Accumulation of environmental chitin in the lungs can lead to pulmonary fibrosis, characterized by inflammatory infiltration and fibrosis in acidic chitinase (Chia)-deficient mice. Transgenic expression of Chia in these mice ameliorated the symptoms, indicating the potential of enzyme supplementation as a promising therapeutic strategy for related lung diseases. This study focuses on utilizing hyperactivated human Chia, which exhibits low activity. We achieved significant activation of human Chia by incorporating nine amino acids derived from the crab-eating monkey (Macaca fascicularis) Chia, known for its robust chitin-degrading activity. The modified human Chia retained high activity across a broad pH spectrum and exhibited enhanced thermal stability. The amino acid substitutions associated with hyperactivation of human Chia activity occurred species specifically in monkey Chia. This discovery highlights the potential of hyperactivated Chia in treating pulmonary diseases resulting from chitin accumulation in human lungs.
- MeSH
- aktivace enzymů účinky léků MeSH
- chitin metabolismus chemie MeSH
- chitinasy * metabolismus genetika chemie MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- Macaca fascicularis MeSH
- myši MeSH
- plíce metabolismus patologie enzymologie MeSH
- stabilita enzymů MeSH
- substituce aminokyselin MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: Sinonasal adenosquamous carcinoma (ASC) is a rare tumour classified as a variant of squamous cell carcinoma, exhibiting both squamous and glandular differentiation. ASC has a poorer prognosis compared to sinonasal mucoepidermoid carcinoma (MEC), another uncommon tumour in this region. ASC is believed to originate from metaplastic squamous epithelium, though it may also arise from respiratory epithelium in respiratory epithelial adenomatoid hamartoma (REAH) or seromucinous glands in seromucinous hamartoma (SH). METHODS AND RESULTS: Five cases of sinonasal ASC were retrieved from our registry. Initially, they were classified as sinonasal MEC (n = 3), ASC (n = 2), and carcinoma ex REAH (n = 1). All cases showed adenosquamous malignant proliferation beneath the surface respiratory epithelium with occasional squamous metaplasia, except for one case that showed dysplasia. The respiratory epithelium exhibited an inverted growth pattern consistent with REAH/SH, and displayed atypical sinonasal glands (ASGSH) arising within seromucinous hamartoma. Next-generation sequencing (NGS) revealed multiple pathogenic mutations in two cases, and in case 4 GGA2::PRKCB and EYA2::SERINC3 gene fusions. One case was positive for high-risk HPV. None of the cases exhibited CRTC1/3::MAML2 gene fusion. CONCLUSION: The connection between ASGSH and ASC has not been described in the literature. There is a growing need for additional studies on the morphological, immunohistochemical, and genetic aspects of these tumours. SH/REAH may serve as precursor lesions in the progression of atypical sinonasal glands to malignancy, and their role in tumour development deserves further investigation.
- MeSH
- adenoskvamózní karcinom * patologie genetika MeSH
- dospělí MeSH
- hamartom * patologie genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory vedlejších dutin nosních patologie genetika MeSH
- respirační sliznice patologie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The small airways, also referred to as the lung's silent zone, are closely associated with poor symptom control and more frequent asthma exacerbations. The oscillometry technique superimposes sound or airwaves onto normal tidal breathing and provides information on resistance and reactance, that is, obstacles to airflow occurring inside and outside of the bronchi. More recently, a management paradigm based on so-called "treatable traits" has been proposed to personalize and improve asthma care for individuals by proactively identifying and targeting modifiable pulmonary, extrapulmonary, and behavioral traits affecting asthma control. In this review article, we evaluate the literature on small airways dysfunction as a potential treatable trait in persistent asthma. In particular, we discuss whole- and intrabreath oscillometry and the impact of extrafine inhaled corticosteroids and systemic biologics on the peripheral airways.
- MeSH
- bronchiální astma * patofyziologie farmakoterapie diagnóza MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- lidé MeSH
- oscilometrie * metody MeSH
- plíce patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The alveolar-capillary interface is the key functional element of gas exchange in the human lung, and disruptions to this interface can lead to significant medical complications. However, it is currently challenging to adequately model this interface in vitro, as it requires not only the co-culture of human alveolar epithelial and endothelial cells but mainly the preparation of a biocompatible scaffold that mimics the basement membrane. This scaffold should support cell seeding from both sides, and maintain optimal cell adhesion, growth, and differentiation conditions. Our study investigates the use of polycaprolactone (PCL) nanofibers as a versatile substrate for such cell cultures, aiming to model the alveolar-capillary interface more accurately. We optimized nanofiber production parameters, utilized polyamide mesh UHELON as a mechanical support for scaffold handling, and created 3D-printed inserts for specialized co-cultures. Our findings confirm that PCL nanofibrous scaffolds are manageable and support the co-culture of diverse cell types, effectively enabling cell attachment, proliferation, and differentiation. Our research establishes a proof-of-concept model for the alveolar-capillary interface, offering significant potential for enhancing cell-based testing and advancing tissue-engineering applications that require specific nanofibrous matrices.
BACKGROUND & AIMS: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints. METHODS: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM). A follow-up interview was performed after at least 6 months. Cohort 2 consisted of 135 Pi∗ZZ subjects without significant liver fibrosis, who received a standardized baseline and follow-up examination at least 2 years later, both including LSM. RESULTS: During 2634 patient-years of follow-up, 39 individuals died, with liver and lung being responsible for 46% and 36% of deaths, respectively. Forty-one Pi∗ZZ subjects who developed a hepatic endpoint presented with significantly higher baseline liver fibrosis surrogates, that is, LSM (24 vs 5 kPa, P < .001) and aspartate aminotransferase-to-platelet ratio index (1.1 vs 0.3 units, P < .001). Liver-related endpoints within 5 years were most accurately predicted by LSM (area under the curve 0.95) followed by aspartate aminotransferase-to-platelet ratio index (0.92). Baseline lung parameters displayed only a moderate predictive utility for lung-related endpoints within 5 years (forced expiratory volume in the first second area under the curve 0.76). Fibrosis progression in those with no/mild fibrosis at baseline was rare and primarily seen in those with preexisting risk factors. CONCLUSIONS: Noninvasive liver fibrosis surrogates accurately stratify liver-related risks in Pi∗ZZ individuals. Our findings have direct implications for routine care and future clinical trials of Pi∗ZZ patients.
- MeSH
- alfa-1-antitrypsin * genetika krev MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- deficit alfa1-antitrypsinu * genetika diagnóza komplikace MeSH
- dospělí MeSH
- elastografie MeSH
- genotyp MeSH
- homozygot MeSH
- jaterní cirhóza * genetika diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- mutace MeSH
- plíce patofyziologie patologie diagnostické zobrazování MeSH
- plicní nemoci genetika etiologie diagnóza MeSH
- progrese nemoci * MeSH
- rizikové faktory MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
AIM: Percutaneous transthoracic needle biopsy (PTNB), an alternative to bronchoscopic confirmation of lung lesions, is today being associated with a risk of pneumothorax and hemorrhage. Further, there are no data on the possible risk of malignant disease spreading to the pleura at the site of the PTNB. Previous studies have dealt with this risk in stage I non-small cell lung cancer only. The aim of this study was thus to assess the risk of pleural recurrence for all types of lung lesions. Secondary objectives included assessment of diagnostic yield and safety with respect to the incidence of pneumothorax and hemorrhage. METHODS: Clinical data of all patients from the University Hospital in Pilsen who had undergone PTNB of lung lesions between 1.1.2018 and 31.12.2022 were included in this retrospective study. RESULTS: Following PTNB, ipsilateral pleural effusion occurred in 4.8% of patients without prior pleural infiltration. The effusion was confirmed as malignant in one patient (0.7%). Diagnostic yield of the method was 86.6%. We recorded pneumothorax or hemorrhage in the lung parenchyma or pleural space requiring medical intervention in 3.4% and 1.1% of patients, respectively. CONCLUSION: In our study, percutaneous transthoracic needle biopsy of lung lesions showed high sensitivity and low degree of acute complications requiring an invasive solution. The risk of pleural recurrence after a biopsy was very low. Consequently, we continue to consider this method to be an alternative to bronchoscopy biopsies.
- MeSH
- dospělí MeSH
- jehlová biopsie škodlivé účinky metody MeSH
- krvácení etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory plic * patologie MeSH
- pleurální výpotek etiologie patologie MeSH
- plíce patologie MeSH
- pneumotorax * etiologie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIM: Transbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease-associated ILD (CTD-ILD) in cryobiopsies. METHODS: We examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)-established CTD-ILD and compared them to a prior series of 121 biopsies from patients with MDD-established IPF or FHP. RESULTS: A non-specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD-ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD-ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD-ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD-ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD-ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD-ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD-ILD over IPF, but were infrequent. CONCLUSIONS: In the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD-ILD in a cryobiopsy, but CTD-ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.
- MeSH
- biopsie metody MeSH
- dospělí MeSH
- idiopatická plicní fibróza patologie komplikace diagnóza MeSH
- intersticiální plicní nemoci * patologie diagnóza komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci pojiva * komplikace patologie diagnóza MeSH
- plíce patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Doležalová k. problematika tuberkulózy a non-tuberkulózních mykobakterióz v pediatrii Tuberkulóza (tB) je infekční onemocnění způsobené Mycobacterium tuberculosis, které postihuje převážně plíce, ale může napadnout kterýkoli orgán. Vysoké riziko tB mají děti ze znevýhodněných sociálních podmínek, děti s rodinnou anamnézou tB, romské děti a migranti z oblastí s vysokou incidencí tB. s nadsázkou tedy můžeme říct, že tB je sociální onemocnění způsobené bakterií. diagnostika tB je založena na třech pilířích: 1. epidemiologická souvislost; pozitivní tuberkulinový kožní test (tst) a interferon gamma release (iGra) test; 3. radiologický nález. léčba tB spočívá v podávání kombinace antituberkulotik a řídí ji pneumolog nejlépe z centra dětské tB.(1) příbuznou nemocí jsou mykobakteriózy (non-tuberkulózní mykobakterie – ntM). u dětí je nejčastěji vídáme v batolecím věku pod obrazem jednostranné krční lymfadenitidy, způsobené Mycobacterium avium. Výskyt ntM krční lymfadenitidy u dětí jednoznačně narostl po zrušení celoplošné kalmetizace.(2)
Doležalová k. pediatric tuberculosis and nontuberculous mycobacterial infections: current challenges and clinical insights Tuberculosis (tB) is an infectious disease caused by Mycobacterium tuberculosis. it primarily affects the lungs but can involve any organ system. children at higher risk include those from socioeconomically disadvantaged environments, with a family history of tB, of roma ethnicity, or migrants from regions with a high incidence of tuberculosis. therefore, tB can be regarded as a social disease caused by a bacterium. diagnosis is based on three main pillars: the presence of an epidemiological link, a positive tuberculin skin test (tst) and interferon gamma release assay (iGra), and characteristic radiological findings. treatment consists of a combination of antituberculosis drugs and is best managed by a pulmonologist, ideally within a specialized pediatric tB center. non-tuberculous mycobacterial infections (ntM) in children most commonly occur in toddlers, typically presenting as unilateral cervical lymphadenitis caused by Mycobacterium avium. the incidence of ntM lymphadenitis in children has clearly increased since the discontinuation of nationwide BcG vaccination.
- MeSH
- antituberkulotika farmakologie terapeutické užití MeSH
- atypické mykobakteriální infekce * diagnóza farmakoterapie MeSH
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- netuberkulózní mykobakterie patogenita MeSH
- plíce diagnostické zobrazování mikrobiologie patologie MeSH
- předškolní dítě MeSH
- tuberkulóza * diagnóza farmakoterapie klasifikace mikrobiologie mortalita MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- Publikační typ
- přehledy MeSH
Neurodegenerative motor disorders affect the neuromuscular system challenging daily life and normal activity. Parkinson's Disease (PD) is among the most prevalent ones, with a large impact and rising prevalence rates. Speech is most affected by PD as far as phonatory and articulatory performance is concerned. Neuromotor activity (NMA) alterations have an impact on larynx muscles responsible for vocal fold adduction and abduction, hampering phonation stability and regularity. The main muscular articulators involved in phonation control are the cricothyroid (tensor) and thyroarytenoid (relaxer) systems, regulated by two distinct direct neuromotor pathways, activated by the precentral gyrus laryngeal control areas. These articulations control the musculus vocalis, directly responsible for regular vocal fold vibration. An indirect estimation of the muscular tension produced by inverse filtering may split into two independent channels, assumed to be the tensor and relaxer neuromotor pathways such as the differential neuromotor activity (DNMA). The amplitude distributions of both DNMA channels allow comparing phonations from PD-affected persons (PDPs) and age-matched healthy control participants (HCPs) with respect to a set of reference mid-age normative participants (RSPs). The comparisons are carried out by Jensen-Shannon distributions of PDP and HCP phonations with respect to those of RSPs. A dataset of 96 phonation samples from participants balanced by gender is used to train a set of decision tree classifiers (DTCs) to distinguish PDP from HCP phonation. The best results from 10-fold cross-validation offered accumulated mismatches of 0.09 and 0.1292 for male and female subsets. The sensitivity, specificity, and accuracy of the classification results when separating PDP from HCP phonatios were 93.33%, 88.23%, and 90.63% (male PDP versus HCP) and 92.86%, 83.33%, and 87.50% (female PDP versus HCP), providing a stratification of PDPs and HCPs by objective disease grading from explainable AI (XAI) methods.
- MeSH
- dospělí MeSH
- fonace * fyziologie MeSH
- laryngální svaly * patofyziologie MeSH
- larynx * patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * patofyziologie komplikace MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cíl: Zjistit, zda by detekce subklinického městnání ultrazvukovým vyšetření plic (lung ultrasound, luS) pacientů se SteMi mohla pomoci předpovědět rozvoj srdečního selhání a systolické, nebo diastolické dysfunkce levé komory. Metody: Do studie bylo zařazeno 150 pacientů. u všech byla provedena úspěšná revaskularizace a při příjmu u nich nebylo z klinického hlediska přítomno srdeční selhání. Během prvních 24 hodin od příjmu u nich bylo provedeno luS s 28 plicními body a byly spočítány B-linie. Pacienti byli rozděleni do dvou skupin: 64 pacientů do skupiny luS pozitivní (se 6 nebo více B-liniemi) a 86 jedinců do skupiny luS negativní; po tříměsíčním sledování byli vyšetřeni na přítomnost srdečního selhání stupně ii nebo vyššího podle klasifikace nYhA, ejekční frakci (ef) ≤40%, a celková longitudinální deformace myokardu (global longitudinal strain, GlS) ≤–16 %. Výsledky: K rozvoji klinického srdečního selhání došlo u většího počtu pacientů ve skupině luS pozitivní (17 vs. 2 ve skupině luS negativní; p < 0,01); totéž platilo pro ef ≤ 40 % (34 vs. 3; p < 0,01) i GlS ≤ –16 % (60 vs. 58; p < 0,01). Křivky operační charakteristiky přijímače (receiver-operating characteristic, roc) prokázaly, že optimální mezní hodnota počtu B-linií pro predikci rozvoje klinického srdečního selhání i poruchy systolické funkce je 6 nebo více (senzitivita = 89,47 %, specificita = 64,62 %, resp. senzitivita = 91,89 %, specificita = 74,11 %). Analýza podskupin podle počáteční diagnózy prokázala, že predikční hodnota luS byla statisticky významná pouze v případě SteMi přední stěny. Závěry: ultrazvukové vyšetření plic u pacientů se SteMi, provedené do 24 hodin od příjmu, dokáže předpovědět rozvoj klinického srdečního selhání nebo systolické dysfunkce do tří měsíců, zvláště v případě infarktu přední stěny.
Aim: To see if the detection of subclinical congestion in STEMI patients by lung ultrasound (LUS) could be helpful in predicting the development of future heart failure, systolic dysfunction or diastolic dysfunction. Methods: 150 patients were included. All patients were successfully revascularized and were not suffering from clinical heart failure on admission. The patients had a 28-point LUS study within the first 24 hours of admission, and B-lines were counted. Patients were divided into two groups: 64 patients into the LUS positive group (with 6 or more B-lines) and 86 into the LUS negative group. They were followed-up after 3 months, looking for heart failure NYHA II or greater, ejection fraction (EF) ≤40%, and global longitudinal strain (GLS) ≤-16%. Results: More patients from the LUS positive group developed clinical heart failure (17 vs 2 in the LUS negative group, p <0.01), EF ≤40% (34 vs 3, p <0.01), GLS ≤-16% (60 vs 58, p <0.01). Optimal cutoff derived from ROC curves revealed that the best B-line number cutoff to predict clinical heart failure as well as impaired systolic function was 6 or greater (sensitivity = 89.47%, specificity = 64.62% and sensitivity = 91.89%, specificity = 74.11%, respectively). Subgroup analysis by initial diagnosis revealed that the predictive power of LUS was significant only in anterior STEMI. Conclusions: LUS in STEMI patients, performed within 24 hours of admission, is able to predict the occurrence of clinical heart failure or systolic dysfunction at 3 months, especially in anterior infarctions.
