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Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

Contains fulltext : 165636.pdf (Publisher’s version ) (Closed access), In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial (NELSON).Europe's largest, sufficiently powered randomised lung cancer screening trial was designed to determine whether low-dose CT screening reduces lung cancer mortality by ?25\% compared with no screening after 10?years of follow-up. The screening arm (n=7915) received screening at baseline, after 1 year, 2 years and 2.5?years. Performance of the NELSON screening strategy in the final fourth round was evaluated. Comparisons were made between lung cancers detected in the first three rounds, in the final round and during the 2.5-year interval.In round 4, 46 cancers were screen-detected and there were 28 interval cancers between the third and fourth screenings. Compared with the second round screening (1-year interval), in round 4 a higher proportion of stage IIIb/IV cancers (17.3\% vs 6.8\%, p=0.02) and higher proportions of squamous-cell, bronchoalveolar and small-cell carcinomas (p=0.001) were detected. Compared with a 2-year interval, the 2.5-year interval showed a higher non-significant stage distribution (stage IIIb/IV 17.3\% vs 5.2\%, p=0.10). Additionally, more interval cancers manifested in the 2.5-year interval than in the intervals of previous rounds (28 vs 5 and 28 vs 19).A 2.5-year interval reduced the effect of screening: the interval cancer rate was higher compared with the 1-year and 2-year intervals, and proportion of advanced disease stage in the final round was higher compared with the previous rounds.ISRCTN63545820.

Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b=-1.27, P=0.02 and b=-0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures.

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.

Background: Patients with chronic obstructive pulmonary disease (COPD) demonstrate reduced levels of daily physical activity (DPA) compared to healthy controls. This results in a higher risk of hospital admission and shorter survival. Performing regular DPA reduces these risks. Objective: To develop an eHealth intervention that will support patients with COPD to improve or maintain their DPA after pulmonary rehabilitation. Methods: The design process consisted of literature research and the iterative developing and piloting phases of the Medical Research Council (MRC) model for complex clinical interventions and the involvement of end users. Participants were healthy adults and persons with COPD. Results: The mobile phone interface met all the set requirements. Participants found that the app was stimulating and that reaching their DPA goals was rewarding. The mean (SD) scores on a 7-point scale for usability, ease of use, ease of learning, and contentment were 3.8 (1.8), 5.1 (1.1), 6.0 (1.6), and 4.8 (1.3), respectively. The mean (SD) correlation between the mobile phone and a validated accelerometer was 0.88 (0.12) in the final test. The idea of providing their health care professional with their DPA data caused no privacy issues in the participants. Battery life lasted for an entire day with the final version, and readability and comprehensibility of text and colors were favorable. Conclusions: By employing a user-centered design approach, a mobile phone was found to be an adequate and feasible interface for an eHealth intervention. The mobile phone and app are easy to learn and use by patients with COPD. In the final test, the accuracy of the DPA measurement was good. The final version of the eHealth intervention is presently being tested by our group for efficacy in a randomized controlled trial in COPD patients.

Physical inactivity in patients with chronic obstructive pulmonary disease (COPD) is associated with poor health status and increased disease burden. The present study aims to test the efficacy of a previously developed mobile (m)Health intervention to improve or maintain physical activity in patients with COPD after pulmonary rehabilitation. A randomised controlled trial was performed in 32 physiotherapy practices in the Netherlands. COPD patients were randomised into intervention or usual care groups. The intervention consisted of a smartphone application for the patients and a monitoring website for the physiotherapists. Measurements were performed at 0, 3, 6 and 12 months. Physical activity, functional exercise capacity, lung function, health-related quality of life and body mass index were assessed. 157 patients started the study and 121 completed it. There were no significant positive effects of the intervention on physical activity (at 0 months: intervention 5824±3418 steps per weekday, usual care 5717±2870 steps per weekday; at 12 months: intervention 4819±2526 steps per weekday, usual care 4950±2634 steps per weekday; p=0.811) or on the secondary end-points. There was a significant decrease over time in physical activity (p

Contains fulltext : 153755.pdf (Publisher’s version ) (Open Access), 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.

Contains fulltext : 153586.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 154320.pdf (Publisher’s version ) (Open Access), Pulmonary subsolid nodules (SSNs) have a high likelihood of malignancy, but are often indolent. A conservative treatment approach may therefore be suitable. The aim of the current study was to evaluate whether close follow-up of SSNs with computed tomography may be a safe approach. The study population consisted of participants of the Dutch-Belgian lung cancer screening trial (Nederlands Leuvens Longkanker Screenings Onderzoek; NELSON). All SSNs detected during the trial were included in this analysis. Retrospectively, all persistent SSNs and SSNs that were resected after first detection were segmented using dedicated software, and maximum diameter, volume and mass were measured. Mass doubling time (MDT) was calculated. In total 7135 volunteers were included in the current analysis. 264 (3.3\%) SSNs in 234 participants were detected during the trial. 147 (63\%) of these SSNs in 126 participants disappeared at follow-up, leaving 117 persistent or directly resected SSNs in 108 (1.5\%) participants available for analysis. The median follow-up time was 95 months (range 20-110). 33 (28\%) SSNs were resected and 28 of those were (pre-) invasive. None of the non-resected SSNs progressed into a clinically relevant malignancy. Persistent SSNs rarely developed into clinically manifest malignancies unexpectedly. Close follow-up with computed tomography may be a safe option to monitor changes.

Contains fulltext : 153772.pdf (Publisher’s version ) (Open Access), The objective of this study was to investigate the association of spirometry and pulmonary CT biomarkers with cardiovascular events.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.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).Pulmonary CT biomarkers and spirometry measurements were significantly associated with cardiovascular events, but did not contain clinically relevant independent prognostic information for cardiovascular events.• 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.

Item does not contain fulltext, 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 (β) 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 (β = -0.46), while for the FEV1/FVC this was emphysema (β = -0.55). For the residual volume (RV) air trapping was most contributing (β = -0.35). Lung diffusion capacity was most influenced by emphysema (β = -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.

Contains fulltext : 137797.pdf (Publisher’s version ) (Open Access), Finding phenotypes within COPD patients may prove imperative for optimizing treatment and prognosis. We hypothesized that it would be possible to discriminate emphysematous, large airway wall thickening and small airways disease dominant phenotypes.Inspiratory and expiratory CTs were performed in 1140 male smokers without or with mild COPD to quantify emphysema, airway wall thickness and air trapping. Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were measured. Dominant phenotype (emphysema, airway wall thickening or air trapping dominant) was defined as one of the respective CT measure in the upper quartile, with the other measures not in the upper quartile.573 subjects had any of the three CT measures in the upper quartile. Of these, 367 (64\%) were in a single dominant group and 206 (36\%) were in a mixed group. Airway wall thickening dominance was associated with younger age (p < 0.001), higher body mass index (p < 0.001), more wheezing (p < 0.05) and lower FEV1 \%predicted (p < 0.001). Emphysema dominant subjects had lower FEV1/FVC (p < 0.05) and Kco \%predicted (p < 0.05). There was no significant difference in respiratory related hospitalizations (p = 0.09).CT measures can discriminate three different CT dominant groups of disease in male smokers without or with mild COPD.ISRCTN63545820, registered at www.trialregister.nl.

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25x10-6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3x10 -9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

Background: Beyond lung cancer, screening CT contains additional information on other smoking related diseases (e.g. chronic obstructive pulmonary disease, COPD). Since pulmonary function testing is not regularly incorporated in lung cancer screening, imaging biomarkers for COPD are likely to provide important surrogate measures for disease evaluation. Therefore, this study aims to determine the independent diagnostic value of CT emphysema, CT air trapping and CT bronchial wall thickness for COPD in low-dose screening CT scans.Methods: Prebronchodilator spirometry and volumetric inspiratory and expiratory chest CT were obtained on the same day in 1140 male lung cancer screening participants. Emphysema, air trapping and bronchial wall thickness were automatically quantified in the CT scans. Logistic regression analysis was performed to derivate a model to diagnose COPD. The model was internally validated using bootstrapping techniques.Results: Each of the three CT biomarkers independently contributed diagnostic value for COPD, additional to age, body mass index, smoking history and smoking status. The diagnostic model that included all three CT biomarkers had a sensitivity and specificity of 73.2% and 88.%, respectively. The positive and negative predictive value were 80.2% and 84.2%, respectively. Of all participants, 82.8% was assigned the correct status. The C-statistic was 0.87, and the Net Reclassification Index compared to a model without any

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.

Several medical associations recommended lung cancer screening by low-dose computed tomography scanning for high-risk groups. Counselling of the candidates on the potential harms and benefits and their lung cancer risk is a prerequisite for screening. In the NELSON trial, screenings are considered positive for (part) solid lung nodules with a volume >500 mm3 and for (part) solid or nonsolid nodules with a volume-doubling time >400 days. For this study, the performance of the NELSON strategy in three screening rounds was evaluated and risk calculations were made for a follow-up period of 5.5 years. 458 (6%) of the 7582 participants screened had a positive screen result and 200 (2.6%) were diagnosed with lung cancer. The positive screenings had a predictive value of 40.6% and only 1.2% of all scan results were false-positive. In a period of 5.5 years, the risk of screen-detected lung cancer strongly depends on the result of the first scan: 1.0% after a negative baseline result, 5.7%after an indeterminate baseline and 48.3% after a positive baseline. The screening strategy yielded few positive and false-positive scans with a reasonable positive predictive value. The 5.5-year lung cancer risk calculations aid clinicians in counselling candidates for lung cancer screening with low-dose computed tomography.

Background:There is increasing evidence that structural lung changes may be present before the occurrence of airflow limitation as assessed by spirometry. This study investigated the prevalence of computed tomography (CT) quantified emphysema, airway wall thickening and gas trapping according to classification of airflow limitation (FEV1/FVC <70% and/or < the lower limit of normal (LLN)) in (heavy) smokers.Methods:A total number of 1,140 male former and current smokers participating in a lung cancer screenings trial (NELSON) were included and underwent chest CT scanning and spirometry. Emphysema was quantified by the 15th percentile, air way wall thickening by the square root of wall area for a theoretical airway with 10mm lumen perimeter (Pi10) and gas trapping by the mean lung density expiratory/inspiratory (E/I)-ratio. Participants were classified by entry FEV1/FVC: group 1>70%; group 2<70% but >LLN; and group 370% but FEV1 <80% predicted, were excluded. Multivariate regression analysis correcting for covariates was used to asses the extent of emphysema, airway wall thickening and gas trapping according to three groups of airflow limitation.Results:Mean (standard deviation) age was 62.5 (5.2) years and packyears smoked was 41.0 (18.0). Group 2 subjects when compared to group 1 had a significantly lower 15th percentile, -920.6 HU versus -912.2 HU; a higher Pi10, 2.87 mm versus 2.57 mm; and a higher E/I-ratio, 88.6% versus 85.6% (all p<0.001).Conclusion:Subjects with an FEV1/FVC<70%, but above the LLN, have a significant greater degree of structural lung changes on CT compared to subjects without airflow limitation.

Rationale: The NELSON (Nederlands Leuvens Longkanker Screenings Onderzoek) trial is, with 15,822 participants, the largest European lung cancer computer tomography screening trial. A volumetrybased screening strategy, stringent criteria for a positive screening, and an increasing length of screening interval are particular features of the NELSON trial. Objectives: To determine the effect of stringent referral criteria and increasing screening interval on the characteristics of screendetected lung cancers, and to compare this across screening rounds, between sexes, and with other screening trials. Methods: All NELSON participants with screen-detectedlung cancer in the first three rounds were included. Lung cancer stage at diagnosis, histological subtype, and tumor localizationwere compared between the screening rounds, the sexes, and with other screening trials. Measurements and Main Results: In the first three screening rounds, 200 participants were diagnosed with 209 lung cancers. Of these lung cancers, 70.8% were diagnosed at stage I and 8.1% at stage IIIB-IV, and 51.2% were adenocarcinomas. There was no significant difference in cancer stage, histology, or tumorlocalization across the screening rounds. Women were diagnosed at a significantly more favorable cancer stage than men. Compared with other trials, the screen-detected lung cancers of the NELSON trial were relatively more often diagnosed at stage I and less often at stage IIIB-IV. Conclusions: Despite stringent criteria for a positive screening, an increasing length of screening interval, and few female participants, the screening strategy of the NELSON trial resulted in a favorable cancer stage distribution at diagnosis, which is essential for the effectiveness of our screening strategy. Clinical trial registered with www.trialregister.nl (ISRCTN63545820).Copyright

Background: Up to 50% of the participants in CT scan lung cancer screening trials have at least one pulmonary nodule. To date, the role of conventional bronchoscopy in the workup of suspicious screen-detected pulmonary nodules is unknown. If a bronchoscopic evaluation could be eliminated, the cost-effectiveness of a screening program could be enhanced and the potential harms of bronchoscopy avoided. Methods: All consecutive participants with a positive result on a CT scan lung cancer screening between April 2004 and December 2008 were enrolled. The diagnostic sensitivity and nega tive predictive value were calculated at the level of the suspicious nodules. In 95% of the nodules, the gold standard for the outcome of the bronchoscopy was based on surgical resection specimens. Results: A total of 318 suspicious lesions were evaluated by bronchoscopy in 308 participants. The mean ± SD diameter of the nodules was 14.6 ± 8.7 mm, whereas only 2.8% of nodules were >30 mm in diameter. The sensitivity of bronchoscopy was 13.5% (95% CI, 9.0%-19.6%); the specificity, 100%; the positive predictive value, 100%; and the negative predictive value, 47.6% (95% CI, 41.8%-53.5%). Of all cancers detected, 1% were detected by bronchoscopy only and were retrospectively invisible on both low-dose CT scan and CT scan with IV contrast. Conclusion: Conventional white-light bronchoscopy should not be routinely recommended for patients with positive test results in a lung cancer screening program. Trial registration: Nederlands Trial Register; No.: ISRCTN63545820; URL: www.trialregister.nl.

Chronic obstructive pulmonary disease (COPD)/emphysema risk groups are well defined and screening allows for early identification of disease. The capability of exhaled volatile organic compounds (VOCs) to detect emphysema, as found by computed tomography (CT) in current and former heavy smokers participating in a lung cancer screening trial, was investigated. CT scans, pulmonary function tests and breath sample collections were obtained from 204 subjects. Breath samples were analyzed with a proton-transfer reaction mass spectrometer (PTR-MS) to obtain VOC profiles listed as ions at various mass-to-charge ratios (m/z). Using bootstrapped stepwise forward logistic regression, we identified specific breath profiles as a potential tool for the diagnosis of emphysema, of airflow limitation or gas-exchange impairment. A marker for emphysema was found at m/z 87 (tentatively attributed to 2-methylbutanal). The area under the receiver operating characteristic curve (ROC) of this marker to diagnose emphysema was 0.588 (95% CI 0.453-0.662). Mass-to-charge ratios m/z 52 (most likely chloramine) and m/z 135 (alkyl benzene) were linked to obstructive disease and m/z 122 (most probably alkyl homologs) to an impaired diffusion capacity. ROC areas were 0.646 (95% CI 0.562-0.730) and 0.671 (95% CI 0.524-0.710), respectively. In the screening setting, exhaled VOCs measured by PTR-MS constitute weak markers for emphysema, pulmonary obstruction and impaired diffusion capacity.

BACKGROUND: The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT. METHODS: A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm3, if it was 50 to 500 mm3 but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more. RESULTS: In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up. CONCLUSIONS: Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.). Copyright

Contains fulltext : 24952___.PDF (publisher's version ) (Open Access)

Contains fulltext : 20808___.PDF (publisher's version ) (Open Access)