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Cystic fibrosis (CF) is an inherited disorder caused by a deleterious mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Given that the CFTR protein is a chloride channel expressed on a variety of cells throughout the human body, mutations in this gene impact several organs, particularly the lungs. For this very reason, research regarding CF disease and CFTR function has historically focused on the lung airway epithelium. Nevertheless, it was discovered more than two decades ago that CFTR is also expressed and functional on endothelial cells. Despite the great strides that have been made in understanding the role of CFTR in the airway epithelium, the role of CFTR in the endothelium remains unclear. Considering that the airway epithelium and endothelium work in tandem to allow gas exchange, it becomes very crucial to understand how a defective CFTR protein can impact the pulmonary vasculature and overall lung function. Fortunately, more recent research has been dedicated to elucidating the role of CFTR in the endothelium. As a result, several vascular dysfunctions associated with CF disease have come to light. Here, we summarize the current knowledge on pulmonary vascular dysfunctions in CF and discuss applicable therapies.
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Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Pulmão , Humanos , Fibrose Cística/fisiopatologia , Fibrose Cística/metabolismo , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Animais , Pulmão/metabolismo , Pulmão/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Endotélio Vascular/patologia , Mutação , Circulação Pulmonar/fisiologiaRESUMO
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) adversely affects normal blood pressure (BP) and may disrupt circadian BP patterns. We sought to examine 24-hour circadian BP rhythms in children with OSA and healthy controls. METHODS: Children 5-14 years with OSA and healthy controls underwent 24-hour BP monitoring and actigraphy to quantify sleep. Shape invariant statistical models compared circadian BP patterns (e.g. times of BP peaks, time arrived at peak BP velocity [TAPV]) in the OSA and control groups. RESULTS: The analytic sample included 219 children (mild OSA: nâ =â 52; moderate-to-severe OSA (MS-OSA): nâ =â 50; controls: nâ =â 117). In the morning, the MS-OSA group had earlier TAPV for DBP than controls (51 minutes, pâ <â 0.001). TAPV in the evening was earlier for the MS-OSA group than controls (SBP: 95 minutes, pâ <â 0.001; DBP: 28 minutes, pâ =â 0.028). At mid-day, SBP and DBP velocity nadirs were earlier for the MS-OSA group than controls (SBP: 57 minutes, pâ <â 0.001; DBP: 38 minutes, pâ <â 0.01). The MS-OSA group reached most BP values significantly earlier than controls; the largest differences were 118 minutes (SBP) and 43 minutes (DBP) (pâ <â 0.001). SBP and DBP were elevated in the MS-OSA group (hours 18-21 and 7--12, respectively, pâ <â 0.01) compared to controls. The MS-OSA group was prone to "non-dipping" compared to controls (SBP: odds ratio [OR]â =â 2.16, 95% CI: 1.09, 4.29; DBP: ORâ =â 3.45, 95% CI: 1.21, 10.23). CONCLUSIONS: Children with MS-OSA had changes in circadian BP patterns, namely earlier TAPV and BP peaks and nadirs than controls. Circadian disturbances in BP rhythms may be key to mapping the natural history of BP dysregulation in children with OSA.
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Hipertensão , Apneia Obstrutiva do Sono , Humanos , Criança , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Apneia Obstrutiva do Sono/complicações , Sono/fisiologia , Monitorização Ambulatorial da Pressão ArterialRESUMO
Introduction: The Cystic Fibrosis (CF) Foundation sponsored the design, pilot testing, and implementation of the CF Learning Network (CFLN) to explore how the Foundation's Care Center Network (CCN) could become a learning health system. Six years after the design, the Foundation commissioned a formative mixed methods evaluation of the CFLN to assess: CFLN participants' understanding of program goals, attributes, and perceptions of current and future impact. Methods: We performed semi-structured interviews with CFLN participants to identify perceived goals, attributes, and impact of the network. Following thematic analyses, we developed and distributed a survey to CFLN members and a matched sample of CCN programs to understand whether the themes were unique to the CFLN. Results: Interviews with 24 CFLN participants were conducted. Interviewees identified the primary CFLN goal as improving outcomes for people living with CF, with secondary goals of providing training in quality improvement (QI), creating a learning community, engaging all stakeholders in improvement, and spreading best practices to the CCN. Project management, use of data, common QI methods, and the learning community were seen as critical to success. Survey responses were collected from 103 CFLN members and 25 CCN members. The data revealed that CFLN respondents were more likely than CCN respondents to connect with other CF programs, routinely use data for QI, and engage patient and family partners in QI. Conclusions: Our study suggests that the CFLN provides value beyond that achieved by the CCN. Key questions remain about whether spread of the CFLN could improve outcomes for more people living with CF.
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Healthy sleep and optimal ventilatory control begin in early development and are crucial for positive child outcomes. This paper summarizes information presented at the Sleep and Ventilatory Control sessions of the National Heart, Lung, and Blood-sponsored 2021 Defining and Promoting Pediatric Pulmonary Health workshop. These sessions focused on pediatric sleep health, screening for sleep health and sleep disorders in primary care using the electronic health record, infant sleep and ventilatory control, and home sleep testing. Throughout this summary, we discuss key gaps in and barriers to promoting sleep and ventilatory health that were identified during the workshop sessions. We conclude with strategies to address these gaps and barriers and directions for future multidisciplinary research, patient care, and training.
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Registros Eletrônicos de Saúde , Coração , Lactente , Humanos , Criança , Pesquisa Interdisciplinar , Sono , PulmãoRESUMO
Introduction: A learning health network is a type of learning health system in which stakeholders use network organization to improve health and health care. Building on existing resources in the cystic fibrosis (CF) community, the Cystic Fibrosis Learning Network (CFLN) was designed to improve medical outcomes and quality of life through an intentional focus on achieving reliable evidence-based chronic care delivery and creating a system for data-driven collaborative learning. Methods: We describe the development and growth of the CFLN considering six domains of a Network Maturity Grid: system leadership; governance and policy management; quality improvement (QI); engagement and community building; data and analytics; and research. We illustrate the impact of the CFLN experience on chronic care processes and indicators of collaborative infrastructure. Results: The CFLN represents 36 accredited care centers in the CF Foundation Care Center Network caring for over 6300 patients. Of 6779 patient clinical care visits/quarter, 77% are entered into the CF Foundation Patient Registry within 30 days, providing timely means to track outcomes. Collaborative visit planning is occurring in 93% of clinical care visits to share agenda setting with patients and families. Almost all CFLN teams (94%, n = 34) have a patient/family partner (PFP), and 74% of PFPs indicate they are actively participating, taking ownership of, or leading QI initiatives with the interdisciplinary care team. In 2022, 97% of centers reported completing 1-13 improvement cycles per month, and 82% contributed to monthly QI progress reports to share learning. Conclusion: The CFLN is a maturing, collaborative infrastructure. CFLN centers practice at an advanced level of coproduction. The CFLN fosters interdisciplinary and PFP leadership and the performance of consistent data-driven improvement cycles. CFLN centers are positioned to respond to rapid changes in evidence-based care and advance the practice of QI and implementation science on a broader scale.
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OBJECTIVE: Caregivers frequently report poor quality of life (QOL) in children with sleep-disordered breathing (SDB). Our objective is to assess the correlation between caregiver- and child-reported QOL in children with mild SDB and identify factors associated with differences between caregiver and child report. STUDY DESIGN: Analysis of baseline data from a multi-institutional randomized trial SETTING: Pediatric Adenotonsillectomy Trial for Snoring, where children with mild SDB (obstructive apnea-hypopnea index <3) were randomized to observation or adenotonsillectomy. METHODS: The Pediatric Quality of Life Inventory (PedsQL) assessed baseline global QOL in participating children 5 to 12 years old and their caregivers. Caregiver and child scores were compared. Multivariable regression assessed whether clinical factors were associated with differences between caregiver and child report. RESULTS: PedsQL scores were available for 309 families (mean child age, 7.0 years). The mean caregiver-reported PedsQL score was higher at 75.2 (indicating better QOL) than the mean child-reported score of 67.9 (P < .001). The agreement between caregiver and child total PedsQL scores was poor, with intraclass correlation coefficients of 0.03 (95% CI, -0.09 to 0.15) for children 5 to 7 years old and 0.21 (95% CI, 0.03-0.38) for children 8 to 12 years old. Higher child age and health literacy were associated with closer agreement between caregiver and child report. CONCLUSION: Caregiver- and child-reported global QOL in children with SDB was weakly correlated, more so for young children. In pediatric SDB, child-perceived QOL may be poorer than that reported by caregivers. Further research is needed to assess whether similar trends exist for disease-specific QOL metrics.
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Cuidadores , Síndromes da Apneia do Sono , Humanos , Criança , Pré-Escolar , Qualidade de Vida , Síndromes da Apneia do Sono/cirurgia , Ronco , AdenoidectomiaRESUMO
BACKGROUND AND OBJECTIVES: Children requiring long-term mechanical ventilation are at high risk of mortality. Setting ventilator alarms may improve safety, but best practices for setting ventilator alarms have not been established. Our objective was to increase the mean proportion of critical ventilator alarms set for those children requiring chronic mechanical ventilation followed in our pulmonary clinic from 63% to >90%. METHODS: Using the Institute for Healthcare Improvement Model for Improvement, we developed, tested, and implemented a series of interventions using Plan-Do-Study-Act cycles. We followed our progress using statistical process control methods. Our primary interventions were: (1) standardization of the clinic workflow, (2) development of an algorithm to guide physicians in selecting and setting ventilator alarms, (3) updating that algorithm based on review of failures and inpatient testing, and (4) enhancing staff engagement to change the culture surrounding ventilator alarms. RESULTS: We collected baseline data from May 1 to July 13, 2017 on 130 consecutive patients seen in the pulmonary medicine clinic. We found that 63% of critical ventilator alarms were set. Observation of the process, standardization of workflow, and adaptation of an alarm algorithm led to an increase to 85.7% of critical alarms set. Through revising our algorithm to include an apnea alarm, and maximizing provider engagement, more than 95% of critical ventilator alarms were set, exceeding our goal. We sustained this improvement through January 2021. CONCLUSIONS: Our stepwise approach, including process standardization, staff engagement, and integration of an alarm algorithm, improved the use of ventilator alarms in chronically ventilated pediatric patients.
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Respiração Artificial , Ventiladores Mecânicos , Algoritmos , Criança , Falha de Equipamento , Humanos , Padrões de ReferênciaRESUMO
STUDY OBJECTIVES: Obstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea. METHODS: Children 3-12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index < 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5-9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2-30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis. RESULTS: The sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30-2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98-5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83-4.34) in children recruited for mild sleep-disordered breathing. CONCLUSIONS: Abnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention. TRIAL REGISTRATION: Pediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859.
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Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Tonsilectomia , Adenoidectomia , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Humanos , Morbidade , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/cirurgia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/cirurgia , Ronco/complicações , Ronco/cirurgiaRESUMO
INTRODUCTION: The Cystic Fibrosis Foundation chronic care guidelines recommend monitoring clinical status of a patient with cystic fibrosis (CF) through quarterly interdisciplinary visits. At the beginning of the COVID-19 pandemic, the Cystic Fibrosis Learning Network (CFLN) designed and initiated a telehealth (TH) innovation lab (TH ILab) to support transition from the classic CF care model of quarterly in-person office visits to a care model that included TH. AIM: The specific aims of the TH ILab were to increase the percentage of virtual visits with interdisciplinary care (IDC) from 60% to 85% and increase the percentage of virtual visits in which patients and families participated in shared agenda setting (AS) from 52% to 85% by 31 December 2020. METHODS: The model for improvement methodology was used to determine the ILab aims, theory, interventions and measures. In the testing phase of the ILab, data related to process and outcome measures as well as learnings from plan-do-study-act cycles were collected, analysed and shared weekly with the TH ILab teams. Participating centres created processes for IDC and AS for TH visits and developed and shared quality improvement tools specific to their local context with other centres during the ILab weekly meetings and via a secure CFLN-maintained platform. RESULTS: Both specific aims were achieved ahead of the expected target date. By August 2020, 85% of the TH ILab visits provided IDC and 92% of patients were seen for CF care by teams from the TH ILab that participated in AS. CONCLUSION: Shared learning through a collaborative, data-driven process in the CFLN TH ILab rapidly led to standardised TH IDC and AS, which achieved reliable and sustainable processes which could be reproduced by other networks.
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COVID-19 , Fibrose Cística , Telemedicina , Fibrose Cística/terapia , Humanos , Pandemias , Melhoria de Qualidade , Telemedicina/métodosRESUMO
This study proposes a Bayesian joint model with extended random effects structure that incorporates nested repeated measures and provides simultaneous inference on treatment effects over time and drop-out patterns. The proposed model includes flexible splines to characterize the circadian variation inherent in blood pressure sequences, and we assess the effectiveness of an intervention to resolve pediatric obstructive sleep apnea. We demonstrate that the proposed model and its conventional two-stage counterpart provide similar estimates of nighttime blood pressure but estimates on the mean evolution of daytime blood pressure are discrepant. Our simulation studies tailored to the motivating data suggest reasonable estimation and coverage probabilities for both fixed and random effects. Computational challenges of model implementation are discussed.
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Hipertensão , Apneia Obstrutiva do Sono , Teorema de Bayes , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Criança , Ritmo Circadiano , HumanosRESUMO
OBJECTIVE: To evaluate structural and functional carotid changes and inflammatory profiles in children with obstructive sleep apnea (OSA) and healthy controls. STUDY DESIGN: Patients with OSA and matched controls (ages 5-13 years) were recruited. Proinflammatory cytokines and acute phase reactants were measured at 6:00 p.m. Common carotid artery measures were determined using ultrasound. Confirmatory factor analysis was used to determine subgroups of cytokines and their effects on carotid measures. RESULTS: Ninety-six patients participated (53 healthy controls, 43 patients with OSA). OSA was associated with increased proinflammatory cytokines (cluster of differentiation-40 ligand [CD40-L], interleukin [IL]-6, and IL-8) and high sensitivity C-reactive protein (P < .05 for all). One cytokine subgroup (IL-6 and IL-8) was negatively associated with markers of carotid function, indicating reduced arterial distensibility and increased stiffness (P < .05 for 3 ultrasound measures); and tumor necrosis factor-α had an opposing effect on carotid function compared with this cytokine subgroup (P < .05 for 2 ultrasound measures). Linear regression demonstrated significant associations between and tumor necrosis factor- α and 2 measures of carotid function (P < .05 for each). Children with OSA did not have functional or structural carotid changes compared with controls. CONCLUSION: OSA was not directly associated with structural and functional carotid changes but was associated with upregulation of key proinflammatory cytokines (sCD40-L, IL-6, and IL-8). Together, IL-6 and IL-8 were associated with changes in carotid function. Longitudinal studies are needed to demonstrate that the inflammatory milieu observed in our population is a precursor of atherosclerosis in children.
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Proteínas de Fase Aguda/metabolismo , Aterosclerose/etiologia , Artéria Carótida Primitiva/fisiopatologia , Citocinas/sangue , Inflamação/etiologia , Apneia Obstrutiva do Sono/fisiopatologia , Adolescente , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/fisiopatologia , Modelos Lineares , Masculino , Estudos Prospectivos , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/complicações , UltrassonografiaRESUMO
Computational fluid dynamics (CFD) simulations of respiratory airflow have the potential to change the clinical assessment of regional airway function in health and disease, in pulmonary medicine and otolaryngology. For example, in diseases where multiple sites of airway obstruction occur, such as obstructive sleep apnea (OSA), CFD simulations can identify which sites of obstruction contribute most to airway resistance and may therefore be candidate sites for airway surgery. The main barrier to clinical uptake of respiratory CFD to date has been the difficulty in validating CFD results against a clinical gold standard. Invasive instrumentation of the upper airway to measure respiratory airflow velocity or pressure can disrupt the airflow and alter the subject's natural breathing patterns. Therefore, in this study, we instead propose phase contrast (PC) velocimetry magnetic resonance imaging (MRI) of inhaled hyperpolarized 129Xe gas as a non-invasive reference to which airflow velocities calculated via CFD can be compared. To that end, we performed subject-specific CFD simulations in airway models derived from 1H MRI, and using respiratory flowrate measurements acquired synchronously with MRI. Airflow velocity vectors calculated by CFD simulations were then qualitatively and quantitatively compared to velocity maps derived from PC velocimetry MRI of inhaled hyperpolarized 129Xe gas. The results show both techniques produce similar spatial distributions of high velocity regions in the anterior-posterior and foot-head directions, indicating good qualitative agreement. Statistically significant correlations and low Bland-Altman bias between the local velocity values produced by the two techniques indicates quantitative agreement. This preliminary in vivo comparison of respiratory airway CFD and PC MRI of hyperpolarized 129Xe gas demonstrates the feasibility of PC MRI as a technique to validate respiratory CFD and forms the basis for further comprehensive validation studies. This study is therefore a first step in the pathway towards clinical adoption of respiratory CFD.
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Isótopos de Xenônio , Humanos , Hidrodinâmica , Imageamento por Ressonância Magnética , TraqueiaRESUMO
OBJECTIVE/HYPOTHESIS: To assess the ability of ultra-short echo time (UTE)-MRI to detect subglottic stenosis (SGS) and evaluate response to balloon dilation. To correlate measurements from UTE-MRI with endotracheal-tube (ETT)-sizing and to investigate whether SGS causes change in airway dynamics. STUDY DESIGN: Animal research study. METHODS: Eight adult New-Zealand white rabbits were used as they approximate neonatal airway-size. The airways were measured using ETT-sizing and 3D UTE-MRI at baseline, 2 weeks post-cauterization induced SGS injury, and post-balloon dilation treatment. UTE-MR images were acquired to determine airway anatomy and motion. Airways were segmented from MR images. Cross-sectional area (CSA), major and minor diameters (Dmajor and Dminor ), and eccentricity were measured. RESULTS: Post-injury CSA at SGS was significantly reduced (mean 38%) compared to baseline (P = .003) using UTE-MRI. ETT-sizing correlated significantly with MRI-measured CSA at the SGS location (r = 0.6; P < .01), particularly at the post-injury timepoint (r = 0.93; P < .01). Outer diameter from ETT-sizing (OD) correlated significantly with Dmajor (r = 0.63; P < .01) from UTE-MRI at the SGS location, especially for the post-injury timepoint (r = 0.91; P < .01). Mean CSA of upper trachea did not change significantly between end-expiration and end-inspiration at any timepoint (all P > .05). Eccentricity of the upper trachea increased significantly post-balloon dilation (P < .05). CONCLUSIONS: UTE-MRI successfully detected SGS and treatment response in the rabbit model, with good correlation to ETT-sizing. Balloon dilation increased CSA at SGS, but not to baseline values. SGS did not alter dynamic motion for the trachea in this rabbit model; however, tracheas were significantly eccentric post-balloon dilation. UTE-MRI can detect SGS without sedation or ionizing radiation and may be a non-invasive alternative to ETT-sizing. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E1971-E1979, 2021.
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Laringoestenose/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Animais , Modelos Animais de Doenças , Feminino , Imageamento Tridimensional , Intubação Intratraqueal , Laringoscopia , CoelhosRESUMO
OBJECTIVES: Subglottic stenosis (SGS) is the most common type of laryngeal stenosis in neonates. SGS severity is currently graded based on percent area of obstruction (%AO) via the Myer-Cotton grading scale. However, patients with similar %AO can have widely different clinical courses. Computational fluid dynamics (CFD) based on patient-specific imaging can quantify the relationship between airway geometry and flow dynamics. We investigated the effect of %AO and axial position of SGS on work of breathing (WOB) in neonates using magnetic resonance imaging. METHODS: High-resolution ultrashort echo-time MRI of the chest and airway was obtained in three neonatal patients with no suspected airway abnormalities; images were segmented to construct three-dimensional (3D) models of the neonatal airways. These models were then modified with virtual SGSs of varying %AO and axial positioning. CFD simulations of peak inspiratory flow were used to calculate patient-specific WOB in nonstenotic and artificially stenosed airway models. RESULTS: CFD simulations demonstrated a relationship between stenosis geometry and WOB increase. WOB rapidly increased with %AO greater than about 70%. Changes in axial position could also increase WOB by approximately the same amount as a 10% increase in %AO. Increased WOB was particularly pronounced when the SGS lumen was misaligned with the glottic jet. CONCLUSION: The results indicate a strong, predictable relationship between WOB and axial position of the stenotic lumen relative to the glottis, which has not been previously reported. These findings may lead to precision diagnosis and treatment prediction tools in individual patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1220-E1226, 2021.
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Laringoestenose/diagnóstico por imagem , Laringoestenose/fisiopatologia , Imageamento por Ressonância Magnética , Trabalho Respiratório , Humanos , Imageamento Tridimensional , Recém-Nascido , Modelagem Computacional Específica para o PacienteRESUMO
General anesthesia decreases the tone of upper airway muscles in a dose-dependent fashion, potentially narrowing the pharyngeal airway. We examined the effects of adding ketamine on the airway configuration after dexmedetomidine administration in spontaneously breathing children with normal airways. 25 children presenting for Magnetic Resonance Imaging (MRI) of the brain/spine under general anesthesia were prospectively recruited in the study. Patients were anesthetized with dexmedetomidine bolus (2 mcg over 10 min) followed by dexmedetomidine infusion (2 mcg·kg-1·h) and ketamine and permitted to breathe spontaneously via the native airway. MR-CINE images of the upper airway were obtained with dexmedetomidine infusion alone (baseline) and 5, 10, and 15 min after administering ketamine bolus (2 mg·kg-1) in two anatomical axial planes at the nasopharynx and the retroglossal upper airway. Airway lumen is segmented with a semi-automatic image processing approach using a region-growing algorithm. Outcome measures of cross-sectional area, transverse and anterior-posterior diameters of the airway in axial planes at the level of the epiglottis in the retroglossal airway, and in the superior nasopharynx were evaluated for changes in airway size with sedation. Airway dimensions corresponding to the maximum, mean, and minimum sizes during a respiratory cycle were obtained to compare the temporal changes in the airway size. The dose-response of adding ketamine to dexmedetomidine alone condition on airway dimensions were examined using mixed-effects of covariance models. 22/25 patients based on inclusion/exclusion criteria were included in the final analysis. The changes in airway measures with the addition of ketamine, when compared to the baseline of dexmedetomidine alone, were statistically insignificant. The modest changes in airway dimensions are clinically less impactful and within the accuracy of the semi-automatic airway segmentation approach. The effect sizes were small for most airway measures. The duration of ketamine seems to not affect the airway size. In conclusion, adding ketamine to dexmedetomidine did not significantly reduce upper airway configuration when compared to dexmedetomidine alone.
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In longitudinal studies in which a medical device is used to monitor outcome repeatedly and frequently on the same patients over a prespecified duration of time, two clustering goals can arise. One goal is to assess the degree of heterogeneity among patient profiles. A second yet equally important goal unique to such studies is to determine frequency and duration of monitoring sufficient to identify longitudinal changes. Considering these goals jointly would identify clusters of patients who share similar patterns over time and characterize temporal stability within each cluster. We use a biclustering approach, allowing simultaneous clustering of observations at both patient and time levels and using a nonparametric hierarchical Bayesian model. Because clustering units at the time level (i.e., time points) are ordered and hence unexchangeable, we utilize a multivariate Dirichlet process mixture model by specifying a Dirichlet process prior at the patient level whose base measure employs change points at the time level to achieve the desired joint clustering. We consider structured covariance between consecutive time points and assess model performance through simulation studies. We apply the model to data on 24-hr ambulatory blood pressure monitoring and examine the relationship between diastolic blood pressure and pediatric obstructive sleep apnoea.
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STUDY OBJECTIVES: The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in children and the effect of adenotonsillectomy are unknown. We aimed to examine the difference in ventilatory control between children with OSA and those without OSA. We also examined the effect of adenotonsillectomy on parameters of ventilatory control. METHODS: Healthy children with OSA and matched controls were recruited. Polysomnography was performed before adenotonsillectomy in the OSA group and 6 months postoperatively. Controls underwent the same assessment at the two time points. Loop gain (LG), controller gain (CG), and plant gain (PG), which reflect the stability of ventilatory control, chemoreceptor sensitivity and the pulmonary control of blood gas in response to a change in ventilation, respectively, were estimated from polysomnographic tracings which included spontaneous sighs and tracings with tidal breathing. A linear mixed model was used to examine the changes of the ventilatory control parameters from baseline to 6 months. RESULTS: Ninety-nine children aged 7-13 were recruited to the study. Fifty-three with OSA and 46 controls. At baseline, compared with controls, children with OSA had higher PG and lower CG. LG did not differ between groups. Six months following adenotonsillectomy, there was a significant decrease in PG in the OSA group, while no change observed in the control group. CONCLUSIONS: The study demonstrates that the pulmonary control of blood gas homeostasis is disturbed in children with OSA and it normalizes following adenotonsillectomy.
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Adenoidectomia/tendências , Ventilação Pulmonar/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia/tendências , Adolescente , Gasometria/tendências , Criança , Feminino , Humanos , Masculino , Polissonografia/tendências , Apneia Obstrutiva do Sono/sangueRESUMO
OSA occurs in approximately 1% to 5% of children in the United States. Long-term cardiovascular risks associated with OSA in the adult population are well documented. Although changes in BP regulation occur in children with OSA, the pathways leading to chronic cardiovascular risks of OSA in children are less clear. Risk factors associated with cardiovascular disease in adult populations could carry the same future risk for children. It is imperative to determine whether known mechanisms of cardiovascular diseases in adults are like those that lead to pediatric disease. Early pathophysiologic changes may lead to a lifetime burden of cardiovascular disease and early mortality. With this perspective in mind, our review discusses pathways leading to cardiovascular pathology in children with OSA and provides a comprehensive overview of recent research findings related to cardiovascular sequelae in the pediatric population.
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Doenças Cardiovasculares/etiologia , Apneia Obstrutiva do Sono/complicações , Pressão Sanguínea , Criança , Humanos , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/fisiopatologiaRESUMO
BACKGROUND: Computational fluid dynamics simulations of respiratory airflow in the upper airway reveal clinically relevant information, including sites of local resistance, inhaled particle deposition, and the effect of pathological constrictions. Unlike previous simulations, which have been performed on rigid anatomical models from static medical imaging, this work utilises ciné imaging during respiration to create dynamic models and more closely represent airway physiology. METHODS: Airway movement maps were obtained from non-rigid image registration of fast-cine MRI and applied to high-spatial-resolution airway surface models. Breathing flowrates were recorded simultaneously with imaging. These data formed the boundary conditions for large eddy simulation computations of the airflow from exterior mask to bronchi. Simulations with rigid geometries were performed to demonstrate the resulting airflow differences between airflow simulations in rigid and dynamic airways. FINDINGS: In the analysed rapid breathing manoeuvre, incorporating airway movement significantly changed the findings of the CFD simulations. Peak resistance increased by 19.8% and occurred earlier in the breath. Overall pressure loss decreased by 19.2%, and the proportion of flow in the mouth increased by 13.0%. Airway wall motion was out-of-phase with the air pressure force, demonstrating the presence of neuromuscular motion. In total, the anatomy did 25.2% more work on the air than vice versa. INTERPRETATIONS: Realistic movement of the airway is incorporated into CFD simulations of airflow in the upper airway for the first time. This motion is vital to producing clinically relevant computational models of respiratory airflow and will allow novel analysis of dynamic conditions, such as sleep apnoea.