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Thymic stromal lymphopoietin (TSLP) is a primarily epithelial-derived cytokine that drives type 2 allergic immune responses. Early life viral respiratory infections elicit high TSLP production, which leads to the development of type 2 inflammation and airway hyperreactivity. The goal of this study was to examine in vivo and in vitro the human airway epithelial responses leading to high TSLP production during viral respiratory infections in early infancy. A total of 129 infants (<1-24 m, median age 10 m) with severe viral respiratory infections were enrolled for in vivo (n = 113), and in vitro studies (n = 16). Infants were classified as 'high TSLP' or 'low TSLP' for values above or below the 50th percentile. High versus low TSLP groups were compared in terms of type I-III IFN responses and production of chemokines promoting antiviral (CXCL10), neutrophilic (CXCL1, CXCL5, CXCL8), and type 2 responses (CCL11, CCL17, CCL22). Human infant airway epithelial cell (AEC) cultures were used to define the transcriptomic (RNAseq) profile leading to high versus low TSLP responses in vitro in the absence (baseline) or presence (stimulated) of a viral mimic (poly I:C). Infants in the high TSLP group had greater in vivo type III IFN airway production (median type III IFN in high TSLP 183.2 pg/mL vs. 63.4 pg/mL in low TSLP group, p = 0.007) and increased in vitro type I-III IFN AEC responses after stimulation with a viral mimic (poly I:C). At baseline, our RNAseq data showed that infants in the high TSLP group had significant upregulation of IFN signature genes (e.g., IFIT2, IFI6, MX1) and pro-inflammatory chemokine genes before stimulation. Infants in the high TSLP group also showed a baseline AEC pro-inflammatory state characterized by increased production of all the chemokines assayed (e.g., CXCL10, CXCL8). High TSLP responses in the human infant airways are associated with pre-activated airway epithelial IFN antiviral immunity and increased baseline AEC production of pro-inflammatory chemokines. These findings present a new paradigm underlying the production of TSLP in the human infant airway epithelium following early life viral exposure and shed light on the long-term impact of viral respiratory illnesses during early infancy and beyond childhood.
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OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) and/or inhaled anesthetics (IAs) are considered in the management of asthma when refractory to conventional therapy. We aimed to compare the outcomes of these two modalities in asthma PICU care and determine associated survival to hospital discharge among patients in a United States database. DESIGN: Retrospective analysis using the Virtual Pediatric Systems (VPS, LLC) database. SETTING: PICUs participating in the VPS database. PATIENTS: Patients less than 18 years old with diagnosis of asthma treated with IA and/or ECMO from January 2010 to December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 221 patients were included; 149 (67%) received ECMO, 62 (28%) received IA, and 10 (5%) received both interventions. We failed to identify any difference between the ECMO and IA groups in demographics, Pediatric Index of Mortality 2 percentage, Pediatric Risk of Mortality 3 score, Pediatric Logistic Organ Dysfunction score, or pre-intervention pH and Pa co2 levels. Use of ECMO versus IA was associated with lower pre-intervention Pa o2 (60 torr [7.99 kPa] vs 78 torr [10.39 kPa]; p < 0.001) and higher utilization of high-frequency oscillatory ventilation. We failed to identify an association between type of intervention (IA vs ECMO) and greater odds of survival (57/62 [92%] vs 128/149 [86%]; odds ratio [OR], 1.87; 95% CI, 0.67-5.21; p = 0.23). However, these data do not exclude the possibility that IA use is associated with more than five-fold greater odds of survival. ECMO use was associated with longer duration of intervention (5 vs 1.3 d; p < 0.001) and PICU length of stay (LOS) (13 vs 7 d; p < 0.001). As expected, ECMO versus IA was also associated with greater odds of undergoing bronchoscopy (34% vs 11%; OR, 3.7; 95% CI, 1.5-9.4; p = 0.004). CONCLUSIONS: In the VPS database of asthma management cases, we failed to identify an association between ECMO versus IA use and survival to hospital discharge. However, ECMO was associated with longer duration of intervention and PICU LOS.
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Asma , Oxigenação por Membrana Extracorpórea , Criança , Humanos , Adolescente , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Tempo , Asma/terapiaRESUMO
BACKGROUND: This study compared sleep duration, screen exposure and sleep quality in school-aged children before COVID-19 to that during school closures and again when schools re-opened in fall 2020. METHODS: Cross-sectional anonymous, online survey of parents of children 5-13 years old. Questions elicited information about sleep timing and quality, screen time, and schooling at three distinct periods: before the pandemic, when schools first closed and then re-opened in the fall. RESULTS: Respondents described 101 children who were an average of 8.5 years old and 51% male. In lockdown, children slept 25 min more (95%CI 00:13-00:38) due to later wake times (75 min, 95% CI 0:57-1:34) with later bedtimes (29 min, 95%CI 0:00-0:58). When schools re-opened, sleep duration returned to pre-pandemic levels, but sleep onset and offset times remained later. Despite more sleep, sleep quality and habits (e.g. bedtime refusal) worsened during lockdown and did not normalize in fall 2020. During lockdown, screen time increased in 65% of all children, and 96% of those in private schools. When schools reopened, 78% of children in hybrid/virtual learning had more than 4 h of screen exposure daily. Less screen time was associated with twofold higher odds of better sleep (OR 2.66, 95%CI 1.15-6.14). CONCLUSIONS: Although school-aged children had more total sleep when schools were closed, sleep quality and habits worsened. Upon return to school, sleep times and quality did not normalize and were linked to screen time.
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COVID-19 , Pandemias , Humanos , Masculino , Criança , Pré-Escolar , Adolescente , Feminino , Tempo de Tela , Estudos Transversais , Controle de Doenças Transmissíveis , Sono , Inquéritos e Questionários , PaisRESUMO
OBJECTIVE: Tracheobronchomalacia (TBM) is common in neonates with bronchopulmonary dysplasia (BPD) and is associated with higher morbidity. This study evaluates the value of a CT protocol to assess the degree of TBM and gauge the adequacy of prescribed PEEP. STUDY DESIGN: Four infants with severe BPD on invasive mechanical ventilation underwent a chest CT protocol, including limited reduced-dose expiratory scans with varying PEEP levels. RESULTS: Baseline PEEP was adjusted in all subjects after performing the Dynamic PEEP CT. In two infants, the PEEP was increased due to significant TBM and in the other two without signs of TBM PEEP was decreased. The clinical course improved in all patients after adjusting PEEP. CONCLUSION: A "Dynamic PEEP" study may be reliable and non-invasive imaging modality for the evaluation of adequate ventilator settings in infants with severe BPD who are not optimal candidates for bronchoscopy.
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Displasia Broncopulmonar , Traqueobroncomalácia , Displasia Broncopulmonar/diagnóstico por imagem , Displasia Broncopulmonar/terapia , Broncoscopia , Criança , Humanos , Lactente , Recém-Nascido , Respiração Artificial , Traqueobroncomalácia/diagnóstico por imagem , Traqueobroncomalácia/terapia , Ventiladores MecânicosRESUMO
INTRODUCTION: IFN lambda (type III-IFN-λ1) is a molecule primarily produced by epithelial cells that provides an important first-line defence against viral respiratory infections and has been linked to the pathogenesis of viral-induced wheezing in early life. The goal of this study was to better understand the regulation of innate IFN-lambda responses in vitro in primary human infant airway epithelial cells (AECs) and in vivo using nasal aspirates during viral respiratory infections. METHODS: IFN-lambda protein levels were quantified: (a) in human infant AECs exposed to (poly(I:C) dsRNA) under different experimental conditions (n = 8 donors); and (b) in nasal aspirates of young children (≤3 years) hospitalized with viral respiratory infection (n = 138) and in uninfected controls (n = 74). In vivo IFN-lambda airway levels during viral infections were correlated with individual characteristics and respiratory disease parameters. RESULTS: Our in vitro experiments showed that the poly(I:C)-induced innate production of IFN lambda in human infant AECs is regulated by (a) p38-MAPK/NF-kB dependent mechanism; and (b) exposure to pro-inflammatory signals such as IL1ß. Our in vivo studies demonstrated that (a) infants (<18 months) had higher virus-induced IFN-lambda airway secretion; (b) subjects with RSV infection showed the highest IFN-lambda airway levels; and (c) individuals with the highest virus-induced IFN-lambda levels (>90th percentile) had higher viral loads and were more likely to have respiratory sick visits within 12 months of discharge (OR = 5.8). CONCLUSION: IFN-lambda responses to dsRNA in the human infant airway epithelium are regulated by p38-MAPK and NF-kB signalling. High in vivo IFN-lambda production is influenced by virus type and associated with recurrent respiratory sick visits in young children.
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Células Epiteliais/imunologia , Imunidade Inata , Interferons/imunologia , Poli I-C/imunologia , RNA de Cadeia Dupla/imunologia , Sistema Respiratório/imunologia , Infecções Respiratórias/imunologia , Viroses/imunologia , Estudos de Casos e Controles , Células Cultivadas , Pré-Escolar , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Lactente , Interferons/metabolismo , Masculino , NF-kappa B/metabolismo , Sistema Respiratório/metabolismo , Sistema Respiratório/virologia , Infecções Respiratórias/metabolismo , Infecções Respiratórias/virologia , Transdução de Sinais , Carga Viral , Viroses/metabolismo , Viroses/virologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
PURPOSE: Patients with neuromuscular disease (NMD) experience weakened cough due to progressive respiratory muscle weakness. Peak cough flow (PCF) measurements derived from adult populations are used to recommend initiation of assisted cough therapies. The objective of this study was to characterize PCF values among pediatric patients with NMD. METHODS: Retrospective chart review was performed for patients seen in the multidisciplinary pediatric muscular dystrophy clinic from 2010 to 2016. Clinical and demographic variables included age, gender, ambulation status, and PCF measurements. RESULTS: 366 patients with an established diagnosis of NMD (median age 11.8 years) were included in this study. 102 (27.8%) out of the 366 patients were affected by Duchenne muscular dystrophy (DMD), 42 (11.5%) by congenital muscular dystrophy (CMD), 42 (11.5%) by Charcot Marie Tooth disease (CMT) and 24 (6.5%) by Becker's muscular dystrophy (BMD). The mean PCF values in DMD (255.8 L/min) and CMD (249.1 L/min) were lower than CMT (321.5 L/min) with p-values of 0.007 and 0.02, respectively. The mean PCF of BMD (333.3 L/min) was higher than that of DMD and CMD but the difference was not statistically significant. PCFs were not statistically different between ambulatory and non-ambulatory status (263.0 L/min versus 290.8 L/min, p = 0.12). Children under 10 years of age had lower PCF relative to older subjects (179.5 L/min versus 300.9 L/min, p < 0.0001). CONCLUSION: Baseline PCF values in young children are below the adult-specific values suggested for starting assisted cough techniques. Further longitudinal trials are required to derive pediatric-specific reference values for PCF in patients with NMD.
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Tosse , Debilidade Muscular , Doenças Neuromusculares , Testes de Função Respiratória , Músculos Respiratórios/fisiopatologia , Criança , Tosse/diagnóstico , Tosse/fisiopatologia , Precisão da Medição Dimensional , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Debilidade Muscular/diagnóstico , Debilidade Muscular/etiologia , Doenças Neuromusculares/complicações , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/fisiopatologia , Pediatria/métodos , Pediatria/normas , Ventilação Pulmonar , Valores de Referência , Testes de Função Respiratória/métodos , Testes de Função Respiratória/normasRESUMO
BACKGROUND: To carry out a complete clinical, pathological, genetic and microbiological characterization of pediatric patients with molecular confirmed cystic fibrosis (CF) attending the Carlos Andrade Marín Hospital (HCAM) within the study period. METHODS: A cross-sectional analysis of the pediatric population with a confirmed diagnosis of CF disease who attended HCAM, one of the largest tertiary-level hospitals in Ecuador, between 2017 and 2018 was performed. All demographic, clinical and genetic variables were obtained from the electronic medical records (EMR) stored by the hospital. RESULTS: Forty seven patients with CF were included in the study. Gender distribution was similar between male (48.9%, n = 23) and female patients (51.1%, n = 24). The Tiffeneau-Pinelli index (FEV1/FVC) changed significantly after nine months post-diagnosis (85.55 ± 13.26; p < 0.05). The most common pathogenic genetic variants were F508del, found in 52.78% of the cohort (n = 19); H609R, found in 36.11% (n = 13); g.204099A > C, found in 14.1% (n = 7), followed by G85E and the N1303K with 11.11% (n = 3) each. CONCLUSIONS: To our best knowledge, this is the first study exploring the clinical, genetic and bacteriological profile of CF's patients in Ecuador. Within the cohort of patients, an important and unique genetic feature was characterized by the presence of the g.204099A > C and the c.206359C > A homozygous polymorphism as well as the presence of the H609R variant, a mutation only reported among Ecuadorians.
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Fibrose Cística , Criança , Estudos Transversais , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Fibrose Cística/microbiologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Equador/epidemiologia , Feminino , Hospitais Públicos , Humanos , Masculino , MutaçãoAssuntos
Citocinas/metabolismo , Mucosa Respiratória/metabolismo , Infecções por Vírus Respiratório Sincicial/metabolismo , Infecções Respiratórias/metabolismo , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Mucosa Respiratória/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/patogenicidade , Infecções Respiratórias/virologia , Linfopoietina do Estroma do TimoRESUMO
BACKGROUND: It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity. METHODS: Nasal airway secretions were collected from 140 children ≤ 3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFNγ, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay. RESULTS: Full-term children with HMPV and RSV infection had increased levels of nasal airway IFNγ, CCL5, and IL-10 along with an elevation in Th1 (IFNγ)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (< 32 wk gestation) did not exhibit increased Th1/Th2 ratios or elevated nasal airway secretion of IFNγ, CCL5, and IL-10 relative to uninfected controls. CONCLUSION: Our study is the first to demonstrate that premature infants have defective IFNγ, CCL5/RANTES, and IL-10 airway responses during HMPV infection and provides novel insights about the potential reason why HMPV causes severe respiratory disease in children with history of prematurity.
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Recém-Nascido Prematuro , Interferon gama/imunologia , Pulmão/imunologia , Metapneumovirus/imunologia , Infecções por Paramyxoviridae/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/imunologia , Quimiocina CCL5/imunologia , Quimiocina CCL5/metabolismo , Pré-Escolar , Estudos Transversais , DNA Viral/genética , Feminino , Idade Gestacional , Interações Hospedeiro-Patógeno , Humanos , Lactente , Interferon gama/metabolismo , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-4/imunologia , Interleucina-4/metabolismo , Pulmão/metabolismo , Pulmão/virologia , Masculino , Metapneumovirus/genética , Metapneumovirus/isolamento & purificação , Infecções por Paramyxoviridae/diagnóstico , Infecções por Paramyxoviridae/metabolismo , Infecções por Paramyxoviridae/virologia , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/metabolismo , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/genética , Vírus Sinciciais Respiratórios/isolamento & purificação , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/virologia , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/virologia , Células Th2/imunologia , Células Th2/metabolismo , Células Th2/virologia , Regulação para CimaRESUMO
BACKGROUND: Rhinovirus (RV) has been linked to the pathogenesis of asthma. Prematurity is a risk factor for severe RV infection in early life, but is unknown if RV elicits enhanced pro-asthmatic airway cytokine responses in premature infants. This study investigated whether young children born severely premature (<32 wks gestation) exhibit airway secretion of Th2 and Th17 cytokines during natural RV infections and whether RV-induced Th2-Th17 responses are linked to more respiratory morbidity in premature children during the first 2 yrs of life. METHODS: We measured Th2 and Th17 nasal airway cytokines in a retrospective cohort of young children aged 0-2 yrs with PCR-confirmed RV infection or non-detectable virus. Protein levels of IL-4, IL-13, TSLP, and IL-17 were determined with multiplex immunoassays. Demographic and clinical variables were obtained by electronic medical record (EMR) review. RESULTS: The study comprised 214 children born full term (n = 108), preterm (n = 44) or severely premature (n = 62). Natural RV infection in severely premature children was associated with elevated airway secretion of Th2 (IL-4 and IL-13) and Th17 (IL-17) cytokines, particularly in subjects with history of bronchopulmonary dysplasia. Severely premature children with high RV-induced airway IL-4 had recurrent respiratory hospitalizations (median 3.65 hosp/yr; IQR 2.8-4.8) and were more likely to have at least one pediatric intensive care unit admission during the first 2 yrs of life (OR 8.72; 95% CI 1.3-58.7; p = 0.02). CONCLUSIONS: Severely premature children have increased airway secretion of Th2 and Th17 cytokines during RV infections, which is associated with more respiratory morbidity in the first 2 yrs of life.
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Resfriado Comum/imunologia , Citocinas/imunologia , Lactente Extremamente Prematuro/imunologia , Sistema Respiratório/imunologia , Sistema Respiratório/virologia , Asma/imunologia , Asma/virologia , Displasia Broncopulmonar/imunologia , Displasia Broncopulmonar/virologia , Estudos de Coortes , Resfriado Comum/complicações , Citocinas/biossíntese , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Reação em Cadeia da Polimerase Multiplex , Estudos Retrospectivos , RhinovirusRESUMO
OBJECTIVES: Airway clearance therapy (ACT) is an important component of therapy for cystic fibrosis (CF) but is associated with significant treatment burden. Highly effective CFTR modulator therapy (HEMT) has improved pulmonary function for many people with CF (pwCF). We sought to understand changes in attitudes and practices about ACT in the post-HEMT era. STUDY DESIGN: Surveys of CF community members and CF care team members. METHODOLOGY: Separate surveys were created for the CF community and CF care providers to evaluate attitudes towards ACT and exercise in the post-HEMT era. We solicited answers from pwCF via the CF Foundation's Community Voice and from CF care providers via CF Foundation listservs. Surveys were available between July 20 and August 3, 2021. RESULTS: Surveys were completed by 153 community members (parents of children and pwCF) and 192 CF care providers. Belief that exercise can substitute partially for ACT was endorsed similarly by community members (59%) and providers (68%). After starting HEMT, 36% of parents of children and 51% of adults did fewer ACT treatments including 13% who stopped ACT. Adults reported altering their ACT regimen more than parents of children, though the sample size was limited. Half of providers had changed their ACT recommendations for those on HEMT. Fifty-three percent of respondents had discussed changing ACT with their care team (36% of parents, 58% of pwCF). CONCLUSIONS: Providers should be aware that ACT management changes may have been undertaken by pwCF who have pulmonary benefits of HEMT. Treatment burden should be considered in co-management decisions regarding ACT and exercise.
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Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Criança , Adulto , Humanos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/tratamento farmacológico , Transdução de SinaisRESUMO
BACKGROUND: Adherence to airway clearance therapy (ACT) in pediatric cystic fibrosis (CF) patients is reported to be below 50% and inability to sustain daily care is linked to poor health outcomes7,8,9. Through a collaboration between a CF care center and several schools, we hypothesized that ACT completed at school by pediatric CF patients will improve lung function while decreasing pulmonary exacerbations (PEx), days of antibiotics (abx) and hospitalizations. METHODS: This was a retrospective case-control study at a single CF care center consisting of 50 CF patients age < 18 at time when data was recorded (2012-2020). The case group used high-frequency chest wall oscillation or positive expiratory pressure devices at school for at least 1 year after self-reported or physician identified inadequate use at home. Lung function and measures of healthcare utilization were collected. RESULTS: In the case group (n = 14), paired t-tests showed that after initiation of ACT at school, there were significant reductions in PEx requiring IV or PO abx (P = 0.010), total days of abx (P = 0.032), and visits to the CF care center (P = 0.037). There was no change in these outcomes in the matched control group (n = 36). CONCLUSIONS: This is the first known study to highlight an initiative between a CF care center and schools which utilized airway clearance devices at school to ensure pediatric CF patients completed ACT. Through increased adherence, this relationship was associated with improved health outcomes. Use of alternative strategies may help patients with CF sustain adequate airway clearance.
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Fibrose Cística , Humanos , Criança , Estudos Retrospectivos , Estudos de Casos e Controles , Volume Expiratório Forçado , Instituições AcadêmicasRESUMO
Pediatric leukodystrophies are rare neurodegenerative diseases involving multiple systems. Each form has unique neurologic features but are characterized by encephalopathy with accompanying impairments evidenced in reflexes, muscle tone and movement control. Weakness of expiratory, inspiratory, and upper airway muscles may lead to impaired airway secretion clearance resulting in recurrent respiratory infections, dysphagia, sleep-disordered breathing, restrictive lung disease, and ultimately chronic respiratory insufficiency.
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Síndromes da Apneia do Sono , Humanos , CriançaRESUMO
BACKGROUND: Antimicrobial stewardship is a systematic effort to change prescribing attitudes that can provide benefit in the provision of care to persons with cystic fibrosis (CF). Our objective was to decrease the unwarranted use of broad-spectrum antibiotics and assess the impact of an empiric antibiotic algorithm using quality improvement methodology. METHODS: We assembled a multidisciplinary team with expertise in CF. We assessed baseline antibiotic use for treatment of pulmonary exacerbation (PEx) and developed an algorithm to guide empiric antibiotic therapy. We included persons with CF admitted to Children's National Hospital for treatment of PEx between January 2017 and March 2020. Our primary outcome measure was reducing unnecessary broad-spectrum antibiotic use, measured by use consistent with the empiric antibiotic algorithm. The primary intervention was the initiation of the algorithm. Secondary outcomes included documentation of justification for broad-spectrum antibiotic use and use of infectious disease (ID) consult. RESULTS: Data were collected from 56 persons with CF who had a total of 226 PEx events. The mean age at first PEx was 12 (SD 6.7) years; 55% were female, 80% were white, and 29% were Hispanic. After initiation of the algorithm, the proportion of PEx with antibiotic use consistent with the algorithm increased from 46.2% to 79.5%. Documentation of justification for broad-spectrum antibiotics increased from 56% to 85%. Use of ID consults increased from 17% to 54%. CONCLUSION: Antimicrobial stewardship initiatives are beneficial in standardizing care and fostering positive working relationships between CF pulmonologists, ID physicians, and pharmacists.
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Fibrose Cística , Algoritmos , Antibacterianos/uso terapêutico , Criança , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Feminino , Hospitalização , Humanos , Pulmão , Masculino , Adulto JovemRESUMO
OBJECTIVE: To assess the effect of Passy-Muir® Valve (PMV) tolerance on respiratory illness and respiratory related hospital admissions in tracheostomy-dependent children. METHODS: Retrospective cohort study of 262 patients who underwent tracheostomy placement between 2012 and 2018 at a tertiary free-standing children's hospital. Outcome measures studied were number of reported upper respiratory infections and respiratory related hospitalizations per year (RRH/year). RESULTS: About 135 (51.5%) tracheostomy-dependent children underwent PMV trials, and 106 (78.5%) of these children were able to tolerate PMV for at least 1 hour daily. When comparing children who tolerated PMV versus those who did not, the latter group had significantly higher rates of subglottic stenosis but no significant differences in RRH/year or average age. In those children who tolerated PMV and achieved routine use of PMV > 1 hour/day, an average of 1.14 RRH/year occurred prior to PMV tolerance, as compared with 0.57 RRH/year after PMV tolerance (P = .003). Multivariate analysis shows that in patients <2 years, there is a significant decrease in RRH/year after PMV tolerance is attained (1.53 vs 0.76, P = .001), independent of indication for tracheostomy. CONCLUSION: In tracheostomy-dependent children who tolerate PMV use routinely >1 hour/day there are decreased rates of respiratory related hospitalizations (RRH). Children <2 years of age have the most impact of RRH, with rates that are significantly lower with routine use of the PMV.
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Hospitalização/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Traqueostomia/instrumentação , Pré-Escolar , Estudos de Coortes , Transtornos de Deglutição/terapia , District of Columbia/epidemiologia , Feminino , Humanos , Masculino , Análise Multivariada , Fonação , Aspiração Respiratória/prevenção & controle , Estudos RetrospectivosRESUMO
Over the past decade, "omics" approaches have advanced our understanding of the molecular programming of the airways in humans. Several studies have identified potential molecular mechanisms that contribute to early life epigenetic reprogramming, including DNA methylation, histone modifications, microRNAs, and the homeostasis of the respiratory mucosa (epithelial function and microbiota). Current evidence supports the notion that early infancy is characterized by heightened susceptibility to airway genetic reprogramming in response to the first exposures in life, some of which can have life-long consequences. Here, we summarize and analyze the latest insights from studies that support a novel epigenetic paradigm centered on human maturational and developmental programs including three cardinal elements: genes, environment, and developmental timing. The combination of these factors is likely responsible for the functional trajectory of the respiratory system at the molecular, functional, and clinical levels.
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Epigênese Genética , MicroRNAs , Doenças Respiratórias/genética , Metilação de DNA , Epigenômica , Humanos , Sistema RespiratórioRESUMO
Spinal muscular atrophy is one of the most common fatal autosomal recessive disorders. Children diagnosed with SMA Type 1 (SMAT1) demonstrate severe oral motor weakness and flaccid dysarthria progressing to complete anarthria. A review of literature illustrates that little has been described regarding augmentative and alternative communication (AAC) use among these children, although communication has a critical impact on quality of life and participation in daily activities. Responses to an investigator-developed parent survey were obtained to appraise communication skills and opportunities among children diagnosed with SMA1. Results illustrate parent perception of greater receptive than expressive language ability and highlight the benefits of implementing speech-generating devices (SGD). Barriers to SGD acquisition and implementation, including access and funding, are reported and described. Overall, families indicated that SGD increases quality of life and provides valued improvements through expanded functional communication.
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Auxiliares de Comunicação para Pessoas com Deficiência , Atrofia Muscular Espinal , Criança , Comunicação , Humanos , Pais , Qualidade de VidaRESUMO
OBJECTIVES: Although recent evidence suggests that management of viral bronchiolitis requires something other than guidelines-guided therapy, there is a lack of evidence supporting the economic benefits of phenotypic-guided bronchodilator therapy for treating this disease. The aim of the present study was to compare the cost-effectiveness of phenotypic-guided versus guidelines-guided bronchodilator therapy in infants with viral bronchiolitis. METHODS: A decision analysis model was developed to compare the cost-effectiveness of phenotypic-guided versus guidelines-guided bronchodilator therapy in infants with viral bronchiolitis. Phenotypic-guided bronchodilator therapy was defined as the administration of albuterol in infants exhibiting a profile of increased likelihood of response to bronchodilators. The effectiveness parameters and costs of the model were obtained from systematic reviews of the literature with meta-analyses and electronic medical records. The main outcome was the avoidance of hospital admission after initial care in the emergency department. RESULTS: Compared to guidelines-guided strategy, treating patients with viral bronchiolitis with the phenotypic-guided bronchodilator therapy strategy was associated with lower total costs (US$250.99; 95% uncertainty interval [UI]: US$184.37 to $336.51 vs. US$263.46; 95% UI: US$189.81 to $349.19 average cost per patient) and a higher probability of avoidance of hospital admission (0.7902; 95% UI: 0.7315-0.8356 vs. 0.7638; 95% UI: 0.7062-0.8201), thus leading to dominance. Results were robust to deterministic and probabilistic sensitivity analyses. CONCLUSIONS: Compared to guidelines-guided strategy, treating infants with viral bronchiolitis using the phenotypic-guided bronchodilator therapy strategy is a more cost-effective strategy, because it involves a lower probability of hospital admission at lower total treatment costs.