Absence Of Lung Research Articles

Diagnostic value of ultrasound for community-acquired pneumonia in children and its correlation with serum PCT level and PCIS.

This study aimed to evaluate the diagnostic value of ultrasound for community-acquired pneumonia (CAP) in children. Clinical information of children diagnosed with CAP and a control group of healthy children was collected, and lung ultrasound detection was performed. The lung ultrasound score (LUS) was assessed, and venous blood samples were collected. Serum indexes, including white blood cell count, were analyzed using an automatic immunoassay analyzer, while serum procalcitonin (PCT) level was measured using an enzyme-linked immunosorbent assay. The pediatric critical illness score (PCIS) was also performed for all subjects. White blood cell count, absolute neutrophil count, and respiratory index were significantly higher in the CAP group than those in the control group, while the oxygenation index was markedly lower. Ultrasound detection results showed that the CAP group exhibited significantly higher detection rates of pleural effusion, interstitial lung changes, lung consolidation, B-lines, air bronchogram signs, and reduced or absent lung sliding signs compared with the control group. In addition, the LUS and PCT levels were markedly higher in the CAP group, while the PCIS was notably lower. Further analysis exhibited that the LUS in the CAP group was significantly positively correlated with PCT levels and negatively correlated with PCIS. The receiver operating characteristic curve indicated that the area under the curve of LUS for diagnosing children with lung infection was 0.841. LUS is closely related to serum PCT level and PCIS. Lung ultrasound detection demonstrates high sensitivity and specificity, indicating its valuable clinical diagnostic utility for CAP in children.

Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity.

Doxorubicin and other anthracyclines are crucial cancer treatment drugs. However, they are associated with significant cardiotoxicity, severely affecting patient care and limiting dosage and usage. Previous studies have shown that low carbon monoxide (CO) concentrations protect against doxorubicin toxicity. However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI-002) that can be easily self-administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract. HBI-002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI-002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of ≈1% to 7%. Heart tissue from mice treated with HBI-002 had a 6.3-fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase-1 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI-002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI-002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function. These findings strongly support using HBI-002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage.

Automated Real-Time Detection of Lung Sliding Using Artificial Intelligence: A Prospective Diagnostic Accuracy Study

Rapid evaluation for pneumothorax is a common clinical priority. Although lung ultrasound (LUS) often is used to assess for pneumothorax, its diagnostic accuracy varies based on patient and provider factors. To enhance the performance of LUS for pulmonary pathologic features, artificial intelligence (AI)-assisted imaging has been adopted; however, the diagnostic accuracy of AI-assisted LUS (AI-LUS) deployed in real time to diagnose pneumothorax remains unknown. In patients with suspected pneumothorax, what is the real-time diagnostic accuracy of AI-LUS to recognize the absence of lung sliding? We performed a prospective AI-assisted diagnostic accuracy study of AI-LUS to recognize the absence of lung sliding in a convenience sample of patients with suspected pneumothorax. After calibrating the model parameters and imaging settings for bedside deployment, we prospectively evaluated its diagnostic accuracy for lung sliding compared with a reference standard of expert consensus. Two hundred forty-one lung sliding evaluations were derived from 62 patients. AI-LUS showed a sensitivity of 0.921 (95%CI, 0.792-0.973), specificity of 0.802 (95%CI, 0.735-0.856), area under the receiver operating characteristic curve of 0.885 (95%CI, 0.828-0.956), and accuracy of 0.824 (95%CI, 0.766-0.870) for the diagnosis of absent lung sliding. Real-time AI-LUS shows high sensitivity and moderate specificity to identify the absence of lung sliding. Further research to improve model performance and optimize the integration of AI-LUS into existing diagnostic pathways is warranted.

Congenital lobar emphysema mis-interpreted as tension pneumothorax: a case report and literature review

Introduction and importance: Congenital lobar emphysema (CLE) is a rare developmental lung anomaly that occasionally remains asymptomatic until adulthood. The right diagnosis is very crucial in its management. Case presentation: The authors report the case of a 29-year-old otherwise healthy, nonsmoker male. Referred after management of a presumptuous diagnosis of tension pneumothorax. His symptoms at initial presentation were a chronic cough and progressive exertional dyspnea. His chest radiography revealed absent lung markings in the right lung field with a trachea deviation to the left, interpreted as a tension pneumothorax. However, chest tube insertion worsened his dyspnea. A computed tomography scan, though initially interpreted as pneumothorax, showed findings consistent with CLE. Discussion: Adult CLE is a very rare presentation. A computed tomography scan is the imaging of choice. Even though watchful waiting is reasonable in selected patients, lobectomy remains the standard of care, preferably via video-assisted thoracic surgery. Conclusion: Failure to recognize CLE or other cystic lung lesions can lead to harmful procedures.

Quantitative Assessment of Lung Volumes and Enhancement in Patients with COVID-19: Role of Dual-Energy CT

Dual-energy computed tomography (DECT) has been used for detecting pulmonary embolism, but the role of lung perfusion DECT as a predictor of prognosis of coronavirus disease 2019 (COVID-19) has not been defined yet. The aim of our study was to explore whether the enhancement pattern in COVID-19+ patients relates to the disease outcome. A secondary aim was to compare the lung volumes in two subgroups of patients. In this observational study, we considered all consecutive COVID-19+ patients who presented to the emergency room between January 2021 and December 2021 with respiratory symptoms (with mild to absent lung consolidation) and were studied by chest contrast-enhanced DECT to be eligible. Two experienced radiologists post-processed the images using the "lung-analysis" software (SyngoVia). Absolute and relative enhancement lung volumes were assessed. Patients were stratified in two subgroups depending on clinical outcome at 30 days: (i) good outcome (i.e., discharge, absence of clinical or imaging signs of disease); (ii) bad outcome (i.e., hospitalization, death). Patient sub-groups were compared using chi-square test or Fisher test for qualitative parameters, chi-square test or Spearman's Rho test for quantitative parameters, Students' t-test for parametric variables and Wilcoxon test for non-parametric variables. We enrolled 78 patients (45M), of whom, 16.7% had good outcomes. We did not observe any significant differences between the two groups, both in terms of the total enhancement evaluation (p = 0.679) and of the relative enhancement (p = 0.918). In contrast, the average lung volume of good outcome patients (mean value of 4262 mL) was significantly larger than that of bad outcome patients (mean value of 3577.8 mL), p = 0.0116. All COVID-19+ patients, with either good or bad outcomes, presented similar enhancement parameters and relative enhancements, underlining no differences in lung perfusion. Conversely, a significant drop in lung volume was identified in the bad outcome subgroup eligible compared to the good outcome subgroup.

Transthoracic sonographic scores in evaluating the success of different scelerosing modalities in patients with malignant pleural effusion

BackgroundMalignant pleural effusions (MPE) mostly arises from metastases to the pleura from other sites. Management of malignant effusions aims to palliate dyspnea and prevent the reaccumulation of pleural fluid to improve patients’ quality of life. Pleurodesis is the most common palliative treatment for patients with refractory MPE. This study was carried out to evaluate the performance of transthoracic sonographic (TUS) scores (pleural sliding and pleural adherence score) in predicting the success of pleurodesis by different modalities in patients with malignant pleural effusion. One hundred malignant pleural effusion patients were enrolled to an interventional clinical trial from September 2019 to April 2021 for palliative management of dyspnea. Pleurodesis for palliative treatment of dyspnea was done either spontaneously by the intercostal chest tube or by a sclerosing agent such as tetracycline solution or tetracycline poudrage or iodopovidine. Patients were randomly allocated to one of these four groups where each group included 25 patients. Transthoracic ultrasound was performed at baseline, and 1 month after pleurodesis and the lung sliding score and pleural adherence score were evaluated.ResultsMajority of patients (78%) had high baseline lung sliding score (7-8). Post pleurodesis only 11.4% had high scores (p<0.001), also the mean lung sliding score decreased significantly in comparison to the baseline values (p˂ 0.001) in the spontaneous, tetracycline solution, tetracycline poudrage, and iodopovidine groups (7.04 ± 1.02 vs. 4.85 ± 1.60, 7.28± 0.98 vs. 4.48± 1.75, 7.20±0.96 vs. 4.44 ± 1.45, 7.04±0.93 vs. 3.35±1.81, respectively). Iodopovidine pleurodesis group in comparison to the other modalities showed the highest pleural adherence score (12.64 ± 2.98) and absent lung sliding in 72.7% of cases and 70 % success rate. Pleural adherence score at cut off ≥ 12 showed 92.75% sensitivity, 89.47% specificity, 92.1 accuracy, and 0.911 area under the curve (AUC) for predicting successful pleurodesis.ConclusionTUS scores is a feasible, bedside, and accurate method to detect the outcome of pleurodesis. Iodopovidone was more effective than tetracycline solution, tetracycline poudrage, and spontaneous pleurodesis.Trial registrationClinicalTrials.gov. NCT04074902. Registered on 29 August 2019

Assessment of diaphragmatic mobility by chest ultrasound and basic echocardiography in patients with malignant pleural effusion undergoing pleurodesis

Background Malignant pleural effusion (MPE) is prevalent, and in cases such as aging patients as well as increased long-term survival for metastatic cancers, the number of patients will continue to elevate in the near future. Aim To assess both the diaphragmatic mobility using chest ultrasound and basic echocardiography before and after pleurodesis in patients with MPE. Patients and methods This study included 35 patients with MPE; the diagnosis is based on positive pleural fluid cytology, thoracoscopic biopsy, and fitted for chemical pleurodesis by bleomycin. Baseline chest ultrasound was done to for assess the diaphragmatic mobility and basic echocardiography. Chemical pleurodesis was done through intrapleural injection of 1 IU/kg bleomycin as a sclerosing agent in 100 ml of normal saline. Results Regarding outcome, 17 (48.6%) patients succeeded (defined as absent lung sliding and no reaccumulation of pleural fluid in the lines examined) and 7 (20%) patients failed (known as reaccumulation of pleural fluid and (even with) no presence of lung sliding). There was a statistically substantial decrease in the diaphragmatic excursion (mobility) at 2 weeks and at 2 months after pleurodesis than before. A significant relation was detected between outcome of the studied patients with lung sliding before pleurodesis, whereas there was a substantial increase in pleurodesis success with no presence of lung sliding at 2 weeks and at 2 months after pleurodesis. Conclusion Ultrasound of the diaphragm is an uncomplicated, noninvasive method for estimating the contractile activity of diaphragm. The decrease in the diaphragmatic excursion at 2 weeks and at 2 months after pleurodesis compared with that before pleurodesis can be used as sign to predict pleurodesis success. There is no significant relation between echocardiography measurements and outcome except that normal left ventricle ejection fraction % has a significant relation with increased success outcome.

Exceptional preservation of organs in Devonian placoderms from the Gogo lagerstätte.

The origin and early diversification of jawed vertebrates involved major changes to skeletal and soft anatomy. Skeletal transformations can be examined directly by studying fossil stem gnathostomes; however, preservation of soft anatomy is rare. We describe the only known example of a three-dimensionally mineralized heart, thick-walled stomach, and bilobed liver from arthrodire placoderms, stem gnathostomes from the Late Devonian Gogo Formation in Western Australia. The application of synchrotron and neutron microtomography to this material shows evidence of a flat S-shaped heart, which is well separated from the liver and other abdominal organs, and the absence of lungs. Arthrodires thus show the earliest phylogenetic evidence for repositioning of the gnathostome heart associated with the evolution of the complex neck region in jawed vertebrates.

POSTERIOR PNEUMOTHORAX IN A PATIENT WITH COVID-19 ON ECMO: A CASE REPORT

TYPE: Case Report TOPIC: Chest Infections INTRODUCTION: Pneumothoraces are a known complication of SARS-CoV-2, but the reported rate varies between studies. Posterior pneumothoraces are extremely uncommon with few published case reports. CASE PRESENTATION: A 51-year-old woman presented with dyspnea, fever, pulmonary infiltrates, and positive SARS-CoV2 nasopharyngeal PCR. Her respiratory status deteriorated, she was intubated, and she ultimately required VV-ECMO cannulation. Her hospital course was complicated by DVT, pulmonary aspergillosis, E coli pneumonia, and left sided hydropneumothorax treated with chest tube drainage. On hospital day 56, the patient abruptly developed a vasopressor requirement with a rapid elevation in lactate. CXR identified a large left air space. POCUS of the chest was remarkable for A-line artifact and absent lung sliding of the left posterior chest. CT confirmed a posterior pneumothorax. A 14Fr small-bore chest tube was placed by IR with improvement in the size of the pneumothorax and hemodynamic status, shown on image C below. The patient’s course was further complicated by right-sided hydropneumothorax due to E. coli and E. faecalis empyema that was treated with 14Fr chest tube drainage. She gradually improved, was decannulated from VV-ECMO, and on hospital day 107 was discharged to an acute rehabilitation facility with all chest tubes removed. DISCUSSION: Here we describe a patient’s hospital course complicated by repeated pneumothoraces including a left posterior loculated pneumothorax causing tension physiology. CONCLUSIONS: Available literature suggests pneumothorax may occur in 11% of COVID-19 patients treated with ECMO. The proper management of these patients is still unclear and clinicians must take these complications into account when directing care. DISCLOSURE: Nothing to declare. KEYWORD: Pneumothorax

Role of lung ultrasound patterns in monitoring coronavirus disease 2019 pneumonia and acute respiratory distress syndrome in children.

Background During the coronavirus disease 2019 (COVID-19) pandemic, lung ultrasonography (US) has been gaining importance in pediatric intensive care and emergency settings for the screening, diagnosis, and monitoring of pulmonary pathology.Purpose To describe the pattern of lung US changes in patients with COVID-19 pneumonia and its potential role in monitoring ventilated patients.Methods This prospective observational study included children aged 1 month to 12 years with a confirmed diagnosis of COVID-19. Lung US was performed using a high-frequency linear probe (5–12 MHz) in all children with moderate/severe respiratory symptoms within 24 hours of admission and then daily until the patient required oxygen therapy. Lung involvement severity was assessed using lung US scores, while lung aeration improvement or deterioration was measured using lung ultrasound reaeration scores (LUSReS).Results Of 85 children with moderate to severe disease, 54 with pulmonary disease were included. Of them, 50 (92.5%) had an interstitial pattern, followed by pleural line abnormalities in 44 (81.5%), reduced or absent lung sliding in 31 (57.4%), and consolidation in 28 (51.8%). A significantly higher lung US score (median, 18; interquartile range [IQR], 11–22) was observed in ventilated versus nonventilated patients (median, 9; IQR, 6–11). LUSReS improvement after positive end-expiratory pressure titration was positively correlated with improved dynamic lung compliance and oxygenation indices and negatively correlated with the requirement for driving pressure. Successful weaning could be predicted with 100% specificity if loss of LUSReS ≤ 5.Conclusion Interstitial syndrome, fragmented pleural line, and subpleural microconsolidation were the most prevalent lung US findings in children with COVID-19 pneumonia. Thus, lung US may have the ability to monitor changes in lung aeration caused by mechanical ventilation and predict its successful weaning in children with COVID-19.

Young Man with Chest Pain

A 24-year-old man presented to the emergency department with right-sided chest pain after falling from a 2-wheeled scooter. His vital signs were unremarkable. He had tenderness on the right side of his chest, and sounds in the right lung were absent. A bedside ultrasound scan of the lung with the patient in a sitting position showed absent lung sliding and an air-fluid interface on the right side (Figure 1; M-mode pattern in Figure 2). The chest radiograph (Figure 3) confirmed the diagnosis.

90 Lung ultrasound in pediatric asthma patients: A pilot study characterizing findings at baseline stat

Abstract Primary Subject area Emergency Medicine - Paediatric Background Unlike the lung ultrasound (LU) findings of pneumonia, bronchiolitis, pleural effusions and pneumothorax, which have all been well described, the sonographic pattern of asthma remains unclear. Previous pediatric studies have shown that pediatric patients with acute asthma exacerbations had positive LU findings. It is also unclear whether these findings were the result of acute infections associated with the exacerbation or if the findings would be present at baseline, outside an exacerbation in an asthmatic patient. Objectives The primary objective of this study is to characterize lung ultrasound (LU) findings in stable asthma pediatric patients presenting in a tertiary care asthma or respiratory clinic. Design/Methods Eligible patients &amp;gt;6 years of age, underwent a LU by the study sonographer between December 19, 2017 to June 25, 2019, during their regular follow up visit at the pulmonology clinic or scheduled pulmonary function test. Patients were defined as asthmatic if they had a positive methacholine challenge test (MCT) or spirometry at the day of the visit or in the past. Patients were excluded if they had an upper respiratory tract infection in the past 4 weeks, or had any other known pulmonary diseases. Baseline demographic and asthma severity (ISAAC score, ACQ-7) questionnaires were filled out by the patients, following which they underwent a LU by a novice sonographer using a 6-zone protocol. A blinded expert sonographer interpreted the images offline. A positive LU was defined as presence of more than 3 B-lines, consolidation (&amp;lt;1cm or &amp;gt;1cm), absent lung slide, and/or presence of pleural fluid. Results Fifty-two patients were enrolled in the study and 19.2% (CI 8.31-30.15) of the asthma patients had positive LU findings. The positive LU findings were diverse including B-lines (80%), small consolidation (80%), pleural line anomalies (10%). Positive LU findings were not correlated to any demographic value. Conclusion In our study, 19.2% of asthma patients at baseline have a positive LU. Lung consolidations larger than 1 cm were rarely seen. There were no significant differences between demographic data in asthmatic patients with positive compared to those with negative LUS. This positive LU scan rate is in keeping with a prior study on LU in pediatrics.

Complement activation on endothelium initiates antibody-mediated acute lung injury.

Antibodies targeting human leukocyte antigen (HLA)/major histocompatibility complex (MHC) proteins limit successful transplantation and transfusion, and their presence in blood products can cause lethal transfusion-related acute lung injury (TRALI). It is unclear which cell types are bound by these anti-leukocyte antibodies to initiate an immunologic cascade resulting in lung injury. We therefore conditionally removed MHC class I (MHC I) from likely cellular targets in antibody-mediated lung injury. Only the removal of endothelial MHC I reduced lung injury and mortality, related mechanistically to absent endothelial complement fixation and lung platelet retention. Restoration of endothelial MHC I rendered MHC I-deficient mice susceptible to lung injury. Neutrophil responses, including neutrophil extracellular trap (NET) release, were intact in endothelial MHC I-deficient mice, whereas complement depletion reduced both lung injury and NETs. Human pulmonary endothelial cells showed high HLA class I expression, and posttransfusion complement activation was increased in clinical TRALI. These results indicate that the critical source of antigen for anti-leukocyte antibodies is in fact the endothelium, which reframes our understanding of TRALI as a rapid-onset vasculitis. Inhibition of complement activation may have multiple beneficial effects of reducing endothelial injury, platelet retention, and NET release in conditions where antibodies trigger these pathogenic responses.

The use of lung ultrasound in the diagnosis of pneumothorax in trauma patients

Introduction and purpose: Pneumothorax is a condition in which air is present in the pleural cavity and often has a traumatic etiology. It can be a life-threatening condition, making quick and effective diagnosis essential. Chest ultrasound can be a useful study for this purpose.A brief description of the state of knowledge: The sonographic signs of pneumothorax are absence of lung sliding, absence of B-lines, absence of lung pulse and presence of lung point. When a pneumothorax is suspected, the supine position is the most appropriate position for the patient. The sonographic technique consists of exploration of the least gravitationally dependent areas progressing more laterally. The bedside sonographic diagnosis of pneumothorax can be performed with most ultrasound machines without the need of any sophisticated functions. The average time to perform this examination varies from two to three minutes. In the most recent meta-analysis chest ultrasound sensitivity and specificity were 0.91 (95% CI: 0.85 to 0.94) and 0.99 (95% CI: 0.97 to 1.00), respectively. There was a significant difference in the sensitivity of CUS compared to CXR with an absolute difference in sensitivity of 0.44 (95% CI: 0.27 to 0.61; P&lt;0.001).Conclusions: Chest ultrasound is a safe, effective and sensitive method of diagnosing pneumothorax. It may be considered as the first study of trauma patients with suspected pneumothorax.

Role of Ultrasound-Guided Evaluation of Dyspnea in the Coronavirus Disease 2019 Pandemic

Role of Ultrasound-Guided Evaluation of Dyspnea in the Coronavirus Disease 2019 Pandemic

Absent Lung Slide but No Pneumothorax: A Case of Spontaneous Diaphragmatic Hernia Presenting with Dyspnea

Spontaneous diaphragmatic rupture is one of the rarest thoracoabdominal emergencies. The diagnosis may be delayed if a patient presents with respiratory symptoms without any history of trauma. In this report, we present a case who was admitted to the emergency department with shortness of breath, nausea, vomiting lasting for 3 h, and was diagnosed initially with pneumothorax based on chest X-ray and ultrasonography thorax findings. An intercostal drain was placed in the emergency ward. This was later diagnosed to have spontaneous diaphragmatic rupture. The patient was operated upon, and the defect was repaired. Diaphragmatic rupture should be considered along with other possible diagnoses, especially in the presence of suspicious appearances on the chest radiography in a patient with respiratory and/or gastrointestinal symptoms. The utility of bedside ultrasound in the diagnosis of spontaneous diaphragmatic hernia is yet unproven. The only treatment is surgical along with supportive care.

Absent pericardium and lung hypoplasia in a child with severe mitral regurgitation

An 8-year-old girl with severe mitral regurgitation presented with symptoms of heart failure. Clinical investigations did not raise suspicion of an absent left pericardium. Congenital defects of the pericardium are rare and frequently associated with other cardiac lesions. We describe a case of severe mitral regurgitation in a child in whom an absent left-sided pericardium with hypoplasia of left lung was found incidentally during surgery to repair the mitral valve. We believe such associations with other heart diseases is usually circumstantial but can influence the perioperative morbidity, length of hospital stay, and even alter the surgical management.

Influence of nasal CPAP on cardiorespiratory control in healthy neonate.

The present study aimed to further unravel the effects of nasal continuous positive airway pressure (nCPAP) on the cardiovascular and respiratory systems in the neonatal period. Six-hour polysomnographic recordings were first performed in seven healthy newborn lambs, aged 2-3 days, without and with nCPAP application at 6 cmH2O (nCPAP-6), in randomized order. The effects of nCPAP-6 on heart rate variability, respiratory rate variability, and cardiorespiratory interrelations were analyzed using a semiautomatic signal processing approach applied to ECG and respiration recordings. Thereafter, a cardiorespiratory mathematical model was adapted to the experimental conditions to gain further physiological interpretation and to simulate higher nCPAP levels (8 and 10 cmH2O). Results from the signal processing approach suggest that nCPAP-6 applied in newborns with healthy lungs: 1) increases heart rate and decreases the time and frequency domain indices of heart rate variability, especially those representing parasympathetic activity, while increasing the complexity of the RR-interval time series; 2) prolongs the respiratory cycle and expiration duration and decreases respiratory rate variability; and 3) slightly impairs cardiorespiratory interrelations. Model-based analysis revealed that nCPAP-6 increases the heart rate and decreases respiratory sinus arrhythmia amplitude, in association with a reduced parasympathetic efferent activity. These results were accentuated when simulating an increased CPAP level. Overall, our results provide a further understanding of the effects of nCPAP in neonates, in the absence of lung disease.NEW & NOTEWORTHY Application of nasal continuous positive airway pressure (CPAP) at 6 cmH2O, a level very frequently used in newborns, alters heart and respiratory rate variability, as well as cardiorespiratory interrelations in a full-term newborn model without lung disease. Moreover, whereas nasal CPAP at 6 cmH2O decreases parasympathetic efferent activity, there is no change in sympathetic efferent activity.

A six-month systems toxicology inhalation/cessation study in ApoE−/− mice to investigate cardiovascular and respiratory exposure effects of modified risk tobacco products, CHTP 1.2 and THS 2.2, compared with conventional cigarettes

Smoking is one of the major modifiable risk factors in the development and progression of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). Modified-risk tobacco products (MRTP) are being developed to provide substitute products for smokers who are unable or unwilling to quit, to lessen the smoking-related health risks. In this study, the ApoE-/- mouse model was used to investigate the impact of cigarette smoke (CS) from the reference cigarette 3R4F, or aerosol from two potential MRTPs based on the heat-not-burn principle, carbon heated tobacco product 1.2 (CHTP1.2) and tobacco heating system 2.2 (THS 2.2), on the cardiorespiratory system over a 6-month period. In addition, cessation or switching to CHTP1.2 after 3 months of CS exposure was assessed. A systems toxicology approach combining physiology, histology and molecular measurements was used to evaluate the impact of MRTP aerosols in comparison to CS. CHTP1.2 and THS2.2 aerosols, compared with CS, demonstrated lower impact on the cardiorespiratory system, including low to absent lung inflammation and emphysematous changes, and reduced atherosclerotic plaque formation. Molecular analyses confirmed the lower engagement of pathological mechanisms by MRTP aerosols than CS. Both cessation and switching to CHTP1.2 reduced the observed CS effects to almost sham exposure levels.

Expression of a novel surfactant protein gene is associated with sites of extrapulmonary respiration in a lungless salamander.

Numerous physiological and morphological adaptations were achieved during the transition to lungless respiration that accompanied evolutionary lung loss in plethodontid salamanders, including those that enable efficient gas exchange across extrapulmonary tissue. However, the molecular basis of these adaptations is unknown. Here, we show that lungless salamanders express in the larval integument and the adult buccopharynx—principal sites of respiratory gas exchange in these species—a novel paralogue of the gene surfactant-associated protein C (SFTPC), which is a critical component of pulmonary surfactant expressed exclusively in the lung in other vertebrates. The paralogous gene appears to be found only in salamanders, but, similar to SFTPC, in lunged salamanders it is expressed only in the lung. This heterotopic gene expression, combined with predictions from structural modelling and respiratory tissue ultrastructure, suggests that lungless salamanders may produce pulmonary surfactant-like secretions outside the lungs and that the novel paralogue of SFTPC might facilitate extrapulmonary respiration in the absence of lungs. Heterotopic expression of the SFTPC paralogue may have contributed to the remarkable evolutionary radiation of lungless salamanders, which account for more than two thirds of urodele species alive today.