Posterior Lung Research Articles

Intermittent sigh breaths during high-frequency oscillatory ventilation in preterm infants: a randomised crossover study

ObjectiveTo determine if combining high-frequency oscillatory ventilation (HFOV) with additional sigh breaths would improve end-expiratory lung volume (EELV) and oxygenation in preterm infants.DesignProspective interventional crossover study.SettingNeonatal intensive care unit.PatientsVentilated preterm...

6564 A Case of Severe Hypercalcemia in Carney's Complex

Abstract Disclosure: J. Chippior: None. M. Rayan: None. L. Wright: None. L.S. Kirschner: Grant Recipient; Self; Medpace, Sparrow, Corcept Therapeutics, Corcept, Spruce, CinCor, Crinetics, Adrenas. S.W. Ing: Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx, Amolyt, Bridge Bio. Carney complex is a rare syndrome with fewer than 750 reported cases, characterized by lentigniosis, myxomas, and the occurrence of both endocrine and non-endocrine tumors. An inactivating mutation PRKAR1A, which encodes for the type 1A regulatory subunit of Protein kinase A, is responsible for over 70% of familial cases and 37% of sporadic cases. A 31-year-old female with a history of Carney complex, Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD), facial lentigines, spinal Schwannomas, and recent ischemic stroke secondary to embolization of a cardiac atrial myxoma, was transferred to our medical center for hyperemesis and severe hypercalcemia. Albumin-corrected serum calcium measured 15.4 mg/dL (8.6-10.5 mg/dL), ionized calcium 7.8 mg/dL (4.6-5.3 mg/dL) associated with suppressed PTH, normal PTH-related protein, and elevated bone turnover markers, C-telopeptide 4,273 pg/ml (150-635) and Procollagen Type 1 N-terminal Propeptide 222 mcg/L (19-83). Evaluation for etiology of hypercalcemia revealed elevated 1,25 dihydroxy vitamin D at 107.0 pg/ml (20-79) and elevated interleukin-6 at 11 pg/ml (<6.4). IL-6 is expressed by cardiac myxomas. Serum angiotensin-converting enzyme level was 50 U/L (16-85) and infectious workup was negative for potential granulomatous causes of elevated calcitriol (including testing for tuberculosis, histoplasma, blastomyces, bartonella, and coccidioides). CT angiogram of the abdomen and pelvis (completed in preparation of atrial myxoma resection) revealed ground-glass opacities in bilateral posterior lung fields and multiple pulmonary nodules, with the largest measuring 8 mm. After treatment with aggressive intravenous fluid resuscitation, intramuscular calcitonin, and intravenous zoledronic acid, corrected calcium normalized to 9.4 mg/dL at discharge. Urinary cortisol was 6.2 mcg per 24-hr (3.5-45), for which she started hydrocortisone 20 mg daily to treat suspected adrenal insufficiency as excess cortisol secretion in PPNAD may be episodic. Thus remission of hypercortisolism may have unmasked an underlying hypercalcemia, and adrenal insufficiency itself may have contributed to this finding. She had excision of left atrial myxoma and has continued to exhibit normal calcium levels on steroid replacement therapy. Repeat chest CT to further characterize these pulmonary findings is planned. This case illustrates a unique constellation of endocrine features associated with severe hypercalcemia in Carney complex. Presentation: 6/1/2024

6564 A Case Of Severe Hypercalcemia In Carney's Complex

Abstract Disclosure: J. Chippior: None. M. Rayan: None. L. Wright: None. L.S. Kirschner: Grant Recipient; Self; Medpace, Sparrow, Corcept Therapeutics, Corcept, Spruce, CinCor, Crinetics, Adrenas. S.W. Ing: Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx, Amolyt, Bridge Bio. Carney complex is a rare syndrome with fewer than 750 reported cases, characterized by lentigniosis, myxomas, and the occurrence of both endocrine and non-endocrine tumors. An inactivating mutation PRKAR1A, which encodes for the type 1A regulatory subunit of Protein kinase A, is responsible for over 70% of familial cases and 37% of sporadic cases. A 31-year-old female with a history of Carney complex, Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD), facial lentigines, spinal Schwannomas, and recent ischemic stroke secondary to embolization of a cardiac atrial myxoma, was transferred to our medical center for hyperemesis and severe hypercalcemia. Albumin-corrected serum calcium measured 15.4 mg/dL (8.6-10.5 mg/dL), ionized calcium 7.8 mg/dL (4.6-5.3 mg/dL) associated with suppressed PTH, normal PTH-related protein, and elevated bone turnover markers, C-telopeptide 4,273 pg/ml (150-635) and Procollagen Type 1 N-terminal Propeptide 222 mcg/L (19-83). Evaluation for etiology of hypercalcemia revealed elevated 1,25 dihydroxy vitamin D at 107.0 pg/ml (20-79) and elevated interleukin-6 at 11 pg/ml (<6.4). IL-6 is expressed by cardiac myxomas. Serum angiotensin-converting enzyme level was 50 U/L (16-85) and infectious workup was negative for potential granulomatous causes of elevated calcitriol (including testing for tuberculosis, histoplasma, blastomyces, bartonella, and coccidioides). CT angiogram of the abdomen and pelvis (completed in preparation of atrial myxoma resection) revealed ground-glass opacities in bilateral posterior lung fields and multiple pulmonary nodules, with the largest measuring 8 mm. After treatment with aggressive intravenous fluid resuscitation, intramuscular calcitonin, and intravenous zoledronic acid, corrected calcium normalized to 9.4 mg/dL at discharge. Urinary cortisol was 6.2 mcg per 24-hr (3.5-45), for which she started hydrocortisone 20 mg daily to treat suspected adrenal insufficiency as excess cortisol secretion in PPNAD may be episodic. Thus remission of hypercortisolism may have unmasked an underlying hypercalcemia, and adrenal insufficiency itself may have contributed to this finding. She had excision of left atrial myxoma and has continued to exhibit normal calcium levels on steroid replacement therapy. Repeat chest CT to further characterize these pulmonary findings is planned. This case illustrates a unique constellation of endocrine features associated with severe hypercalcemia in Carney complex. Presentation: 6/1/2024

Lung Ultrasound as an Adjunct to Pulse Oximetry and Respiratory Symptoms in the Diagnosis of Freediving-Induced Pulmonary Syndrome.

B-lines on lung ultrasound have been found in asymptomatic competitive breath-hold divers, but their significance and time to resolution are not well understood. We sought to investigate the relationship between B-lines, oxygen saturation, and respiratory symptoms after competitive dives to diagnose pulmonary injury. We performed lung ultrasounds before (predive), immediately after (postdive), and within 1 h (follow-up) of a competitive dive. B-lines were counted in each intercostal space in the anterior, lateral, and posterior lung fields, and the highest number of B-lines within a space was recorded for each lung region. At follow-up, each diver's oxygen saturation and respiratory symptoms were recorded. Statistical analysis included the Kruskal-Wallis test, Spearman's correlation, and sensitivity and specificity calculations. Forty-four divers completed 143 individual dives of four different disciplines. The median number of B-lines was 0 (IQR inclusive=0) predive, 1 (IQR=3) postdive, and 0 (IQR=1) at follow-up. There was a significant difference in total B-lines between measurement times (p<0.001). Sensitivity and specificity of hypoxemia, clinically significant B-lines, and both measures in tandem in detecting respiratory symptomatology were 52% and 76%, 24% and 92%, and 24% and 95%, respectively. B-lines are a common phenomenon in competitive breath-hold divers on surfacing and decrease within 1 h, suggesting a physiologic fluid shift. B-lines are negatively correlated with oxygen saturation, indicating that extravascular fluid impairs gas exchange in the lung. Neither hypoxemia nor clinically significant B-lines were found to be reliable indicators for respiratory symptomatology, suggesting that there may be multiple phenotypes of freediving-induced pulmonary syndrome.

Lung ultrasound score evaluation of the effect of pressure-controlled ventilation volume-guaranteed on patients undergoing laparoscopic-assisted radical gastrectomy.

Laparoscopic-assisted radical gastrectomy (LARG) is the standard treatment for early-stage gastric carcinoma (GC). However, the negative impact of this procedure on respiratory function requires the optimized intraoperative management of patients in terms of ventilation. To investigate the influence of pressure-controlled ventilation volume-guaranteed (PCV-VG) and volume-controlled ventilation (VCV) on blood gas analysis and pulmonary ventilation in patients undergoing LARG for GC based on the lung ultrasound score (LUS). The study included 103 patients with GC undergoing LARG from May 2020 to May 2023, with 52 cases undergoing PCV-VG (research group) and 51 cases undergoing VCV (control group). LUS were recorded at the time of entering the operating room (T0), 20 minutes after anesthesia with endotracheal intubation (T1), 30 minutes after artificial pneumoperitoneum (PP) establishment (T2), and 15 minutes after endotracheal tube removal (T5). For blood gas analysis, arterial partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) were observed. Peak airway pressure (Ppeak), plateau pressure (Pplat), mean airway pressure (Pmean), and dynamic pulmonary compliance (Cdyn) were recorded at T1 and T2, 1 hour after PP establishment (T3), and at the end of the operation (T4). Postoperative pulmonary complications (PPCs) were recorded. Pre- and postoperative serum interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Compared with those at T0, the whole, anterior, lateral, posterior, upper, lower, left, and right lung LUS of the research group were significantly reduced at T1, T2, and T5; in the control group, the LUS of the whole and partial lung regions (posterior, lower, and right lung) decreased significantly at T2, while at T5, the LUS of the whole and some regions (lateral, lower, and left lung) increased significantly. In comparison with the control group, the whole and regional LUS of the research group were reduced at T1, T2, and T5, with an increase in PaO2, decrease in PaCO2, reduction in Ppeak at T1 to T4, increase in Pmean and Cdyn, and decrease in Pplat at T4, all significant. The research group showed a significantly lower incidence of PPCs than the control group within 3 days postoperatively. Postoperative IL-1β, IL-6, and TNF-α significantly increased in both groups, with even higher levels in the control group. LUS can indicate intraoperative non-uniformity and postural changes in pulmonary ventilation under PCV-VG and VCV. Under the lung protective ventilation strategy, the PCV-VG mode more significantly improved intraoperative lung ventilation in patients undergoing LARG for GC and reduced lung injury-related cytokine production, thereby alleviating lung injury.

Pulmonary inflammation decreases with ultra-protective ventilation in experimental ARDS under VV-ECMO: a positron emission tomography study.

Experimentally, ultra-protective ventilation (UPV, tidal volumes [VT] < 4 mL.kg-1) strategies in conjunction with veno-venous extracorporeal membrane oxygenation (VV-ECMO) are associated with lesser ventilator-induced lung injuries (VILI) during acute respiratory distress syndrome (ARDS). However, whether these strategies reduce lung inflammation more effectively than protective ventilation (PV) remains unclear. We aimed to demonstrate that a UPV strategy decreases acute lung inflammation in comparison with PV in an experimental swine model of ARDS. ARDS was induced by tracheal instillation of chlorhydric acid in sedated and paralyzed animals under mechanical ventilation. Animals were randomized to receive either UPV (VT 1 mL.kg-1, positive end-expiration pressure [PEEP] set to obtain plateau pressure between 20 and 25 cmH2O and respiratory rate [RR] at 5 min-1 under VV-ECMO) or PV (VT 6 mL.kg-1, PEEP set to obtain plateau pressure between 28 and 30 cmH2O and RR at 25 min-1) during 4 h. After 4 h, a positron emission tomography with [11C](R)-PK11195 (ligand to TSPO-bearing macrophages) injection was realized, coupled with quantitative computerized tomography (CT). Pharmacokinetic multicompartment models were used to quantify regional [11C](R)-PK11195 lung uptake. [11C](R)-PK11195 lung uptake and CT-derived respiratory variables were studied regionally across eight lung regions distributed along the antero-posterior axis. Five pigs were randomized to each study group. Arterial O2 partial pressure to inspired O2 fraction were not significantly different between study groups after experimental ARDS induction (75 [68-80] mmHg in a PV group vs. 87 [69-133] mmHg in a UPV group, p = 0.20). Compared to PV animals, UPV animals exhibited a significant decrease in the regional non-aerated compartment in the posterior lung levels, in mechanical power, and in regional dynamic strain and no statistical difference in tidal hyperinflation after 4 h. UPV animals had a significantly lower [11C](R)-PK11195 uptake, compared to PV animals (non-displaceable binding potential 0.35 [IQR, 0.20-0.59] in UPV animals and 1.01 [IQR, 0.75-1.59] in PV animals, p = 0.01). Regional [11C](R)-PK11195 uptake was independently associated with the interaction of regional tidal hyperinflation and regional lung compliance. In an experimental model of ARDS, 4 h of UPV strategy significantly decreased lung inflammation, in relation to the control of VT-derived determinants of VILI.

FRI201 A Rare Case Of Severe Ectopic ACTH Syndrome Presenting With Thrombocytopenia And Hemolytic Anemia

Abstract Disclosure: N. Mohammad: None. A. Scott: None. N. Raja-Khan: None. Background: Ectopic ACTH syndrome (EAS) is a rare but serious endocrine emergency requiring urgent diagnostic and therapeutic intervention due to the severity of hypercortisolism induced by ACTH-secreting tumors. Here we present an unusual case of EAS associated with hemolytic anemia and thrombocytopenia. Case Presentation: A 64-year-old female with a history of COPD presented with ongoing fatigue, weakness, and bruising of the extremities. The patient was lethargic, then became hypotensive and encephalopathic. Physical exam revealed diffuse ecchymoses. Patient otherwise had no symptoms or physical stigmata of Cushing’s. Labs were significant for hypokalemia, hemolytic anemia, thrombocytopenia, and lactic acidosis. CT demonstrated consolidation in the right hilum, right posterior lung pleural thickening, hypodense lesion in the right hepatic lobe, and bilateral adrenal hyperplasia. Treatment with antibiotics and plasmapheresis was initiated due to suspicion for thrombotic thrombocytopenic purpura and sepsis. Further workup revealed elevated ACTH 1819pg/mL and AM cortisol 102.4ug/dL. Pituitary MRI was normal. Treatment with etomidate infusion was recommended given the severity of hypercortisolism which was refractory to ketoconazole. However, due to clinical deterioration comfort care was initiated. Autopsy revealed metastatic small cell lung cancer. Conclusion: To our knowledge, this is the first report of EAS presenting with thrombocytopenia and hemolytic anemia. Urgent diagnosis and treatment of hypercortisolism is needed to reduce morbidity and mortality in EAS. While surgical excision of the ACTH-secreting tumor is the mainstay of treatment, cortisol levels should be decreased with medication prior to surgery. In severe cases that are refractory to ketoconazole, etomidate infusion can be considered. Presentation: Friday, June 16, 2023

Slight Bronchopneumonia in A Centenarian Diagnosed by Chest CT Scan with Maximum Intensity Projection (MIP)

The current case is a 102-year-old female centenarian with slight bronchopneumonia. She did not have any remarkable health or medical problems until 2022. In May 2023, she developed a cough and fever and underwent a lung CT scan, which revealed a consolidation shadow in the left posterior middle lung. This image was created with a 1mm width for each 1mm interval. Additionally, a further image was generated using maximum intensity projection (MIP) with a 3mm width for a slab thickness of 20mm. Based on this data, a diagnosis of slight bronchopneumonia in the left lung was made. She was treated with levofloxacin 500mg/day for 5 days, which led to clinical improvement.

Prone position PET/CT is useful in reducing gravity-dependent opacity-related [18F]fluorodeoxyglucose uptake.

This study aimed to investigate whether performing [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in the prone position could reduce [18F]FDG uptake in dependent lungs. Patients who underwent [18F]FDG PET/CT in both supine and prone positions from October 2018 to September 2021 were reviewed retrospectively. [18F]FDG uptake of dependent and nondependent lungs was analysed visually and semi-quantitatively. A linear regression analysis was performed to examine the association between the mean standardised uptake value (SUVmean) and the Hounsfield unit (HU). A total of 135 patients (median age, 66years [interquartile range: 58-75years]; 80 men) were included. Dependent lungs showed significantly higher SUVmean and HU than nondependent lungs on supine position PET/CT (sPET/CT, 0.59 ± 0.14 vs. 0.36 ± 0.09, p < 0.001; - 671 ± 66 vs. - 802 ± 43, p < 0.001, respectively) and prone position PET/CT (pPET/CT, 0.45 ± 0.12 vs. 0.42 ± 0.08, p < 0.001; - 731 ± 67 vs. - 790 ± 40, p < 0.001, respectively). Linear regression analysis revealed a strong association between the SUVmean and HU in sPET/CT (R = 0.86, p < 0.001) and moderate association in pPET/CT (R = 0.65, p < 0.001). One hundred and fifteen patients (85.2%) had visually discernible [18F]FDG uptake in the posterior lung on sPET/CT, which disappeared on pPET/CT in all but one patient (0.7%, p < 0.001). [18F]FDG uptake of the lung had moderate-to-strong associations with HU. Gravity-dependent opacity-related [18F]FDG uptake can be effectively reduced on prone position PET/CT. Prone position PET/CT effectively reduces gravity-dependent opacity-related [18F]fluorodeoxyglucose uptake in the lung, potentially improving diagnostic accuracy in evaluating nodules in dependent lungs and offering a more accurate assessment of lung inflammation parameters in interstitial lung disease evaluations. •The study evaluated whether performing [18F]fluorodeoxyglucose ([18F]FDG) PET/CT could reduce [18F]FDG uptake in lungs. •In prone and supine position PET/CT, the [18F]FDG uptake and Hounsfield unit were moderately to strongly associated. •Prone position PET/CT can reduce gravity-dependent opacity-related [18F]FDG uptake by the posterior lung.

Assessment of a Perfusion and Ventilation Method for Detecting Lung and Liver Injury in a Cadaveric Model.

Surgical simulation models have been developed using post-mortem human subjects (PMHS). These models involve the pressurization and ventilation of the PMHS to create a more realistic environment for training and the practice of surgical procedures. The overall objective of this study was to determine the feasibility of a previously developed surgical simulation model to detect soft tissue injuries during a ballistic impact to the torso. One of the main limitations of using PMHS for the assessment of soft tissue injuries in the field of injury biomechanics is the lack of physiological blood flow. To overcome this limitation, the assessment of the surgical simulation model for use in injury biomechanics applications was conducted based on data collected from behind armor blunt trauma (BABT) case studies. Documented injuries in real-world cases included anterior lung contusion, posterior lung contusion, and liver contusion. These real-world injuries were compared to those seen post-impact in the PMHS using pathological and histological techniques. Discussion of limitations and future work is presented.

A brief overview on COVID-19 and its comparison with SARS, MERS, and H1N1

The coronavirus disease 2019 (COVID-19) is a global pandemic infectious disease with higher potential for outbreaks than the other epidemic disease such as severe acute respiratory syndrome (SARS), influenza A (H1N1), and the Middle East respiratory syndrome (MERS), which identified in China on December 31, 2019. The common clinical feature of COVID-19 are including fever, cough, normal or decreased white blood cells (WBCs), and multiple patchy glassy shadows on CT images of the peripheral and posterior lungs. The median of the age of peoples infected with COVID-19 is above 40 years and children are less susceptible to COVID-19 infections. Studies on the epidemiological parameters of COVID-19 reveal its high potential for outbreaks, as now we see around the world.Regarding themechanism action of 2019-nCoV, some researchers suggested that the ACE2 is the receptor of this novel virus. Concerning the clinical diagnosis, CT scans can be used as a highly accurate method for the clinical diagnosis of the COIVD-19 along with the rRT-PCR. In comparison with SARS, MERS, and H1N1, although the novel COVID-19 shows the same clinical features with these diseases, it reveals the higher potential for outbreaks and consequently for causing global pandemics than MERS, H1N1, and SARS.

Effectiveness of T2 biologics in patients with common variable immune deficiency and allergic respiratory disease

IntroductionMany patients with common variable immune deficiency (CVID) have a history suggestive of allergic respiratory disease including chronic rhinosinusitis (CRS) and asthma. The underlying immunologic defect, the presence of comorbid conditions such as bronchiectasis or interstitial lung disease, and recurrent infections may make the diagnosis of these conditions difficult. T2 biologics targeting allergic inflammatory pathways are now the standard of care for severe persistent asthma and CRS with nasal polyposis (CRSwNP). The efficacy of these agents in patients with CVID is unknown. MethodsWe performed a retrospective analysis of patients with CVID at a single academic medical center and identified those who had ever been prescribed a T2 biologic. ResultsWe identified 8 patients with CVID who had ever been prescribed T2 biologics: 6 patients with severe persistent asthma and 2 patients with CRSwNP. All patients had CVID without inflammatory complications with therapeutic IgG levels on immune globulin replacement therapy. Comorbid bronchiectasis was identified in 3 patients and no patients had GLILD. Two patients were taking omalizumab, two on mepolizumab, 1 on benralizumab, and 1 on dupilumab for severe persistent asthma and 2 on dupilumab for CRSwNP. Only 4 patients in this group (50%) had subjective improvement of symptoms and objective clinical benefit based on ability to wean off of corticosteroids and fewer exacerbations per year. Only 1 of these patients had objective improvement in FEV1 by >200mL. Neither of the 2 patients treated with dupilumab for CRswNP reported improvement and the biologic was discontinued. Of the 2 patients with asthma who were found to have eosinophilia on bronchoalveolar fluid analysis, both of these patients had clinical improvement on eosinophil-targeted biologic therapy. All 3 patients who were tested were found to have elevated serum T2 cytokines including IL-4, but this did not predict response to therapy.Table 1(abstract: 191) Demographic and immunologic data of 8 patients with CVID on T2 biologiesAgeGenderT2 biologicIndicationBronchiectasisIncrease in FEV1 by >200mLClinical responseIgG (mg/dL)IgA (mg/dL)IgM (mg/dL)IgE (kU/L)Absolute eosinophil count(K/μL)CD19B cell count (cells/μL)Th2 Cytokine PanelBAL Eosinophils%CT ThoraxBronchoscopy-Pathology82Fomalizumabsevere persistent asthmayesnono1551522923430049Not availableNot availableBasal abnormalitycharacterized by ground glass opacities (GGO), centrilobular nodularity with small focus of consolidation posterior right lower lobe (RLL). Additional focus of patchy groundglass posterior right lung (RL).Not available74Mmepolizumabsevere persistent asthmayesnoyes11681623141681600176Not available25Resolution of right upper lobe (RUL) apical nodule and branching tubular opacity. New clustered nodularity in the posterior RLL with faint GGO in the upper lobes. Moderate bronchial wall thickening, greatest in the lower lobes.Bronchial wall with smooth muscle hypertrophy. Lung parenchyma without evidence of inflammation, fibrosis, or malignancy.57Fomalizumabsevere persistent asthmanonoyes89725221687100103Not available0Diffuse bronchial dilation without bronchial wall thickening. Mild patchy air trapping.Largely denuded and edematous bronchial wall with minima] chronic inflammation, focal subepithelial elastosis, focal expansion of the subbasal lamina, mild increase in mucous secretion.37Fdupilumabchronic rhinosinusitis with nasal Polyposisnonot applicableno787<10<20<2100187elevated IL-4, IL-6Not availableResolved patchy GGO with exception of a new tiny focus of GGO in the basal RLL. Stable mild diffuse bronchial wall thickening.Not available73Fbenralizumabsevere persistentnoyesyes84635<20<2100179Not available4Mild to moderate airway inflammation and diffuse air-trapping. Minimal left basilar linear atelectasis/scarring is new. TracheobronchomalaciaBronchial wall with moderate chronic inflammation and eosionphils (peak 12/hpf), thickened subbasal lamina, mild smooth muscle hypertrophy.43Fdupilumabsevere persistent asthmanonot availableyes12614313556.5056elevated IL-4, IL-5, IL-6Not availableBenign right oblique fissure. 2 small nodules.Not available56Fdupilumabyesnot applicableno95476602.625027Not available1chronic rhinosinusitis with nasal polyposisMultiple new areas of peribronchovascular consolidation and confluent GGO. Widespread tree-inbud nodularity. Mild cylindricalbronchiectasis. Dilated main pulmonary trunk.Bronchial wall with moderate chronic inflammation and scattered eosinophils (6/hpf), thickened subbasal lamina. No granulomas. Right lung bronchial wall with moderate chronic inflammation. Lung parenchyma with airway centered mild interstitial chronic inflammation49 Fmepolizumabsevere persistent asthmanonono166845189510049Not available0Mild bronchial wall thickening and scattered air trapping. Patchy GGO in the left upper lobe with minimal involvement of the lower lobes. Dynamic expiratory images demonstrates evidence of tracheobronchomalacia.Bronchial wall with patchy mild to moderate chronic inflammation with rare neutrophils and eosinophils. Mild smooth muscle hypertrophy. Patchy squamous metaplasia and respiratory bronchiolitis in the left lung.*Clinical response is measured by reduction in exacerbations and/or ability to wean off of corticosteroids for individuals with severe asthma and is measured by improvement in sinonasal symptoms and reduced nasal polypoid burden for CRSwNP. [Display omitted] [Display omitted] ConclusionPatients with CVID may benefit from more direct sampling of nasal mucosal and bronchial secretions (sputum, bronchoalveolar lavage) to determine the potential benefit from T2 biologics in severe allergic respiratory disease. Prospective analyses in larger cohorts following objective indices of improvement as well as changes in serum and mucosal biomarkers are necessary.

Three Zone Scanning Protocol For Lung Ultrasound: An Anatomical Basis.

Lung ultrasound is rapidly gaining popularity based on point of care ease of use, diagnostic fidelity and lack of ionizing radiation. This was particularly notable at the beginning of the COVID-19 pandemic, where concerns of contamination of the x-ray department led to a reluctance to order frequent chest x-rays. Early COVID-19 lung involvement is of a bronchopneumonia, and patches of consolidation adjacent to the chest wall were easily detectable by ultrasound. A large number of proposed scanning protocols were advocated and are often complex and largely based on traditional stethoscope examination or access points on the chest wall rather than the underlying lung anatomy. A surgical understanding of lung anatomy and related surface anatomy has led us to develop a simplified three zone scanning protocol in 2013. The anterior zone corresponds to the upper lobe, and the posterior zone is divided between upper lobe and lower lobe. The relationship between lung lobes and the surface of the chest wall provides the anatomical basis for a simple three scanning zone lung ultrasound protocol.

Lung ultrasound to evaluate aeration changes in response to recruitment maneuver and prone positioning in intubated patients with COVID-19 pneumonia: preliminary study

BackgroundThis single-center preliminary prospective observational study used bedside ultrasound to assess the lung aeration modifications induced by recruitment maneuver and pronation in intubated patients with acute respiratory disease syndrome (ARDS) related to coronavirus 2019 disease (COVID-19).All adult intubated COVID-19 patients suitable for pronation were screened. After enrollment, patients underwent 1 h in a volume-controlled mode in supine position (baseline) followed by a 35-cmH2O-recruitment maneuver of 2 min (recruitment). Final step involved volume-controlled mode in prone position set as at baseline (pronation). At the end of the first two steps and 1 h after pronation, a lung ultrasound was performed, and global and regional lung ultrasound score (LUS) were analyzed. Data sets are presented as a median and 25th–75th percentile.ResultsFrom January to May 2022, 20 patients were included and analyzed. Global LUS reduced from 26.5 (23.5–30.0) at baseline to 21.5 (18.0–23.3) and 23.0 (21.0–26.3) at recruitment (p < 0.001) and pronation (p = 0.004). In the anterior lung regions, the regional LUS were 1.8 (1.1–2.0) following recruitment and 2.0 (1.6–2.2) in the supine (p = 0.008) and 2.0 (1.8–2.3) in prone position (p = 0.023). Regional LUS diminished from 2.3 (2.0–2.5) in supine to 2.0 (1.8–2.0) with recruitment in the lateral lung zones (p = 0.036). Finally, in the posterior lung units, regional LUS improved from 2.5 (2.3–2.8) in supine to 2.3 (1.8–2.5) through recruitment (p = 0.003) and 1.8 (1.3–2.2) with pronation (p < 0.0001).ConclusionsIn our investigation, recruitment maneuver and prone positioning demonstrated an enhancement in lung aeration when compared to supine position, as assessed by bedside lung ultrasound.Trial registration: www.clinicaltrials.gov, Number NCT05209477, prospectively registered and released on 01/26/2022.

Prone position decreases acute lung inflammation measured by [11C](R)-PK11195 positron emission tomography in experimental acute respiratory distress syndrome.

Whether prone positioning (PP) modulates acute lung inflammation by the modulation of biomechanical forces of ventilator-induced lung injuries (VILIs) remains unclear. We aimed to demonstrate that PP decreases acute lung inflammation in animals with experimental acute respiratory distress syndrome (ARDS). Animals were under general anesthesia and protective ventilation (tidal volume 6 mL·kg-1, PEEP 5 cmH2O). ARDS was induced by intratracheal instillation of chlorohydric acid. Animals were then randomized to PP, or to supine position (SP). After 4 h, a positron emission tomography (PET) acquisition with [11C](R)-PK11195 was performed coupled with computerized tomography (CT) acquisitions, allowing the CT quantification of VILI-associated parameters. [11C](R)-PK11195 lung uptake was quantified using pharmacokinetic multicompartment models. Analyses were performed on eight lung sections distributed along the antero-posterior dimension. Six animals were randomized to PP, five to SP (median [Formula: see text]/[Formula: see text] [interquartile range]: 164 [102-269] mmHg). The normally aerated compartment was significantly redistributed to the posterior lung regions of animals in PP, compared with SP. Dynamic strain was significantly increased in posterior regions of SP animals, compared with PP. After 4 h, animals in PP had a significantly lower uptake of [11C](R)-PK11195, compared with SP. [11C](R)-PK11195 regional uptake was independently associated with the study group, dynamic strain, tidal hyperinflation, and regional respiratory system compliance in multivariate analysis. In an experimental model of ARDS, 4 h of PP significantly decreased acute lung inflammation assessed with PET. The beneficial impact of PP on acute lung inflammation was consecutive to the combination of decreased biomechanical forces and changes in the respiratory system mechanics.NEW & NOTEWORTHY Prone position decreases acute lung macrophage inflammation quantified in vivo with [11C](R)-PK11195 positron emission tomography in an experimental acute respiratory distress syndrome. Regional macrophage inflammation is maximal in the most anterior and posterior lung section of supine animals, in relation with increased regional tidal strain and hyperinflation, and reduced regional lung compliance.

The Screening and Diagnostic Value of Posterior Lung Field Angles on Abnormal Pulmonary Function

The Screening and Diagnostic Value of Posterior Lung Field Angles on Abnormal Pulmonary Function

Combination of Radiomics Features and Functional Radiosensitivity Enhances Prediction of Acute Pulmonary Toxicity in a Prospective Validation Cohort of Patients with a Locally Advanced Lung Cancer Treated with VMAT-Radiotherapy.

The standard of care for people with locally advanced lung cancer (LALC) who cannot be operated on is (chemo)-radiation. Despite the application of dose constraints, acute pulmonary toxicity (APT) still often occurs. Prediction of APT is of paramount importance for the development of innovative therapeutic combinations. The two models were previously individually created. With success, the Rad-model incorporated six radiomics functions. After additional validation in prospective cohorts, a Pmap-model was created by identifying a specific region of the right posterior lung and incorporating several clinical and dosimetric parameters. To create and test a novel model to forecast the risk of APT in two cohorts receiving volumetric arctherapy radiotherapy (VMAT), we aimed to include all the variables in this study. In the training cohort, we retrospectively included all patients treated by VMAT for LALC at one institution between 2015 and 2018. APT was assessed according to the CTCAE v4.0 scale. Usual clinical and dosimetric features, as well as the mean dose to the pre-defined Pmap zone (DMeanPmap), were processed using a neural network approach and subsequently validated on an observational prospective cohort. The model was evaluated using the area under the curve (AUC) and balanced accuracy (Bacc). 165 and 42 patients were enrolled in the training and test cohorts, with APT rates of 22.4 and 19.1%, respectively. The AUCs for the Rad and Pmap models in the validation cohort were 0.83 and 0.81, respectively, whereas the AUC for the combined model (Comb-model) was 0.90. The Bacc for the Rad, Pmap, and Comb models in the validation cohort were respectively 78.7, 82.4, and 89.7%. The accuracy of prediction models were increased by combining radiomics, DMeanPmap, and common clinical and dosimetric features. The use of this model may improve the evaluation of APT risk and provide access to novel therapeutic alternatives, such as dose escalation or creative therapy combinations.

VMAT-Based Planning Allows Sparing of a Spatial Dose Pattern Associated with Radiation Pneumonitis in Patients Treated with Radiotherapy for a Locally Advanced Lung Cancer

<h3>Purpose/Objective(s)</h3> In patients treated with radiotherapy for a locally advanced lung cancer, respect of dose constraints to organs at risks (OARs) insufficiently protects patients from acute pulmonary toxicity (APT), such toxicities being associated with a potential impact on treatment's completion and the patients' quality of life. Dosimetric planning doesn't take into account regional lung functionality. An APT prediction model combining usual dosimetry features with the mean dose (DMean_Pmap) received by a voxel-based volume (Pmap) localized in the posterior right lung has been previously developed. A DMean_Pmap ≥ 30.3Gy was associated with a higher risk of APT. In the present study, the authors aim to demonstrate the possibility of decreasing the DMean_Pmap via a volumetric arc therapy (VMAT)-based adapted planning and evaluate the impact on the risk of APT. <h3>Materials/Methods</h3> Among the 207 patients included in the initial study, only patients who presented with an APT ≥ grade 2 and with a probability of APT (Prob_APT) ≥ 8% based on the prediction model were included. Dosimetry planning was optimized with a new constraint (DMean_Pmap < 30.3Gy) added to the usual constraints. Initial and optimized treatment plans were compared using the T-test for independent variables and the non-parametric Mann-Whitney U test otherwise, regarding both doses to OARs and PTV (Planning Target Volume) coverage. Conformity and heterogeneity indexes were also compared. Risk of APT was recalculated using the new dosimetric features and the APT prediction model. <h3>Results</h3> Dosimetric optimization was considered successful for 27 out of the 44 included patients (61.4%), meaning the dosimetric constraint on the Pmap region was achieved without compromising the PTV coverage (p = 0.61). Optimization significantly decreased median DMean_Pmap from 28.8Gy (IC95% 24.2-33.4) to 22.1Gy (IC95% 18.3-26.0). When recomputing the risk of APT using the new dosimetric features, optimization significantly reduced the risk of APT (p < 0.0001) by reclassifying 43.2% (19/44) of the patients. <h3>Conclusion</h3> Our approach appears as both easily implementable on a daily basis and efficient at reducing the risk of APT. Regional radiosensitivity should be considered in usual lung dose constraints, opening the possibility of an easily implementable adaptive dosimetry planning.

VMAT-Based Planning Allows Sparing of a Spatial Dose Pattern Associated with Radiation Pneumonitis in Patients Treated with Radiotherapy for a Locally Advanced Lung Cancer.

Simple SummaryA sub-region localized in the posterior right lung was significantly associated with the risk of grade ≥ 2 acute pulmonary toxicity in patients with locally advanced lung cancer treated with radiotherapy. Avoiding this sub-region with volumetric-arctherapy-based planification leads to a significant reduction of the predicted APT risk by reclassifying 43.2% (19/44) of the patients.Introduction: In patients treated with radiotherapy for locally advanced lung cancer, respect for dose constraints to organs at risk (OAR) insufficiently protects patients from acute pulmonary toxicity (APT), such toxicities being associated with a potential impact on the treatment’s completion and the patient’s quality of life. Dosimetric planning does not take into account regional lung functionality. An APT prediction model combining usual dosimetry features with the mean dose (DMeanPmap) received by a voxel-based volume (Pmap) localized in the posterior right lung has been previously developed. A DMeanPmap of ≥30.3 Gy or a predicted APT probability (ProbAPT) of ≥8% were associated with a higher risk of APT. In the present study, the authors aim to demonstrate the possibility of decreasing the DMeanPmap via a volumetric arctherapy (VMAT)-based adapted planning and evaluate the impact on the risk of APT. Methods: Among the 207 patients included in the initial study, only patients who presented with APT of ≥grade 2 and with a probability of APT ≥ 8% based on the prediction model were included. Dosimetry planning was optimized with a new constraint (DMeanPmap < 30.3 Gy) added to the usual constraints. The initial and optimized treatment plans were compared using the t-test for the independent variables and the non-parametric Mann–Whitney U test otherwise, regarding both doses to the OARs and PTV (Planning Target Volume) coverage. Conformity and heterogeneity indexes were also compared. The risk of APT was recalculated using the new dosimetric features and the APT prediction model. Results: Dosimetric optimization was considered successful for 27 out of the 44 included patients (61.4%), meaning the dosimetric constraint on the Pmap region was achieved without compromising the PTV coverage (p = 0.61). The optimization significantly decreased the median DMeanPmap from 28.8 Gy (CI95% 24.2–33.4) to 22.1 Gy (CI95% 18.3–26.0). When recomputing the risk of APT using the new dosimetric features, the optimization significantly reduced the risk of APT (p < 0.0001) by reclassifying 43.2% (19/44) of the patients. Conclusion: Our approach appears to be both easily implementable on a daily basis and efficient at reducing the risk of APT. Regional radiosensitivity should be considered in usual lung dose constraints, opening the possibility of new treatment strategies, such as dose escalation or innovative treatment associations.

Lung perfusion during veno-venous extracorporeal membrane oxygenation in a model of hypoxemic respiratory failure

BackgroundVeno-venous extracorporeal membrane oxygenation (ECMO) provides blood oxygenation and carbon dioxide removal in acute respiratory distress syndrome. However, during ECMO support, the native lungs still play an important role in gas exchange, functioning as a second oxygenator in series with ECMO. The hypoxic vasoconstriction mechanism diverts regional blood flow within the lungs away from regions with low oxygen levels, optimizing ventilation/perfusion matching. ECMO support has the potential to reduce this adaptive pulmonary response and worsen the ventilation/perfusion mismatch by raising venous oxygen partial pressure. Thus, the objective of this study was to evaluate the effect of ECMO on regional pulmonary perfusion and pulmonary hemodynamics during unilateral ventilation and posterior lung collapse.MethodsFive Agroceres pigs were instrumented, monitored and submitted to ECMO. We used the Electrical Impedance Tomography (EIT) to evaluate lung ventilation and perfusion in all protocol steps. Effects of ECMO support on pulmonary hemodynamics and perfusion involving two different scenarios of ventilation/perfusion mismatch: (1) right-lung selective intubation inducing collapse of the normal left lung and (2) dorsal lung collapse after repeated lung lavage. Data including hemodynamics, respiratory, lung perfusion/ventilation, and laboratory data over time were analyzed with a mixed generalized model using the subjects as a random factor.ResultsThe initiation of ECMO support provided a significant reduction in Mean Pulmonary Artery Pressure (PAPm) in both situations of ventilation/perfusion mismatch. However, distribution of lung perfusion did not change with the use of ECMO support.ConclusionsWe found that the use of ECMO support with consequent increase in venous oxygen pressure induced a significant drop in PAPm with no detectable effect on regional lung perfusion in different scenarios of ventilation/perfusion mismatch.