今日の臨床サポート 今日の臨床サポート

著者: 山沢英明 国際医療福祉大病院 呼吸器内科

監修: 杉山幸比古 練馬光が丘病院 呼吸器内科

著者校正済:2025/03/12
現在監修レビュー中
参考ガイドライン:
  1. 日本呼吸器外科学会:膿胸治療ガイドライン(2022年)
  1. The American Association for Thoracic Surgery consensus guidelines for the management of empyema 2017
  1. Management of Pleural Infection in Adults: British Thoracic Society Pleural Disease Guideline 2010
患者向け説明資料

改訂のポイント:
  1. 定期レビューを行い、以下について加筆・修正した。
  1. 胸水原因の診断における胸膜クライオ生検について、最近の報告についての追記を行った。
  1. 急性膿胸に対する線維素溶解剤の胸腔内注⼊について、日本呼吸器外科学会の『膿胸治療ガイドライン』における見解を追記した。

概要・推奨   

  1. 胸水の原因疾患は多岐にわたるが、胸腔穿刺を行い胸水の性状を調べることで、原因疾患をある程度鑑別していくことができる(推奨度1)
  1. Lightの基準を用いて、胸水が漏出性か滲出性かの鑑別をする(推奨度1)
  1. Lightの基準:以下の3項目のうち少なくとも1項目を満たせば滲出性、いずれも満たさなければ漏出性と判断する。
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病態・疫学・診察 

疫学情報・病態・注意事項  
  1. 胸膜は胸腔内面を覆う壁側胸膜と肺表面を覆う臓側胸膜からなり、両者で囲まれた胸膜腔には生理的な少量の胸水が存在する。
  1. 胸水は主として壁側胸膜のリンパ管から吸収されるが、産生と吸収のバランスが崩れると臨床的に胸水が認められるようになる。
 
正常状態における胸水のターンオーバー

胸膜の毛細血管より産生された胸水は、壁側胸膜と臓側胸膜でその一部が再吸収される。残りは胸膜中皮細胞層を通過して胸腔へ流れ、壁側胸膜のリンパ管を通じて吸収される。

出典

著者提供
 
  1. 胸水が貯留する機序:①毛細管透過性の亢進、②静水圧の上昇、③膠質浸透圧の低下。滲出性胸水は主として、①により生じ、漏出性胸水は、②や③による。
  1. 胸水は多くの疾患の合併症として出現し得る。頻度の高いものとして、うっ血性心不全、悪性腫瘍、肺炎、結核および肺塞栓が挙げられる。
問診・診察のポイント  
  1. 胸水貯留はまず胸部X線でその存在を疑う。少量の場合には側臥位撮影(デクビタス)にて確認されることもある。また、胸部CTや胸部エコーでも証明することができる。

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最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
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文献 

Collins TR, Sahn SA.
Thoracocentesis. Clinical value, complications, technical problems, and patient experience.
Chest. 1987 Jun;91(6):817-22. doi: 10.1378/chest.91.6.817.
Abstract/Text A prospective study of 129 consecutive thoracocentesis in 86 patients at a university medical center evaluated the clinical value, complications, and patient experience with thoracocentesis. Pleural fluid analysis in conjunction with the clinical presentation placed 78 pleural fluids into diagnostic categories: definitive 14 (18 percent), presumptive 44 (56 percent), and nondiagnostic 20 (26 percent). Fourteen of 78 (18 percent) of the nondiagnostic fluids were useful, while only six (8 percent) were not useful clinically; therefore, 92 percent of thoracocentesis provided clinically useful information. Using sequential data analysis, initial diagnostic categorizations of eight of 78 patients were upgraded from presumptive or nondiagnostic to definitive based on data available 24 hours following thoracocentesis. Thus, 70 patients were categorized based on the pleural fluid data obtained within the first 24 hours of thoracocentesis. Thirty-four objective complications occurred in 26 of 129 (20 percent) thoracocentesis. The most common complications were pneumothorax, 15 of 129 (12 percent), and cough, 12 of 129 (9 percent). Sixty-five subjective complications occurred in 56 of 123 (46 percent) thoracocentesis. Anxiety, 26 of 123 (21 percent), and site pain, 24 of 123 (20 percent), were the most common subjective complications noted. Thirty technical problems occurred in 129 (23 percent) thoracocentesis with blood contamination, 14 of 129 (11 percent), and dry tap, nine of 129 (7 percent), being the most common. We conclude that diagnostic thoracocentesis is a clinically valuable procedure if used in conjunction with the patient presentation with an understanding of its limitations for providing a specific etiologic diagnosis. When performed by physicians in training, the number of complications are substantial and the operator often underestimates the degree of patient discomfort. Awareness of the clinical value and complications of thoracocentesis should lead to improved use and safety of this procedure.

PMID 3581930
Wong CL, Holroyd-Leduc J, Straus SE.
Does this patient have a pleural effusion?
JAMA. 2009 Jan 21;301(3):309-17. doi: 10.1001/jama.2008.937.
Abstract/Text CONTEXT: Pleural effusion is a common finding among patients presenting with respiratory symptoms. The value of the bedside examination to detect pleural effusion is unclear.
OBJECTIVE: To systematically review the evidence regarding the accuracy of the physical examination in assessing the probability of a pleural effusion.
DATA SOURCES: We searched MEDLINE (1950-October 2008) and EMBASE (1980-October 2008) using Ovid to identify English-language studies conducted in a clinical setting. Additional studies were identified by searching the bibliographies of retrieved articles and contacting experts in the field.
STUDY SELECTION: We included prospective studies of diagnostic accuracy that compared at least 1 physical examination maneuver with radiographic confirmation of pleural effusion.
DATA EXTRACTION: Three authors independently appraised study quality and extracted relevant data. Data regarding participant recruitment, reference standard, diagnostic test(s), and test accuracy were extracted. Disagreements were resolved by consensus.
DATA SYNTHESIS: We identified 310 unique citations, but only 5 prospectively conducted studies met inclusion criteria (N = 934 patients). A random-effects model was used for quantitative synthesis. Of the 8 physical examination maneuvers evaluated in the included studies (conventional percussion, auscultatory percussion, breath sounds, chest expansion, tactile vocal fremitus, vocal resonance, crackles, and pleural friction rub), dullness to conventional percussion was most accurate for diagnosing pleural effusion (summary positive likelihood ratio, 8.7; 95% confidence interval, 2.2-33.8), while the absence of reduced tactile vocal fremitus made pleural effusion less likely (negative likelihood ratio, 0.21; 95% confidence interval, 0.12-0.37).
CONCLUSIONS: Based on the limited number of studies, dullness to percussion and tactile fremitus are the most useful findings for pleural effusion. Dull chest percussion makes the probability of a pleural effusion much more likely but requires a chest radiograph to confirm the diagnosis. When the pretest probability of pleural effusion is low, the absence of reduced tactile vocal fremitus makes pleural effusion less likely so that a chest radiograph might not be necessary depending on the overall clinical situation.

PMID 19155458
Rahman NM, Ali NJ, Brown G, Chapman SJ, Davies RJ, Downer NJ, Gleeson FV, Howes TQ, Treasure T, Singh S, Phillips GD; British Thoracic Society Pleural Disease Guideline Group.
Local anaesthetic thoracoscopy: British Thoracic Society Pleural Disease Guideline 2010.
Thorax. 2010 Aug;65 Suppl 2:ii54-60. doi: 10.1136/thx.2010.137018.
Abstract/Text
PMID 20696694
Boutin C, Viallat JR, Cargnino P, Farisse P.
Thoracoscopy in malignant pleural effusions.
Am Rev Respir Dis. 1981 Nov;124(5):588-92. doi: 10.1164/arrd.1981.124.5.588.
Abstract/Text In a consecutive series of 1,000 patients admitted since 1970 for pleural effusions, 215 with undiagnosed chronic effusions (with previous negative cytologic and needle biopsy results) underwent thoracoscopy. The investigation was usually performed under general anesthesia, originally with a 9-mm diameter cold light laparoscope, but, since 1978, with a 7-mm diameter thoracoscope of our design with biopsy forceps connected to a diathermocoagulating device. Thoracoscopy diagnosed 131 of 150 malignant effusions in the series. We observed no false positive results. A repeat pleural cytology and needle biopsy performed the day before thoracoscopy yielded only 41% positive results. The higher yield by our new thoracoscope (97% positive results, versus 78% with the laparoscope) can be accounted for by a better visualization of the pleural space, easier handling of biopsy material, and the systematic use of diathermocoagulation. Complications were rare, minor, and not life-threatening.

PMID 7305114
Venekamp LN, Velkeniers B, Noppen M.
Does 'idiopathic pleuritis' exist? Natural history of non-specific pleuritis diagnosed after thoracoscopy.
Respiration. 2005 Jan-Feb;72(1):74-8. doi: 10.1159/000083404.
Abstract/Text BACKGROUND: Even after a complete work-up including thoracoscopic biopsies, a significant number of patients with pleural exudates are diagnosed with 'non-specific pleuritis', and no specific diagnosis can be made. The natural evolution of these patients is poorly understood.
OBJECTIVES: To study the natural evolution of patients with non-specific pleuritis diagnosed after thoracoscopy and to evaluate whether the histological diagnosis of non-specific pleuritis corresponds with the clinical diagnosis of 'idiopathic pleuritis'.
METHODS: We retrospectively studied the evolution of 75 patients between 1992 and 2002 (49 men and 26 women), mean (+/- SD) age 63.4 (+/- 13.3) years, who underwent diagnostic thoracoscopy because of an unexplained exudative pleural effusion, and in whom the histological diagnosis of non-specific pleuritis was made. Follow-up data were obtained through medical files and/or telephone contacts with general practitioners.
RESULTS: Of these 75 patients, 8.3% eventually developed a malignancy during the follow-up period. In the remaining patients (91.7%), the clinical evolution followed a benign course. Ultimately, a probable cause was established on clinical grounds in 40 patients. True idiopathic pleuritis was finally observed in 25% of patients with the histological diagnosis of non-specific pleuritis. Recurrence of the effusion occurred in 10 out of 60 (16.7%) patients, after a mean period of 26.2 months.
CONCLUSIONS: The majority of non-specific pleuritis patients (91.7%) followed a benign course, with a spontaneous resolution of the effusion in 81.8% of cases. In the majority of patients, a probable cause of the pleuritis was identified. True 'idiopathic benign pleuritis' hence occurs in only a minority (25%) of patients.

Copyright (c) 2005 S. Karger AG, Basel.
PMID 15753638
Shafiq M, Sethi J, Ali MS, Ghori UK, Saghaie T, Folch E.
Pleural Cryobiopsy: A Systematic Review and Meta-Analysis.
Chest. 2020 Jan;157(1):223-230. doi: 10.1016/j.chest.2019.09.023. Epub 2019 Oct 11.
Abstract/Text BACKGROUND: Pleural biopsy using either video-assisted thoracoscopic surgery or medical pleuroscopy is the current diagnostic criterion standard for pleural pathology with a high, yet imperfect, diagnostic yield. Cryobiopsy may provide greater tissue, increase depth of sampled tissue, and/or reduce crush artifact. However, its impact on diagnostic yield remains uncertain, and there are potential concerns regarding its safety too. We performed a systematic review and meta-analysis to investigate the same.
METHODS: We performed a systematic search of MEDLINE, Embase, and Google Scholar for studies evaluating the performance of pleural cryobiopsy, assessing the quality of each study using the Quality Assessment, Data Abstraction and Synthesis-2 tool. Using inverse variance weighting, we performed a meta-analysis of diagnostic yield estimations. We also reviewed specimen characteristics and complications related to the procedure.
RESULTS: Seven observational studies involving 586 pleural biopsies (311 cryobiopsies and 275 flexible forceps biopsies) were evaluated. All but one study used a semi-rigid thoracoscope. Meta-analysis generated a diagnostic yield of 96.5% for cryobiopsy and 93.1% for forceps biopsy with an inverse variance-weighted OR of 1.61 (95% CI, 0.71-3.66) and an I2 of 16%. No instances of moderate to severe bleeding were reported with cryobiopsy. A funnel plot illustrated no major publication bias.
CONCLUSIONS: Based on analysis of relatively homogenous observational data, pleural cryobiopsy is safe but does not increase diagnostic yield over flexible forceps biopsy. Adequately powered multicenter randomized trials are needed for further investigation.

Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
PMID 31610161
Heffner JE, Brown LK, Barbieri CA.
Diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Primary Study Investigators.
Chest. 1997 Apr;111(4):970-80. doi: 10.1378/chest.111.4.970.
Abstract/Text STUDY OBJECTIVE: To (1) determine appropriate decision thresholds and diagnostic accuracies for pleural fluid (PF) tests that discriminate between exudative and transudative pleural effusions, and (2) evaluate the quality of the primary investigations.
DESIGN: Formal meta-analysis of studies that report the diagnostic value of pleural fluid tests.
SETTING: Data collected from international academic medical centers.
PATIENTS: Hospitalized patients undergoing thoracentesis for pleural effusions.
INTERVENTIONS: Primary investigators were requested to transmit original data from patients described in their studies.
MEASUREMENTS AND RESULTS: Eight primary studies described 1,448 patients with one or more of the following tests: protein (P)-PF, P-PF/serum ratio (R), bilirubin (BILI)-R, lactate dehydrogenase (LDH)-PF, LDH-R, cholesterol (C)-PF, C-R, and albumin gradient. We found that all eight tests had similar diagnostic accuracies when evaluated by receiver operating characteristic (ROC) analysis except for BILI-R, which was less diagnostically accurate. Decision thresholds determined by ROC analysis differed from previously reported values for LDH-PF (>0.45 upper limits of normal) and C-PF (>45 mg/dL). Paired and triplet test combinations tended to have higher diagnostic accuracies compared with individual tests, but examination of the odds ratios with 95% confidence intervals did not identify a clearly superior test combination. Limitations of the primary studies presented a high likelihood of bias affecting their results.
CONCLUSIONS: Several strategies exist for clinicians in utilizing PF tests to classify effusions as exudates or transudates but accurate interpretations of these test results will require better designed studies.

PMID 9106577
Shaw P, Agarwal R.
Pleurodesis for malignant pleural effusions.
Cochrane Database Syst Rev. 2004;(1):CD002916. doi: 10.1002/14651858.CD002916.pub2.
Abstract/Text BACKGROUND: Approximately half of all patients with metastatic cancer develop a malignant pleural effusion which is likely to lead to a significant reduction in quality of life secondary to symptoms such as dyspnoea and cough. The aim of pleurodesis in these patients is to prevent re-accumulation of the effusion and thereby of symptoms, and avoid the need for repeated hospitalization for thoracocentesis. Numerous clinical studies have been performed to try to determine the optimal pleurodesis strategy, and synthesis of the available evidence should facilitate this.
OBJECTIVES: The aims of this review were to ascertain the optimal technique of pleurodesis in cases of malignant pleural effusion; to confirm the need for a sclerosant; and to clarify which, if any, of the sclerosants is the most effective.
SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials was searched for studies on 'pleurodesis'. Studies for inclusion were also identified from MEDLINE (1980 to June 2002) and EMBASE (1980 to May 2002). No language restriction was applied.
SELECTION CRITERIA: RCTs of adults subjects undergoing pleurodesis for pleural effusion in the context of metastatic malignancy (or a malignant process leading to pleural effusion) were included.
DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies for inclusion in the review, and extracted data using a standard data collection form. Primary outcome measures sought were effectiveness of pleurodesis as defined by freedom from recurrence of effusions, and mortality after pleurodesis. Secondary outcomes were adverse events due to pleurodesis. Dichotomous data were meta-analysed using a fixed effect model and expressed as relative risk. The number-needed-to-treat (NNT) was calculated for pleurodesis efficacy. In addition, for adverse events, the overall percentage of patients across studies exhibiting a particular adverse effect such as fever, pain, or gastrointestinal symptoms was calculated.
MAIN RESULTS: A total of 36 RCTs with 1499 subjects were eligible for meta-analysis. The use of sclerosants (mitozantrone, talc and tetracycline combined)compared with control (instillation of isotonic saline or equivalent pH isotonic saline or tube drainage alone) was associated with an increased efficacy of pleurodesis. The relative risk (RR) of non-recurrence of an effusion is 1.20 (95% CI 1.04 to 1.38) in favour of the use of sclerosants based on five studies with a total 228 subjects. Comparing different sclerosants, talc was found to be the most efficacious. The RR of effusion non-recurrence was 1.34 (95% CI 1.16 to 1.55) in favour of talc compared with bleomycin, tetracycline, mustine or tube drainage alone based on 10 studies comprising 308 subjects. This was not associated with increased mortality post pleurodesis. The RR of death was 1.19 (95% CI 0.08 to 1.77) for talc compared to bleomycin, tetracycline, mustine and tube drainage alone based on six studies of 186 subjects. Death was not reported in all studies and, when reported, was attributed to underlying disease, only one death being reported as procedure-related. In the comparison of thoracoscopic versus medical pleurodesis, thoracoscopic pleurodesis was found to be more effective. The RR of non-recurrence of effusion is 1.19 (95% CI 1.04 to 1.36) in favour of thoracoscopic pleurodesis compared with tube thoracostamy pleurodesis utilizing talc as sclerosant based on two studies with 112 subjects. Comparing thoracoscopic versus bedside instillation (with different sized chest tubes) of various sclerosants (tetracycline, bleomycin, talc or mustine) the RR of non-recurrence of effusion is 1.68 (95% CI 1.35 to 2.10) based on five studies with a total of 145 participants.Adverse events were not reported adequately to enable meta-analysis.
REVIEWER'S CONCLUSIONS: The available evidence supports the need for chemical sclerosants for successful pleurodesis, the use of talc as the sclerosant of choice, and thoracoscopic pleurodesis as the preferred technique for pleurodesis based on efficacy. There was no evidence for an increase in mortality following talc pleurodesis.

PMID 14973997
Inoue T, Ishida A, Nakamura M, Nishine H, Mineshita M, Miyazawa T.
Talc pleurodesis for the management of malignant pleural effusions in Japan.
Intern Med. 2013;52(11):1173-6. doi: 10.2169/internalmedicine.52.9281.
Abstract/Text OBJECTIVE: Malignant pleural effusions are commonly treated with tube drainage followed by chemical pleurodesis to maintain the patient's quality of life. While talc is now accepted to be a worldwide gold-standard sclerosing agent for treating malignant pleural effusion, it is not yet approved in Japan. Instead, many patients are administered OK-432 for pleurodesis, which carries the risk of complications such as high-grade fever, chest pain, anaphylactic shock, interstitial pneumonia and acute renal failure. To assess the efficacy and safety of talc as a sclerosing agent in the management of malignant pleural effusions in Japanese patients.
METHODS: Pleurodesis was performed using 4 g of sterile talc with thoracoscopic talc poudrage or the administration of talc slurry via a chest tube in patients with malignant pleural effusions.
RESULTS: A total of 57 patients were included. The success rate of pleurodesis assessed on chest radiography at 30, 90 and 180 days was 90.6%, 80.9% and 76.1%, respectively. Complications occurring after talc pleurodesis included fever in 10.5% of the patients and chest pain in 14.0% of the patients. No major complications were reported.
CONCLUSION: Talc pleurodesis is an effective and safe treatment for the management of malignant pleural effusion in Japanese patients.

PMID 23728550
Han ZJ, Wu XD, Cheng JJ, Zhao SD, Gao MZ, Huang HY, Gu B, Ma P, Chen Y, Wang JH, Yang CJ, Yan ZH.
Diagnostic Accuracy of Natriuretic Peptides for Heart Failure in Patients with Pleural Effusion: A Systematic Review and Updated Meta-Analysis.
PLoS One. 2015;10(8):e0134376. doi: 10.1371/journal.pone.0134376. Epub 2015 Aug 5.
Abstract/Text BACKGROUND: Previous studies have reported that natriuretic peptides in the blood and pleural fluid (PF) are effective diagnostic markers for heart failure (HF). These natriuretic peptides include N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and midregion pro-atrial natriuretic peptide (MR-proANP). This systematic review and meta-analysis evaluates the diagnostic accuracy of blood and PF natriuretic peptides for HF in patients with pleural effusion.
METHODS: PubMed and EMBASE databases were searched to identify articles published in English that investigated the diagnostic accuracy of BNP, NT-proBNP, and MR-proANP for HF. The last search was performed on 9 October 2014. The quality of the eligible studies was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. The diagnostic performance characteristics (sensitivity, specificity, and other measures of accuracy) were pooled and examined using a bivariate model.
RESULTS: In total, 14 studies were included in the meta-analysis, including 12 studies reporting the diagnostic accuracy of PF NT-proBNP and 4 studies evaluating blood NT-proBNP. The summary estimates of PF NT-proBNP for HF had a diagnostic sensitivity of 0.94 (95% confidence interval [CI]: 0.90-0.96), specificity of 0.91 (95% CI: 0.86-0.95), positive likelihood ratio of 10.9 (95% CI: 6.4-18.6), negative likelihood ratio of 0.07 (95% CI: 0.04-0.12), and diagnostic odds ratio of 157 (95% CI: 57-430). The overall sensitivity of blood NT-proBNP for diagnosis of HF was 0.92 (95% CI: 0.86-0.95), with a specificity of 0.88 (95% CI: 0.77-0.94), positive likelihood ratio of 7.8 (95% CI: 3.7-16.3), negative likelihood ratio of 0.10 (95% CI: 0.06-0.16), and diagnostic odds ratio of 81 (95% CI: 27-241). The diagnostic accuracy of PF MR-proANP and blood and PF BNP was not analyzed due to the small number of related studies.
CONCLUSIONS: BNP, NT-proBNP, and MR-proANP, either in blood or PF, are effective tools for diagnosis of HF. Additional studies are needed to rigorously evaluate the diagnostic accuracy of PF and blood MR-proANP and BNP for the diagnosis of HF.

PMID 26244664
Porcel JM.
Biomarkers in the diagnosis of pleural diseases: a 2018 update.
Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618808660. doi: 10.1177/1753466618808660.
Abstract/Text The use of biomarkers on pleural fluid (PF) specimens may assist the decision-making process and enhance clinical diagnostic pathways. Three paradigmatic examples are heart failure, tuberculosis and, particularly, malignancy. An elevated PF concentration of the amino-terminal fragment of probrain natriuretic peptide (>1500 pg/ml) is a hallmark of acute decompensated heart failure. Adenosine deaminase, interferon-γ and interleukin-27 are three valuable biomarkers for diagnosing tuberculous pleurisy, yet only the first has been firmly established in clinical practice. Diagnostic PF biomarkers for malignancy can be classified as soluble-protein based, immunocytochemical and nucleic-acid based. Soluble markers (e.g. carcinoembryonic antigen (CEA), carbohydrate antigen 15-3, mesothelin) are only indicative of cancer, but not confirmatory. Immunocytochemical studies on PF cell blocks allow: (a) to distinguish mesothelioma from reactive mesothelial proliferations (e.g. loss of BAP1 nuclear expression, complemented by the demonstration of p16 deletion using fluorescence in situ hybridization, indicate mesothelioma); (b) to separate mesothelioma from adenocarcinoma (e.g. calretinin, CK 5/6, WT-1 and D2-40 are markers of mesothelioma, whereas CEA, EPCAM, TTF-1, napsin A, and claudin 4 are markers of carcinoma); and (c) to reveal tumor origin in pleural metastases of an unknown primary site (e.g. TTF-1 and napsin A for lung adenocarcinoma, p40 for squamous lung cancer, GATA3 and mammaglobin for breast cancer, or synaptophysin and chromogranin A for neuroendocrine tumors). Finally, PF may provide an adequate sample for analysis of molecular markers to guide patients with non-small cell lung cancer to appropriate targeted therapies. Molecular testing must include, at least, mutations of epidermal growth-factor receptor and BRAF V600E, translocations of rat osteosarcoma and anaplastic lymphoma kinase, and expression of programmed death ligand 1.

PMID 30354850
Colice GL, Curtis A, Deslauriers J, Heffner J, Light R, Littenberg B, Sahn S, Weinstein RA, Yusen RD.
Medical and surgical treatment of parapneumonic effusions : an evidence-based guideline.
Chest. 2000 Oct;118(4):1158-71. doi: 10.1378/chest.118.4.1158.
Abstract/Text OBJECTIVE: A panel was convened by the Health and Science Policy Committee of the American College of Chest Physicians to develop a clinical practice guideline on the medical and surgical treatment of parapneumonic effusions (PPE) using evidence-based methods.
OPTIONS AND OUTCOMES CONSIDERED: Based on consensus of clinical opinion, the expert panel developed an annotated table for evaluating the risk for poor outcome in patients with PPE. Estimates of the risk for poor outcome were based on the clinical judgment that, without adequate drainage of the pleural space, the patient with PPE would be likely to have any or all of the following: prolonged hospitalization, prolonged evidence of systemic toxicity, increased morbidity from any drainage procedure, increased risk for residual ventilatory impairment, increased risk for local spread of the inflammatory reaction, and increased mortality. Three variables, pleural space anatomy, pleural fluid bacteriology, and pleural fluid chemistry, were used in this annotated table to categorize patients into four separate risk levels for poor outcome: categories 1 (very low risk), 2 (low risk), 3 (moderate risk), and 4 (high risk). The panel's consensus opinion supported drainage for patients with moderate (category 3) or high (category 4) risk for a poor outcome, but not for patients with very low (category 1) or low (category 2) risk for a poor outcome. The medical literature was reviewed to evaluate the effectiveness of medical and surgical management approaches for patients with PPE at moderate or high risk for poor outcome. The panel grouped PPE management approaches into six categories: no drainage performed, therapeutic thoracentesis, tube thoracostomy, fibrinolytics, video-assisted thoracoscopic surgery (VATS), and surgery (including thoracotoiny with or without decortication and rib resection). The fibrinolytic approach required tube thoracostomy for administration of drug, and VATS included post-procedure tube thoracostomy. Surgery may have included concomitant lung resection and always included postoperative tube thoracostomy. All management approaches included appropriate treatment of the underlying pneumonia, including systemic antibiotics. Criteria for including articles in the panel review were adequate data provided for >/=20 adult patients with PPE to allow evaluation of at least one relevant outcome (death or need for a second intervention to manage the PPE); reasonable assurance provided that drainage was clinically appropriate (patients receiving drainage were either category 3 or category 4) and drainage procedure was adequately described; and original data were presented. The strength of panel recommendations on management of PPE was based on the following approach: level A, randomized, controlled trials with consistent results or individual randomized, controlled trial with narrow confidence interval (CI); level B, controlled cohort and case control series; level C, historically controlled series and case series; and level D, expert opinion without explicit critical appraisal or based on physiology, bench research, or "first principles."
EVIDENCE: The literature review revealed 24 articles eligible for full review by the panel, 19 of which dealt with the primary management approach to PPE and 5 with a rescue approach after a previous approach had failed. Of the 19 involving the primary management approach to PPE, there were 3 randomized, controlled trials, 2 historically controlled series, and 14 case series. The number of patients included in the randomized controlled trials was small; methodologic weaknesses were found in the 19 articles describing the results of primary management approaches to PPE. The proportion and 95% CI of patients suffering each of the two relevant outcomes (death and need for a second intervention to manage the PPE) were calculated for the pooled data for each management approach from the 19 articles on the primary management approach. (ABST

PMID 11035692
Janda S, Swiston J. Intrapleural fibrinolytic therapy for treatment of adult parapneumonic effusions and empyemas: A systematic review and meta-analysis. Chest. American College of Chest Physicians; 2012;142(2):401–411.
Davies HE, Davies RJ, Davies CW; BTS Pleural Disease Guideline Group.
Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010.
Thorax. 2010 Aug;65 Suppl 2:ii41-53. doi: 10.1136/thx.2010.137000.
Abstract/Text
PMID 20696693
Shen KR, Bribriesco A, Crabtree T, Denlinger C, Eby J, Eiken P, Jones DR, Keshavjee S, Maldonado F, Paul S, Kozower B.
The American Association for Thoracic Surgery consensus guidelines for the management of empyema.
J Thorac Cardiovasc Surg. 2017 Jun;153(6):e129-e146. doi: 10.1016/j.jtcvs.2017.01.030. Epub 2017 Feb 4.
Abstract/Text
PMID 28274565
日本呼吸器外科学会. 膿胸治療ガイドライン. 2023.
Porcel JM, Vives M.
Differentiating tuberculous from malignant pleural effusions: a scoring model.
Med Sci Monit. 2003 May;9(5):CR175-80.
Abstract/Text BACKGROUND: Patients with tuberculous or malignant pleural effusions frequently have similar clinical manifestations and pleural fluid profile. The aim of our study was to derive a simple clinical score for differential diagnosis of these two clinical entities.
MATERIAL/METHODS: Our retrospective study involved 106 patients with tuberculous pleurisy and 286 with malignant effusions, seen during a 9-year period. Clinical and laboratory variables with (model 1) and without (model 2) the addition of pleural adenosine deaminase entered into a multivariate analysis to calculate a scoring system (range 0 to 10) for the detection of tuberculous effusions.
RESULTS: In model 1, four variables predicted a tuberculous etiology: adenosine deaminase > or = 40 U/L (5 points), age <35 years (2), temperature > or 37.8 degrees C (2), and pleural fluid red blood cell count < 5 x 10(9)/L (1). In addition to the last three items, model 2 identified other predictive parameters: no history of malignancy (3), pleural protein > or = 50 g/L (1), and pleural fluid to serum lactate dehydrogenase ratio > or 2.2 (1). Summated scores of > or 5 in model 1 and > or 6 in model 2 yielded measures of sensitivity (95% and 97%), and specificity (94% and 91%) for discriminating tuberculous from malignant effusions, respectively. The area under the ROC curve for models 1 and 2 was 0.987 and 0.982, respectively.
CONCLUSIONS: The combination of clinical data and pleural fluid chemistry profile into a score-based model can facilitate differential diagnosis between tuberculous and malignant effusions.

PMID 12761453
Liang QL, Shi HZ, Wang K, Qin SM, Qin XJ.
Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis.
Respir Med. 2008 May;102(5):744-54. doi: 10.1016/j.rmed.2007.12.007. Epub 2008 Jan 28.
Abstract/Text BACKGROUND: Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of adenosine deaminase (ADA) in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a meta-analysis to determine the accuracy of ADA measurements in the diagnosis of tuberculous pleurisy.
METHODS: After a systematic review of English language studies, sensitivity, specificity, and other measures of accuracy of ADA concentration in the diagnosis of pleural effusion were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance.
RESULTS: Sixty-three studies met our inclusion criteria. The summary estimates for ADA in the diagnosis of tuberculous pleurisy in the studies included were sensitivity 0.92 (95% confidence interval 0.90-0.93), specificity 0.90 (95% confidence interval 0.89-0.91), positive likelihood ratio 9.03 (95% confidence interval 7.19-11.35), negative likelihood ratio 0.10 (95% confidence interval 0.07-0.14), and diagnostic odds ratio 110.08 (95% confidence interval 69.96-173.20).
CONCLUSIONS: ADA determination is a relative sensitive and specific test for the diagnosis of tuberculous pleurisy. Measurement of ADA in pleural effusion is thus likely to be a useful diagnostic tool for tuberculous pleurisy. The results of ADA assays should be interpreted in parallel with clinical findings and the results of conventional tests.

PMID 18222681
Burgess LJ, Maritz FJ, Le Roux I, Taljaard JJ.
Combined use of pleural adenosine deaminase with lymphocyte/neutrophil ratio. Increased specificity for the diagnosis of tuberculous pleuritis.
Chest. 1996 Feb;109(2):414-9. doi: 10.1378/chest.109.2.414.
Abstract/Text UNLABELLED: Increased pleural fluid adenosine deaminase (ADA) activity is classically associated with tuberculous pleuritis. However, increased activity can also occur in a number of other diseases and this may negatively affect the diagnostic utility of ADA measurements and decrease its specificity for the diagnosis of tuberculosis (TB). The presence of ADA in pleural fluids reflects the cellular immune response in the pleural cavity and in particularly, the activation of T lymphocytes. Different disease entities are typically associated with the presence of particular types of leukocytes.
OBJECTIVE: To determine whether the combined use of ADA activity and differential cell counts would provide a more efficient means for diagnosing tuberculous pleurisy than the use of ADA levels alone.
METHODS: Biochemistry, cytology, and microbiology studies were performed on 472 consecutive pleural fluids. ADA and differential cell counts were determined on all exudative effusions.
RESULTS: ADA activity in tuberculous effusions was significantly higher than in any other diagnostic group (p < 0.005). At a level of 50 U/L, the sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv), and efficiency for the identification of TB were calculated at 91%, 81%, 84%, 89%, and 86%, respectively. When the additional requirement of a lymphocyte neutrophil ratio of 0.75 or greater was included, the sensitivity, specificity, ppv, npv, and efficiency for the identification of TB were calculated at 88%, 95%, 95%, 88%, and 92%, respectively.
CONCLUSION: ADA, especially when combined with differential cell counts and lymphocyte/neutrophil ratios, remains a useful test in the diagnosis tuberculous pleuritis.

PMID 8620715
Lee YC, Rogers JT, Rodriguez RM, Miller KD, Light RW.
Adenosine deaminase levels in nontuberculous lymphocytic pleural effusions.
Chest. 2001 Aug;120(2):356-61. doi: 10.1378/chest.120.2.356.
Abstract/Text OBJECTIVES: Adenosine deaminase (ADA) can aid in the diagnosis of tuberculous pleural effusions, but false-positive findings from lymphocytic effusions have been reported. We studied the ADA levels in a variety of nontuberculous lymphocytic effusions and analyzed the relationships between ADA and conventional hematologic and biochemical parameters.
METHODS: One hundred six lymphocytic pleural fluid samples (lymphocyte count > 50%) were analyzed. These included post-coronary artery bypass grafting (CABG) effusions (n = 45), malignant effusions (n = 27), miscellaneous exudative effusions (n = 10), and transudative effusions (n = 24). ADA levels were determined using the Giusti method. In 22 randomly selected cases, ADA was measured again on the same sample 6 weeks later.
RESULTS: The ADA level reached the diagnostic cutoff for tuberculosis (40 U/L) in only three cases (2.8%): two lymphomas and one complicated parapneumonic effusion. There was no significant correlation between effusion ADA levels and the total leukocyte (r = 0.08), differential lymphocyte (r = 0.18) or monocyte (r = - 0.18) counts. ADA levels were significantly lower in the transudative effusions (7.2 +/- 3.5 U/L) than in post-CABG (16.6 +/- 7.2 U/L), malignant (15.3 +/- 11.2 U/L), and other exudative (15.4 +/- 13.1 U/L) effusions (p < 0.001). ADA measurements were consistent when assayed 6 weeks apart (r = 0.95; p < 0.00001; coefficient of variation, 14%).
CONCLUSIONS: ADA levels in nontuberculous lymphocytic effusions seldom exceeded the diagnostic cutoff for TB. Effusion ADA levels cannot be predicted from total or differential leukocyte counts. Post-CABG pleural fluids had ADA levels similar to other nontuberculous lymphocytic effusions. ADA is stable in effusion fluids, and its measurement is reproducible.

PMID 11502629
Jiang J, Shi HZ, Liang QL, Qin SM, Qin XJ.
Diagnostic value of interferon-gamma in tuberculous pleurisy: a metaanalysis.
Chest. 2007 Apr;131(4):1133-41. doi: 10.1378/chest.06-2273.
Abstract/Text BACKGROUND: Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of interferon (IFN)-gamma measurements in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a metaanalysis to determine the accuracy of IFN-gamma measurements in the diagnosis of tuberculous pleurisy.
METHODS: After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of IFN-gamma concentrations in the diagnosis of pleural effusion were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance.
RESULTS: Twenty-two studies met our inclusion criteria. The summary estimates for IFN-gamma in the diagnosis of tuberculous pleurisy in the studies included were as follows: sensitivity, 0.89 (95% confidence interval [CI], 0.87 to 0.91); specificity, 0.97 (95% CI, 0.96 to 0.98); positive likelihood ratio, 23.45 (95% CI, 17.31 to 31.78); negative likelihood ratio, 0.11 (95% CI, 0.07 to 0.16); and diagnostic odds ratio, 272.7 (95% CI, 147.5 to 504.2).
CONCLUSIONS: IFN-gamma determination is a sensitive and specific test for the diagnosis of tuberculous pleurisy. The measurement of IFN-gamma levels in pleural effusions is thus likely to be a useful tool for diagnosing tuberculous pleurisy. The results of IFN-gamma assays should be interpreted in parallel with clinical findings and the results of conventional tests.

PMID 17426220
Villena V, López-Encuentra A, Pozo F, Echave-Sustaeta J, Ortuño-de-Solo B, Estenoz-Alfaro J, Martín-Escribano P.
Interferon gamma levels in pleural fluid for the diagnosis of tuberculosis.
Am J Med. 2003 Oct 1;115(5):365-70. doi: 10.1016/s0002-9343(03)00423-6.
Abstract/Text PURPOSE: To assess the utility of interferon gamma levels, including identification of the best cutoff for the diagnosis of tuberculosis.
METHODS: We prospectively studied consecutive patients in a tertiary care, university-affiliated hospital who had pleural effusions. Interferon gamma levels were measured blindly by radioimmunoassay. The diagnosis of tuberculosis was established using prespecified standard criteria.
RESULTS: Of the 595 patients with pleural effusions, 82 patients (14%) had tuberculosis. The area under the receiver operating characteristic (ROC) curve for elevated interferon gamma levels in the diagnosis of tuberculosis was 0.99 (95% confidence interval [CI]: 0.97 to 1.00). A cutoff of 3.7 IU/mL yielded a sensitivity of 0.98 (95% CI: 0.91 to 1.00) and a specificity of 0.98 (95% CI: 0.96 to 0.99). The areas under the ROC curves, and the test's sensitivity and specificity, were similar among patients of different ages and by percentage of lymphocytes in the pleural fluid. In 5 of the 28 patients with hematologic malignancies, interferon gamma levels were slightly above the cutoff; no patient with vasculitis or granulomatous diseases had levels higher than 3.7 IU/mL. The 14 immunocompromised patients and the 3 transplantation patients with tuberculosis had interferon gamma levels greater than the cutoff.
CONCLUSION: Elevated pleural interferon gamma levels (>3.7 IU/mL) are very valuable in diagnosing pleural tuberculosis. Patients with pleural effusion due to hematologic neoplasms occasionally have levels slightly above the cutoff.

PMID 14553871
Pai M, Flores LL, Hubbard A, Riley LW, Colford JM Jr.
Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis.
BMC Infect Dis. 2004 Feb 23;4:6. doi: 10.1186/1471-2334-4-6. Epub 2004 Feb 23.
Abstract/Text BACKGROUND: Conventional tests for tuberculous pleuritis have several limitations. A variety of new, rapid tests such as nucleic acid amplification tests--including polymerase chain reaction--have been evaluated in recent times. We conducted a systematic review to determine the accuracy of nucleic acid amplification (NAA) tests in the diagnosis of tuberculous pleuritis.
METHODS: A systematic review and meta-analysis of 38 English and Spanish articles (with 40 studies), identified via searches of six electronic databases, hand searching of selected journals, and contact with authors, experts, and test manufacturers. Sensitivity, specificity, and other measures of accuracy were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Heterogeneity in study results was formally explored using subgroup analyses.
RESULTS: Of the 40 studies included, 26 used in-house ("home-brew") tests, and 14 used commercial tests. Commercial tests had a low overall sensitivity (0.62; 95% confidence interval [CI] 0.43, 0.77), and high specificity (0.98; 95% CI 0.96, 0.98). The positive and negative likelihood ratios for commercial tests were 25.4 (95% CI 16.2, 40.0) and 0.40 (95% CI 0.24, 0.67), respectively. All commercial tests had consistently high specificity estimates; the sensitivity estimates, however, were heterogeneous across studies. With the in-house tests, both sensitivity and specificity estimates were significantly heterogeneous. Clinically meaningful summary estimates could not be determined for in-house tests.
CONCLUSIONS: Our results suggest that commercial NAA tests may have a potential role in confirming (ruling in) tuberculous pleuritis. However, these tests have low and variable sensitivity and, therefore, may not be useful in excluding (ruling out) the disease. NAA test results, therefore, cannot replace conventional tests; they need to be interpreted in parallel with clinical findings and results of conventional tests. The accuracy of in-house nucleic acid amplification tests is poorly defined because of heterogeneity in study results. The clinical applicability of in-house NAA tests remains unclear.

PMID 15102325
Porcel JM.
Pearls and myths in pleural fluid analysis.
Respirology. 2011 Jan;16(1):44-52. doi: 10.1111/j.1440-1843.2010.01794.x.
Abstract/Text Virtually all patients with a newly discovered pleural effusion should undergo thoracentesis to aid in diagnosis and management. The routine pleural fluid (PF) evaluation usually includes the following: cell count and differential; tests for protein, LDH, glucose, adenosine deaminase, cytology and, if infection is a concern, pH and bacterial and mycobacterial cultures. Distinguishing transudates from exudates with Light's criteria is a pragmatic first step. If the effusion is an exudate, various PF tests have proven diagnostic utility: adenosine deaminase levels >35 IU/L usually indicate tuberculosis in lymphocyte-predominant PF; pH < 7.2 or glucose less than 60 mg/dL allow the clinician to identify complicated parapneumonic effusions; and conventional cytology may reveal malignant cells in 60% of the patients with malignant effusions. A number of optional PF tests may complement the diagnostic approach to an undiagnosed pleural effusion. For example, natriuretic peptide assays significantly improve the accuracy of a diagnosis of cardiac pleural effusion, whereas PF mesothelin levels greater than 20 nmol/L are highly suggestive of mesothelioma.

© 2010 The Author. Journal compilation © 2010 Asian Pacific Society of Respirology.
PMID 20573057
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、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐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。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※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、実際の保険適応の査定において保険適応及び保険適応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応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:
山沢英明 : 特に申告事項無し[2025年]
監修:杉山幸比古 : 特に申告事項無し[2025年]

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