The Clinical Respiratory Journal
ORIGINAL ARTICLE
Moderate hemoptysis: recurrent hemoptysis and mortality according to bronchial artery embolization Myoung Kyu Lee1, Sang-Ha Kim1, Suk Joong Yong1, Kye Chul Shin1, Hyun Sik Kim1, Tae-Sun Yu1, Eun Hee Choi2 and Won-Yeon Lee1 1 Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea 2 Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
Abstract Introduction: The studies on hemoptysis have focused mainly on hemoptysis causes and massive or life-threatening hemoptysis. And there is a limited data that non-massive hemoptysis, especially moderate hemoptysis. Objectives: We analyzed the prognosis and severity of bleeding on flexible bronchoscopy (FB) between moderate and massive hemoptysis. Methods: We reviewed total 852 subjects (59.9 ± 16.0 years) identified with hemoptysis. Reviewed database included severity of subjective hemoptysis, bleeding on FB, comorbid conditions, time from admission to bronchial artery embolization (BAE), recurrent hemoptysis and mortality. Results: In subjective hemoptysis, recurrent hemoptysis occurred in mild 8.0%, moderate 40.7%, massive hemoptysis 33.8%, and mortality was 4.7%, 13.4% and 13.5%. Especially, no statistical difference was shown in recurrent hemoptysis [hazard ratio (HR) = 0.795; 95% confidence interval (CI) 0.562–1.125, P = 0.196] and mortality (HR = 1.054; 95% CI 0.596–1.864, P = 0.856) between moderate and massive hemoptysis. In moderate hemoptysis patients, oozing or active bleeding on FB took up 83.3%. In this review, recurrent hemoptysis was more in oozing bleeding than active bleeding (HR = 1.781; 95% CI 1.214–2.431, P = 0.002), but mortality was similar (HR = 1.611; 95% CI 0.930–2.790, P = 0.089). Recurrent hemoptysis significantly decreased in the group with BAE performed within 24 h (HR = 0.308; 95% CI 0.149–0.637, P = 0.001) in moderate hemoptysis. Also, recurrent hemoptysis and mortality were significantly increased in the patients with smoking (≥40 pack-years), oozing or active bleeding on FB, and hypertension. Conclusion: Moderate hemoptysis has shown similar prognosis of recurrent hemoptysis and mortality to massive hemoptysis. Therefore, the more aggressive FB and BAE should be considered in moderate hemoptysis.
Key words bronchial artery embolization – flexible bronchoscopy – mortality – recurrent hemoptysis
Please cite this paper as: Lee MK, Kim S-H, Yong SJ, Shin KC, Kim HS, Yu T-S, Choi EH and Lee W-Y. Moderate hemoptysis: recurrent hemoptysis and mortality according to bronchial artery embolization. Clin Respir J 2015; 9: 53–64.
Ethics Research is based on administrative data treated anonymously in the analysis. Research was conducted in compliance with the requirements and under the authorization of the local institutional review board (IRB No. CR312038).
Abbreviations: BAE bronchial artery embolization CI confidence interval COPD chronic obstructive pulmonary disease DM diabetes mellitus FB flexible bronchoscopy HR hazard ratio py pack-years SD standard deviation
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Correspondence Won-Yeon Lee, MD, Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsandong Wonju Gangwon, Korea 220-701 Tel: 82 33 741 1234 0926 Fax: 82 33 741 0928 email: [email protected] Received: 17 July 2013 Revision requested: 24 November 2013 Accepted: 04 January 2014 DOI:10.1111/crj.12104 Authorship and contributorship Myoung Kyu Lee designed this investigation and wrote the manuscript. Sang-Ha Kim, Suk Joong Yong and Kye Chul Shin contributed to study design. Hyun Sik Kim and Tae-Sun Yu collected and analyzed the data. Eun Hee Choi conducted statistical analysis and revision of the manuscript. Won-Yeon Lee designed this investigation and reviewed the manuscript.
Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
53
The prognosis of moderate hemoptysis
Lee et al.
Introduction
Materials and methods
Hemoptysis is the spitting of blood that originated in the lungs and bronchial tubes (1). In general, diseases that cause hemoptysis include bronchiectasis, active pulmonary tuberculosis, lung cancer, pulmonary hypertension, aspergilloma, chronic bronchitis and coagulation disorders (2, 3). In addition, massive hemoptysis is a life-threatening condition that should require prompt examination and aggressive treatment (4). When hemoptysis occurs, it is important to find out cause of disease and hemoptysis amount, and to determine therapeutic bronchial artery embolization (BAE) or surgical treatment (5, 6). BAE is a valuable therapeutic option in patients who are not candidates for surgery or who do not respond to conservative treatments (7, 8). However, current studies have focused on treatment of massive hemoptysis. And the definition of massive hemoptysis varies such as bleeding in 100– 1000 mL (9) or 200–600 mL (10) for 24 h. It is also difficult to measure subjective hemoptysis amount because the methods to measure amount vary according to area, using a paper cup (11) or a glass in 240 cc (12). Therefore, it is not easy to separate massive or non-massive hemoptysis. And there is relatively less research for treatment guidelines of non-massive hemoptysis. Non-massive hemoptysis is divided to mild and moderate hemoptysis (5, 10, 13). Mild hemoptysis is known to be easily subsided when underlying disease is treated (5, 14, 15). On the other hand, in moderate hemoptysis, the most critical aspect is the difficulty maintaining an acceptable level of interpersonal relationships and the psychological implications of this call for an effective therapeutic solution (16). And moderate hemoptysis usually should be distinguished by quantifying daily bleeding amount, and flexible bronchoscopy (FB) is recommended when hemoptysis persists during treatment of underlying disease (10, 17). But it could be subjective to separate between moderate and massive hemoptysis by quantifying daily bleeding amount, and we could not be sure that treatment according to guidelines of moderate hemoptysis showed better prognosis than massive hemoptysis. Therefore, the authors performed a cohort study to compare prognosis including recurrent hemoptysis and mortality according to severity of subjective hemoptysis and degree of bleeding identified in FB. And we analyzed the differences of prognosis between moderate and massive hemoptysis.
Patients
54
We reviewed total 852 patients among 2058 hemoptysis patients aged 18 or higher who visited a respiratory center of Yonsei University Wonju Christian Hospital from January 2008 to February 2012. Exclusion criteria were as follows: traumatic hemoptysis, gastrointestinal or oropharyngeal bleeding, heart failure, and follow-up loss within 6 months. The following information of each patient was reviewed: baseline demographics, initial clinical presentation and laboratory data, chest radiography, contrast-enhanced computed tomography (CT) scan when performed, severity of subjective hemoptysis, degree of bleeding on FB, cause of hemoptysis, comorbid conditions including aspirin medication, smoking amount, time from admission to BAE, recurrent hemoptysis, and mortality (Fig. 1). The median period of observation was 2.8 years (0.5–4.5 years).
Severity of subjective hemoptysis and degree of bleeding on FB In order to measure amount of hemoptysis, we assessed according to (i) severity of subjective hemoptysis and (ii) degree of bleeding on FB. According to severity of subjective hemoptysis, it was classified to‘mild’ (200 cc) if more than 4 cups of hemoptysis. According to degree of bleeding on FB, it was classified to ‘recent bleeding’ if no further bleeding after removing the hemorrhage, ‘oozing bleeding’if continued small amount of bleeding enough to determine the location of bleeding, and ‘active bleeding’ if continued bleeding and it was difficult to determine the location of bleeding after removing the hemorrhage (Fig. 2).
FB FB was done in a special procedure suite. BF-260 (Olympus, Tokyo, Japan) was used, and FB was performed by two expertized pulmonologists who had been training more than 10 years to confirm degree of bleeding and reduce complications. In the procedure area, all patients were connected to a pulse-oximeter to monitor the oxygen level. Blood pressure and heart rate were also monitored. And they also treated with a local anesthetic spray to prevent coughing and gagging during the procedure.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Lee et al.
The prognosis of moderate hemoptysis
BAE
Figure 1. Flowchart patients.
shows
identification
of
hemoptysis
Conservative treatment All patients received conservative treatment: strict bed rest, nothing by mouth, oxygen supply and continuous oxygen saturation monitoring. Central venous or a large-bore intravenous catheter was inserted, and all medications potentially increasing the risk of bleeding were stopped. And also, 1.0–2.0 iu/8 hours of botropase (haemocoagulase) and/or 1.0–2.0 mg/4–6 h of terlipressin for bleeding control was inserted intravenously if not contraindicated.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
BAE was performed by one expertized angiographer during active bleeding or soon after bleeding cessation. The site of bleeding was lateralized by chest radiography or FB. All patients underwent BAE with a digital subtraction angiography unit (BV 5000; Philips Medical System, Best, the Netherlands) through the right femoral artery approach with an introducer sheath using the Seldinger technique. Non-ionic contrast material (Iopamiron 300; Bayer Japan, Tokyo, Japan) was used. Selective angiograms with a 4-french (F) catheter (Michaelson or Shepherd Hook type; Medikit Co Ltd, Tokyo, Japan, or Cobra 2 Glidecath, Terumo®, Tokyo, Japan) were performed for the bronchial artery and non-bronchial systemic collateral branches arise from the subclavian, axillary and internal mammary arteries. Pathological artery was considered when tortuous hypertrophy, regions of hypervascularity, systemic-to-pulmonary shunting or extravasation of the contrast agent was found (18, 19). Pulmonary angiography was performed when no abnormality was found on bronchial angiography. The BAE was performed as follows: an angiographic catheter was inserted to the level of the origin or proximal segment of medium-sized vessels including the bronchial, intercostal, internal thoracic or lateral thoracic arteries. Superselective arteriography with a 2.0- or 2.7-F Progreat™ microcatheter (Terumo) was inserted coaxially into the angiographic catheter and advanced through the pathological arteries at the most possible distal portion to prevent leakage of embolic materials into the anterior spinal artery or thoracic aorta. After the microcatheter was inserted, embolization materials with a 355- to 500-μm-sized polyvinyl alcohol (Contour Emboli, Boston Scientific, Natick, MA, USA) were injected into the pathological arteries. Successful BAE was defined that embolization materials were completely composed on bleeding arterial sites and that bleeding was successfully controlled immediately after BAE (6, 9, 18) (Fig. 2). Complications associated with BAE were investigated including chest pain, dyspnea, arterial dissection and neurological discomfort.
End points Two kinds of end point were reviewed in hemoptysis patients, recurrent hemoptysis and mortality. Recurrent hemoptysis was defined that hemoptysis was relapsed at least 24 h after performed successful BAE or spontaneously stopped (17, 20), and mortality was defined as the death associated with hemoptysis. Then, 55
The prognosis of moderate hemoptysis
Lee et al.
Figure 2. Depending on degree of bleeding observed by flexible bronchoscopy, it was classified (A) recent bleeding if no further bleeding after removing the hemorrhage, (B) oozing bleeding if continued small amount of bleeding enough to determine the location of bleeding, (C) active bleeding if continued bleeding in trachea (arrow) and it was difficult to determine the location of bleeding after removing the hemorrhage. (D) Bronchial angiography showed hypertrophic change in right bronchial artery, and hypervascularity and hyperemic strain in intercostal arteries and right lower lung field, (E) embolization performed in right bronchial artery (arrows) with 355- to 500-μm-sized polyvinyl alcohol. (F) Bronchial angiography showed hypervascularity in right bronchial artery, (G) embolization performed in right bronchial artery (arrow).
we compared recurrent hemoptysis and mortality according to severity of subjective hemoptysis and degree of bleeding on FB.
Data analysis SPSS 18.0 (SPSS, Inc., Chicago, IL, USA) were used for statistical analysis. Chi-squared test was used for categorical data, and one-way analysis of variance (ANOVA) test was used to compare continuous data among three groups. Cox proportional hazard model was used to estimate hazard ratio (HR) for recurrent hemoptysis and mortality between two groups. Cumulative survival and cumulative recurrent hemoptysis were evaluated using a Kaplan–Meier approach and the log-rank test. Univariate and multivariate analysis was performed to determine risk factors of recurrent hemoptysis and mortality. Continuous variables were
56
expressed in the form of mean value ± standard deviation, and P value less than 0.05 was considered to be statistically significant.
Results Total subjects The total 852 patients included 553 (64.9%) men. The mean age was 59.9 ± 16.0 years. Laboratory findings in the patients were shown in Tables 1 and 2. According to severity of subjective hemoptysis, there were separated to 488 (57.2%) patients with mild, 216 (25.4%) moderate and 148 (17.4%) massive hemoptysis. And according to degree of bleeding on FB, there were separated to 504 (59.2%) patients with recent bleeding, 137 (16.1%) oozing bleeding and 211 (24.7%) active bleeding. A total of 320 (37.6%) patients had successful
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
The prognosis of moderate hemoptysis
220 (25.8) 187 (21.9) 64 (7.5) 75 (8.8) 119 (14.0) 359 (42.1) 33.5 ± 16.3 209 (24.6) 30.8 ± 13.0 284 (33.3)
*Arterial blood gas analysis results including pH, PaO2, PaCO2 and SaO2 were available for total 624 patients. †Complications after BAE included chest discomfort (n = 16), dyspnea (n = 7), minor femoral arterial dissection (n = 4), major arterial dissection (n = 1) and dizziness but transient (n = 3). BAE, bronchial artery embolization; CT, computed tomography; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; FB, flexible bronchoscopy; n, number; PaCO2, arterial carbon dioxide pressure; PaO2, arterial oxygen pressure; SaO2, oxygen saturation of arterial blood; SD, standard deviation.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
PaCO2, arterial carbon dioxide pressure; PaO2, arterial oxygen pressure; SaO2, oxygen saturation of arterial blood.
245 (28.8) 173 (20.3) 159 (18.7) 85 (10.0) 64 (7.5) 36 (4.2) 29 (3.4) 61 (7.1)
Variables, mean ± SD
504 (59.2) 137 (16.1) 211 (24.7) 320 (37.6) 237 83 31 177 (20.8) 72 (8.5)
3
713 (83.7) 522 (61.3) 488 (57.2) 216 (25.4) 148 (17.4)
8807 ± 3280 (5010–17 660) 11.5 ± 1.6 (8.2–15.1) 279 640 ± 101 982 (77 000–506 000) 90 ± 13 (56–115) 1.0 ± 0.1 (0.8–1.1) 18.7 ± 16.9 (6.0–90.0) 7.43 ± 0.05 (7.32–7.54) 81.0 ± 13.1 (62.3–99.3) 30.6 ± 4.5 (22.6–35.6) 93.3 ± 14.4 (31.3–99.5) 8293 ± 3404 (1840–22 270) 12.8 ± 2.0 (8.2–16.7) 278 660 ± 101 255 (65 000–570 000) 91 ± 20 (24–121) 1.0 ± 0.3 (0.7–2.1) 17.7 ± 7.9 (10.0–51.0) 7.41 ± 0.03 (7.34–7.47) 76.1 ± 12.6 (47.2–98.5) 34.3 ± 6.0 (28.1–45.1) 95.3 ± 3.2 (84.5–98.8)
Massive hemoptysis
16.5 ± 9.5 (6.0–90.0) 7.41 ± 0.06 (7.13–7.54) 79.4 ± 13.1 (47.2–99.3) 34.8 ± 6.0 (22.6–50.9) 95.5 ± 6.4 (31.3–99.5) 809 (95.0)
Table 2. The laboratory findings according to severity of subjective hemoptysis
ORIGINAL ARTICLE
Moderate hemoptysis: recurrent hemoptysis and mortality according to bronchial artery embolization Myoung Kyu Lee1, Sang-Ha Kim1, Suk Joong Yong1, Kye Chul Shin1, Hyun Sik Kim1, Tae-Sun Yu1, Eun Hee Choi2 and Won-Yeon Lee1 1 Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea 2 Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
Abstract Introduction: The studies on hemoptysis have focused mainly on hemoptysis causes and massive or life-threatening hemoptysis. And there is a limited data that non-massive hemoptysis, especially moderate hemoptysis. Objectives: We analyzed the prognosis and severity of bleeding on flexible bronchoscopy (FB) between moderate and massive hemoptysis. Methods: We reviewed total 852 subjects (59.9 ± 16.0 years) identified with hemoptysis. Reviewed database included severity of subjective hemoptysis, bleeding on FB, comorbid conditions, time from admission to bronchial artery embolization (BAE), recurrent hemoptysis and mortality. Results: In subjective hemoptysis, recurrent hemoptysis occurred in mild 8.0%, moderate 40.7%, massive hemoptysis 33.8%, and mortality was 4.7%, 13.4% and 13.5%. Especially, no statistical difference was shown in recurrent hemoptysis [hazard ratio (HR) = 0.795; 95% confidence interval (CI) 0.562–1.125, P = 0.196] and mortality (HR = 1.054; 95% CI 0.596–1.864, P = 0.856) between moderate and massive hemoptysis. In moderate hemoptysis patients, oozing or active bleeding on FB took up 83.3%. In this review, recurrent hemoptysis was more in oozing bleeding than active bleeding (HR = 1.781; 95% CI 1.214–2.431, P = 0.002), but mortality was similar (HR = 1.611; 95% CI 0.930–2.790, P = 0.089). Recurrent hemoptysis significantly decreased in the group with BAE performed within 24 h (HR = 0.308; 95% CI 0.149–0.637, P = 0.001) in moderate hemoptysis. Also, recurrent hemoptysis and mortality were significantly increased in the patients with smoking (≥40 pack-years), oozing or active bleeding on FB, and hypertension. Conclusion: Moderate hemoptysis has shown similar prognosis of recurrent hemoptysis and mortality to massive hemoptysis. Therefore, the more aggressive FB and BAE should be considered in moderate hemoptysis.
Key words bronchial artery embolization – flexible bronchoscopy – mortality – recurrent hemoptysis
Please cite this paper as: Lee MK, Kim S-H, Yong SJ, Shin KC, Kim HS, Yu T-S, Choi EH and Lee W-Y. Moderate hemoptysis: recurrent hemoptysis and mortality according to bronchial artery embolization. Clin Respir J 2015; 9: 53–64.
Ethics Research is based on administrative data treated anonymously in the analysis. Research was conducted in compliance with the requirements and under the authorization of the local institutional review board (IRB No. CR312038).
Abbreviations: BAE bronchial artery embolization CI confidence interval COPD chronic obstructive pulmonary disease DM diabetes mellitus FB flexible bronchoscopy HR hazard ratio py pack-years SD standard deviation
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Correspondence Won-Yeon Lee, MD, Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsandong Wonju Gangwon, Korea 220-701 Tel: 82 33 741 1234 0926 Fax: 82 33 741 0928 email: [email protected] Received: 17 July 2013 Revision requested: 24 November 2013 Accepted: 04 January 2014 DOI:10.1111/crj.12104 Authorship and contributorship Myoung Kyu Lee designed this investigation and wrote the manuscript. Sang-Ha Kim, Suk Joong Yong and Kye Chul Shin contributed to study design. Hyun Sik Kim and Tae-Sun Yu collected and analyzed the data. Eun Hee Choi conducted statistical analysis and revision of the manuscript. Won-Yeon Lee designed this investigation and reviewed the manuscript.
Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
53
The prognosis of moderate hemoptysis
Lee et al.
Introduction
Materials and methods
Hemoptysis is the spitting of blood that originated in the lungs and bronchial tubes (1). In general, diseases that cause hemoptysis include bronchiectasis, active pulmonary tuberculosis, lung cancer, pulmonary hypertension, aspergilloma, chronic bronchitis and coagulation disorders (2, 3). In addition, massive hemoptysis is a life-threatening condition that should require prompt examination and aggressive treatment (4). When hemoptysis occurs, it is important to find out cause of disease and hemoptysis amount, and to determine therapeutic bronchial artery embolization (BAE) or surgical treatment (5, 6). BAE is a valuable therapeutic option in patients who are not candidates for surgery or who do not respond to conservative treatments (7, 8). However, current studies have focused on treatment of massive hemoptysis. And the definition of massive hemoptysis varies such as bleeding in 100– 1000 mL (9) or 200–600 mL (10) for 24 h. It is also difficult to measure subjective hemoptysis amount because the methods to measure amount vary according to area, using a paper cup (11) or a glass in 240 cc (12). Therefore, it is not easy to separate massive or non-massive hemoptysis. And there is relatively less research for treatment guidelines of non-massive hemoptysis. Non-massive hemoptysis is divided to mild and moderate hemoptysis (5, 10, 13). Mild hemoptysis is known to be easily subsided when underlying disease is treated (5, 14, 15). On the other hand, in moderate hemoptysis, the most critical aspect is the difficulty maintaining an acceptable level of interpersonal relationships and the psychological implications of this call for an effective therapeutic solution (16). And moderate hemoptysis usually should be distinguished by quantifying daily bleeding amount, and flexible bronchoscopy (FB) is recommended when hemoptysis persists during treatment of underlying disease (10, 17). But it could be subjective to separate between moderate and massive hemoptysis by quantifying daily bleeding amount, and we could not be sure that treatment according to guidelines of moderate hemoptysis showed better prognosis than massive hemoptysis. Therefore, the authors performed a cohort study to compare prognosis including recurrent hemoptysis and mortality according to severity of subjective hemoptysis and degree of bleeding identified in FB. And we analyzed the differences of prognosis between moderate and massive hemoptysis.
Patients
54
We reviewed total 852 patients among 2058 hemoptysis patients aged 18 or higher who visited a respiratory center of Yonsei University Wonju Christian Hospital from January 2008 to February 2012. Exclusion criteria were as follows: traumatic hemoptysis, gastrointestinal or oropharyngeal bleeding, heart failure, and follow-up loss within 6 months. The following information of each patient was reviewed: baseline demographics, initial clinical presentation and laboratory data, chest radiography, contrast-enhanced computed tomography (CT) scan when performed, severity of subjective hemoptysis, degree of bleeding on FB, cause of hemoptysis, comorbid conditions including aspirin medication, smoking amount, time from admission to BAE, recurrent hemoptysis, and mortality (Fig. 1). The median period of observation was 2.8 years (0.5–4.5 years).
Severity of subjective hemoptysis and degree of bleeding on FB In order to measure amount of hemoptysis, we assessed according to (i) severity of subjective hemoptysis and (ii) degree of bleeding on FB. According to severity of subjective hemoptysis, it was classified to‘mild’ (200 cc) if more than 4 cups of hemoptysis. According to degree of bleeding on FB, it was classified to ‘recent bleeding’ if no further bleeding after removing the hemorrhage, ‘oozing bleeding’if continued small amount of bleeding enough to determine the location of bleeding, and ‘active bleeding’ if continued bleeding and it was difficult to determine the location of bleeding after removing the hemorrhage (Fig. 2).
FB FB was done in a special procedure suite. BF-260 (Olympus, Tokyo, Japan) was used, and FB was performed by two expertized pulmonologists who had been training more than 10 years to confirm degree of bleeding and reduce complications. In the procedure area, all patients were connected to a pulse-oximeter to monitor the oxygen level. Blood pressure and heart rate were also monitored. And they also treated with a local anesthetic spray to prevent coughing and gagging during the procedure.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
Lee et al.
The prognosis of moderate hemoptysis
BAE
Figure 1. Flowchart patients.
shows
identification
of
hemoptysis
Conservative treatment All patients received conservative treatment: strict bed rest, nothing by mouth, oxygen supply and continuous oxygen saturation monitoring. Central venous or a large-bore intravenous catheter was inserted, and all medications potentially increasing the risk of bleeding were stopped. And also, 1.0–2.0 iu/8 hours of botropase (haemocoagulase) and/or 1.0–2.0 mg/4–6 h of terlipressin for bleeding control was inserted intravenously if not contraindicated.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
BAE was performed by one expertized angiographer during active bleeding or soon after bleeding cessation. The site of bleeding was lateralized by chest radiography or FB. All patients underwent BAE with a digital subtraction angiography unit (BV 5000; Philips Medical System, Best, the Netherlands) through the right femoral artery approach with an introducer sheath using the Seldinger technique. Non-ionic contrast material (Iopamiron 300; Bayer Japan, Tokyo, Japan) was used. Selective angiograms with a 4-french (F) catheter (Michaelson or Shepherd Hook type; Medikit Co Ltd, Tokyo, Japan, or Cobra 2 Glidecath, Terumo®, Tokyo, Japan) were performed for the bronchial artery and non-bronchial systemic collateral branches arise from the subclavian, axillary and internal mammary arteries. Pathological artery was considered when tortuous hypertrophy, regions of hypervascularity, systemic-to-pulmonary shunting or extravasation of the contrast agent was found (18, 19). Pulmonary angiography was performed when no abnormality was found on bronchial angiography. The BAE was performed as follows: an angiographic catheter was inserted to the level of the origin or proximal segment of medium-sized vessels including the bronchial, intercostal, internal thoracic or lateral thoracic arteries. Superselective arteriography with a 2.0- or 2.7-F Progreat™ microcatheter (Terumo) was inserted coaxially into the angiographic catheter and advanced through the pathological arteries at the most possible distal portion to prevent leakage of embolic materials into the anterior spinal artery or thoracic aorta. After the microcatheter was inserted, embolization materials with a 355- to 500-μm-sized polyvinyl alcohol (Contour Emboli, Boston Scientific, Natick, MA, USA) were injected into the pathological arteries. Successful BAE was defined that embolization materials were completely composed on bleeding arterial sites and that bleeding was successfully controlled immediately after BAE (6, 9, 18) (Fig. 2). Complications associated with BAE were investigated including chest pain, dyspnea, arterial dissection and neurological discomfort.
End points Two kinds of end point were reviewed in hemoptysis patients, recurrent hemoptysis and mortality. Recurrent hemoptysis was defined that hemoptysis was relapsed at least 24 h after performed successful BAE or spontaneously stopped (17, 20), and mortality was defined as the death associated with hemoptysis. Then, 55
The prognosis of moderate hemoptysis
Lee et al.
Figure 2. Depending on degree of bleeding observed by flexible bronchoscopy, it was classified (A) recent bleeding if no further bleeding after removing the hemorrhage, (B) oozing bleeding if continued small amount of bleeding enough to determine the location of bleeding, (C) active bleeding if continued bleeding in trachea (arrow) and it was difficult to determine the location of bleeding after removing the hemorrhage. (D) Bronchial angiography showed hypertrophic change in right bronchial artery, and hypervascularity and hyperemic strain in intercostal arteries and right lower lung field, (E) embolization performed in right bronchial artery (arrows) with 355- to 500-μm-sized polyvinyl alcohol. (F) Bronchial angiography showed hypervascularity in right bronchial artery, (G) embolization performed in right bronchial artery (arrow).
we compared recurrent hemoptysis and mortality according to severity of subjective hemoptysis and degree of bleeding on FB.
Data analysis SPSS 18.0 (SPSS, Inc., Chicago, IL, USA) were used for statistical analysis. Chi-squared test was used for categorical data, and one-way analysis of variance (ANOVA) test was used to compare continuous data among three groups. Cox proportional hazard model was used to estimate hazard ratio (HR) for recurrent hemoptysis and mortality between two groups. Cumulative survival and cumulative recurrent hemoptysis were evaluated using a Kaplan–Meier approach and the log-rank test. Univariate and multivariate analysis was performed to determine risk factors of recurrent hemoptysis and mortality. Continuous variables were
56
expressed in the form of mean value ± standard deviation, and P value less than 0.05 was considered to be statistically significant.
Results Total subjects The total 852 patients included 553 (64.9%) men. The mean age was 59.9 ± 16.0 years. Laboratory findings in the patients were shown in Tables 1 and 2. According to severity of subjective hemoptysis, there were separated to 488 (57.2%) patients with mild, 216 (25.4%) moderate and 148 (17.4%) massive hemoptysis. And according to degree of bleeding on FB, there were separated to 504 (59.2%) patients with recent bleeding, 137 (16.1%) oozing bleeding and 211 (24.7%) active bleeding. A total of 320 (37.6%) patients had successful
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
The prognosis of moderate hemoptysis
220 (25.8) 187 (21.9) 64 (7.5) 75 (8.8) 119 (14.0) 359 (42.1) 33.5 ± 16.3 209 (24.6) 30.8 ± 13.0 284 (33.3)
*Arterial blood gas analysis results including pH, PaO2, PaCO2 and SaO2 were available for total 624 patients. †Complications after BAE included chest discomfort (n = 16), dyspnea (n = 7), minor femoral arterial dissection (n = 4), major arterial dissection (n = 1) and dizziness but transient (n = 3). BAE, bronchial artery embolization; CT, computed tomography; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; FB, flexible bronchoscopy; n, number; PaCO2, arterial carbon dioxide pressure; PaO2, arterial oxygen pressure; SaO2, oxygen saturation of arterial blood; SD, standard deviation.
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2014 John Wiley & Sons Ltd
PaCO2, arterial carbon dioxide pressure; PaO2, arterial oxygen pressure; SaO2, oxygen saturation of arterial blood.
245 (28.8) 173 (20.3) 159 (18.7) 85 (10.0) 64 (7.5) 36 (4.2) 29 (3.4) 61 (7.1)
Variables, mean ± SD
504 (59.2) 137 (16.1) 211 (24.7) 320 (37.6) 237 83 31 177 (20.8) 72 (8.5)
3
713 (83.7) 522 (61.3) 488 (57.2) 216 (25.4) 148 (17.4)
8807 ± 3280 (5010–17 660) 11.5 ± 1.6 (8.2–15.1) 279 640 ± 101 982 (77 000–506 000) 90 ± 13 (56–115) 1.0 ± 0.1 (0.8–1.1) 18.7 ± 16.9 (6.0–90.0) 7.43 ± 0.05 (7.32–7.54) 81.0 ± 13.1 (62.3–99.3) 30.6 ± 4.5 (22.6–35.6) 93.3 ± 14.4 (31.3–99.5) 8293 ± 3404 (1840–22 270) 12.8 ± 2.0 (8.2–16.7) 278 660 ± 101 255 (65 000–570 000) 91 ± 20 (24–121) 1.0 ± 0.3 (0.7–2.1) 17.7 ± 7.9 (10.0–51.0) 7.41 ± 0.03 (7.34–7.47) 76.1 ± 12.6 (47.2–98.5) 34.3 ± 6.0 (28.1–45.1) 95.3 ± 3.2 (84.5–98.8)
Massive hemoptysis
16.5 ± 9.5 (6.0–90.0) 7.41 ± 0.06 (7.13–7.54) 79.4 ± 13.1 (47.2–99.3) 34.8 ± 6.0 (22.6–50.9) 95.5 ± 6.4 (31.3–99.5) 809 (95.0)
Table 2. The laboratory findings according to severity of subjective hemoptysis
