Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Mona BafadhelSusan McKennaSarah TerryVijay MistryCarlene ReidPranabashis HaldarMargaret McCormickKoirobi HaldarTatiana KebadzeAnnelyse DuvoixKerstin LindbladHemu PatelPaul RugmanP M DodsonMartin JenkinsMichael D. SaundersPaul NewboldRuth H. GreenPer VengeDavid A. LomasMichael R. BarerSebastian L. JohnstonIan PavordChristopher E. Brightling
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Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology.Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation.Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated.A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed “pauciinflammatory.” Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1β, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83–0.95); serum CXCL10, 0.83 (95% CI, 0.70–0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78–0.93), respectively.The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1β, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.现在，医药社区应该很好知道长期的妨碍的肺的疾病(COPD ) 的重要性，有高病态和死亡的一个逐渐地普通的条件。在现代条款， COPD 来了意味着并发的长期的支气管炎，气喘的支气管炎和肺气肿。香烟吸烟长作为占优势的病因论的代理人被认出了。动脉的 hypoxaemia， COPD 的经常的复杂并发症，能导致肺的高血压和英国管 pulmonale。COPD 影响超过 5% 成年人口并且是其病态和死亡在几个国家正在增加的死亡的唯一的主要原因。在中国，确定是困难的多少人与 COPD 被影响。然而，最近的流行病学的调查显示那 COPD 流行在中国是 8.2% 。在男人的 COPD 流行比在女人显著地高(12.4% cf 5.1%) 。在农村区域的流行在城市的区域(8.8%cf7.8%) 比那高。有 COPD 的病人， 61.5% 是吸烟者。报告也声明 COPD 是在在中国和在城市的区域的死亡的第四个领先的原因的农村区域的死亡的主要原因，升起到在 2020 的死亡的第三个领先的原因。疾病的流行与年龄增加，最高的率在超过 70 年岁的人看。COPD 是有升起的发生和世界范围的流行的死亡的唯一的主要原因，显示它一逐渐地使人烦恼的。
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Background/aim: Respiratory and peripheral muscle strength are reduced in chronic obstructive pulmonary disease (COPD). There is a well-known correlation between handgrip strength (HGS) and strenght extremity muscles. Our aim in this study was to measure HGS and investigate the related factors in COPD patients with exacerbation.Materials and methods: Subjects with COPD exacerbation (n = 101) and stable COPD (n = 22), and subjects without COPD (n = 201), were enrolled in this study. Age, sex, and body mass index were similar. HGS was measured using a Vigorimeter. Pulmonary function tests and 6-min walk tests were performed.Results: The mean HGS was significantly lower in subjects with COPD exacerbation than those with stable COPD and subjects without COPD. The mean HGS was similar between stable COPD and non-COPD subjects. The mean 6-min walk distance (6MWD) was significantly lower in subjects with COPD exacerbation than stable COPD. There was a significant correlation between HGS and 6MWD but no correlation between HGS and pulmonary function tests.Conclusion: In subjects with COPD exacerbation, the HGS was lower than that of stable COPD patients, and this difference was not explained by age, comorbidities, severity of obstruction, or smoking. Physical inactivity and steroid use during exacerbation might be possible factors affecting HGS. HGS was moderately correlated with 6MWD in cases of exacerbation. It may be used as a measure of muscle performance in COPD exacerbation, especially when the 6-min walk test cannot be performed
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The use of sputum eosinophil count in asthma clinics is rapidly expanding as it has been reported as being a useful indicator of the worsening of asthma symptoms and that its normalisation reduces asthma exacerbations and admissions. Without additional steroids, levels of sputum eosinophils have been shown to be highly variable in severe asthmatic patients. Furthermore, precise patient phenotyping is increasingly becoming important as our understanding of the physiopathology of severe asthma widens. We introduced sputum differential cell counting in our severe asthma clinic, with a view to first reducing sputum eosinophils below 3% by augmenting anti-inflammatory therapy, and attempting steroid withdrawal once patients became sputum eosinophil negative (E−). To date, 264 patients have been investigated for sputum eosinophils, using induction with nebulised sodium chloride if necessary and suitable. This paper presents our yearly update of the anti-inflammatory (steroid) therapy of the first successive patients with at least two successful sputum counts (current n=71), specifically investigating patients’ management in the light of their positive sputum eosinophil levels at baseline assessment. Twenty patients were sputum eosinophil positive (E+) on their initial visit and 25 had reduced eosinophil levels (p=0.001) on a subsequent visit, including 14 becoming E−. Nineteen were offered a trial of steroid augmentation: 11 patients with a trial of IM triamcinolone (all patients had subsequent reduced eosinophils levels, 9 becoming E−, p=0.003); 5 patients with increased oral prednisolone treatment (four patients with reduced eosinophils levels, one becoming E−); 3 with increased inhaled steroid therapy (all with reduced eosinophil levels, 1 becoming E−). 66% of patients with uncontrolled sputum eosinophilia were treated with an increase in anti-inflammatory maintenance therapy. Sputum eosinophil levels decreased for 95% of these as already reported, but only 11/19 achieved full control of sputum eosinophilia with 2/11 failing to normalise eosinophils despite IM triamcinolone (representing a population of confirmed steroid resistance. Sputum eosinophil negativity used as a surrogate marker for asthma control has been shown to be an essential tool in identification and management of patients with asthma at risk of deterioration and admission.
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瞄准：为了调查手术后的肺的复杂并发症(POPC ) 的各种各样的类型的发生并且评估起作用的仙子的意义，在有食道的癌症的病人的动脉的血气体在食管切除术以后与长期的妨碍的肺的疾病(COPD ) 伴随了。方法：358 个病人被划分成 POPC 组和 COPD 组。我们为食道的癌症在食管切除术以后执行了 358 个连续病人的回顾的评论与或没有 COPD 在手术后的肺的复杂并发症上估计 COPD 的可能的影响。我们在 1 s (FEV1 ) 根据预言百分比的强迫的吐气的体积分类 COPD 进四个等级并且在四个等级之中分析了复杂并发症的发生率。Perioperative 动脉的血气体在 COPD 组并且与 POPC 组相比在病人被测试与或没有肺的复杂并发症。结果：有 COPD 的病人(29/86， 33.7%) 没有 COPD，比那些有更肺的复杂并发症(36/272， 13.2%)(P 或 =80% 预言) COPD (P < 0.05 ) 。PaO (2 ) 被减少， PaCO (2 ) 在第一个手术后的星期内在 COPD 组与肺的复杂并发症在病人被增加。结论：COPD 的标准是为在经历食管切除术的食道的癌症病人的肺的复杂并发症的批评预言者。COPD 的严厉影响肺的复杂并发症的发生率，并且预言百分比的 FEV1 是为在有 COPD 的病人的肺的复杂并发症的一个好预兆的变量。动脉的血气体在指导起作用的仙子是有用的管理。
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서론: 만성폐쇄성폐질환(chronic obstructive pulmonary disease, COPD)는 최근 사망률과 유병률이 증가하는 만성적인 질환이다. 국내에서의 유병률은 간헐적으로 보고되고 있지만, 수년간에 걸친 COPD 유병률의 변화와 그리고 COPD 위험인자의 변화에 관한 연구는 없었다. 이 연구는 국민건강영양조사 자료를 이용하여 8년 간의 COPD 빈도와 위험인자의 변화에 관해 알아보고자 하였다. 방법: 2007년부터 2014년 간의 국민건강영양조사 원시자료를 이용하였으며, 이중 나이 40세 이상이면서 폐기능 검사를 시행한 총 24,500명 (남자 43.8%, 여자 56.2%)의 자료를 분석하였다. COPD의 진단은 FEV1/FVC 비가 0.7 미만인 경우로 하였다. COPD 위험인자의 분석에는 거주 지역, 소득, 교육, 흡연, BMI, vitamin D를 이용하였다. 결과: COPD 빈도는 2007년도에 18.4%로 가장 높았으며, 이후 감소하는 추세를 보여 2009년에는 11.9% 였다. 2011년도부터 다시 증가하기 시작하여 2014년도 까지 COPD 빈도는 13.5%에서 15.4 % 였다. 여자와 남자 모두 비슷한 형태를 보였다. 다항 로지스틱 회귀 분석에서 2007년도부터 2014년 전체를 대상으로 하였을 때, COPD 위험인자는 저소득, 낮은 교육, 흡연, 낮은 BMI 와 혈중 vitamin D 였으며, 거주 지역은 위험인자가 아니었다. 년도별 분석에서도 저소득, 흡연, 낮은 BMI는 COPD의 위험인자였지만, 낮은 교육은 2009년도 이후부터는 COPD의 위험인자가 아니었다. Vitamin D는 년도에 따라 다른 결과를 보였다. 결론: 낮은 교육 수준은 COPD의 위험인자가 아니었다.
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Background: Blood eosinophil counts can help guide physicians treating patients with COPD and a history of exacerbations, and predict patients' response to ICS treatment. However, studies of eosinophil count as a predictor of future exacerbation risk are inconsistent. In a large patient dataset, we investigated whether blood eosinophil counts can be used as a biomarker for exacerbation rate. Methods: We pooled baseline eosinophil count data for patients with COPD in 16 studies from the tiotropium, olodaterol and tiotropium/olodaterol clinical trial programmes and the WISDOM ICS withdrawal study. Results: Overall, 24,103 patients had eosinophil data available. Median baseline eosinophil count was 170 cells/µL, 20% of patients had an eosinophil count >300 cells/µL and 46% had ≤150 cells/µL (Figure). Distribution of eosinophil counts was similar in patients with ≤1 exacerbation in the previous year (20% >300 cells/µL and 46% ≤150 cells/µL) and in patients with ≥2 exacerbations (21% >300 cells/µL and 46% ≤150 cells/µL), and it was not influenced by ICS use at baseline. The percentages of patients with >300 eosinophils/µL and ≥2 exacerbations were between 4% (without ICS at baseline) and 6% (with ICS at baseline). Conclusions: Although guidelines use blood eosinophil count to identify ICS-responsive patients, we did not find evidence that the blood eosinophil count showed a relationship with exacerbation history.
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To secure true causatives from the expectorated sputum in respiratory infectious diseases, a washing method of the sputum has been applied in this department of internal medicine. The purpose is to wash out the contaminants.In this paper, the author evaluated this method with basic experiments using 233 and 400 specimens obtained from treated and not yet treated respiratory patients with chemotherapy, respectively.The initial sputum was put in the saline solution in the plate, stirred and broken down into the fine fragments by platinum loop. Several fragments of these were transferred to the next plate and processed as same as above. This procedure was repeated several times. The last fragments were cultured. Nonprocessed sputum was also cultured at the same time in comparison.The results were studied regarding colony-counts, appearance of the sputum, the number of squamous cells, chronological aspects of sputum collecting, reproducibility of the tests. Long term observation was especially done on chronic respiratory patients.The results were summarized as follows:1) Mostly one species, infrequently two species, of “potential pathogens” remained by washing the purulent or mucopurulent sputum. No definite pathogen was obtained from mucous or mucoserous sputum by this method.2) Microscopically, squamous cells in the purulent or mucopurulent sputum were markedly decreased or disappeared by washing, suggesting the elimination of secretion from upper respiratory tract.3) Reproducible results were obtained from purulent and mucopurulent sputum. But this was not the case in mucous and mucoserous sputum.4) It was clear that sputum specimen collected in the morning was preferrable for the etiological test.5) In most cases in which causative pathogen could be estimated sputum was purulent or mucopurulent and squamous cells were markedly decreased by washing.6) Long term observations were done in patients with chronic respiratory infection by repeating this technique (method). It was speculated that in those patients one or two species of “potential pathogens” resided in the upper respiratory tract even during symptom free period and that exacerbation could take place by their invasion down to lower respiratory tract.
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・GOLD (Global Initiative for Chronic Obstructive Lung Disease) は, EBM (evidence based medi-cine) に基づいて作成され, 2001年に公表されたCOPD (Chronic Obstructive Pulmonary Dis-ease) の治療と管理に関する国際的ガイドラインである。・COPDに関して, 定義, 危険因子, 診断, 管理計画, 薬物治療, 患者教育, 急性増悪の7つのキーポイントを指摘している。・従来の慢性気管支炎や肺気腫などの診断名は用いず, COPDという診断名で新しい定義を規定している。・COPD発症のもっとも重要な危険因子は喫煙である。・COPDの診断にスパイロメトリーが必須である。・COPDの病期分類は, 一秒量 (FEV1) の程度にしたがって重症度を軽症-最重症の4段階に分類しているが, 新たに呼吸機能は正常であるが呼吸器症状 (咳, 痰) がある群をstage 0として設定し, 早期診断と早期予防を重視している。・COPDの管理として, 疾患の評価とモニタリング, 危険因子の縮小, 安定期COPDの管理, 急性増悪の管理の4つの要素を指摘している.・治療は, 全ての病期で, 危険因子の回避 (特に禁煙) とインフルエンザワクチンの接種を推奨している。・薬物治療と非薬物治療に関して, EBMに基づいて段階的治療を推奨している。
Obstructive lung disease
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Higher blood and sputum eosinophil counts are associated with a greater response to corticosteroids in COPD. Low blood eosinophil counts exhibit greater stability over time whereas higher counts demonstrate more variability. Stability of airway eosinophil levels is less well understood. We have studied the stability of sputum eosinophil counts. Differential cell count data for COPD patients (n = 100) were analysed. Subjects with two sputum eosinophil counts, 6 months apart, were included in the analysis. Patients were stratified based on baseline sputum eosinophil count into ‘low’, ‘intermediate’ and ‘high’ groups: eosinophilLOW (<1%), eosinophilINT (1–3%) and eosinophilHIGH (≥3%). Sputum eosinophil counts showed good stability (rho = 0.61, p < 0.0001, ICC of 0.77), with 67.4% of eosinophilLOW patients remaining in the same category on repeat sampling. Bland–Altman analysis of the whole cohort (median difference between measurements = 0.00%, 90th percentile = −1.4 and 4.7%) showed greater variation at higher counts. This was confirmed by the wider 90th centiles in the eosinophilINT (−1.50 to 5.65) and eosinophilHIGH groups (−5.33 to 9.80) compared to the eosinophilLOW group (−0.40 to 1.40). The repeatability of sputum eosinophil counts was related to the baseline eosinophil count; sputum eosinophilLOW COPD patients were relatively stable over time, while the eosinophilHIGH group showed greater variability. These results can facilitate the identification of COPD endotypes with differential responses to treatment.
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Background: There is conflicting evidence from previous studies as to whether eosinophil counts predict the risk of future exacerbations in COPD. Aims: In this post hoc analysis, we investigated the link between baseline eosinophil count and moderate/severe exacerbation rates during the DYNAGITO trial. Methods: DYNAGITO was a 52-week, double-blind, randomised trial in patients with COPD with FEV1 <60% predicted, at least 1 moderate/severe exacerbation in the previous year and no diagnosis of asthma (NCT02296138). Exacerbation rates were analysed using a negative binomial model adjusting for prognostic factors such as region and exacerbation history. Results: At baseline, 81% of patients had an eosinophil count ≤300 cells/µL and 49% had an eosinophil count ≤150 cells/µL. 65–76% of patients were receiving ICS across eosinophil subgroups. Similar rates of moderate/severe exacerbations were observed across eosinophil subgroups (Figure). Rates were similar across eosinophil counts in patient subgroups with low or high exacerbation history. Conclusions: Relatively few patients had an eosinophil count >300 cells/µL, and there was no increase in exacerbation rates with increasing baseline eosinophil count in the total population, or in patients with low or high exacerbation history. In this population, many of whom were receiving ICS, exacerbation history, but not blood eosinophil count, was an important determinant of exacerbation risk.
Copd exacerbation
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