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BACKGROUND: The limits of reproducibility of the lung clearance index (LCI) are higher in children with cystic fibrosis (CF) compared with healthy children, and it is currently unclear what defines a clinically meaningful change. METHODS: In a prospective multisite observational study of children with CF and healthy controls (HCs), we measured LCI, FEV1% predicted and symptom scores at quarterly visits over 2 years. Two reviewers performed a detailed review of visits to evaluate the frequency that between visit LCI changes outside ±10%, ±15%, ±20% represented a clinically relevant signal. In the setting of acute respiratory symptoms, we used a generalised estimating equation model, with a logit link function to determine the ability of LCI worsening at different thresholds to predict failure of lung function recovery at follow-up. RESULTS: Clinically relevant LCI changes outside ±10%, ±15% and ±20% were observed at 25.7%, 15.0% and 8.3% of CF visits (n=744), respectively. The proportions of LCI changes categorised as noise, reflecting biological variability, were comparable between CF and HC at the 10% (CF 9.9% vs HC 13.0%), 15% (CF 4.3% vs HC 3.1%) and 20% (CF 2.4% vs HC 1.0%) thresholds. Compared with symptomatic CF visits without a worsening in LCI, events with ≥10% LCI increase were more likely to fail to recover baseline LCI at follow-up. CONCLUSION: The limits of reproducibility of the LCI in healthy children can be used to detect clinically relevant changes and thus inform clinical care in children with CF.
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Fibrosis Quística , Humanos , Niño , Estudios Prospectivos , Reproducibilidad de los Resultados , Volumen Espiratorio Forzado , PulmónRESUMEN
Nasal nitric oxide (nNO) is extremely low in most people with primary ciliary dyskinesia (PCD) and its measurement is an important contributor to making the diagnosis. Existing guidelines and technical standards focus on nNO measurements in older, cooperative children using chemiluminescence analysers. However, measurements of nNO in pre-school-age children (age 2-5â years) may facilitate early diagnosis and electrochemical rather than chemiluminescence analysers are widely used. Pre-schoolers often need different methods to be employed when measuring nNO. Hence, a European Respiratory Society Task Force has developed this technical standard as the first step towards standardising sampling, analysis and reporting of nNO measured as part of the diagnostic testing for PCD in all age groups, including pre-school-age children. Furthermore, we considered both chemiluminescence and electrochemical analysers that are in use worldwide. There was a paucity of quality evidence for electrochemical analysers and sampling methods used in young children, and the Task Force proposes future research priorities to allow updates of this technical standard.
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Trastornos de la Motilidad Ciliar , Síndrome de Kartagener , Humanos , Niño , Preescolar , Anciano , Óxido Nítrico/análisis , Síndrome de Kartagener/diagnóstico , Pruebas Respiratorias/métodos , Diagnóstico Precoz , Frecuencia Respiratoria , Trastornos de la Motilidad Ciliar/diagnósticoRESUMEN
Hydrocephalus is one of the most prevalent form of developmental central nervous system (CNS) malformations. Cerebrospinal fluid (CSF) flow depends on both heartbeat and body movement. Furthermore, it has been shown that CSF flow within and across brain ventricles depends on cilia motility of the ependymal cells lining the brain ventricles, which play a crucial role to maintain patency of the narrow sites of CSF passage during brain formation in mice. Using whole-exome and whole-genome sequencing, we identified an autosomal-dominant cause of a distinct motile ciliopathy related to defective ciliogenesis of the ependymal cilia in six individuals. Heterozygous de novo mutations in FOXJ1, which encodes a well-known member of the forkhead transcription factors important for ciliogenesis of motile cilia, cause a motile ciliopathy that is characterized by hydrocephalus internus, chronic destructive airway disease, and randomization of left/right body asymmetry. Mutant respiratory epithelial cells are unable to generate a fluid flow and exhibit a reduced number of cilia per cell, as documented by high-speed video microscopy (HVMA), transmission electron microscopy (TEM), and immunofluorescence analysis (IF). TEM and IF demonstrate mislocalized basal bodies. In line with this finding, the focal adhesion protein PTK2 displays aberrant localization in the cytoplasm of the mutant respiratory epithelial cells.
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Ventrículos Cerebrales/patología , Ciliopatías/genética , Factores de Transcripción Forkhead/genética , Hidrocefalia/genética , Mutación/genética , Cuerpos Basales/patología , Cilios/genética , Cilios/patología , Ciliopatías/patología , Epéndimo/patología , Células Epiteliales/patología , Humanos , Hidrocefalia/patologíaRESUMEN
Rationale: The lung clearance index (LCI) is responsive to acute respiratory events in preschool children with cystic fibrosis (CF), but its utility to identify and manage these events in school-age children with CF is not well defined.Objectives: To describe changes in LCI with acute respiratory events in school-age children with CF.Methods: In a multisite prospective observational study, the LCI and FEV1 were measured quarterly and during acute respiratory events. Linear regression was used to compare relative changes in LCI and FEV1% predicted at acute respiratory events. Logistic regression was used to compare the odds of a significant worsening in LCI and FEV1% predicted at acute respiratory events. Generalized estimating equation models were used to account for repeated events in the same subject.Measurements and Main Results: A total of 98 children with CF were followed for 2 years. There were 265 acute respiratory events. Relative to a stable baseline measure, LCI (+8.9%; 95% confidence interval, 6.5 to 11.3) and FEV1% predicted (-6.6%; 95% confidence interval, -8.3 to -5.0) worsened with acute respiratory events. A greater proportion of events had a worsening in LCI compared with a decline in FEV1% predicted (41.7% vs. 30.0%; P = 0.012); 53.9% of events were associated with worsening in LCI or FEV1. Neither LCI nor FEV1 recovered to baseline values at the next follow-up visit.Conclusions: In school-age children with CF, the LCI is a sensitive measure to assess lung function worsening with acute respiratory events and incomplete recovery at follow-up. In combination, the LCI and FEV1 capture a higher proportion of events with functional impairment.
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Fibrosis Quística/complicaciones , Fibrosis Quística/fisiopatología , Volumen Espiratorio Forzado/fisiología , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/terapia , Adolescente , Niño , Femenino , Humanos , Indiana , Masculino , Ontario , Estudios Prospectivos , Pruebas de Función RespiratoriaRESUMEN
The lung clearance index (LCI) measured by the multiple breath washout (MBW) test is sensitive to early lung disease in children with cystic fibrosis. While LCI worsens during the preschool years in cystic fibrosis, there is limited evidence to clarify whether this continues during the early school age years, and whether the trajectory of disease progression as measured by LCI is modifiable.A cohort of children (healthy and cystic fibrosis) previously studied for 12â months as preschoolers were followed during school age (5-10â years). LCI was measured every 3â months for a period of 24â months using the Exhalyzer D MBW nitrogen washout device. Linear mixed effects regression was used to model changes in LCI over time.A total of 582 MBW measurements in 48 healthy subjects and 845 measurements in 64 cystic fibrosis subjects were available. The majority of children with cystic fibrosis had elevated LCI at the first preschool and first school age visits (57.8% (37 out of 64)), whereas all but six had normal forced expiratory volume in 1â s (FEV1) values at the first school age visit. During school age years, the course of disease was stable (-0.02â units·year-1 (95% CI -0.14-0.10). LCI measured during preschool years, as well as the rate of LCI change during this time period, were important determinants of LCI and FEV1, at school age.Preschool LCI was a major determinant of school age LCI; these findings further support that the preschool years are critical for early intervention strategies.
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Fibrosis Quística , Pruebas Respiratorias , Niño , Preescolar , Progresión de la Enfermedad , Volumen Espiratorio Forzado , Humanos , Pulmón , Pruebas de Función RespiratoriaRESUMEN
Primary ciliary dyskinesia (PCD) is a rare inherited condition affecting motile cilia and leading to organ laterality defects, recurrent sino-pulmonary infections, bronchiectasis, and severe lung disease. Research over the past twenty years has revealed variability in clinical presentations, ranging from mild to more severe phenotypes. Genotype and phenotype relationships have emerged. The increasing availability of genetic panels for PCD continue to redefine these genotype-phenotype relationships and reveal milder forms of disease that had previously gone unrecognized.
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Trastornos de la Motilidad Ciliar/genética , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Animales , Cilios/metabolismo , Cilios/ultraestructura , Trastornos de la Motilidad Ciliar/metabolismo , Trastornos de la Motilidad Ciliar/patología , HumanosRESUMEN
OBJECTIVE: To evaluate the predictive value of cumulative oxygen exposure thresholds over the first 2 postnatal weeks, linking them to bronchopulmonary dysplasia (BPD) and 1-year pulmonary morbidity and lung function in extremely low gestational age newborns. STUDY DESIGN: Infants (N = 704) enrolled in the Prematurity and Respiratory Outcomes Program, a multicenter prospective cohort study, that survived to discharge were followed through their neonatal intensive care unit hospitalization to 1-year corrected age. Cumulative oxygen exposure (OxygenAUC14) thresholds were derived from univariate models of BPD, stratifying infants into high-, intermediate-, and low-oxygen exposure groups. These groups were then used in multivariate logistic regressions to prospectively predict post-prematurity respiratory disease (PRD), respiratory morbidity score (RMS) in the entire cohort, and pulmonary function z scores (N = 108 subset of infants) at 1-year corrected age. RESULTS: Over the first 14 postnatal days, infants exposed to high oxygen averaged ≥33.1% oxygen, infants exposed to intermediate oxygen averaged 29.1%-33.1%, and infants exposed to low oxygen were below both cutoffs. In multivariate models, infants exposed to high oxygen showed increased PRD and RMS, whereas infants exposed to intermediate oxygen demonstrated increased moderate/severe RMS. Infants in the high/intermediate groups had decreased forced expiratory volume at 0.5 seconds/forced vital capacity ratio. CONCLUSIONS: OxygenAUC14 establishes 3 thresholds of oxygen exposure that risk stratify infants early in their neonatal course, thereby predicting short-term (BPD) and 1-year (PRD, RMS) respiratory morbidity. Infants with greater OxygenAUC14 have altered pulmonary function tests at 1 year of age, indicating early evidence of obstructive lung disease and flow limitation, which may predispose extremely low gestational age newborns to increased long-term pulmonary morbidity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01435187.
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Displasia Broncopulmonar/etiología , Oxígeno/efectos adversos , Respiración Artificial/efectos adversos , Displasia Broncopulmonar/fisiopatología , Femenino , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Masculino , Oxígeno/administración & dosificación , Estudios Prospectivos , Respiración Artificial/métodos , Respiración Artificial/mortalidad , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Capacidad VitalRESUMEN
RATIONALE: In primary ciliary dyskinesia, factors leading to disease heterogeneity are poorly understood. OBJECTIVES: To describe early lung disease progression in primary ciliary dyskinesia and identify associations between ultrastructural defects and genotypes with clinical phenotype. METHODS: This was a prospective, longitudinal (5 yr), multicenter, observational study. Inclusion criteria were less than 19 years at enrollment and greater than or equal to two annual study visits. Linear mixed effects models including random slope and random intercept were used to evaluate longitudinal associations between the ciliary defect group (or genotype group) and clinical features (percent predicted FEV1 and weight and height z-scores). MEASUREMENTS AND MAIN RESULTS: A total of 137 participants completed 732 visits. The group with absent inner dynein arm, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) (n = 41) were significantly younger at diagnosis and in mixed effects models had significantly lower percent predicted FEV1 and weight and height z-scores than the isolated outer dynein arm defect (n = 55) group. Participants with CCDC39 or CCDC40 mutations (n = 34) had lower percent predicted FEV1 and weight and height z-scores than those with DNAH5 mutations (n = 36). For the entire cohort, percent predicted FEV1 decline was heterogeneous with a mean (SE) decline of 0.57 (0.25) percent predicted/yr. Rate of decline was different from zero only in the IDA/MTD/CA group (mean [SE], -1.11 [0.48] percent predicted/yr; P = 0.02). CONCLUSIONS: Participants with IDA/MTD/CA defects, which included individuals with CCDC39 or CCDC40 mutations, had worse lung function and growth indices compared with those with outer dynein arm defects and DNAH5 mutations, respectively. The only group with a significant lung function decline over time were participants with IDA/MTD/CA defects.
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Cilios/genética , Cilios/ultraestructura , Síndrome de Kartagener/genética , Niño , Estudios de Cohortes , Femenino , Genotipo , Humanos , Síndrome de Kartagener/fisiopatología , Estudios Longitudinales , Pulmón/fisiopatología , Masculino , Mutación/genética , Fenotipo , Estudios Prospectivos , Pruebas de Función RespiratoriaAsunto(s)
Pediatría , Humanos , Estados Unidos , Niño , Centros Médicos Académicos , Facultades de MedicinaRESUMEN
BACKGROUND: Obstructive airway disease is nonuniformly distributed throughout the bronchial tree, although the extent to which this occurs can vary among conditions. The multiple-breath washout (MBW) test offers important insights into pediatric lung disease, not available through spirometry or resistance measurements. The European Respiratory Society/American Thoracic Society inert gas washout consensus statement led to the emergence of validated commercial equipment for the age group 6 years and above; specific recommendations for preschool children were beyond the scope of the document. Subsequently, the focus has shifted to MBW applications within preschool subjects (aged 2-6 yr), where a "window of opportunity" exists for early diagnosis of obstructive lung disease and intervention. METHODS: This preschool-specific technical standards document was developed by an international group of experts, with expertise in both custom-built and commercial MBW equipment. A comprehensive review of published evidence was performed. RESULTS: Recommendations were devised across areas that place specific age-related demands on MBW systems. Citing evidence where available in the literature, recommendations are made regarding procedures that should be used to achieve robust MBW results in the preschool age range. The present work also highlights the important unanswered questions that need to be addressed in future work. CONCLUSIONS: Consensus recommendations are outlined to direct interested groups of manufacturers, researchers, and clinicians in preschool device design, test performance, and data analysis for the MBW technique.
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Pruebas Respiratorias/métodos , Diagnóstico Precoz , Enfermedades Pulmonares/diagnóstico , Niño , Preescolar , Femenino , Humanos , Pulmón/fisiopatología , Enfermedades Pulmonares/fisiopatología , Masculino , Pruebas de Función Respiratoria/métodos , Sociedades Médicas , Estados UnidosRESUMEN
RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence. OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence. METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial in children with CF, 6 months to 18 years of age, with early Pa. Azithromycin or placebo was given 3× weekly with standardized TIS. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the time to pulmonary exacerbation requiring antibiotics and the secondary endpoint was the time to Pa recurrence, in addition to other clinical and safety outcomes. A total of 221 participants (111 placebo, 110 azithromycin) out of a planned 274 were enrolled. Enrollment was stopped early by the NHLBI because the trial had reached the prespecified interim boundary for efficacy. The risk of pulmonary exacerbation was reduced by 44% in the azithromycin group as compared with the placebo group (hazard ratio, 0.56; 95% confidence interval, 0.37-0.83; P = 0.004). Weight increased by 1.27 kg in the azithromycin group compared with the placebo group (95% confidence interval, 0.01-2.52; P = 0.046). No significant differences were seen in microbiological or other clinical or safety endpoints. CONCLUSIONS: Azithromycin was associated with a significant reduction in the risk of pulmonary exacerbation and a sustained improvement in weight, but had no impact on microbiological outcomes in children with early Pa. Clinical trial registered with clinicaltrials.gov (NCT02054156).
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Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Fibrosis Quística/complicaciones , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Administración por Inhalación , Adolescente , Niño , Preescolar , Método Doble Ciego , Quimioterapia Combinada/métodos , Femenino , Humanos , Lactante , Masculino , Pseudomonas aeruginosa/efectos de los fármacos , Recurrencia , Factores de Tiempo , Tobramicina/administración & dosificación , Tobramicina/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: This document presents the American Thoracic Society clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD). TARGET AUDIENCE: Clinicians investigating adult and pediatric patients for possible PCD. METHODS: Systematic reviews and, when appropriate, meta-analyses were conducted to summarize all available evidence pertinent to our clinical questions. Evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for diagnosis and discussed by a multidisciplinary panel with expertise in PCD. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists. Three conflicted individuals were also prohibited from writing, editing, or providing feedback on the relevant sections of the manuscript. RESULTS: After considering diagnostic test accuracy, confidence in the estimates for each diagnostic test, relative importance of test results studied, desirable and undesirable direct consequences of each diagnostic test, downstream consequences of each diagnostic test result, patient values and preferences, costs, feasibility, acceptability, and implications for health equity, the panel made recommendations for or against the use of specific diagnostic tests as compared with using the current reference standard (transmission electron microscopy and/or genetic testing) for the diagnosis of PCD. CONCLUSIONS: The panel formulated and provided a rationale for the direction as well as for the strength of each recommendation to establish the diagnosis of PCD.
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Cilios/patología , Técnicas y Procedimientos Diagnósticos/normas , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/genética , Guías de Práctica Clínica como Asunto , Estudios de Cohortes , Estudios Transversales , Predisposición Genética a la Enfermedad , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Sensibilidad y Especificidad , Sociedades Médicas , Estados UnidosRESUMEN
BACKGROUND: Antibiotic treatment for pulmonary symptoms in preschool children with cystic fibrosis (CF) varies among clinicians. The lung clearance index (LCI) is sensitive to early CF lung disease, but its utility to monitor pulmonary exacerbations in young children has not been assessed. OBJECTIVE: We aim to (1) understand how LCI changes during lower respiratory tract symptoms relative to a recent clinically stable measurement, (2) determine whether LCI can identify antibiotic treatment response and (3) compare LCI changes to changes in spirometric indices. METHODS: LCI and spirometry were measured at quarterly clinic visits over a 12-month period in preschool children with CF. Symptomatic visits were identified and classified as treated or untreated. Treatment response was estimated using propensity score matching methods. RESULTS: 104 symptomatic visits were identified in 78 participants. LCI increased from baseline in both treated (mean relative change +23.8% (95% CI 16.2 to 31.4)) and untreated symptomatic visits (mean relative change +11.2% (95% CI 2.4 to 19.9)). A significant antibiotic treatment effect was observed when LCI was used as the outcome measure (average treatment effect -15.5% (95% CI -25.4 to -5.6)) but not for z-score FEV1. CONCLUSION: LCI significantly deteriorated with pulmonary symptoms relative to baseline and improved with antibiotic treatment. These data suggest that LCI may have a role in the routine clinical care of preschool children with CF.
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Antibacterianos/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/fisiopatología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/fisiopatología , Pruebas Respiratorias , Preescolar , Fibrosis Quística/complicaciones , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Infecciones del Sistema Respiratorio/etiología , Espirometría , Evaluación de Síntomas , Resultado del TratamientoRESUMEN
RATIONALE: Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. OBJECTIVES: To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progression in preschool children with CF. METHODS: Children with CF between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy control subjects were enrolled at three North American CF centers. Multiple breath washout tests were performed at baseline, 1, 3, 6, and 12 months to mimic time points chosen in clinical care and interventional trials; spirometry was also conducted. A generalized linear mixed-effects model was used to distinguish LCI changes associated with normal growth and development (i.e., healthy children) from the progression of CF lung disease. MEASUREMENTS AND MAIN RESULTS: Data were collected on 156 participants with 800 LCI measurements. Although both LCI and spirometry discriminated health from disease, only the LCI identified significant deterioration of lung function in CF over time. The LCI worsened during cough episodes and pulmonary exacerbations, whereas similar symptoms in healthy children were not associated with increased LCI values. CONCLUSIONS: LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF.
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Fibrosis Quística/complicaciones , Enfermedades Pulmonares/etiología , Niño , Preescolar , Fibrosis Quística/patología , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado , Humanos , Estudios Longitudinales , Pulmón/patología , Enfermedades Pulmonares/patología , Masculino , Pruebas de Función Respiratoria , EspirometríaRESUMEN
The lung clearance index (LCI) has strong intra-test repeatability; however, the inter-test reproducibility of the LCI is poorly defined.The aim of the present study was to define a physiologically meaningful change in LCI in preschool children, which discriminates changes associated with disease progression from biological variability.Repeated LCI measurements from a longitudinal cohort study of children with cystic fibrosis and age-matched controls were collected to define the inter-visit reproducibility of the LCI. Absolute change, the coefficient of variation, Bland-Altman limits of agreement, the coefficient of repeatability, intra-class correlation coefficient, and percentage changes were calculated.LCI measurements (n=505) from 71 healthy and 77 cystic fibrosis participants (aged 2.6-6â years) were analysed. LCI variability was proportional to its magnitude, such that reproducibility defined by absolute changes is biased. A physiologically relevant change for quarterly LCI measurements in health was defined as exceeding ±15%. In clinically stable cystic fibrosis participants, the threshold was higher (±25%); however, for measurements made 24â h apart, the threshold was similar to that observed in health (±17%).A percentage change in LCI greater than ±15% in preschool children can be considered physiologically relevant and greater than the biological variability of the test.
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Fibrosis Quística , Depuración Mucociliar , Pruebas Respiratorias/métodos , Preescolar , Fibrosis Quística/diagnóstico , Fibrosis Quística/fisiopatología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Gravedad del Paciente , Pronóstico , Reproducibilidad de los ResultadosAsunto(s)
Internado y Residencia , Pediatría , Selección de Profesión , Niño , Humanos , Especialización , Estados UnidosRESUMEN
BACKGROUND: Asthma is the most common chronic disease of childhood and a leading cause of hospitalization in children. A primary goal of asthma control is prevention of hospitalizations. A hospital admission is the single strongest predictor of future hospital admissions for asthma. The 30-day asthma readmission rate at our institution was significantly higher than that of other hospitals in the Children's Hospital Association. As a result, a multifaceted quality improvement project was undertaken with the goal of reducing the 30-day inpatient asthma readmission rate by 50% within two years. METHODS: Analysis of our institution's readmission patterns, value stream mapping of asthma admission, discharge, and follow-up processes, literature review, and examination of comparable successful programs around the United States were all utilized to identify potential targets for intervention. Interventions were implemented in a stepwise manner, and included increasing inhaler availability after discharge, modifying asthma education strategies, and providing in-home post-discharge follow-up. The primary outcome was a running 12-month average 30-day inpatient readmission rate. Secondary outcomes included process measures for individual interventions. RESULTS: From a peak of 7.98% in January 2013, a steady decline to 1.65% was observed by July 2014, which represented a 79.3% reduction in 30-day readmissions. CONCLUSION: A significant decrease in hospital readmissions for pediatric asthma is possible, through comprehensive, multidisciplinary quality improvement that spans the continuum of care.