There is no direct evidence for the exact cilia-inhibitory effects of opioids, which are generally used to achieve general anesthesia in combination with other anesthetic drugs. These are the ...reasons, why we analysed direct concentration-dependent or systemic effects of anesthetics (propofol, sufentanil, and midazolam) at a recommended doses administered individually or simultaneously on the tracheal ciliary beat frequency (CBF) in in vitro experimental conditions. Brush biopsy technique was used to remove the tracheal epithelia of guinea pigs for microscopy evaluation of ciliary beating monitored by high-speed video camera and analysed by Ciliary Analysis software. The tracheal CBF was significantly lower in the presence of sufentanil (10−8 mol/L) than in the control group; similarly for midazolam-sufentanil (10−8 - 10−5 mol/L), as well as for midazolam-propofol (10−5 and 10−3 mol/L) combinations. The fact that concurrent administration of benzodiazepine significantly increased the risk of sufentanil-induced cilia-inhibition was pharmacologically confirmed using GABAA receptor antagonist, bicuculline methiodide. The benefit of propofol on the potent cilia-inhibitory effect achieved by benzodiazepine–opioid combination was non-significant. We highlight the pharmacodynamics interaction between anesthetic drugs mediated via GABAA receptor with negative impact on the CBF in a respiratory epithelium under experimental condition rather than the effect of individual anesthetic.
The mutations in the
(retinitis pigmentosa GTPase regulator) gene are the most common cause of X-linked retinitis pigmentosa (XLRP), a rare genetic disorder affecting the photoreceptor cells in the ...retina. Several reported cases identified this gene as a genetic link between retinitis pigmentosa (RP) and primary ciliary dyskinesia (PCD), characterised by impaired ciliary function predominantly in the respiratory tract. Since different mutations in the same gene can result in various clinical manifestations, it is important to describe a correlation between the gene variant and the observed phenotype.
Two young brothers from a non-consanguineous Slovak family with diagnosed retinal dystrophy and recurrent respiratory infections were examined. Suspected PCD was diagnosed based on a PICADAR questionnaire, nasal nitric oxide analysis, transmission electron microscopy, high-speed video microscopy analysis, and genetic testing.
We identified a novel frameshift
mutation NM_001034853: c.309_310insA, p.Glu104Argfs*12, resulting in a complex X-linked phenotype combining PCD and RP. In our patients, this mutation was associated with normal ultrastructure of respiratory cilia, reduced ciliary epithelium, more aciliary respiratory epithelium, shorter cilia, and uncoordinated beating with a frequency at a lower limit of normal beating, explaining the clinical manifestation of PCD in our patients.
The identified novel pathogenic mutation in the
gene expands the spectrum of genetic variants associated with the X-linked PCD phenotype overlapping with RP, highlighting the diversity of mutations contributing to the disorder. The described genotype-phenotype correlation can be useful in clinical practice to recognise a broader spectrum of PCD phenotypes as well as for future research focused on the genetic basis of PCD, gene interactions, the pathways implicated in PCD pathogenesis, and the role of RPGR protein for the proper functioning of cilia in various tissues throughout the body.
Background: The aim of this study was to clarify changes of transnasal airflow resulting from adenoidectomy and to assess the effect of surgery depending on adenoid hypertrophy (AH) obstruction ...grade. Materials and Methods: Altogether fifty children having symptoms of nasal obstruction and adenoids were submitted to a rhinomanometric assessment before and after adenoidectomy. At the same time, using the nasal fiberoptic endoscopy, the grade of AH obstruction was determined, according to which the children were divided into four classes. We assessed the change of total transnasal inspiratory airflow and total nasal resistance due to adenoidectomy. Results: Values of transnasal airflow and nasal resistance measured in the study group of fifty children were preoperatively 262 mL/s and 0.565 kPa/L/s; postoperatively 288 mL/s and 0.52 kPa/L/s. We have noticed statistically significant increase of the airflow (P = 0.015); however, decrease of the resistance (P = 0.054) was not significant. In the group of children suffering from the 1st to 2nd grade (29 children) preoperatively measured values presented 280 mL/s and 0.52 kPa/L/s; postoperatively, 276 mL/s and 0.54 kPa/L/s; change of the airflow (P = 0.634) and resistance (P = 0.829) was not significant. In the study group having the 3rd and 4th grade (21 children), the values indicated preoperatively 240 mL/s and 0.62 kPa/L/s; postoperatively, 340 mL/s and 0.44 kPa/L/s; there were significant airflow increase (P = 0.012) and resistance decrease (P = 0.033). Conclusions: Adenoidectomy significantly increased the airflow; however, we observed the different effect in the group of children with the 1st and 2nd grade compared to the group with the 3rd and 4th grade. A significant increase of the airflow and decrease of the resistance were present only in the group with the 3rd and 4th grade; therefore, the significant reduction of nasal obstruction symptoms might be expected only in this group of patients.
The study assessed the presence of sleep abnormalities in children who had recently been diagnosed with celiac disease (CD) and not started a gluten free diet (GFD). The children's polysomnographic ...profiles were also characterized and further compared with healthy children of the same age.
This prospective cross-sectional study involved 46 pediatric subjects (aged 1-19 years) who had recently been diagnosed with CD and not started a GFD. The control group consisted of 32 healthy children (aged 2-17 years). All children underwent anthropometric measurement, laboratory testing and standard overnight observation with in-laboratory video-PSG. The study and control group were divided into subgroups according to the subjects' median ages (8.1 years): celiac children aged less than 8.1 years (n = 23) and more than 8.1 years (n = 23), healthy children less aged than 8.1 years (n = 16) and more than 8.1 years (n = 16).
No significant differences in the basic demographic and anthropometric parameters between the celiac and control group were observed. Significantly prolonged sleep latency (SOL) was evident in the celiac subjects (21.89 ± 20.77 min. vs. 10.99 ± 7.94 min, p = 0.02), with a probability of prolonged SOL of 4.23-fold greater (OR = 4.23; 95 % CI 1.1-16.22) than the healthy controls, especially in the subgroup of older celiac patients. No significant differences in the sleep period time (SPT), total sleep time (TST), wake during sleep (WASO), sleep efficiency (SE) and sleep stage distribution and cyclization were found. The respiratory rates during sleep indicated a significantly greater incidence of the central apnea-hypopnea index (CAHI) (0.54 ± 0.78 vs. 0.18 ± 0.24, p = 0.03) with a 3.16-fold greater probability of pathological CAHI (OR = 3.16; 95 % CI 1.02-9.77) than the control group. An increased incidence of CSA in the subgroup of younger celiac patients compared to younger healthy controls was especially evident.
The findings of our study suggest a difference in sleep architecture and an increased incidence of CSA in children with untreated CD, but additional research is required to verify the results.
Bronchial asthma is a heterogeneous respiratory condition characterized by chronic airway inflammation, airway hyperresponsiveness and airway structural changes (known as remodeling). The clinical ...symptoms can be evoked by (non)specific triggers, and their intensity varies over time. In the past, treatment was mainly focusing on symptoms’ alleviation; in contrast modern treatment strategies target the underlying inflammation, even during asymptomatic periods. Components of airway remodeling include epithelial cell shedding and dysfunction, goblet cell hyperplasia, subepithelial matrix protein deposition, fibrosis, neoangiogenesis, airway smooth muscle cell hypertrophy and hyperplasia. Among the other important, and frequently forgotten aspects of airway remodeling, also loss of epithelial barrier integrity, immune defects in anti-infectious defence and mucociliary clearance (MCC) dysfunction should be pointed out. Mucociliary clearance represents one of the most important defence airway mechanisms. Several studied in asthmatics demonstrated various dysfunction in MCC – e.g., ciliated cells displaying intracellular disorientation, abnormal cilia and cytoplasmic blebs. Moreover, excessive mucus production and persistent cough are one of the well-recognized features of severe asthma and are also associated with defects in MCC. Damaged airway epithelium and impaired function of the ciliary cells leads to MCC dysfunction resulting in higher susceptibility to infection and inflammation. Therefore, new strategies aimed on restoring the remodeling changes and MCC dysfunction could present a new therapeutic approach for the management of asthma and other chronic respiratory diseases.
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•Bronchial asthma is a complex multi-facetted disease which develops as a consequence of the interplay between genes and factors or triggers from the external and internal environment.•Immune defects, epithelial barrier dysfunction and mucociliary clearance dysfunction are important features of bronchial asthma and should be considered in the context of airway remodeling.•So far, only selected molecules used in asthma treatment showed some capacity to affect and modify remodeling process, but more studies are needed.•New therapeutic options for allergies and bronchial asthma should be aimed at the restoration of the mucociliary clearance and epithelial barrier function.•Therapeutic modulation of associated immune deficiencies could decrease the susceptibility of asthma patients to respiratory infections and thus help to prevent exacerbations.
In children, the effect of the common phenotype of obstructive sleep apnea (OSA) on sleep architecture is not adequately documented. The aim of this study was to evaluate sleep architecture in a ...pediatric population with the common phenotype of OSA.
The prospective cross-sectional study included 116 children in the age range of 3 to 8 years with suspected OSA and 51 healthy children. All children underwent standard overnight in-laboratory video polysomnography. Patients with obstructive apnea-hypopnea index ≥ 1, adenotonsillar hypertrophy, a long face, narrow palate or minor malocclusions, and no obesity were defined as a common phenotype. Polysomnographic parameters of sleep architecture and sleep clinical record were statistically analyzed according to OSA and its severity.
In total, 94 pediatric patients (59.60% male) received the diagnosis of the common phenotype of OSA (mean age of 5.25 ± 1.39 years). A lower percentage of stage N3 sleep (27.70 ± 3.76% versus 31.02 ± 4.23%;
< .05), a greater percentage of stage N1 sleep (8.40 ± 3.98% versus 2.68 ± 3.02%,
< .01), reduced deep sleep efficiency (46.01 ± 4.98% versus 50.25 ± 3.72%;
< .05) and longer sleep latency (18.40 ± 8.48 minutes versus 9.90 ± 11.55 minutes,
< .01) were found in children with the common phenotype of OSA compared with healthy controls. No significant differences were found in total sleep time, sleep efficiency, and percentage of stage R sleep and stage N2 sleep between groups and in sleep stage distribution and cyclization.
These findings suggest that the most common phenotype of pediatric OSA has a negative effect on the structure of sleep, but other clinical studies are needed to confirm this result.
An increase in the incidence of narcolepsy after the pandemic influenza with the H1N1 vaccination in 2009 resulted in an interest in narcolepsy epidemiology. The aim of the study was to examine the ...incidence and prevalence rates of narcolepsy and to describe the associated characteristics in Slovakia.
Epidemiology data were calculated for each year from 2000 to 2017 based on records found in specialized centres. In sum, 61 narcoleptic patients were diagnosed, of which 51 (84%) had narcolepsy type 1 (NT1). Clinical data and results of polysomnography (PSG), Human Leukocyte Antigen (HLA)-typing, hypocretin (HCRT)-1 levels and body mass index (BMI) were summarised and evaluated for NT1 and narcolepsy type2 (NT2). Later, 244 sex and age matched controls were chosen to evaluate the comorbid diagnoses.
The prevalence of narcolepsy in 2017 in Slovakia was 10.47 (CI 95% 8.26–14) cases/million inhabitants, and the mean incidence rate (2000–2017) was 0.57 (CI 95% 0.4–0.74) cases/million inhabitants.
Narcoleptic patients were comorbid with arterial hypertension (17%), ischemic heart disease (8%), dyslipidaemia (18%), diabetes mellitus type 2 (10%), cardiac arrhythmia/atrial fibrillation (5%), autoimmune disorders (20%), allergy (11%), malignancy (3%), headache (15%) and mental disorders (20%). Patients with narcolepsy showed double the excess prevalence in mental disorders (OR 2.15, p < 0.05), and dyslipidaemia (OR 2.22, p < 0.05). The presence of autoimmune disorders and allergy showed a mild increase in the narcolepsy group (OR 1.46, resp. 1.63). Hashimoto thyroiditis (HT) was the most frequent autoimmune disorder.
Narcolepsy is a rare disorder in Slovakia. From the phenotype, genetic characteristics and comorbidities the disorder does not vary from other European countries.
•Narcolepsy is a rare disorder in Slovakia.•Its phenotype, genetic features and comorbidity do not vary from other European countries.•The comorbidity with the greatest excess prevalence in the narcolepsy cohort is a mental disorder.•Two of three adolescent patients experienced psychotic episode at the onset of narcolepsy.
Background
Children with adenoid hypertrophy (AH) have impaired respiratory system defense mechanisms, such as mucociliary clearance. We hypothesized that AH negatively affects one of the most ...important aspects of mucociliary clearance—ciliary beat frequency (CBF) and that adenoidectomy could potentially restore this essential defence mechanism of the airways. This study evaluated the influence of AH and endoscopic adenoidectomy on the CBF of the nasal respiratory epithelium in children.
Methods
This prospective study included 64 children with confirmed AH aged 3 to 18 years and 43 age‐ and sex‐matched healthy controls. Nasal CBF was analyzed using a digital high‐speed video microscope and the software application Ciliary Analysis (NI LabVIEW). The preoperative adenoid size was assessed according to Cassano. Clinical symptoms of chronic rhinosinusitis were evaluated using the SNOT‐20 questionnaire.
Results
Children with AH had a median CBF of 5.35 ± 1.06 Hz. Six months after surgery, the median CBF was significantly higher (6.48 ± 0.88 Hz; P < .001) and reached the values of healthy children (6.37 ± 0.71 Hz; P = .512). The size of the adenoid tissue did not correlate with the CBF. No influence of age or gender on the CBF was found. After adenoidectomy, a significant reduction of the mean total SNOT‐20 score was recorded (P < .01).
Conclusion
Children with clinically symptomatic AH have impaired mucociliary clearance due to decreased nasal CBF. Removal of hypertrophic adenoid tissue normalizes the CBF and reduces the presence of clinical symptoms of rhinosinusitis.
Narcolepsy type 1 (NT1), a central disorder of hypersomnolence, is associated with mood, anxiety or hyperactivity mental disorders. Association with psychotic episode or schizophrenia is rare and ...could be the source of diagnostic and therapeutic difficulties. Their frequency in the national narcolepsy database has not been systematically studied. The aim of the presented study was to calculate the frequency of NT1 patients diagnosed with psychosis and/or schizophrenia, to identify clinical characteristics of these cases, and to look for narcoleptic and psychotic symptoms during re-evaluation years later. We identified three (4%) cases diagnosed with a psychotic episode in the course of NT1. They were diagnosed with NT1 by age ≤18 years. In the re-evaluation (mean follow-up 9.8 years), we identified one case with a dual diagnosis of NT1 and schizophrenia; two cases were diagnosed with a solitary psychotic episode in the course of NT1. NT1 patients diagnosed in the age ≤18 years are at higher risk of psychotic episode, and this may be related to higher vulnerability during the ongoing neurodevelopmental period. Comorbid schizophrenia with NT1 in the Slovakian Narcolepsy Database was within the prevalence expected in the general population. The solitary psychotic episode in the course of NT1 did not reduce the possibility of subsequent symptomatic treatment afterwards.
Background and objective
Cryotherapy in interventional bronchoscopy is a new treatment modality, which has recently been made available for the paediatric airway. Lack of experience and safety ...concerns have led to hesitant adaptation. The aim of this study was to assess indications, success rates and complications of airway cryotherapy in children.
Methods
Bronchoscopists from medical centre performing cryotherapy in patients between 0 and 18 years were invited to participate in a prospective study based on an online questionnaire. Patient and participant data were collected between June 2020 and June 2021.
Results
A total of 69 cryotherapy procedures were performed in 57 patients a for three main indications: Biopsy (30), restoration of airway patency (23) and foreign body aspiration (16). The overall success rate was 93%, the remaining 7% were performed for foreign body removal and required a switch of technique. Restoration of airway patency was successfully applied in various pathologies, including mucus plugs, bronchial casts and post traumatic stenosis. The diagnostic yield of transbronchial biopsies was 96%. No severe complications were encountered; one pneumothorax following a cryobiopsy required a chest drain for 48 h. No child was admitted to intensive care or died from a procedural complication.
Conclusion
In this largest paediatric case collection to date, cryotherapy was safe and carried a high success rate. Cryobiopsy compares favourably to the widely used forceps biopsy and could replace it in the future. Paediatric bronchoscopists are encouraged to add cryotherapy to their armamentarium of airway interventions.
This largest case collection of cryotherapy procedures in the paediatric airway to date demonstrates that cryotherapy can be safely and successfully applied for cryobiopsy, restoration of airway patency and foreign body removal. Paediatric interventional bronchoscopists are encouraged to add cryotherapy to their armamentarium of airway interventions in the paediatric airway.
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