Single breath N2-test and exhaled nitric oxide in men

SummaryThe N2 slope is an index of inhomogeneous distribution of ventilation and has been suggested to be suited for early testing of chronic obstructive pulmonary disease (COPD) in smokers. The aim of the present study was to examine the association between the fraction of exhaled nitric oxide (FENO) and the N2 slope in a random population of smoking and non-smoking men. Altogether 57 subjects were included in the study, 24 never-smokers, seven ex-smokers and 26 current smokers. Subjects were examined twice, in 1995 when they regarded themselves as healthy, and in a follow-up in 2001. Spirometry, N2 slope and high-resolution computed tomography (HRCT) were performed in 1995 while the follow-up examination included also measurement of FENO.The FENO value was significantly lower and the N2 slope higher in current smokers. In smokers but not in never- or ex-smokers FENO was correlated to the difference in N2 slope between 1995 and 2001 (rs=0.49, P=0.01). We analysed the data by multiple linear regression adjusted for smoking, mild respiratory symptoms and inhaled steroids. There were significant associations between FENO and the N2 slope both in 1995 and in 2001. The strongest association was found to exist with the change in N2 slope during these years.Sixteen of the subjects could be classified as having COPD, six with mild and ten with moderate COPD. There was a trend for an increase in N2 slope with increased severity of COPD; among subjects with no COPD the N2 slope in 2001 was 2.3% N2/L, and those with mild and moderate COPD had 2.5% N2/L and 3.9% N2/L, respectively (P=0.0004). No such trend was seen for FENO (17.8, 15.5 and 20.3 parts per billion (ppb), respectively, P=0.8).The results show that FENO is associated with the N2 slope, indicating that FENO reflects inflammatory changes in the peripheral airways of both non-smoking and smoking subjects

High resolution computed tomography in smoking induced disease

Chronic obstructive pulmonary disease (COPD), usually caused by smoking, is common. It has high morbidity and mortality, and the prevalence is expected to increase. In Sweden about 500 000 individuals are affected, and COPD is the third most common cause of death among men. COPD is due to various combinations of small airway disease and emphysema. Early detected small airways disease is in contrast to emphysema potentially reversible. The overall aim with the thesis was to evaluate the potential of high resolution computed tomography (HRCT) to diagnose early smoking induced disease. We wanted to investigate I. if the disability of emptying the lungs at expiration, in terms of diffuse or focal retention of air, is a sensitive indicator of obstruction in bronchiolitisII. which type of parenchymal findings are to be expected in smokers, and to evaluate what happens to these findings when smoking is continued or stoppedIII. which factors influence the computerized quantification of mild emphysema, and validate a new software especially developed for this purposeIV. the relationship between the density of lung parenchyma and lung volume, and to evaluate whether it is possible to visually recognize full inspiration on HRCT images In study I-III healthy smokers and never smokers from a population study were investigated. HRCT was done twice, with a time elapse of six years. The lung was examined in full inspiration and at three levels in full expiration. In study I the general ability to exhale was investigated by a computerized method, and the focal visually. Neither the general nor the focal ability to exhale differed between smokers without emphysema and never smokers. No correlation to lung function tests sensitive to small airways disease was found. In study II emphysema and other HRCT variables related to smoking were evaluated visually. All variables except emphysema were also found in never smokers. Some variables were found in significantly more smokers, and increased at follow-up. No progress was seen in those who stopped smoking. In study III mild emphysema was analyzed by conventional and new software. The influence of slice thickness, reconstruction algorithm, motion artifacts and gravity was analyzed. The new software could separate the group with mild emphysema form those without. In study IV life long never smokers where investigated by HRCT at different levels of inspiration under spirometrical control. A great variation in lung attenuation at full inspiration was found. The relationship between lung attenuation and volume was inverse linear in the examined interval. It was not possible to visually evaluate if an image was taken in full inspiration or not. Conclusion: Images taken at expiration do not contribute to diagnosis of early smoking induced disease. Emphysema, but also parenchymal nodules and ground glass opacities, indicate smoking induce disease. The disease seems to cease when smoking is stopped. It is not possible to reliable quantify mild emphysema with conventional software. The problem may be solved with specially developed software and proper examination technique. It is not possible to visually evaluate if an image is taken in full inspiration or not. The detection of mild emphysema by HRCT may prevent the occurrence of obstructive ventilatory impairment by giving support for smoking cessation programs. Therefore, HRCT examination should be added to the basic investigation when smoking induced disease is suspected

Detection of pulmonary nodules in chest tomosynthesis: Comparison with chest radiography, evaluation of learning effects and investigation of radiation dose level dependency

Chest tomosynthesis is a relatively recently introduced technique in healthcare, which produces section images of the chest at a lower radiation dose than computed tomography (CT) and with better depth resolution than conventional chest radiography. The primary aims of the studies described in this dissertation were to compare chest tomosynthesis with conventional radiography, to evaluate the effects of clinical experience and learning with feedback on the performance of observers analyzing tomosynthesis images, and to investigate the effect of radiation dose level in tomosynthesis, in the detection of pulmonary nodules. Human observer studies were performed, in which radiologists were instructed to localize and rate pulmonary nodules in patient images. Chest CT was used as reference. The observers' performance regarding the detection of nodules was used as measure of detectability. The results of the studies indicate that the detection of pulmonary nodules is better in chest tomosynthesis than in conventional chest radiography, that experienced thoracic radiologists can quickly adapt to the new technique, that inexperienced observers may perform at a similar level to experienced radiologists after a learning session with feedback, and that a substantial reduction in the effective dose to the patient may be possible

Incidental findings and their handling in the Swedish CArdioPulmonary bioimage study (SCAPIS)

The Swedish CArdioPulmonary bioImage Study (SCAPIS) combines the use of new imaging technologies, large-scale proteomics/metabolomics/genomics, and epidemiological analyses to extensively characterize a Swedish cohort of 30,000 men and women aged between 50 and 64 years. Its main aims are to improve risk prediction and to optimize our ability to study mechanisms of cardiopulmonary diseases. SCAPIS is currently recruiting at six sites in Sweden, and a pilot study was conducted in 2012 to test the feasibility of the comprehensive study protocol. In the planning phase, it was recognized that the detailed phenotyping used in SCAPIS would identify a large number of clinical findings in need of medical attention. This was confirmed by evaluation of results from the pilot study. Here we focus on pulmonary nodules and asymptomatic coronary artery stenosis. These clinical features were observed in a large number of participants, and the clinical handing and prognosis related to these observations are unclear. They thus posed great challenges for the study in their practical and ethical handling. This chapter describes how we developed procedures to handle these findings based on existing evidence and expert consensus as well as deliberations on ethical issues

Visual and Quantitative Evaluation of Emphysema : A Case -Control Study of 1111 Participants in the Pilot Swedish CArdioPulmonary BioImage Study (SCAPIS)

Rationale and Objectives: Emphysema is a hallmark of chronic obstructive pulmonary disease. The primary aim of this study was to investigate inter- and intraobserver agreement of visual assessment of mild emphysema in low-dose multidetector computed tomography of subjects in the pilot SCAPIS in order to certify consistent detection of mild emphysema. The secondary aim was to investigate the performance of quantitative densitometric measurements in the cohort. Materials and Methods: Participants with emphysema (n = 100, 56 males and 44 females) reported in the electronic case report form of pilot SCAPIS and 100 matched controls (gender, age, height, and weight) without emphysema were included. To assess interobserver variability the randomized examinations were evaluated by two thoracic radiologists. For intraobserver variability three radiologists re-evaluated randomized examinations which they originally evaluated. The results were evaluated statistically by Krippendorff's α. The dataset was also assessed quantitively for % lung attenuation value −950 HU (LAV950), mean lung density and total lung volume by commercially available software. Results: Emphysema was visually scored as mild and Krippendorff's α was ≥0.8 for both the inter- and intraobserver agreement regarding presence of emphysema and approaching 0.8 regarding presence and extent of emphysema by location in the upper lobes. Mean LAV950 was not different between the emphysematous and the nonemphysematous participants; 8.3% and 8.4%, respectively. Conclusion: The inter- and intraobserver agreement for visual detection of mild emphysema in low-dose multidetector computed tomography was good. Surprisingly, quantitative analysis could not reliably identify participants with mild emphysema, which hampers the use of automatic evaluation

Vital capacity and COPD: the Swedish CArdioPulmonary bioImage Study (SCAPIS)

Background: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value &amp;lt;0.7 or below the lower limit of normal (LLN). Forced vital capacity (FVC) is a proxy for VC. The first aim was to compare the use of FVC and VC, assessed as the highest value of FVC or slow vital capacity (SVC), when assessing the FEV1/VC ratio in a general population setting. The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC. Methods: Subjects (n=1,050) aged 50-64 years were investigated with FEV1, FVC, and SVC after bronchodilation. Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPDFVC was defined as FEV1/FVC &amp;lt;0.7, GOLDCOPD(VC) as FEV1/VC &amp;lt;0.7 using the maximum value of FVC or SVC, LLNCOPDFVC as FEV1/FVC below the LLN, and LLNCOPDVC as FEV1/VC below the LLN using the maximum value of FVC or SVC. Results: Prevalence of GOLDCOPD(FVC) was 10.0% (95% confidence interval [CI] 8.2-12.0) and the prevalence of LLNCOPDFVC was 9.5% (95% CI 7.8-11.4). When estimates were based on VC, the prevalence became higher; 16.4% (95% CI 14.3-18.9) and 15.6% (95% CI 13.5-17.9) for GOLDCOPD(VC) and LLNCOPDVC, respectively. The group of additional subjects classified as having COPD based on VC, had lower FEV1, more wheeze and higher residual volume compared to subjects without any COPD. Conclusion: The prevalence of COPD was significantly higher when the ratio FEV1/VC was calculated using the highest value of SVC or FVC compared with using FVC only. Subjects classified as having COPD when using the VC concept were more obstructive and with indications of air trapping. Hence, the use of only FVC when assessing airflow limitation may result in a considerable under diagnosis of subjects with mild COPD.Funding Agencies|Swedish Heart Lung Foundation; Knut and Alice Wallenberg Foundation; Swedish Research Council (VR); VINNOVA; Swedish Council for Working Life, Health, and Welfare (FORTE); Sahlgrenska Academy at the University of Gothenburg, Krefting Research Centre; ALF/LUA in western Sweden</p