Analysis of the interactions between small pulmonary nodules, clinical factors and the risk of malignancy in the chest following diagnosis of head and neck cancer.

BACKGROUND: This study aims to investigate radiological and clinical factors which predict malignancy in indeterminate pulmonary nodules in patients with head and neck cancer (HNC). METHODS: Prospective data were collected in 424 patients who were reviewed in the NHS Lothian HNC multidisciplinary meeting from May 2016 to May 2018. Staging and follow-up CT chest imaging were reviewed to identify and assess pulmonary nodules in all patients. RESULTS: About 61.8% of patients had at least one pulmonary nodule at staging CT. In total, 25 patients developed malignancy in the chest. Metastatic disease in the chest was significantly associated with unknown or negative p16 status (p < .0005). Pleural indentation and spiculation were associated with indeterminate nodules, subsequently being shown to represent metastatic disease (p > .0005 and p = .046, respectively). CONCLUSION: Negative or unknown p16 status was associated with an increased propensity to develop metastatic disease in the chest in patients with HNC.

Predicting outcomes in rheumatoid arthritis related interstitial lung disease.

The aim of this study was to compare radiology-based prediction models in rheumatoid arthritis-related interstitial lung disease (RAILD) to identify patients with a progressive fibrosis phenotype.RAILD patients had computed tomography (CT) scans scored visually and using CALIPER and forced vital capacity (FVC) measurements. Outcomes were evaluated using three techniques, as follows. 1) Scleroderma system evaluating visual interstitial lung disease extent and FVC values; 2) Fleischner Society idiopathic pulmonary fibrosis (IPF) diagnostic guidelines applied to RAILD; and 3) CALIPER scores of vessel-related structures (VRS). Outcomes were compared to IPF patients.On univariable Cox analysis, all three staging systems strongly predicted outcome (scleroderma system hazard ratio (HR) 3.78, p=9×10-5; Fleischner system HR 1.98, p=2×10-3; and 4.4% VRS threshold HR 3.10, p=4×10-4). When the scleroderma and Fleischner systems were combined, termed the progressive fibrotic system (C-statistic 0.71), they identified a patient subset (n=36) with a progressive fibrotic phenotype and similar 4-year survival to IPF. On multivariable analysis, with adjustment for patient age, sex and smoking status, when analysed alongside the progressive fibrotic system, the VRS threshold of 4.4% independently predicted outcome (model C-statistic 0.77).The combination of two visual CT-based staging systems identified 23% of an RAILD cohort with an IPF-like progressive fibrotic phenotype. The addition of a computer-derived VRS threshold further improved outcome prediction and model fit, beyond that encompassed by RAILD measures of disease severity and extent.

Management of pulmonary nodules in head and neck cancer patients - Our experience and interpretation of the British Thoracic Society Guidelines.

BACKGROUND: and purpose of the study: The frequency of lung nodules in the head and neck cancer population is unknown, currently the only guidance available recommends following local policy. The aim of this study was to determine the incidence of pulmonary nodules in our head and neck cancer group and interpret the recently updated British Thoracic Society (BTS) Lung Nodule Guidelines in a head and neck cancer setting. METHODS: 100 patients were diagnosed with head and neck cancer between July 2013-March 2014, clinico-pathological, demographic and radiological data was extracted from the electronic records. Images with lung findings were re-reviewed by a single consultant radiologist for patients with lung pathology on the initial staging CT report. RESULTS: Twenty patients (20%) had discreet pulmonary findings on CT. Eleven (11%) had lung nodules, 6 (6%) had lesions suspicious for metastasis and 3 (3%) had co-incidental bronchogenic primary cancers. These patients were re-imaged between 6 and 18 months and in 1 patient the previously identified 7 mm nodule had progressed to 16 mm at 1 year. There was no set follow up imaging protocol used. CONCLUSION: The MDT in NHS Lothian has reviewed the BTS guidance and now has a local policy for the management of lung nodules in head and neck cancer patients. Lung Nodules in the head and neck cancer population are common >10%. Higher risk patients with larger nodules should be risk assessed with validated assessment tools. PET-CT has a place in the assessment of lung nodules when risk of malignancy is high.

Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD.

Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic-femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=-0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05).In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.

Association Between Interstitial Lung Abnormalities and All-Cause Mortality.

IMPORTANCE: Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated. OBJECTIVE: To investigate whether interstitial lung abnormalities are associated with increased mortality. DESIGN, SETTING, AND POPULATION: Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006). EXPOSURES: Interstitial lung abnormality status as determined by chest CT evaluation. MAIN OUTCOMES AND MEASURES: All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort. RESULTS: Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P < .001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis. CONCLUSIONS AND RELEVANCE: In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.

Lung ultrasonography as a direct measure of evolving respiratory dysfunction and disease severity in patients with acute pancreatitis.

BACKGROUND: The value of lung ultrasonography in the diagnosis of respiratory dysfunction and severity stratification in patients with acute pancreatitis (AP) was investigated. METHODS: Over a 3-month period, 41 patients (median age: 59.1 years; 21 males) presenting with a diagnosis of potential AP were prospectively recruited. Each participant underwent lung ultrasonography and the number of comet tails was linked with contemporaneous clinical data. Group comparisons, areas under the curve (AUC) and respective measures of diagnostic accuracy were investigated. RESULTS: A greater number of comet tails were evident in patients with respiratory dysfunction (P = 0.021), those with severe disease (P < 0.001) and when contemporaneous and maximum CRP exceeded 100 mg/L (P = 0.048 and P = 0.003 respectively). Receiver-operator characteristic plot area under the curve (AUC) was greater when examining upper lung quadrants, using respiratory dysfunction and AP severity as variables of interest (AUC = 0.783, 95% C.I.: 0.544-0.962, and AUC = 0.996, 95% C.I.: 0.982-1.000, respectively). Examining all lung quadrants except for the lower lateral resulted in greater AUCs for contemporaneous and maximum CRP (AUC = 0.708, 95% C.I.: 0.510-0.883, and AUC = 0.800, 95% C.I.: 0.640-0.929). DISCUSSION: Ultrasonography of non-dependent lung parenchyma can reliably detect evolving respiratory dysfunction in AP. This simple bedside technique shows promise as an adjunct to severity stratification.

Lung ultrasonography as a direct measure of evolving respiratory dysfunction and disease severity in patients with acute pancreatitis.

BACKGROUND: The value of lung ultrasonography in the diagnosis of respiratory dysfunction and severity stratification in patients with acute pancreatitis (AP) was investigated. METHODS: Over a 3-month period, 41 patients (median age: 59.1 years; 21 males) presenting with a diagnosis of potential AP were prospectively recruited. Each participant underwent lung ultrasonography, and the number of comet tails present on scans was linked with contemporaneous clinical data. Group comparisons, areas under the curve (AUC) and respective measures of diagnostic accuracy were investigated. RESULTS: A greater number of comet tails were evident in patients with respiratory dysfunction (P = 0.013), those with severe disease (P = 0.001) and when contemporaneous and maximum in-patient C-reactive protein (CRP) exceeded 150 mg/l (P = 0.018 and P = 0.049, respectively). Receiver-operator characteristic plot area under the curve (AUC) was greater when examining upper lung quadrants, using respiratory dysfunction and AP severity as variables of interest (AUC = 0.803, 95% CI: 0.583-1.000, and AUC = 0.996, 95% CI: 0.983-1.000, respectively). Examining all lung quadrants resulted in greater AUCs for contemporaneous and maximum CRP (AUC = 0.764, 95% CI: 0.555-0.972, and AUC = 0.704, 95% CI: 0.510-0.898). DISCUSSION: Ultrasonography of non-dependent lung parenchyma can reliably detect evolving respiratory dysfunction in AP. This simple bedside technique shows promise as an adjunct to severity stratification.

Coronary artery calcification is increased in patients with COPD and associated with increased morbidity and mortality.

BACKGROUND: Coronary artery calcification is pathognomonic of coronary artery disease (CAD). Whether CAD in patients with COPD is linked to lung function, functional capacity and/or clinically relevant outcomes is unknown. The objective was to assess the association between CAD and disease severity, functional capacity and outcomes in patients with COPD. METHODS: Coronary artery calcium score (CACS; Agatston score) was measured using chest CT in patients with COPD, smokers with normal spirometry and non-smokers from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. RESULTS: CACS was measured in 942 subjects: 672 with COPD (mean age±SD, 63±7 years; FEV1 49±16% predicted), 199 smokers with normal spirometry (54±9 years; FEV1 110±12% predicted) and 71 non-smokers (55±9 years; FEV1 114±14% predicted). CACS was higher in patients with COPD than smokers or non-smokers (median (IQR), 128 (492) vs 0 (75) vs 0 (3) Agatston units (AU), p<0.001). In patients with COPD, CACS correlated with age, pack-years, 6 min walking distance, modified Medical Research Council Dyspnoea score and circulating levels of interleukin (IL)-6, IL-8, Clara Cell protein 16, surfactant protein D and peripheral blood neutrophil count, but not with emphysema, exacerbation frequency, % predicted FEV1 or decline in FEV1. CACS was higher in patients with COPD who died than in those who survived until 3-year follow-up (CACS 406 vs 103 AU, p<0.001), and was associated with mortality in a Cox proportional hazards model (p=0.036). CONCLUSIONS: Patients with COPD have more CAD than controls and this is associated with increased dyspnoea, reduced exercise capacity and increased mortality. These data indicate that the presence of CAD in patients with COPD is associated with poor clinical outcomes.

Low sputum MMP-9/TIMP ratio is associated with airway narrowing in smokers with asthma.

Asthmatic smokers have poor symptom control and accelerated decline in lung function. A reduced ratio of matrix metalloproteinase (MMP)-9/tissue inhibitors of metalloproteinases (TIMPs) in nonsmokers with asthma has been implicated in airway remodelling. We tested the hypothesis that sputum MMP-9 activity/TIMPs ratios are reduced in smokers compared with never-smokers with asthma and are associated with reduced lung function and altered computed tomography (CT) measures of airway wall dimensions. Lung function, airway dimensions by CT, and induced sputum concentrations (and activity) of MMP-9 and TIMP-1 and -2 were measured in 81 asthmatics and 43 healthy subjects (smokers and never-smokers). Respiratory epithelial MMP9 and TIMP mRNA was quantified in 31 severe asthmatics and 32 healthy controls. Sputum MMP-9 activity/TIMP-1 and TIMP-2 ratios, and nasal epithelial MMP9/TIMP1 and MMP9/TIMP2 expression ratios were reduced in smokers with asthma compared with never-smokers with asthma. Low sputum ratios in asthmatic smokers were associated with reduced post-bronchodilator forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity ratio and segmental airway lumen area. The association of a low sputum MMP-9 activity/TIMP-1 ratio with persistent airflow obstruction and reduced CT airway lumen area in smokers with asthma may indicate that an imbalance of MMP-9 and TIMPs contributes to structural changes to the airways in this group.

Associations between COPD related manifestations: a cross-sectional study.

BACKGROUND: Cardiovascular disease, osteoporosis and emphysema are associated with COPD. Associations between these factors and whether they predict all-cause mortality in COPD patients are not well understood. Therefore, we examined associations between markers of cardiovascular disease (coronary artery calcification [CAC], thoracic aortic calcification [TAC] and arterial stiffness), bone density (bone attenuation of the thoracic vertebrae), emphysema (PI-950 and 15th percentile) and all-cause mortality in a COPD cohort. METHODS: We assessed CAC, TAC, bone attenuation of the thoracic vertebrae, PI-950 and 15th percentile on low-dose chest computed tomography in COPD subjects. We measured arterial stiffness as carotid-radial pulse wave velocity (PWV), and identified deaths from the national register. RESULTS: We studied 119 COPD subjects; aged 67.8 ±7.3, 66% were males and mean FEV1% predicted was 46.0 ±17.5. Subjects were classified into three pre-specificed groups: CAC = 0 (n = 14), 0 < CAC ≤ 400 (n = 41) and CAC > 400 (n = 64). Subjects with higher CAC were more likely to be older (p < 0.001) and male (p = 0.03), and more likely to have higher systolic blood pressure (p = 0.001) and a history of hypertension (p = 0.002) or ischemic heart disease (p = 0.003). Higher CAC was associated with higher PWV (OR 1.62, p = 0.04) and lower bone attenuation (OR 0.32, p = 0.02), but not with 15th percentile, after adjustment for age, sex and pack-years of smoking. In a Cox proportional hazards model, CAC, TAC and 15th percentile predicted all-cause mortality (HR 2.01, 2.09 and 0.66, respectively). CONCLUSIONS: Increased CAC was associated with increased arterial stiffness and lower bone density in a COPD cohort. In addition, CAC, TAC and extent of emphysema predicted all-cause mortality. TRIAL REGISTRATION: Lothian NHS Board, Lothian Research Ethics Committee, LREC/2003/8/28.

Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: relationship to disease severity.

BACKGROUND: Matrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known. OBJECTIVES: We sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD. METHODS: In 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (Dlco), and CT assessment of emphysema (percentage of low-attenuation areas at less -950 Hounsfield units). RESULTS: Sputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity. CONCLUSIONS: Sputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema.

Systemic elastin degradation in chronic obstructive pulmonary disease.

BACKGROUND: Development of emphysema and vascular stiffness in chronic obstructive pulmonary disease (COPD) may be due to a common mechanism of susceptibility to pulmonary and systemic elastin degradation. OBJECTIVES: To investigate whether patients with COPD have evidence of systemic elastin degradation in the skin. METHODS: The authors measured cutaneous elastin degradation using immunohistochemistry (percentage area of elastin fibres) in sun-exposed (exposed) and non-sun-exposed (non-exposed) skin biopsies in 16 men with COPD and 15 controls matched for age and cigarette smoke exposure. Quantitative PCR of matrix metalloproteinase (MMP)-2, -9, -12 and tissue inhibitor of metalloproteinase-1 mRNA and zymography for protein expression of MMP-2 and -9 were performed on homogenised skin. Arterial stiffness and emphysema severity were measured using carotid-femoral pulse wave velocity and quantitative CT scanning. RESULTS: Skin elastin degradation was greater in exposed and non-exposed skin of patients with COPD compared with controls (exposed, mean (SD); 43.5 (12.1)% vs 26.3 (6.9)%, p<0.001; non-exposed 22.4 (5.2)% vs 18.1 (4.3)%, p=0.02). Cutaneous expression of MMP-9 mRNA and proMMP-9 concentrations was increased in exposed skin of COPD patients (p=0.004 and p=0.02, respectively) and was also associated with increased skin elastin degradation (r=0.62, p<0.001 and r=0.47, p=0.01, respectively). In the entire cohort of ex-smokers, cutaneous elastin degradation was associated with emphysema severity, FEV(1) and pulse wave velocity. CONCLUSIONS: Patients with COPD have increased skin elastin degradation compared with controls, which is related to emphysema severity and arterial stiffness. Systemic elastin degradation due to increased proteolytic activity may represent a novel shared mechanism for the pulmonary, vascular and cutaneous features of COPD.

Survey of UK radiology trainees in the aftermath of 'Modernising Medical Careers'.

BACKGROUND: Following implementation of Modernising Medical Careers (MMC) in the UK, potential radiology trainees must decide on their career and apply sooner than ever before. We aimed to determine whether current trainees were sufficiently informed to make an earlier career decision by comparing the early radiology experiences of Traditional and Foundation Trainees. METHODS: 344 radiology trainees were appointed through MMC in 2007/08. This cohort was surveyed online. RESULTS: Response rate was 174/344 (51%). Traditional Trainees made their career decision 2.6 years after graduation compared with 1.2 years for Foundation Trainees (57/167, 34%). Nearly half of responders (79/169, 47%) experienced no formal radiology teaching as undergraduates. Most trainees regularly attended radiology meetings, spent time in a radiology department and/or performed radiology research. Many trainees received no career advice specific to radiology (69/163, 42%) at any point prior to entering the specialty; this includes both formal and informal advice. Junior doctor experiences were more frequently cited as influencing career choice (98/164, 60%). An earlier career decision was associated with; undergraduate radiology projects (-0.72 years, p = 0.018), career advice (-0.63 years, p = 0.009) and regular attendance at radiology meetings (-0.65 years, p = 0.014). CONCLUSION: Early experience of radiology enables trainees to make an earlier career decision, however current radiology trainees were not always afforded relevant experiences prior to entering training. Radiologists need to be more proactive in encouraging the next generation of trainees.

Validation of a deep learning computer aided system for CT based lung nodule detection, classification, and growth rate estimation in a routine clinical population.

OBJECTIVE: In this study, we evaluated a commercially available computer assisted diagnosis system (CAD). The deep learning algorithm of the CAD was trained with a lung cancer screening cohort and developed for detection, classification, quantification, and growth of actionable pulmonary nodules on chest CT scans. Here, we evaluated the CAD in a retrospective cohort of a routine clinical population. MATERIALS AND METHODS: In total, a number of 337 scans of 314 different subjects with reported nodules of 3-30 mm in size were included into the evaluation. Two independent thoracic radiologists alternately reviewed scans with or without CAD assistance to detect, classify, segment, and register pulmonary nodules. A third, more experienced, radiologist served as an adjudicator. In addition, the cohort was analyzed by the CAD alone. The study cohort was divided into five different groups: 1) 178 CT studies without reported pulmonary nodules, 2) 95 studies with 1-10 pulmonary nodules, 23 studies from the same patients with 3) baseline and 4) follow-up studies, and 5) 18 CT studies with subsolid nodules. A reference standard for nodules was based on majority consensus with the third thoracic radiologist as required. Sensitivity, false positive (FP) rate and Dice inter-reader coefficient were calculated. RESULTS: After analysis of 470 pulmonary nodules, the sensitivity readings for radiologists without CAD and radiologist with CAD, were 71.9% (95% CI: 66.0%, 77.0%) and 80.3% (95% CI: 75.2%, 85.0%) (p < 0.01), with average FP rate of 0.11 and 0.16 per CT scan, respectively. Accuracy and kappa of CAD for classifying solid vs sub-solid nodules was 94.2% and 0.77, respectively. Average inter-reader Dice coefficient for nodule segmentation was 0.83 (95% CI: 0.39, 0.96) and 0.86 (95% CI: 0.51, 0.95) for CAD versus readers. Mean growth percentage discrepancy of readers and CAD alone was 1.30 (95% CI: 1.02, 2.21) and 1.35 (95% CI: 1.01, 4.99), respectively. CONCLUSION: The applied CAD significantly increased radiologist's detection of actionable nodules yet also minimally increasing the false positive rate. The CAD can automatically classify and quantify nodules and calculate nodule growth rate in a cohort of a routine clinical population. Results suggest this Deep Learning software has the potential to assist chest radiologists in the tasks of pulmonary nodule detection and management within their routine clinical practice.

Copy number variation of FCGR3B is associated with susceptibility to idiopathic pulmonary fibrosis.

BACKGROUND: Several genes exhibit copy number variation (CNV), including FCGR3B which encodes the IgG receptor FcγRIIIb. Engagement of Fcγ receptors by IgG complexes may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To investigate whether FCGR3B CNV is associated with susceptibility to IPF. METHODS: In a case-control study we compared FCGR3B copy number in 142 patients with IPF and in 221 controls by real-time quantitative PCR using CD36 as gene copy control. RESULTS: Significantly increased FCGR3B:CD36 ratio was evident in the IPF cohort compared to controls (p = 0.009). Association of FCGR3B copy number with IPF susceptibility was further confirmed by a likelihood ratio statistical approach (p = 0.003). FCGR3B copy number assignment based on FCGR3B:CD36 ratios revealed significant skewing in the distribution of FCGR3B copy number between IPF patients and controls. In the IPF cohort, there was increased frequency of >2 FCGR3B copies compared to controls (0.30 vs. 0.19; χ(2) = 9.27; d.f. 2; p = 0.0097). The presence of >2 FCGR3B copies was associated with higher risk of IPF (p = 0.01, OR: 1.914, 95% CI: 1.17-3.12). CONCLUSIONS: These findings support an association of FCGR3B copy number with susceptibility to IPF and propose a novel role for Fcγ receptors in IPF disease pathogenesis.

Coronary Artery Calcification on Thoracic Computed Tomography Is an Independent Predictor of Mortality in Patients With Bronchiectasis.

PURPOSE: Coronary artery calcification (CAC) on thoracic computed tomography (CT) can identify patients at risk of coronary artery disease (CAD) mortality. However, the overlap between bronchiectasis and CAC severity for predicting subsequent outcomes is unknown. MATERIALS AND METHODS: CT images from 362 patients (mean age 66±14 y, 38% male) with known bronchiectasis were assessed. Bronchiectasis severity was assessed using the Bronchiectasis Severity Index (0 to 4, mild; 5 to 8, moderate; and ≥9, severe). CAC was assessed with a visual ordinal score (0, none; 1, mild; 2, moderate; 3, severe) in each of the left main stem, left anterior descending, left circumflex, and right coronary arteries. Vessel CAC scores were summed and categorized as none (0), mild (1 to 3), moderate (4 to 8), and severe (9 to 12). RESULTS: Patients with severe bronchiectasis were older (P<0.001), but were not more likely to have a history of CAD, hypertension, or smoking. CAC was present in 196 (54%). Over a mean of 6±2 years, 59 (16%) patients died. Patients with moderate or severe CAC were 5 times more likely to die than patients without CAC (hazard ratio: 5.49, 95% confidence interval: 2.82-10.70, P<0.001). Patients with severe bronchiectasis were 10 times more likely to die than patients with mild bronchiectasis (hazard ratio: 10.11, 95% confidence interval: 4.22-24.27, P<0.001). CAC and bronchiectasis severity were independent predictors of mortality, but age, sex, smoking, and history of CAD or cerebrovascular disease were not. CONCLUSIONS: CAC is common in patients with bronchiectasis, and both CAC and bronchiectasis severity are independent predictors of mortality.

Pulmonary embolism severity before and during the COVID-19 pandemic.

OBJECTIVES: Early in the coronavirus 2019 (COVID-19) pandemic, a high frequency of pulmonary embolism was identified. This audit aims to assess the frequency and severity of pulmonary embolism in 2020 compared to 2019. METHODS: In this retrospective audit, we compared computed tomography pulmonary angiography (CTPA) frequency and pulmonary embolism severity in April and May 2020, compared to 2019. Pulmonary embolism severity was assessed with the Modified Miller score and the presence of right heart strain was assessed. Demographic information and 30-day mortality was identified from electronic health records. RESULTS: In April 2020, there was a 17% reduction in the number of CTPA performed and an increase in the proportion identifying pulmonary embolism (26%, n = 68/265 vs 15%, n = 47/320, p < 0.001), compared to April 2019. Patients with pulmonary embolism in 2020 had more comorbidities (p = 0.026), but similar age and sex compared to 2019. There was no difference in pulmonary embolism severity in 2020 compared to 2019, but there was an increased frequency of right heart strain in May 2020 (29 vs 12%, p = 0.029). Amongst 18 patients with COVID-19 and pulmonary embolism, there was a larger proportion of males and an increased 30 day mortality (28% vs 6%, p = 0.008). CONCLUSION: During the COVID-19 pandemic, there was a reduction in the number of CTPA scans performed and an increase in the frequency of CTPA scans positive for pulmonary embolism. Patients with both COVID-19 and pulmonary embolism had an increased risk of 30-day mortality compared to those without COVID-19. ADVANCES IN KNOWLEDGE: During the COVID-19 pandemic, the number of CTPA performed decreased and the proportion of positive CTPA increased. Patients with both pulmonary embolism and COVID-19 had worse outcomes compared to those with pulmonary embolism alone.

Can dynamic imaging, using 18F-FDG PET/CT and CT perfusion differentiate between benign and malignant pulmonary nodules?

BACKGROUND: The aim of the study was to derive and compare metabolic parameters relating to benign and malignant pulmonary nodules using dynamic 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) PET/CT, and nodule perfusion parameters derived through perfusion computed tomography (CT). PATIENTS AND METHODS: Twenty patients with 21 pulmonary nodules incidentally detected on CT underwent a dynamic 18F-FDG PET/CT and a perfusion CT. The maximum standardized uptake value (SUVmax) was measured on conventional 18F-FDG PET/CT images. The influx constant (Ki ) was calculated from the dynamic 18F-FDG PET/CT data using Patlak model. Arterial flow (AF) using the maximum slope model and blood volume (BV) using the Patlak plot method for each nodule were calculated from the perfusion CT data. All nodules were characterized as malignant or benign based on histopathology or 2 year follow up CT. All parameters were statistically compared between the two groups using the nonparametric Mann-Whitney test. RESULTS: Twelve malignant and 9 benign lung nodules were analysed (median size 20.1 mm, 9-29 mm) in 21 patients (male/female = 11/9; mean age ± SD: 65.3 ± 7.4; age range: 50-76 years). The average SUVmax values ± SD of the benign and malignant nodules were 2.2 ± 1.7 vs. 7.0 ± 4.5, respectively (p = 0.0148). Average Ki values in benign and malignant nodules were 0.0057 ± 0.0071 and 0.0230 ± 0.0155 min-1, respectively (p = 0.0311). Average BV for the benign and malignant nodules were 11.6857 ± 6.7347 and 28.3400 ± 15.9672 ml/100 ml, respectively (p = 0.0250). Average AF for the benign and malignant nodules were 74.4571 ± 89.0321 and 89.200 ± 49.8883 ml/100g/min, respectively (p = 0.1613). CONCLUSIONS: Dynamic 18F-FDG PET/CT and perfusion CT derived blood volume had similar capability to differentiate benign from malignant lung nodules.

Fcγ receptor IIIb (CD16b) polymorphisms are associated with susceptibility to idiopathic pulmonary fibrosis.

An excess of neutrophils in the alveoli and lung interstitium has been described in idiopathic pulmonary fibrosis (IPF). Engagement of neutrophil Fcγ receptors with IgG complexes may contribute to the pathogenesis of IPF. The neutrophil FcγRIIIb receptor occurs in two codominantly expressed allelic variants, NA1 and NA2, which exhibit different binding affinities for IgG1 and IgG3 subclasses. The aim of this study was to investigate whether FcγRIIIb genotype is associated with IPF susceptibility or disease progression. In a case-control study we compared the distribution of FcγRIIIb NA1/2 polymorphisms in 142 patients with IPF and in 218 controls using allele-specific PCR amplification. Significant skewing in the distribution of FcγRIIIb genotypes was observed between patients with IPF and control subjects. In the IPF cohort, there was higher frequency of the NA1/NA1 genotype (0.19 vs. 0.07), and lower NA2/NA2 frequency (0.31 vs. 0.50; χ(2) = 17.71, df = 2, P < 0.001). The overall frequency of the NA1 allele was increased in IPF patients compared to controls (0.44 vs. 0.29; P < 0.0001, odds ratio [OR] = 1.93, 95% confidence interval [CI] = 1.42-2.64). Heterozygotes and homozygotes of the NA1 allele were at higher risk of developing IPF (OR = 2.19, 95% CI = 1.40-3.41, P = 0.0005), whereas the NA2 allele was protective against IPF (OR = 0.34, 95% CI = 0.17-0.65, P = 0.0014). There was no association of FcγRIIIb genotype with disease progression as assessed by serial lung function measurements. FcγRIIIb NA1/2 polymorphisms are associated with IPF disease susceptibility. These results support a role for immunological mechanisms contributing to IPF pathogenesis.