Increases in the low attenuation areas (LAA) of chest x-ray computed tomography images in patients with chronic obstructive pulmonary disease (COPD) have been reported to ref lect the development of pathological emphysema. We examined the statistical properties of LAA clusters in COPD patients and in healthy subjects. In COPD patients, the percentage of the lung field occupied by LAAs (LAA%) ranged from 2.6 to 67.6. In contrast, LAA% was always <30% in healthy subjects. The cumulative size distribution of the LAA clusters followed a power law characterized by an exponent D. We show that D is a measure of the complexity of the terminal airspace geometry. The COPD patients with normal LAA% had significantly smaller D values than the healthy subjects, and the D values did not correlate with pulmonary function tests except for the diffusing capacity of the lung. We interpret these results by using a large elastic spring network model and find that the neighboring smaller LAA clusters tend to coalesce and form larger clusters as the weak elastic fibers separating them break under tension. This process leaves LAA% unchanged whereas it decreases the number of small clusters and increases the number of large clusters, which results in a reduction in D similar to that observed in early emphysema patients. These findings suggest that D is a sensitive and powerful parameter for the detection of the terminal airspace enlargement that occurs in early emphysema.High-resolution computed tomography (CT) is a sensitive and noninvasive tool for assessing alterations in lung structure induced by various disease processes. Increases in the low attenuation areas (LAA) in the lung regions of chest x-ray CT images in patients with chronic obstructive pulmonary disease (COPD) have been reported to reflect the development of pathological emphysema (1-4). Nevertheless, previous methods of analyzing lung CT images are limited for general clinical diagnostic purposes (5) because the size and spatial distribution of LAAs are not taken into account. Recently, Uppaluri et al. (6) found that a texture-based adaptive multiple feature method could differentiate between normal and emphysematous tissue with 100% accuracy. However, it is not clear whether this method would detect early emphysema. More recently, Shimizu et al. (7) proposed a promising fractal analysis method for assessing ground-glass opacities in lung CT images. Their approach was able to successfully differentiate between fibrotic and nonfibrotic disease processes.The concept of fractal geometry was developed by Mandelbrot (8) to quantitatively describe the random variations in size and shape seen in natural objects. A fractal object is said to be scale-free because its characteristics are invariant under isotropic scale transformations. Such scale-invariance can be achieved if the object is formed by parts that are similar to the whole. In other words, fractals are self-similar and hence are characterized by power law functions (the only mathematical functions obeying s...

Background: Chronic obstructive pulmonary disease (COPD) is characterised by the presence of airflow limitation caused by loss of lung elasticity and/or airway narrowing. The pathological hallmark of loss of lung elasticity is emphysema, and airway wall remodelling contributes to the airway narrowing. Using CT, these lesions can be assessed by measuring low attenuation areas (LAA) and airway wall thickness/luminal area, respectively. As previously reported, COPD can be divided into airway dominant, emphysema dominant and mixed phenotypes using CT. In this study, it is postulated that a patient's physique may be associated with the relative contribution of these lesions to airflow obstruction. Methods: CT was used to evaluate emphysema and airway dimensions in 201 patients with COPD. Emphysema was evaluated using percentage of LAA voxels (LAA%) and airway lesion was estimated by percentage wall area (WA%). Patients were divided into four phenotypes using LAA% and WA%. Results: Body mass index (BMI) was significantly lower in the higher LAA% phenotype (ie, emphysema dominant and mixed phenotypes). BMI correlated with LAA% (r = 20.557, p,0.0001) but not with WA%. BMI was significantly lower in the emphysema dominant phenotype than in the airway dominant phenotype, while there was no difference in forced expiratory volume in 1 s %predicted between the two. Conclusion: A low BMI is associated with the presence of emphysema, but not with airway wall thickening, in male smokers who have COPD. These results support the concept of different COPD phenotypes and suggest that there may be different systemic manifestations of these phenotypes.Chronic obstructive pulmonary disease (COPD) is characterised by the presence of airflow limitation caused by loss of lung elastic recoil and/or airway narrowing.1 Emphysema is the pathological lesion that correlates most closely with loss of lung elastic recoil, 2 while the airway component is characterised by thickening and narrowing of membranous bronchioles. 3 We have previously reported that the relative contributions of these processes to airflow obstruction in individual patients with COPD can be assessed by measuring low attenuation area (LAA) and airway wall thickness/luminal area using CT.4 5 Dividing patients with COPD into airway dominant, emphysema dominant and mixed phenotypes may aid in the study of the pathogenesis, in the assessment of pharmacological interventions and ultimately in the choice of patient specific therapy. 6 There is increasing evidence that COPD is a systemic illness 7 8 and low body weight is a prominent systemic manifestation. The cachexia associated with COPD was traditionally believed to be more prevalent among those whose airflow limitation was due to predominant emphysema and those who had a relatively maintained ventilatory drive (the ''pink puffer'' hypothesis). 9The ability to make quantitative estimates of the degree of emphysema in individual patients allows a test of the longstanding hypothesis that emphysema predominant patients...

Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1؊/؊ mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be antifibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1 ؊/؊ mice com- Abnormal accumulation of fibrin occurs within the interstitium and alveolar spaces of the lung in a variety of pulmonary diseases in which the integrity of the capillary alveolar barrier is damaged.

No abstract