CORRESPONDENCE 4. Dubrey SW, Falk RH. Diagnosis and management of cardiac sarcoidosis. Prog Cardiovasc Dis 2010;52:336–346. 5. Fabre A, Sheppard MN. Sudden adult death syndrome and other non-ischaemic causes of sudden cardiac death. Heart 2006;92:316–320. 6. Thomsen TK, Eriksson T. Myocardial sarcoidosis in forensic medicine. Am J Forensic Med Pathol 1999;20:52–56. 7. Freeman AM, Curran-Everett D, Weinberger HD, Fenster BE, Buckner JK, Gottschall EB, Sauer WH, Maier LA, Hamzeh NY. Predictors of cardiac sarcoidosis using commonly available cardiac studies. Am J Cardiol 2013;112:280–285. 8. Patel MR, Cawley PJ, Heitner JF, Klem I, Parker MA, Jaroudi WA, Meine TJ, White JB, Elliott MD, Kim HW, et al. Detection of myocardial damage in patients with sarcoidosis. Circulation 2009;120:1969–1977. 9. Larsen F, Pehrsson SK, Hammar N, Skold ¨ CM, Izumi T, Nagai S, Shigematsu M, Eklund A. ECG-abnormalities in Japanese and Swedish patients with sarcoidosis: a comparison. Sarcoidosis Vasc Diffuse Lung Dis 2001;18:284–288. 10. Smedema JP, Snoep G, van Kroonenburgh MP, van Geuns RJ, Dassen WR, Gorgels AP, Crijns HJ. Evaluation of the accuracy of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis. J Am Coll Cardiol 2005;45: 1683–1690. 11. Vohringer ¨ M, Mahrholdt H, Yilmaz A, Sechtem U. Significance of late gadolinium enhancement in cardiovascular magnetic resonance imaging (CMR). Herz 2007;32:129–137. 12. Yamagishi H, Shirai N, Takagi M, Yoshiyama M, Akioka K, Takeuchi K, Yoshikawa J. Identification of cardiac sarcoidosis with (13)N-NH(3)/ (18)F-FDG PET. J Nucl Med 2003;44:1030–1036. 13. Thavendiranathan P, Walls M, Giri S, Verhaert D, Rajagopalan S, Moore S, Simonetti OP, Raman SV. Improved detection of myocardial involvement in acute inflammatory cardiomyopathies using T2 mapping. Circ Cardiovasc Imaging 2012;5:102–110. 14. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007; 357:2153–2165. 15. Giri S, Shah S, Xue H, Chung YC, Pennell ML, Guehring J, Zuehlsdorff S, Raman SV, Simonetti OP. Myocardial T₂ mapping with respiratory navigator and automatic nonrigid motion correction. Magn Reson Med 2012;68:1570–1578. 16. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS; American Heart Association Writing Group on Myocardial Segmentation and Registration for Cardiac Imaging. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002;105:539–542. 17. Eitel I, Friedrich MG. T2-weighted cardiovascular magnetic resonance in acute cardiac disease. J Cardiovasc Magn Reson 2011;13:13. 18. Yang Y, Safka K, Graham JJ, Roifman I, Zia MI, Wright GA, Balter M, Dick AJ, Connelly KA. Correlation of late gadolinium enhancement MRI and quantitative T2 measurement in cardiac sarcoidosis. J Magn Reson Imaging (In press) 19. Ohira H, Tsujino I, Ishimaru S, Oyama N, Takei T, Tsukamoto E, Miura M, Sakaue S, Tamaki N, Nishimura M. Myocardial imaging with 18F-fluoro-2deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis. Eur J Nucl Med Mol Imaging 2008;35:933–941.
Copyright © 2014 by the American Thoracic Society
Thromboendarterectomy for Chronic Thromboembolic Pulmonary Hypertension in Hereditary Hemorrhagic Telangiectasia To the Editor: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of pulmonary vascular blood flow 112
due to incomplete lysis of acute pulmonary emboli, and resulting in cicatricial organization and adherence to the vessel walls (1). Pulmonary thromboendarterectomy (PTE) can potentially be curative for patients with CTEPH; however, careful candidate selection is necessary. Hereditary hemorrhagic telangiectasia (HHT) is inherited as an autosomal dominant trait that affects approximately 1 in 5,000 people (2). Patients with HHT have been reported to have pulmonary arteriovenous malformations (PAVMs) (3); pulmonary hypertension (4); paradoxical emboli resulting in cardiac ischemia (5), stroke (6), and brain abscesses (7); and poorer quality of life (8). Although pulmonary thromboemboli complicating HHT have been reported (9), CTEPH has not. Patients with PAVMs may be at higher risk for complications during PTE surgery. One particular concern is that rupture of a PAVM, due to dissection through a feeding vessel during or after PTE surgery, could theoretically cause severe bleeding. We report a case of successful PTE surgery for CTEPH in the presence of PAVMs associated with HHT. A 54-year-old white female with HHT and recurrent venous thromboembolism (VTE) was referred for worsening dyspnea on exertion over a 6-month duration. She was first diagnosed with a pulmonary embolism in January 2011, and anticoagulation with warfarin was initiated. Chest computed tomography (CT) at that time showed bilateral emboli, a right pulmonary infarct and pleural effusion, and right ventricular (RV) dilation. She improved initially but was rehospitalized in February 2012 with worsening dyspnea and hypotension. Despite continued anticoagulation, a chest CT showed new pulmonary emboli. Along with dyspnea, she had progressive lower extremity edema, palpitations, and syncope. There was no fever, chest pain, or hemoptysis. She was a lifelong nonsmoker, and there was no family history of VTE. She was diagnosed with HHT by genetic testing in 2011. She had frequent epistaxis since childhood, and although her brother died from a ruptured cerebral AVM, she had no cerebral AVMs demonstrated by magnetic resonance imaging. Physical examination revealed a middle-aged female in no distress. Heart rate was 104 min21, blood pressure 87/51 mm Hg, and SpO2 78% (room air). Lungs were clear to auscultation. There was a regular heart rate and rhythm with prominent P2 and RV heave. There was no ascites or edema. Telangiectasias were present on the tongue, abdomen, and extremities. Renal profile, liver function studies, and complete blood count were normal. On a 6-minute walk, she achieved a distance of 290 m with a room air oxygen saturation nadir at 78%. Laboratory studies were notable for a low serum iron (9 mg/dl), elevated total ironbinding capacity (514 mg/dl), and low serum ferritin (4 ng/ml). An echocardiogram showed moderate to severe right atrial and RV dilation with severe RV dysfunction, tricuspid regurgitation, and an estimated pulmonary artery systolic pressure greater than 60 mm Hg. Right heart catheterization showed a right atrial pressure of 12 mm Hg, pulmonary artery pressure of 99/31 mm Hg, pulmonary capillary wedge pressure of 16 mm Hg, pulmonary vascular resistance of 608 dyn$s$cm25, and cardiac index (Fick) of 2.38 L/min. A chest CT (Figure 1) demonstrated filling defects and fibrous webs in both upper lobe pulmonary arteries and the left lower lobe pulmonary artery, along with mosaic perfusion abnormalities. Multiple AVMs, the largest (shown in Figures 1 and 2) measuring 1.7 3 1.4 cm (with a feeding artery measuring 4.5 mm), were observed in both upper and lower lobes. An underlying hypercoagulable state was not identified.
American Journal of Respiratory and Critical Care Medicine Volume 189 Number 1 | January 2014
CORRESPONDENCE
Figure 1. Preoperative and postoperative chest computed tomography imaging. (A) Preoperatively, there is near-complete occlusion of the right lower lobe pulmonary artery (PA) branch (circle). A web is present in the dilated left lower lobe PA (arrow). (B) Postoperatively, there is a widely patent right lower lobe PA branch (circle). The left lower PA is smaller in caliber, and no residual webs are seen. (C) Preoperatively, there is a faint web (thin arrows) in the left lower PA proximal and distal to the feeding vessel of an arteriovenous malformation (thick, straight arrow). The lingular PA branch is occluded (curved arrow). (D) Webs are not seen after endarterectomy, and the lingular PA branch is well opacified (curved arrow). The arteriovenous malformation feeder is unchanged (straight arrow). A = arteriovenous malformation.
Tadalafil and treprostinil were initiated, but symptoms progressed and she was subsequently referred for PTE. She was found to have surgically accessible chronic thromboembolic disease. PTE was performed using cardiopulmonary bypass, circulatory arrest, profound hypothermia, and antegrade cerebral perfusion. The operation and postoperative convalescence were uneventful and the postoperative pulmonary artery pressure was 38/10 mm Hg. At 6 months after surgery, she has a satisfactory exercise capacity without cardiopulmonary symptoms. This case is interesting for several reasons. First, while the bleeding complications of HHT are well known, the associated thrombotic disorders, including venous thromboemboli and ischemic stroke, are less recognized, and experience with anticoagulant or antiplatelet therapy in HHT varies considerably (10). Second, this case illustrates the pathophysiology of PAVMs with CTEPH: in contrast to patients with isolated PAVMs, where hypoxemia is generally well tolerated, patients with PAVMs and CTEPH have progressive dyspnea and hypoxemia. Third, the potentially hazardous consequences of thrombosis
Correspondence
are evident. Although PTE events may initially mimic a therapeutic embolization procedure, recanalization of emboli may result in recurrent right-to-left shunting, and progressive clot organization and propagation may result in CTEPH. Finally, the ability to perform PTE in the presence of PAVMs has not been clearly described in the literature. Although the true incidence of CTEPH is unknown, it may occur in up to 4% of individuals by 2 years after an acute pulmonary embolus (11, 12). Patients with HHT may have an increased risk of VTE related to iron deficiency (9, 13). In a single-center study of 609 patients with HHT, Livesey and colleagues found that low serum iron levels, thought to be related to inadequate iron replacement after hemorrhage, were associated with elevated factor VIII plasma levels and an increased risk of VTE (age-adjusted odds ratio of VTE per 1 mmol/L increase in serum iron was 0.91 [95% confidence interval, 0.86–0.97]) (13). Despite the potential for increased bleeding, patients with HHT can be anticoagulated but require careful monitoring (14). For patients with PAVMs who also develop CTEPH, endarterectomy may still
113
CORRESPONDENCE
Figure 2. Sagittal oblique maximum intensity projection view demonstrates a complex arteriovenous malformation in the superior segment of the left lower lobe (arrow) along with a smaller arteriovenous malformation (circle) seen in the posterior left lower lobe.
be a treatment option. In summary, PAVMs should not disqualify patients with CTEPH from being considered for surgery. In selected patients with CTEPH and HHT, a satisfactory outcome may result after PTE surgery. n
5. Clark K, Pyeritz RE, Trerotola SO. Angina pectoris or myocardial infarctions, pulmonary arteriovenous malformations, hereditary hemorrhagic telangiectasia, and paradoxical emboli. Am J Cardiol 2013;112:731–734. 6. Maher CO, Piepgras DG, Brown RD Jr, Friedman JA, Pollock BE. Cerebrovascular manifestations in 321 cases of hereditary hemorrhagic telangiectasia. Stroke 2001;32:877–882. 7. Mathis S, Dupuis-Girod S, Plauchu H, Giroud M, Barroso B, Ly KH, Ingrand P, Gilbert B, Godeneche ` G, Neau JP. Cerebral abscesses in hereditary haemorrhagic telangiectasia: a clinical and microbiological evaluation. Clin Neurol Neurosurg 2012;114:235–240. 8. Geirdal AO, Dheyauldeen S, Bachmann-Harildstad G, Heimdal K. Quality of life in patients with hereditary hemorrhagic telangiectasia in Norway: a population based study. Am J Med Genet A 2012;158A: 1269–1278. 9. Roked F, Jackson JE, Fuld J, Basheer FT, Chilvers ER, Beattie S, Shovlin CL. Pulmonary thromboemboli modifying the natural history of pulmonary arteriovenous malformations. Am J Respir Crit Care Med 2011;183:828–829. 10. Devlin HL, Hosman AE, Shovlin CL. Antiplatelet and anticoagulant agents in hereditary hemorrhagic telangiectasia. N Engl J Med 2013; 368:876–878. 11. Fedullo PF, Auger WR, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. N Engl J Med 2001;345:1465–1472. 12. Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, Albanese P, Biasiolo A, Pegoraro C, Iliceto S, et al.; Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004;350:2257–2264. 13. Livesey JA, Manning RA, Meek JH, Jackson JE, Kulinskaya E, Laffan MA, Shovlin CL. Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia. Thorax 2012;67:328–333. 14. Edwards CP, Shehata N, Faughnan ME. Hereditary hemorrhagic telangiectasia patients can tolerate anticoagulation. Ann Hematol 2012;91:1959–1968.
Copyright © 2014 by the American Thoracic Society
Author disclosures are available with the text of this letter at www. atsjournals.org. Keith M. Wille, M.D., M.S.P.H. S. Christopher Bellot, M.D. Deepak Acharya, M.D. University of Alabama at Birmingham Birmingham, Alabama Micheal M. Madani, M.D. University of California at San Diego San Diego, California Satinder P. Singh, M.D. David C. McGiffin, M.D. University of Alabama at Birmingham Birmingham, Alabama
References 1. Auger WR, Fedullo PF. Chronic thromboembolic pulmonary hypertension. Semin Respir Crit Care Med 2009;30:471–483. 2. Shovlin CL. Hereditary haemorrhagic telangiectasia: pathophysiology, diagnosis and treatment. Blood Rev 2010;24:203–219. 3. Ogul H, Aydın Y, Ozgokce M, Orsal E, Kantarci M, Eroglu A. Pulmonary arteriovenous malformations and hepatic involvement in a patient with Osler-Rendu-Weber disease. Ann Thorac Surg 2012;94:e155. ´ıguez MT, Portela D, Rivera A, Freire M, Mart´ınez4. Sopeña B, Perez-Rodr ´ Vazquez ´ C. High prevalence of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. Eur J Intern Med 2013;24: e30–e34.
114
Asbestosis, Not Asbestos Exposure, Is the Primary Risk Factor for Lung Cancer To the Editor: I enjoyed reading the article regarding asbestos, asbestosis, smoking, and lung cancer by Markowitz and colleagues (1). It reconfirms the relationship between asbestosis and lung cancer and finds that it is supraadditive but likely less than multiplicative. However, it also strongly suggests that asbestos exposure alone, at least among ever-smokers, is not a major risk factor for lung cancer. This study represents the heaviest of the amphibole asbestos–exposed Americans presently alive. Thus, this article gives information regarding the highest risk of lung cancer among people exposed to asbestos but without radiographic evidence of asbestosis, as all these insulators had heavy exposure over many years. In Markowitz and colleagues’ Table 2, the adjusted rate ratio for ever-smoker insulators with radiographic evidence of asbestosis around 1980, compared with Cancer Prevention Study II eversmokers, was 36.79/10.29 = 3.58. That is, those with asbestosis were at a marked increased risk for lung cancer. Further, this ratio is similar to what has been found in other studies of people with asbestosis (2, 3). Also in their Table 2, the adjusted rate ratio for the 665 ever-smoker insulators without radiographic evidence of asbestosis
American Journal of Respiratory and Critical Care Medicine Volume 189 Number 1 | January 2014
Copyright © 2014 by the American Thoracic Society
Thromboendarterectomy for Chronic Thromboembolic Pulmonary Hypertension in Hereditary Hemorrhagic Telangiectasia To the Editor: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of pulmonary vascular blood flow 112
due to incomplete lysis of acute pulmonary emboli, and resulting in cicatricial organization and adherence to the vessel walls (1). Pulmonary thromboendarterectomy (PTE) can potentially be curative for patients with CTEPH; however, careful candidate selection is necessary. Hereditary hemorrhagic telangiectasia (HHT) is inherited as an autosomal dominant trait that affects approximately 1 in 5,000 people (2). Patients with HHT have been reported to have pulmonary arteriovenous malformations (PAVMs) (3); pulmonary hypertension (4); paradoxical emboli resulting in cardiac ischemia (5), stroke (6), and brain abscesses (7); and poorer quality of life (8). Although pulmonary thromboemboli complicating HHT have been reported (9), CTEPH has not. Patients with PAVMs may be at higher risk for complications during PTE surgery. One particular concern is that rupture of a PAVM, due to dissection through a feeding vessel during or after PTE surgery, could theoretically cause severe bleeding. We report a case of successful PTE surgery for CTEPH in the presence of PAVMs associated with HHT. A 54-year-old white female with HHT and recurrent venous thromboembolism (VTE) was referred for worsening dyspnea on exertion over a 6-month duration. She was first diagnosed with a pulmonary embolism in January 2011, and anticoagulation with warfarin was initiated. Chest computed tomography (CT) at that time showed bilateral emboli, a right pulmonary infarct and pleural effusion, and right ventricular (RV) dilation. She improved initially but was rehospitalized in February 2012 with worsening dyspnea and hypotension. Despite continued anticoagulation, a chest CT showed new pulmonary emboli. Along with dyspnea, she had progressive lower extremity edema, palpitations, and syncope. There was no fever, chest pain, or hemoptysis. She was a lifelong nonsmoker, and there was no family history of VTE. She was diagnosed with HHT by genetic testing in 2011. She had frequent epistaxis since childhood, and although her brother died from a ruptured cerebral AVM, she had no cerebral AVMs demonstrated by magnetic resonance imaging. Physical examination revealed a middle-aged female in no distress. Heart rate was 104 min21, blood pressure 87/51 mm Hg, and SpO2 78% (room air). Lungs were clear to auscultation. There was a regular heart rate and rhythm with prominent P2 and RV heave. There was no ascites or edema. Telangiectasias were present on the tongue, abdomen, and extremities. Renal profile, liver function studies, and complete blood count were normal. On a 6-minute walk, she achieved a distance of 290 m with a room air oxygen saturation nadir at 78%. Laboratory studies were notable for a low serum iron (9 mg/dl), elevated total ironbinding capacity (514 mg/dl), and low serum ferritin (4 ng/ml). An echocardiogram showed moderate to severe right atrial and RV dilation with severe RV dysfunction, tricuspid regurgitation, and an estimated pulmonary artery systolic pressure greater than 60 mm Hg. Right heart catheterization showed a right atrial pressure of 12 mm Hg, pulmonary artery pressure of 99/31 mm Hg, pulmonary capillary wedge pressure of 16 mm Hg, pulmonary vascular resistance of 608 dyn$s$cm25, and cardiac index (Fick) of 2.38 L/min. A chest CT (Figure 1) demonstrated filling defects and fibrous webs in both upper lobe pulmonary arteries and the left lower lobe pulmonary artery, along with mosaic perfusion abnormalities. Multiple AVMs, the largest (shown in Figures 1 and 2) measuring 1.7 3 1.4 cm (with a feeding artery measuring 4.5 mm), were observed in both upper and lower lobes. An underlying hypercoagulable state was not identified.
American Journal of Respiratory and Critical Care Medicine Volume 189 Number 1 | January 2014
CORRESPONDENCE
Figure 1. Preoperative and postoperative chest computed tomography imaging. (A) Preoperatively, there is near-complete occlusion of the right lower lobe pulmonary artery (PA) branch (circle). A web is present in the dilated left lower lobe PA (arrow). (B) Postoperatively, there is a widely patent right lower lobe PA branch (circle). The left lower PA is smaller in caliber, and no residual webs are seen. (C) Preoperatively, there is a faint web (thin arrows) in the left lower PA proximal and distal to the feeding vessel of an arteriovenous malformation (thick, straight arrow). The lingular PA branch is occluded (curved arrow). (D) Webs are not seen after endarterectomy, and the lingular PA branch is well opacified (curved arrow). The arteriovenous malformation feeder is unchanged (straight arrow). A = arteriovenous malformation.
Tadalafil and treprostinil were initiated, but symptoms progressed and she was subsequently referred for PTE. She was found to have surgically accessible chronic thromboembolic disease. PTE was performed using cardiopulmonary bypass, circulatory arrest, profound hypothermia, and antegrade cerebral perfusion. The operation and postoperative convalescence were uneventful and the postoperative pulmonary artery pressure was 38/10 mm Hg. At 6 months after surgery, she has a satisfactory exercise capacity without cardiopulmonary symptoms. This case is interesting for several reasons. First, while the bleeding complications of HHT are well known, the associated thrombotic disorders, including venous thromboemboli and ischemic stroke, are less recognized, and experience with anticoagulant or antiplatelet therapy in HHT varies considerably (10). Second, this case illustrates the pathophysiology of PAVMs with CTEPH: in contrast to patients with isolated PAVMs, where hypoxemia is generally well tolerated, patients with PAVMs and CTEPH have progressive dyspnea and hypoxemia. Third, the potentially hazardous consequences of thrombosis
Correspondence
are evident. Although PTE events may initially mimic a therapeutic embolization procedure, recanalization of emboli may result in recurrent right-to-left shunting, and progressive clot organization and propagation may result in CTEPH. Finally, the ability to perform PTE in the presence of PAVMs has not been clearly described in the literature. Although the true incidence of CTEPH is unknown, it may occur in up to 4% of individuals by 2 years after an acute pulmonary embolus (11, 12). Patients with HHT may have an increased risk of VTE related to iron deficiency (9, 13). In a single-center study of 609 patients with HHT, Livesey and colleagues found that low serum iron levels, thought to be related to inadequate iron replacement after hemorrhage, were associated with elevated factor VIII plasma levels and an increased risk of VTE (age-adjusted odds ratio of VTE per 1 mmol/L increase in serum iron was 0.91 [95% confidence interval, 0.86–0.97]) (13). Despite the potential for increased bleeding, patients with HHT can be anticoagulated but require careful monitoring (14). For patients with PAVMs who also develop CTEPH, endarterectomy may still
113
CORRESPONDENCE
Figure 2. Sagittal oblique maximum intensity projection view demonstrates a complex arteriovenous malformation in the superior segment of the left lower lobe (arrow) along with a smaller arteriovenous malformation (circle) seen in the posterior left lower lobe.
be a treatment option. In summary, PAVMs should not disqualify patients with CTEPH from being considered for surgery. In selected patients with CTEPH and HHT, a satisfactory outcome may result after PTE surgery. n
5. Clark K, Pyeritz RE, Trerotola SO. Angina pectoris or myocardial infarctions, pulmonary arteriovenous malformations, hereditary hemorrhagic telangiectasia, and paradoxical emboli. Am J Cardiol 2013;112:731–734. 6. Maher CO, Piepgras DG, Brown RD Jr, Friedman JA, Pollock BE. Cerebrovascular manifestations in 321 cases of hereditary hemorrhagic telangiectasia. Stroke 2001;32:877–882. 7. Mathis S, Dupuis-Girod S, Plauchu H, Giroud M, Barroso B, Ly KH, Ingrand P, Gilbert B, Godeneche ` G, Neau JP. Cerebral abscesses in hereditary haemorrhagic telangiectasia: a clinical and microbiological evaluation. Clin Neurol Neurosurg 2012;114:235–240. 8. Geirdal AO, Dheyauldeen S, Bachmann-Harildstad G, Heimdal K. Quality of life in patients with hereditary hemorrhagic telangiectasia in Norway: a population based study. Am J Med Genet A 2012;158A: 1269–1278. 9. Roked F, Jackson JE, Fuld J, Basheer FT, Chilvers ER, Beattie S, Shovlin CL. Pulmonary thromboemboli modifying the natural history of pulmonary arteriovenous malformations. Am J Respir Crit Care Med 2011;183:828–829. 10. Devlin HL, Hosman AE, Shovlin CL. Antiplatelet and anticoagulant agents in hereditary hemorrhagic telangiectasia. N Engl J Med 2013; 368:876–878. 11. Fedullo PF, Auger WR, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. N Engl J Med 2001;345:1465–1472. 12. Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, Albanese P, Biasiolo A, Pegoraro C, Iliceto S, et al.; Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004;350:2257–2264. 13. Livesey JA, Manning RA, Meek JH, Jackson JE, Kulinskaya E, Laffan MA, Shovlin CL. Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia. Thorax 2012;67:328–333. 14. Edwards CP, Shehata N, Faughnan ME. Hereditary hemorrhagic telangiectasia patients can tolerate anticoagulation. Ann Hematol 2012;91:1959–1968.
Copyright © 2014 by the American Thoracic Society
Author disclosures are available with the text of this letter at www. atsjournals.org. Keith M. Wille, M.D., M.S.P.H. S. Christopher Bellot, M.D. Deepak Acharya, M.D. University of Alabama at Birmingham Birmingham, Alabama Micheal M. Madani, M.D. University of California at San Diego San Diego, California Satinder P. Singh, M.D. David C. McGiffin, M.D. University of Alabama at Birmingham Birmingham, Alabama
References 1. Auger WR, Fedullo PF. Chronic thromboembolic pulmonary hypertension. Semin Respir Crit Care Med 2009;30:471–483. 2. Shovlin CL. Hereditary haemorrhagic telangiectasia: pathophysiology, diagnosis and treatment. Blood Rev 2010;24:203–219. 3. Ogul H, Aydın Y, Ozgokce M, Orsal E, Kantarci M, Eroglu A. Pulmonary arteriovenous malformations and hepatic involvement in a patient with Osler-Rendu-Weber disease. Ann Thorac Surg 2012;94:e155. ´ıguez MT, Portela D, Rivera A, Freire M, Mart´ınez4. Sopeña B, Perez-Rodr ´ Vazquez ´ C. High prevalence of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. Eur J Intern Med 2013;24: e30–e34.
114
Asbestosis, Not Asbestos Exposure, Is the Primary Risk Factor for Lung Cancer To the Editor: I enjoyed reading the article regarding asbestos, asbestosis, smoking, and lung cancer by Markowitz and colleagues (1). It reconfirms the relationship between asbestosis and lung cancer and finds that it is supraadditive but likely less than multiplicative. However, it also strongly suggests that asbestos exposure alone, at least among ever-smokers, is not a major risk factor for lung cancer. This study represents the heaviest of the amphibole asbestos–exposed Americans presently alive. Thus, this article gives information regarding the highest risk of lung cancer among people exposed to asbestos but without radiographic evidence of asbestosis, as all these insulators had heavy exposure over many years. In Markowitz and colleagues’ Table 2, the adjusted rate ratio for ever-smoker insulators with radiographic evidence of asbestosis around 1980, compared with Cancer Prevention Study II eversmokers, was 36.79/10.29 = 3.58. That is, those with asbestosis were at a marked increased risk for lung cancer. Further, this ratio is similar to what has been found in other studies of people with asbestosis (2, 3). Also in their Table 2, the adjusted rate ratio for the 665 ever-smoker insulators without radiographic evidence of asbestosis
American Journal of Respiratory and Critical Care Medicine Volume 189 Number 1 | January 2014
