Sexual dimorphism in the human respiratory system has been previously reported at the skeletal (cranial and thoracic) level, but also at the pulmonary level. Regarding lungs, foregoing studies have ...yielded sex‐related differences in pulmonary size as well as lung shape details, but different methodological approaches have led to discrepant results on differences in respiratory patterns between males and females. The purpose of this study is to analyse sexual dimorphism in human lungs during forced respiration using 3D geometric morphometrics. Eighty computed tomographies (19 males and 21 females) were taken in maximal forced inspiration (FI) and expiration (FE), and 415 (semi)landmarks were digitized on 80 virtual lung models for the 3D quantification of pulmonary size, shape and kinematic differences. We found that males showed larger lungs than females (P < 0.05), and significantly greater size and shape differences between FI and FE. Morphologically, males have pyramidal lung geometry, with greater lower lung width when comparing with the apices, in contrast to the prismatic lung shape and similar widths at upper and lower lungs of females. Multivariate regression analyses confirmed the effect of sex on lung size (36.26%; P < 0.05) and on lung shape (7.23%; P < 0.05), and yielded two kinematic vectors with a small but statistically significant angle between them (13.22°; P < 0.05) that confirms sex‐related differences in the respiratory patterns. Our 3D approach shows sexual dimorphism in human lungs likely due to a greater diaphragmatic action in males and a predominant intercostal muscle action in females during breathing. These size and shape differences would lead to different respiratory patterns between sexes, whose physiological implications need to be studied in future research.
Objectives
Sexual dimorphism is an important biological factor underlying morphological variation in the human skeleton. Previous research found sex‐related differences in the static ribcage, with ...males having more horizontally oriented ribs and a wider lower ribcage than females. Furthermore, a recent study found sex‐related differences in the kinematics of the human lungs, with cranio‐caudal movements of the caudal part of the lungs accounting for most of the differences between sexes. However, these movements cannot be quantified in the skeletal ribcage, so we do not know if the differences observed in the lungs are also reflected in sex differences in the motion of the skeletal thorax.
Materials and methods
To address this issue, we quantified the morphological variation of 42 contemporary human ribcages (sex‐balanced) in both maximal inspiration and expiration using 526 landmarks and semilandmarks. Thoracic centroid size differences between sexes were assessed using a t test, and shape differences were assessed using Procrustes shape coordinates, through mean comparisons and dummy regressions of shape on kinematic status. A principal components analysis was used to explore the full range of morphological variation.
Results
Our results show significant size differences between males and females both in inspiration and expiration (p < .01) as well as significant shape differences, with males deforming more than females during inspiration, especially in the mediolateral dimension of the lower ribcage. Finally, dummy regressions of shape on kinematic status showed a small but statistically significant difference in vectors of breathing kinematics between males and females (14.78°; p < .01).
Discussion
We support that sex‐related differences in skeletal ribcage kinematics are discernible, even when soft tissues are not analyzed. We hypothesize that this differential breathing pattern is primarily a result of more pronounced diaphragmatic breathing in males, which might relate to differences in body composition, metabolism, and ultimately greater oxygen demand in males compared to females. Future research should further explore the links between ribcage morphological variation and basal metabolic rate.
Objectives
The human respiratory apparatus is characterized by sexual dimorphism, the cranial airways of males being larger (both absolutely and relatively) than those of females. These differences ...have been linked to sex‐specific differences in body composition, bioenergetics, and respiratory function. However, whether morpho‐functional variation in the thorax is also related to these features is less clear. We apply 3D geometric morphometrics to study these issues and their implications for respiratory function.
Material and methods
Four hundred two landmarks and semilandmarks were measured in CT‐reconstructions of rib cages from adult healthy subjects (Nmale = 18; Nfemale = 24) in maximal inspiration (MI) and maximal expiration (ME). After Procrustes registration, size and shape data were analyzed by mean comparisons and regression analysis. Respiratory function was quantified through functional size, which is defined as the difference of rib cage size between MI and ME.
Results
Males showed significantly larger thorax size (p < .01) and functional size (p < .05) than females. In addition, the 3D‐shape differed significantly between sexes (p < .01). Male rib cages were wider (particularly caudally) and shorter, with more horizontally oriented ribs when compared to females. While thorax widening and rib orientation were unrelated to allometry, thorax shortening showed a slight allometric signal.
Conclusions
Our findings are in line with previous research on sexual dimorphism of the respiratory system. However, we add that thorax shortening observed previously in males is the only feature caused by allometry. The more horizontally oriented ribs and the wider thorax of males may indicate a greater diaphragmatic contribution to rib cage kinematics than in females, and differences in functional size fit with the need for greater oxygen intake in males.
IMPORTANCE More than 70% of patients with resistant hypertension have obstructive sleep apnea (OSA). However, there is little evidence about the effect of continuous positive airway pressure (CPAP) ...treatment on blood pressure in patients with resistant hypertension. OBJECTIVE To assess the effect of CPAP treatment on blood pressure values and nocturnal blood pressure patterns in patients with resistant hypertension and OSA. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized, multicenter clinical trial of parallel groups with blinded end point design conducted in 24 teaching hospitals in Spain involving 194 patients with resistant hypertension and an apnea-hypopnea index (AHI) of 15 or higher. Data were collected from June 2009 to October 2011. INTERVENTIONS CPAP or no therapy while maintaining usual blood pressure control medication. MAIN OUTCOMES AND MEASURES The primary end point was the change in 24-hour mean blood pressure after 12 weeks. Secondary end points included changes in other blood pressure values and changes in nocturnal blood pressure patterns. Both intention-to-treat (ITT) and per-protocol analyses were performed. RESULTS A total of 194 patients were randomly assigned to receive CPAP (n = 98) or no CPAP (control; n = 96). The mean AHI was 40.4 (SD, 18.9) and an average of 3.8 antihypertensive drugs were taken per patient. Baseline 24-hour mean blood pressure was 103.4 mm Hg; systolic blood pressure (SBP), 144.2 mm Hg; and diastolic blood pressure (DBP), 83 mm Hg. At baseline, 25.8% of patients displayed a dipper pattern (a decrease of at least 10% in the average nighttime blood pressure compared with the average daytime blood pressure). The percentage of patients using CPAP for 4 or more hours per day was 72.4%. When the changes in blood pressure over the study period were compared between groups by ITT, the CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg 95% CI, 0.6 to 5.6; P = .02) and 24-hour DBP (3.2 mm Hg 95% CI, 1.0 to 5.4; P = .005), but not in 24-hour SBP (3.1 mm Hg 95% CI, −0.6 to 6.7; P = .10) compared with the control group. Moreover, the percentage of patients displaying a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in the CPAP group than in the control group (35.9% vs 21.6%; adjusted odds ratio OR, 2.4 95% CI, 1.2 to 5.1; P = .02). There was a significant positive correlation between hours of CPAP use and the decrease in 24-hour mean blood pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P = .005). CONCLUSIONS AND RELEVANCE Among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with control resulted in a decrease in 24-hour mean and diastolic blood pressure and an improvement in the nocturnal blood pressure pattern. Further research is warranted to assess longer-term health outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00616265
Background Understanding the enduring respiratory consequences of severe COVID-19 is crucial for comprehensive patient care. This study aims to evaluate the impact of post-COVID conditions on ...respiratory sequelae of severe acute respiratory distress syndrome (ARDS). Methods We examined 88 survivors of COVID-19-associated severe ARDS six months post-intensive care unit (ICU) discharge. Assessments included clinical and functional evaluation as well as plasma biomarkers of endothelial dysfunction, inflammation, and viral response. Additionally, an in vitro model using human umbilical vein endothelial cells (HUVECs) explored the direct impact of post-COVID plasma on endothelial function. Results Post-COVID patients with impaired gas exchange demonstrated persistent endothelial inflammation marked by elevated ICAM-1, IL-8, CCL-2, and ET-1 plasma levels. Concurrently, systemic inflammation, evidenced by NLRP3 overexpression and elevated levels of IL-6, sCD40-L, and C-reactive protein, was associated with endothelial dysfunction biomarkers and increased in post-COVID patients with impaired gas exchange. T-cell activation, reflected in CD69 expression, and persistently elevated levels of interferon-beta (IFN-beta) further contributed to sustained inflammation. The in vitro model confirmed that patient plasma, with altered levels of sCD40-L and IFN-beta proteins, has the capacity to alter endothelial function. Conclusions Six months post-ICU discharge, survivors of COVID-19-associated ARDS exhibited sustained elevation in endothelial dysfunction biomarkers, correlating with the severity of impaired gas exchange. NLRP3 inflammasome activity and persistent T-cell activation indicate on going inflammation contributing to persistent endothelial dysfunction, potentially intensified by sustained viral immune response. Keywords: Acute respiratory distress syndrome, Post-COVID-19 syndrome, Endothelial dysfunction, ICAM-1, Inflammation
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of NLRP3 ...(nucleotide-binding oligomerization domain-like receptor 3).
To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA.
We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein, caspase-1, Gasdermin D, IL-1β, IL-18, and tissue factor, in monocytes and plasma from patients with severe OSA and control subjects without sleep apnea. We explored the association of the different key markers with inflammatory comorbidities.
Monocytes from patients with severe OSA presented higher NLRP3 activity than those from control subjects, which directly correlated with the apnea-hypopnea index and hypoxemic indices. NLRP3 overactivity triggered inflammatory cytokines (IL-1β and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released.
models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia in a hypoxia-inducible factor-1α-dependent manner, and/or in combination with plasma from patients with OSA. Plasma concentrations of tissue factor were higher in patients with OSA with systemic inflammatory comorbidities than in those without them.
In patients with severe OSA, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory response.
Background There are a variable number of obese subjects with self-reported diagnosis of asthma but without current or previous evidence of airflow limitation, bronchial reversibility, or airway ...hyperresponsiveness (misdiagnosed asthma). However, the mechanisms of asthma-like symptoms in obesity remain unclear. Objectives We sought to evaluate the perception of dyspnea during bronchial challenge and exercise testing in obese patients with asthma and misdiagnosed asthma compared with obese control subjects to identify the mechanisms of asthma-like symptoms in obesity. Methods In a cross-sectional study we included obese subjects with asthma (n = 25), misdiagnosed asthma (n = 23), and no asthma or respiratory symptoms (n = 27). Spirometry, lung volumes, exhaled nitric oxide levels, and systemic biomarker levels were measured. Dyspnea scores during adenosine bronchial challenge and incremental exercise testing were obtained. Results During bronchial challenge, patients with asthma or misdiagnosed asthma reached a higher Borg-FEV1 slope than control subjects. Moreover, maximum dyspnea and the Borg–oxygen uptake (V′O2 ) slope were significantly greater during exercise in subjects with asthma or misdiagnosed asthma than in control subjects. The maximum dyspnea achieved during bronchial challenge correlated with IL-1β levels, whereas peak respiratory frequency, ventilatory equivalent for CO2 , and IL-6 and IL-1β levels were independent predictors of the Borg-V′O2 slope during exercise ( r 2 = 0.853, P < .001). Conclusions A false diagnosis of asthma (misdiagnosed asthma) in obese subjects is attributable to an increased perception of dyspnea, which, during exercise, is mainly associated with systemic inflammation and excessive ventilation for metabolic demands.
Introduction
Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. ...Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy.
Methods
The expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using
in vitro
models. In addition, PSGL-1 impact on T-cells function was evaluated by
ex vivo
models.
Results
Data showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia.
Discussion
In conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.
COVID-19 has emerged as a devastating disease in the last 2 years. Many authors appointed to the importance of kallikrein-kinin system (KKS) in COVID-19 pathophysiology as it is involved in ...inflammation, vascular homeostasis, and coagulation. We aim to study the bradykinin cascade and its involvement in severity of patients with COVID-19. This is an observational cohort study involving 63 consecutive patients with severe COVID-19 pneumonia and 27 healthy subjects as control group. Clinical laboratory findings and plasma protein concentration of KKS peptides bradykinin (BK), BK1-8, KKS proteins high–molecular weight kininogen (HK), and KKS enzymes carboxypeptidase N subunit 1 (CPN1), kallikrein B1 (KLKB1), angiotensin converting enzyme 2 (ACE2), and C1 esterase inhibitor (C1INH) were analyzed. We detected dysregulated KKS in patients with COVID-19, characterized by an accumulation of BK1-8 in combination with decreased levels of BK. Accumulated BK1-8 was related to severity of patients with COVID-19. A multivariate logistic regression model retained BK1-8, BK, and D-dimer as independent predictor factors to intensive care unit (ICU) admission. A Youden’s optimal cutoff value of −0.352 was found for the multivariate model score with an accuracy of 92.9%. Multivariate model score-high group presented an odds ratio for ICU admission of 260.0. BK1-8 was related to inflammation, coagulation, and lymphopenia. Our data suggest that BK1-8/BK plasma concentration in combination with D-dimer levels might be retained as independent predictors for ICU admission in patients with COVID-19. Moreover, we reported KKS dysregulation in patients with COVID-19, which was related to disease severity by means of inflammation, hypercoagulation, and lymphopenia.
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