Physiological and morphological determinants of maximal expiratory flow in chronic obstructive lung disease

Maximal expiratory flow in chronic obstructive pulmonary disease (COPD) could be reduced by three different mechanisms; loss of lung elastic recoil, decreased airway conductance upstream of flow-limiting segments; and increased collapsibility of airways. We hypothesized that decreased upstream conductance would be related to inflammation and thickening of the airway walls, increased collapsibility would be related to decreased airway cartilage volume, and decreased collapsibility to inflammation and thickening of the airway walls. Lung tissue was obtained from 72 patients with different degrees of COPD, who were operated upon for a solitary peripheral lung lesion. Maximal flow-static recoil (MFSR) plots to estimate upstream resistance and airway collapsibility were derived in 59 patients from preoperatively measured maximal expiratory flow-volume and pressure-volume curves. In 341 transversely cut airway sections, airway size, airway wall dimensions and inflammatory changes were measured. Airflow obstruction correlated with lung elastic recoil and the MFSR estimate of airway conductance but not to airway collapsibility or to the amount of airway cartilage. The upstream conductance decreased as the inner wall became thicker. Airway collapsibility did not correlate with the amount of airway cartilage, inflammation, or airway wall thickness. We conclude that the maximal flow-static recoil model does not adequately reflect the collapsibility of the flow-limiting segment

Estimation of lung growth using computed tomography

Anatomical studies suggest that normal lungs grow by rapid alveolar addition until about 2 yrs of age followed by a gradual increase in alveolar dimensions. The aim of this study was to examine the hypothesis that normal lung growth can be monitored by computed tomography (CT). Therefore, the gas volume per gram of lung tissue was estimated from measurements of lung density obtained from CT scans performed on children throughout the growth period. CT scans were performed on 17 males and 18 females, ranging in age from 15 days-17.6 yrs. CT-measured lung weight was correlated with predicted post mortem values and CT measured gas volume with predicted values of functional residual capacity. The median value for lung expansion was 1.86 mL x g(-1) at 15 days, decreased to 0.79 mL x g(-1) by 2 yrs and then increased steadily to 5.07 mL x g(-1) at 17 yrs. Computed tomography scans can be used to estimate lung weight, gas volume and expansion of normal lungs during the growth period. The increase in the lung expansion after the age of 2 yrs suggests progressive alveolar expansion with increasing lung volume

Respiratory system impedance with impulse oscillometry in healthy and COPD subjects: ECLIPSE baseline results

SummaryRationaleCurrent assessment of COPD relies extensively on the use of spirometry, an effort-dependent maneuver. Impulse oscillometry (IOS) is a non-volitional way to measure respiratory system mechanics, but its relationship to structural and functional measurements in large groups of patients with COPD is not clear.ObjectivesWe evaluated the ability of IOS to detect and stage COPD severity in the prospective ECLIPSE cohort of COPD patients defined spirometrically, and contrasted with smoking and non-smoking healthy subjects. Additionally, we assessed whether IOS relates to extent of CT-defined emphysema.MethodsWe measured lung impedance with IOS in healthy non-smokers (n = 233), healthy former smokers (n = 322) or patients with COPD (n = 2054) and related these parameters with spirometry and areas of low attenuation in lung CT.Measurements and main resultsIn healthy control subjects, IOS demonstrated good repeatability over 3 months. In the COPD group, respiratory system impedance was worse compared with controls as was frequency dependence of resistance, which related to GOLD stage. However, 29–86% of the COPD subjects had values that fell within the 90% confidence interval of several parameters of the healthy non-smokers. Although mean values for impedance parameters and CT indices worsened as GOLD severity increased, actual correlations between them were poor (r ≤ 0.16).ConclusionsIOS can be reliably used in large cohorts of subjects to assess respiratory system impedance. Cross-sectional data suggest that it may have limited usefulness in evaluating the degree of pathologic disease, whereas its role in assessing disease progression in COPD currently remains undefined

Quantifying the extent of emphysema: factors associated with radiologists' estimations and quantitative indices of emphysema severity using the ECLIPSE cohort

RATIONALE AND OBJECTIVES: This study investigated what factors radiologists take into account when estimating emphysema severity and assessed quantitative computed tomography (CT) measurements of low attenuation areas. MATERIALS AND METHODS: CT scans and spirometry were obtained on 1519 chronic obstructive pulmonary disease (COPD) subjects, 269 smoker controls, and 184 nonsmoker controls from the Evaluation of COPD Longitudinally to Indentify Surrogate Endpoints (ECLIPSE) study. CT scans were analyzed using the threshold technique (%<-950HU) and a low attenuation cluster analysis. Two radiologists scored emphysema severity (0 to 5 scale), described the predominant type and distribution of emphysema, and the presence of suspected small airways disease. RESULTS: The percent low attenuation area (%LAA) and visual scores of emphysema severity correlated well (r = 0.77, P < .001). %LAA, low attenuation cluster analysis, and absence of radiologist described gas trapping, distribution, and predominant type of emphysema were predictors of visual scores of emphysema severity (all P < .001). CT scans scored as showing regions of gas trapping had smaller lesions for a similar %LAA than those without (P < .001). CONCLUSIONS: Visual estimates of emphysema are not only determined by the extent of LAA, but also by lesion size, predominant type, and distribution of emphysema and presence/absence of areas of small airways disease. A computer analysis of low attenuation cluster size helps quantitative algorithms discriminate low attenuation areas from gas trapping, image noise, and emphysema

Estimation of cancer mortality associated with repetitive computed tomography scanning

Rationale: Low-dose radiation from computed tomography (CT) may increase the risk of certain cancers, especially in children. Objective: We sought to estimate the excess all-cause and cancerspecific mort

Genome-wide Association Study Identifies BICD1 as a Susceptibility Gene for Emphysema

Rationale: Chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. Pulmonary emphysema is a major but variable component of COPD; familial data suggest that different components of COPD, such as emphysema, may be influenced by specific genetic factors

Polymorphisms in the superoxide dismutase-3 gene are associated with emphysema in COPD

Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and previous studies have indicated a possible role of this gene in chronic obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the SOD3 gene would be associated with COPD and COPD-related phenotypes. We genotyped three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1), and rs1799895 (R213G)) in a case-control cohort, with severe COPD cases from the National Emphysema Treatment Trial (NETT, n = 389) and smoking controls from the Normative Aging Study (NAS, n = 472). We examined whether the single nucleotide polymorphisms (SNPs) were associated with COPD status, lung function variables, and quantitative computed tomography (CT) measurements of emphysema and airway wall thickness. Furthermore, we tried to replicate our initial findings in two family-based studies, the International COPD Genetics Network (ICGN, n = 3061) and the Boston Early-Onset COPD Study (EOCOPD, n = 949). In NETT COPD cases, the minor alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema (%LAA950) on chest CT scan (p = .029 and p = .0058). The association with E1 was replicated in the ICGN family study, where the minor allele was associated with more emphysema (p = .048). Airway wall thickness was positively associated with the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative CT data were not available in EOCOPD. The SNPs were not associated with lung function variables or COPD status in any of the populations. In conclusion, polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD susceptibility, highlighting the importance of phenotype definition in COPD genetics studies