Who is at risk of lung nodules on low-dose CT in a Western country? A population-based approach.

BACKGROUND: This population-based study aimed to identify the risk factors for lung nodules in a Western European general population. METHODS: We quantified the presence or absence of lung nodules among 12 055 participants of the Dutch population-based ImaLife (Imaging in Lifelines) study (≥45 years) who underwent low-dose chest computed tomography. Outcomes included the presence of 1) at least one solid lung nodule (volume≥30 mm3) and 2) a clinically relevant lung nodule (volume≥100 mm3). Fully adjusted multivariable logistic regression models were applied overall and stratified by smoking status to identify independent risk factors for nodules presence. RESULTS: Among the 12 055 participants (44.1% men; median age 60 years; 39.9% never smokers; 98.7% Caucasian), we found lung nodules in 41.8% (5045 out of 12 055) and clinically relevant nodules in 11.4% (1377 out of 12 055); the corresponding figures among never smokers were 38.8% and 9.5%. Factors independently associated with increased odds of having any lung nodule included male-sex, older-age, low-educational level, former smoking, asbestos exposure, and chronic obstructive pulmonary disease. Among never smokers, a family history of lung cancer increased the odds of both lung nodules and clinically relevant nodules. Among former and current smokers, low educational level was positively associated with lung nodules, whereas being overweight was negatively associated. Among current smokers, asbestos exposure and low physical activity were associated with clinically relevant nodules. CONCLUSIONS: The study provides a large-scale evaluation of lung nodules and associated risk factors in a Western European general population: lung nodules and clinically relevant nodules were prevalent, and never smokers with a family history of lung cancer were a non-negligible group.

CT characteristics of solid pulmonary nodules of never smokers versus smokers: A population-based study.

PURPOSE: Aim was to assess CT characteristics of lung nodules in never and former smokers compared to current smokers in a population-based setting. METHOD: We included individuals aged 45-60 years taking part in the ImaLife (Imaging in Lifelines) study, with at least one solid lung nodule (≥30 mm3) on low-dose chest CT. Qualitative (location, shape, margin, nodule type, attached structures) and quantitative (count, diameter, volume) nodule characteristics were evaluated. Based on Fleischner criteria, 'high risk' nodules were defined. To examine the association between smoking status and nodule CT characteristics of participants, multi-level multinomial logistic regression corrected for clustering of nodules within participants was performed, where all odds ratios (aORs) were adjusted for age and sex. RESULTS: Overall, 1,639 individuals (median age: 55.0, IQR:50.5-58.5, 50.5% men) were included, with 42.1% never smokers, 35.3% former smokers and 22.6% current smokers. A total of 3,222 solid nodules were identified; 39.7% of individuals had multiple nodules. Nodule size, location, type and attachment were similar for never compared to current smokers. The odds of nodules with an irregular shape and irregular margin was lower in never smokers (aOR:0.64, 95 %CI:0.44-0.93; aOR:0.60, 95 %CI:0.41-0.88, respectively) and former smokers (aOR:0.61, 95 %CI:0.41-0.90; aOR:0.57, 95 %CI:0.38-0.85, respectively) compared to current smokers. The odds of a detected nodule being 'high risk' was similar for never versus current smokers (never smokers: aOR = 0.90; 95% CI:0.73-1.11). CONCLUSIONS: CT-based characteristics of solid lung nodules in never and former smokers differed only slightly from current smokers. Among individuals with solid nodules, 'high-risk' nodules were equally common in never smokers and current smokers.

Relationship between biomarkers and findings on low-dose computed tomography in hospitalised patients with acute exacerbation of COPD.

Background: Acute exacerbations of COPD (AECOPD) and community acquired pneumonia (CAP) often coexist. Although chest radiographs may differentiate between these diagnoses, chest radiography is known to underestimate the incidence of CAP in AECOPD. In this exploratory study, we prospectively investigated the incidence of infiltrative changes using low-dose computed tomography (LDCT). Additionally, we investigated whether clinical biomarkers of CAP differed between patients with and without infiltrative changes. Methods: Patients with AECOPD in which pneumonia was excluded using chest radiography underwent additional LDCT-thorax. The images were read independently by two radiologists; a third radiologist was consulted as adjudicator. C-reactive protein (CRP), procalcitonin (PCT), and serum amyloid A (SAA) at admission were assessed. Results: Out of the 100 patients included, 24 had one or more radiographic abnormalities suggestive of pneumonia. The interobserver agreement between two readers (Cohen's κ) was 0.562 (95% CI 0.371-0.752; p<0.001). Biomarkers were elevated in the group with radiological abnormalities compared to the group without abnormalities. Median (interquartile range (IQR)) CRP was 76 (21.5-148.0) mg·L-1 compared to 20.5 (8.8-81.5) mg·L -1 (p=0.018); median (IQR) PCT was 0.09 (0.06-0.15) µg·L-1 compared to 0.06 (0.04-0.08) µg·L-1 (p=0.007); median (IQR) SAA was 95 (7-160) µg·mL-1 compared to 16 (3-89) µg·mL-1 (p=0.019). Sensitivity and specificity for all three biomarkers were moderate for detecting radiographic abnormalities by LDCT in this population. The area under the receiver operating characteristic curve was 0.66 (95% CI 0.52-0.80) for CRP, 0.66 (95% CI 0.53-0.80) for PCT and 0.69 (95% CI 0.57-0.81) for SAA. Conclusion: LDCT can detect additional radiological abnormalities that may indicate acute-phase lung involvement in patients with AECOPD without infiltrate(s) on the chest radiograph. Despite CRP, PCT and SAA being significantly higher in the group with radiological abnormalities on LDCT, they proved unable to reliably detect or exclude CAP. Further research is warranted.

Bronchiectasis in Severe Asthma: Does It Make a Difference?

BACKGROUND: Asthma and bronchiectasis are 2 heterogeneous diseases that frequently coexist, particularly in severe asthma. Recognition of this co-diagnosis may importantly affect treatment decisions and outcome. Previous studies in asthma with bronchiectasis show inconsistent outcomes, probably due to the heterogeneity of the included asthma cohorts. OBJECTIVES: We hypothesized that bronchiectasis contributes to asthma severity and that patients with severe asthma and bronchiectasis present with distinct characteristics resulting in different treatable traits. In addition, we explored whether bronchiectasis in severe asthma is more common in a specific phenotype. METHODS: This is a single-center study consecutively including patients with severe asthma from a tertiary referral center. Severe asthma was diagnosed according to the ATS/ERS guidelines. Asthma and infectious exacerbations were defined by the attending specialist as respiratory symptoms requiring treatment with systemic steroids or antibiotics, respectively. Two independent blinded radiologists evaluated each CT. RESULTS: 19% of patients with severe asthma showed bronchiectasis on CT. Patients with bronchiectasis had a lower FEV1% predicted (p = 0.02) and FEV1/FVC (p = 0.004) and more infectious exacerbations (p = 0.003) compared to patients without bronchiectasis. Bronchiectasis is more common in patients with a longer duration of asthma, sensitization to A. fumigatus or a positive sputum culture. Sputum cultures of patients with severe asthma and bronchiectasis revealed more P. aeruginosa, S. maltophilia, H. parainfluenzae, and A. fumigates compared to the non-bronchiectasis group. The adult-onset, eosinophilic asthma phenotype showed the highest prevalence of bronchiectasis (29.4%). CONCLUSIONS: Patients with severe asthma and coexisting bronchiectasis were found to represent a distinct group, in terms of disease severity, microbiology, and asthma phenotype. Performing (HR)CT and sputum cultures can help to identify these patients. These results can possibly contribute to early recognition and targeted treatment of this patient group.

Evolution of high-resolution CT-scan in systemic sclerosis-associated interstitial lung disease: Description and prognosis factors.

OBJECTIVE: The aims of our study were to describe the evolution of interstitial lung disease (ILD) extent on HRCT scan in systemic sclerosis (SSc), to identify baseline prognostic factors associated with ILD evolution and to assess whether the evolution of pulmonary function tests (PFTs) correlated with this evolution. METHODS: 58 SSc with ILD (SSc-ILD) patients were included. All HRCT scans and PFTs available were collected. We modelized PFTs and HRCT scans evolution using linear mixed model with random effect. RESULTS: Patients underwent a median number of 3 HRCT scans (total n = 203) and 5 PFTs (total n = 329), during a mean follow-up of 5.3 ± 4.9 years. Mean SSc duration was 2.5 ± 3.1 years at the diagnosis of ILD. Mean baseline ILD extent was 32.3 ± 28.7%. We found a significant mean progression of ILD extent on serial HRCT scans of 0.92 ± 0.36% per year (p = 0.018). Male sex, diffuse cutaneous SSc (dcSSc), presence of anti-topoisomerase 1 antibodies, a higher DLCO, limited ILD and a low coarseness score at baseline in bivariate analysis, and presence of antitopoisomerase 1 antibodies and a coarseness score of 0 in multivariate analysis, were associated with faster progression of ILD extent over time There was a significant correlation between the progression of ILD extent and the decline of DLCO but only a trend for FVC. ILD extent at baseline and during follow-up was associated with survival. CONCLUSION: Male sex, dcSSc, anti-topoisomerase 1 antibodies and a less severe ILD at baseline were associated with a faster progression of ILD over time. Evolution of DLCO significantly correlated with change in ILD extent on HRCT scan. Our study helps defining the profile of patients at risk of experiencing a progression of ILD on HRCT scans.

Cardiac sarcoidosis: the challenge of radiologic-pathologic correlation: from the radiologic pathology archives.

Cardiac sarcoidosis is a rare but potentially fatal disorder with a nonspecific spectrum of clinical manifestations, including conduction disorders, congestive heart failure, ventricular arrhythmias, and sudden cardiac death. Although early treatment to improve morbidity and mortality is desirable, sensitive and accurate detection of cardiac sarcoidosis remains a challenge. Except for the histopathologic finding of noncaseating granulomas in an endomyocardial biopsy specimen, most diagnostic tests are limited and nonspecific at best. Therefore, the decision to initiate treatment is based largely on the patient's clinical symptoms and the course of the disease, rather than histologic confirmation. Successful recognition of cardiac sarcoidosis ultimately requires rigorous collaboration among a clinician, radiologist, and pathologist. Advanced imaging modalities, such as cardiac magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose, have become increasingly useful in facilitating diagnosis and therapeutic monitoring, although limited prospective studies exist. This article describes the clinical parameters and pathologic findings of cardiac sarcoidosis and the advanced imaging features and differential diagnostic challenges that must be considered for a successful diagnostic approach. In addition, to improve the understanding of abnormalities detected with different imaging modalities, we suggest a unified terminology in describing radiologic findings related to cardiac sarcoidosis.

EEG functional connectivity and ApoE genotype in Alzheimer's disease and controls.

OBJECTIVE: We examined the relation between Apolipoprotein E epsilon4 allele (ApoE epsilon4) genotype and functional connectivity measured by Electroencephalography (EEG) in patients with Alzheimer's disease (AD) and patients with subjective complaints (SC). METHODS: We included 43 patients with AD (age (SD)=74.2 (4.0), m/f=22/21; 30 of ApoE epsilon4 carriers) and 21 patients with SC (age (SD)=73.2 (5.2), m/f=13/8; 7 ApoE epsilon4 carriers) for this study. Resting state EEGs were recorded in all subjects. Synchronisation likelihood (SL) between local cortical areas was compared in the alpha and beta band according to ApoE epsilon4 status and diagnosis. RESULTS: ApoE epsilon4 carriers had higher SL values in lower and upper alpha band, in both diagnostic groups. In upper alpha band and beta band AD patients had lower SL than patients with SC, was irrespective of ApoE status. CONCLUSION: The effects of AD and ApoE epsilon4 on functional connectivity are opposite and independent. SIGNIFICANCE: The observed increase in SL in both AD and patients with SC carrying ApoE epsilon4 suggests a strong genetic impact of ApoE epsilon4 on brain function.