Phase-contrast virtual chest radiography.

Respiratory X-ray imaging enhanced by phase contrast has shown improved airway visualization in animal models. Limitations in current X-ray technology have nevertheless hindered clinical translation, leaving the potential clinical impact an open question. Here, we explore phase-contrast chest radiography in a realistic in silico framework. Specifically, we use preprocessed virtual patients to generate in silico chest radiographs by Fresnel-diffraction simulations of X-ray wave propagation. Following a reader study conducted with clinical radiologists, we predict that phase-contrast edge enhancement will have a negligible impact on improving solitary pulmonary nodule detection (6 to 20 mm). However, edge enhancement of bronchial walls visualizes small airways (< 2 mm), which are invisible in conventional radiography. Our results show that phase-contrast chest radiography could play a future role in observing small-airway obstruction (e.g., relevant for asthma or early-stage chronic obstructive pulmonary disease), which cannot be directly visualized using current clinical methods, thereby motivating the experimental development needed for clinical translation. Finally, we discuss quantitative requirements on distances and X-ray source/detector specifications for clinical implementation of phase-contrast chest radiography.

Deep learning to detect left ventricular structural abnormalities in chest X-rays.

BACKGROUND AND AIMS: Early identification of cardiac structural abnormalities indicative of heart failure is crucial to improving patient outcomes. Chest X-rays (CXRs) are routinely conducted on a broad population of patients, presenting an opportunity to build scalable screening tools for structural abnormalities indicative of Stage B or worse heart failure with deep learning methods. In this study, a model was developed to identify severe left ventricular hypertrophy (SLVH) and dilated left ventricle (DLV) using CXRs. METHODS: A total of 71 589 unique CXRs from 24 689 different patients completed within 1 year of echocardiograms were identified. Labels for SLVH, DLV, and a composite label indicating the presence of either were extracted from echocardiograms. A deep learning model was developed and evaluated using area under the receiver operating characteristic curve (AUROC). Performance was additionally validated on 8003 CXRs from an external site and compared against visual assessment by 15 board-certified radiologists. RESULTS: The model yielded an AUROC of 0.79 (0.76-0.81) for SLVH, 0.80 (0.77-0.84) for DLV, and 0.80 (0.78-0.83) for the composite label, with similar performance on an external data set. The model outperformed all 15 individual radiologists for predicting the composite label and achieved a sensitivity of 71% vs. 66% against the consensus vote across all radiologists at a fixed specificity of 73%. CONCLUSIONS: Deep learning analysis of CXRs can accurately detect the presence of certain structural abnormalities and may be useful in early identification of patients with LV hypertrophy and dilation. As a resource to promote further innovation, 71 589 CXRs with adjoining echocardiographic labels have been made publicly available.

Recurrence of ventricular fibrillation in out-of-hospital cardiac arrest: Clinical evidence and underlying ionic mechanisms.

Defibrillation remains the optimal therapy for terminating ventricular fibrillation (VF) in out-of-hospital cardiac arrest (OHCA) patients, with reported shock success rates of ∼90%. A key persistent challenge, however, is the high rate of VF recurrence (∼50-80%) seen during post-shock cardiopulmonary resuscitation (CPR). Studies have shown that the incidence and time spent in recurrent VF are negatively associated with neurologically-intact survival. Recurrent VF also results in the administration of extra shocks at escalating energy levels, which can cause cardiac dysfunction. Unfortunately, the mechanisms underlying recurrent VF remain poorly understood. In particular, the role of chest-compressions (CC) administered during CPR in mediating recurrent VF remains controversial. In this review, we first summarize the available clinical evidence for refibrillation occurring during CPR in OHCA patients, including the postulated contribution of CC and non-CC related pathways. Next, we examine experimental studies highlighting how CC can re-induce VF via direct mechano-electric feedback. We postulate the ionic mechanisms involved by comparison with similar phenomena seen in commotio cordis. Subsequently, the hypothesized contribution of partial cardiac reperfusion (either as a result of CC or CC independent organized rhythm) in re-initiating VF in a globally ischaemic heart is examined. An overview of the proposed ionic mechanisms contributing to VF recurrence in OHCA during CPR from a cellular level to the whole heart is outlined. Possible therapeutic implications of the proposed mechanistic theories for VF recurrence in OHCA are briefly discussed.

For Tuberculosis, Not "To Screen or Not to Screen?" but "Who?" and "How?"

Active case finding leveraging new molecular diagnostics and chest X-rays with automated interpretation algorithms is increasingly being developed for high-risk populations to drive down tuberculosis incidence. We consider why such an approach did not deliver a decline in tuberculosis prevalence in Brazilian prison populations and what to consider next.

Chest Radiograph Screening for Detecting Subclinical Tuberculosis in Asymptomatic Household Contacts, Peru.

The World Health Organization's end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74-31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.

Acute chest syndrome in children with sickle cell disease: Data from a national AIEOP cohort identify priority areas of intervention in a hub-and-spoke system.

Acute chest syndrome (ACS) is a frequent cause of hospitalization in sickle cell disease (SCD). Despite advances in acute care, many settings still lack knowledge about ACS best practices. After the AIEOP Guidelines were published in 2012, suggesting standardized management in Italy, a retrospective study was performed to assess the diagnostic and therapeutic pathways of ACS in children. From 2013 to 2018, 208 ACS episodes were presented by 122/583 kids in 11 centres. 73 were male, mean age 10.9 years, 85% African, 92% HbSS or Sß°. In our hub-and-spoke system, a good adherence to Guidelines was documented, but discrepancies between reference centres and general hospitals were noted. Improvement is needed for timely transfer to reference centres, use of incentive spirometry, oxygen therapy and pain management.

Sputum interleukin-6 level as a marker of severity during acute chest syndrome in children with sickle cell disease.

Acute chest syndrome (ACS) is a leading cause of morbimortality in sickle cell disease (SCD). In this prospective observational study, we investigated sputum interleukin-6 (IL-6) level as an ACS severity marker during 30 ACS episodes in 26 SCD children. Sputum IL-6 levels measured within the first 72 h of hospitalisation for ACS were significantly higher in patients with oxygen requirement ≥2 L/min, ventilation (invasive and/or non-invasive) length ≥5 days, bilateral and/or extensive opacities on chest X-ray or erythrocytapheresis requirement. Sputum IL-6 could serve as an ACS severity marker to help identify patients requiring targeted anti-inflammatory treatments such as tocilizumab.

Left ventricular global longitudinal strain and acute myocardial injury in patients with sickle cell disease admitted to the intensive care unit for vaso-occlusive crisis.

In patients with sickle cell disease (SCD), SCD-related cardiomyopathy may be partly due to repeated ischaemic events related to sickling during vaso-occlusive crises, but few clinical studies support this hypothesis. We evaluated the incidence of acute myocardial ischaemia during vaso-occlusive crises as assessed by the left ventricular global longitudinal strain (LVGLS) and high-sensitive cardiac troponin T (hs-cTnT). We included adult patients with SCD admitted to the intensive care unit (ICU) for vaso-occlusive crisis. We collected hs-cTnT and measured LVGLS with echocardiography at admission (day 1), day 2, day 3 and ICU discharge. Among 55 patients included, considering only the first hospitalization of patients admitted several times, 3 (5%) had elevated hs-cTnT at ≥1 time point of the ICU stay. It was ≤2 times the upper limit of normal in two of these patients. LVGLS was altered at ≥1 time point of the ICU stay in 13 (24%) patients. Both hs-cTnT and LVGLS were abnormal at ≥1 time point of the hospital stay in 2 (4%) patients. Acute myocardial injury as assessed by troponin elevation and LVGLS impairment was a rare event during vaso-occlusive crises.

A novel method for the percutaneous induction of myocardial infarction by occlusion of small coronary arteries in the rabbit.

Arrhythmic sudden cardiac death (SCD) is an important cause of mortality following myocardial infarction (MI). The rabbit has similar cardiac electrophysiology to humans and is therefore an important small animal model to study post-MI arrhythmias. The established approach of surgical coronary ligation results in thoracic adhesions that impede epicardial electrophysiological studies. Adhesions are absent following a percutaneously induced MI, which is also associated with reduced surgical morbidity and so represents a clear refinement of the approach. Percutaneous procedures have previously been described in large rabbits (3.5-5.5 kg). Here, we describe a novel method of percutaneous MI induction in smaller rabbits (2.5-3.5 kg) that are readily available commercially. New Zealand White rabbits (n = 51 males, 3.1 ± 0.3 kg) were anesthetized using isoflurane (1.5-3%) and underwent either a percutaneous MI procedure involving microcatheter tip deployment (≤1.5 Fr, 5 mm), coronary ligation surgery, or a sham procedure. Electrocardiography (ECG) recordings were used to confirm ST-segment elevation indicating coronary occlusion. Blood samples (1 and 24 h) were taken for cardiac troponin I (cTnI) levels. Ejection fraction (EF) was measured at 6-8 wk. Rabbits were then euthanized (Euthatal) and hearts were processed for magnetic resonance imaging and histology. Mortality rates were similar in both groups. Scar volume, cTnI, and EF were similar between both MI groups and significantly different from their respective sham controls. Thus, percutaneous coronary occlusion by microcatheter tip deployment is feasible in rabbits (2.5-3.5 kg) and produces an MI with similar characteristics to surgical ligation with lower procedural trauma and without epicardial adhesions.NEW & NOTEWORTHY Surgical coronary ligation is the standard technique to induce myocardial infarction (MI) in rabbits but is associated with procedural trauma and the generation of thoracic adhesions. Percutaneous coronary occlusion avoids these shortcomings and is established in pigs but has only been applicable to large rabbits because of a mismatch between the equipment used and target vessel size. Here, we describe a new scalable approach to percutaneous MI induction that is safe and effective in 2.5-3.5-kg rabbits.

Establishment of nonobstructive coronary microcirculatory disorders in rabbits using three established methods and a comparative study.

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared. The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (ß, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability. This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.

Ten-year trend analysis of breast cancer, oncoplastic, and reconstructive breast surgery in a single institution (2010-2019), what has not changed?

PURPOSE: There has been a UK national directive to ensure that patients are offered reconstructive surgical options. We aimed to assess any change in oncoplastic practice over a 10-year period. METHODS: The surgical management of 7019 breast cancers was retrospectively assessed at Nightingale Breast Centre, Manchester University UK, from 2010 to 2019. The procedures were categorised into breast conservative surgery (BCS) and mastectomy ± immediate reconstruction. The data were analysed using inclusion and exclusion criteria. RESULTS: The overall rates of BCS and mastectomy were 60.1% and 39.9% respectively. No statistically significant change in the overall rates of BCS or mastectomy was observed over the last decade (p = 0.08). The rate of simple wide local excision (WLE) decreased from 98.7% to 89.3% (p < 0.001), whilst the rate of therapeutic mammoplasty (TM) increased from 1.3% to 8% (p < 0.01). The rate of chest wall perforator flaps (CWPF) changed from zero to account for 2.7% of all BCS by 2019. The overall rate of immediate breast reconstruction (IBR) did not significantly change over the study period, but it consistently remained above the national average of 27%. The rate of implant-based IBR increased from 61.3% to 76.5% (p = 0.012), whilst the rate of Latissimus Dorsi (LD) reconstruction decreased from 26.7% to 5.1% (p < 0.05). Additionally, the rate of nipple-sparing mastectomy significantly increased from 5.2% to 24%. CONCLUSION: No significant changes in the overall rates of BCS was observed, the rates of advanced breast conservation techniques, nipple-sparing mastectomy, and implant-based IBR all have increased, whilst the use of LD reconstruction decreased.

Complications of Outpatient Chest Tube Management for Prolonged Air Leaks After Pulmonary Surgery.

PURPOSE: Air leaks are common after pulmonary surgery. Prolonged air leaks (PALs) may persist through discharge and often are managed with one-way valve devices (OWD). We sought to determine the course and complications of patients discharged with OWDs, risk factors for complications, and to evaluate the utility of clamp trials before chest tube (CT) removal. METHODS: Single-institution, retrospective review of patients discharged with a OWD after pulmonary surgery between 2008 and 2022. Charts were examined for the presence of complications and CT duration. Differences in CT duration were compared by using the Wilcoxon rank-sum test. RESULT: Sixty-four of 1917 (3.3%) pulmonary surgeries resulted in OWD use. Twelve of 64 (19%) patients discharged with a OWD suffered a complication. Nine of 64 (14%) had a CT-related readmission, and seven of 64 (11%) required PAL intervention. Patients sustaining a complication demonstrated longer CT durations before complication compared with duration in patients without complications, with median days of 13 [IQR 6-21] vs. 7 [IQR 6-12], p = 0.04). Five (7.8%) OWD patients developed an empyema; only one (20%) occurred before a CT duration of 14 days. Sixteen of 64 (25%) patients underwent a clamp trial before CT removal. One of ten (10%) failed even with no air leak present, whereas one of six (17%) failed with a present/questionable air leak. CONCLUSIONS: One-way valve device use has a substantial complication rate, and chest tube duration is a risk factor. In-hospital interventions might benefit patients with larger leaks that likely require prolonged OWD use. Because clamp trials occasionally fail, we contend that a clamp trial is the safest course before CT removal.

Associations of triglyceride-glucose (TyG) index with chest pain incidence and mortality among the U.S. population.

BACKGROUND: The triglyceride and glucose (TyG) index, a simple surrogate marker of insulin resistance, is related to cardiovascular disease. However, there is a lack of evidence for the relationship between the TyG index and chest pain. This study aimed to investigate the association of the TyG index with chest pain and to evaluate the relationship between the TyG index and all-cause mortality in participants with or without chest pain. METHODS: The present study utilized data from the 2001-2012 National Health and Nutrition Examination Survey (NHANES), employing a combination of cross-sectional and cohort study designs. The association between the TyG index and chest pain was investigated using weighted logistic regression models. Weighted Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality. Restricted cubic spline analysis was used to explore linear or nonlinear relationships between the TyG index and chest pain or all-cause mortality. RESULTS: The findings revealed a positive correlation between the TyG index and chest pain, even after adjusting for potential confounding factors (quartile 4 versus quartile 1, odds ratio [OR] 1.42, 95% confidence interval [CI] 1.14-1.77, P = 0.002). During a mean follow-up time of 139 months, a total of 2286 individuals (27.43%) experienced mortality. Weighted multivariate Cox regression models indicated that for each one-unit increase in the TyG index, the adjusted hazard ratio (HR) for mortality was 1.14 (95% CI = 0.94-1.37) for participants with chest pain and 1.25 (95% CI = 1.09-1.43) for those without chest pain. Furthermore, restricted cubic spline analysis revealed a linear relationship between the TyG index and chest pain (P for nonlinearity = 0.902), whereas a nonlinear relationship was shown between the TyG index and all-cause mortality among populations regardless of chest pain (all P for nonlinearity < 0.01). CONCLUSION: The TyG index was positively linked to a higher incidence of chest pain. Moreover, the TyG index was associated with all-cause mortality not only in participants with chest pain but also in those without chest pain.

In-Hospital Adverse Events of Pheochromocytoma-Induced Takotsubo Syndrome: A Literature Review and Cluster Analysis of 172 Cases.

Background: Pheochromocytoma-induced takotsubo syndrome (Pheo-TTS) significantly increases the risk of adverse events for inpatient. The early identification of risk factors at admission is crucial for effective risk stratification and minimizing complications in Pheo-TTS patients. Methods: We conducted a systematic review combined with hierarchical cluster and feature importance analysis of demographic, clinical and laboratory data upon admission, alongside in-hospital complication data for Pheo-TTS patients. We analyzed cases published in PubMed and Embase from 2 May 2006 to 27 April 2023. Results: Among 172 Pheo-TTS patients, cluster analysis identified two distinct groups: a chest pain dominant (CPD) group (n = 86) and a non-chest pain dominant (non-CPD) group (n = 86). The non-CPD group was characterized by a younger age (44.0 ± 15.2 vs. 52.4 ± 14.4, p < 0.001), a higher prevalence of neurological/psychiatric disorders (53.5% vs. 32.6%), and increased presentation of dyspnea (87.2% vs. 17.4%), pulmonary rales (59.3% vs. 8.1%), and tachycardia (77.9% vs. 30.2%). Additionally, they exhibited more atypical takotsubo syndrome (TTS) imaging phenotypes (55.8% vs. 36.5%, all p < 0.05). The non-CPD group experienced more than a 2-fold increase for in-hospital adverse events compared to the CPD group (70.9% vs. 30.2%, p < 0.001). After adjusting for confounding factors, the absence of chest pain (odds ratio [OR] = 0.407, 95% confidence interval [CI] 0.169-0.979, p = 0.045), the presence of abdominal symptoms (OR = 3.939, 95% CI 1.770-8.766, p = 0.001), pulmonary rales (OR = 4.348, 95% CI 1.857-10.179, p = 0.001), and atypical TTS imaging phenotype (OR = 3.397, 95% CI 1.534-7.525, p = 0.003) remained as independent predictors of in-hospital complications. Conclusions: Clinical manifestations and imaging features at admission help to predict in-hospital complications for Pheo-TTS patients.

Coronary Artery Calcium Score-Weighted Clinical Likelihood Model Performance in Patients with Stable Chest Pain and Coronary Artery Calcium Scores of Zero.

Background: For individuals with persistent stable chest pain (SCP) and a coronary artery calcium score (CACS) of 0, it might be challenging to establish the best risk assessment method for determining the individuals who will not benefit from further cardiovascular imaging testing (CIT). Thus, we investigated the CACS-weighted clinical likelihood (CACS-CL) model in SCP patients with a CACS of 0. Methods: Thus, to assess SCP, we originally enrolled 14,232 individuals for CACS and coronary computed tomography angiography (CCTA) scans between January 2016 and January 2018. Finally, patients with a CACS of 0 were included and followed up ​until January 2022. According to the established CACS-CL cutoffs of 15% and 5%, the associations between coronary artery disease (CAD) and major adverse cardiovascular events (MACEs) in risk groups were evaluated, alongside the net reclassification improvement (NRI). Results: Of the 6689 patients with a CACS of 0, the prevalence of CAD increased significantly (p < 0.0001) in patients with higher CACS-CL. However, there was no significant difference in the CAD distribution (p = 0.0637) between patients with CACS-CL < 5% and 5-15%. The association between the CACS-CL = 15%-determined risk groups and the occurrence of MACEs was stronger than for a CACS-CL = 5% (adjusted hazard ratio (HR): 7.24 (95% CI: 1.93-16.42) versus 3.68 (95% CI: 1.50-8.26)). Compared with the cutoff for CACS-CL = 5%, the NRI was 10.61% when using a cutoff for CACS-CL = 15%. Conclusions: Among patients with an SCP and CACS of 0, the CACS-CL model provided accurate predictions of CAD and MACEs. Compared to the cutoff for CACS-CL = 5%, the cutoff for CACS-CL = 15% seemed to be more effective and safer for deferring further CIT. Clinical Trial registration: NCT04691037.

Chest Pain: Wellens Syndrome Due to Spontaneous Dissection of the Left Anterior Descending Coronary Artery - A Case Report and Literature Review.

Wellens syndrome is an abnormal electrocardiographic pattern characterized by biphasic (type A) or deeply inverted (type B) T waves in leads V2-V3. It is typically caused by temporary obstruction of the left anterior descending (LAD) coronary artery due to the rupture of an atherosclerotic plaque leading to occlusion. Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and even a rarer cause of Wellens Syndrome. It occurs when an intramural hematoma forms, leading to the separation of the tunica intima from the outer layers and creating a false lumen that protrudes into the real lumen, ultimately reducing blood flow and thus resulting in myocardial infarction. Here we report a case of SCAD presenting as an acute coronary syndrome with self-resolving chest pain, slightly elevated myocardial necrosis markers and electrocardiographic changes consistent with Wellens pattern type A first, and type B afterwards, that were not present upon arrival to the emergency department.

Using time-series chest radiographs and laboratory data by machine learning for identifying pulmonary infection and colonization of Acinetobacter baumannii.

BACKGROUND: Accurately distinguishing between pulmonary infection and colonization in patients with Acinetobacter baumannii is of utmost importance to optimize treatment and prevent antibiotic abuse or inadequate therapy. An efficient automated sorting tool could prompt individualized interventions and enhance overall patient outcomes. This study aims to develop a robust machine learning classification model using a combination of time-series chest radiographs and laboratory data to accurately classify pulmonary status caused by Acinetobacter baumannii. METHODS: We proposed nested logistic regression models based on different time-series data to automatically classify the pulmonary status of patients with Acinetobacter baumannii. Advanced features were extracted from the time-series data of hospitalized patients, encompassing dynamic pneumonia indicators observed on chest radiographs and laboratory indicator values recorded at three specific time points. RESULTS: Data of 152 patients with Acinetobacter baumannii cultured from sputum or alveolar lavage fluid were retrospectively analyzed. Our model with multiple time-series data demonstrated a higher performance of AUC (0.850, with a 95% confidence interval of [0.638-0.873]), an accuracy of 0.761, a sensitivity of 0.833. The model, which only incorporated a single time point feature, achieved an AUC of 0.741. The influential model variables included difference in the chest radiograph pneumonia score. CONCLUSION: Dynamic assessment of time-series chest radiographs and laboratory data using machine learning allowed for accurate classification of colonization and infection with Acinetobacter baumannii. This demonstrates the potential to help clinicians provide individualized treatment through early detection.

Malignant pleural effusion: current understanding and therapeutic approach.

Malignant pleural effusion (MPE) is a common complication of thoracic and extrathoracic malignancies and is associated with high mortality and elevated costs to healthcare systems. Over the last decades the understanding of pathophysiology mechanisms, diagnostic techniques and optimal treatment intervention in MPE have been greatly advanced by recent high-quality research, leading to an ever less invasive diagnostic approach and more personalized management. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. In the next future, because of a better understanding of underlying tumor biology together with more sensitive molecular diagnostic techniques, it is likely that combined diagnostic and therapeutic procedures allowing near total outpatient management of MPE will become popular. This article provides a review of the current advances, new discoveries and future directions in the pathophysiology, diagnosis and management of MPE.

Local heterogeneity of normal lung parenchyma and small airways disease are associated with COPD severity and progression.

BACKGROUND: Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline. METHODS: PRM metrics of normal lung (PRMNorm) and functional SAD (PRMfSAD) were generated from CT scans collected as part of the COPDGene study (n = 8956). Volume density (V) and Euler-Poincaré Characteristic (χ) image maps, measures of the extent and coalescence of pocket formations (i.e., topologies), respectively, were determined for both PRMNorm and PRMfSAD. Association with COPD severity, emphysema, and spirometric measures were assessed via multivariable regression models. Readouts were evaluated as inputs for predicting FEV1 decline using a machine learning model. RESULTS: Multivariable cross-sectional analysis of COPD subjects showed that V and χ measures for PRMfSAD and PRMNorm were independently associated with the amount of emphysema. Readouts χfSAD (ß of 0.106, p < 0.001) and VfSAD (ß of 0.065, p = 0.004) were also independently associated with FEV1% predicted. The machine learning model using PRM topologies as inputs predicted FEV1 decline over five years with an AUC of 0.69. CONCLUSIONS: We demonstrated that V and χ of fSAD and Norm have independent value when associated with lung function and emphysema. In addition, we demonstrated that these readouts are predictive of spirometric decline when used as inputs in a ML model. Our topological PRM approach using PRMfSAD and PRMNorm may show promise as an early indicator of emphysema onset and COPD progression.

Exploring the link between a novel approach for computer aided lung sound analysis and imaging biomarkers: a cross-sectional study.

BACKGROUND: Computer Aided Lung Sound Analysis (CALSA) aims to overcome limitations associated with standard lung auscultation by removing the subjective component and allowing quantification of sound characteristics. In this proof-of-concept study, a novel automated approach was evaluated in real patient data by comparing lung sound characteristics to structural and functional imaging biomarkers. METHODS: Patients with cystic fibrosis (CF) aged > 5y were recruited in a prospective cross-sectional study. CT scans were analyzed by the CF-CT scoring method and Functional Respiratory Imaging (FRI). A digital stethoscope was used to record lung sounds at six chest locations. Following sound characteristics were determined: expiration-to-inspiration (E/I) signal power ratios within different frequency ranges, number of crackles per respiratory phase and wheeze parameters. Linear mixed-effects models were computed to relate CALSA parameters to imaging biomarkers on a lobar level. RESULTS: 222 recordings from 25 CF patients were included. Significant associations were found between E/I ratios and structural abnormalities, of which the ratio between 200 and 400 Hz appeared to be most clinically relevant due to its relation with bronchiectasis, mucus plugging, bronchial wall thickening and air trapping on CT. The number of crackles was also associated with multiple structural abnormalities as well as regional airway resistance determined by FRI. Wheeze parameters were not considered in the statistical analysis, since wheezing was detected in only one recording. CONCLUSIONS: The present study is the first to investigate associations between auscultatory findings and imaging biomarkers, which are considered the gold standard to evaluate the respiratory system. Despite the exploratory nature of this study, the results showed various meaningful associations that highlight the potential value of automated CALSA as a novel non-invasive outcome measure in future research and clinical practice.