Individualized positive end-expiratory pressure reduces driving pressure in obese patients during laparoscopic surgery under pneumoperitoneum: a randomized clinical trial.

Introduction: During pneumoperitoneum (PNP), airway driving pressure (ΔPRS) increases due to the stiffness of the chest wall and cephalic shift of the diaphragm, which favors atelectasis. In addition, depending on the mechanical power (MP) formulas, they may lead to different interpretations. Methods: Patients >18 years of age with body mass index >35 kg/m2 were included in a single-center randomized controlled trial during their admission for bariatric surgery by abdominal laparoscopy. Intra-abdominal pressure was set at 15 mmHg at the pneumoperitoneum time point (PNP). After the recruitment maneuver, the lowest respiratory system elastance (ERS) was detected during the positive end-expiratory pressure (PEEP) step-wise decrement. Patients were randomized to the 1) CTRL group: ventilated with PEEP of 5 cmH2O and 2) PEEPIND group: ventilated with PEEP value associated with ERS that is 5% higher than its lowest level. Respiratory system mechanics and mean arterial pressure (MAP) were assessed at the PNP, 5 min after randomization (T1), and at the end of the ventilation protocol (T2); arterial blood gas was assessed at PNP and T2. ΔPRS was the primary outcome. Three MP formulas were used: MPA, which computes static PEEP × volume, elastic, and resistive components; MPB, which computes only the elastic component; and MPC, which computes static PEEP × volume, elastic, and resistive components without inspiratory holds. Results: Twenty-eight patients were assessed for eligibility: eight were not included and 20 patients were randomized and allocated to CTRL and PEEPIND groups (n = 10/group). The PEEPIND ventilator strategy reduced ΔPRS when compared with the CTRL group (PEEPIND, 13 ± 2 cmH2O; CTRL, 22 ± 4 cmH2O; p < 0.001). Oxygenation improved in the PEEPIND group when compared with the CTRL group (p = 0.029), whereas MAP was comparable between the PEEPIND and CTRL groups. At the end of surgery, MPA and MPB were correlated in both the CTRL (rho = 0.71, p = 0.019) and PEEPIND (rho = 0.84, p = 0.020) groups but showed different bias (CTRL, -1.9 J/min; PEEPIND, +10.0 J/min). At the end of the surgery, MPA and MPC were correlated in both the CTRL (rho = 0.71, p = 0.019) and PEEPIND (rho = 0.84, p = 0.020) groups but showed different bias (CTRL, -1.9 J/min; PEEPIND, +10.0 J/min). Conclusion: Individualized PEEP was associated with a reduction in ΔPRS and an improvement in oxygenation with comparable MAP. The MP, which solely computes the elastic component, better reflected the improvement in ΔPRS observed in the individualized PEEP group. Clinical Trial Registration: The protocol was registered at the Brazilian Registry of Clinical Trials (U1111-1220-7296).

Natural Language Processing for the Identification of Incidental Lung Nodules in Computed Tomography Reports: A Quality Control Tool.

PURPOSE: To evaluate the diagnostic performance of a natural language processing (NLP) model in detecting incidental lung nodules (ILNs) in unstructured chest computed tomography (CT) reports. METHODS: All unstructured consecutive reports of chest CT scans performed at a tertiary hospital between 2020 and 2021 were retrospectively reviewed (n = 21,542) to train the NLP tool. Internal validation was performed using reference readings by two radiologists of both CT scans and reports, using a different external cohort of 300 chest CT scans. Second, external validation was performed in a cohort of all random unstructured chest CT reports from 57 different hospitals conducted in May 2022. A review by the same thoracic radiologists was used as the gold standard. The sensitivity, specificity, and accuracy were calculated. RESULTS: Of 21,542 CT reports, 484 mentioned at least one ILN (mean age, 71 ± 17.6 [standard deviation] years; women, 52%) and were included in the training set. In the internal validation (n = 300), the NLP tool detected ILN with a sensitivity of 100.0% (95% CI, 97.6 to 100.0), a specificity of 95.9% (95% CI, 91.3 to 98.5), and an accuracy of 98.0% (95% CI, 95.7 to 99.3). In the external validation (n = 977), the NLP tool yielded a sensitivity of 98.4% (95% CI, 94.5 to 99.8), a specificity of 98.6% (95% CI, 97.5 to 99.3), and an accuracy of 98.6% (95% CI, 97.6 to 99.2). Twelve months after the initial reports, 8 (8.60%) patients had a final diagnosis of lung cancer, among which 2 (2.15%) would have been lost to follow-up without the NLP tool. CONCLUSION: NLP can be used to identify ILNs in unstructured reports with high accuracy, allowing a timely recall of patients and a potential diagnosis of early-stage lung cancer that might have been lost to follow-up.

Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients.

BACKGROUND: The profile of changes in airway driving pressure (dPaw) induced by positive-end expiratory pressure (PEEP) might aid for individualized protective ventilation. Our aim was to describe the dPaw versus PEEP curves behavior in ARDS from COVID-19 patients. METHODS: Patients admitted in three hospitals were ventilated with fraction of inspired oxygen (FiO2) and PEEP initially adjusted by oxygenation-based table. Thereafter, PEEP was reduced from 20 until 6 cmH2O while dPaw was stepwise recorded and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was assessed. Each dPaw vs PEEP curve was classified as J-shaped, inverted-J-shaped, or U-shaped according to the difference between the minimum dPaw and the dPaw at the lowest and highest PEEP. In one hospital, hyperdistention and collapse at each PEEP were assessed by electrical impedance tomography (EIT). RESULTS: 184 patients (41 including EIT) were studied. 126 patients (68%) exhibited a J-shaped dPaw vs PEEP profile (PEEPmin_dPaw of 7.5 ± 1.9 cmH2O). 40 patients (22%) presented a U (PEEPmin_dPaw of 12.2 ± 2.6 cmH2O) and 18 (10%) an inverted-J profile (PEEPmin_dPaw of 14,6 ± 2.3 cmH2O). Patients with inverted-J profiles had significant higher body mass index (BMI) and lower baseline partial pressure of arterial oxygen/FiO2 ratio. PEEPmin_dPaw was associated with lower fractions of both alveolar collapse and hyperinflation. CONCLUSIONS: A PEEP adjustment procedure based on PEEP-induced changes in dPaw is feasible and may aid in individualized PEEP for protective ventilation. The PEEP required to minimize driving pressure was influenced by BMI and was low in the majority of patients.

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.

Quantitative Computed Tomography: What Clinical Questions Can it Answer in Chronic Lung Disease?

Quantitative computed tomography (QCT) has recently gained an important role in the functional assessment of chronic lung disease. Its capacity in diagnostic, staging, and prognostic evaluation in this setting is similar to that of traditional pulmonary function testing. Furthermore, it can demonstrate lung injury before the alteration of pulmonary function test parameters, and it enables the classification of disease phenotypes, contributing to the customization of therapy and performance of comparative studies without the intra- and inter-observer variation that occurs with qualitative analysis. In this review, we address technical issues with QCT analysis and demonstrate the ability of this modality to answer clinical questions encountered in daily practice in the management of patients with chronic lung disease.

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.

Case Report: Incidental Finding of COVID-19 Infection after Positron Emission Tomography/CT Imaging in a Patient with a Diagnosis of Histoplasmosis and Recurring Fever.

This is a case report of a 37-year-old woman evaluated with 18F-fludeoxyglucose (18F-FDG) positron emission computed tomography/CT with recurrent fever after treatment with itraconazole for 6 weeks for histoplasmosis. The examination demonstrated a decrease in the dimensions of the pulmonary opacities previously identified in the left lower lobe and attributed to histoplasmosis. In addition to these pulmonary opacities, increased FDG uptake was also observed in lymph nodes present in the cervical region, mediastinum, left lung hilum, and hepatic hilum. Notably, other pulmonary opacities with ground-glass pattern that were not present in the previous computed tomography were detected in the right lower lobe, with mild 18F-FDG uptake. Nasal swab performed shortly after the examination was positive for COVID-19. In this case, the 18F-FDG positron emission computed tomography/CT study demonstrated findings consistent with active COVID-19 infection coexisting with inflammatory changes associated with histoplasmosis infection.

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.

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.

Pulmonary Densitovolumetry Using Computed Tomography in Patients with Nontuberculous Mycobacteria: Correlation with Pulmonary Function Tests.

BACKGROUND: Since nontuberculous mycobacterial pulmonary disease (NTM-PD) is a condition with increasing morbidity, a more detailed knowledge of radiological aspects and pulmonary function plays a relevant role in the diagnosis and appropriate therapeutic management of these patients. OBJECTIVES: The purpose of this study was to evaluate changes in lung parenchyma through computed tomography (CT) densitometry and, secondarily, to analyze its correlation with pulmonary function testing (PFT) in patients with NTM-PD. METHODS: This is a cross-sectional study in which 31 patients with NTM-PD and 27 controls matched by sex, age, and body mass index underwent CT pulmonary densitovolumetry and pulmonary function tests including spirometry and body plethysmograph. RESULTS: Based on the total lung volume (TLV) and total lung mass (TLM) measurements, the cumulative mass ratios were calculated for 3% (M3), 15% (M15), 85% (M85), and 97% (M97) of the TLV. We also calculated the complement, which is represented by TLM (100%) minus the mass of 15% (C85) or 3% (C97) of the TLV. Patients with NTM-PD presented lower values of M3 and M15 than controls, with greater significant differences in the apical third and middle third measurements. Compared to controls, patients with NTM-PD showed higher values of C85 and C97, although significant differences were observed only in the basal third measurements. There were negative correlations of total lung capacity with M3 and M15 in the middle third and apical third measurements. There were positive correlations of residual volume and airway resistance with M3 at the apical third measurement. CONCLUSIONS: Patients with NTM-PD show reduced lung mass and increased lung mass in the apical and basal regions of the lungs, respectively. Furthermore, there is a relationship between lung mass measurements and pulmonary function parameters.

Association of respiratory integer and fractional-order models with structural abnormalities in silicosis.

BACKGROUND AND OBJECTIVE: Integer and fractional-order models have emerged as powerful methods for obtaining information regarding the anatomical or pathophysiological changes that occur during respiratory diseases. However, the precise interpretation of the model parameters in light of the lung structural changes is not known. This study analyzed the associations of the integer and fractional-order models with structural changes obtained using multidetector computed tomography densitometry (MDCT) and pulmonary function analysis. METHODS: Integer and fractional-order models were adjusted to data obtained using the forced oscillation technique (FOT). The results obtained in controls (n = 20) were compared with those obtained in patients with silicosis (n = 32), who were submitted to spirometry, body plethysmograph, FOT, diffusing capacity of the lungs for carbon monoxide (DLCO), and MDCT. The diagnostic accuracy was also investigated using ROC analysis. RESULTS: The observed changes in the integer and fractional-order models were consistent with the pathophysiology of silicosis. The integer-order model showed association only between inertance and the non-aerated compartment (R = -0.69). This parameter also presented the highest associations with spirometry (R = 0.81), plethysmography (-0.61) and pulmonary diffusion (R = 0.53). Considering the fractional-order model, the increase in the poorly aerated and non-aerated regions presented direct correlations with the fractional inertance (R = 0.48), respiratory damping (R = 0.37) and hysteresivity (R = 0.54) and inverse associations with its fractional exponent (R = -0.62) and elastance (-0.35). Significant associations were also observed with spirometry (R = 0.63), plethysmography (0.37) and pulmonary diffusion (R = 0.51). Receiver operator characteristic analysis showed a higher accuracy in the FrOr model (0.908) than the eRIC model (0.789). CONCLUSIONS: Our study has shown clear associations of the integer and fractional-order parameters with anatomical changes obtained via MDCT and pulmonary function measurements. These findings help to elucidate the physiological interpretation of the integer and fractional-order parameters and provide evidence that these parameters are reflective of the abnormal changes in silicosis. We also observed that the fractional-order model showed smaller curve-fitting errors, which resulted in a higher diagnostic accuracy than that of the eRIC model. Taken together, these results provide strong motivation for further studies exploring the clinical and scientific use of these models in respiratory medicine.

Driving pressure and long-term outcomes in moderate/severe acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) patients may present impaired in lung function and structure after hospital discharge that may be related to mechanical ventilation strategy. The aim of this study was to evaluate the association between functional and structural lung impairment, N-terminal-peptide type III procollagen (NT-PCP-III) and driving pressure during protective mechanical ventilation. It was a secondary analysis of data from randomized controlled trial that included patients with moderate/severe ARDS with at least one follow-up visit performed. We obtained serial measurements of plasma NT-PCP-III levels. Whole-lung computed tomography analysis and pulmonary function test were performed at 1 and 6 months of follow-up. A health-related quality of life survey after 6 months was also performed. RESULTS: Thirty-three patients were enrolled, and 21 patients survived after 6 months. In extubation day an association between driving pressure and NT-PCP-III was observed. At 1 and 6 months forced vital capacity (FVC) was negatively correlated to driving pressure (p < 0.01). At 6 months driving pressure was associated with lower FVC independently on tidal volume, plateau pressure and baseline static respiratory compliance after adjustments (r2 = 0.51, p = 0.02). There was a significant correlation between driving pressure and lung densities and nonaerated/poorly aerated lung volume after 6 months. Driving pressure was also related to general health domain of SF-36 at 6 months. CONCLUSION: Even in patients ventilated with protective tidal volume, higher driving pressure is associated with worse long-term pulmonary function and structure.

Computed tomography trachea volumetry in patients with scleroderma: Association with clinical and functional findings.

BACKGROUND: In scleroderma, excessive collagen production can alter tracheal geometry, and computed tomography (CT) volumetry of this structure may aid in detecting possible abnormalities. The objectives of this study were to quantify the morphological abnormalities in the tracheas of ​​patients with scleroderma and to correlate these findings with data on clinical and pulmonary function. METHODS: This was a cross-sectional study in which 28 adults with scleroderma and 27 controls matched by age, gender and body mass index underwent chest CT with posterior segmentation and skeletonization of the images. In addition, all participants underwent pulmonary function tests and clinical evaluation, including the modified Rodnan skin score (mRSS). RESULTS: Most patients (71.4%) had interstitial lung disease on CT. Compared to controls, patients with scleroderma showed higher values ​​in the parameters measured by CT trachea volumetry, including area, eccentricity, major diameter, minor diameter, and tortuosity. The tracheal area and equivalent diameter were negatively correlated with the ratio between forced expiratory flow and forced inspiratory flow at 50% of forced vital capacity (FEF50%/FIF50%) (r = -0.44, p = 0.03 and r = -0.46, p = 0.02, respectively). The tracheal tortuosity was negatively correlated with peak expiratory flow (r = -0.51, p = 0.008). The mRSS showed a positive correlation with eccentricity (r = 0.62, p < 0.001) and tracheal tortuosity (r = 0.51, p = 0.007), while the presence of anti-topoisomerase I antibody (ATA) showed a positive correlation with tracheal tortuosity (r = 0.45, p = 0.03). CONCLUSIONS: In a sample composed predominantly of scleroderma patients with associated interstitial lung disease, there were abnormalities in tracheal geometry, including greater eccentricity, diameter and tortuosity. In these patients, abnormalities in the geometry of the trachea were associated with functional markers of obstruction. In addition, tracheal tortuosity was correlated with cutaneous involvement and the presence of ATA.

Variable Ventilation Associated With Recruitment Maneuver Minimizes Tissue Damage and Pulmonary Inflammation in Anesthetized Lung-Healthy Rats.

BACKGROUND: Recruitment maneuver and positive end-expiratory pressure (PEEP) can be used to counteract intraoperative anesthesia-induced atelectasis. Variable ventilation can stabilize lung mechanics by avoiding the monotonic tidal volume and protect lung parenchyma as tidal recruitment is encompassed within the tidal volume variability. METHODS: Forty-nine (7 per group) male Wistar rats were anesthetized, paralyzed, and mechanically ventilated. A recruitment maneuver followed by stepwise decremental PEEP titration was performed while continuously estimating respiratory system mechanics using recursive least squares. After a new recruitment, animals were ventilated for 2 hours in volume-control with monotonic (VCV) or variable (VV) tidal volumes. PEEP was adjusted at a level corresponding to the minimum elastance or 2 cm H2O above or below this level. Lungs were harvested for histologic analysis (left lung) and cytokines measurement (right lung). Seven animals were euthanized before the first recruitment as controls. RESULTS: A time-dependent increase in respiratory system elastance was observed and significantly minimized by PEEP (P < .001). Variable ventilation attenuated the amount of concentrations of proinflammatory mediators in lung homogenate: neutrophil cytokine-induced neutrophil chemoattractant 1 (VV = 40 ± 5 and VCV = 57 ± 8 pg/mg; P < .0001) and interleukin-1ß (VV = 59 ± 25 and VCV = 261 ± 113 pg/mg; P < .0001). Variable ventilation was also associated with lower structural lung parenchyma damage. Significant reductions in air fraction at dorsal and caudal lung regions were observed in all ventilated animals (P < .001). CONCLUSIONS: Variable ventilation was more protective than conventional ventilation within the applied PEEP levels.

Alveolar Tidal recruitment/derecruitment and Overdistension During Four Levels of End-Expiratory Pressure with Protective Tidal Volume During Anesthesia in a Murine Lung-Healthy Model.

PURPOSE: We compared respiratory mechanics between the positive end-expiratory pressure of minimal respiratory system elastance (PEEPminErs) and three levels of PEEP during low-tidal-volume (6 mL/kg) ventilation in rats. METHODS: Twenty-four rats were anesthetized, paralyzed, and mechanically ventilated. Airway pressure (Paw), flow (F), and volume (V) were fitted by a linear single compartment model (LSCM) Paw(t) = Ers × V(t) + Rrs × F(t) + PEEP or a volume- and flow-dependent SCM (VFDSCM) Paw(t) = (E1 + E2 × V(t)) × V(t) + (K1 + K2 × |F(t)|) × F(t) + PEEP, where Ers and Rrs are respiratory system elastance and resistance, respectively; E1 and E2× V are volume-independent and volume-dependent Ers, respectively; and K1 and K2 × F are flow-independent and flow-dependent Rrs, respectively. Animals were ventilated for 1 h at PEEP 0 cmH2O (ZEEP); PEEPminErs; 2 cmH2O above PEEPminErs (PEEPminErs+2); or 4 cmH2O above PEEPminErs (PEEPminErs+4). Alveolar tidal recruitment/derecruitment and overdistension were assessed by the index %E2 = 100 × [(E2 × VT)/(E1 + |E2| × VT)], and alveolar stability by the slope of Ers(t). RESULTS: %E2 varied between 0 and 30% at PEEPminErs in most respiratory cycles. Alveolar Tidal recruitment/derecruitment (%E2 < 0) and overdistension (%E2 > 30) were predominant in the absence of PEEP and in PEEP levels higher than PEEPminErs, respectively. The slope of Ers(t) was different from zero in all groups besides PEEPminErs+4. CONCLUSIONS: PEEPminErs presented the best compromise between alveolar tidal recruitment/derecruitment and overdistension, during 1 h of low-VT mechanical ventilation.

Oxidative imbalance in mice intoxicated by microcystin-LR can be minimized.

Microcystins-LR (MC-LR) is a cyanotoxin produced by cyanobacteria. We evaluated the antioxidant potential of LASSBio-596 (LB-596, inhibitor of phosphodiesterases 4 and 5), per os, and biochemical markers involved in lung and liver injury induced by exposure to sublethal dose of MC-LR. Fifty male Swiss mice received an intraperitoneal injection of 60 µL of saline (CTRL group, n = 20) or a sublethal dose of MC-LR (40 µg/kg, TOX group, n = 20). After 6 h the animals received either saline (TOX and CTRL groups) or LB-596 (50 mg/kg, TOX + LASS group, n = 10) by gavage. At 6 h after exposure, respiratory mechanics was evaluated in 10 CTRL and 10 TOX mice: there was a significant increase of all lung mechanics parameters (static elastance, viscoelastic component of elastance and lung resistive and viscoelastic/inhomogeneous pressures) in TOX compared to CTRL. 8 h after saline or MC-LR administration, i.e., 2 h after treatment with LB-596, blood serum levels of alanine aminotransferase and aspartate aminotransferase, activity of superoxide dismutase, catalase, and content of malondialdehyde and carbonyl in lung and liver, NADPH oxidase 2 and 4 mRNA expressions, dual oxidase enzyme activity and H2O2 generation were analyzed in lung homogenates. All parameters were significantly higher in TOX than in the other groups. There was no significant difference between CTRL and TOX + LASS. MC-LR deteriorated lung and liver functions and induced redox imbalance in them, which was prevented by oral administration of LB-596.

SinusCor: an advanced tool for heart rate variability analysis.

BACKGROUND: Heart rate variability (HRV) is a widespread non-invasive technique to assess cardiac autonomic function. Time and frequency domain analyses have been used in HRV studies, and their interpretations are linked with both clinical prognostic and diagnostic information. Statistical and geometrical parameters, Fast Fourier Transform and Autoregressive based periodograms are commonly used approaches for the assessment of stationary RR intervals (RRi) signals. However, some conditions result in non-stationary HRV behavior such as the "tilt test" and exercise. This study presents the SinusCor, a new free software for HRV analysis that includes the classical time and frequency domain indices and also techniques for non-stationary data analyses in both time (i.e. root mean squared of successive differences; RMSSD calculated with moving segments) and frequency domains (i.e. time-frequency analysis). RESULTS: An example of RRi was acquired from a young male subject and its time and frequency domain indices were calculated. Time-varying and time-frequency analyses were also presented using the RMSSD and total power, respectively. Validation of the present software against a standard software for HRV analysis (Kubios v 3.0.1) was also performed [SinusCor vs. Kubios: RMSSD-93.96 (41.55) vs. 93.96 (41.55) ms; SDNN-101.29 (29.03) vs. 101.29 (29.03) ms; LF-50.42 (19.76) vs. 50.56 (19.56) n.u.; HF-49.57 (19.76) vs. 49.38 (19.56) n.u.; LF/HF-1.38 (1.08) vs. 1.38 (1.07)]. CONCLUSIONS: SinusCor might be a useful tool for classical stationary and non-stationary HRV analysis.

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease.

BACKGROUND: Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. OBJECTIVES: The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. METHODS: To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. FINDINGS: At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. MAIN CONCLUSIONS: iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice.