Effects of centipedic acid on acute lung injury: A dose-response study in a murine model.

Centipedic Acid (CPA), a natural diterpene from Egletes viscosa, an endemic species of the Caatinga biome, has shown antioxidant and anti-inflammatory properties. However, no report on the CPA on respiratory system mechanics has been so far advanced. We aimed to investigate the dose-response behavior of CPA on E. coli lipopolysaccharide (LPS)-triggered acute lung injury (ALI). Forty-eight C57BL/6 mice were randomly divided into six groups: control (SS), induced to ALI (LPS), 4 groups induced to ALI pre-treated with 12.5, 25, 50 and 100 mg/kg of CPA (CPA12.5, CPA25, CPA50 and CPA100 groups). CPA 100 mg/kg could prevent inflammatory cell infiltration, alveolar collapse, changes in tissue micromechanics and lung function (airway resistance, tissue elastance, tissue resistance and Static compliance). These results indicate preventive potential of this compound in the installation of ALI.

Lung inflammation induced by silica particles triggers hippocampal inflammation, synapse damage and memory impairment in mice.

BACKGROUND: Considerable evidence indicates that a signaling crosstalk between the brain and periphery plays important roles in neurological disorders, and that both acute and chronic peripheral inflammation can produce brain changes leading to cognitive impairments. Recent clinical and epidemiological studies have revealed an increased risk of cognitive impairment and dementia in individuals with impaired pulmonary function. However, the mechanistic underpinnings of this association remain unknown. Exposure to SiO2 (silica) particles triggers lung inflammation, including infiltration by peripheral immune cells and upregulation of pro-inflammatory cytokines. We here utilized a mouse model of lung silicosis to investigate the crosstalk between lung inflammation and memory. METHODS: Silicosis was induced by intratracheal administration of a single dose of 2.5 mg SiO2/kg in mice. Molecular and behavioral measurements were conducted 24 h and 15 days after silica administration. Lung and hippocampal inflammation were investigated by histological analysis and by determination of pro-inflammatory cytokines. Hippocampal synapse damage, amyloid-ß (Aß) peptide content and phosphorylation of Akt, a proxy of hippocampal insulin signaling, were investigated by Western blotting and ELISA. Memory was assessed using the open field and novel object recognition tests. RESULTS: Administration of silica induced alveolar collapse, lung infiltration by polymorphonuclear (PMN) cells, and increased lung pro-inflammatory cytokines. Lung inflammation was followed by upregulation of hippocampal pro-inflammatory cytokines, synapse damage, accumulation of the Aß peptide, and memory impairment in mice. CONCLUSION: The current study identified a crosstalk between lung and brain inflammatory responses leading to hippocampal synapse damage and memory impairment after exposure to a single low dose of silica in mice.

Increased Lung Immune Metabolic Activity in COVID-19 Survivors.

PURPOSE: We quantified lung glycolytic metabolic activity, clinical symptoms and inflammation, coagulation, and endothelial activation biomarkers in 2019 coronavirus disease (COVID-19) pneumonia survivors. METHODS: Adults previously hospitalized with moderate to severe COVID-19 pneumonia were prospectively included. Subjects filled out a questionnaire on clinical consequences, underwent chest CT and 18 F-FDG PET/CT, and provided blood samples on the same day. Forty-five volunteers served as control subjects. Analysis of CT images and quantitative voxel-based analysis of PET/CT images were performed for both groups. 18 F-FDG uptake in the whole-lung volume and in high- and low-attenuation areas was calculated and normalized to liver values. Quantification of plasma markers of inflammation (interleukin 6), d -dimer, and endothelial cell activation (angiopoietins 1 and 2, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1) was also performed. RESULTS: We enrolled 53 COVID-19 survivors (62.3% were male; median age, 50 years). All survivors reported at least 1 persistent symptom, and 41.5% reported more than 6 symptoms. The mean lung density was greater in survivors than in control subjects, and more metabolic activity was observed in normal and dense lung areas, even months after symptom onset. Plasma proinflammatory, coagulation, and endothelial activation biomarker concentrations were also significantly higher in survivors. CONCLUSION: We observed more metabolic activity in areas of high and normal lung attenuation several months after moderate to severe COVID-19 pneumonia. In addition, plasma markers of thromboinflammation and endothelial activation persisted. These findings may have implications for our understanding of the in vivo pathogenesis and long-lasting effects of COVID-19 pneumonia.

Subacute and sublethal ingestion of microcystin-LR impairs lung mitochondrial function by an oligomycin-like effect.

Microcystin-LR (MC-LR) is a potent cyanotoxin that can reach several organs. However subacute exposure to sublethal doses of MC-LR has not yet well been studied. Herein, we evaluated the outcomes of subacute and sublethal MC-LR exposure on lungs. Male BALB/c mice were exposed to MC-LR by gavage (30 µg/kg) for 20 consecutive days, whereas CTRL mice received filtered water. Respiratory mechanics was not altered in MC-LR group, but histopathology disclosed increased collagen deposition, immunological cell infiltration, and higher percentage of collapsed alveoli. Mitochondrial function was extensively affected in MC-LR animals. Additionally, a direct in vitro titration of MC-LR revealed impaired mitochondrial function. In conclusion, MC-LR presented an intense deleterious effect on lung mitochondrial function and histology. Furthermore, MC-LR seems to exert an oligomycin-like effect in lung mitochondria. This study opens new perspectives for the understanding of the putative pulmonary initial mechanisms of damage resulting from oral MC-LR intoxication.

Comparison of 68Ga-DOTATOC and 18F-FDG Thoracic Lymph Node and Pulmonary Lesion Uptake Using PET/CT in Postprimary Tuberculosis.

Tuberculosis (TB) remains one of the world's leading infectious cause of morbidity and mortality. Positron emission tomography (PET) associated with computed tomography (CT) allows a structural and metabolic evaluation of TB lesions, being an excellent noninvasive alternative for understanding its pathogenesis. DOTATOC labeled with gallium-68 (68Ga-DOTATOC) can bind to somatostatin receptors present in activated macrophages and lymphocytes, cells with a fundamental role in TB pathogenesis. We describe 68Ga-DOTATOC uptake distribution and patterns in thoracic lymph nodes (LN) and pulmonary lesions (PL) in immunocompetent patients with active postprimary TB, analyze the relative LN/PL uptake, and compare this two tracer's uptake. High uptake of both radiotracers in PL and LN was demonstrated, with higher LN/PL ratio on 68Ga-DOTATOC (P < 0.05). Considering that LN in immunocompetent patients are poorly studied, 68Ga-DOTATOC can contribute to the understanding of the complex immunopathogenesis of TB.

Pulmonary impairment in type 2 diabetic rats and its improvement by exercise.

AIM: We aimed to evaluate whether the streptozotocin-induced diabetic model can generate lung functional, histological and biochemical impairments and whether moderate exercise can prevent these changes. METHODS: Wistar rats were assigned to control (CTRL), exercise (EXE), diabetic (D) and diabetic with exercise (D+EXE) groups. We used the n5-STZ model of diabetes mellitus triggered by a single injection of streptozotocin (STZ, 120 mg/kg b.w., i.p.) in newborn rats on their 5th day of life. EXE and D+EXE rats were trained by running on a motorized treadmill, 5 days a week for 9 weeks. Blood glucose, body weight, food intake, exercise capacity, lung mechanics, morphology, and antioxidant enzymatic activity were analysed. RESULTS: On the 14th week of life, diabetic rats exhibited a significant impairment in post-prandial glycaemia, glucose tolerance, body weight, food intake, lung function (tissue viscance, elastance, Newtonian resistance and hysteresis), morphological parameters, redox balance and exercise capacity. Physical training completely prevented the diabetes-induced alterations, except for those on fasting blood glucose, which nevertheless remained stable. CONCLUSIONS: Mild diabetes in n5-STZ-treated rats jeopardized pulmonary mechanics, morphology and redox balance, which confirms the occurrence of diabetes-induced pneumopathy. Moreover, moderate exercise completely prevented all diabetes-induced respiratory alterations.

Isolation of Mitochondria From Fresh Mice Lung Tissue.

Direct analysis of isolated mitochondria enables a better understanding of lung dysfunction. Despite well-defined mitochondrial isolation protocols applicable to other tissues, such as the brain, kidney, heart, and liver, a robust and reproductive protocol has not yet been advanced for the lung. We describe a protocol for the isolation of mitochondria from lung tissue aiming for functional analyses of mitochondrial O2 consumption, transmembrane potential, reactive oxygen species (ROS) formation, ATP production, and swelling. We compared our protocol to that used for heart mitochondrial function that is well-established in the literature, and achieved similar results.

Different Tidal Volumes May Jeopardize Pulmonary Redox and Inflammatory Status in Healthy Rats Undergoing Mechanical Ventilation.

Mechanical ventilation (MV) is essential for the treatment of critical patients since it may provide a desired gas exchange. However, MV itself can trigger ventilator-associated lung injury in patients. We hypothesized that the mechanisms of lung injury through redox imbalance might also be associated with pulmonary inflammatory status, which has not been so far described. We tested it by delivering different tidal volumes to normal lungs undergoing MV. Healthy Wistar rats were divided into spontaneously breathing animals (control group, CG), and rats were submitted to MV (controlled ventilation mode) with tidal volumes of 4 mL/kg (MVG4), 8 mL/kg (MVG8), or 12 mL/kg (MVG12), zero end-expiratory pressure (ZEEP), and normoxia (FiO2 = 21%) for 1 hour. After ventilation and euthanasia, arterial blood, bronchoalveolar lavage fluid (BALF), and lungs were collected for subsequent analysis. MVG12 presented lower PaCO2 and bicarbonate content in the arterial blood than CG, MVG4, and MVG8. Neutrophil influx in BALF and MPO activity in lung tissue homogenate were significantly higher in MVG12 than in CG. The levels of CCL5, TNF-α, IL-1, and IL-6 in lung tissue homogenate were higher in MVG12 than in CG and MVG4. In the lung parenchyma, the lipid peroxidation was more important in MVG12 than in CG, MVG4, and MVG8, while there was more protein oxidation in MVG12 than in CG and MVG4. The stereological analysis confirmed the histological pulmonary changes in MVG12. The association of controlled mode ventilation and high tidal volume, without PEEP and normoxia, impaired pulmonary histoarchitecture and triggered redox imbalance and lung inflammation in healthy adult rats.

Pulmonary Emphysema Regional Distribution and Extent Assessed by Chest Computed Tomography Is Associated With Pulmonary Function Impairment in Patients With COPD.

Objective: This study aimed to evaluate how emphysema extent and its regional distribution quantified by chest CT are associated with clinical and functional severity in patients with chronic obstructive pulmonary disease (COPD). Methods/Design: Patients with a post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) < 0.70, without any other obstructive airway disease, who presented radiological evidence of emphysema on visual CT inspection were retrospectively enrolled. A Quantitative Lung Imaging (QUALI) system automatically quantified the volume of pulmonary emphysema and adjusted this volume to the measured (EmphCTLV) or predicted total lung volume (TLV) (EmphPLV) and assessed its regional distribution based on an artificial neural network (ANN) trained for this purpose. Additionally, the percentage of lung volume occupied by low-attenuation areas (LAA) was computed by dividing the total volume of regions with attenuation lower or equal to -950 Hounsfield units (HU) by the predicted [LAA (%PLV)] or measured CT lung volume [LAA (%CTLV)]. The LAA was then compared with the QUALI emphysema estimations. The association between emphysema extension and its regional distribution with pulmonary function impairment was then assessed. Results: In this study, 86 patients fulfilled the inclusion criteria. Both EmphCTLV and EmphPLV were significantly lower than the LAA indices independently of emphysema severity. CT-derived TLV significantly increased with emphysema severity (from 6,143 ± 1,295 up to 7,659 ± 1,264 ml from mild to very severe emphysema, p < 0.005) and thus, both EmphCTLV and LAA significantly underestimated emphysema extent when compared with those values adjusted to the predicted lung volume. All CT-derived emphysema indices presented moderate to strong correlations with residual volume (RV) (with correlations ranging from 0.61 to 0.66), total lung capacity (TLC) (from 0.51 to 0.59), and FEV1 (~0.6) and diffusing capacity for carbon monoxide DLCO (~0.6). The values of FEV1 and DLCO were significantly lower, and RV (p < 0.001) and TLC (p < 0.001) were significantly higher with the increasing emphysema extent and when emphysematous areas homogeneously affected the lungs. Conclusions: Emphysema volume must be referred to the predicted and not to the measured lung volume when assessing the CT-derived emphysema extension. Pulmonary function impairment was greater in patients with higher emphysema volumes and with a more homogeneous emphysema distribution. Further studies are still necessary to assess the significance of CTpLV in the clinical and research fields.

Estimating COVID-19 Pneumonia Extent and Severity From Chest Computed Tomography.

BACKGROUND: COVID-19 pneumonia extension is assessed by computed tomography (CT) with the ratio between the volume of abnormal pulmonary opacities (PO) and CT-estimated lung volume (CTLV). CT-estimated lung weight (CTLW) also correlates with pneumonia severity. However, both CTLV and CTLW depend on demographic and anthropometric variables. PURPOSES: To estimate the extent and severity of COVID-19 pneumonia adjusting the volume and weight of abnormal PO to the predicted CTLV (pCTLV) and CTLW (pCTLW), respectively, and to evaluate their possible association with clinical and radiological outcomes. METHODS: Chest CT from 103 COVID-19 and 86 healthy subjects were examined retrospectively. In controls, predictive equations for estimating pCTLV and pCTLW were assessed. COVID-19 pneumonia extent and severity were then defined as the ratio between the volume and the weight of abnormal PO expressed as a percentage of the pCTLV and pCTLW, respectively. A ROC analysis was used to test differential diagnosis ability of the proposed method in COVID-19 and controls. The degree of pneumonia extent and severity was assessed with Z-scores relative to the average volume and weight of PO in controls. Accordingly, COVID-19 patients were classified as with limited, moderate and diffuse pneumonia extent and as with mild, moderate and severe pneumonia severity. RESULTS: In controls, CTLV could be predicted by sex and height (adjusted R 2 = 0.57; P < 0.001) while CTLW by age, sex, and height (adjusted R 2 = 0.6; P < 0.001). The cutoff of 20% (AUC = 0.91, 95%CI 0.88-0.93) for pneumonia extent and of 50% (AUC = 0.91, 95%CI 0.89-0.92) for pneumonia severity were obtained. Pneumonia extent were better correlated when expressed as a percentage of the pCTLV and pCTLW (r = 0.85, P < 0.001), respectively. COVID-19 patients with diffuse and severe pneumonia at admission presented significantly higher CRP concentration, intra-hospital mortality, ICU stay and ventilatory support necessity, than those with moderate and limited/mild pneumonia. Moreover, pneumonia severity, but not extent, was positively and moderately correlated with age (r = 0.46) and CRP concentration (r = 0.44). CONCLUSION: The proposed estimation of COVID-19 pneumonia extent and severity might be useful for clinical and radiological patient stratification.

Acute cylindrospermopsin exposure: Pulmonary and liver harm and mitigation by dexamethasone.

Cylindrospermopsin (CYN) is a cyanotoxin of increasing worldwide environmental importance as it can harm human beings. Dexamethasone is a steroidal anti-inflammatory agent. Thus, we aimed at evaluating the pulmonary outcomes of acute CYN intoxication and their putative mitigation by dexamethasone. Male BALB/c mice received intratracheally a single dose of saline or CYN (140 µg/kg). Eighteen hours after exposure, mice instilled with either saline solution (Ctrl) or CYN were intramuscularly treated with saline (Tox) or 2 mg/kg dexamethasone (Tox + dexa) every 6 h for 48 h. Pulmonary mechanics was evaluated 66 h after instillation using the forced oscillation technique (flexiVent) to determine airway resistance (RN), tissue viscance (G) and elastance (H). After euthanasia, the lungs were removed and separated for quantification of CYN, myeloperoxidase activity and IL-6 and IL-17 levels plus histological analysis. CYN was also measured in the liver. CYN increased G and H, alveolar collapse, PMN cells infiltration, elastic and collagen fibers, activated macrophages, peroxidase activity in lung and hepatic tissues, as well as IL-6 and IL-17 levels in the lung. Tox + Dexa mice presented total or partial reversion of the aforementioned alterations. Briefly, CYN impaired pulmonary and hepatic characteristics that were mitigated by dexamethasone.

Acute exposure to C60 fullerene damages pulmonary mitochondrial function and mechanics.

C60 fullerene (C60) nanoparticles, a nanomaterial widely used in technology, can offer risks to humans, overcome biological barriers, and deposit onto the lungs. However, data on its putative pulmonary burden are scanty. Recently, the C60 interaction with mitochondria has been described in vitro and in vivo. We hypothesized that C60 impairs lung mechanics and mitochondrial function. Thirty-five male BALB/c mice were randomly divided into two groups intratracheally instilled with vehicle (0.9% NaCl + 1% Tween 80, CTRL) or C60 (1.0 mg/kg, FUL). Twenty-four hours after exposure, 15 FUL and 8 CTRL mice were anesthetized, paralyzed, and mechanically ventilated for the determination of lung mechanics. After euthanasia, the lungs were removed en bloc at end-expiration for histological processing. Lung tissue elastance and viscance were augmented in FUL group. Increased inflammatory cell number, alveolar collapse, septal thickening, and pulmonary edema were detected. In other six FUL and six CTRL mice, mitochondria expressed reduction in state 1 respiration [FUL = 3.0 ± 1.14 vs. CTRL = 4.46 ± 0.9 (SEM) nmol O2/min/mg protein, p = 0.0210], ATP production (FUL = 122.6 ± 18 vs. CTRL = 154.5 ± 14 µmol/100 µg protein, p = 0.0340), and higher oxygen consumption in state 4 [FUL = 12.56 ± 0.9 vs. CTRL = 8.26 ± 0.6], generation of reactive oxygen species (FUL 733.1 ± 169.32 vs. CTRL = 486.39 ± 73.1 nmol/100 µg protein, p = 0.0313) and reason ROS/ATP [FUL = 8.73 ± 2.3 vs. CTRL = 2.99 ± 0.3]. In conclusion, exposure to fullerene C60 impaired pulmonary mechanics and mitochondrial function, increased ROS concentration, and decrease ATP production.

Eugenol mitigated acute lung but not spermatic toxicity of C60 fullerene emulsion in mice.

C60 fullerene (C60) is a nano-pollutant that can damage the respiratory system. Eugenol exhibits significant anti-inflammatory and antioxidant properties. We aimed to investigate the time course of C60 emulsion-induced pulmonary and spermatic harms, as well as the effect of eugenol on C60 emulsion toxicity. The first group of mice (protocol 1) received intratracheally C60 emulsion (1.0 mg/kg BW) or vehicle and were tested at 12, 24, 72 and 96 h (F groups) thereafter. The second group of mice (protocol 2) received intratracheally C60 emulsion or vehicle, 1 h later were gavaged with eugenol (150 mg/kg) or vehicle, and experiments were done 24 h after instillation. Lung mechanics, morphology, redox markers, cytokines and epididymal spermatozoa were analyzed. Protocol 1: Tissue damping (G) and elastance (H) were significantly higher in F24 than in others groups, except for H in F72. Morphological and inflammatory parameters were worst at 24 h and subsequently declined until 96 h, whereas redox and spermatic parameters worsened over the whole period. Eugenol eliminated the increase in G, H, cellularity, and cytokines, attenuated oxidative stress induced by C60 exposure, but had no effect on sperm. Hence, exposure to C60 emulsion deteriorated lung morphofunctional, redox and inflammatory characteristics and increased the risk of infertility. Furthermore, eugenol avoided those changes, but did not prevent sperm damage.

On some factors determining the pressure drop across tracheal tubes during high-frequency percussive ventilation: a flow-independent model.

To provide an in vitro estimation of the pressure drop across tracheal tubes (ΔPTT) in the face of given pulsatile frequencies and peak pressures (Pwork) delivered by a high-frequency percussive ventilator (HFPV) applied to a lung model. Tracheal tubes (TT) 6.5, 7.5 and 8.0 were connected to a test lung simulating the respiratory system resistive (R = 5, 20, 50 cmH2O/L/s) and elastic (C = 10, 20, and 50 mL/cmH2O) loads. The model was ventilated by HFPV with a pulse inspiratory peak pressure (work pressure Pwork) augmented in 5-cmH2O steps from 20 to 45 cmH2O, yielding 6 diverse airflows. The percussive frequency (f) was set to 300, 500 and 700 cycles/min, respectively. Pressure (Paw and Ptr) and flow (V') measurements were performed for all 162 possible combinations of loads, frequencies, and work pressures for each TT size, thus yielding 486 determinations. For each respiratory cycle ΔPTT was calculated by subtracting each peak Ptr from its corresponding peak Paw. A non-linear model was constructed to assess the relationships between single parameters. Performance of the produced model was measured in terms of root mean square error (RMSE) and the coefficient of determination (r2). ΔPTT was predicted by Pwork (exponential Gaussian relationship), resistance (quadratic and linear terms), frequency (quadratic and linear terms) and tube diameter (linear term), but not by compliance. RMSE of the model on the testing dataset was 1.17 cmH2O, r2 was 0.79 and estimation error was lower than 1 cmH2O in 68% of cases. As a result, even without a flow value, the physician would be able to evaluate ΔPTT pressure. If the present results of our bench study could be clinically confirmed, the use of a nonconventional ventilatory strategy as HFPV, would be safer and easier.

COVID-19 Chest Computed Tomography to Stratify Severity and Disease Extension by Artificial Neural Network Computer-Aided Diagnosis.

Purpose: This work aims to develop a computer-aided diagnosis (CAD) to quantify the extent of pulmonary involvement (PI) in COVID-19 as well as the radiological patterns referred to as lung opacities in chest computer tomography (CT). Methods: One hundred thirty subjects with COVID-19 pneumonia who underwent chest CT at hospital admission were retrospectively studied (141 sets of CT scan images). Eighty-eight healthy individuals without radiological evidence of acute lung disease served as controls. Two radiologists selected up to four regions of interest (ROI) per patient (totaling 1,475 ROIs) visually regarded as well-aerated regions (472), ground-glass opacity (GGO, 413), crazy paving and linear opacities (CP/LO, 340), and consolidation (250). After balancing with 250 ROIs for each class, the density quantiles (2.5, 25, 50, 75, and 97.5%) of 1,000 ROIs were used to train (700), validate (150), and test (150 ROIs) an artificial neural network (ANN) classifier (60 neurons in a single-hidden-layer architecture). Pulmonary involvement was defined as the sum of GGO, CP/LO, and consolidation volumes divided by total lung volume (TLV), and the cutoff of normality between controls and COVID-19 patients was determined with a receiver operator characteristic (ROC) curve. The severity of pulmonary involvement in COVID-19 patients was also assessed by calculating Z scores relative to the average volume of parenchymal opacities in controls. Thus, COVID-19 cases were classified as mild (

Automatic Quantification of Interstitial Lung Disease From Chest Computed Tomography in Systemic Sclerosis.

Background: Interstitial lung disease (ILD) is a common complication in patients with systemic sclerosis (SSc), and its diagnosis contributes to early treatment decisions. Purposes: To quantify ILD associated with SSc (SSc-ILD) from chest CT images using an automatic quantification method based on the computation of the weight of interstitial lung opacities. Methods: Ninety-four patients with SSc underwent CT, forced vital capacity (FVC), and carbon monoxide diffusion capacity (DLCO) tests. Seventy-three healthy individuals without radiological evidence of lung disease served as controls. After lung and airway segmentation, the ratio between the weight of interstitial opacities [densities between -500 and +50 Hounsfield units (HU)] and the total lung weight (densities between -1,000 and +50 HU) was used as an ILD indicator (ILD[%] = 100 × [LW(-500 to +50HU)/LW(-1, 000 to +50HU)]). The cutoff of normality between controls and SSc was determined with a receiver operator characteristic curve. The severity of pulmonary involvement in SSc patients was also assessed by calculating Z scores of ILD relative to the average interstitial opacities in controls. Accordingly, SSc-ILD was classified as SSc Limited-ILD (Z score < 3) and SSc Extensive-ILD (Z score ≥ 3 or FVC < 70%). Results: Seventy-eight (83%) SSc patients were classified as presenting SSc-ILD (optimal ILD threshold of 23.4%, 0.83 sensitivity, 0.92 specificity, and 0.94 area under the receiver operator characteristic curve, 95% CI from 0.89 to 0.96, 0.93 positive predictive value, and 0.81 negative predictive value, p < 0.001) and exhibited radiological attenuations compatible with interstitial pneumonia dispersed in the lung parenchyma. Thirty-six (38%) patients were classified as SSc Extensive-ILD (ILD threshold ≥ 29.6% equivalent to a Z score ≥ 3) and 42 (45%) as SSc Limited-ILD. Eighteen (50%) patients with SSc Extensive-ILD presented FVC < 70%, being only five patients classified exclusively based on FVC. SSc Extensive-ILD also presented lower DLCO (57.9 ± 17.9% vs. 73.7 ± 19.8%; p < 0.001) and total lung volume (2,916 ± 674 vs. 4,286 ± 1,136, p < 0.001) compared with SSc Limited-ILD. Conclusion: The proposed method seems to provide an alternative to identify and quantify the extension of ILD in patients with SSc, mitigating the subjectivity of semiquantitative analyzes based on visual scores.

Panic disorder respiratory subtype: psychopathology and challenge tests - an update

Panic disorder (PD) pathophysiology is very heterogeneous, and the discrimination of distinct subtypes could be very useful. A subtype based on respiratory symptoms is known to constitute a specific subgroup. However, evidence to support the respiratory subtype (RS) as a distinct subgroup of PD with a well-defined phenotype remains controversial. Studies have focused on characterization of the RS based on symptoms and response to CO2. In this line, we described clinical and biological aspects focused on symptomatology and CO2 challenge tests in PD RS. The main symptoms that characterize RS are dyspnea (shortness of breath) and a choking sensation. Moreover, patients with the RS tended to be more responsive to CO2 challenge tests, which triggered more panic attacks in this subgroup. Future studies should focus on discriminating respiratory-related clusters and exploring psychophysiological and neuroimaging outcomes in order to provide robust evidence to confirm RS as a distinct subtype of PD.

P2Y12 Receptor Antagonist Clopidogrel Attenuates Lung Inflammation Triggered by Silica Particles.

Silicosis is an occupational lung disease caused by inhalation of silica particles. It is characterized by intense lung inflammation, with progressive and irreversible fibrosis, leading to impaired lung function. Purinergic signaling modulates silica-induced lung inflammation and fibrosis through P2X7 receptor. In the present study, we investigate the role of P2Y12, the G-protein-coupled subfamily prototype of P2 receptor class in silicosis. To that end, BALB/c mice received an intratracheal injection of PBS or silica particles (20 mg), without or with P2Y12 receptor blockade by clopidogrel (20 mg/kg body weight by gavage every 48 h) - groups CTRL, SIL, and SIL + Clopi, respectively. After 14 days, lung mechanics were determined by the end-inflation occlusion method. Lung histology was analyzed, and lung parenchyma production of nitric oxide and cytokines (IL-1ß, IL-6, TNF-α, and TGF-ß) were determined. Silica injection reduced animal survival and increased all lung mechanical parameters in relation to CTRL, followed by diffuse lung parenchyma inflammation, increased neutrophil infiltration, collagen deposition and increased pro-inflammatory and pro-fibrogenic cytokine secretion, as well as increased nitrite production. Clopidogrel treatment prevented silica-induced changes in lung function, and significantly reduced lung inflammation, fibrosis, as well as cytokine and nitrite production. These data suggest that inhibition of P2Y12 signaling improves silica-induced lung inflammation, preventing lung functional changes and mortality. Our results corroborate previous observations of silica-induced lung changes and expand the understanding of purinergic signaling in this process.

Panic disorder respiratory subtype: psychopathology and challenge tests - an update.

Panic disorder (PD) pathophysiology is very heterogeneous, and the discrimination of distinct subtypes could be very useful. A subtype based on respiratory symptoms is known to constitute a specific subgroup. However, evidence to support the respiratory subtype (RS) as a distinct subgroup of PD with a well-defined phenotype remains controversial. Studies have focused on characterization of the RS based on symptoms and response to CO2. In this line, we described clinical and biological aspects focused on symptomatology and CO2 challenge tests in PD RS. The main symptoms that characterize RS are dyspnea (shortness of breath) and a choking sensation. Moreover, patients with the RS tended to be more responsive to CO2 challenge tests, which triggered more panic attacks in this subgroup. Future studies should focus on discriminating respiratory-related clusters and exploring psychophysiological and neuroimaging outcomes in order to provide robust evidence to confirm RS as a distinct subtype of PD.