minor adverse events were recorded in 174 (52%) BAL procedures (137 altered cough, 41 fever <38.5 degrees C). Low percentage BAL return (P = 0.002) and focal bronchitis (P = 0.02) were associated with clinically significant deterioration. Multivariable analysis identified Streptococcus pneumoniae (OR 22.3; 95% confidence interval (CI); 6.9,72), Pseudomonas aeruginosa (OR 2.4; 95% CI 1.0, 5.8), respiratory signs (OR 5.0; 95% CI 1.7, 14.6) and focal bronchitis (OR 5.9; 95% CI 1.2, 29.8) as independent risk factors for post-bronchoscopy fever >or=38.5 degrees C. CONCLUSIONS: Adverse events are common with BAL in young CF children, but are usually transient and well tolerated. Parents should be counseled that signs of a pre-existing lower respiratory infection are associated with increased risk of post-BAL fever.
Assuntos
Lavagem Broncoalveolar/efeitos adversos , Fibrose Cística/terapia , Broncoscopia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Fatores de RiscoRESUMO
BACKGROUND: Low and moderate dose anthracycline therapy used in current treatment protocols, may be associated with subclinical abnormalities of cardiac function and late presentation with congestive heart failure. Exercise echocardiography is a useful and non-invasive means of uncovering latent cardiac dysfunction in other settings. The purpose of this study is to determine whether exercise echocardiography has the potential to detect subclinical abnormalities of cardiac function in children treated with anthracyclines. PROCEDURE: One hundred ten children previously treated with anthracycline, in remission and off treatment for >12 months were assessed, together with 31 control subjects. Each subject had a resting ECG and echocardiogram performed, and following exercise on a treadmill according to the Bruce protocol, a repeat echocardiogram was performed. RESULTS: Cumulative anthracycline dose was the only patient variable related to any of the outcome measures. Resting fractional shortening was normal in the majority of treated patients but was inversely related to cumulative anthracycline dose (rate of decline 1.2%/100 mg/m(2)). Following peak exercise, the inverse relationship between fractional shortening and anthracycline dose was more pronounced (rate 2.7%/100 mg/m(2)). CONCLUSIONS: Higher anthracycline doses are associated with a greater difference in peak fractional shortening between treated subjects and controls. Exercise echocardiography is a simple, relatively inexpensive tool that may enhance the detection of latent cardiac dysfunction after anthracycline administration during childhood.