Polymorphism of SERPINE2 gene is associated with pulmonary emphysema in consecutive autopsy cases

<p>Abstract</p> <p>Background</p> <p>The <it>SERPINA1</it>, <it>SERPINA3</it>, and <it>SERPINE2 </it>genes, which encode antiproteases, have been proposed to be susceptible genes for of chronic obstructive pulmonary disease (COPD) and related phenotypes. Whether they are associated with emphysema is not known.</p> <p>Methods</p> <p>Twelve previously reported single nucleotide polymorphisms (SNPs) in <it>SERPINA1 </it>(rs8004738, rs17751769, rs709932, rs11832, rs1303, rs28929474, and rs17580), <it>SERPINA3 </it>(rs4934, rs17473, and rs1800463), and <it>SERPINE2 </it>(rs840088 and rs975278) were genotyped in samples obtained from 1,335 consecutive autopsies of elderly Japanese people. The association between these SNPs and the severity of emphysema, as assessed using macroscopic scores, was determined.</p> <p>Results</p> <p>Emphysema of more than moderate degree was detected in 189 subjects (14.1%) and showed a significant gender difference (males, 20.5% and females, 7.0%; p < 0.0001). Among the 12 examined SNPs, only rs975278 in the <it>SERPINE2 </it>gene was positively associated with emphysema. Unlike the major alleles, homozygous minor alleles of rs975278 were associated with emphysema (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.02-2.30; p = 0.037) and the association was very prominent in smokers (OR = 2.02; 95% CI = 1.29-3.15; p = 0.002).</p> <p>Conclusions</p> <p><it>SERPINE2 </it>may be a risk factor for the development of emphysema and its association with emphysema may be stronger in smokers.</p

Emphysema Then and Now

The present definition or emphysema has three components: enlargement of airspaces. destruction or their walls and lack of fibrosis. Enlargement can be recognized by measuring the intcralvcolar wall distance or by comparing the airspaces under cnnsiJcration with adjacent or distant normal lung. Most recently. destruction has been defined as disappearance or disturbance or the orderly appearance or the pulmonary acinus (gas exchanging tissue). Other authors have also suggested that destruction can be recognized by abnonnal holes (fenestrae) in airspace walls or by the 'destructive index '. fibrosis appears to be an integral part of centrilobular. distal acinar and irregular airspace enlargement. The presence of fibrosis should not preclude emphysema by definition. Emphysema should be recognized by practicable methods and should be measured in some way. Evidence is presented that abnormal elastic properties of the lung are not due to emphysema but reside in the surrounding lung; the altered elastic properties may be due to alterations in the glycoprotein matrix of the lung. Altered elastic properties arc a relatively poor predictor of emphysema as gellerally defined and recognized. Computed tomography can recognize emphysema quite well, but appears to underestimate it and is not accurate in lungs with mild or no emphysema. Emphysema can be best diagnosed in life with an in tegrated approach using clinical data. radiological evidence of lung enlargement and the single breath diffusing capacity (transfer factor) for carbon monoxide. While knowledge of emphysema has dramatically increased in the past 30 years. much more remains to be done. and this requires new and more thorough approaches

Chronic airflow obstruction in lung disease

xiii+456hlm.;23c

The resistance of collateral channels in excised human lungs

We measured the resistance of collateral channels, R(col), in incomplete interlobar fissures in eight normal and eight emphysematous excised human lungs. Similar measurements were also made from the basal segments to the superior segment of the lower lobe in three normal and five emphysematous lungs. The lobe or segments were inflated through a bronchial cannula; air leaked through collateral channels and out of the other lobe or segment through a pneumotachograph which measured flow. Catheters inserted directly into the lung through the pleural surface on either side of the collateral channels measured the alveolar pressure difference producing collateral flow. R(col) is the ratio of this pressure difference to flow. By also measuring the inflating pressure and the airway pressure at the pneumotachograph, we calculated the lobar or segmental airway resistance, R(aw). In the normal lungs R(col) varied inversely with lung volume and was higher on inflation than on deflation. R(aw) was very small compared to R(col) which ranged from 260 to 3300 cm H(2)O/liter per sec when the distending pressure was 20 cm H(2)O. In the emphysematous lungs on the other hand, R(col) was markedly decreased and ranged from 5 to 20 cm H(2)O/liters per sec at the same distending pressure and was less than R(aw). We conclude that collateral channels are important ventilatory pathways in emphysema. When many units within a lung are ventilated by these pathways there may be disturbances of gas exchange and phase differences between normally and abnormally ventilated areas