Differential regulation of lung homeostasis and silicosis by the TAM receptors MerTk and Axl.

Introduction: TAM receptor-mediated efferocytosis plays an important function in immune regulation and may contribute to antigen tolerance in the lungs, a site with continuous cellular turnover and generation of apoptotic cells. Some studies have identified failures in efferocytosis as a common driver of inflammation and tissue destruction in lung diseases. Our study is the first to characterize the in vivo function of the TAM receptors, Axl and MerTk, in the innate immune cell compartment, cytokine and chemokine production, as well as the alveolar macrophage (AM) phenotype in different settings in the airways and lung parenchyma. Methods: We employed MerTk and Axl defective mice to induce acute silicosis by a single exposure to crystalline silica particles (20 mg/50 µL). Although both mRNA levels of Axl and MerTk receptors were constitutively expressed by lung cells and isolated AMs, we found that MerTk was critical for maintaining lung homeostasis, whereas Axl played a role in the regulation of silica-induced inflammation. Our findings imply that MerTk and Axl differently modulated inflammatory tone via AM and neutrophil recruitment, phenotype and function by flow cytometry, and TGF-ß and CXCL1 protein levels, respectively. Finally, Axl expression was upregulated in both MerTk-/- and WT AMs, confirming its importance during inflammation. Conclusion: This study provides strong evidence that MerTk and Axl are specialized to orchestrate apoptotic cell clearance across different circumstances and may have important implications for the understanding of pulmonary inflammatory disorders as well as for the development of new approaches to therapy.

Post-COVID-19 respiratory sequelae two years after hospitalization: an ambidirectional study.

Background: COVID-19 lung sequelae can impact the course of patient lives. We investigated the evolution of pulmonary abnormalities in post-COVID-19 patients 18-24 months after hospital discharge. Methods: A cohort of COVID-19 patients admitted to the Hospital das Clínicas da Faculdade de Medicina da USP in São Paulo, Brazil, between March and August of 2020, were followed-up 6-12 months after hospital discharge. A subset of patients with pulmonary involvement and chest computed tomography (CT) scans were eligible to participate in this second follow-up (18-24 months). Data was analyzed in an ambidirectional manner, including retrospective data from the hospitalization, and from the first follow-up (6-12 months after discharge), and compared with the prospective data collected in this new follow-up. Findings: From 348 patients eligible, 237 (68%) participated in this follow-up. Among participants, 139 (58%) patients presented ground-glass opacities and reticulations, and 80 (33%) presented fibrotic-like lesions (traction bronchiectasis and architectural distortion). Five (2%) patients improved compared to the 6-12-month assessment, but 20 (25%) of 80 presented worsening of lung abnormalities. For those with relevant assessments on both occasions, comparing the CT findings between this follow-up with the previous assessment, there was an increase in patients with architectural distortion (43 [21%] of 204 vs 57 [28%] of 204, p = 0.0093), as well as in traction bronchiectasis (55 [27%] of 204 vs 69 [34%] of 204, p = 0.0043). Patients presented a persistent functional impairment with demonstrated restrictive pattern in both follow-ups (87 [42%] of 207 vs 91 [44%] of 207, p = 0.76), as well as for the reduced diffusion capacity (88 [42%] of 208 vs 87 [42%] of 208, p = 1.0). Length of hospitalization (OR 1.04 [1.01-1.07], p = 0.0040), invasive mechanical ventilation (OR 3.11 [1.3-7.5] p = 0.011), patient's age (OR 1.03 [1.01-1.06] p = 0.0074 were consistent predictors for development of fibrotic-like lung lesions in post-COVID-19 patients. Interpretation: Post-COVID-19 lung sequelae can persist and progress after hospital discharge, suggesting airways involvement and formation of new fibrotic-like lesions, mainly in patients who were in intensive care unit (ICU). Funding: São Paulo Research Foundation (22/01769-5) and Instituto Todos pela Saúde (C1721).

Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS). METHODS: Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-ß expression, and infiltration of LAM cells and inflammatory cells within the small airway walls. RESULTS: The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content. CONCLUSION: LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).

Exhaled breath condensate analysis in horses: A scoping review.

Exhaled breath condensate (EBC) collection is a non-invasive sampling method that provides valuable information regarding the health status of the respiratory system by measuring inflammatory mediators, such as pH, hydrogen peroxide, and leukotriene B4. This scoping review aimed to provide an update on the collection and analysis of EBC in horses. A systematic search of three electronic databases, PubMed, Google Scholar, Science Direct, identified 40,978 articles, of which 1590 duplicates were excluded. Moreover, 39,388 articles were excluded because of irrelevance to this review, such as studies on other species, studies on respiratory exhalation, reviews, and theses. Finally, we evaluated 14 articles in this review. Our review revealed significant differences in the collection, storage, and processing of EBC samples, emphasizing the need for standardizing the technique and using specific equipment to improve the interpretation of the results.

Análisis bidimensional de la permeabilidad de vías aéreas con el tamaño de senos maxilares y su relación con el desarrollo de la clase esqueletal en una población mexicana / Two-dimensional analysis of airway permeability with maxillary sinus size and its relationship with the development of skeletal class in a Mexican population

Comparar la permeabilidad de las vías aéreas y el tamaño de los senos maxilares en relación con la clase esqueletal. se midieron 90 radiografías lateral de cráneo, divididas en 3 grupos, comparando las 3 clases esqueletales, las cuales se determinaron con la medida ANB de Steiner, y estas a su vez en dos subgrupos que fueron hombres y mujeres, en las cuales se utilizó el análisis de McNamara para el análisis de vías aéreas y para el área del seno maxilar se tomaron dos medidas una antero-posterior y cefálica-caudal. Al comparar los hombres con las mujeres se identificó significancia estadística en vía área superior de clase II (p=≤0.017), vía aérea inferior de clase III (p=≤0.006). Al comparar las clases esqueletales en hombres se identificó diferencias en la vía aérea superior en las clases I vs III (p=≤0.05), inferior en la clase I vs III (p=≤0,001) y II vs III (p=≤0.044). Con respecto a mujeres se identificó significancia en la vía aérea superior al comparar la clase I vs II (p=≤0,043), vía aérea inferior en la clase II vs III (p=≤0.05), longitud del seno maxilar al comparar clase I vs II (p=≤0.017). Entre la clase I esqueletal y la clase II, el tamaño de los senos maxilares resulto menor en longitud en las mujeres de clase II esqueletal. Entre la clase I y clase III esqueletal en hombres, se encontró una longitud menor en la vía aérea superior e inferior en la clase I. Las vías aéreas resultaron en menor tamaño en sujetos de clase II.

SUMMARY: To compare the airway permeability and the size of the maxillary sinuses in relation to the skeletal class. 90 lateral skull radiographs were divided into 3 groups, comparing the 3 skeletal classes, which were determined with Steiner's ANB measurement, and these were once in two subgroups that were men and women, in any McNamara analysis was used for the analysis of airways and for the maxillary sinus area measurements were made an antero-posterior and cephalic-caudal. When comparing males with females, statistical significance was identified in the upper class II route (p=≤0,017), lower class III airway (p=≤0.006). At least skeletal classes in men, differences were identified in the upper airway in classes I vs III (p=≤0.05), lower in class I vs III (p=≤0.001) and II vs III (p=≤0.044). With respect to women, significance was identified in the upper airway when comparing class I vs II (p=≤0.043), lower airway in class II vs. III (p=≤0.05), maxillary sinus length to class I vs II (p=≤0.017). Between skeletal class I and class II, maxillary sinus size was shorter in length in skeletal class II women. Between class I and skeletal class III in men, a lower length was found in the upper and lower airways in class I. The airways were found to be smaller in class II subjects.

Morphometric analysis of airways in pre-COPD and mild COPD lungs using continuous surface representations of the bronchial lumen.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent respiratory disease that presents a high rate of underdiagnosis during onset and early stages. Studies have shown that in mild COPD patients, remodeling of the small airways occurs concurrently with morphological changes in the proximal airways. Despite this evidence, the geometrical study of the airway tree from computed tomography (CT) lung images remains underexplored due to poor representations and limited tools to characterize the airway structure. Methods: We perform a comprehensive morphometric study of the proximal airways based on geometrical measures associated with the different airway generations. To this end, we leverage the geometric flexibility of the Snakes IsoGeometric Analysis method to accurately represent and characterize the airway luminal surface and volume informed by CT images of the respiratory tree. Based on this framework, we study the airway geometry of smoking pre-COPD and mild COPD individuals. Results: Our results show a significant difference between groups in airway volume, length, luminal eccentricity, minimum radius, and surface-area-to-volume ratio in the most distal airways. Discussion: Our findings suggest a higher degree of airway narrowing and collapse in COPD patients when compared to pre-COPD patients. We envision that our work has the potential to deliver a comprehensive tool for assessing morphological changes in airway geometry that take place in the early stages of COPD.

[Comparison of pharyngeal airway space on lateral head radiographs of skeletal class I and II individuals]. / Comparación del espacio de la vía aérea faríngea en radiografías laterales de cabeza de individuos de clase I y II esquelética.

Objective: To compare the space of the pharyngeal airway (nasopharynx and oropharynx) through lateral X-ray analysis in skeletal class II individuals with a control group composed of skeletal class I individuals. Materials and methods: This study was of the observational, descriptive, transversal, and prospective type. The sample was made up by 60 lateral head radiographs distributed between 30 class I (ANB 2°±2° and class I malocclusion) and 30 skeletal class II radiographs (ANB>5° and malocclusion class II-1). Measurements of the airway space in the oropharynx and nasopharynx were taken in mm through the McNamara method on lateral head radiographs. Results: The average space found in the oropharynx in class I was 11.71mm ± 3.18mm. In the class II group, it was 10.73mm ± 2.36mm. No significant differences were found (p=0.18). The average space found in the nasopharynx in the class I group was 18.45mm ± 4.11mm. In the class II group, it was 19.10mm ± 3.89mm. There were no significant differences found (p=0.53). Conclusion: The airway space in mm. of the nasopharynx presents similar values in millimeters in subjects with Class I and Class II skeletal malocclusion. There is no difference in the airway spaces of the oropharynx in subjects with Class I and Class II Malocclusions.

Systematic review and meta-analysis of efficacy and safety of continuous positive airways pressure versus high flow oxygen cannula in acute bronchiolitis.

INTRODUCTION: There are a trend towards increasing use of High-Flow Nasal Cannula (HFNC), outside of paediatric intensive care unit. Give this trend is necessary to update the actual evidence and to assess available published literature to determinate the efficacy of HFNC over Continuous Positive Air Pressure (CPAP) as treatment for children with severe bronchiolitis. METHODS: We searched MEDLINE, EMBASE, LILACS, and COCHRANE Central, and gray literature in clinical trials databases ( www. CLINICALTRIALS: gov ), from inception to June 2022. The inclusion criteria for the literature were randomized clinical trials (RCTs) that included children < 2 years old, with acute moderate or severe bronchiolitis. All study selection and data extractions are performed independently by two reviewers. RESULTS: The initial searches including 106 records. Only five randomized controlled trial that met the inclusion criteria were included in meta-analysis. The risk of invasive mechanical ventilation was not significantly different in CPAP group and HFNC group [OR: 1.18, 95% CI (0.74, 1.89), I² = 0%] (very low quality). The risk of treatment failure was less significantly in CPAP group than HFNC group [OR: 0.51, 95% CI (0.36, 0.75), I² = 0%] (very low quality). CONCLUSION: In conclusion, there was no significant difference between HFNC and CPAP in terms of risk of invasive mechanical ventilation. CPAP reduces de risk of therapeutic failure with a highest risk of non severe adverse events. More trials are needed to confirm theses results.

Effect of the application of software on the volumetric and cross-sectional assessment of the oropharyngeal airway of patients with and without an open bite: A CBCT study.

BACKGROUND: Using different software to evaluate the airways, with different thresholds, but within the range for airway recognition, could yield different measurements in the same patient with or without craniofacial disharmony. OBJECTIVES: The aim of the present study was to compare the volume and the most constricted area (MCA) of the oropharynx in individuals with or without an open bite by using 2 software programs meant for cone-beam computed tomography (CBCT). MATERIAL AND METHODS: This comparative study included 60 cases selected from 137 CBCT scans obtained from individuals with the presence or absence of an open bite. Each group included adults of both genders - in total 30 women and 30 men - with a mean age of 27.57 ±11.85 years in the open bite group and 26.23 ±6.78 years in the control group. The oropharyngeal volume and MCA were measured with 2 three-dimensional (3D) software packages: Planmeca Romexis®; and Nemotec NemoStudio®. Two calibrated orthodontists trained in the use of the software made the measurements. Data was analyzed using Student's t tests for independent and paired samples (p < 0.05). RESULTS: In general, the oropharynx volume measurements obtained with the NemoStudio software were significantly higher than those obtained with Romexis (19,007.17 ±8005.79 mm3 and 17,823.47 ±7148.62 mm3, respectively) (p = 0.020). However, when the groups were analyzed separately, the measurements of the group with an open bite did not differ according to the software used (p = 0.352). The measurements of the MCA of the oropharynx were significantly higher when obtained with the NemoStudio software (MD (mean difference) = 19.02 mm2) (p = 0.005). In contrast, no difference in the MCA results for the 2 software packages was found in the open bite group (p = 0.728). CONCLUSIONS: The volumetric and cross-sectional measurements of the oropharyngeal airway, particularly in individuals without an open bite, were affected by the software used.

Death by massive air sac fluke (Trematoda: Bothriogaster variolaris) infection in a free-ranging snail kite (Rostrhamus sociabilis).

Helminths are not usually considered important pathogens for birds of prey. There is a single published report of mortality in raptors due to an air sac trematode infection. We report a well-documented death case from massive infection by an air sac trematode of the family Cyclocoelidae in a wild-caught, juvenile male Snail Kite (Rostrhamus sociabilis) in Ecuador. The necropsy of a Snail Kite revealed more than 200 trematodes among air sacs, lungs, heart, gizzard, proventriculus, and liver. Within air sacs and lungs, mature flukes were associated with sacculitis, bronchitis, pneumonia, and atelectasis. Using an integrative taxonomic approach with morphological and molecular data, we identified the parasites as Bothrigaster variolaris (Trematoda: Cyclocoelidae: Ophthalmophaginae). This case provides the first evidence for the pathologic presence of air sac trematodes associated with morbidity in birds of prey in South America. Our results suggest that cyclocoelids may cause debilitation and significant clinical lesions in birds of prey, with potentially fatal consequences.

Cuerpo extraño de presentación tardía en bronquiotronco izquierdo. Caso clínico

RESUMEN Introducción: la introducción fortuita de un cuerpo extraño en las vías respiratorias es un accidente dramático que puede provocar complicaciones, aunque raro en los adultos, y sobre todo su presentación tardía, y en bronquio izquierdo. Caso clínico: se reporta el caso de un paciente de 71 años con un cuerpo extraño de presentación tardía en bronquiotronco izquierdo, que consultó por un cuadro de sepsis respiratoria, sin otros síntomas asociados, cuatro meses posteriores a referir haberse tragado un hueso de pollo, ocasión ésta en que el examen físico y los estudios radiológicos fueron negativos. Se realizó estudio con TAC de tórax y broncoscopia flexible evidenciándose una imagen sugerente de un cuerpo extraño en el bronquiotronco izquierdo. Discusión: después de realizar broncoscopia rígida y extracción de cuerpo extraño, presenta varias complicaciones, que requieren ingreso en terapia intensiva, la evolución clínica posterior fue favorable, con radiografía de tórax de control con adecuada reexpansión pulmonar y dándose de alta a los 55 días después del diagnóstico. Conclusiones: en presencia de un paciente con sepsis respiratoria después de un cuadro de broncoaspiración se debe tener en cuenta el diagnóstico de aspiración de un cuerpo extraño. La extracción del cuerpo extraño resulta la solución definitiva.

ABSTRACT Introduction: the fortuitous introduction of a foreign body in the respiratory tract is a dramatic accident that can cause complications, although rare in adults, and especially its late presentation, and in the left bronchus. Clinical case: we report the case of a 71-year-old patient with a late-onset foreign body in the left bronchial trunk, who consulted for respiratory sepsis, with no other associated symptoms, four months after reporting having swallowed a chicken bone. On which occasion the physical examination and radiological studies were negative. A CT scan of the chest and flexible bronchoscopy were performed, revealing an image suggestive of a foreign body in the left bronchial trunk. Discussion: after performing rigid bronchoscopy and extraction of a foreign body, he presented several complications, which required admission to intensive care, the subsequent clinical evolution was favorable, with a control chest X-ray with adequate lung re-expansion and being discharged 55 days later. of the diagnosis. Conclusions: in the presence of a patient with respiratory sepsis after a picture of bronchoaspiration, the diagnosis of aspiration of a foreign body should be taken into account. Extraction of the foreign body is the definitive solution.

RESUMO Introdução: a introdução fortuita de corpo estranho no trato respiratório é um acidente dramático que pode causar complicações, embora raras em adultos, e principalmente sua apresentação tardia, e no brônquio esquerdo. Caso clínico: relatamos o caso de um paciente de 71 anos com corpo estranho de início tardio no tronco brônquico esquerdo, que consultou por sepse respiratória, sem outros sintomas associados, quatro meses após relatar ter engolido osso de galinha. ocasião em que o exame físico e os estudos radiológicos foram negativos. Realizou-se TC de tórax e broncoscopia flexível, revelando imagem sugestiva de corpo estranho em tronco brônquico esquerdo. Discussão: após realização de broncoscopia rígida e extração de corpo estranho, apresentou diversas complicações, que exigiram internação em terapia intensiva, a evolução clínica posterior foi favorável, com radiografia de tórax de controle com reexpansão pulmonar adequada e alta hospitalar 55 dias depois do diagnóstico. Conclusões: na presença de um paciente com sepse respiratória após quadro de broncoaspiração, deve-se levar em consideração o diagnóstico de aspiração de corpo estranho. A extração do corpo estranho é a solução definitiva.

Induced sputum abnormalities in gas station attendants.

PURPOSE: To investigate inflammatory changes in the induced sputum (IS) of gas station attendants (GSAs) at risk of exposure to fuel vapors through inhalation and susceptible to respiratory complaints and impaired lung function. METHODS: Hypertonic saline-IS was collected from 52 GSAs who had never smoked (42 men, age = 35.9 ± 8.9 years) and had no known comorbidities. A group of 22 non-smokers (11 men, age = 30.5 ± 5.1 years) selected from the University staff served as control. The GSAs answered a questionnaire and underwent spirometry and chest tomography. A total of 15 inflammatory biomarkers associated with inflammation, including cytokines, chemokines, and mediators of immunological response, were also measured. RESULTS: The most common symptoms of GSAs were coughing (42.3%) and dyspnea (59.6%) based on the New York Heart Association (NYHA; Class II) classification. Significant elevations (p < 0.05) in forced vital capacity and forced expiratory volume within the first second were observed in the GSAs relative to those in the controls (GSA vs. control: 99 ± 12% vs. 90 ± 9% and 94 ± 11% vs. 87 ± 10%, respectively). The GSAs had a lower percentage of IS lymphocytes than that in the control group (4.5 ± 5.7% vs. 7.7 ± 9.8%). The GSAs also had significantly lower concentrations of IL-4, IL-5, IL-10, IL-12P70, IFN-γ, and MIP-1α, but IL-3 levels were higher. No differences were observed in the airway thickness and the amount of emphysema between the GSAs and the controls. CONCLUSION: Despite normal lung function and absence of abnormalities on HRCT, GSAs have a higher frequency of respiratory complaints, with evidence of impairment of lymphocytic activity in the airways.

Efeitos do posicionamento sagital da mandíbula na morfometria das vias aéreas superiores / Efects of sagital positioning of the mandibule in upper airway morphometry

O objetivo do presente estudo foi analisar as dimensões das vias aéreas superiores (VAS) em indivíduos com diferentes posicionamentos sagitais da mandíbula, bem como a sua relação com o comprimento efetivo mandibular (CoGn). A amostra foi constituída por 63 exames de tomografia computadorizada de feixe cônico (TCFC) de indivíduos com idade entre 13 e 35 anos, alocados em três grupos conforme os valores angulares de SNB: grupo com retrognatismo mandibular (RMand); grupo com posicionamento normal da mandíbula (NMand) e grupo com prognatismo mandibular (PMand). Com o auxílio do programa Dolphin Imaging® (versão 11.95 Premium), as VAS foram subdivididas em Nasofaringe (NF), Orofaringe (OF) e Hipofaringe (HF), e o volume (Vol) e área axial mínima (Axmin) de cada região mensurados, assim como a altura (Alt) da OF e HF. A medida linear CoGn também foi averiguada e sua influência sobre as dimensões das VAS avaliada. MANCOVA foi utilizada para comparar o conjunto de variáveis das VAS entre os grupos de acordo com o padrão mandibular. Além disso, modelos de regressão linear foram implementados para estimar, independentemente, o efeito x do SNB e CoGn nas dimensões das VAS. Indivíduos com prognatismo mandibular apresentaram medidas significativamente maiores para NF-Axmin e OF-Vol, quando comparados aos indivíduos que mostraram normalidade e retrognatismo mandibular (P < 0,05). Não foram observadas diferenças entre os grupos para quaisquer das outras medidas consideradas no estudo. A variável CoGn foi relacionada às medidas de volume de todas as regiões avaliadas das VAS e também à HF-Alt. Concluiu-se que indivíduos com prognatismo mandibular apresentaram, de modo expressivo, maior área axial mínima da Nasofaringe e maior volume da Orofaringe quando comparados àqueles com normalidade e retrognatismo mandibular; destacando-se que o comprimento efetivo mandibular demonstrou ser um preditor mais relevante nas dimensões das VAS em comparação ao SNB. (AU)

The aim of the present study was to analyze the dimensions of the upper airways (UA) in individuals with different sagittal positioning of the mandible, as well as its relationship with the effective mandibular length (CoGn). The sample consisted of 63 cone beam computed tomography (CBCT) scans of individuals aged between 13 and 35 years, allocated into three groups according to the angular values of SNB: Group with Mandibular Retrognathism (RMand); Group with Normal Jaw and Group with Mandibular Prognathism (PMand). Using Dolphin Imaging® program (version 11.95 Premium), the UA were subdivided into Nasopharynx (NP), Oropharynx (OP) and Hypopharynx (HP), and the volume (Vol) and minimum axial area (Axmin) of each region measured, as well as the total height (Ht) of the OP and HP. The linear measure CoGn was also investigated and its influence on the dimensions of the VAS evaluated. MANCOVA was used to compare the set of VAS variables between the groups according to the mandibular pattern. In addition, linear regression models were implemented to independently estimate the effect of SNB and CoGn on UA xii dimensions. Individuals with mandibular prognathism had significantly higher measurements for NP-Axmin and OP-Vol, when compared to individuals with harmony and mandibular retrognathism (P < 0.05). No differences were observed between groups for any of the other measures considered in the study. The CoGn variable was related to the volume measurements of all the evaluated regions of the UA and also to the HP-Ht. It was concluded that individuals with mandibular prognathism significantly presented a greater minimum axial area of the Nasopharynx and greater volume of the Oropharynx when compared to those with harmony and mandibular retrognathism; highlighting that the effective mandibular length proved to be a more relevant predictor in the dimensions of the UA compared to the SNB. (AU)

Extraluminal nitinol prosthesis in the treatment of intrathoracic tracheal collapse in a dog / Uso de prótese extraluminal de nitinol no tratamento de colapso traqueal intratorácico em um cão

A six-month-old male Brazilian Terrier with persistent cough and dyspnea was diagnosed with intrathoracic tracheal collapse and pneumonia after chest radiographics. The medical treatment was performed, and an extraluminal nitinol prosthesis was placed through thoracic access. The dog did not presented recurrence of dyspnea or pneumonia for four years after the surgical procedure. Placement of the extraluminal prosthesis with the thoracic approach effectively stabilized intrathoracic tracheal collapse without causing any structural damage in the thoracic region. Therefore, this is the first report of a successful use of this prosthesis with an intercostal approach in dogs for intrathoracic trachea collapse.

Um cão macho, da raça Terrier Brasileiro de seis meses de idade, com dispnéia e tosse persistente foi diagnosticado com colapso traqueal intratorácico e pneumonia após estudo radiográfico de tórax. Foi instituído tratamento médico e realizada toracotomia para a implantação de prótese traqueal extraluminal de nitinol. O animal não manifestou dispneia ou pneumonia durante os quatro anos posteriores ao procedimento. A implantação da prótese extraluminal através da toracotomia foi eficaz para o tratamento do colapso traqueal intratorácico, sem provocar danos estruturais na região torácica. Desta forma, este é primeiro relato da utilização bem-sucedida deste tipo de prótese, a partir da abordagem intercostal, no tratamento de cães com colapso traqueal intratorácico.

Methylglyoxal Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via RAGE-Induced ROS Generation: Protective Effects of Metformin.

PURPOSE: Methylglyoxal (MGO) is a highly reactive dicarbonyl species implicated in diabetic-associated diseases. Acute lung injury (ALI) symptoms and prognosis are worsened by diabetes and obesity. Here, we hypothesized that elevated MGO levels aggravate ALI, which can be prevented by metformin. Therefore, this study evaluated the lung inflammation in lipopolysaccharide (LPS)-exposed mice pretreated with MGO. METHODS: C57Bl/6 male mice treated or not with MGO for 12 weeks were intranasally instilled with LPS (30 µg) to induce ALI, and metformin (300 mg/kg) was given as gavage in the last two weeks of treatment. After 6 h, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to quantify the cell infiltration, cytokine levels, reactive-oxygen species (ROS) production, and RAGE expression. RESULTS: LPS exposure markedly increased the neutrophil infiltration in BALF and lung tissue, which was accompanied by higher levels of IFN-γ, TNF-α and IL-1ß compared with untreated group. MGO treatment significantly increased the airways neutrophil infiltration and mRNA expressions of TNF-α and IL-1ß, whereas COX-2 expression remained unchanged. In lung tissues of LPS-exposed mice, MGO treatment significantly increased the immunostaining and mRNA expression of RAGE, and the ROS levels. Serum MGO concentration achieved after 12-week intake was 9.2-fold higher than control mice, which was normalized by metformin treatment. Metformin also reduced the inflammatory markers in response to MGO. CONCLUSION: MGO intake potentiates the LPS-induced ALI, increases RAGE expression and ROS generation, which is normalized by metformin. MGO scavengers may be a good adjuvant therapy to reduce ALI in patients with cardiometabolic diseases.

Horse choanae are directionally asymmetric / Las coanas de los caballos son direccionalmente asimétricas

SUMMARY: Studies related to the upper respiratory pathway asymmetries are still scarce in the veterinary literature. We present here a study of choanae asymmetries of a pure horses belonging to "Cavall Pirinenc Català" (Pyrenean Horse Breed). For this goal, the palates of 23 dry skulls with no apparent pathologies were photographed and evaluated using geometric morphometrics. On each photo, we identified and digitized a total of 26 points (subset of 2 mid-sagittal, 4 paired landmarks (discrete homologous points) and 10 semilandmarks (points on an outline determined by extrinsic criteria) per side on the choana. Both fluctuating and directional asymmetries appeared statistically significant, the latter accounting more than half of the total variation. The lateral bend observed in horse choanae may be due to the asymmetrically positioned nasal passages. So detected equine choana asymmetry must rather be considered functional, with no clinical implication and presents an important consideration when equine choanae shape.

RESUMEN: Los estudios relacionados con las asimetrías de las vías respiratorias superiores aún son escasos en la literatura veterinaria. Presentamos un estudio de coanas asimetrías de un caballo puro perteneciente al "Cavall Pirinenc Català" (Raza del Caballo de los Pirineos). Para ello, se fotografiaron y evaluaron los paladares de 23 cráneos secos sin patologías aparentes mediante morfometría geométrica. En cada foto, identificamos y digitalizamos un total de 26 puntos (subconjunto de 2 puntos medio sagitales, 4 puntos de referencia emparejados (puntos homólogos discretos) y 10 puntos semillanos (puntos en un contorno determinado por criterios extrínsecos) por lado de la coana. Ambos fluctúan Las asimetrías direccionales aparecieron estadísticamente significativas, representando estas últimas más de la mitad de la variación total. La curvatura lateral observada en las coanas de caballo puede deberse a los conductos nasales asimétricamente posicionados. Por lo tanto, la asimetría de coanas equinas detectada debería considerarse funcional, sin implicación clínica y presenta una importante consideración cuando se forman coanas equinas.

Extracellular metabolism of 3',5'-cyclic AMP as a source of interstitial adenosine in the rat airways.

In the respiratory tract, intracellular 3',5'-cAMP mediates smooth muscle relaxation triggered by the ß2-adrenoceptor/Gs protein/adenylyl cyclase axis. More recently, we have shown that ß2-adrenoceptor agonists also increase extracellular 3',5'-cAMP levels in isolated rat trachea, which leads to contraction of airway smooth muscle. In many other tissues, extracellular 3',5'-cAMP is metabolized by ectoenzymes to extracellular adenosine, a catabolic pathway that has never been addressed in airways. In order to evaluate the possible extracellular degradation of 3',5'-cAMP into 5'-AMP and adenosine in the airways, isolated rat tracheas were incubated with exogenous 3',5'-cAMP and the amount of 5'-AMP, adenosine and inosine (adenosine metabolite) produced was evaluated using ultraperformance liquid chromatography-tandem mass spectrometry. Incubation of tracheal tissue with 3',5'-cAMP induced a time- and concentration-dependent increase in 5'-AMP, adenosine and inosine in the medium. Importantly, IBMX (non-selective phosphodiesterase (PDE) inhibitor) and DPSPX (selective ecto-PDE inhibitor) reduced the extracellular conversion of 3',5'-cAMP to 5'-AMP. In addition, incubation of 3',5'-cAMP in the presence of AMPCP (inhibitor of ecto-5'-nucleotidase) increased extracellular levels of 5'-AMP while drastically reducing extracellular levels of adenosine and inosine. These results indicate that airways express an extracellular enzymatic system (ecto-phosphodiesterase, ecto-5'-nucleotidase and adenosine deaminase) that sequentially converts 3',5'-cAMP into 5'-AMP, adenosine and inosine. The observation that extracellular 3',5'-cAMP is a source of interstitial adenosine supports the idea that the extrusion and extracellular metabolism of 3',5'-cAMP has a role in respiratory physiology and pathophysiology.

The effect of the volumetric flow rate and endotracheal tube diameter on the pressure distribution in human airways.

The comprehension of the fluid flow in the upper airways is of paramount importance when treating patients under clinical conditions that demand mechanical ventilation. Barotrauma and overdistension are related to undesirable pressures and might be responsible for morbidity and mortality. In the current work we use computational fluid dynamics to investigate the pressure field in the upper respiratory airways. We performed a set of simulations varying the volumetric flow rate of mechanical ventilators and we have shown that the pressure profile can be calculated by means of the volumetric flow rate in accordance with a mathematical expression given by Pav=aV˙2, where Pav is the average pressure at selected sections of the upper airways and V˙ is the volumetric flow rate. Numerical findings provide evidence that the constant a varies with the location of the plane in the upper airways. We also show that some particular diameters of endotracheal tubes (ETT) must be used with care for a given range of volumetric flow rates. Overall, we document an important relationship among pressure, volumetric flow rate and selected internal diameters from ETT.

International psychometric validation of the Living with Chronic Illness Scale in Spanish-speaking patients with chronic obstructive pulmonary disease.

OBJECTIVES: To validate the Living with Chronic Illness (LW-CI) Scale in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Observational, cross-sectional validation study with retest. Acceptability, reliability, precision and construct validity were tested. SETTING: The study took place in primary and secondary specialised units of public and private hospitals of Spain and Colombia. PARTICIPANTS: The study included 612 patients with COPD assessed from May 2018 to May 2019. A consecutive cases sampling was done. Inclusion criteria included: (A) patients with a diagnosis of COPD; (B) native Spanish speaking; (C) able to read and understand questionnaires; and (D) able to provide informed consent. Exclusion criteria included: (A) cognitive deterioration and (B) pharmacological effect or disorder that could disrupt the assessment. RESULTS: The LW-CI-COPD presented satisfactory data quality, with no missing data or floor/ceiling effects, showing high internal consistency for all the domains (Cronbach's alpha for the total score 0.92). Test-retest reliability was satisfactory (intraclass correlation coefficient=0.92). The LW-CI-COPD correlated 0.52-0.64 with quality of life and social support measures. The scale demonstrated satisfactory known-groups validity, yielding significantly different scores in patients grouped according to COPD severity levels. CONCLUSIONS: This has been the first validation study of the LW-CI-COPD. It is a feasible, reliable, valid and precise self-reported scale to measure living with COPD in the Spanish-speaking population. Therefore, it could be recommended for research and clinical practice to measure this concept and evaluate the impact of centred-care interdisciplinary interventions based on the patients' perspective, focused on providing holistic and comprehensive care to patients with COPD.

Influence of Complete Denture Use on Respiratory Capacity: A Systematic Review.

AIM AND OBJECTIVE: This study aimed to determine whether the use of complete dentures has an influence on the respiratory capacity, assessed by the spirometry examination. MATERIALS AND METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis and registered in the International Prospective Register of Systematic Reviews (CRD42021255224). The PICO question (population/exposure/comparison/outcome) was "Does the use of complete dentures influence the respiratory capacity of a toothless subject?" A search strategy was adapted for the PubMed/MEDLINE, The Cochrane Library, OpenGrey, Lilacs, Scopus, and Embase databases. Inclusion criteria were prospective and retrospective studies. The new castle ottawa (NOS) scale and the Methodological Index for Non-randomized studies were selected to assess the quality of the included studies. RESULTS: Four studies were selected, totalizing the evaluation of 242 participants, aged ranging from 40 to 73 years old. Two studies concluded that the use of complete dentures can negatively affect the respiratory capacity. One study stated that it did not interfere regardless of its use during spirometric measurements, and the other reported that dental prosthesis was required in cases of evaluation of the extrathoracic airways. CONCLUSION: The use of complete dentures did not represent relevant changes from the reference values for pulmonary function in the spirometry test. Considering the results of this review, it is not yet possible to establish a clinical protocol for the use of complete dentures during the test. CLINICAL SIGNIFICANCE: Oral rehabilitation with conventional complete dentures is widely used for the treatment of edentulism, especially in elderly patients. In addition, with aging, many complex changes in immunity and respiratory function contribute to the increase in the development of lung diseases. Therefore, it is important to establish a guidance regarding the use or not of the removable dental prostheses in the respiratory capacity test through spirometry examination.