Computer quantification of airway collapse on forced expiration to predict the presence of emphysema.

BACKGROUND: Spirometric parameters are the mainstay for diagnosis of COPD, but cannot distinguish airway obstruction from emphysema. We aimed to develop a computer model that quantifies airway collapse on forced expiratory flow-volume loops. We then explored and validated the relationship of airway collapse with computed tomography (CT) diagnosed emphysema in two large independent cohorts. METHODS: A computer model was developed in 513 Caucasian individuals with ≥15 pack-years who performed spirometry, diffusion capacity and CT scans to quantify emphysema presence. The model computed the two best fitting regression lines on the expiratory phase of the flow-volume loop and calculated the angle between them. The collapse was expressed as an Angle of collapse (AC) which was then correlated with the presence of emphysema. Findings were validated in an independent group of 340 individuals. RESULTS: AC in emphysema subjects (N = 251) was significantly lower (131° ± 14°) compared to AC in subjects without emphysema (N = 223), (152° ± 10°) (p < 0.0001). Multivariate regression analysis revealed AC as best indicator of visually scored emphysema (R2 = 0.505, p < 0.0001) with little significant contribution of KCO, %predicted and FEV1, %predicted to the total model (total R2 = 0.626, p < 0.0001). Similar associations were obtained when using CT-automated density scores for emphysema assessment. Receiver operating characteristic (ROC) curves pointed to 131° as the best cut-off for emphysema (95.5% positive predictive value, 97% specificity and 51% sensitivity). Validation in a second group confirmed the significant difference in mean AC between emphysema and non-emphysema subjects. When applying the 131° cut-off, a positive predictive value of 95.6%, a specificity of 96% and a sensitivity of 59% were demonstrated. CONCLUSIONS: Airway collapse on forced expiration quantified by a computer model correlates with emphysema. An AC below 131° can be considered as a specific cut-off for predicting the presence of emphysema in heavy smokers.

The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema.

RATIONALE: Genome-wide association studies have identified genetic variants in the nicotinic acetylcholine receptor (nAChR) on chromosome 15q24/25 as a risk for nicotine dependence, lung cancer, and chronic obstructive pulmonary disease (COPD). Assessment of bronchial obstruction by spirometry, typically used for diagnosing COPD, fails, however, to detect emphysema. OBJECTIVES: To determine the association of the 15q24/25 locus with emphysema. METHODS: The rs1051730 variant on 15q24/25 was genotyped in two independent white cohorts of 661 and 456 heavy smokers. Participants underwent pulmonary function tests and computed tomography (CT) of the chest, and took questionnaires assessing smoking behavior and health status. MEASUREMENTS AND MAIN RESULTS: The rs1051730 A-allele correlated with reduced FEV(1) and with increased susceptibility for bronchial obstruction with a pooled odds ratio (OR) of 1.33 (95% confidence interval [CI] = 1.11-1.61; P = 0.0026). In both studies a correlation between the rs1051730 A-allele and lung diffusing capacity (Dl(CO)) and diffusing capacity per unit alveolar volume (Kco) was observed. Consistently, the rs1051730 A-allele conferred increased risk for emphysema as assessed by CT (P = 0.0097 and P = 0.019), with a pooled OR of 1.39 (CI = 1.15-1.68; P = 0.00051). Visual emphysema scores and scores based on densities quantified on CT were more pronounced in A-allele carriers, indicating that rs1051730 correlates with the severity of emphysema. CONCLUSIONS: The 15q24/25 locus in nAChR is associated with the presence and severity of emphysema. This association was independent of pack-years smoking, suggesting that nAChR is causally involved in alveolar destruction as a potentially shared pathogenic mechanism in lung cancer and COPD.

Central tumour location should be considered when comparing N1 upstaging between thoracoscopic and open surgery for clinical stage I non-small-cell lung cancer.

OBJECTIVES: Nodal upstaging is a quality indicator for oncological thoracic surgery and is found in up to 25% of patients with clinical stage I (cStage-I) non-small-cell lung cancer (NSCLC). In large retrospective series, lower N1 upstaging was reported after video-assisted thoracic surgery (VATS) resections. We studied the impact of central primary tumour location on nodal upstaging in cStage-I NSCLC. METHODS: Consecutive patients operated for cStage-I NSCLC were selected from a prospectively managed surgical database. Tumour location was classified as central if the lesion was visible during standard video bronchoscopy. A nodal station mapping was drawn for each patient based on final pathological examination. Univariable and additive multivariable binary logistic regression analyses were performed. RESULTS: Between 2007-2014, 334 patients underwent anatomical resection for cStage-I NSCLC, either by open thoracotomy (n = 158) or by VATS (n = 176; conversion rate 1.7%). All patients underwent imaging with [(18)F]-fluorodeoxyglucose positron emission tomography and computer tomography. Invasive mediastinal staging was performed in 24.6% of patients. There were more central tumours in the open group (24.1%, n = 38) compared with the VATS group (4.5%, n = 8). There was no significant difference between the number (mean ± standard deviation) of nodal stations examined (open 5 ± 1.9 vs VATS 5 ± 1.7, P = 0.99). Pathological nodal upstaging was found in 15.9% (n = 53) of cStage-I patients. Nodal pN1 and pN2 upstaging were 13.3 and 8.2%, respectively, for the open group, and 6.3 and 4.5%, respectively, for the VATS group. In 32.6% (n = 15/46) of patients with a central cStage-I tumour pN1, upstaging was found. A binary logistic regression model (including tumour location, technique, tumour size, gender and histology) showed that only tumour location had a significant impact on pN1 upstaging [peripheral versus central; odds ratio (OR) 5.07 (confidence interval, CI: 1.89-13.60), P = 0.001], while surgical technique had no significant impact [VATS versus open; OR 0.74 (CI: 0.31-1.78), P = 0.50]. CONCLUSIONS: The number of lymph node stations examined during VATS resections is similar to open resections for cStage-I NSCLC. Almost one-third of the patients with a central cStage-I NSCLC were upstaged to pN1. Tumour location was the only independent variable for pN1 upstaging in logistic regression analysis. It is a potential bias in retrospective studies and should therefore be accounted for when comparing different surgical resection techniques for cStage-I NSCLC.