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INTRODUCTION AND IMPORTANCE: Congenital epidermolysis bullosa (EB) is a group of rare genetic conditions characterized by fragile skin that blisters easily. Anaesthesia management in these patients is complex due to mucocutaneous fragility, which can complicate surgical procedures and airway management. Our study aimed to report a case of successful general anaesthesia in two patients with congenital epidermolysis bullosa undergoing oesophagal dilatation. CASE PRESENTATION: The case involved a brother and sister, aged 21 and 15 respectively, both of whom have congenital epidermolysis bullosa and presented with solid dysphagia due to double stenosis of the oesophagus. Anaesthesia management included meticulous preoperative planning, use of non-adhesive monitoring equipment, careful management with video laryngoscopy, and minimisation of skin trauma. CLINICAL DISCUSSION: Both patients underwent successful esophageal dilation under general anaesthesia without perioperative complications. Airway management was achieved in the first attempt using video laryngoscopy. Analgesia was effectively treated with paracetamol and tramadol. CONCLUSION: This case illustrates the complexities and necessary precautions for anaesthesia management in patients with epidermolysis bullosa. Detailed preoperative evaluation, careful monitoring, and specific handling techniques can mitigate perioperative risks and ensure patient safety.
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Horses maintained outdoors may experience a lower-allergenic environment compared to their stabled counterparts. This study hypothesizes that climatic changes in southern Brazil can influence respiratory status. To test this hypothesis, we evaluated the lower airways of 17 horses from a teaching herd in southern Brazil, maintained outdoors, during winter, spring, and summer. Except for one mare with a history of severe asthma, all horses were considered healthy and underwent a physical examination. Airway endoscopic evaluation included scoring for tracheal mucus (0-5) and bronchial septum thickness (1-5). Bronchoalveolar lavage fluid (BALF) was collected at three time points, while bronchial septum biopsies were performed during spring and summer for airway epithelial investigation. Data analysis involved repeated measures ANOVA and Wilcoxon tests (p < 0.05). Tracheal mucus score and septal thickness did not differ across investigation periods. In BALF cytology, the mean percentage of neutrophils was higher in spring than summer (7.9 ± 13.4â¯% vs. 4.5 ± 11.7â¯%, P = 0.037), and eosinophil count was higher in winter than spring (0.64 ± 1.29â¯% vs. 0.03 ± 0.13â¯%, P = 0.034) and summer (0.64 ± 1.29â¯% vs. 0.14 ± 0.60â¯%, P = 0.023). Histopathological observations showed no differences between time points, and no correlations were observed with BALF analyses (P > 0.05). This study demonstrates that, even in an outdoor environment, horses' airways exhibit cytological modifications associated with different seasons, indicating a need for deeper investigation; endobronchial biopsy did not contribute to the clinical diagnosis.
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INTRODUCTION: If Multiple Breath Washout (MBW) derived acinar ventilation heterogeneity (Sacin) really represents peripheral units, the N2 phase-III of the first MBW exhalation should be curvilinear. This is due to the superposed effect of gas diffusion and convection resulting in an equilibration of N2 concentrations between neighbouring lung units throughout exhalation. We investigated this in smokers with CT-proven functional small airway disease. METHODS: Instantaneous N2slopes were computed over 40ms intervals throughout phase-III and normalized by mean phase-III N2 concentration. N2phase-III (concave) curvilinearity was quantified as the rate at which the instantaneous N2 slope decreases past the phase-II peak over a 1s interval; for a linear N2phase-III unaffected by diffusion, this rate would amount to 0L-1/s. N2phase-III curvilinearity was obtained on the experimental curves and on existing model simulations of N2curves from a normal peripheral lung model and one with missing terminal bronchioles (either 50% or 30% TB left). RESULTS: In forty-six smokers (66 (+8) years; 49 (+26) packyears) with CT-evidence of peripheral lung destruction, instantaneous N2 slope decrease was compared between those with (fSAD+fEmphys)>20% (-0.26+0.14(SD) L-1/s;n=24) and those with (fSAD+fEmphys)<20% (-0.16+0.12(SD)L-1/s;n=22) (P=0.014). Experimental values fell in the range predicted by a realistic peripheral lung model with progressive reduction of terminal bronchioles: values of instantaneous N2-slope decrease obtained from model simulations were -0.09L-1/s (normal lung;100%TB left), -0.17L-1/s (normal lung 50%TB left) and -0.29L-1/s (30%TB left). DISCUSSION : In smokers with CT-based evidence of functional small airways alterations, it is possible to demonstrate that Sacin really does represent the most peripheral airspaces.
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Stereology, the gold standard of lung morphometry, critically depends on sampling of tissue for analysis. Random sampling approaches guarantee each part of the organ an equal chance of being included in the analysis, hence they guarantee a representative sample of the whole. However, when biological or pathological structures of interest are rare and/or heterogeneously distributed over the whole lung, the random sampling approach can be inefficient or even result in meaningless data. In such cases, a targeted sampling approach can be useful which helps to relate the analytical items to an appropriate reference space. Targeted stereology greatly benefits from the increasing availability of multi-resolution imaging techniques at macroscopic and microscopic level as well as digital tools of segmentation. As such, the present article outlines two basic sampling scenarios: 1. In the first scenario, computed tomography and microscopy are subsequently used to segment the airway/arterial tree and perform stereological measurements on specific branches of the tree. 2. The second scenario deals with heterogeneous distribution of pathological lesions. This type of analysis can be divided into two stages: assessment of lesions of interest (LOI) within the lung and assessment of subcompartments within LOI. Taken together, targeted stereology has a thorough foundation in stereological theory and is not only able to significantly increase the efficiency of the analysis but also to yield new types of information that would be lost with the classical random sampling approach.
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Background: Prior observational research has indicated a potential link between pediatric asthma and united airways disease (UAD). However, these findings could be subject to confounding factors and reverse causation. Therefore, our study utilizes Mendelian randomization (MR) method to further investigate the causal relationship between pediatric asthma and UAD. Methods: We conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the association between pediatric asthma and seven groups of UAD, including chronic sinusitis, chronic rhinitis, nasopharyngitis and pharyngitis, chronic diseases of tonsils and adenoids, chronic laryngitis and laryngotracheitis, chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD). The present study employed a range of methods for two-sample MR analysis, including inverse variance weighted (IVW), MR-Egger regression, Simple mode, weighted median, and weighted models. The conclusion of the MR analysis primarily relies on the IVW results, while other analytical methods are utilized as supplementary evidence to ensure result robustness in this MR analysis. And sensitivity analyses were conducted, including heterogeneity test, horizontal pleiotropy test, MR-PRESSO test, and leave-one-out analysis to validate the results. Results: The results of the MR analysis indicate significant causal effects of pediatric asthma on chronic rhinitis, nasopharyngitis and pharyngitis (IVW: OR = 1.15, 95%CI: 1.05-1.26, p-value = 0.003), chronic diseases of tonsils and adenoids (IVW: OR = 1.07, 95%CI: 1.00-1.15, p-value = 0.038), chronic bronchitis (IVW: OR = 1.51, 95%CI: 1.42-1.62, p-value <0.001), bronchiectasis (IVW: OR = 1.51, 95%CI: (1.30-1.75), p-value <0.001), and COPD (IVW: OR = 1.43, 95%CI: 1.34-1.51, p-value <0.001). However, no significant causal association was observed between pediatric asthma and chronic sinusitis (IVW: OR = 1.00, 95%CI: 1.00-1.00, p-value = 0.085), chronic laryngitis and laryngotracheitis (IVW: OR = 1.05, 95%CI: 0.90-1.21, p-value = 0.558). Conclusion: Our findings support a potential causal relationship between pediatric asthma and UAD, suggesting that pediatric asthma may be a potential risk factor for various UAD.
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Introduction: Impaired lung function has been observed in patients following COVID-19 infection, with studies reporting persistent lung volume and diffusing capacity impairments. Some studies have demonstrated significantly higher small airway resistance in COVID-19 positive cases. This retrospective study aims to examine impulse oscillometry (IOS) data of patients with persistent symptoms after COVID-19 infection, focusing on the relationship between time and symptoms. Material and Method: The study analyzed data from adult patients with persistent symptoms who underwent IOS testing within and after 84 days from the diagnosis date. Result: The results showed that patients within 84 days and those between 31 and 84 days had higher small airway resistance values, indicating peripheral airway disease. Patients with dyspnea exhibited higher IOS values compared to those with cough symptoms, suggesting more significant impairment in the peripheral airways. Conclusion: The study highlights the importance of using comprehensive diagnostic tools like IOS to assess respiratory impairments in post-COVID-19 patients, particularly in the small airways. Understanding the relationship between time and symptoms can provide valuable insights for the treatment of peripheral airway dysfunction in post-COVID-19 patients.
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Objective: Since 2015, Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) has been used in general anesthesia for preoxygenation or difficult exposure airway management. Its use offers new opportunities in laryngology. THRIVE increases apnea time and frees the access to the upper airway. However, its use may be less stable than orotracheal intubation. The main objective of this work was to evaluate the feasibility of laryngeal microsurgery under THRIVE including using Laser. Study Design: Retrospective. Setting: A total of N = 99 patients with laryngeal microsurgery (with or without CO2 laser) under THRIVE were included successively from January 1, 2020 to January 30, 2022. Method: Medical history, comorbidities, clinical and surgical data were extracted and analyzed. Two groups were constituted regarding the "success" (use of THRIVE along all the procedure) or the "failure" (need for an endotracheal tube) of the use of THRIVE during the procedure. Results: A failure occurred in N = 15/99 patients (15.2%) mainly due to refractory hypoxia. The odd ratios (OR) for THRIVE failure were: OR = 6.6 [2.9-35] for overweight (BMI >25 kg/m2); OR = 3.8 [1.7-18.7] for ASA score >2; OR = 4.7 [2.3-24.7] for the use of CO2 laser. Elderly patients and patients with pulmonary pathology were not statistically at greater risk of THRIVE failure. No adverse event was described. Conclusion: This work confirms the feasibility of laryngeal microsurgery under THRIVE, including with CO2 laser. Overweight, ASA >2 and lower fraction of inspired oxygen during CO2 laser use increased the risk for orotracheal intubation.
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Chronic obstructive pulmonary disease (COPD) is caused by the inhalation of noxious particles such as cigarette smoke. The pathophysiological features include airway inflammation, alveolar destruction and poorly reversible airflow obstruction. A sub-group of COPD patients have higher blood eosinophil counts (BECs), associated with an increased response to inhaled corticosteroids and increased biomarkers of pulmonary type 2 (T2) inflammation. Emerging evidence shows that COPD patients with increased pulmonary eosinophil counts have an altered airway microbiome. Higher BECs are also associated with increased lung function decline, implicating T2 inflammation in progressive pathophysiology in COPD. We provide a narrative review of the role of eosinophils and T2 inflammation in the pathophysiology of COPD, encompassing the lung microbiome, pharmacological targeting of T2 pathways in COPD, and the clinical use of BEC as a COPD biomarker.
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BACKGROUND: We have previously shown that asthma-like airways inflammation may be induced by topical exposure to respiratory tract pathogens such as S. pneumoniae (SP) in concert with epithelial alarmins such as IL-33. Details of the pathogenesis of this murine surrogate remain however unexplored. METHODS: Airways inflammation was induced by repeated, intranasal exposure of Il-4-/-, Rag1-/- and Rag2-/-Il2rg-/- mice (in which B lymphocyte IgE switching, adaptive and innate immunity are respectively ablated) as well as wild type mice to inactivated SP, IL-33 or both. Airways pathological changes were analysed, and the subsets and functions of locally accumulated ILC2s investigated by single cell RNA sequencing and flow cytometry. RESULTS: In the presence of IL-33, repeated exposure of the airways to inactivated SP caused marked eosinophil- and neutrophil-rich inflammation and local accumulation of ILC2s, which was retained in the Il-4-/- and Rag1-/- deficient mice but abolished in the Rag2-/-Il2rg-/- mice, an effect partly reversed by adoptive transfer of ILC2s. Single cell sequencing analysis of ILC2s recruited following SP and IL-33 exposure revealed a Klrg1+Ly6a+subset, expressing particularly elevated quantities of the pro-inflammatory cytokine IL-6, type 2 cytokines (IL-5 and IL-13) and MHC class II molecules, promoting type 2 inflammation as well as involved in neutrophil-mediated inflammatory responses. CONCLUSION: Local accumulation of KLRG1+Ly6a+ ILC2s in the lung tissue is a critical aspect of the pathogenesis of airways eosinophilic and neutrophil-rich inflammation induced by repeated exposure to SP in the presence of the epithelial alarmin IL-33.
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Interleucina-33 , Streptococcus pneumoniae , Animais , Interleucina-33/imunologia , Interleucina-33/genética , Streptococcus pneumoniae/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pulmão/imunologia , Pulmão/patologia , Pulmão/microbiologia , Linfócitos/imunologia , Inflamação/imunologia , Camundongos , Feminino , Alarminas/imunologia , Proteínas de HomeodomínioRESUMO
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. COPD is often diagnosed late in the disease leading to a delay in management. Notably, tumor necrosis factor-α (TNF-α) polymorphisms may serve an important role in the development of COPD. A single-center, case-control study was conducted to determine the presence of the TNF-α -308 G/A polymorphism among patients diagnosed with COPD presenting with hyperactive airways, patients without COPD presenting with hyperactive airways, and normal study participants without pulmonary comorbidities. Three genotypes: G/G (94%; 157/167), G/A (5%; 9/167) and A/A (1%; 1/167) were detected by quantitative PCR. The present study showed that the presence of the TNF-α -308 G/A polymorphism reduced the odds of having hyperactive airways with COPD by 29.3% and hyperactive airways without COPD by 26.3%. Multinomial logistic regression analysis showed that having the TNF-α -308 G/A polymorphism did not significantly reduce the odds of having hyperactive airways with COPD and without COPD compared to those with the G/G genotype. In conclusion, the presence of the TNF-α -308 G/A gene polymorphism showed no significant association with patients with COPD with or without hyperactive airways. The presence of the TNF-α -308 G/A polymorphism instead had a weak association with the reduction in the development of COPD regardless of the presence or absence of airway hyperactivity.
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The fact that some SARS-CoV-2 pneumonia patients benefit from changing body position, and some from continuous positive airways pressure (CPAP), indicates the functional character of hypoxia. We hypothesize that such effects could be explained by the closure of small airways. To prove the hypothesis, we evaluated the patency of small airways in 30 oxygen-dependent, spontaneously breathing patients with SARS-CoV-2 pneumonia during their hospital stay using the FOT method and then compared the results with data obtained three months later. During the acute period, total resistance (R5) and peripheral resistance (R5-20) rose above the upper limit of normal (ULN) in 28% and 50% of all patients, respectively. Reactance indices X5, AX and Fres exceeded ULN in 55%, 68% and 66% of cases. Significant correlations were observed between PaO2/FiO2, the time spent in the hospital and R5, X5, AX and Fres. After 3 months, 18 patients were re-examined. During the hospital stay, 11 of them had risen above the upper limit of normal (ULN), for both resistance (R5-20) and reactance (X5, AX) values. Three months later, ULN for R5-20 was exceeded in only four individuals, but ULN for X5 and AX was exceeded in five individuals. Lung function examination revealed a combined restrictive/obstructive ventilatory failure and reduced CO transfer factor. We interpret these changes as lung tissue remodeling due to the process of fibrosis. We conclude that during acute period of SARS-CoV-2 pneumonia, dilated pulmonary blood vessels and parenchymal oedema induce functional closure of small airways, which in turn induce atelectasis with pulmonary right-to-left shunting, followed by the resulting hypoxemia.
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Tosse Crônica , Oscilometria , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tosse Crônica/diagnóstico , Estudos de CoortesAssuntos
Cartilagem , Traqueia , Traqueia/cirurgia , Humanos , Cartilagem/transplante , Aorta/cirurgiaRESUMO
Toll-like receptor 5 (TLR5) signaling plays a key role in antibacterial defenses. We previously showed that respiratory administration of flagellin, a potent TLR5 agonist, in combination with amoxicillin improves the treatment of primary pneumonia or superinfection caused by amoxicillin-sensitive or -resistant Streptococcus pneumoniae. Here, the impact of adjunct flagellin therapy on antibiotic dose/regimen and the selection of antibiotic-resistant S. pneumoniae was investigated using superinfection with isogenic antibiotic-sensitive and -resistant bacteria and population dynamics analysis. Our findings demonstrate that flagellin allows for a 200-fold reduction in the antibiotic dose, achieving the same therapeutic effect observed with antibiotic alone. Adjunct treatment also reduced the selection of antibiotic-resistant bacteria in contrast to the antibiotic monotherapy. Finally, we developed a mathematical model that captured the population dynamics and estimated a 20-fold enhancement immune-modulatory factor on bacterial clearance. This work paves the way for the development of host-directed therapy and refinement of treatment by modeling.
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Home Respiratory Therapies (HRT) encompass a variety of treatments for patients with chronic respiratory diseases, administered at home over extended periods. The Service Providers of HRT (SPHRT) collaborate with hospital resources to address chronic respiratory diseases, acting as strategic partners. The contracting of HRT in the public health system involves contests where the SPHRT present technical and economic offers. The purpose of this document is to provide a technical basis that can assist professionals, SPHRT, and the administration in making decisions when calling for, evaluating, and deciding on such contests.
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INTRODUCTION AND AIMS: Workplace exposures are widely known to cause specific occupational diseases such as silicosis and asbestosis, but they also can contribute substantially to causation of common respiratory diseases. In 2019, the American Thoracic Society (ATS) and the European Respiratory Society (ERS) published a joint statement on the occupational burden of respiratory diseases. Our aim on this narrative review is to summarise the most recent evidence published after the ATS/ERS statement as well as to provide information on traditional occupational lung diseases that can be useful for clinicians and researchers. RESULTS: Newer publications confirm the findings of the ATS/ERS statement on the role of workplace exposure in contributing to the aetiology of the respiratory diseases considered in this review (asthma, COPD, chronic bronchitis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, infectious pneumonia). Except for COPD, chronic bronchitis and infectious pneumonia, the number of publications in the last 5 years for the other diseases is limited. For traditional occupational lung diseases such as silicosis and asbestosis, there are old as well as novel sources of exposure and their burden continues to be relevant, especially in developing countries. CONCLUSIONS: Occupational exposure remains an important risk factor for airways and interstitial lung diseases, causing occupational lung diseases and contributing substantially in the aetiology of common respiratory diseases. This information is critical for public health professionals formulating effective preventive strategies but also for clinicians in patient care. Effective action requires shared knowledge among clinicians, researchers, public health professionals, and policy makers.
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Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are two common respiratory tract pathogens often associated with acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) as well as with otitis media (OM) in children. Although there is evidence that these pathogens can adopt persistence mechanisms such as biofilm formation, the precise means through which they contribute to disease severity and chronicity remains incompletely understood, posing challenges for their effective eradication. The identification of potential vaccine candidates frequently entails the characterization of the host-pathogen interplay in vitro even though this approach is limited by the fact that conventional models do not permit long term bacterial infections. In the present work, by using air-liquid-interface (ALI) human airway in vitro models, we aimed to recreate COPD-related persistent bacterial infections. In particular, we explored an alternative use of the ALI system consisting in the assembly of an inverted epithelium grown on the basal part of a transwell membrane with the aim to enable the functionality of natural defense mechanisms such as mucociliary clearance and cellular extrusion that are usually hampered during conventional ALI infection experiments. The inversion of the epithelium did not affect tissue differentiation and considerably delayed NTHi or Mcat infection progression, allowing one to monitor host-pathogen interactions for up to three weeks. Notably, the use of these models, coupled with confocal and transmission electron microscopy, revealed unique features associated with NTHi and Mcat infection, highlighting persistence strategies including the formation of intracellular bacterial communities (IBCs) and surface-associated biofilm-like structures. Overall, this study demonstrates the possibility to perform long term host-pathogen investigations in vitro with the aim to define persistence mechanisms adopted by respiratory pathogens and individuate potential new vaccine targets.
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Biofilmes , Haemophilus influenzae , Moraxella catarrhalis , Infecções por Moraxellaceae , Moraxella catarrhalis/fisiologia , Humanos , Haemophilus influenzae/fisiologia , Haemophilus influenzae/patogenicidade , Biofilmes/crescimento & desenvolvimento , Infecções por Moraxellaceae/microbiologia , Infecção Persistente/microbiologia , Interações Hospedeiro-Patógeno , Infecções por Haemophilus/microbiologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Modelos Biológicos , Infecções Respiratórias/microbiologia , Células Epiteliais/microbiologiaRESUMO
OBJECTIVE: The objective was to study the effect of orthodontic therapy regarding the position of the hyoid bone and upper airways in nighty-one 6-21 year-old Caucasian patients with normoclussion. METHODS: Nineteen variables were analyzed by teleradiography. The differences were analyzed with the ANOVA test of repeated measures with an intra-group factor for two occasions. RESULTS: The statistical analysis revealed a greater influence on the variables Hy-MP (12.3 vs 14.2), Hps-C3 (25.2 vs 28.1), Hpi-C3 (28.8 vs 35.5), H°-C3 (14.4 vs 12.7), Hps-Rg (36.0 vs 42.7), Hpi-Rg (34.1 vs 39.7), USP (16.2 vs 20.2), MPP (12.9 vs 14.8), C3P (10.6 vs 12.8), PNS-Ba (43.5 vs 66.5), PtV-Ad (12.0 vs 17.1) and PtM-Ba (33.9 vs 35.9), and Ad2-SO (24.16 vs 20.87). DISCUSSION: Significant differences were observed between most of the airway and hyoid bone variables before and after orthodontic treatment in our Spanish pediatric population, especially in the nasopharynx.