Alpha-1-antitrypsin and the pathogenesis of emphysema

The review examines the relationship between alpha₁-antitrypsin (α ₁AT) and emphysema. Although other defects occur in subjects with alpha₁-antitrypsin deficiency, it seems likely that a reduction in inhibition due to loss of this inhibitor explains their emphysema. There is a great deal of controversy, however, concerning the role of alpha₁-antitrypsin in subjects without inherited deficiency. There is uncertainty about the presence and function of other elastase inhibitors in the peripheral lung. The function of lungα ₁AT and the presence of elastase activity are dependent upon the techniques used and this probably accounts for different results between research groups. In addition, other relevant factors such as which enzymes cause lung elastolysis, control of neutrophil chemotaxis, and mechanisms of elastin synthesis and repair are less well studied. The overall conclusion is that many aspects of the elastase/antielastase hypothesis of emphysema are poorly understood. Without further information the true role ofα ₁AT will remain largely speculative.     

Genetic variants of alpha-1-antitrypsin (AAT)

Abstract: This paper reviews the genetic variants of alpha-1-antitrypsin (AAT) which have been sequenced with special emphasis on the s.c. deficiency variants. These result in AAT low plasma levels via three main mechanisms: 1) intracellular storage; 2) intracellular degradation; 3) lack of synthesis. Intracellular storage occurs with the classical Z variant and with a few variants called M-like, because of their isoelectric focusing (IF) pattern. The storage phenomen causes liver damage and can be demonstrated at both light and electron microscopic level with the help of immuno-histochemistry. We report a new deficiency variant of AAT (M-Cagliari) characterized by very low plasma levels, massive storage of AAT and liver cirrhosis. By using immunohistochemical techniques and DNA analysis we could demonstrate that M-Cagliari has antigenic and genetic properties other than the Z AAT.     

戒烟对稳定期慢性阻塞性肺疾病的治疗作用

目的探讨戒烟对稳定期COPD的治疗作用。方法纳入2011年7月-2013年7月经福建医科大学附属泉州第一医院肺功能室检查确诊的稳定期COPD患者193例,按是否采用戒烟治疗及最终完成情况分为戒烟成功组、戒烟失败组及非戒烟组：戒烟成功亚组62例,均为男性,平均年龄为（60．82±5．63）岁,平均吸烟指数为（852±100）年·支;戒烟失败亚组36例,均为男性,平均年龄为（60．61±4．91）岁,平均吸烟指数为（812±139）年·支;非戒烟组95例,均为男性,平均年龄为（60．49±8．77）岁,平均吸烟指数为（833土143）年·支。采用FEV。为肺功能评价指标,CAT评分为COPD病情评价指标。进行为期半年的随访。结果各试验组患者在年龄、体质量指数及吸烟指数等方面差异无统计学意义。戒烟成功组患者治疗后体质量增加（2．85±1．27）kg,CAT评分下降（6．05±2．60）分,戒烟前后对比差异有统计学意义（t值分别为17．763、18．351,P值均d0．01）;FEV,增加（O．04±0．18）L,戒烟前后对比差异无统计学意义（t=1．900,P=0．062）。而戒烟失败组及未戒烟组治疗前后体质量、CAT评分及FEV,变化差异均无统计学意义（P值均〉0．05）。结论戒烟半年即对稳定期COPD具有=定的治疗作用,主要表现在体质量增加、临床症状减轻,而肺功能则无明显改善。     

COPD assessment tests scores are associated with exacerbated chronic obstructive pulmonary disease in Japanese patients

BackgroundGuidelines recommend chronic obstructive pulmonary disease (COPD) assessment tests (CATs) for evaluation of symptoms and management risks. To investigate whether CAT can predict moderate or severe exacerbations in Japanese COPD patients, a single-blinded prospective study was performed.MethodsA 123 Japanese COPD patients were classified into high-CAT (n=64) and low-CAT (n=59) groups. The frequencies and periods of moderate or severe exacerbation and hospitalization were compared between the two groups. Multivariate logistic regression analysis was performed to investigate whether CAT could predict exacerbations. A receiver operating characteristic (ROC) curve analysis was employed to find an appropriate CAT score for exacerbation.ResultsThe high-CAT group was significantly older, had a lower body mass index, and had a lower airflow obstruction as compared to the low CAT group. The frequency of moderate or severe exacerbation (1.3±1.3 events per patient per year, p<0.0001) and hospitalizations (0.2±0.4, p=0.0202) in the high-CAT group was significantly higher than in the low-CAT group (0.4±0.7 and 0.0±0.1, respectively). Multivariate logistic regression analysis showed that both high CAT score and low airflow obstruction were independently predictive of frequent moderate or severe COPD exacerbation. ROC analysis showed that the best cut-off CAT score for moderate or severe COPD exacerbation was 8 points.ConclusionOur present results indicate that COPD Japanese patients showing high CAT scores have a poor prognosis, and that the CAT score is able to predict exacerbation in Japanese COPD.     

Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantion

Background/Aim: Alpha-1-antitrypsin deficiency (α₁ATD) is the commonest metabolic disease leading to liver transplantation (LT) in children. Approximately 10–15% of the PiZZ population develops liver disease. Five percent of them will require LT within the first 4 years of life. This study aimed to investigate the prognosis of the liver disease associated with PiZZ α₁ATD in the era of liver transplantation and to determine predictors of outcome.Methods: We reviewed retrospectively the clinical notes of 97 consecutive patients referred from January 1989, when LT became routinely available in our Unit, to July 1998.Results: Of 26 (27%) patients who developed endstage liver disease, 24 have been transplanted and two are waiting for LT. Twenty-one (81%) of these patients presented with neonatal hepatitis at a median age of 2.1 months. Of 71 (73%) children who have not required LT, 61 (86%) presented with neonatal hepatitis at a median age of 1.6 months. Among infants with neonatal hepatitis who required LT, 18 out of 21 (86%) had jaundice for more than 6 weeks compared with 34 of 61 (56%) who survived without LT (p<0.01). Children requiring LT had higher aspartate aminotransferase (AST) at presentation (p<0.0001) and both higher AST and gamma-glutamyl transferase (GGT) at 6 months (p<0.001), 1-year (p<0.0003) and 5-year (p0.01) follow up when compared to those who are well without LT. Furthermore, children who developed end-stage liver disease more frequently had severe bile duct reduplication (p<0.01), severe fibrosis (p<0.03) with bridging septa (p<0.02) and established cirrhosis (p<0.04) in the initial liver biopsy. Ninety-five of the 97 children (98%) are currently alive; two died after LT.Conclusions: The advent of liver transplantation has significantly improved the prognosis of liver disease associated with PiZZ α₁ATD. Duration of jaundice, severity of histological features and biochemical abnormalities predict outcome at an early stage of the disease.     

Late manifestation of chronic liver disease in adults with alpha-1-antitrypsin deficiency

A review of 19 adult patients with alpha-1-antitrypsin deficiency (A₁AT deficiency) and chronic liver disease revealed a late onset of symptomatic hepatic abnormalities in this condition. Thirteen patients (68%) were 60 years or older when the liver disease was discovered. The mean age of the patients with the ZZ, SZ, and MZ phenotypes was 58, 66, and 72.5 years, respectively; this suggested a later onset of the liver disease in the heterozygotes. At the time of diagnosis, the hepatic condition usually was advanced; in eight patients (42%) the survival was less than two years. The most important associated condition was chronic obstructuve lung disease which was found in 10 patients (53%). We conclude that advanced age and the high incidence of obstructive lung disease make it unlikely that liver transplantation will become a common therapeutic option for adult patients with A₁AT deficiency and associated liver disease. Periodic screening of liver function may be indicated in patients with A₁AT deficiency so that chronic liver disease can be diagnosed early, particularly if current attempts to develop effective medical therapy for this condition are successful.     

COPD急发期患者血清尿酸水平的相关性研究

目的分析COPD患者急性期及缓解期血清中尿酸的水平,及其与肺功能、氧合指数的相关性。方法将47名COPD急性期患者分为A、B组（A组22名FEV1％〉50％,B组25名FEV1％〈50％）,C组为血氧正常的对照组。测量三组及COPD组治疗后血尿酸,血肌酐,肺功能FEV1％值、氧合指数。结果治疗前,COPD的A、B组血尿酸／肌酐值高于对照组（P〈0．01）,而A、B组间无明显差异（P〉0．05）,A、B、C三组间FEV1值及氧合指数有明显差异（P〈0．01）。治疗后A组尿酸水平明显下降（P〈0．05）,而B组变化不明显（P〉0．05）。二者间有明显差异（P〈0．05）。治疗后A组肺功能FEV1％明显改善（P〈0．05）,B组改善不明显（P〉0．05）。二者间有明显差异（P〈0．01）。治疗后A、B组氧合指数明显改善（P〈0．01）。COPD患者UA／Crea值与FEV1值及氧合指数无明显相关（分别r=0．096及r=0．137,P〉0．05）。但治疗前后UA／Crea值变化与FEV1变化呈明显负相关（r=0．258,P〈0．05）。结论COPD急发期患者血清UA／Crea水平是增高的,随病情缓解而下降,其变化与肺功能相关,而与血氧合不相关。可作为病情监测的指标之一。     

COPD患者伴发抑郁障碍及其相关因素的研究

目的了解慢性阻塞性肺病（chronic obstructive pulmonary disease,COPD）患者伴发抑郁障碍的情况,并分析其可能的影响因素。方法运用ZUNG抑郁自评量表对87例COPD患者伴发抑郁障碍的情况进行调查,依据患者的年龄、性别、文化程度、付费方式、患病时间及住院次数等因素进行分组研究,应用SPSS10．0统计软件进行数据的统计学检验。结果48．2％的COPD住院患者合并有不同程度的抑郁障碍。其中女性患者、大学或大学以上文化程度的患者、小学文化程度和文盲患者、自费患者伴发抑郁障碍的比例较高;而住院次数及年龄则不影响合并抑郁障碍的情况。结论COPD住院患者伴发抑郁障碍的比例较高,性别、文化程度、付费方式等是其主要影响因素。     

缺氧诱导因子1α在慢阻肺中的表达及肺血管重构的关系

目的通过检测缺氧诱导因子1α(HIF-1α)及肺血管重构相关指标在慢性阻塞性肺病(简称慢阻肺)中的表达,分析HIF-1α与慢阻肺及肺血管重构的关系。方法建立大鼠慢阻肺模型作为实验组,对照组选取健康大鼠,采集大鼠静脉血,取肺组织,检测两组气道阻力、平均肺动脉压、肺血管重构相关指标WA%、WV%、血液及组织中HIF-1α的表达。结果与对照组比较,实验组气道阻力、平均肺动脉压(m PAP)较对照组明显增加,差异有统计学意义(P0.05);实验组肺血管重构相关指标WT%、WA%明显增高,差异有统计学意义(P0.05);实验组HIF-1α水平明显升高,差异有统计学意义(P0.05);实验组肺组织中HIF-1α表达阳性率高达80%,差异有统计学意义(P0.05)。结论慢阻肺病程中,气道阻力、平均肺动脉压增加,肺血管重构相关指标WT%、WA%明显增高,血液及肺组织中HIF-1α的表达水平均升高,表明HIF-1α可能参与了慢阻肺的发生过程,并与肺血管重构密切相关。     

Autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD)

It has been recognized that chronic obstructive pulmonary disease (COPD) is a systemic disease which has been shown to negatively affect the cardiovascular and autonomic nerve system. The complexity of the physiologic basis by which autonomic dysfunction occurs in patients with COPD is considerable and the knowledge in this field remains elementary. The purpose of this review is to provide an overview of important potential mechanisms which might affect the autonomic nervous system in patients with COPD. This review aims to summarize the basic research in the field of autonomic dysfunction in patients with COPD. In COPD patients the activity of sympathetic nerves may be affected by recurrent hypoxemia, hypercapnia, increased intrathoracic pressure swings due to airway obstruction, increased respiratory effort, systemic inflammation and the use of betasympathomimetics. Furthermore, experimental findings suggest that autonomic dysfunction characterized by a predominance of sympathetic activity can significantly modulate further inflammatory reactions. The exact relationship between autonomic dysfunction and health status in COPD remains to be elucidated. Treatment aimed to restore the sympathovagal balance towards a reduction of resting sympathetic activity may modulate the inflammatory state, and possibly contributes to improved health status in COPD.     

血清尿酸与AECOPD相关性分析

目的 探讨血清尿酸(UA)与COPD急性加重期(AECOPD)的关系及与COPD严重度关系,并探讨其临床意义.方法 AECOPD组80例.根据AECOPD患者治疗后肺功能分为COPD Ⅰ级组(n=10),COPDⅡ级组(n=15),COPDⅢ级组(n=29),COPDⅣ级组(n=26).健康老年组75例为对照组,分别监测血清尿酸,并计算高尿酸血症(HUA)检出率.结果 AECOPD组血尿酸显著高于健康老年对照组,两组比较差异有统计学意义,(P＜0.05).COPD分级越重,其血清尿酸水平及高尿酸血症检出率越高,差异有统计学意义(P＜0.05).结论 AECOPD组血尿酸水平与HUA检出率均高于健康老年对照组,且血清尿酸水平及高尿酸血症检出率与COPD严重程度呈正相关,可作为病情监测的指标之一.     

Pain and quality of life with chronic obstructive pulmonary disease

Background

Pain as a symptom may be underrecognized in patients with chronic obstructive pulmonary disease (COPD).

Objective

The aim of this study is to explore the prevalence and intensity of pain, its location, how demographic and clinical variables may be related to pain, and how pain is associated with quality of life (QOL).

Methods

In this cross-sectional study, 154 patients with COPD answered the Brief Pain Inventory, Respiratory Quality of Life Questionnaire, and Quality of Life Scale, and performed spirometry.

Results

Seventy-two percent of the patients indicated the location of pain on a body diagram. Lower lung function, higher score of pain intensity, and pain interference were associated with lower disease QOL. A higher score of pain interference was associated with lower global QOL. When controlling for disease QOL in the equation of global QOL, pain interference was no longer significant.

Conclusion

The experience of pain is related to disease QOL in patients with COPD.     

肺移植对5例慢性阻塞性肺疾病患者肺功能的影响

目的研究单肺移植手术治疗慢性阻塞性肺疾病(COPD)对呼吸生理及肺功能的影响。方法5例患者均为Ⅳ级COPD男性患者,年龄51～63岁。术前2周测定患者用力肺活量(FVC)、第一秒用力呼气容积(FEV1)、FEV1/FVC、最大通气量(MVV)、残气容积(RV)、肺总量(TLC)、残总比(RV/TLC)、深吸气量(IC)、胸腔气体容积(TGV)、呼气峰流量(PEF)、总气道阻力(Rawtotal)、肺一氧化碳弥散量(DLCO)、每升肺泡容积肺一氧化碳弥散量(DLCO/V·A)、6分钟行走距离(6MWD)、动脉血氧分压(PaO2)、肺泡气动脉血氧分压差[P(Aa)O2]、动脉血氧饱和度(SaO2)、动脉血二氧化碳分压(PaCO2)及平均肺动脉压(mPAP)等参数。术后2个月再行上述测定。结果5例患者术前2周、术后2个月检测的参数为MVV(23.6±5.8)、(71.6±21.8)L,FEV1(0.68±0.21)、(1.85±0.46)L,FEV1/FVC(37.4±8.3)、(75.6±13.9)%,PaO2(60.0±9.1)、(86.2±2.9)mmHg(1mmHg=0.133kPa),SaO2(90.0±4.6)%、(96.8±0.5)%及mPAP(31.2±5.5)、(16.6±1.8)mmHg,均有显著改善(P均<0.05);3例患者IC[(1.16±0.26)、(1.83±0.35)L]、TGV[(6.52±0.27)、(4.52±0.29)L]、RV[(5.12±0.39)、(3.20±0.32)L]、RV/TLC[(71.0±5.6)、(51.3±2.5)%]及Rawtotal[(6.62±0.99)、(2.48±0.87)cmH2O·L-1·s-1]改善显著(P均<0.05);4例患者PEF[(1.65±0.40)、(3.92±1.63)L/s]、DLCO[(8.5±3.0)、(21.0±6.2)ml·min-1·mmHg-1]及6MWD[(46.8±14.7)、(246.8±51.9)m]也显著增加(P均<0.05);FVC[(1.85±0.40)、(2.45±0.49)L]、TLC[(7.19±0.15)、(6.26±0.73)L]、DLCO/V·A[(2.90±1.50)、(5.41±0.87)L·min-1·mmHg-1]、P(Aa)O2[(37.6±16.3)、(17.8±6.3)mmHg]及PaCO2[(44.6±7.7)、(37.4±3.4)mmHg]有所改善,但差异无统计学意义(P均>0.05)。结论COPD患者肺移植术后肺通气、气道阻力、残气、弥散、运动耐力及气体交换功能均明显改善。     

Protease inhibitor phenotypes and serum alpha-1-antitrypsin levels in patients with COPD: a study from Hong Kong

OBJECTIVE: Many studies have suggested that an imbalance of protease activation and inhibition might result in COPD with emphysema. Levels of alpha-1-antitrypsin (alpha1-AT), the key protease inhibitor, are genetically determined by alleles that present in many phenotypes/subtypes, some of which are associated with deficiency of the protein. We prospectively evaluated the prevalence of the protease inhibitor (Pi) alleles and phenotypes together with the serum alpha1-AT levels in Chinese patients with COPD. METHODOLOGY: The study population comprised 356 patients with COPD. The male-to-female ratio was 4 : 1 with a mean age of 72.4 years (range 44-93 years). Isoelectric focusing was used for Pi phenotyping/subtyping. The frequencies of Pi alleles and phenotypes were compared with the frequencies in 1085 healthy unrelated Chinese control subjects. The serum alpha1-AT levels were measured by the Cobas Fara assay. RESULTS: PiZ was not detected. No significant difference in distribution of PiM phenotypes/subtypes between patients with COPD and healthy controls was observed, except for M1M3 and M2M3. There was also a significant difference in the proportion of variant S and F alleles between the disease group and the control population. CONCLUSION: The low prevalence of deficiency Pi phenotypes/subtypes suggests a lack of contribution of alpha1-AT deficiency to the pathogenesis of COPD in Chinese patients. The strategy of launching an alpha1-AT deficiency detection program among COPD patients, based on the recommendation of the World Health Organization, may not be readily applicable in our local setting.