Background In the search for specific phenotypes of chronic obstructive pulmonary disease (COPD) computed tomography (CT) derived Parametric Response Mapping (PRM) has been introduced. This study evaluates the association between PRM and currently available biomarkers of disease severity in COPD. Methods Smokers with and without COPD were characterized based on questionnaires, pulmonary function tests, body plethysmography, and low-dose chest CT scanning. PRM was used to calculate the amount of emphysema (PRMEmph) and non-emphysematous air trapping (i.e. functional small airway disease, PRMfSAD). PRM was first compared with other biomarkers for emphysema (Perc15) and air trapping (E/I-ratioMLD). Consequently, linear regression models were utilized to study associations of PRM measurements with clinical parameters. Results 166 participants were included with a mean ± SD age of 50.5 ± 17.7 years. Both PRMEmph and PRMfSAD were more strongly correlated with lung function parameters as compared to Perc15 and E/I-ratioMLD. PRMEmph and PRMfSAD were higher in COPD participants than non-COPD participants (14.0% vs. 1.1%, and 31.6% vs. 8.2%, respectively, both p < 0.001) and increased with increasing GOLD stage (all p < 0.001). Multivariate analysis showed that PRMfSAD was mainly associated with total lung capacity (TLC) (β = −7.90, p < 0.001), alveolar volume (VA) (β = 7.79, p < 0.001), and residual volume (β = 6.78, p < 0.001), whilst PRMEmph was primarily associated with Kco (β = 8.95, p < 0.001), VA (β = −6.21, p < 0.001), and TLC (β = 6.20, p < 0.001). Conclusions PRM strongly associates with the presence and severity of COPD. PRM therefore appears to be a valuable tool in differentiating COPD phenotypes.

Airway wall thickening in cigarette smokers is thought to be a result of inflammatory changes and airway remodeling. This study investigates if CT-derived airway wall thickening associates to disease severity in smokers with and without COPD and if airway wall thickening is reversible by smoking cessation. We examined 2000 smokers and 46 never-smokers who returned for a 5-year follow-up visit in the COPDGene-study. Multivariable regression analyses were performed at visit 1 to associate airway wall thickness (expressed as Pil0) with percent predicted forced expiratory volume in one second (FEV1%-predicted), 6-minute walking distance (6MWD), and St. George Respiratory Questionnaire (SGRQ). Longitudinal analyses were performed to assess the effect of smoking cessation on Pi10 using linear mixed models. A higher Pi10 was significantly associated with worse FEV1%-predicted, 6MWD, and SGRQ in all GOLD-stages. Longitudinal analyses showed that subjects that quit smoking significantly decreased in Pil0 (ΔPil0=−0.18mm, p<0.001). Subjects that started smoking had a significant increase in Pil0 (ΔPil0=0.14mm, p<0.001). Pil0 is a clinically relevant biomarker of smoking-related airway injury in smokers with and without COPD. The change in Pil0 with change in smoking status suggests that it can quantify a reversible component of smoking-related airway inflammation.

A voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease.

• 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.

ObjectiveTo determine inter-observer and inter-examination variability of manual attenuation measurements of the vertebrae in low-dose unenhanced chest computed tomography (CT).MethodsThree 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.ResultsInter-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.ConclusionsVertebral 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00330-015-4145-x) contains supplementary material, which is available to authorized users.