Abnormal Lung Research Articles

Imaging of Pulmonary Fibrosis: An Update, From the AJR Special Series on Imaging of Fibrosis.

Pulmonary fibrosis is recognized as occurring in association with a wide and increasing array of conditions, and it presents with a spectrum of chest CT appearances. Idiopathic pulmonary fibrosis (IPF), which corresponds histologically with usual interstitial pneumonia and represents the most common idiopathic interstitial pneumonia, is a chronic progressive fibrotic interstitial lung disease (ILD) of unknown cause. Progressive pulmonary fibrosis (PPF) describes the radiologic development of pulmonary fibrosis in patients with ILD of a known or unknown cause other than IPF. The recognition of PPF impacts management of patients with ILD-for example, in guiding initiation of antifibrotic therapy. Interstitial lung abnormalities are an incidental CT finding in patients without suspected ILD and may represent an early intervenable form of pulmonary fibrosis. Traction bronchiectasis and/or bronchiolectasis, when detected in the setting of chronic fibrosis, is generally considered evidence of irreversible disease, and progression predicts worsening mortality risk. Awareness of the association between pulmonary fibrosis and connective tissue diseases, particularly rheumatoid arthritis, is increasing. This review provides an update on the imaging of pulmonary fibrosis, with attention given to recent advances in disease understanding with relevance to radiologic practice. The essential role of a multidisciplinary approach to clinical and radiologic data is highlighted.

Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study.

Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab. This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥5% or ≥10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV1) by Week 12, annualized severe asthma exacerbation rates from Week 12-52, and mean change from baseline in ppFEV1 to Week 12. At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥5% in ppFEV1; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV1 ≥10%. During the Week 12-52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52-60% (all P<0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV1 (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of ≥5%. Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV1, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV1 response at Week 12. NCT02948959.

Pets, furry animal allergen components, and asthma in childhood

AbstractBackgroundThe use of component‐resolved allergy diagnostics has provided a clearer understanding of the species‐specific sensitization and severity of potential allergic reactions. This cross‐sectional study aimed to determine whether sensitization to allergen components in furry animals is indicative of blood eosinophilia, a positive fractional exhaled nitric oxide (FeNO) test, abnormal lung function, and asthma symptoms in children. Additionally, we investigated whether having pets during childhood affects the development of asthma or allergic sensitization to furry animals.MethodsWe recruited 203 children aged 4–17 years with asthma diagnosis based on abnormal lung function and 33 controls. IgE‐sensitization to allergen components for dogs, cats, and horses was analyzed using a multiplex microarray. Children were tested with FeNO, impulse oscillometry, spirometry, methacholine challenge, and skin prick test. A questionnaire was used to investigate pet ownership and symptom profile.ResultsFeNO results and blood eosinophilia revealed a correlation with sensitization to all furry animal allergens, particularly lipocalins (r = 0.203–0.560 and 0.206–0.560, respectively). Can f 3 was found to correlate with baseline R5 (r = 0.298). No association between methacholine challenge results and sensitization to furry animal allergens was found. Children with asthma who were sensitized to Can f 1, Can f 6, or both frequently reported asthma symptoms. Dog ownership was associated with a lower level of IgE‐sensitization to lipocalins, fewer asthma symptoms, and less blood eosinophilia.ConclusionFurry animal allergen component IgE‐sensitization is a risk factor for type 2‐inflammation and asthma symptoms.

Adverse effects of cigarette filter silica on lungs: Comparison with natural crystalline silica particles.

As a common additive in cigarette filters, nanosilica has been implemented to reduce the release of harmful substances in cigarette smoke. However, the potential risk of occupational exposure for cigarette factory workers is unknown. We collected physical examination data from 710 cigarette factory workers to evaluate the adverse effects of cigarette filter silica exposure. We also established mouse models induced by cigarette filter silica and crystalline silica separately to compare the lung inflammation, pulmonary function, apoptosis, and fibrosis of the two models. Workers in the rolling and packing workshop exposed to cigarette filter silica had a higher rate of abnormal lung function (17.75%) than those in the cutting workshop (0.87%). Animal experiments showed that compared with the same dose of crystalline silica, cigarette filter silica resulted in higher levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) of mice at day 7, and lower levels of total lung capacity (TLC), inspiratory capacity (IC), vital capacity (VC), and forced vital capacity (FVC) in mice at day 28. Additionally, both exposed groups of mice showed increased levels of caspase 3, collagen I (Col-Ⅰ), α-smooth muscle actin (α-SMA) and hydroxyproline (HYP) in the lungs, as well as collagen accumulation and fibrous nodules at day 28, with no significant difference between the two groups. The results suggested that cigarette filter silica caused more severe early lung inflammation and late ventilation impairment than the same dose of crystalline silica. In the future, we need to pay more attention to nanosilica protection in cigarette factories to prevent pulmonary dysfunction in workers.

Implementation of an Interstitial Lung Abnormality Clinic and Multidisciplinary Discussion.

Implementation of an Interstitial Lung Abnormality Clinic and Multidisciplinary Discussion.

Dysregulation of CITED2 in abnormal lung development in the nitrofen rat model.

CITED2 both modulates lung, heart and diaphragm development. The role of CITED2 in the pathogenesis of congenital diaphragmatic hernia (CDH) is unknown. We aimed to study CITED2 during abnormal lung development in the nitrofen model. Timed-pregnant rats were given nitrofen on embryonic day (E) 9 to induce CDH. Fetal lungs were harvested on E15, 18 and 21. We performed RT-qPCR, RNAscope™ in situ hybridization and immunofluorescence staining for CITED2. We observed no difference in RT-qPCR (control: 1.09 ± 0.22 and nitrofen: 0.95 ± 0.18, p = 0.64) and in situ hybridization (1.03 ± 0.03; 1.04 ± 0.03, p = 0.97) for CITED2 expression in E15 nitrofen and control pups. At E18, CITED2 expression was reduced in in situ hybridization of nitrofen lungs (1.47 ± 0.05; 1.14 ± 0.07, p = 0.0006), but not altered in RT-qPCR (1.04 ± 0.16; 0.81 ± 0.13, p = 0.33). In E21 nitrofen lungs, CITED2 RNA expression was increased in RT-qPCR (1.04 ± 0.11; 1.52 ± 0.17, p = 0.03) and in situ hybridization (1.08 ± 0.07, 1.29 ± 0.04, p = 0.02). CITED2 protein abundance was higher in immunofluorescence staining of E21 nitrofen lungs (2.96 × 109 ± 0.13 × 109; 4.82 × 109 ± 0.25 × 109, p < 0.0001). Our data suggest that dysregulation of CITED2 contributes to abnormal lung development of CDH, as demonstrated by the distinct spatial-temporal distribution in nitrofen-induced lungs.

Assessment of mediastinal shift angles in congenital pulmonary airway malformation: a new fetal magnetic resonance imaging indicator of congenital lung disease.

The mediastinal shift angle is a new fetal magnetic resonance imaging (MRI) index that is reportedly correlated with postnatal survival in fetuses with congenital diaphragmatic hernia. However, its correlation in patients with congenital pulmonary airway malformation (CPAM) has not been assessed. This study aimed to establish a normal range for the right/left mediastinal shift angles, to evaluate the mediastinal shift angle in fetuses with CPAM, to compare the mediastinal shift angle with the CPAM volume ratio, and to evaluate the predictive value of the mediastinal shift angle measurements. To establish the normal range, we measured the mediastinal shift angle bilaterally in 124 fetuses without any lung abnormality (the control group). Subsequently, the mediastinal shift angle was measured in 32 fetuses pathologically diagnosed with CPAM. Moreover, the mediastinal shift angle and CPAM volume ratio were compared using fetal MRI. The mean values for the right/left mediastinal shift angles were 18.6°/26.3° and 39.2°/35.9° for control fetuses and fetuses with CPAM, respectively. The mediastinal shift angle and the CPAM volume ratio showed a positive statistical correlation. The area under the curve demonstrated high discriminatory accuracy for the mediastinal shift angle (0.76). The mediastinal shift angle has potential to replace the CPAM volume ratio for evaluating the severity of CPAM infetal MRI.

HUBUNGAN KADAR LEUKOSIT DAN TOTAL LIMFOSIT DENGAN KELAINAN PARU PADA PASIEN COVID-19

Before the administration of vaccine, the impact of COVID-19 infection on the lungs was significant, affecting the prognosis and quality of life of patients. Identifying the severity of lung damage requires markers to identify the patient's condition early on, preventing further damage and abnormalities that may arise, especially in the lungs. The aim of this study is to reduce the occurrence of post-COVID-19 lung fibrosis by assessing the relationship between leukocyte and total lymphocyte levels and lung abnormalities in COVID-19 patients. The research method used is observational analytics with a cross-sectional design. The data used are secondary data, consisting of medical records of 112 COVID-19 patients as research subjects. The variables studied are leukocyte and total lymphocyte levels according to laboratory result, and documented lung abnormalities in medical records. The data is then analyzed using the Chi-square test with a significance level of p&lt;0.05. Lung abnormalities, particularly pneumonia, are dominated by increased leukocyte levels in 62 individuals (91.2%) and decreased total lymphocyte levels in 63 individuals (94.1%). There is a significant association between leukocyte levels with lung abnormalities (p = 0.021), and total lymphocytes with lung abnormalities (p = 0.001).

Pretreatment Interstitial Lung Abnormalities Detected on Abdominal Computed Tomography Scans in Prostate Cancer Patients.

Prostate cancer and interstitial lung abnormality (ILA) share similar risk factor, which is men and older age. The purpose of this study was to investigate the prevalence of pretreatment ILA among prostate cancer patients who underwent abdominal computed tomography (CT) within 1 year at their first visit to the urology department. In addition, we aimed to assess the association between pretreatment ILA and long-term survival in prostate cancer patients. This study was conducted in patients who had a first visit for prostate cancer at urology department between 2005 and 2016 and underwent an abdominal CT within 1 year. A thoracic radiologist evaluated the presence of ILA through inspecting the lung base scanned on an abdominal CT. The association between pretreatment ILA and survival was assessed using Kaplan-Meier analysis with log-rank test. Specific survival rates at 12, 36, and 60 months according to the presence of ILA were evaluated using z -test. Cox regression analysis was used to assess the risk factors of mortality. A total of 173 patients were included (mean age, 70.23 ± 7.98 years). Pretreatment ILA was observed in 10.4% of patients. Patients with ILA were more likely to be older and current smokers. Pretreatment ILA was associated with poor survival ( P < 0.001). Age ≥70 years (hazards ratio [HR], 1.98; 95% confidence interval [CI], 1.24-3.16; P = 0.004), metastatic stage (HR, 2.26; 95% CI, 1.36-3.74; P = 0.002), and ILA (HR, 1.96; 95% CI, 1.06-3.60; P = 0.031) were the independent risk factors of mortality. An ILA (HR, 3.94; 95% CI, 1.78-8.72; P = 0.001) was the only independent risk factor of mortality in localized stage prostate cancer patients. This study provides important insights into the unexplored effect of pretreatment ILA in prostate cancer patients. Pretreatment ILAs were observed considerably in the lung bases scanned on the abdominal CT scans among prostate cancer patients. Furthermore, pretreatment ILAs were the risk factor of mortality. Therefore, lung bases should be routinely inspected in the abdominal CT scans of prostate cancer patients. This result may help clinicians in establishing personalized management strategy of prostate cancer patients.

Hyperoxia prevents the dynamic neonatal increases in lung mesenchymal cell diversity

Rapid expansion of the pulmonary microvasculature through angiogenesis drives alveolarization, the final stage of lung development that occurs postnatally and dramatically increases lung gas-exchange surface area. Disruption of pulmonary angiogenesis induces long-term structural and physiologic lung abnormalities, including bronchopulmonary dysplasia, a disease characterized by compromised alveolarization. Although endothelial cells are primary determinants of pulmonary angiogenesis, mesenchymal cells (MC) play a critical and dual role in angiogenesis and alveolarization. Therefore, we performed single cell transcriptomics and in-situ imaging of the developing lung to profile mesenchymal cells during alveolarization and in the context of lung injury. Specific mesenchymal cell subtypes were present at birth with increasing diversity during alveolarization even while expressing a distinct transcriptomic profile from more mature correlates. Hyperoxia arrested the transcriptomic progression of the MC, revealed differential cell subtype vulnerability with pericytes and myofibroblasts most affected, altered cell to cell communication, and led to the emergence of Acta1 expressing cells. These insights hold the promise of targeted treatment for neonatal lung disease, which remains a major cause of infant morbidity and mortality across the world.

Enhancing lung abnormalities diagnosis using hybrid DCNN-ViT-GRU model with explainable AI: A deep learning approach

In this study, we propose a novel approach called DCNN-ViT-GRU, which combines deep Convolutional Neural Networks (CNNs) with Gated Recurrent Units (GRUs) and the Vision Transformer (ViT) model for the accurate detection and classification of lung abnormalities. By leveraging the strengths of both CNNs and the ViT model, our architecture automatically extracts meaningful features from lung images, leading to improved diagnostic capabilities. The DCNN-ViT-GRU model utilizes a combination of deep CNN and GRU layers, allowing it to effectively capture local and global patterns. This comprehensive feature representation enhances the model's ability to identify various abnormalities in lung images, including lung cancer, COVID-19, and pneumonia. To further enhance the interpretability and transparency of our model, we integrate Explainable Artificial Intelligence (XAI) techniques, including LIME and SHAP. This integration provides valuable insights into the decision-making process of the DCNN-ViT-GRU model, enabling clinicians to understand and validate the predictions made by the model. We evaluated the performance of our proposed approach on diverse datasets containing cases of lung abnormalities. Through cross-validation, our DCNN-ViT-GRU model achieved impressive weighted mean accuracy of 99% and 99.86% for two distinct datasets, demonstrating its superior performance. Furthermore, in hold-out validation on separate datasets, the model achieved accuracies of 99.09% and 99.87%, respectively. Integrating the XAI techniques enhances the interpretability of the DCNN-ViT-GRU model and provides clinicians with valuable insights regarding the factors contributing to the diagnosis of lung abnormalities. This approach presents a promising solution for accurate and interpretable lung abnormalities detection and classification, with potential implications for improved patient care and treatment planning.

An Advanced Deep Learning Framework for Multi-Class Diagnosis from Chest X-ray Images

Chest X-ray imaging plays a vital and indispensable role in the diagnosis of lungs, enabling healthcare professionals to swiftly and accurately identify lung abnormalities. Deep learning (DL) approaches have attained popularity in recent years and have shown promising results in automated medical image analysis, particularly in the field of chest radiology. This paper presents a novel DL framework specifically designed for the multi-class diagnosis of lung diseases, including fibrosis, opacity, tuberculosis, normal, viral pneumonia, and COVID-19 pneumonia, using chest X-ray images, aiming to address the need for efficient and accessible diagnostic tools. The framework employs a convolutional neural network (CNN) architecture with custom blocks to enhance the feature maps designed to learn discriminative features from chest X-ray images. The proposed DL framework is evaluated on a large-scale dataset, demonstrating superior performance in the multi-class diagnosis of the lung. In order to evaluate the effectiveness of the presented approach, thorough experiments are conducted against pre-existing state-of-the-art methods, revealing significant accuracy, sensitivity, and specificity improvements. The findings of the study showcased remarkable accuracy, achieving 98.88%. The performance metrics for precision, recall, F1-score, and Area Under the Curve (AUC) averaged 0.9870, 0.9904, 0.9887, and 0.9939 across the six-class categorization system. This research contributes to the field of medical imaging and provides a foundation for future advancements in DL-based diagnostic systems for lung diseases.

The Effects of Early Mobilization Protocol on Pre and Post Operative Functional Performance for Individuals with Post Abdominal Surgery

Background: The post surgical period of abdominal incision was accompanied with respiratory muscle dysfunctionand diminished physical capability. Limited upright mobilisation, exhaustion, and restricted lung abnormalities,among other functional issues, are linked to the early postoperative days. Improving pre-operative levels ofphysical functioning in individuals might be beneficial for post operative outcome.Aim: Aim of the study was to find out on which post-operative day the abdominal surgery participants get to thesame functional status as pre-operative status.Method: 40 Individuals hospitalized for abdominal surgery at Saveetha Medical College and Hospital werechosen for the study based on the inclusion and exclusion criteria. The selected participants were treated withdiaphragmatic breathing exercise, Incentive spirometry, thoracic expansion exercise, splinted coughing technique,active range of motion exercise for upper extremity and lower extremity for pre-operative abdominal surgeryparticipants. Post operative participants were treated with physiotherapy from POD 1 till the time their functionalstatus become same as the pre-operative status. Six- minute walk test, hospital anxiety and depression scale wereused in this study. Their scores were calculated and analysed.Result: Similar pre-operative mean (365.25±25.92) was attained at POD-7 (350.75±25.46). Day of POD-5, the HADSscore was normal (0 to7) in depression.Conclusion: This study shows the post-operative status is attained back on POD-7 with using 6MWT. Depressionwas relieved at POD-5 with a value of mean and standard deviation in HADS.

Lung abnormalities on computed tomography of Vietnamese patients with COVID-19 and the association with medical variables

ObjectivesPatients with COVID-19 may experience a lung injury without presenting clinical symptoms. Early detection of lung injury in patients with COVID-19 is required to enhance prediction and prevent severe progression. MethodsLung lesions in patients with COVID-19 were defined using the Fleischner Society terminology. Chest computed tomography lesions and their correlation with demographic characteristics and medical variables were identified. ResultsPatients with mild and moderate COVID-19 had up to 45% lung injuries, whereas critical patients had 55%. However, patients with mild and moderate COVID-19 typically had low-level lung injuries. Ground-glass (68.1%), consolidation (48.8%), opacity (36.3%), and nodular (6.9%) lung lesions were the most prevalent in patients with COVID-19. Patients with COVID-19 infected with the Delta variant had worse lung injury than those infected with the Alpha and Omicron. People vaccinated with ≥2 doses showed a lower risk of lung injury than those vaccinated with <1 dose. Patients <18 years old were less likely to have a lung injury than patients >18 years old. The treatment outcomes were unaffected by the severity of the lung injury. ConclusionPatients with mild COVID-19 had a similar risk of lung injury as patients with severe COVID-19. Thus, using chest computed tomography to detect lung injury can enhance the treatment outcomes and reduce the patient's risk of pulmonary complications.

Risk Factors and Determinants of Pulmonary Function Impairments in Chronic Respiratory Diseases in Ethiopia: A Hospital-based Cross-Sectional Study

Introduction: Chronic respiratory diseases (CRDs) are diseases of the airways and lung parenchyma. Although they are leading causes of morbidity and mortality globally, chronic respiratory diseases have received relatively little public attention. This study aimed to characterize the common chronic respiratory diseases, along with their lung function and possible determinants in symptomatic patients attending clinics at Bishoftu General Hospital, Ethiopia.&#x0D; Methods: A cross-sectional study was conducted at the outpatient department of Bishoftu Hospital from June 2019 to March 2020. Consecutive adult patients aged 18 and above with chronic respiratory symptoms (lasting more than 8 weeks) and no evidence of active tuberculosis were recruited. Questionnaires were used to collect data on demographics, symptoms, diagnoses, and potential risk factors. Lung function was measured by spirometry. Allergic status was assessed through allergen skin prick testing with standard allergens. &#x0D; Results: A total of 170 participants were recruited, with the majority being female (102, 60.0%). The mean age was 49 years (SD=16). The most common symptoms reported were wheezing in the last twelve months 156 (91.8%), cough 138 (81.2%) and severe exertional breathlessness 137 (80.6%). Thirty-nine (22.9%) participants were either active or passive smokers. Half of the patients (50.3%) were exposed daily to vapors, dust, gases, or fumes and 58 (34.3%) were exposed to biomass smoke. In total, 138 (81.2%) had a positive allergen skin prick test. Chronic bronchitis (49.1%) and asthma (36.1%) were the most common clinical diagnoses. Classification of lung function revealed 23 (15%) normal, 29 (19%) obstructive, 36(23.5%) restrictive and 61(39.9%) mixed obstructive/ restrictive patterns. Airflow obstruction (FEV1/FVC ratio) was independently associated with increasing age (p&lt;0.05), exertional breathlessness (p&lt;0.001), previous history of asthma (p&lt;0.05), BMI (p&lt;0.05), and doctordiagnosed chronic obstructive pulmonary disease (p&lt;0.001) and asthma (p&lt;0.05).&#x0D; Conclusion: This study demonstrated a high burden of abnormal lung function in patients attending clinics due to chronic respiratory symptoms. Increasing age, exertional breathlessness, prior diagnosis of asthma, BMI, and clinically diagnosed COPD and asthma were independently associated with obstructed lung function. These find ings highlight the critical need for spirometry services to identify lung abnormalities in patients with chronic respiratory symptoms. Epidemiology, and the findings should be factored into clinical decision making and program design for disease prevention, screening, and treatment. It also calls for further prospective research to learn more about the conditions in the context of additional relevant personal and clinical characteristics.

Feasibility of high-frequency percussions in people with severe acquired brain injury and tracheostomy: an observational study.

People with severe acquired brain injury (pwSABI) frequently experience pulmonary complications. Among these, atelectasis can occur as a result of pneumonia, thus increasing the chance of developing acute respiratory failure. Respiratory physiotherapy contribution to the management of atelectasis in pwSABI is yet poorly understood. We conducted a retrospective analysis on 15 non-cooperative pwSABI with tracheostomy and spontaneously breathing, hospitalized and treated with high-frequency percussion physiotherapy between September 2018 and February 2021 at the Neurological Rehabilitation Unit of the IRCCS "S.Maria Nascente - Fondazione Don Gnocchi", Milan. Our primary aim was to investigate the feasibility of such a physiotherapy intervention method. Then, we assessed changes in respiratory measures (arterial blood gas analysis and peripheral night-time oxygen saturation) and high-resolution computed tomography lung images, evaluated before and after the physiotherapy treatment. The radiological measures were a modified radiological atelectasis score (mRAS) assigned by two radiologists, and an opacity score automatically provided by the software CT Pneumonia Analysis® that identifies the regions of abnormal lung patterns. Treatment diaries showed that all treatments were completed, and no adverse events during treatment were registered. Among the 15 pwSABI analyzed, 8 were treated with IPV® and 7 with MetaNeb®. After a median of 14 (I-III quartile=12.5-14.5) days of treatment, we observed a statistical improvement in various arterial blood gas measures and peripheral night-time oxygen saturation measures. We also found radiological improvement or stability in more than 80% of pwSABI. In conclusion, our physiotherapy approach was feasible, and we observed respiratory parameters and radiological improvements. Using technology to assess abnormal tomographic patterns could be of interest to disentangle the short-term effects of respiratory physiotherapy on non-collaborating people.

Robust explanation supervision for false positive reduction in pulmonary nodule detection.

Lung cancer is the deadliest and second most common cancer in the United States due to the lack of symptoms for early diagnosis. Pulmonary nodules are small abnormal regions that can be potentially correlated to the occurrence of lung cancer. Early detection of these nodules is critical because it can significantly improve the patient's survival rates. Thoracic thin-sliced computed tomography (CT) scanning has emerged as a widely used method for diagnosing and prognosis lung abnormalities. The standard clinical workflow of detecting pulmonary nodules relies on radiologists to analyze CT images to assess the risk factors of cancerous nodules. However, this approach can be error-prone due to the various nodule formation causes, such as pollutants and infections. Deep learning (DL) algorithms have recently demonstrated remarkable success in medical image classification and segmentation. As an ever more important assistant to radiologists in nodule detection, it is imperative ensure the DL algorithm and radiologist to better understand the decisions from each other. This study aims to develop a framework integrating explainable AI methods to achieve accurate pulmonary nodule detection. A robust and explainable detection (RXD) framework is proposed, focusing on reducing false positives in pulmonary nodule detection. Its implementation is based on an explanation supervision method, which uses nodule contours of radiologists as supervision signals to force the model to learn nodule morphologies, enabling improved learning ability on small dataset, and enable small dataset learning ability. In addition, two imputation methods are applied to the nodule region annotations to reduce the noise within human annotations and allow the model to have robust attributions that meet human expectations. The 480, 265, and 265 CT image sets from the public Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) dataset are used for training, validation, and testing. Using only 10, 30, 50, and 100 training samples sequentially, our method constantly improves the classification performance and explanation quality of baseline in terms of Area Under the Curve (AUC) and Intersection over Union (IoU). In particular, our framework with a learnable imputation kernel improves IoU from baseline by 24.0% to 80.0%. A pre-defined Gaussian imputation kernel achieves an even greater improvement, from 38.4% to 118.8% from baseline. Compared to the baseline trained on 100 samples, our method shows less drop in AUC when trained on fewer samples. A comprehensive comparison of interpretability shows that our method aligns better with expert opinions. A pulmonary nodule detection framework was demonstrated using public thoracic CT image datasets. The framework integrates the robust explanation supervision (RES) technique to ensure the performance of nodule classification and morphology. The method can reduce the workload of radiologists and enable them to focus on the diagnosis and prognosis of the potential cancerous pulmonary nodules at the early stage to improve the outcomes for lung cancer patients.

Magnetic Resonance Imaging of Pulmonary and Paranasal Sinus Abnormalities in Children with Primary Ciliary Dyskinesia Compared to Children with Cystic Fibrosis.

Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are characterized by inherited impaired mucociliary clearance leading to chronic progressive lung disease as well as chronic rhinosinusitis (CRS). The diseases share morphological and functional commonalities on magnetic resonance imaging (MRI) of the lungs and paranasal sinuses, but comparative MRI studies are lacking. Objectives: To determine whether PCD shows different associations of pulmonary and paranasal sinus abnormalities on MRI and lung function test results in children (infants to adolescents) compared with children with CF. Methods: Eighteen children with PCD (median age, 9.5 [IQR, 3.4-12.7] yr; range, 0-18 yr) and 36 age-matched CF transmembrane conductance regulator modulator-naive children with CF (median age, 9.4 [3.4-13.2] yr; range, 0-18 yr) underwent same-session chest and paranasal sinus MRI as well as spirometry (to determine forced expiratory volume in 1 s percent predicted) and multiple-breath washout (to determine lung clearance index z-score). Pulmonary and paranasal sinus abnormalities were assessed using previously validated chest MRI and CRS-MRI scoring systems. Results: Mean chest MRI global score was similar in children with PCD and CF (15.0 [13.5-20.8] vs. 15.0 [9.0-15.0]; P = 0.601). Consolidations were more prevalent and severe in children with PCD (56% vs. 25% and 1.0 [0.0-2.8] vs. 0.0 [0.0-0.3], respectively; P < 0.05). The chest MRI global score correlated moderately with forced expiratory volume in 1 second percent predicted in children with PCD and children with CF (r = -0.523 and -0.687; P < 0.01) and with lung clearance index in children with CF (r = 0.650; P < 0.001) but not in PCD (r = 0.353; P = 0.196). CRS-MRI sum score and mucopyocele subscore were lower in children with PCD than in children with CF (27.5 [26.3-32.0] vs. 37.0 [37.8-40.0] and 2.0 [0.0-2.0] vs. 7.5 [4.8-9.0], respectively; P < 0.01). CRS-MRI sum score did not correlate with chest MRI score in PCD (r = 0.075-0.157; P = 0.557-0.788) but correlated moderately with MRI morphology score in CF (r = 0.437; P < 0.01). Conclusions: MRI detects differences in lung and paranasal sinus abnormalities between children with PCD and those with CF. Lung disease does not correlate with CRS in PCD but correlates in CF.

Antenatal Endotoxin Induces Dysanapsis in Experimental Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is characterized by impaired lung development with sustained functional abnormalities due to alterations of airways and the distal lung. Although clinical studies have shown striking associations between antenatal stress and BPD, little is known about the underlying pathogenetic mechanisms. Whether dysanapsis, the concept of discordant growth of the airways and parenchyma, contributes to late respiratory disease as a result of antenatal stress is unknown. We hypothesized that antenatal endotoxin (ETX) impairs juvenile lung function as a result of altered central airway and distal lung structure, suggesting the presence of dysanapsis in this preclinical BPD model. Fetal rats were exposed to intraamniotic ETX (10 μg) or saline solution (control) 2 days before term. We performed extensive structural and functional evaluation of the proximal airways and distal lung in 2-week-old rats. Distal lung structure was quantified by stereology. Conducting airway diameters were measured using micro-computed tomography. Lung function was assessed during invasive ventilation to quantify baseline mechanics, response to methacholine challenge, and spirometry. ETX-exposed pups exhibited distal lung simplification, decreased alveolar surface area, and decreased parenchyma-airway attachments. ETX-exposed pups exhibited decreased tracheal and second- and third-generation airway diameters. ETX increased respiratory system resistance and decreased lung compliance at baseline. Only Newtonian resistance, specific to large airways, exhibited increased methacholine reactivity in ETX-exposed pups compared with controls. ETX-exposed pups had a decreased ratio of FEV in 0.1 second to FVC and a normal FEV in 0.1 second, paralleling the clinical definition of dysanapsis. Antenatal ETX causes abnormalities of the central airways and distal lung growth, suggesting that dysanapsis contributes to abnormal lung function in juvenile rats.

Identification of circulating autoantibodies to non-modified proteins associated with ACPA status in early rheumatoid arthritis.

To discover autoantibodies to non-modified proteins associated with the presence/absence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). The autoantibody repertoire of 80 ACPA negative and 80 ACPA positive RA subjects from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort was screened using a suspension bead array built on protein fragments earlier described as autoimmunity targets. Four autoantibodies positive in the initial screening were validated in another set of EIRA samples containing 317 ACPA-positive, 302 ACPA-negative and 372 age- and sex-matched controls. The relationship between the four autoantibodies and lung abnormalities on high-resolution computed tomography (HRTC) was examined in 93 early RA patients from LURA cohort. Association between the autoantibodies, smoking and MHC class II alleles was assessed by logistic regression analysis. : Anti-ANOS1 and anti-MURC IgG levels were associated with ACPA-positive status (OR = 3.02; 95% CI 1.87-4.89; and OR = 1.86; 95% CI 1.16-2.97, respectively) and increased in ACPA-positive patients compared with controls. Anti-ANOS1 IgG was associated with smoking habit (OR = 2.11; 95% CI 1.22-3.69) and anti-MURC IgG with the presence of the MHC class II "shared-epitope" genes (OR = 1.95; 95% CI 1.11-3.46). Anti-TSPYL4 IgG was associated with ACPA-negative (OR = 0.41; 95% CI 0.19-0.89). Anti-TSPYL4 IgG and anti-MAP2K6 IgG levels were increased in the ACPA-negative patients compared with controls. Presence of anti-MAP2K6 IgG and anti-TSPYL4 IgG correlated negatively with HRCT-defined lung abnormalities. These four autoantibodies may be useful in diagnostics and in predicting clinical phenotypes of RA.