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2.
J Clin Sleep Med ; 20(2): 245-251, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37772702

RESUMO

STUDY OBJECTIVES: Behavioral insomnia of childhood (BIC) and obstructive sleep apnea (OSA) are highly prevalent conditions affecting 10%-20% and 1%-5% of children, respectively. Studies in adults and adolescents have suggested that comorbid insomnia and OSA may have distinct clinical characteristics. The association between the two conditions in the pediatric population has not been thoroughly investigated. This study aimed to examine the association between BIC and OSA in young children. METHODS: Children, 6 months to 10 years old, referred to a sleep specialist and polysomnography at the Hadassah Medical Center between 2018 and 2021 were included in this retrospective analysis. We excluded children with chromosomal and craniofacial abnormalities, posttonsillectomy, or neurological impairment. BIC diagnosis was extracted from the electronic health records in accordance with the International Classification of Sleep Disorders, third edition criteria. OSA was diagnosed by polysomnography (apnea-hypopnea index > 2 events/h). RESULTS: Of 312 children (age 4.42 ± 2.42 years), 126 (40.4%) were non-OSA non-BIC, 125 (40.1%) OSA non-BIC, 34 (10.9%) BIC non-OSA, and 27 (8.7%) comorbid insomnia and OSA. OSA and non-OSA children had a similar prevalence of BIC. Children in the comorbid insomnia and OSA group were significantly younger (2.22 ± 1.21 years). Younger age at polysomnography, premature birth, and increased periodic leg movements on polysomnography were independently associated with OSA in a multivariable analysis. Lower body mass index, regardless of OSA, was associated with BIC. CONCLUSIONS: Current findings do not support an association between behavioral insomnia of childhood and obstructive sleep apnea in children. Healthcare providers should consider each of these sleep disorders in children presenting with sleep difficulties since each has distinct diagnostic and therapeutic options. CITATION: Yelov L, Reiter J, Meira E Cruz M, Gileles-Hillel A. The association of obstructive sleep apnea and behavioral insomnia in children ages 10 and under. J Clin Sleep Med. 2024;20(2):245-251.


Assuntos
Apneia Obstrutiva do Sono , Distúrbios do Início e da Manutenção do Sono , Adulto , Adolescente , Humanos , Criança , Pré-Escolar , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudos Retrospectivos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Sono , Polissonografia
3.
J Clin Med ; 12(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38137681

RESUMO

Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are associated with sleep disturbances affecting quality of life (QOL) in both children and adults. However, little is known about the progression of these complaints over time, and the effect of CFTR modulator (CFTRm) therapies. Participants completed sleep quality (SDSC, PSQI) and quality of life questionnaires (PedQL, QOL-BE) as well as the Epworth sleepiness scale (ESS) at baseline and after 4 years. Medical records were reviewed for clinical data and correlations were sought between sleep, QOL, and clinical parameters. A total of 67 patients (33 pediatric), 37 pancreatic insufficient CF (CF-PI), 15 pancreatic sufficient CF (CF-PS), and 15 PCD patients, completed the study. In adults, global sleep quality decreased from 85.8% (76.2-90.5) to 80.9% (71.4-85.7); (p = 0.009). Analysis by disease cohort showed a significant deterioration only in the CF-PS group. In adults off CFTRm, sleep quality decreased from 85.7% (78.6-88.2) to 80.9% (71.4-87.3); (p = 0.021) and from 85.8% (76.2-92.9) to 76.2% (71.4-85.8); (p = 0.078) in people on CFTRm. Changes in sleep quality and changes in QOL over time were strongly associated with each other. In conclusion sleep quality deteriorates over time, correlates with QOL, and is driven primarily by adults and CF-PS patients. CFTRm has a possible effect on sleep initiation; however, results are mixed, and further long-term studies are required.

4.
J Cyst Fibros ; 22(6): 1062-1069, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37331863

RESUMO

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) significantly improves health outcomes in people with cystic fibrosis (pwCF) carrying one or two F508del mutations. According to in vitro assays performed in FRT cells, 178 additional mutations respond to ELX/TEZ/IVA. The N1303K mutation is not included in this list of mutations. Recent in vitro data suggested that ELX/TEZ/IVA increases N1303K-CFTR activity. Based on the in vitro response, eight patients commenced treatment with ELX/TEZ/IVA. METHODS: Two homozygotes; and six compound heterozygotes N1303K/nonsense or frameshift mutation pwCF were treated off label with ELX/TEZ/IVA. Clinical data before and 8 weeks after starting treatment were prospectively collected. The response to ELX/TEZ/IVA was assessed in intestinal organoids derived from 5 study patients and an additional patient carrying N1303K that is not receiving treatment. RESULTS: Compared to the values before commencing treatment, mean forced expiratory volume in 1 second increased by 18.4 percentage points and 26.5% relative to baseline, mean BMI increased by 0.79 Kg/m2, and mean lung clearance index decreased by 3.6 points and 22.2%. There was no significant change in sweat chloride. Nasal potential difference normalized in four patients and remained abnormal in three. Results in 3D intestinal organoids and 2D nasal epithelial cultures showed a response in CFTR channel activity. CONCLUSIONS: This report supports the previously reported in vitro data, performed in human nasal and bronchial epithelial cells and intestinal organoids, that pwCF who carry the N1303K mutation have a significant clinical benefit by ELX/TEZ/IVA treatment.


Assuntos
Fibrose Cística , Humanos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Mutação , Benzodioxóis/uso terapêutico , Aminofenóis/uso terapêutico , Agonistas dos Canais de Cloreto/uso terapêutico
5.
Pediatr Pulmonol ; 58(7): 1959-1966, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37083198

RESUMO

BACKGROUND: Less invasive forms of ventilation have evolved aiming to decrease bronchopulmonary dysplasia (BPD) morbidity. It is unclear whether changes in ventilation practices have been associated with improvements in respiratory outcomes. OBJECTIVE: To examine the changes in ventilation modes in preterm neonates between two periods during the last decade and their impact on BPD prevalence. METHODS: A retrospective chart review of very low birth weight infants and those born at less than 32 weeks gestation hospitalized during two periods: the years 2012-2013 and 2018-2019. The primary outcome was the prevalence of BPD. Study variables included the mode and duration of ventilation, duration of oxygen need, and perinatal clinical parameters. RESULTS: Four hundred eighty-one infants were enrolled. Between the two study periods, a significant increase was observed in invasive (33%-47%, p = 0.002), and noninvasive ventilation rates (44%-72%, p < 0.001). The average duration of noninvasive ventilation increased significantly (from 9.24 to 14.08 days, p = 0.016). The total duration of respiratory support remained unchanged. The overall prevalence of moderate and severe BPD at 36 weeks corrected age remained approximately 40% in preterm infants born at less than 28 weeks gestation. CONCLUSION: The increasing use of non-invasive ventilation was not accompanied by a reduction in the use of invasive ventilation, nor by a reduced prevalence of BPD. The high prevalence of BPD remains a significant problem in extreme prematurity. Other interventions, in addition to less aggressive ventilation, need to be explored.


Assuntos
Displasia Broncopulmonar , Recém-Nascido Prematuro , Lactente , Gravidez , Feminino , Recém-Nascido , Humanos , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/complicações , Prevalência , Estudos Retrospectivos , Recém-Nascido de muito Baixo Peso
6.
Pediatr Pulmonol ; 58(2): 500-506, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36314650

RESUMO

BACKGROUND: Pulmonary disease is the leading cause of morbidity and mortality in people with cystic fibrosis (pwCF). Several studies have shown no benefit for bronchoscopy and bronchoalveolar lavage (BAL) over sputum to obtain microbiological cultures, hence the role of bronchoscopy in pwCF is unclear. AIM: To analyze how bronchoscopy results affected clinical decision-making in pwCF and assess safety. METHODS: A retrospective analysis of all charts of pwCF from three CF centers in Israel, between the years 2008 and 2019. We collected BAL culture results as well as sputum cultures obtained within 1 month of the BAL sample. A meaningful yield was defined as a decision to start antibiotics, change the antibiotic regimen, hospitalize the patient for treatment, or the resolution of the problem that led to bronchoscopy (e.g., atelectasis or hemoptysis). RESULTS: During the study years, of the 428 consecutive patient charts screened, 72 patients had 154 bronchoscopies (2.14 bronchoscopies/patient). Forty-five percent of the bronchoscopies had a meaningful clinical yield. The finding of copious sputum on bronchoscopy was strongly associated with a change in treatment (OR: 5.25, 95%CI: 2.1-13.07, p < 0.001). BAL culture results were strongly associated with a meaningful yield, specifically isolation of Aspergillus spp. (p = 0.003), Haemophilus influenza (p = 0.001). Eight minor adverse events following bronchoscopy were recorded. CONCLUSIONS: In this multicenter retrospective analysis of bronchoscopy procedures from three CF centers, we have shown that a significant proportion of bronchoscopies led to a change in treatment, with no serious adverse events. Our findings suggest that bronchoscopy is a safe procedure that may assist in guiding treatment in some pwCF. Future studies should evaluate whether BAL-guided decision-making may also lead to a change in clinical outcomes in pwCF.


Assuntos
Broncoscopia , Fibrose Cística , Humanos , Fibrose Cística/tratamento farmacológico , Líquido da Lavagem Broncoalveolar/microbiologia , Estudos Retrospectivos , Lavagem Broncoalveolar , Antibacterianos/uso terapêutico
7.
J Clin Sleep Med ; 19(3): 591-594, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36546369

RESUMO

STUDY OBJECTIVES: Celiac disease (CD), an immune-mediated enteropathy, has a clinical spectrum that is remarkably wide and includes neuropsychiatric manifestations. While studies of adults have shown sleep disturbances, there is limited data in children. Our objectives were to assess the association between sleep disturbances and CD in children, and the effect of a gluten-free diet. METHODS: Parents of children 3-12 years old referred for endoscopy completed the Sleep Disturbance Scale for Children and modified Epworth Sleepiness Scale. Children with CD were compared with healthy controls and children with abdominal pain but no definitive findings on investigation. Parents of children with CD and abdominal pain were contacted after 6 months for follow-up. RESULTS: We enrolled 101 patients, mean age 6.5 (2.8), 51% female, 38 with CD, 18 abdominal pain, and 45 healthy. Sleep Disturbance Scale for Children scores were 37.4 (8.7), 41.3 (11.3), and 45.4 (13.7) in healthy controls, CD, and abdominal pain, respectively (P = .024). There was a significant difference in the disorders of arousal domain (P = .044). There were no significant differences on the modified Epworth Sleepiness Scale. A trend toward improvement in Sleep Disturbance Scale for Children scores was seen in children with CD presenting with abdominal pain after 6 months on a gluten-free diet (P = .07). CONCLUSIONS: In this first prospective study of sleep disturbances in children with CD, we show high rates of disturbed sleep compared with healthy children. Sleep disturbances did not improve on a gluten-free diet and may be driven by abdominal pain. CITATION: Reiter J, Abuelhija H, Slae M, et al. Sleep disorders in children with celiac disease: a prospective study. J Clin Sleep Med. 2023;19(3):591-594.


Assuntos
Doença Celíaca , Transtornos do Sono-Vigília , Humanos , Criança , Feminino , Pré-Escolar , Masculino , Doença Celíaca/psicologia , Estudos Prospectivos , Sonolência , Dor Abdominal
8.
Int J Mol Sci ; 23(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36555109

RESUMO

Obstructive sleep apnea (OSA) is a highly prevalent condition, characterized by intermittent hypoxia (IH), sleep disruption, and altered autonomic nervous system function. OSA has been independently associated with dyslipidemia, insulin resistance, and metabolic syndrome. Brown adipose tissue (BAT) has been suggested as a modulator of systemic glucose tolerance through adaptive thermogenesis. Reductions in BAT mass have been associated with obesity and metabolic syndrome. No studies have systematically characterized the effects of chronic IH on BAT. Thus, we aimed to delineate IH effects on BAT and concomitant metabolic changes. C57BL/6J 8-week-old male mice were randomly assigned to IH during sleep (alternating 90 s cycles of 6.5% FIO2 followed by 21% FIO2) or normoxia (room air, RA) for 10 weeks. Mice were subjected to glucose tolerance testing and 18F-FDG PET-MRI towards the end of the exposures followed by BAT tissues analyses for morphological and global transcriptomic changes. Animals exposed to IH were glucose intolerant despite lower total body weight and adiposity. BAT tissues in IH-exposed mice demonstrated characteristic changes associated with "browning"-smaller lipids, increased vascularity, and a trend towards higher protein levels of UCP1. Conversely, mitochondrial DNA content and protein levels of respiratory chain complex III were reduced. Pro-inflammatory macrophages were more abundant in IH-exposed BAT. Transcriptomic analysis revealed increases in fatty acid oxidation and oxidative stress pathways in IH-exposed BAT, along with a reduction in pathways related to myogenesis, hypoxia, and IL-4 anti-inflammatory response. Functionally, IH-exposed BAT demonstrated reduced absorption of glucose on PET scans and reduced phosphorylation of AKT in response to insulin. Current studies provide initial evidence for the presence of a maladaptive response of interscapular BAT in response to chronic IH mimicking OSA, resulting in a paradoxical divergence, namely, BAT browning but tissue-specific and systemic insulin resistance. We postulate that oxidative stress, mitochondrial dysfunction, and inflammation may underlie these dichotomous outcomes in BAT.


Assuntos
Resistência à Insulina , Síndrome Metabólica , Apneia Obstrutiva do Sono , Masculino , Animais , Camundongos , Resistência à Insulina/fisiologia , Síndrome Metabólica/complicações , Camundongos Endogâmicos C57BL , Hipóxia/metabolismo , Obesidade/complicações , Insulina , Glucose/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Tecido Adiposo Marrom/metabolismo , Sono
9.
Pediatr Pulmonol ; 57(11): 2774-2780, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35999051

RESUMO

BACKGROUND: Consistently abnormal glucose levels on oral glucose tolerance test (OGTT) are the most effective screening tool for cystic fibrosis-related diabetes (CFRD). However, some cystic fibrosis (CF) patients demonstrate abnormal glucose profiles not reaching levels required for CFRD diagnosis and are, therefore, left untreated. Since CFRD is associated with disease deterioration, early diagnosis and treatment are desirable. AIM: To explore the association between the area under the curve of glucose (G-AUC) obtained during a five-point 2-h standard OGTT and CF disease severity parameters. METHODS: All CF patients referred for an annual routine OGTT at the Hadassah CF Center between 2002 and 2018, were included. Disease severity parameters were correlated with the G-AUC. RESULTS: Two hundred forty-two OGTTs were performed in 81 patients (mean age 19.7 ± 9.0 years); 54% were normal, 14% showed impaired glucose tolerance (IGT), 5% had values in the indeterminate range (INDET), 11% had both IGT and INDET and 16% were diagnosed with CFRD. A gradual increase in mean G-AUC was observed among the groups. In multivariate regression models, G-AUC ≥ 295 mg h/dl was independently associated with an increased number of pulmonary exacerbations (PEx). Not all the patients having this value met the CFRD definition. CONCLUSION: Patients who do not fulfill the criteria for CFRD may have abnormal glucose metabolism identifiable by abnormally high G-AUC values, which may be associated with more PEx. The potential advantage of treating these patients with insulin and the subsequent reduction in PEx needs further investigation.


Assuntos
Fibrose Cística , Diabetes Mellitus , Intolerância à Glucose , Adolescente , Adulto , Glicemia/metabolismo , Criança , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Diabetes Mellitus/diagnóstico , Glucose , Intolerância à Glucose/complicações , Intolerância à Glucose/diagnóstico , Teste de Tolerância a Glucose , Humanos , Insulina , Adulto Jovem
10.
Proc Natl Acad Sci U S A ; 119(27): e2200047119, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35759656

RESUMO

Adequate pain management is one of the biggest challenges of the modern healthcare system. Physician perception of patient subjective pain, which is crucial to pain management, is susceptible to a host of potential biases. Here we explore the timing of physicians' work as a previously unrecognized source of systematic bias in pain management. We hypothesized that during night shifts, sleep deprivation, fatigue, and stress would reduce physicians' empathy for others' pain, leading to underprescription of analgesics for patient pain relief. In study 1, 67 resident physicians, either following a night shift or not, performed empathy for pain assessment tasks and simulated patient scenarios in laboratory conditions. As predicted, following a night shift, physicians showed reduced empathy for pain. In study 2, we explored this phenomenon in medical decisions in the field. We analyzed three emergency department datasets from Israel and the United States that included discharge notes of patients arriving with pain complaints during 2013 to 2020 (n = 13,482). Across all datasets, physicians were less likely to prescribe an analgesic during night shifts (compared to daytime shifts) and prescribed fewer analgesics than generally recommended by the World Health Organization. This effect remained significant after adjusting for patient, physician, type of complaint, and emergency department characteristics. Underprescription for pain during night shifts was particularly prominent for opioids. We conclude that night shift work is an important and previously unrecognized source of bias in pain management, likely stemming from impaired perception of pain. We consider the implications for hospitals and other organizations employing night shifts.


Assuntos
Analgésicos , Prescrições de Medicamentos , Empatia , Relações Médico-Paciente , Médicos , Jornada de Trabalho em Turnos , Analgésicos/uso terapêutico , Conjuntos de Dados como Assunto , Humanos , Israel , Dor/tratamento farmacológico , Médicos/psicologia , Jornada de Trabalho em Turnos/psicologia , Privação do Sono , Estados Unidos
11.
Pediatr Pulmonol ; 57(6): 1552-1554, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35322603

RESUMO

We report physiotherapy management of two patients with severe cystic fibrosis (CF) lung disease and upper limb deep vein thrombosis (DVT). These patients were admitted due to a pulmonary exacerbation. Following peripherally inserted central catheters, they were diagnosed with an upper limb DVT. Due to their underlying lung disease, physiotherapy was mandatory for improvement. However, the DVT and anticoagulation treatment raised concerns for pulmonary emboli and hemoptysis. A framework for physiotherapy management in these patients, using a set of precautions and restrictions to maintain airway clearance while minimizing the risk for pulmonary emboli and hemoptysis, was established. Using this set of instructions, the patients experienced no major adverse events while maintaining sufficient airway clearance to allow respiratory improvement. These precautions were continued until the upper limb DVTs were resolved. To our knowledge, there are currently no guidelines or expert opinions available. Therefore, this framework can help guide physiotherapy management.


Assuntos
Fibrose Cística , Embolia Pulmonar , Trombose Venosa , Fibrose Cística/complicações , Fibrose Cística/terapia , Hemoptise , Humanos , Modalidades de Fisioterapia , Fatores de Risco , Extremidade Superior , Trombose Venosa/complicações , Trombose Venosa/terapia
12.
13.
Pediatr Pulmonol ; 57(8): 1944-1951, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33974362

RESUMO

Cystic fibrosis (CF) is a chronic multisystem disease with manifestations from birth. It involves the entire respiratory system, with increased cough, and recurrent pulmonary infections, and it also leads to intestinal malabsorption, all of which can have an impact on sleep. In this review, we summarize the available literature on the various sleep disturbances in children with CF. Sleep quality and sleep efficiency are often impaired in children with CF. They may be accompanied by symptoms associated with sleep-disordered breathing (SDB), and objective findings, such as nocturnal hypoxemia. Importantly, a strong association has been shown between SDB and the severity of lung disease, and some studies have reported a similar association for sleep quality. Further research is needed to better characterize the association of sleep disturbances with respiratory outcomes and the impact of treatment of sleep disorders on pulmonary status in children with CF.


Assuntos
Fibrose Cística , Síndromes da Apneia do Sono , Transtornos do Sono-Vigília , Criança , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Humanos , Hipóxia/complicações , Sono , Síndromes da Apneia do Sono/complicações , Transtornos do Sono-Vigília/etiologia
14.
Eur J Pediatr ; 181(3): 973-978, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34652509

RESUMO

Familial Mediterranean fever is a common autoinflammatory disease characterized by periodic attacks of fever and serositis. There are few reports describing neurological symptoms in patients with FMF. The aim of this study was to systematically assess the neurologic and developmental involvement in pediatric patients with FMF. Between the years 2016 and 2019, parents of children with FMF were asked to complete a questionnaire regarding the presence of neurological and developmental symptoms in their children with and without FMF. Demographic data, clinical characteristics, and disease course of FMF patients were collected from the medical charts. Neurodevelopmental manifestations were compared between the children with FMF and their siblings. A total of 205 children were enrolled (11.6 ± 4.7 years of age): 111 children with FMF and 94 healthy siblings in the control group. Neurological morbidity was frequently reported in children with FMF: 44 (40%) had recurrent headaches, 31 (28%) ADHD symptoms, 27 (24%) learning disabilities, and 10 (9%) febrile convulsions. Headaches and febrile convulsions were significantly more prevalent in children with FMF as compared to their siblings (ps < 0.05). ADHD and learning disabilities were associated with poor adherence to colchicine treatment.Conslusions: The present study found an increased prevalence of ADHD, learning disabilities, headaches, and febrile seizures in children with FMF. The findings underscore the importance of addressing the neurodevelopmental domain in children with FMF. In addition, detection and treatment of ADHD and learning disabilities could improve adherence with therapy and control of the underlying disease. What is Known: • Familial Mediterranean fever (FMF) is the most common inherited auto-inflammatory disease, characterized by recurrent attacks of fever, serositis, and arthritis. • Some previous case reports also described rare neurological manifestations in children with FMF. What is New: • The study found an increased prevalence of headaches, febrile seizures, ADHD, and learning disabilities, in children with FMF. • The findings underscore the importance of addressing the neurological domain in this population, which could potentially improve adherence with therapy and control of the underlying disease.


Assuntos
Febre Familiar do Mediterrâneo , Adolescente , Criança , Colchicina/uso terapêutico , Progressão da Doença , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/epidemiologia , Febre/tratamento farmacológico , Humanos , Pirina , Irmãos , Inquéritos e Questionários
15.
Pediatr Pulmonol ; 57(8): 1851-1859, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33647191

RESUMO

Asthma and sleep disorders are both common in childhood, and often co-exist in the same child. Moreover, studies have shown that in many children the rate of one is influenced by the other. Sleep disorders can be classified into six different groups-insomnia, hypersomnia, parasomnia, movement disorders, circadian disorders, and sleep-related breathing disorders. Children with asthma often present with complaints of insomnia with poor sleep quality, difficulty falling asleep and sleep disruptions. These complains are often associated with asthma control. They may also complain of daytime sleepiness and have higher rates of parasomnias, such as night terrors and nocturnal enuresis when compared with their healthy peers. Whether movement and circadian disorders are also more prevalent in children with asthma is less clear. Finally, there is a complex bidirectional interaction between sleep-related breathing disorders and asthma: poor sleep and sleep disorders may worsen asthma, and asthma, particularly when it is poorly controlled, may impair sleep. In the current review we examine the association of each of the sleep disorders with asthma and review the common pathophysiological pathways. We hope to convince the reader that appropriate management of asthma must include inquiries into the patient's sleep, and vice versa.


Assuntos
Asma , Parassonias , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Asma/complicações , Asma/epidemiologia , Criança , Humanos , Parassonias/complicações , Parassonias/epidemiologia , Sono , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/etiologia , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia
16.
Cancers (Basel) ; 13(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638272

RESUMO

Obstructive sleep apnea (OSA) is associated with increased cutaneous melanoma incidence and adverse outcomes. Exosomes are secreted by most cells, and play a role in OSA-associated tumor progression and metastasis. We aimed to study the effects of plasma exosomes from OSA patients before and after adherent treatment with continuous positive airway pressure (CPAP) on melanoma cells lines, and also to identify exosomal miRNAs from melanoma cells exposed to intermittent hypoxia (IH) or normoxia. Plasma-derived exosomes were isolated from moderate-to-severe OSA patients before (V1) and after (V2) adherent CPAP treatment for one year. Exosomes were co-incubated with three3 different melanoma cell lines (CRL 1424; CRL 1619; CRL 1675) that are characterized by genotypes involving different mutations in BRAF, STK11, CDKN2A, and PTEN genes to assess the effect of exosomes on cell proliferation and migration, as well as on pAMK activity in the presence or absence of a chemical activator. Subsequently, CRL-1424 and CRL-1675 cells were exposed to intermittent hypoxia (IH) and normoxia, and exosomal miRNAs were identified followed by GO and KEG pathways and gene networks. The exosomes from these IH-exposed melanoma cells were also administered to THP1 macrophages to examine changes in M1 and M2 polarity markers. Plasma exosomes from V1 increased CRL-1424 melanoma cell proliferation and migration compared to V2, but not the other two cell lines. Exposure to CRL-1424 exosomes reduced pAMPK/tAMPK in V1 compared to V2, and treatment with AMPK activator reversed the effects. Unique exosomal miRNAs profiles were identified for CRL-1424 and CRL-1675 in IH compared to normoxia, with six miRNAs being regulated and several KEGG pathways were identified. Two M1 markers (CXCL10 and IL6) were significantly increased in monocytes when treated with exosomes from IH-exposed CRL-1424 and CRL-1625 cells. Our findings suggest that exosomes from untreated OSA patients increase CRL-1424 melanoma malignant properties, an effect that is not observed in two other melanoma cell lines. Exosomal cargo from CRL-1424 cells showed a unique miRNA signature compared to CRL-1675 cells after IH exposures, suggesting that melanoma cells are differentially susceptible to IH, even if they retain similar effects on immune cell polarity. It is postulated that mutations in STK-11 gene encoding for the serine/threonine kinase family that acts as a tumor suppressor may underlie susceptibility to IH-induced metabolic dysfunction, as illustrated by CRL-1424 cells.

17.
EMBO Rep ; 22(12): e52058, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34693619

RESUMO

Patient-derived human organoids can be used to model a variety of diseases. Recently, we described conditions for long-term expansion of human airway organoids (AOs) directly from healthy individuals and patients. Here, we first optimize differentiation of AOs towards ciliated cells. After differentiation of the AOs towards ciliated cells, these can be studied for weeks. When returned to expansion conditions, the organoids readily resume their growth. We apply this condition to AOs established from nasal inferior turbinate brush samples of patients suffering from primary ciliary dyskinesia (PCD), a pulmonary disease caused by dysfunction of the motile cilia in the airways. Patient-specific differences in ciliary beating are observed and are in agreement with the patients' genetic mutations. More detailed organoid ciliary phenotypes can thus be documented in addition to the standard diagnostic procedure. Additionally, using genetic editing tools, we show that a patient-specific mutation can be repaired. This study demonstrates the utility of organoid technology for investigating hereditary airway diseases such as PCD.


Assuntos
Transtornos da Motilidade Ciliar , Organoides , Cílios , Transtornos da Motilidade Ciliar/genética , Humanos , Mutação , Fenótipo
19.
Isr J Health Policy Res ; 10(1): 48, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407864

RESUMO

Among the challenges presented by the SARS-CoV2 pandemic are those related to balancing societal priorities with averting threats to population health. In this exceptional context a group of Israeli physicians and public health scholars (multidisciplinary academic group on children and coronavirus [MACC]) coalesced, examining the role of children in viral transmission and assessing the necessity and consequences of restricted in-class education. Combining critical appraisal and analytical skills with public health experience, MACC advocated for safe and monitored school re-opening, stressing the importance of education as a determinant of health, continuously weighing this stance against evolving COVID-19-risk data. MACC's activities included offering research-based advice to government agencies including Ministries of Health, Finance, and Education. In a setting where government bodies were faced with providing practical solutions to both decreasing disease transmission and maintaining society's vital activities, and various advisors presented decision-makers with disparate views, MACC contributed epidemiological, clinical and health policy expertise to the debate regarding school closure as a pandemic control measure, and adaptations required for safe re-opening. In this paper, we describe the evolution, activities, policy inputs and media profile of MACC, and discuss the role of academics in advocacy and activism in the midst of an unprecedented public health crisis. A general lesson learned is that academics, based on the rigor of their scientific work and their perceived objectivity, can and should be mobilized to pursue and promote policies based on shared societal values as well as empiric data, even when considerable uncertainty exists about the appropriate course of action. Mechanisms should be in place to open channels to multidisciplinary academic groups and bring their input to bear on decision-making.


Assuntos
COVID-19/prevenção & controle , Comunicação Interdisciplinar , Pandemias/prevenção & controle , Instituições Acadêmicas/organização & administração , COVID-19/epidemiologia , COVID-19/transmissão , Criança , Humanos , Israel/epidemiologia , Médicos/psicologia , Saúde Pública
20.
Pediatr Pulmonol ; 56(7): 2265-2273, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33887116

RESUMO

BACKGROUND: A parent survey was conducted to assess the sleep habits of children residing in various countries before and during the SARS-CoV-2 pandemic. It was hypothesized that lockdown would be associated with increased sleep duration. METHODS: Outcomes were changes in bedtime, wake time, and sleep duration in the pandemic compared to before. Logistic regression was applied to evaluate the effects of age and covariates on outcomes. RESULTS: A total of 845 questionnaires completed from May 1 to June 10, 2020 were analyzed (45.8% female; age 3-17 years). During the pandemic, 23.1% of preschoolers, 46.2% of school-age children, and 89.8% of adolescents were going to bed after 10 p.m. on weekdays compared to 7.1%, 9.4%, and 57.1% respectively before the pandemic, with these proportions being higher on weekends. Likewise, 42.5% of preschoolers, 61.3% of school-age children, and 81.2% of adolescents were waking after 8 a.m. on weekdays (11.6%, 4.9%, and 10.3%, before) with these proportions being greater on weekends. Sleep duration did not change in 43% of participants on weekdays and in 46.2% on weekends. The 14-17 years group had fourfold increased odds for longer sleep duration on weekdays (p < .01), and children aged 6-13 years had twofold increased odds for longer sleep duration on weekends relative to the 3-5 years age group (p = .01). CONCLUSIONS: Although lockdown was associated with later bedtime and wake time, this shift did not alter sleep duration in more than 40% of children. Yet, compared to preschoolers, high school-aged children were more likely to sleep more on weekdays and primary school children on weekends.


Assuntos
COVID-19/epidemiologia , Quarentena , Sono , Adolescente , COVID-19/virologia , Criança , Pré-Escolar , Controle de Doenças Transmissíveis , Feminino , Humanos , Modelos Logísticos , Masculino , Pais , SARS-CoV-2/isolamento & purificação , Instituições Acadêmicas , Inquéritos e Questionários
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