The Effect of Chronic Sputum Production on Respiratory Symptoms in Severe COPD

Background: Chronic sputum production is a significant but variable complaint in COPD; its effect on symptom burden has not been comprehensively described. We sought to characterize the daily burden of chronic sputum production in severe COPD and the phenotype of those with chronic sputum symptoms. Methods: We studied 50 outpatients with severe COPD who used an electronic diary to document peak expiratory flow (PEF) and respiratory symptoms daily for up to 2 years. A sputum index was derived based on complaints of sputum quantity, color, and consistency, and patients were divided into groups based on average daily sputum index (Low, Medium, High). The presence and severity of respiratory symptoms were scored by a novel method using daily changes in symptoms and PEF from baseline and were categorized into mild, moderate, and severe. Percent emphysema was measured using quantitative CT. Results: In the 14,500 observation days, severe symptom days were greater in the Medium and High groups (379/6089, 1609/4091, and 2624/4317 observation days in Low, Medium, and High, p < 0.0001). The same trend was found even when sputum complaints were removed from the symptom severity score. Observed/predicted PEF ratio was lower in the High group (0.56 ± 0.24, 0.55 ± 0.19, and 0.42 ± 0.12 in each group, p < 0.05 for High compared to Medium and Low). Percent emphysema inversely correlated with average sputum index and quantity (r = ?0.449 and r = ?0.584, respectively, p < 0.05). Conclusions: Increased sputum production in severe COPD is frequently encountered daily and is associated with more respiratory symptoms, worse airflow obstruction, and less emphysema.     

Polymorphisms in the Superoxide Dismutase-3 Gene Are Associated with Emphysema in COPD

ABSTRACT

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.     

Different Modulation of Decorin Production by Lung Fibroblasts from Patients with Mild and Severe Emphysema

We have previously reported diminished immunohistochemical staining of decorin in lung tissue from patients with severe emphysema. The aim of this study is to investigate whether this diminished staining is due to a quantitative abnormal production of decorin by pulmonary fibroblasts in vitro. Therefore, we measured decorin (Western blot), collagen type I (ELISA), and fibronectin (ELISA) production by fibroblasts obtained from lung tissue of patients with severe and mild emphysema at basal culture conditions and after modulation with transforming growth factor-β₁, basic fibroblast growth factor, and interferon-γ. Decorin production at basal culture conditions was significantly higher in fibroblast cultures from patients with severe emphysema compared to fibroblasts from mild emphysema. After stimulation with transforming growth factor-β₁ and basic fibroblast growth factor, decorin production was significantly more reduced in fibroblast cultures from patients with severe emphysema whereas collagen type I and fibronectin production were not affected. We conclude that decorin production by lung fibroblasts of patients with severe emphysema is dysregulated after modulation with cytokines known to be important in smoking associated inflammation. This dysregulation of decorin production may contribute to the impaired lung tissue repair, present in patients with emphysema, since these alterations in the extracellular matrix may cause diminished cytokine binding and neutralization.     

Long-term Variability of Desmosine/Isodesmosine as Biomarker in Alpha-1-antritrypsin Deficiency–related COPD

Desmosine and isodesmosine are products of elastin breakdown which are candidate biomarkers to measure lung destruction in COPD. Data exist on the burden of desmosines in urine and plasma in COPD but long-term changes have never been investigated. We determined the changes of desmosine levels over 14 months in urine and plasma of patients with type ZZ alpha-1-antitryspsin deficiency-related COPD. Urines and plasma for determination of desmosines were collected from 11 ex-smokers with moderate/severe emphysema at monthly intervals for 14 months. Spirometry and gas transfer were assessed at baseline and 6-month intervals. At baseline and month 14, eleven healthy partners of patients volunteered to give a blood sample for detection of desmosines. Desmosines were determined by capillary electrophoresis combined with laser-induced fluorescence. Urine and plasma desmosines were significantly increased after 14 months in patients (p = 0.027 and p = 0.0005, respectively). Plasma desmosines of healthy partners at baseline were 4-fold lower than from patients and not significantly different from values at month 14. Only a significant decline in lung gas transfer occurred in patients (p = 0.015). The variability of desmosines was higher in urine than in plasma (coefficient of variation 0.17 and 0.087, respectively). As longitudinal desmosine changes likely reflect the elevated elastic fiber turnover associated with the progression of lung damage and destruction in COPD, they appear to be a suitable marker for application in long-term studies. Plasma desmosines were more stable long-term biomarkers than desmosines in urine.     

Physiologic Correlates of Sleep Quality in Severe Emphysema

Background: Sleep quality is poor in severe emphysema. We hypothesized that in addition to nocturnal oxygen desaturation, the severity of airflow obstruction and degree of thoracic hyperinflation are responsible. Methods: Twenty-five patients (14 males, 64 ± 6 [ ± SD] yrs, BMI 24.7 ± 4.2 kg/m²) with severe emphysema (FEV₁ = 28 ± 8% predicted, TLC = 125 ± 14% predicted) were studied. Measurements included spirometry, lung volumes, arterial blood gas, length of the diaphragm's zone of apposition (LZAP) and a polysomnogram. Results: Total sleep time (TST) was 227 ± 93 minutes with a sleep efficiency (SE) of 56 ± 21%. The mean SaO₂, lowest SaO₂, and% TST with a SaO₂ < 90% were 90 ± 5%, 83 ± 8% and 29 ± 40%, respectively. TST correlated with FEV₁% (r = 0.5, p = 0.02), FVC% (r = 0.4, p = 0.03) and LZAP (r = 0.5, p = 0.01). SE correlated with FEV₁% (r = 0.5, p = 0.02) and LZAP (r = 0.5, p = 0.01), but not with FVC% (r = 0.4, p = 0.07). Additionally, TST and SE correlated negatively with residual volume% (r = -0.4, p = 0.046, and r = -0.4, p = 0.03, respectively). There was no correlation between TST and SE and measures of nocturnal oxygenation. Multiple linear regression was used to predict TST, with 50% (r² = 0.49) explained by a combination of LZAP (27%), mean SaO₂ (23%), and the lowest SaO₂ (< 1%). To predict SE, 44% (r² = 0.43) was explained by a combination of LZAP (29%), mean SaO₂ (14%), and the lowest SaO₂ (1%). Conclusion: Although parameters of respiratory function and mechanics correlate with sleep quality, both nocturnal oxygenation and measurements of respiratory function/mechanics predict sleep quality in severe emphysema.     

Longitudinal study of the radiology of coal workers' pneumoconiosis

Summary In fifteen hundred sixty-one radiographs from 318 coal workers with different grades of pneumoconiosis, the prevalence of perinodular, perinodal, and generalized emphysema has been examined. Furthermore, the prevalence of enlarged hili was determined. These data have been correlated with age and the type, number and density of small pneumoconiotic opacities and with the size and localization of large pneumoconiotic opacities.Some form of emphysema was found in 86.7% of all radiographs, most frequently in the form of generalized emphysema (63.6%). The prevalence increases with severity of pneumoconiosis. The same holds for enlarged hili.With support of the European Communities, Luxembourg     

木瓜蛋白酶及胰蛋白酶所致大鼠肺气肿模型的差异及对比

目的研究木瓜蛋白酶及胰蛋白酶所致大鼠肺气肿模型的差异。方法采用猪胰蛋白酶和木瓜蛋白酶气管内滴注的方法,将体质量170～220 g的60只SPF级SD大鼠随机分为正常对照组(A组),猪胰蛋白酶组（B组）,木瓜蛋白酶组（C组）,各20只,B组、C组气管内分别滴入猪胰蛋白酶1 U/g、5％木瓜蛋白酶0.001 ml/kg造模...     

α1-抗胰蛋白酶缺乏症1例并文献复习

报道1例以黄疸为表现的α1-抗胰蛋白酶缺乏症病例,该例患者初始起病以黄疸为表现,病程10年,通过肝活检组织病理确诊。结合文献对α1-抗胰蛋白酶缺乏症的流行病学现状、病因机制、临床表现及治疗预后加以复习,藉此对临床遗传性肝病的诊治提供参考。     

Potential effects of peroxisome proliferator-activated receptor activator on LPS-induced lung injury in rats

Multiple factors contribute to the pathogenesis and prognosis of chronic obstructive pulmonary disease (COPD), still requiring new therapeutic strategies and medications for the disease. The aim of the present study is to investigate the model of lipopolysaccharide (LPS)-induced chronic lung injury and hyperinflation and test therapeutic effects of peroxisome proliferator-activated receptor (PPAR)-γ agonist. Wister rats were challenged with intra-tracheal instillation of LPS at concentrations of 0.006, 0.060, 0.600, and 6.000 mg/ml per kg, twice a week, for 1, 2, 4 and 6 weeks. PPAR activator, 15-deoxy-Δ^12,14-prostaglandin J2 (15D-PGJ2), or vehicle (PBS) was administered orally and daily at the dose of 1 and 10 mg/ml per kg in animals challenged with LPS or PBS at the dose of 0.060 mg/ml per kg body weight twice a week for 4 weeks. We found that intra-tracheal exposure of LPS resulted in a dose-dependent pattern of chronic lung hyperinflation and hypertrophy, increased alveolar enlargement, reduced vascular endothelial growth factor (VEGF) and elevated tissue inhibitor of metalloproteinases (TIMP)-1 levels in bronchoalveolar lavage (BAL) fluid, and early changes of leukocyte influx and interferon (IFN)-γ levels in bronchoalveolar lavage (BAL) fluid. PPAR-γ agonist ameliorated these changes related with the dose used. LPS-induced lung disease model shows some similarities with human disease, and PPAR-γ agonist may be an alternative for COPD therapy.     

经支气管镜肺减容术研究进展

肺减容术是治疗晚期肺气肿的选择之一,外科肺减容术由于其并发症、病死率及治疗费用等限制其发展.但促进了经支气管镜肺减容术的发展.目前包括经支气管镜旁路通气法肺减容术,经支气管镜生物学肺减容术,经支气管镜单向活瓣放置肺减容术,其微创、简便、痛苦及其并发症少等特点展现了其巨大的临床应用前景.