Comparison of Commercial AI Software Performance for Radiograph Lung Nodule Detection and Bone Age Prediction.

Background Multiple commercial artificial intelligence (AI) products exist for assessing radiographs; however, comparable performance data for these algorithms are limited. Purpose To perform an independent, stand-alone validation of commercially available AI products for bone age prediction based on hand radiographs and lung nodule detection on chest radiographs. Materials and Methods This retrospective study was carried out as part of Project AIR. Nine of 17 eligible AI products were validated on data from seven Dutch hospitals. For bone age prediction, the root mean square error (RMSE) and Pearson correlation coefficient were computed. The reference standard was set by three to five expert readers. For lung nodule detection, the area under the receiver operating characteristic curve (AUC) was computed. The reference standard was set by a chest radiologist based on CT. Randomized subsets of hand (n = 95) and chest (n = 140) radiographs were read by 14 and 17 human readers, respectively, with varying experience. Results Two bone age prediction algorithms were tested on hand radiographs (from January 2017 to January 2022) in 326 patients (mean age, 10 years ± 4 [SD]; 173 female patients) and correlated strongly with the reference standard (r = 0.99; P < .001 for both). No difference in RMSE was observed between algorithms (0.63 years [95% CI: 0.58, 0.69] and 0.57 years [95% CI: 0.52, 0.61]) and readers (0.68 years [95% CI: 0.64, 0.73]). Seven lung nodule detection algorithms were validated on chest radiographs (from January 2012 to May 2022) in 386 patients (mean age, 64 years ± 11; 223 male patients). Compared with readers (mean AUC, 0.81 [95% CI: 0.77, 0.85]), four algorithms performed better (AUC range, 0.86-0.93; P value range, <.001 to .04). Conclusions Compared with human readers, four AI algorithms for detecting lung nodules on chest radiographs showed improved performance, whereas the remaining algorithms tested showed no evidence of a difference in performance. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Omoumi and Richiardi in this issue.

Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial.

BACKGROUND: There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS: A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants. RESULTS: Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 person-years in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9. CONCLUSIONS: In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.).

Prospective of 31 P MR Spectroscopy in Hepatopancreatobiliary Cancer: A Systematic Review of the Literature.

BACKGROUND: The incidence of liver and pancreatic cancer is rising. Patients benefit from current treatments, but there are limitations in the evaluation of (early) response to treatment. Tumor metabolic alterations can be measured noninvasively with phosphorus (31 P) magnetic resonance spectroscopy (MRS). PURPOSE: To conduct a quantitative analysis of the available literature on 31 P MRS performed in hepatopancreatobiliary cancer and to provide insight into its current and potential for therapy (non-) response assessment. POPULATION: Patients with hepatopancreatobiliary cancer. FIELD STRENGTH/SEQUENCE: 31 P MRS. ASSESSMENT: The PubMed, EMBASE, and Cochrane library databases were systematically searched for studies published to 17 March 17, 2022. All 31 P MRS studies in hepatopancreatobiliary cancer reporting 31 P metabolite levels were included. STATISTICAL TESTS: Relative differences in 31 P metabolite levels/ratios between patients before therapy and healthy controls, and the relative changes in 31 P metabolite levels/ratios in patients before and after therapy were determined. RESULTS: The search yielded 10 studies, comprising 301 subjects, of whom 132 (44%) healthy volunteers and 169 (56%) patients with liver cancer of various etiology. To date, 31 P MRS has not been applied in pancreatic cancer. In liver cancer, alterations in levels of 31 P metabolites involved in cell proliferation (phosphomonoesters [PMEs] and phosphodiesters [PDEs]) and energy metabolism (ATP and inorganic phosphate [Pi]) were observed. In particular, liver tumors were associated with elevations of PME/PDE and PME/Pi compared to healthy liver tissue, although there was a broad variety among studies (elevations of 2%-267% and 21%-233%, respectively). Changes in PME/PDE in liver tumors upon therapy were substantial, yet very heterogeneous and both decreases and increases were observed, whereas PME/Pi was consistently decreased after therapy in all studies (-13% to -76%). DATA CONCLUSION: 31 P MRS has great potential for treatment monitoring in oncology. Future studies are needed to correlate the changes in 31 P metabolite levels in hepatopancreatobiliary tumors with treatment response. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Bronchiectasis is associated with lower lung function in lung cancer screening participants.

BACKGROUND AND OBJECTIVE: Bronchiectasis is a frequent incidental finding on chest computed tomography (CT), but its relevance in lung cancer screening is not fully understood. We investigated the association between bronchiectasis and respiratory symptoms, pulmonary function, and emphysema in lung cancer screening participants with and without chronic obstructive pulmonary disease (COPD). METHODS: We included 3260 (ex-)smokers from the Dutch-Belgian lung cancer screening trial (NELSON). Bronchiectasis was scored by chest radiologists. The relationship with pulmonary function (FEV1%predicted, FEV1/FVC), respiratory complaints (cough, dyspnea, wheezing, mucus hypersecretion), and CT-quantified emphysema (15th percentile) was examined with independent t-tests and multivariate regression. RESULTS: Bronchiectasis was present in 5.4% (n = 175/3260). There was no difference in prevalence between subjects with and without COPD (68/1121 [5.9%] vs. 109/2139 [5.1%]; p = .368). COPD subjects with bronchiectasis had a lower FEV1%predicted (76.2% vs. 85.0%; p < .001), lower FEV1/FVC (0.58 vs. 0.62; p < .001), and more emphysema (- 938 HU vs. - 930 HU; p = .001) than COPD subjects without bronchiectasis. In COPD subjects, bronchiectasis was independently associated with a lower FEV1%predicted (B = - 7.7; CI [- 12.3, - 3.3]), lower FEV1/FVC (B = - 2.5; CI [- 4.3, - 0.8]), more cough (OR 2.4; CI [1.3, 4.3]), more mucus hypersecretion (OR 1.8; CI [1.0, 3.1]) and more dyspnea (OR 2.3; CI [1.3, 3.9]). In those without COPD (n = 2139), bronchiectasis was associated with more cough, mucus hypersecretion, and wheezing, but not with deteriorating lung function. CONCLUSION: Bronchiectasis was present in 5.4% of our lung cancer screening participants and was associated with more respiratory symptoms and, in those with COPD, with lower lung function and more emphysema. CLINICAL RELEVANCE STATEMENT: In a lung cancer screening population, bronchiectasis has a prevalence of 5.4% with a mainly mild severity. This finding is of little clinical relevance unless mild COPD is also present. In those subjects, bronchiectasis was associated with a lower lung function, more respiratory symptoms, and more emphysema. KEY POINTS: • Bronchiectasis was found in 5.4% of lung cancer screening participants, consisting of (ex-)smokers with and without mild COPD. • In those with mild COPD, bronchiectasis was associated with a lower lung function, more respiratory symptoms, and more emphysema. • Incidental findings of mild bronchiectasis are not very relevant in a lung cancer screening population, unless COPD is also present.

Real world impact of added FFR-CT to coronary CT angiography on clinical decision-making and patient prognosis - IMPACT FFR study.

OBJECTIVES: The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). METHODS: This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan-Meier curves were used to visualize the occurrence of safety outcomes over time. RESULTS: A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p < 0.001 for all three options). The revascularization rate after ICA was similar between groups (p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). CONCLUSION: Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. KEY POINTS: • Previous studies have shown that computed tomography-derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.

Multi-source data approach for personalized outcome prediction in lung cancer screening: update from the NELSON trial.

Trials show that low-dose computed tomography (CT) lung cancer screening in long-term (ex-)smokers reduces lung cancer mortality. However, many individuals were exposed to unnecessary diagnostic procedures. This project aims to improve the efficiency of lung cancer screening by identifying high-risk participants, and improving risk discrimination for nodules. This study is an extension of the Dutch-Belgian Randomized Lung Cancer Screening Trial, with a focus on personalized outcome prediction (NELSON-POP). New data will be added on genetics, air pollution, malignancy risk for lung nodules, and CT biomarkers beyond lung nodules (emphysema, coronary calcification, bone density, vertebral height and body composition). The roles of polygenic risk scores and air pollution in screen-detected lung cancer diagnosis and survival will be established. The association between the AI-based nodule malignancy score and lung cancer will be evaluated at baseline and incident screening rounds. The association of chest CT imaging biomarkers with outcomes will be established. Based on these results, multisource prediction models for pre-screening and post-baseline-screening participant selection and nodule management will be developed. The new models will be externally validated. We hypothesize that we can identify 15-20% participants with low-risk of lung cancer or short life expectancy and thus prevent ~140,000 Dutch individuals from being screened unnecessarily. We hypothesize that our models will improve the specificity of nodule management by 10% without loss of sensitivity as compared to assessment of nodule size/growth alone, and reduce unnecessary work-up by 40-50%.

Diffuse idiopathic skeletal hyperostosis is associated with incident stroke in patients with increased cardiovascular risk.

OBJECTIVES: Earlier retrospective studies have suggested a relation between DISH and cardiovascular disease, including myocardial infarction. The present study assessed the association between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk. METHODS: In this prospective cohort study, we included 4624 patients (mean age 58.4 years, 69.6% male) from the Second Manifestations of ARTerial disease cohort. The main end point was major cardiovascular events (MACE: stroke, myocardial infarction and vascular death). Secondary endpoints included all-cause mortality and separate vascular events. Cause-specific proportional hazard models were used to evaluate the risk of DISH on all outcomes, and subdistribution hazard models were used to evaluate the effect of DISH on the cumulative incidence. All models were adjusted for age, sex, body mass index, blood pressure, diabetes, non-HDL cholesterol, packyears, renal function and C-reactive protein. RESULTS: DISH was present in 435 (9.4%) patients. After a median follow-up of 8.7 (IQR 5.0-12.0) years, 864 patients had died and 728 patients developed a MACE event. DISH was associated with an increased cumulative incidence of ischaemic stroke. After adjustment in cause-specific modelling, DISH remained significantly associated with ischaemic stroke (HR 1.55; 95% CI: 1.01, 2.38), but not with MACE (HR 0.99; 95% CI: 0.79, 1.24), myocardial infarction (HR 0.88; 95% CI: 0.59, 1.31), vascular death (HR 0.94; 95% CI: 0.68, 1.27) or all-cause mortality (HR 0.94; 95% CI: 0.77, 1.16). CONCLUSION: The presence of DISH is independently associated with an increased incidence and risk for ischaemic stroke, but not with MACE, myocardial infarction, vascular death or all-cause mortality.

Histology and computed tomography of incidental calcifications in the human basal ganglia.

Incidental basal ganglia calcifications are a common finding on computed tomography (CT). We investigated the histological characteristics of these calcifications and their association with CT findings, using post-mortem basal ganglia tissue from 22 patients. Eight patients had basal ganglia calcifications on histology, and six patients had calcifications on CT, varying from mild to severe. Four patients had calcifications identified by both histology and CT, and two patients had calcifications detected by CT but not by histology, possibly because of insufficient tissue available. Calcifications were found mainly in the tunica media of arterioles located in the globus pallidus, which suggests that incidental CT calcifications are vascular in nature. However, tunica media calcifications, and thereby incidental basal ganglia calcifications, are probably not related to atherosclerosis.

Computed tomographic findings in subjects who died from respiratory disease in the National Lung Screening Trial.

We evaluated the prevalence of significant lung abnormalities on computed tomography (CT) in patients who died from a respiratory illness other than lung cancer in the National Lung Screening Trial (NLST).In this retrospective case-control study, NLST participants in the CT arm who died of respiratory illness other than lung cancer were matched for age, sex, pack-years and smoking status to a surviving control. A chest radiologist and a radiology resident blinded to the outcome independently scored baseline CT scans visually and qualitatively for the presence of emphysema, airway wall thickening and fibrotic lung disease. The prevalence of CT abnormalities was compared between cases and controls by using chi-squared tests.In total, 167 participants died from a respiratory cause other than lung cancer. The prevalence of severe emphysema, airway wall thickening and fibrotic lung disease were 28.7% versus 4.8%, 26.9% versus 13.2% and 18.6% versus 0.5% in cases and controls, respectively. Radiological findings were significantly more prevalent in deaths compared with controls (all p<0.001).CT-diagnosed severe emphysema, airway wall thickening and fibrosis were much more common in NLST participants who died from respiratory disease, and CT may provide an additional means of identifying these diseases.

Inter-observer and inter-examination variability of manual vertebral bone attenuation measurements on computed tomography.

OBJECTIVE: To determine inter-observer and inter-examination variability of manual attenuation measurements of the vertebrae in low-dose unenhanced chest computed tomography (CT). METHODS: Three hundred and sixty-seven lung cancer screening trial participants who underwent baseline and repeat unenhanced low-dose CT after 3 months because of an indeterminate lung nodule were included. The CT attenuation value of the first lumbar vertebrae (L1) was measured in all CTs by one observer to obtain inter-examination reliability. Six observers performed measurements in 100 randomly selected CTs to determine agreement with limits of agreement and Bland-Altman plots and reliability with intraclass correlation coefficients (ICCs). Reclassification analyses were performed using a threshold of 110 HU to define osteoporosis. RESULTS: Inter-examination reliability was excellent with an ICC of 0.92 (p < 0.001). Inter-examination limits of agreement ranged from -26 to 28 HU with a mean difference of 1 ± 14 HU. Inter-observer reliability ICCs ranged from 0.70 to 0.91. Inter-examination variability led to 11.2 % reclassification of participants and inter-observer variability led to 22.1 % reclassification. CONCLUSIONS: Vertebral attenuation values can be manually quantified with good to excellent inter-examination and inter-observer reliability on unenhanced low-dose chest CT. This information is valuable for early detection of osteoporosis on low-dose chest CT. KEY POINTS: • Vertebral attenuation values can be manually quantified on low-dose unenhanced CT reliably. • Vertebral attenuation measurements may be helpful in detecting subclinical low bone density. • This could become of importance in the detection of osteoporosis.

Airway wall thickness associated with forced expiratory volume in 1 second decline and development of airflow limitation.

Airway wall thickness and emphysema contribute to airflow limitation. We examined their association with lung function decline and development of airflow limitation in 2021 male smokers with and without airflow limitation. Airway wall thickness and emphysema were quantified on chest computed tomography and expressed as the square root of wall area of a 10-mm lumen perimeter (Pi10) and the 15th percentile method (Perc15), respectively. Baseline and follow-up (median (interquartile range) 3 (2.9-3.1) years) spirometry was available. Pi10 and Perc15 correlated with baseline forced expiratory volume in 1 s (FEV1) (r= -0.49 and 0.11, respectively (p<0.001)). Multiple linear regression showed that Pi10 and Perc15 at baseline were associated with a lower FEV1 after follow-up (p<0.05). For each sd increase in Pi10 and decrease in Perc15 the FEV1 decreased by 20 mL and 30.2 mL, respectively. The odds ratio for developing airflow limitation after 3 years was 2.45 for a 1-mm higher Pi10 and 1.46 for a 10-HU lower Perc15 (p<0.001). A greater degree of airway wall thickness and emphysema was associated with a higher FEV1 decline and development of airflow limitation after 3 years of follow-up.

Intravenous contrast injection significantly affects bone mineral density measured on CT.

OBJECTIVE: The objective is to evaluate the effect of intravenous contrast media on bone mineral density (BMD) assessment by comparing unenhanced and contrast-enhanced computed tomography (CT) examinations performed for other indications. METHODS: One hundred and fifty-two patients (99 without and 53 with malignant neoplasm) who underwent both unenhanced and two contrast-enhanced (arterial and portal venous phase) abdominal CT examinations in a single session between June 2011 and July 2013 were included. BMD was evaluated on the three examinations as CT-attenuation values in Hounsfield Units (HU) in the first lumbar vertebra (L1). RESULTS: CT-attenuation values were significantly higher in both contrast-enhanced phases, compared to the unenhanced phase (p < 0.01). In patients without malignancies, mean ± standard deviation (SD) HU-values increased from 128.8 ± 48.6 HU for the unenhanced phase to 142.3 ± 47.2 HU for the arterial phase and 147.0 ± 47.4 HU for the portal phase (p < 0.01). In patients with malignancies, HU-values increased from 112.1 ± 38.1 HU to 126.2 ± 38.4 HU and 130.1 ± 37.3 HU (p < 0.02), respectively. With different thresholds to define osteoporosis, measurements in the arterial and portal phase resulted in 7-25% false negatives. CONCLUSIONS: Our study showed that intravenous contrast injection substantially affects BMD-assessment on CT and taking this into account may improve routine assessment of low BMD in nonquantitative CT. KEY POINTS: • Routine CT may gain a role in bone attenuation measurements for osteoporosis • Contrast media injection has substantial influence on CT-derived bone density • Contrast-enhanced CT leads to underestimation of osteoporosis compared to unenhanced CT • Adjusting for contrast injection phase may improve CT screening protocols for osteoporosis.

Pulmonary function and CT biomarkers as risk factors for cardiovascular events in male lung cancer screening participants: the NELSON study.

OBJECTIVE: The objective of this study was to investigate the association of spirometry and pulmonary CT biomarkers with cardiovascular events. METHODS: In this lung cancer screening trial 3,080 male participants without a prior cardiovascular event were analysed. Fatal and non-fatal cardiovascular events were included. Spirometry included forced expiratory volume measured in units of one-second percent predicted (FEV1%predicted) and FEV1 divided by forced vital capacity (FVC; FEV1/FVC). CT examinations were quantified for coronary artery calcium volume, pulmonary emphysema (perc15) and bronchial wall thickness (pi10). Data were analysed via a Cox proportional hazard analysis, net reclassification improvement (NRI) and C-indices. RESULTS: 184 participants experienced a cardiovascular event during a median follow-up of 2.9 years. Age, pack-years and smoking status adjusted hazard ratios were 0.992 (95% confidence interval (CI) 0.985-0.999) for FEV1%predicted, 1.000 (95%CI 0.986-1.015) for FEV1/FVC, 1.014 (95%CI 1.005-1.023) for perc15 per 10 HU, and 1.269 (95%CI 1.024-1.573) for pi10 per 1 mm. The incremental C-index (<0.015) and NRI (<2.8%) were minimal. Coronary artery calcium volume had a hazard ratio of 1.046 (95%CI 1.034-1.058) per 100 mm(3), an increase in C-index of 0.076 and an NRI of 16.9% (P < 0.0001). CONCLUSIONS: Pulmonary CT biomarkers and spirometry measurements were significantly associated with cardiovascular events, but did not contain clinically relevant independent prognostic information for cardiovascular events. KEY POINTS: • Pulmonary CT biomarkers and spirometry are associated with cardiovascular events • These pulmonary measurements do not contain clinically relevant independent prognostic information • Only coronary calcium score improved cardiovascular risk prediction above age and smoking.

Contribution of CT quantified emphysema, air trapping and airway wall thickness on pulmonary function in male smokers with and without COPD.

Emphysema, airway wall thickening and air trapping are associated with chronic obstructive pulmonary disease (COPD). All three can be quantified by computed tomography (CT) of the chest. The goal of the current study is to determine the relative contribution of CT derived parameters on spirometry, lung volume and lung diffusion testing. Emphysema, airway wall thickening and air trapping were quantified automatically on CT in 1,138 male smokers with and without COPD. Emphysema was quantified by the percentage of voxels below -950 Hounsfield Units (HU), airway wall thickness by the square root of wall area for a theoretical airway with 10 mm lumen perimeter (Pi10) and air trapping by the ratio of mean lung density at expiration and inspiration (E/I-ratio). Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were obtained. Standardized regression coefficients (ß) were used to analyze the relative contribution of CT changes to pulmonary function measures. The independent contribution of the three CT measures differed per lung function parameter. For the FEV1 airway wall thickness was the most contributing structural lung change (ß = -0.46), while for the FEV1/FVC this was emphysema (ß = -0.55). For the residual volume (RV) air trapping was most contributing (ß = -0.35). Lung diffusion capacity was most influenced by emphysema (ß = -0.42). In a cohort of smokers with and without COPD the effect of different CT changes varies per lung function measure and therefore emphysema, airway wall thickness and air trapping need to be taken in account.

Pulmonary Computed Tomography Screening Frequency in Primary Antibody Deficiency.

BACKGROUND: Patients with primary antibody deficiency (PAD) frequently suffer from pulmonary complications, associated with severe morbidity and mortality. Hence, regular pulmonary screening by computed tomography (CT) scanning is advised. However, predictive risk factors for pulmonary morbidity are lacking. OBJECTIVE: To identify patients with PAD at risk for pulmonary complications necessitating regular CT screening. METHODS: A retrospective, longitudinal cohort study of patients with PAD (median follow-up 7.4 [2.3-14.8] years) was performed. CTs were scored using the modified Brody-II scoring system. Clinical and laboratory parameters were retrospectively collected. Potential risk factors were identified by univariate analysis when P < .2 and confirmed by multivariable logistic regression when P < .05. RESULTS: The following independent risk factors for progression of airway disease (AD) were identified: (1) diagnosis of X-linked agammaglobulinemia (XLA), (2) recurrent airway infections (2.5/year), and (3) the presence of AD at baseline. Signs of AD progression were detected in 5 of 11 patients with XLA and in 17 of 80 of the other patients with PAD. Of the 22 patients who progressed, 17 had pre-existent AD scores ≥7.0%. Increased AD scores were related to poorer forced expiratory volume in 1 second values and chronic cough. Common variable immunodeficiency and increased CD4 effector/memory cells were risk factors for an interstitial lung disease (ILD) score ≥13.0%. ILD ≥13.0% occurred in 12 of 80 patients. Signs of ILD progression were detected in 8 of 80 patients, and 4 of 8 patients showing progression had pre-existent ILD scores ≥13.0%. CONCLUSION: We identified risk factors that distinguished patients with PAD at risk for AD and ILD presence and progression, which could guide future screening frequency; however, independent and preferably prospective validation is needed.

The relationship of fat and muscle measurements with emphysema and bronchial wall thickening in smokers.

Introduction: Differences in body composition in patients with COPD may have important prognostic value and may provide opportunities for patient-specific management. We investigated the relation of thoracic fat and muscle with computed tomography (CT)-measured emphysema and bronchial wall thickening. Methods: Low-dose baseline chest CT scans from 1031 male lung cancer screening participants from one site were quantified for emphysema, bronchial wall thickening, subcutaneous fat, visceral fat and skeletal muscle. Body composition measurements were performed by segmenting the first slice above the aortic arch using Hounsfield unit thresholds with region growing and manual corrections. COPD presence and severity were evaluated with pre-bronchodilator spirometry testing. Results: Participants had a median age of 61.5 years (58.6-65.6, 25th-75th percentile) and median number of 38.0 pack-years (28.0-49.5); 549 (53.2%) were current smokers. Overall, 396 (38.4%) had COPD (256 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1, 140 GOLD 2-3). Participants with COPD had less subcutaneous fat, visceral fat and skeletal muscle (p<0.001 for all). With increasing GOLD stages, subcutaneous (p=0.005) and visceral fat values (p=0.004) were higher, and skeletal muscle was lower (p=0.004). With increasing severity of CT-derived emphysema, subcutaneous fat, visceral fat and skeletal muscle values were lower (p<0.001 for all). With increasing CT-derived bronchial wall thickness, subcutaneous and visceral fat values were higher (p<0.001 for both), without difference in skeletal muscle. All statistical relationships remained when adjusted for age, pack-years and smoking status. Conclusion: COPD presence and emphysema severity are associated with smaller amounts of thoracic fat and muscle, whereas bronchial wall thickening is associated with fat accumulation.

Long COVID exhibits clinically distinct phenotypes at 3-6 months post-SARS-CoV-2 infection: results from the P4O2 consortium.

BACKGROUND: Four months after SARS-CoV-2 infection, 22%-50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient. METHODS: Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3-6 months after infection. Unsupervised hierarchical clustering was performed on patient characteristics, characteristics from acute SARS-CoV-2 infection, long COVID symptom data, lung function and questionnaires describing the impact and severity of long COVID. To assess robustness, partitioning around medoids was used as alternative clustering. RESULTS: Three distinct clusters of patients with long COVID were revealed. Cluster 1 (44%) represented predominantly female patients (93%) with pre-existing asthma and suffered from a median of four symptom categories, including fatigue and respiratory and neurological symptoms. They showed a milder SARS-CoV-2 infection. Cluster 2 (38%) consisted of predominantly male patients (83%) with cardiovascular disease (CVD) and suffered from a median of three symptom categories, most commonly respiratory and neurological symptoms. This cluster also showed a significantly lower forced expiratory volume within 1 s and diffusion capacity of the lung for carbon monoxide. Cluster 3 (18%) was predominantly male (88%) with pre-existing CVD and diabetes. This cluster showed the mildest long COVID, and suffered from symptoms in a median of one symptom category. CONCLUSIONS: Long COVID patients can be clustered into three distinct phenotypes based on their clinical presentation and easily obtainable information. These clusters show distinction in patient characteristics, lung function, long COVID severity and acute SARS-CoV-2 infection severity. This clustering can help in selecting the most beneficial monitoring and/or treatment strategies for patients suffering from long COVID. Follow-up research is needed to reveal the underlying molecular mechanisms implicated in the different phenotypes and determine the efficacy of treatment.

Rate of progression of CT-quantified emphysema in male current and ex-smokers: a follow-up study.

BACKGROUND: Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV1-decline in male heavy smokers. METHODS: 3,670 male smokers with mean (SD) 40.8 (17.9) packyears underwent chest CT scans and pulmonary function tests at baseline and after 1 and 3 years follow-up. Smoking status (quitted ≥5, ≥1-<5, <1 years or current smoker) was noted. Rate of progression of emphysema and FEV1-decline after follow-up were assessed by analysis of variance adjusting for age, height, baseline pulmonary function and emphysema severity, packyears, years in study and respiratory symptoms. The quitted ≥5 group was used as reference. RESULTS: Median (Q1-Q3) emphysema severity,<-950 HU, was 8.8 (5.1 - 14.1) and mean (SD) FEV1 was 3.4 (0.73) L or 98.5 (18.5) % of predicted. The group quitted '>5 years' showed significantly lower rates of progression of emphysema compared to current smokers, 1.07% and 1.12% per year, respectively (p<0.001). Current smokers had a yearly FEV1-decline of 69 ml, while subjects quit smoking >5 years had a yearly decline of 57.5 ml (p<0.001). CONCLUSION: Quit smoking >5 years significantly slows the rate of emphysema progression and lung function decline. TRIAL REGISTRATION: Registered at http://www.trialregister.nl with trial number ISRCTN63545820.

A Systematic Review of Chest Imaging Findings in Long COVID Patients.

Long COVID is the persistence of one or more COVID-19 symptoms after the initial viral infection, and there is evidence supporting its association with lung damage. In this systematic review, we provide an overview of lung imaging and its findings in long COVID patients. A PubMed search was performed on 29 September 2021, for English language studies in which lung imaging was performed in adults suffering from long COVID. Two independent researchers extracted the data. Our search identified 3130 articles, of which 31, representing the imaging findings of 342 long COVID patients, were retained. The most common imaging modality used was computed tomography (CT) (N = 249). A total of 29 different imaging findings were reported, which were broadly categorized into interstitial (fibrotic), pleural, airway, and other parenchymal abnormalities. A direct comparison between cases, in terms of residual lesions, was available for 148 patients, of whom 66 (44.6%) had normal CT findings. Although respiratory symptoms belong to the most common symptoms in long COVID patients, this is not necessarily linked to radiologically detectable lung damage. Therefore, more research is needed on the role of the various types of lung (and other organ) damage which may or may not occur in long COVID.

Radiological and long-term clinical response to elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with advanced lung disease.

INTRODUCTION: A triple combination of CFTR modulators ELE/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor, Trikafta™) has been evaluated in clinical trials for people with cystic fibrosis (pwCF) and was approved to the European and US market. During registration and settling reimbursement in Europe, it could be requested on a compassionate use basis, for patients with advanced lung disease (ppFEV1 < 40). AIM: The aim of this study is to evaluate 2 years of experience with the clinical and radiological response of ELE/TEZ/IVA in pwCF in a compassionate use setting. METHODS: pwCF who started ELE/TEZ/IVA in a compassionate use setting were prospectively followed with assessment of spirometry, BMI, chest CT, CFQ-R and sweat chloride concentration (SCC) before start and after 3 months. Furthermore, spirometry, sputum cultures, and BMI were repeated after 1, 6, 12, 18, and 24 months. RESULTS: Eighteen patients were eligible for this evaluation, nine with F508del/F508del genotype (eight of whom were using dual CFTR modulators) and nine with F508del/minimal function mutation. After 3 months, mean change in SCC was -44.9 (p ≤ 0.001), together with significant improvement in CT (change in Brody score: -28.27 p ≤ 0.001) and CFQ-R results (change in respiratory domain: +18.8, p = 0.002). After 24 months, ppFEV1 change was +8.89 (p = 0.002), BMI had improved by +1.53 kg/m2 (p ≤ 0.001) and exacerbation rate declined from 5.94 in 24 months before start to 1.17 (p ≤ 0.001) in the 24 months after. CONCLUSION: pwCF with advanced lung disease experience relevant clinical benefit after 2 years of treatment with ELE/TEZ/IVA in a compassionate use setting. Structural lung damage, quality of life, exacerbation rate, and BMI improved significantly with treatment. Gain in ppFEV1 is lower compared to the phase III trials that included younger patients with moderately affected lung function.