Celiac disease in children - diagnosis in light of the current 2020 ESPGHAN guidelines

Celiac disease is a chronic immune disorder of the small intestine that is triggered by the consumption of gluten in genetically predisposed individuals. The disease is difficult to diagnose and treat, and its incidence is increasing. It can have different symptoms and clinical manifestations in individuals. Diagnosis is usually based on the presence of specific antibodies and histopathological examination of biopsy specimens from the small intestine. The only effective treatment is a gluten-free diet for life. Diagnosis of celiac disease in children is mainly based on the presence of specific an- tibodies in the blood, such as antibodies to tissue transglutaminase (tTG), antibodies to endomysium (EMA) or deamidated gliadin peptides (DGP). In addition, genetic testing is also used in diagnosis to detect the presence of HLA DQ2 or DQ8 genes, which are often present in people with celiac disease. The final diagnosis of celiac disease is based on a combination of the results of these tests and the presence of characteristic lesions in the small intestine, which are detected during endoscopy and small bowel biopsy

The role of microRNAs in pathophysiology and diagnostics of metabolic complications in obstructive sleep apnea patients

Obstructive sleep apnea (OSA) is one of the most common sleep disorders, which is characterized by recurrent apneas and/or hypopneas occurring during sleep due to upper airway obstruction. Among a variety of health consequences, OSA patients are particularly susceptible to developing metabolic complications, such as metabolic syndrome and diabetes mellitus type 2. MicroRNAs (miRNAs) as epigenetic modulators are promising particles in both understanding the pathophysiology of OSA and the prediction of OSA complications. This review describes the role of miRNAs in the development of OSA-associated metabolic complications. Moreover, it summarizes the usefulness of miRNAs as biomarkers in predicting the aforementioned OSA complications

The Role of Brain-Derived Neurotrophic Factor in Immune-Related Diseases: A Narrative Review

Brain-derived neurotrophic factor (BDNF) is a neurotrophin regulating synaptic plasticity, neuronal excitability, and nociception. It seems to be one of the key molecules in interactions between the central nervous system and immune-related diseases, i.e., diseases with an inflammatory background of unknown etiology, such as inflammatory bowel diseases or rheumatoid arthritis. Studies show that BDNF levels might change in the tissues and serum of patients during the course of these conditions, e.g., affecting cell survival and modulating pain severity and signaling pathways involving different neurotransmitters. Immune-related conditions often feature psychiatric comorbidities, such as sleep disorders (e.g., insomnia) and symptoms of depression/anxiety; BDNF may be related as well to them as it seems to exert an influence on sleep structure; studies also show that patients with psychiatric disorders have decreased BDNF levels, which increase after treatment. BDNF also has a vital role in nociception, particularly in chronic pain, hyperalgesia, and allodynia, participating in the formation of central hypersensitization. In this review, we summarize the current knowledge on BDNF’s function in immune-related diseases, sleep, and pain. We also discuss how BDNF is affected by treatment and what consequences these changes might have beyond the nervous system

The Association between Idiopathic Pulmonary Fibrosis and Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis

The prevalence of obstructive sleep apnea (OSA) has greatly increased in recent years. Recent data suggest that severe and moderate forms of OSA affect between 6 and 17% of adults in the general population. Many papers are reporting the significantly increased prevalence of OSA in patients suffering from fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Therefore, we performed a systematic review and meta-analysis regarding the dependency between IPF and OSA. Due to the lack of papers focusing on IPF among OSA patients, we focused on the prevalence of OSA among IPF patients. In the search strategy, a total of 684 abstracts were identified, 496 after the removal of duplicates. After the screening of titles and abstracts, 31 studies were qualified for further full-text analysis for eligibility criteria. The final analysis was performed on 614 IPF patients from 18 studies, which met inclusion criteria. There were 469 (76.38%) IPF patients with OSA and 145 (23.62%) without. The mean age varied from 60.9 ± 8.1 up to 70.3 ± 7.9. The obtained prevalence was 76.4 (95% CI: 72.9–79.7) and 75.7 (95% CI: 70.1–80.9) for fixed and random effects, respectively. The median prevalence of OSA among non-IPF patients for all the ethnics groups included in this study was 16,4% (IQR: 3.4%–26.8%). The study provides strong evidence for the increased prevalence of OSA in IPF patients when comparing with the general OSA prevalence

Adolescent Congenital Central Hypoventilation Syndrome: An Easily Overlooked Diagnosis

Congenital central hypoventilation syndrome (CCHS), also known as Ondine’s curse, is a rare, potentially fatal genetic disease, manifesting as a lack of respiratory drive. Most diagnoses are made in pediatric patients, however late-onset cases have been rarely reported. Due to the milder symptoms at presentation that might easily go overlooked, these late-onset cases can result in serious health consequences later in life. Here, we present a case report of late-onset CCHS in an adolescent female patient. In this review we summarize the current knowledge about symptoms, as well as clinical management of CCHS, and describe in detail the molecular mechanism responsible for this disorder

REM-OSA as a Tool to Understand Both the Architecture of Sleep and Pathogenesis of Sleep Apnea—Literature Review

Sleep is a complex physiological state, which can be divided into the non-rapid eye movement (NREM) phase and the REM phase. Both have some unique features and functions. This difference is best visible in electroencephalography recordings, respiratory system activity, arousals, autonomic nervous system activity, or metabolism. Obstructive sleep apnea (OSA) is a common condition characterized by recurrent episodes of pauses in breathing during sleep caused by blockage of the upper airways. This common condition has multifactorial ethiopathogenesis (e.g., anatomical predisposition, sex, obesity, and age). Within this heterogenous syndrome, some distinctive phenotypes sharing similar clinical features can be recognized, one of them being REM sleep predominant OSA (REM-OSA). The aim of this review was to describe the pathomechanism of REM-OSA phenotype, its specific clinical presentation, and its consequences. Available data suggest that in this group of patients, the severity of specific cardiovascular and metabolic complications is increased. Due to the impact of apneas and hypopneas predominance during REM sleep, patients are more prone to develop hypertension or glucose metabolism impairment. Additionally, due to the specific function of REM sleep, which is predominantly fragmented in the REM-OSA, this group presents with decreased neurocognitive performance, reflected in memory deterioration, and mood changes including depression. REM-OSA clinical diagnosis and treatment can alleviate these outcomes, surpassing the traditional treatment and focusing on a more personalized approach, such as using longer therapy of continuous positive airway pressure or oral appliance use

Serum Levels of Chemerin in Patients with Inflammatory Bowel Disease as an Indicator of Anti-TNF Treatment Efficacy

Chemerin belongs to the adipokines—proteins secreted by white adipose tissue. It plays an important role in angiogenesis and metabolism and its levels correlate with inflammation severity in many clinical states. Circulating chemerin levels in IBD are only rarely evaluated, with inconsistent results. The possible impact of anti-TNF therapy treatment in IBD on chemerin levels has not been addressed. The study aim was to evaluate the serum levels of chemerin in patients with inflammatory bowel disease (IBD), depending on disease severity as well as anti-TNF treatment. Serum chemerin was measured with ELISA in 77 patients with IBD as well as in 42 healthy controls (HCs). Twenty-six participants who underwent anti-TNF therapy were re-examined after 14 weeks. Overall, IBD patients had significantly higher serum chemerin levels than HCs. In patients with IBD exacerbation, chemerin levels were significantly higher compared to the remission group. Serum chemerin levels were significantly higher in UC patients compared to CD. Chemerin correlated with the severity of CD, but not with UC. Serum levels of chemerin decreased significantly after 14 weeks of anti-TNF treatment. Chemerin correlated with the clinical severity of IBD, and its levels decreased after anti-TNF treatment, which suggests its relationship with disease activity. It may be assumed that chemerin levels may possibly be useful for anti-TNF clinical course and treatment monitoring

Disruption of Circadian Rhythm Genes in Obstructive Sleep Apnea Patients—Possible Mechanisms Involved and Clinical Implication

Obstructive sleep apnea (OSA) is a chronic condition characterized by recurrent pauses in breathing caused by the collapse of the upper airways, which results in intermittent hypoxia and arousals during the night. The disorder is associated with a vast number of comorbidities affecting different systems, including cardiovascular, metabolic, psychiatric, and neurological complications. Due to abnormal sleep architecture, OSA patients are at high risk of circadian clock disruption, as has been reported in several recent studies. The circadian clock affects almost all daily behavioral patterns, as well as a plethora of physiological processes, and might be one of the key factors contributing to OSA complications. An intricate interaction between the circadian clock and hypoxia may further affect these processes, which has a strong foundation on the molecular level. Recent studies revealed an interaction between hypoxia-inducible factor 1 (HIF-1), a key regulator of oxygen metabolism, and elements of circadian clocks. This relationship has a strong base in the structure of involved elements, as HIF-1 as well as PER, CLOCK, and BMAL, belong to the same Per-Arnt-Sim domain family. Therefore, this review summarizes the available knowledge on the molecular mechanism of circadian clock disruption and its influence on the development and progression of OSA comorbidities

“Leaky Gut” as a Keystone of the Connection between Depression and Obstructive Sleep Apnea Syndrome? A Rationale and Study Design

Obstructive sleep apnea (OSA) and depression are highly comorbid. Immune alterations, oxidative stress or microbiota dysfunction have been proposed as some mechanisms underlying this association. The aim of the proposed study is to assess the severity and profile of OSA and depressive symptoms in the context of serum microbiota metabolites, biomarkers of intestinal permeability, inflammation and oxidative stress in adult patients diagnosed with OSA syndrome. The study population consists of 200 subjects. An apnoea-hypopnoea index ≥ 5/hour is used for the diagnosis. Depressive symptoms are assessed with Beck Depression Inventory. Measured serum markers are: tumour necrosis factor–alpha and interleukin-6 for inflammation, total antioxidant capacity and malondialdehyde concentration for oxidative stress, zonulin, calprotectin, lipopolisaccharide-binding protein and intestinal fatty acids-binding protein for intestinal permeability. All of the above will be measured by enzyme-linked immunosorbent assay (ELISA). Associations between clinical symptoms profile and severity and the above markers levels will be tested. It would be valuable to seek for overlap indicators of depression and OSA to create this endophenotype possible biomarkers and form new prophylactic or therapeutic methods. The results may be useful to establish a subpopulation of patients sensitive to microbiota therapeutic interventions (probiotics, prebiotics, and microbiota transplantation)

Potential Role of Sleep Deficiency in Inducing Immune Dysfunction

Sleep deficiency and insomnia deteriorate the quality of patients’ lives, yet the exact influence of these factors on the immune system has only begun to gain interest in recent years. Growing evidence shows that insomnia is a risk factor for numerous diseases, including common infections and autoimmune diseases. Levels of inflammatory markers also seem to be abnormal in sleep deficient individuals, which may lead to low-grade inflammation. The interpretation of studies is difficult due to the equivocal term “sleep disturbances,” as well as due to the various criteria used in studies. This narrative review aims to summarize the available knowledge regarding the bidirectional influence of the immune system and sleep disturbances