Distribution of emphysema in heavy smokers: Impact on pulmonary function

SummaryPurposeTo investigate impact of distribution of computed tomography (CT) emphysema on severity of airflow limitation and gas exchange impairment in current and former heavy smokers participating in a lung cancer screening trial.Materials and MethodsIn total 875 current and former heavy smokers underwent baseline low-dose CT (30mAs) in our center and spirometry and diffusion capacity testing on the same day as part of the Dutch–Belgian Lung Cancer Screening Trial (NELSON). Emphysema was quantified for 872 subjects as the number of voxels with an apparent lowered X-ray attenuation coefficient. Voxels attenuated <−950HU were categorized as representing severe emphysema (ES950), while voxels attenuated between −910HU and −950HU represented moderate emphysema (ES910). Impact of distribution on severity of pulmonary function impairment was investigated with logistic regression, adjusted for total amount of emphysema.ResultsFor ES910 an apical distribution was associated with more airflow obstruction and gas exchange impairment than a basal distribution (both p<0.01). The FEV1/FVC ratio was 1.6% (95% CI 0.42% to 2.8%) lower for apical predominance than for basal predominance, for Tlco/VA the difference was 0.12% (95% CI 0.076–0.15%). Distribution of ES950 had no impact on FEV1/FVC ratio, while an apical distribution was associated with a 0.076% (95% CI 0.038–0.11%) lower Tlco/VA (p<0.001).ConclusionIn a heavy smoking population, an apical distribution is associated with more severe gas exchange impairment than a basal distribution; for moderate emphysema it is also associated with a lower FEV1/FVC ratio. However, differences are small, and likely clinically irrelevant

Volumetric measurement of pulmonary nodules at low-dose chest CT: effect of reconstruction setting on measurement variability

To assess volumetric measurement variability in pulmonary nodules detected at low-dose chest CT with three reconstruction settings. The volume of 200 solid pulmonary nodules was measured three times using commercially available semi-automated software of low-dose chest CT data-sets reconstructed with 1 mm section thickness and a soft kernel (A), 2 mm and a soft kernel (B), and 2 mm and a sharp kernel (C), respectively. Repeatability coefficients of the three measurements within each setting were calculated by the Bland and Altman method. A three-level model was applied to test the impact of reconstruction setting on the measured volume. The repeatability coefficients were 8.9, 22.5 and 37.5% for settings A, B and C. Three-level analysis showed that settings A and C yielded a 1.29 times higher estimate of nodule volume compared with setting B (P = 0.03). The significant interaction among setting, nodule location and morphology demonstrated that the effect of the reconstruction setting was different for different types of nodules. Low-dose CT reconstructed with 1 mm section thickness and a soft kernel provided the most repeatable volume measurement. A wide, nodule-type-dependent range of agreement between volume measurements with different reconstruction settings suggests strict consistency is required for serial CT studies

COVID outcome prediction in the emergency department (COPE):using retrospective Dutch hospital data to develop simple and valid models for predicting mortality and need for intensive care unit admission in patients who present at the emergency department with suspected COVID-19

OBJECTIVES: Develop simple and valid models for predicting mortality and need for intensive care unit (ICU) admission in patients who present at the emergency department (ED) with suspected COVID-19.DESIGN: Retrospective.SETTING: Secondary care in four large Dutch hospitals.PARTICIPANTS: Patients who presented at the ED and were admitted to hospital with suspected COVID-19. We used 5831 first-wave patients who presented between March and August 2020 for model development and 3252 second-wave patients who presented between September and December 2020 for model validation.OUTCOME MEASURES: We developed separate logistic regression models for in-hospital death and for need for ICU admission, both within 28 days after hospital admission. Based on prior literature, we considered quickly and objectively obtainable patient characteristics, vital parameters and blood test values as predictors. We assessed model performance by the area under the receiver operating characteristic curve (AUC) and by calibration plots.RESULTS: Of 5831 first-wave patients, 629 (10.8%) died within 28 days after admission. ICU admission was fully recorded for 2633 first-wave patients in 2 hospitals, with 214 (8.1%) ICU admissions within 28 days. A simple model-COVID outcome prediction in the emergency department (COPE)-with age, respiratory rate, C reactive protein, lactate dehydrogenase, albumin and urea captured most of the ability to predict death. COPE was well calibrated and showed good discrimination for mortality in second-wave patients (AUC in four hospitals: 0.82 (95% CI 0.78 to 0.86); 0.82 (95% CI 0.74 to 0.90); 0.79 (95% CI 0.70 to 0.88); 0.83 (95% CI 0.79 to 0.86)). COPE was also able to identify patients at high risk of needing ICU admission in second-wave patients (AUC in two hospitals: 0.84 (95% CI 0.78 to 0.90); 0.81 (95% CI 0.66 to 0.95)).CONCLUSIONS: COPE is a simple tool that is well able to predict mortality and need for ICU admission in patients who present to the ED with suspected COVID-19 and may help patients and doctors in decision making.</p

A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients

An analytical assay has been developed and validated for ultrafast and high-throughput mass spectrometric determination of pemetrexed concentrations in plasma using matrix assisted laser desorption/ionization–triple quadrupole–tandem mass spectrometry. Patient plasma samples spiked with the internal standard methotrexate were measured by multiple reaction monitoring. The detection limit was 0.4 fmol/μL, lower limit of quantification was 0.9 fmol/μL, and upper limit of quantification was 60 fmol/μL, respectively. Overall observed pemetrexed concentrations in patient samples ranged between 8.7 (1.4) and 142.7 (20.3) pmol/μL (SD). The newly developed mass spectrometric assay is applicable for (routine) therapeutic drug monitoring of pemetrexed concentrations in plasma from non-small cell lung cancer patients

Informed decision making does not affect health-related quality of life in lung cancer screening (NELSON trial)

Background: It is believed that making an informed decision about (screening) participation is associated with better health-related quality of life (HRQoL) outcomes. This is the first study in cancer screening to explore this association in subjects participating in a lung cancer computed tomography (CT) screening trial. Methods: Participants that made either an informed decision to participate (n = 155) or not (n = 133) were selected for this study. Differences in HRQoL, measured as generic HRQoL (Short Form 12 [SF-12] and EuroQol questionnaire [EQ-5D]), anxiety/distress (State-Trait Anxiety Inventory [STAI-6], Impact of Event Scale [IES] and Consequences of Screening-Lung Cancer [COS-LC]), were tested with Mann-Whitney U tests and ANOVA at three assessment points (when deciding about participation, before trial randomisation and 2 months after receiving the CT result). Results: Subjects who made an informed decision to participate had no better scores than those who did not make an informed decision for 23 out of 24 HRQoL comparisons, except for a better mean score for mental health (Mental Component Summary (MCS) = 53.9 +/- 9.2 versus 51.0 +/- 10.1, p = 0.003) before randomisation. For subjects with an indeterminate CT result (n = 64), no significant differences were found between subjects with (n = 35) or without (n = 29) an informed decision. Conclusion: Subjects who did not make an informed decision to participate in lung cancer CT screening trial did not experience worse HRQoL during screening than subjects who did make an informed decision, either in general or after receiving an indeterminate result. (C) 2010 Elsevier Ltd. All rights reserve

Subphenotypes of mild-to-moderate COPD by factor and cluster analysis of pulmonary function, CT imaging and breathomics in a population-based survey

Classification of COPD is currently based on the presence and severity of airways obstruction. However, this may not fully reflect the phenotypic heterogeneity of COPD in the (ex-) smoking community. We hypothesized that factor analysis followed by cluster analysis of functional, clinical, radiological and exhaled breath metabolomic features identifies subphenotypes of COPD in a community-based population of heavy (ex-) smokers. Adults between 50-75 years with a smoking history of at least 15 pack-years derived from a random population-based survey as part of the NELSON study underwent detailed assessment of pulmonary function, chest CT scanning, questionnaires and exhaled breath molecular profiling using an electronic nose. Factor and cluster analyses were performed on the subgroup of subjects fulfilling the GOLD criteria for COPD (post-BD FEV1/FVC < 0.70). Three hundred subjects were recruited, of which 157 fulfilled the criteria for COPD and were included in the factor and cluster analysis. Four clusters were identified: cluster 1 (n = 35; 22%): mild COPD, limited symptoms and good quality of life. Cluster 2 (n = 48; 31%): low lung function, combined emphysema and chronic bronchitis and a distinct breath molecular profile. Cluster 3 (n = 60; 38%): emphysema predominant COPD with preserved lung function. Cluster 4 (n = 14; 9%): highly symptomatic COPD with mildly impaired lung function. In a leave-one-out validation analysis an accuracy of 97.4% was reached. This unbiased taxonomy for mild to moderate COPD reinforces clusters found in previous studies and thereby allows better phenotyping of COPD in the general (ex-) smoking populatio

The effectiveness of a computer-tailored smoking cessation intervention for participants in lung cancer screening: A randomised controlled trial

Background: Lung cancer screening might be a teachable moment for smoking cessation intervention. The objective was to investigate whether a tailored self-help smoking cessation intervention is more effective in inducing smoking cessation compared to a standard brochure in male smokers who participate in the Dutch-Belgian randomised controlled lung cancer screening trial (NELSON trial). Methods: Two random samples of male smokers who had received either a standard brochure (n = 642) or a tailoring questionnaire for computer-tailored smoking cessation information (n = 642) were sent a questionnaire to measure smoking behaviour two years after randomisation. Results:Twenty-three percent of the male smokers in the tailored information group returned a completed tailoring questionnaire and thus received the tailored advice. The prolonged smoking abstinence was slightly, but not statistically significant, lower amongst those randomised in the tailored information group (12.5%) compared with the brochure group (15.6%) (OR = 0.77 (95%-CI: 0.56-1.06). The level of education and intention to quit smoking significantly predicted smoking cessation at follow- Conclusion: The current study showed no advantage of tailored smoking cessation information over standard self-help information amongst male smokers with a long term smoking history who participate in a lung cancer screening trial after two years of follow-up. However, the low percentage participants who actually received the tailored advice limited the ability to find an advantage. (C) 2011 Elsevier Ireland Ltd. All rights reserved

The impact of a lung cancer computed tomography screening result on smoking abstinence

Receiving a lung cancer computed tomography screening result might be a teachable moment for smoking cessation, but it might also unintentionally reassure smokers to continue smoking. The objective of the present study was to investigate whether test results were associated with smoking abstinence in the Dutch-Belgian Randomised Controlled Lung Cancer Screening Trial (NELSON trial). Two random samples of male smokers who had received either only negative test results (n=550) or one or more indeterminate test result (n=440) were sent a questionnaire 2 yrs after randomisation. Smokers with an indeterminate result reported more quit attempts (p=0.02), but the prolonged abstinence rate in smokers receiving a negative test (46 (8.9%) out of 519 subjects) was comparable with the abstinence rate in smokers with one or more indeterminate results (48 (11.5%) out of 419 subjects) (p=0.19). A statistically insignificant increase was found after one or more indeterminate test result (10.9 and 15.0%, respectively) compared with receiving only negative test results (8.9%) (p=0.26). In conclusion, the outcome of the screening test had no impact on future smoking abstinence in male smokers, although all results suggest more favourable implications after one or more follow-up recommendations. Screening test outcomes could be used as a teachable moment for smoking cessation