今日の臨床サポート

慢性閉塞性肺疾患

著者: 長瀬隆英 東京大学 内科学専攻器官病態内科学講座

監修: 長瀬隆英 東京大学 内科学専攻器官病態内科学講座

著者校正/監修レビュー済:2021/03/24
患者向け説明資料

概要・推奨   

  1. 喫煙は気流閉塞を引き起こし、肺機能低下の経年変化を促進させる。禁煙は肺機能の低下速度を遅延させ、その後の死亡率を減少させる。禁煙は、COPDの発症リスクを減らし、COPDの進行を停止させる最も効果的な方法である(推奨度1)。
  1. インフルエンザワクチンはCOPDの増悪による死亡率を約50%下げるため、すべての患者に接種を勧める(推奨度1)。
  1. 経口ステロイド薬の長期投与は推奨されない。吸入ステロイド薬(単剤)は高用量であっても、1秒量の経年的な減少で評価したCOPDの進展への抑制効果は示さない。ただし、%1秒量が50%未満の重症以上のCOPDで増悪を繰り返す患者(例えば過去3年に3回以上)では、持続的な高用量吸入ステロイド薬は増悪の頻度を減少させる(推奨度4)。
  1. 吸入ステロイド薬・長時間作用型β2刺激薬(配合薬)は、COPD患者の肺機能や運動耐容能や呼吸困難感をより改善し、増悪を減少させる可能性がある。ただし、総死亡数に影響はない結果が有り、また、長期安全性に関しては、肺炎のリスクが増加する可能性が報告されている(推奨度1)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
長瀬隆英 : 講演料(アストラゼネカ),研究費・助成金など(中外製薬)[2021年]
監修:長瀬隆英 : 講演料(アストラゼネカ),研究費・助成金など(中外製薬)[2021年]

改訂のポイント:
  1. 定期レビューを行い、新型コロナウイルス感染の影響、およびα1-アンチトリプシン欠乏症について加筆した。 

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 慢性閉塞性肺疾患(chronic obstructive pulmonary disease、COPD)は、タバコ煙を主とする有害物質を長期に吸入曝露することで生ずる肺の炎症性疾患であり、呼吸機能検査で正常に復することのない気流閉塞を示す。
  1. COPDの病因として最も重要なものが喫煙であり、また喫煙者におけるCOPD発症率は年齢とともに増加する。
  1. 日本のCOPD患者数は500万人以上と推定されている。
  1. 気流閉塞は末梢気道病変と気腫性病変がさまざまな割合で複合的に作用することにより起こり、進行性である。
  1. 臨床的には徐々に生じる体動時の呼吸困難や慢性の咳、痰を特徴とする。
 
COPD患者にみられる息切れの進行の悪循環

COPD患者では、発症早期から運動耐容能が低下し、運動を避けることが多い。そのため、運動機能の低下が加速度的に進行する。

出典

img1:  著者提供
 
 
 
  1. COPDは呼吸機能検査の異常が診断基準となっているように、呼吸生理学的に定義された疾患である。なお臨床の場では、慢性気管支炎や肺気腫などの疾患名が汎用されている。
  1. 慢性気管支炎は咳や喀痰などの徴候により定義された疾患であり、肺気腫は病理形態学的に定義された疾患である。
  1. 慢性気管支炎の定義: 喀痰症状が年に3カ月以上あり、それが2年以上連続して認められることが基本条件となる。この病状がほかの肺疾患や心疾患に起因する場合には本症として取り扱わない。
  1. 肺気腫の定義: 終末細気管支より末梢の気腔が肺胞壁の破壊を伴いながら異常に拡大しており、明らかな線維化は認められない病変を指す。
  1. COPD患者が新型コロナウイルス(SARS-Cov-2)に感染した場合、健常者より重症化する可能性が指摘されている。
問診・診察のポイント  
  1. 理学所見については、典型的には胸郭前後径の拡大、口すぼめ呼吸、聴診上肺音の減弱などが知られているが、これらがみられなくてもCOPDを否定することはできない。

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文献 

著者: Phunsup Wongsurakiat, Khun Nanta Maranetra, Chantapong Wasi, Uraiwan Kositanont, Wanchai Dejsomritrutai, Suchai Charoenratanakul
雑誌名: Chest. 2004 Jun;125(6):2011-20.
Abstract/Text STUDY OBJECTIVES: To determine the effectiveness of influenza vaccination on influenza-related acute respiratory illness (ARI) and overall ARI in patients with COPD, and its relationship to the degree of airflow obstruction.
DESIGN: Stratified, randomized, double-blind, placebo-controlled trial.
SETTING: From June 1997 to November 1998 at a single university hospital. Patients and interventions: One hundred twenty-five patients with COPD were stratified based on their FEV(1) as having mild, moderate, and severe COPD. Within each group, they were randomized to the vaccine group (62 patients who received purified, trivalent, split-virus vaccine) or the placebo group (63 patients).
MEASUREMENTS: The number of episodes and severity of total ARI, classified as outpatient treatment, hospitalization, and requirement of mechanical ventilation; and the number of episodes and severity of influenza-related ARI.
RESULTS: The incidence of influenza-related ARI was 28.1 per 100 person-years and 6.8 per 100 person-years in the placebo group and vaccine group, respectively (relative risk [RR], 0.24 [p = 0.005]; vaccine effectiveness, 76%). The incidences were 28.2, 23.8, and 31.2 per 100 person-years in the patients with mild, moderate, and severe COPD, respectively, in the placebo group, and 4.5, 13.2, and 4.6 per 100 person-years in the patients with mild, moderate, and severe COPD, respectively, in the vaccine group (RR, 0.16 [p = 0.06]; vaccine effectiveness, 84%; RR, 0.55 [p = 0.5]; vaccine effectiveness, 45%; and RR, 0.15 [p = 0.04]; vaccine effectiveness, 85%, in the patients with mild, moderate, and severe COPD, respectively). Bivariate analysis revealed that the effectiveness of influenza vaccination was not modified by the severity of COPD, comorbid diseases, age, gender, or current smoking status. There was no difference in the incidence or severity of total ARI between the placebo group and the vaccine group.
CONCLUSIONS: Influenza vaccination is highly effective in the prevention of influenza-related ARI regardless of the severity of COPD. Influenza vaccination does not prevent other ARIs unrelated to influenza. The effectiveness of influenza vaccination in the prevention of overall ARI in patients with COPD will depend on how much the proportion of influenza-related ARI contributes to the incidence of total ARI. Influenza vaccination should be recommended to all patients with COPD.

PMID 15189916  Chest. 2004 Jun;125(6):2011-20.
著者: K L Nichol, K L Margolis, J Wuorenma, T Von Sternberg
雑誌名: N Engl J Med. 1994 Sep 22;331(12):778-84. doi: 10.1056/NEJM199409223311206.
Abstract/Text BACKGROUND: Despite recommendations for annual vaccination against influenza, more than half of elderly Americans do not receive this vaccine. In a serial cohort study, we assessed the efficacy and cost effectiveness of influenza vaccine administered to older persons living in the community.
METHODS: Using administrative data bases, we studied men and women over 64 years of age who were enrolled in a large health maintenance organization in the Minneapolis-St. Paul area. We examined the rate of vaccination and the occurrence of influenza and its complications in each of three seasons: 1990-1991, 1991-1992, and 1992-1993. Outcomes were adjusted for age, sex, diagnoses indicating a high risk, use of medications, and previous use of health care services.
RESULTS: Each cohort included more than 25,000 persons 65 years of age or older. Immunization rates ranged from 45 percent to 58 percent. Although the vaccine recipients had more coexisting illnesses at base line than those who did not receive the vaccine, during each influenza season vaccination was associated with a reduction in the rate of hospitalization for pneumonia and influenza (by 48 to 57 percent, P < or = 0.002) and for all acute and chronic respiratory conditions (by 27 to 39 percent, P < or = 0.01). Vaccination was also associated with a 37 percent reduction (P = 0.04) in the rate of hospitalization for congestive heart failure during the 1991-1992 season, when influenza A was epidemic. The costs of hospitalization for all types of illness studied were lower in the vaccinated group during 1991-1992 (range of reduction, 47 to 66 percent; P < 0.005) and for acute and chronic respiratory conditions and congestive heart failure in 1990-1991 (reductions of 37 percent and 43 percent, respectively; P < or = 0.05). Direct savings per year averaged $117 per person vaccinated (range, $21 to $235), with cumulative savings of nearly $5 million. Vaccination was also associated with reductions of 39 to 54 percent in mortality from all causes during the three influenza seasons (P < 0.001).
CONCLUSIONS: For elderly citizens living in the community, vaccination against influenza is associated with reductions in the rate of hospitalization and in deaths from influenza and its complications, as compared with the rates in unvaccinated elderly persons, and vaccination produces direct dollar savings.

PMID 8065407  N Engl J Med. 1994 Sep 22;331(12):778-84. doi: 10.1056/・・・
著者: Donald P Tashkin, Bartolome Celli, Stephen Senn, Deborah Burkhart, Steven Kesten, Shailendra Menjoge, Marc Decramer, UPLIFT Study Investigators
雑誌名: N Engl J Med. 2008 Oct 9;359(15):1543-54. doi: 10.1056/NEJMoa0805800. Epub 2008 Oct 5.
Abstract/Text BACKGROUND: Previous studies showing that tiotropium improves multiple end points in patients with chronic obstructive pulmonary disease (COPD) led us to examine the long-term effects of tiotropium therapy.
METHODS: In this randomized, double-blind trial, we compared 4 years of therapy with either tiotropium or placebo in patients with COPD who were permitted to use all respiratory medications except inhaled anticholinergic drugs. The patients were at least 40 years of age, with a forced expiratory volume in 1 second (FEV(1)) of 70% or less after bronchodilation and a ratio of FEV(1) to forced vital capacity (FVC) of 70% or less. Coprimary end points were the rate of decline in the mean FEV(1) before and after bronchodilation beginning on day 30. Secondary end points included measures of FVC, changes in response on St. George's Respiratory Questionnaire (SGRQ), exacerbations of COPD, and mortality.
RESULTS: Of a total of 5993 patients (mean age, 65+/-8 years) with a mean FEV(1) of 1.32+/-0.44 liters after bronchodilation (48% of predicted value), we randomly assigned 2987 to the tiotropium group and 3006 to the placebo group. Mean absolute improvements in FEV(1) in the tiotropium group were maintained throughout the trial (ranging from 87 to 103 ml before bronchodilation and from 47 to 65 ml after bronchodilation), as compared with the placebo group (P<0.001). After day 30, the differences between the two groups in the rate of decline in the mean FEV(1) before and after bronchodilation were not significant. The mean absolute total score on the SGRQ was improved (lower) in the tiotropium group, as compared with the placebo group, at each time point throughout the 4-year period (ranging from 2.3 to 3.3 units, P<0.001). At 4 years and 30 days, tiotropium was associated with a reduction in the risks of exacerbations, related hospitalizations, and respiratory failure.
CONCLUSIONS: In patients with COPD, therapy with tiotropium was associated with improvements in lung function, quality of life, and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV(1). (ClinicalTrials.gov number, NCT00144339.)

2008 Massachusetts Medical Society
PMID 18836213  N Engl J Med. 2008 Oct 9;359(15):1543-54. doi: 10.1056/・・・
著者: Jin-Ping Zheng, Jian Kang, Shao-Guang Huang, Ping Chen, Wan-Zen Yao, Lan Yang, Chun-Xue Bai, Chang-Zheng Wang, Chen Wang, Bao-Yuan Chen, Yi Shi, Chun-Tao Liu, Ping Chen, Qiang Li, Zhen-Shan Wang, Yi-Jiang Huang, Zhi-Yang Luo, Fei-Peng Chen, Jian-Zhang Yuan, Ben-Tong Yuan, Hui-Ping Qian, Rong-Chang Zhi, Nan-Shan Zhong
雑誌名: Lancet. 2008 Jun 14;371(9629):2013-8. doi: 10.1016/S0140-6736(08)60869-7.
Abstract/Text BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation, and has many components including mucus hypersecretion, oxidative stress, and airway inflammation. We aimed to assess whether carbocisteine, a mucolytic agent with anti-inflammatory and antioxidation activities, could reduce the yearly exacerbation rate in patients with COPD.
METHODS: We did a randomised, double-blind, placebo-controlled study of 709 patients from 22 centres in China. Participants were eligible if they were diagnosed as having COPD with a postbronchodilator forced expiratory volume in 1 s (FEV(1)) to forced vital capacity (FVC) ratio (FEV(1)/FVC) of less than 0.7 and an FEV(1) between 25% and 79% of the predicted value, were aged between 40 and 80 years, had a history of at least two COPD exacerbations within the previous 2 years, and had remained clinically stable for over 4 weeks before the study. Patients were randomly assigned to receive 1500 mg carbocisteine or placebo per day for a year. The primary endpoint was exacerbation rate over 1 year, and analysis was by intention to treat. This trial is registered with the Japan Clinical Trials Registry (http://umin.ac.jp/ctr/index/htm) number UMIN-CRT C000000233.
FINDINGS: 354 patients were assigned to the carbocisteine group and 355 to the placebo group. Numbers of exacerbations per patient per year declined significantly in the carbocisteine group compared with the placebo group (1.01 [SE 0.06] vs 1.35 [SE 0.06]), risk ratio 0.75 (95% CI 0.62-0.92, p=0.004). Non-significant interactions were found between the preventive effects and COPD severity, smoking, as well as concomitant use of inhaled corticosteroids. Carbocisteine was well tolerated.
INTERPRETATION: Mucolytics, such as carbocisteine, should be recognised as a worthwhile treatment for prevention of exacerbations in Chinese patients with COPD.

PMID 18555912  Lancet. 2008 Jun 14;371(9629):2013-8. doi: 10.1016/S014・・・
著者:
雑誌名: Lancet. 1981 Mar 28;1(8222):681-6.
Abstract/Text A controlled trial of long term domiciliary oxygen therapy has been carried out in three centres in the U.K. The 87 patients, all under 70 years of age, who took part had chronic bronchitis or emphysema with irreversible airways obstruction, severe arterial hypoxaemia, carbon dioxide retention, and a history of congestive heart failure. The patients were randomised to oxygen therapy (treated) or no oxygen (controls). Oxygen was given by nasal prongs for at least 15 h daily, usually at 2 1/min. The two groups were well matched, both clinically and in terms of lung function and other laboratory findings. 19 of the 42 oxygen treated patients died in the five years of survival follow-up compared with 30 out of 45 controls: in the 66 men in this trial the survival advantage of oxygen did not emerge until 500 days had elapsed. Survival for the 12 female controls was surprisingly poor, 8 of them being dead at 3 years. Mortality was not easy to predict, though a summation of arterial carbon dioxide tension and red cell mass was helpful. Neither time spent in hospital because of exacerbations of respiratory failure nor work attendance were affected by oxygen therapy, but these patients were very ill at the start of the trial and many had already retired on grounds of age or ill-health. Physiological measurements suggested that oxygen did not slow the progress of respiratory failure in those who died early. However, in longer term survivors on oxygen, arterial oxygenation did seem to stop deterioration.

PMID 6110912  Lancet. 1981 Mar 28;1(8222):681-6.
著者:
雑誌名: Ann Intern Med. 1980 Sep;93(3):391-8.
Abstract/Text At six centers, 203 patients with hypoxemic chronic obstructive lung disease were randomly allocated to either continuous oxygen (O2) therapy or 12-hour nocturnal O2 therapy and followed for at least 12 months (mean, 19.3 months). The two groups were initially well matched in terms of physiological and neuropsychological function. Compliance with each oxygen regimen was good. Overall mortality in the nocturnal O2 therapy group was 1.94 times that in the continuous O2 therapy group (P = 0.01). This trend was striking in patients with carbon dioxide retention and also present in patients with relatively poor lung function, low mean nocturnal oxygen saturation, more severe brain dysfunction, and prominent mood disturbances. Continuous O2 therapy also appeared to benefit patients with low mean pulmonary artery pressure and pulmonary vascular resistance and those with relatively well-preserved exercise capacity. We conclude that in hypoxemic chronic obstructive lung disease, continuous O2 therapy is associated with a lower mortality than is nocturnal O2 therapy. The reason for this difference is not clear.

PMID 6776858  Ann Intern Med. 1980 Sep;93(3):391-8.
著者: Peter M A Calverley, Julie A Anderson, Bartolome Celli, Gary T Ferguson, Christine Jenkins, Paul W Jones, Julie C Yates, Jørgen Vestbo, TORCH investigators
雑誌名: N Engl J Med. 2007 Feb 22;356(8):775-89. doi: 10.1056/NEJMoa063070.
Abstract/Text BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids are used to treat chronic obstructive pulmonary disease (COPD), but their effect on survival is unknown.
METHODS: We conducted a randomized, double-blind trial comparing salmeterol at a dose of 50 microg plus fluticasone propionate at a dose of 500 microg twice daily (combination regimen), administered with a single inhaler, with placebo, salmeterol alone, or fluticasone propionate alone for a period of 3 years. The primary outcome was death from any cause for the comparison between the combination regimen and placebo; the frequency of exacerbations, health status, and spirometric values were also assessed.
RESULTS: Of 6112 patients in the efficacy population, 875 died within 3 years after the start of the study treatment. All-cause mortality rates were 12.6% in the combination-therapy group, 15.2% in the placebo group, 13.5% in the salmeterol group, and 16.0% in the fluticasone group. The hazard ratio for death in the combination-therapy group, as compared with the placebo group, was 0.825 (95% confidence interval [CI], 0.681 to 1.002; P=0.052, adjusted for the interim analyses), corresponding to a difference of 2.6 percentage points or a reduction in the risk of death of 17.5%. The mortality rate for salmeterol alone or fluticasone propionate alone did not differ significantly from that for placebo. As compared with placebo, the combination regimen reduced the annual rate of exacerbations from 1.13 to 0.85 and improved health status and spirometric values (P<0.001 for all comparisons with placebo). There was no difference in the incidence of ocular or bone side effects. The probability of having pneumonia reported as an adverse event was higher among patients receiving medications containing fluticasone propionate (19.6% in the combination-therapy group and 18.3% in the fluticasone group) than in the placebo group (12.3%, P<0.001 for comparisons between these treatments and placebo).
CONCLUSIONS: The reduction in death from all causes among patients with COPD in the combination-therapy group did not reach the predetermined level of statistical significance. There were significant benefits in all other outcomes among these patients. (ClinicalTrials.gov number, NCT00268216 [ClinicalTrials.gov].).

Copyright 2007 Massachusetts Medical Society.
PMID 17314337  N Engl J Med. 2007 Feb 22;356(8):775-89. doi: 10.1056/N・・・

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