Lung Disease in Antiphospholipid Syndrome

Gabriella Maioli; Giulia Calabrese; Franco Capsoni; Maria Gerosa; Pier Luigi Meroni; Cecilia Beatrice Chighizola

doi:10.1055/s-0039-1683994

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2019; 40(02): 278-294
DOI: 10.1055/s-0039-1683994

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Lung Disease in Antiphospholipid Syndrome

Gabriella Maioli

¹ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

² Division of Rheumatology, ASST G. Pini & CTO, Milan, Italy

,

Giulia Calabrese

¹ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

² Division of Rheumatology, ASST G. Pini & CTO, Milan, Italy

,

Franco Capsoni

³ Department of Biomedical Sciences for Health, University of Milan, Milan, Italy

⁴ Allergology, Clinical Immunology & Rheumatology Unit, San Luca Hospital, IRCCS Istituto Auxologico Italiano, Milan, Italy

,

Maria Gerosa

¹ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

² Division of Rheumatology, ASST G. Pini & CTO, Milan, Italy

,

Pier Luigi Meroni

⁴ Allergology, Clinical Immunology & Rheumatology Unit, San Luca Hospital, IRCCS Istituto Auxologico Italiano, Milan, Italy

⁵ Experimental Laboratory of Immunological and Rheumatologic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Milan, Italy

,

Cecilia Beatrice Chighizola

⁴ Allergology, Clinical Immunology & Rheumatology Unit, San Luca Hospital, IRCCS Istituto Auxologico Italiano, Milan, Italy

⁵ Experimental Laboratory of Immunological and Rheumatologic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Milan, Italy

› Author Affiliations

Abstract

Antiphospholipid syndrome (APS) is an acquired prothrombotic condition characterized by vascular thrombosis and/or obstetric complications, in the persistent positivity of circulating antiphospholipid antibodies (aPLs). The clinical spectrum of manifestations associated with aPL positivity is progressively expanding, including the description of several lung manifestations. The most common pulmonary involvement related to aPL positivity is pulmonary embolism (PE), which has been reported to occur in 14.1% of APS patients during disease course. PE acknowledges a purely thrombotic etiology and thus might be accounted as a criterion for APS, making imperative to test aPL in young subjects with unprovoked PE. Pulmonary hypertension (PH) can manifest in APS patients, being the second most common lung complication of the syndrome, with a prevalence ranging between 1.8 and 3.5%. aPL-positive patients might present PH following a PE, might develop pulmonary arterial hypertension associated with connective tissue disease, or might present pulmonary venous hypertension due to Libman–Sacks endocarditis. Additional lung manifestations, such as diffuse alveolar hemorrhage, acute respiratory distress syndrome, and pulmonary fibrosis, are rarely described in APS patients; it is still not clear whether in these settings aPLs exert a pathogenic role or is a mere epiphenomenon. Hereby we discuss impact, clinical presentation, histopathologic findings, etiology, and treatment of each aPL-associated lung manifestation.

Keywords

antiphospholipid syndrome - antiphospholipid antibodies - lung manifestation - venous thromboembolism - pulmonary hypertension - diffuse alveolar hemorrhage - acute respiratory distress syndrome - pulmonary fibrosis

Full Text

References

References
1 Hughes GRV. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant. Br Med J (Clin Res Ed) 1983; 287 (6399): 1088-1089
2 Miyakis S, Lockshin MD, Atsumi T. , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (02) 295-306
3 Cervera R, Khamashta MA, Shoenfeld Y. , et al; Euro-Phospholipid Project Group (European Forum on Antiphospholipid Antibodies). Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2009; 68 (09) 1428-1432
4 Cervera R, Piette JC, Font J. , et al; Euro-Phospholipid Project Group. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46 (04) 1019-1027
5 Chighizola CB, Andreoli L, Gerosa M, Tincani A, Ruffatti A, Meroni PL. The treatment of anti-phospholipid syndrome: a comprehensive clinical approach. J Autoimmun 2018; 90: 1-27
6 Meroni PL, Chighizola CB, Rovelli F, Gerosa M. Antiphospholipid syndrome in 2014: more clinical manifestations, novel pathogenic players and emerging biomarkers. Arthritis Res Ther 2014; 16 (02) 209
7 Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, Ramire de Jesus G, Erkan D. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res (Hoboken) 2013; 65 (11) 1869-1873
8 Chighizola CB, Raschi E, Borghi MO, Meroni PL. Update on the pathogenesis and treatment of the antiphospholipid syndrome. Curr Opin Rheumatol 2015; 27 (05) 476-482
9 Chighizola CB, Raschi E, Borghi MO, Meroni PL. Mechanisms of action of the anti-phospholipid antibodies. In: Cervera R, Espinosa G, Khamashta M. , eds. Antiphospholipid Syndrome in Systemic Autoimmune Diseases. 2nd ed. Amsterdam: Elsevier; 2016: 31-43
10 Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrøm J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 5 (04) 692-699
11 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107 (23) (Suppl. 01) I4-I8
12 Heit JA. Venous thromboembolism: disease burden, outcomes and risk factors. J Thromb Haemost 2005; 3 (08) 1611-1617
13 Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol 2007; 44 (02) 62-69
14 Douketis JD, Kearon C, Bates S, Duku EK, Ginsberg JS. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. JAMA 1998; 279 (06) 458-462
15 Spencer FA, Emery C, Joffe SW. , et al. Incidence rates, clinical profile, and outcomes of patients with venous thromboembolism. The Worcester VTE study. J Thromb Thrombolysis 2009; 28 (04) 401-409
16 Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 2003; 101 (05) 1827-1832
17 Cervera R, Serrano R, Pons-Estel GJ. , et al; Euro-Phospholipid Project Group (European Forum on Antiphospholipid Antibodies). Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2015; 74 (06) 1011-1018
18 Tromeur C, Sanchez O, Presles E. , et al; PADIS-PE Investigators18. Risk factors for recurrent venous thromboembolism after unprovoked pulmonary embolism: the PADIS-PE randomised trial. Eur Respir J 2018; 51 (01) 1701202
19 Ruiz-Irastorza G, Hunt BJ, Khamashta MA. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum 2007; 57 (08) 1487-1495
20 Ginsburg KS, Liang MH, Newcomer L. , et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med 1992; 117 (12) 997-1002
21 Pengo V, Ruffatti A, Legnani C. , et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost 2010; 8 (02) 237-242
22 Galli M, Borrelli G, Jacobsen EM. , et al. Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study. Blood 2007; 110 (04) 1178-1183
23 Pengo V, Biasiolo A, Pegoraro C, Cucchini U, Noventa F, Iliceto S. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost 2005; 93 (06) 1147-1152
24 Miniati M, Cenci C, Monti S, Poli D. Clinical presentation of acute pulmonary embolism: survey of 800 cases. PLoS One 2012; 7 (02) e30891
25 Madsen PH, Hess S. Symptomatology, clinical presentation and basic work up in patients with suspected pulmonary embolism. Adv Exp Med Biol 2017; 906: 33-48
26 Tritschler T, Kraaijpoel N, Le Gal G, Wells PS. Venous thromboembolism: advances in diagnosis and treatment. JAMA 2018; 320 (15) 1583-1594
27 Lim W, Le Gal G, Bates SM. , et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism. Blood Adv 2018; 2 (22) 3226-3256
28 Reyes E, Alarcon-Segovia D. Pathology of the antiphospholipid syndrome. In: Asherson RA. et al. eds. The Antiphospholipid Syndrome II: Autoimmune Thrombosis. Amsterdam: Elsevier; 2002: 131-136
29 Hughson MD, McCarty GA, Brumback RA. Spectrum of vascular pathology affecting patients with the antiphospholipid syndrome. Hum Pathol 1995; 26 (07) 716-724
30 Knight JS, Meng H, Coit P. , et al. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target. JCI Insight 2017; 2 (18) 93897
31 von Brühl ML, Stark K, Steinhart A. , et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 2012; 209 (04) 819-835
32 Kambas K, Mitroulis I, Ritis K. The emerging role of neutrophils in thrombosis-the journey of TF through NETs. Front Immunol 2012; 3: 385
33 van den Hoogen LL, Fritsch-Stork RD, van Roon JA, Radstake TR. Low-density granulocytes are increased in antiphospholipid syndrome and are associated with anti-β2-glycoprotein I antibodies: comment on the article by Yalavarthi et al. Arthritis Rheumatol 2016; 68 (05) 1320-1321
34 Tedesco F, Borghi MO, Gerosa M. , et al. Pathogenic role of complement in antiphospholipid syndrome and therapeutic implications. Front Immunol 2018; 9: 1388
35 Prashanth P, Mukhaini MK. Primary antiphospholipid syndrome with recurrent coronary thrombosis, acute pulmonary thromboembolism and intracerebral hematoma. J Invasive Cardiol 2009; 21 (12) E254-E258
36 Derksen RH, de Groot PG, Kater L, Nieuwenhuis HK. Patients with antiphospholipid antibodies and venous thrombosis should receive long term anticoagulant treatment. Ann Rheum Dis 1993; 52 (09) 689-692
37 Bauersachs R, Berkowitz SD, Brenner B. , et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510
38 Agnelli G, Buller HR, Cohen A. , et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (09) 799-808
39 Chighizola CB, Moia M, Meroni PL. New oral anticoagulants in thrombotic antiphospholipid syndrome. Lupus 2014; 23 (12) 1279-1282
40 Franchini M, Mannucci PM. Direct oral anticoagulants and venous thromboembolism. Eur Respir Rev 2016; 25 (141) 295-302
41 Cohen H, Hunt BJ, Efthymiou M. , et al; RAPS trial investigators. Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial. Lancet Haematol 2016; 3 (09) e426-e436
42 Pengo V, Denas G, Zoppellaro G. , et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood 2018; 132 (13) 1365-1371
43 Woller SC, Stevens SM, Kaplan DA. , et al. Apixaban for the secondary prevention of thrombosis among patients with antiphospholipid syndrome: study rationale and design (ASTRO-APS). Clin Appl Thromb Hemost 2016; 22 (03) 239-247
44 Schmidt-Tanguy A, Voswinkel J, Henrion D. , et al. Antithrombotic effects of hydroxychloroquine in primary antiphospholipid syndrome patients. J Thromb Haemost 2013; 11 (10) 1927-1929
45 Galiè N, Humbert M, Vachiery J-L. , et al; ESC Scientific Document Group. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2016; 37 (01) 67-119
46 Kovacs G, Dumitrescu D, Barner A. , et al. Definition, clinical classification and initial diagnosis of pulmonary hypertension: updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol 2018; 272S: 11-19
47 Espinosa G, Cervera R, Font J, Asherson RA. The lung in the antiphospholipid syndrome. Ann Rheum Dis 2002; 61 (03) 195-198
48 Kanakis MA, Kapsimali V, Vaiopoulos AG, Vaiopoulos GA, Samarkos M. The lung in the spectrum of antiphospholipid syndrome. Clin Exp Rheumatol 2013; 31 (03) 452-457
49 Vianna JL, Khamashta MA, Ordi-Ros J. , et al. Comparison of the primary and secondary antiphospholipid syndrome: a European multicenter study of 114 patients. Am J Med 1994; 96 (01) 3-9
50 Asherson RA, Morgan SH, Harris N, Gharavi AE, Hughes GR, Millar AB. Pulmonary hypertension and chronic cutaneous lupus erythematosus: association with the lupus anticoagulant. Arthritis Rheum 1985; 28 (01) 118
51 Pardos-Gea J, Avegliano G, Evangelista A, Vilardell M, Ordi-Ros J. Cardiac manifestations other than valvulopathy in antiphospholipid syndrome: long-time echocardiography follow-up study. Int J Rheum Dis 2015; 18 (01) 76-83
52 Anderson NE, Ali MR. The lupus anticoagulant, pulmonary thromboembolism, and fatal pulmonary hypertension. Ann Rheum Dis 1984; 43 (05) 760-763
53 Pepke-Zaba J, Delcroix M, Lang I. , et al. Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation 2011; 124 (18) 1973-1981
54 Cheng CY, Zhang YX, Denas G, Du Y, Jing ZC, Pengo V. Prevalence of antiphospholipid (aPL) antibodies among patients with chronic thromboembolic pulmonary hypertension: a systematic review and meta-analysis. Intern Emerg Med 2019 (e-pub ahead of print). Doi: 10.1007/s11739-018-02021-z
55 Martinuzzo ME, Pombo G, Forastiero RR, Cerrato GS, Colorio CC, Carreras LO. Lupus anticoagulant, high levels of anticardiolipin, and anti-beta2-glycoprotein I antibodies are associated with chronic thromboembolic pulmonary hypertension. J Rheumatol 1998; 25 (07) 1313-1319
56 Bonderman D, Wilkens H, Wakounig S. , et al. Risk factors for chronic thromboembolic pulmonary hypertension. Eur Respir J 2009; 33 (02) 325-331
57 Karmochkine M, Cacoub P, Dorent R. , et al. High prevalence of antiphospholipid antibodies in precapillary pulmonary hypertension. J Rheumatol 1996; 23 (02) 286-290
58 Coghlan JG, Wolf M, Distler O. , et al. Incidence of pulmonary hypertension and determining factors in patients with systemic sclerosis. Eur Respir J 2018; 51 (04) 1701197
59 Ihn H, Sato S, Fujimoto M. , et al. Measurement of anticardiolipin antibodies by ELISA using beta 2-glycoprotein I (beta 2-GPI) in systemic sclerosis. Clin Exp Immunol 1996; 105 (03) 475-479
60 Launay D, Hachulla E, Hatron PY. , et al. Dépistage de l'hypertension artérielle pulmonaire au cours de la sclérodermie systémique: étude d'une cohorte de 67 patients. Rev Med Interne 2001; 22 (09) 819-829
61 Antonioli CM, Danieli E, Airò P, Cattaneo R, Tincani A. More on anticardiolipin and anti-beta2 glycoprotein I in systemic sclerosis. Ann Rheum Dis 2003; 62 (06) 589-590
62 Assous N, Allanore Y, Batteux F. , et al. Prevalence of antiphospholipid antibodies in systemic sclerosis and association with primitive pulmonary arterial hypertension and endothelial injury. Clin Exp Rheumatol 2005; 23 (02) 199-204
63 Marie I, Jouen F, Hellot M-F, Levesque H. Anticardiolipin and anti-β2 glycoprotein I antibodies and lupus-like anticoagulant: prevalence and significance in systemic sclerosis. Br J Dermatol 2008; 158 (01) 141-144
64 Gupta R, Thabah MM, Gupta S, Shankar S, Kumar A. Clinical significance of antiphospholipid antibodies in Indian scleroderma patients. Rheumatol Int 2009; 30 (02) 277-279
65 Boin F, Franchini S, Colantuoni E, Rosen A, Wigley FM, Casciola-Rosen L. Independent association of anti-β(2)-glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients. Arthritis Rheum 2009; 60 (08) 2480-2489
66 Touré AO, Ly F, Sall A. , et al. Antiphospholipid antibodies and systemic scleroderma. Turk J Haematol 2013; 30 (01) 32-36
67 Mellal Y, Djidjik R, Tahiat A. , et al. Anticardiolipin antibodies are associated with pulmonary arterial hypertension in Algerian systemic scleroderma patients. Indian J Rheumatol 2014; 9 (01) 48-49
68 Morrisroe KB, Stevens W, Nandurkar H. , et al. The association of antiphospholipid antibodies with cardiopulmonary manifestations of systemic sclerosis. Clin Exp Rheumatol 2014; 32 (06) (Suppl. 86) S-133-S-137
69 Alarcón-Segovia D, Delezé M, Oria CV. , et al. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients. Medicine (Baltimore) 1989; 68 (06) 353-365
70 Zuily S, Domingues V, Suty-Selton C. , et al. Antiphospholipid antibodies can identify lupus patients at risk of pulmonary hypertension: a systematic review and meta-analysis. Autoimmun Rev 2017; 16 (06) 576-586
71 Hussein A, Trowitzsch E, Brockmann M. Pulmonary veno-occlusive disease, antiphospholipid antibody and pulmonary hypertension in an adolescent. Klin Padiatr 1999; 211 (02) 92-95
72 Moyssakis I, Tektonidou MG, Vasilliou VA, Samarkos M, Votteas V, Moutsopoulos HM. Libman-Sacks endocarditis in systemic lupus erythematosus: prevalence, associations, and evolution. Am J Med 2007; 120 (07) 636-642
73 Khamashta MA, Cervera R, Asherson RA. , et al. Association of antibodies against phospholipids with heart valve disease in systemic lupus erythematosus. Lancet 1990; 335 (8705): 1541-1544
74 Galve E, Ordi J, Barquinero J, Evangelista A, Vilardell M, Soler-Soler J. Valvular heart disease in the primary antiphospholipid syndrome. Ann Intern Med 1992; 116 (04) 293-298
75 Prete M, Fatone MC, Vacca A, Racanelli V, Perosa F. Severe pulmonary hypertension as the initial manifestation of systemic lupus erythematosus: a case report and review of the literature. Clin Exp Rheumatol 2014; 32 (02) 267-274
76 Zuily S, Regnault V, Selton-Suty C. , et al. Increased risk for heart valve disease associated with antiphospholipid antibodies in patients with systemic lupus erythematosus: meta-analysis of echocardiographic studies. Circulation 2011; 124 (02) 215-224
77 Ford HJ, Roubey RAS. Pulmonary manifestations of the antiphospholipid antibody syndrome. Clin Chest Med 2010; 31 (03) 537-545
78 Asherson RA, Higenbottam TW, Dinh Xuan AT, Khamashta MA, Hughes GR. Pulmonary hypertension in a lupus clinic: experience with twenty-four patients. J Rheumatol 1990; 17 (10) 1292-1298
79 Zuily S, Wahl D. Pulmonary hypertension in antiphospholipid syndrome. Curr Rheumatol Rep 2015; 17 (01) 478
80 Atsumi T, Khamashta MA, Haworth RS. , et al. Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic role for endothelin 1. Arthritis Rheum 1998; 41 (05) 800-807
81 Mocumbi AO, Thienemann F, Sliwa K. A global perspective on the epidemiology of pulmonary hypertension. Can J Cardiol 2015; 31 (04) 375-381
82 Sandoval J, Amigo MC, Barragan R. , et al. Primary antiphospholipid syndrome presenting as chronic thromboembolic pulmonary hypertension. Treatment with thromboendarterectomy. J Rheumatol 1996; 23 (04) 772-775
83 Kamezaki F, Tasaki H, Yamanaka A. , et al. Successful thromboendarterectomy for severe chronic thromboembolic pulmonary hypertension caused by primary antiphospholipid syndrome. J UOEH 2004; 26 (03) 287-294
84 Peng SW, Mitchell JP. Thromboendarterectomy as treatment in the antiphospholipid syndrome. MedGenMed 2006; 8 (03) 7
85 Li C, Zhao J, Liu S. , et al. Pulmonary thromboendarterectomy is a curative resolution for chronic thromboembolic pulmonary hypertension associated with antiphospholipid syndrome: a retrospective cohort study. Lupus 2018; 27 (14) 2206-2214
86 D'Armini AM, Totaro P, Nicolardi S. , et al. Impact of high titre of antiphospholipid antibodies on postoperative outcome following pulmonary endarterectomy. Interact Cardiovasc Thorac Surg 2010; 10 (03) 418-422
87 Camous J, Decrombecque T, Louvain-Quintard V, Doubine S, Dartevelle P, Stéphan F. Outcomes of patients with antiphospholipid syndrome after pulmonary endarterectomy. Eur J Cardiothorac Surg 2014; 46 (01) 116-120
88 Auger WR, Kim NH, Kerr KM, Test VJ, Fedullo PF. Chronic thromboembolic pulmonary hypertension. Clin Chest Med 2007; 28 (01) 255-269 , x
89 Smith ZR, Makowski CT, Awdish RL. Treatment of patients with chronic thrombo embolic pulmonary hypertension: focus on riociguat. Ther Clin Risk Manag 2016; 12: 957-964
90 Kim NH, Delcroix M, Jais X. , et al. Chronic thromboembolic pulmonary hypertension. Eur Respir J 2019; 53 (01) 1801915
91 Schmitt-Opitz I, Ulrich S. Chronic thromboembolic pulmonary hypertension. Swiss Med Wkly 2018; 148: w14702
92 Ghofrani H-A, D'Armini AM, Grimminger F. , et al; CHEST-1 Study Group. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013; 369 (04) 319-329
93 Naclerio C, D'Angelo S, Baldi S, Tagliamonte G, Scarpato S. Efficacy of bosentan in the treatment of a patient with mixed connective tissue disease complicated by pulmonary arterial hypertension. Clin Rheumatol 2010; 29 (06) 687-690
94 Jaïs X, D'Armini AM, Jansa P. , et al; Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension Study Group. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol 2008; 52 (25) 2127-2134
95 de la Mata J, Gomez-Sanchez MA, Aranzana M, Gomez-Reino JJ. Long-term iloprost infusion therapy for severe pulmonary hypertension in patients with connective tissue diseases. Arthritis Rheum 1994; 37 (10) 1528-1533
96 Humbert M, Sanchez O, Fartoukh M, Jagot JL, Sitbon O, Simonneau G. Treatment of severe pulmonary hypertension secondary to connective tissue diseases with continuous IV epoprostenol (prostacyclin). Chest 1998; 114 (1, Suppl): 80S-82S
97 Tam LS, Li EK. Successful treatment with immunosuppression, anticoagulation and vasodilator therapy of pulmonary hypertension in SLE associated with secondary antiphospholipid syndrome. Lupus 1998; 7 (07) 495-497
98 Specks U. Diffuse alveolar hemorrhage syndromes. Curr Opin Rheumatol 2001; 13 (01) 12-17
99 Cartin-Ceba R, Peikert T, Ashrani A. , et al. Primary antiphospholipid syndrome-associated diffuse alveolar hemorrhage. Arthritis Care Res (Hoboken) 2014; 66 (02) 301-310
100 Yachoui R, Sehgal R, Amlani B, Goldberg JW. Antiphospholipid antibodies-associated diffuse alveolar hemorrhage. Semin Arthritis Rheum 2015; 44 (06) 652-657
101 Scheiman Elazary A, Cohen MJ, Aamar S. , et al. Pulmonary hemorrhage in antiphospholipid antibody syndrome. J Rheumatol 2012; 39 (08) 1628-1631
102 Deane KD, West SG. Antiphospholipid antibodies as a cause of pulmonary capillaritis and diffuse alveolar hemorrhage: a case series and literature review. Semin Arthritis Rheum 2005; 35 (03) 154-165
103 Asherson RA, Greenblatt MA. Recurrent alveolar hemorrhage and pulmonary capillaritis in the “primary” antiphospholipid syndrome. J Clin Rheumatol 2001; 7 (01) 30-33
104 Gertner E, Lie JT. Pulmonary capillaritis, alveolar hemorrhage, and recurrent microvascular thrombosis in primary antiphospholipid syndrome. J Rheumatol 1993; 20 (07) 1224-1228
105 Strieter RM, Belperio JA, Keane MP. Host innate defenses in the lung: the role of cytokines. Curr Opin Infect Dis 2003; 16 (03) 193-198
106 Aslanidis S, Pyrpasopoulou A, Doumas M, Triantafyllou A, Chatzimichailidou S, Zamboulis C. Association of capillaroscopic microhaemorrhages with clinical and immunological antiphospholipid syndrome. Clin Exp Rheumatol 2011; 29 (02) 307-309
107 Martínez-Martínez MU, Oostdam DAH, Abud-Mendoza C. Diffuse alveolar hemorrhage in autoimmune diseases. Curr Rheumatol Rep 2017; 19 (05) 27
108 Aakjær S, Bendstrup E, Ivarsen P, Madsen LB. Continous Rituximab treatment for recurrent diffuse alveolar hemorrhage in a patient with systemic lupus erythematosus and antiphosholipid syndrome. Respir Med Case Rep 2017; 22: 263-265
109 Gertner E. Diffuse alveolar hemorrhage in the antiphospholipid syndrome: spectrum of disease and treatment. J Rheumatol 1999; 26 (04) 805-807
110 Janowiak P, Siemińska A, Porzezińska M, Smoleńska Ż, Suchanek H, Jassem E. Difficulties in the treatment of recurring diffuse alveolar hemorrhage accompanying primary antiphospholipid syndrome: a case report and literature review. Adv Respir Med 2018; 86: 126-130 . Doi: 10.5603/ARM.2018.0020
111 Waterer GW, Latham B, Waring JA, Gabbay E. Pulmonary capillaritis associated with the antiphospholipid antibody syndrome and rapid response to plasmapheresis. Respirology 1999; 4 (04) 405-408
112 Dabar G, Harmouch C. [Alveolar haemorrhage associated with the primary antiphospholipid syndrome]. Rev Mal Respir 2013; 30 (01) 71-76
113 Ranieri VM, Rubenfeld GD, Thompson BT. , et al; ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012; 307 (23) 2526-2533
114 Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000; 342 (18) 1334-1349
115 Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med 2017; 377 (06) 562-572
116 Ware LB, Zhao Z, Koyama T. , et al. Long-term ozone exposure increases the risk of developing the acute respiratory distress syndrome. Am J Respir Crit Care Med 2016; 193 (10) 1143-1150
117 Dancer RCA, Parekh D, Lax S. , et al. Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax 2015; 70 (07) 617-624
118 Iribarren C, Jacobs Jr DR, Sidney S, Gross MD, Eisner MD. Cigarette smoking, alcohol consumption, and risk of ARDS: a 15-year cohort study in a managed care setting. Chest 2000; 117 (01) 163-168
119 Brun-Buisson C, Minelli C, Bertolini G. , et al; ALIVE Study Group. Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study. Intensive Care Med 2004; 30 (01) 51-61
120 Rubenfeld GD, Caldwell E, Peabody E. , et al. Incidence and outcomes of acute lung injury. N Engl J Med 2005; 353 (16) 1685-1693
121 Villar J, Blanco J, Kacmarek RM. Current incidence and outcome of the acute respiratory distress syndrome. Curr Opin Crit Care 2016; 22 (01) 1-6
122 Nakos G, Kitsiouli E, Maneta-Peyret L, Cassagne C, Tsianos E, Lekka M. The characteristics of bronchoalveolar lavage from a patient with antiphospholipid syndrome who developed acute respiratory distress syndrome. Clin Rheumatol 2001; 20 (02) 91-97
123 Ingram SB, Goodnight Jr SH, Bennett RM. An unusual syndrome of a devastating noninflammatory vasculopathy associated with anticardiolipin antibodies: report of two cases. Arthritis Rheum 1987; 30 (10) 1167-1172
124 Hillerdal G, Hägg A, Licke G, Wegenius G, Scheibenpflug L. Intra-alveolar haemorrhage in the anticardiolipin antibody syndrome. Scand J Rheumatol 1991; 20 (01) 58-62
125 Ghosh S, Walters HD, Joist JH, Osborn TG, Moore TL. Adult respiratory distress syndrome associated with antiphospholipid antibody syndrome. J Rheumatol 1993; 20 (08) 1406-1408
126 Asherson RA, Cervera R. Review: antiphospholipid antibodies and the lung. J Rheumatol 1995; 22 (01) 62-66
127 Kennedy M, Jackson J, Khan I, Keeling PWN, Gaffney E. Catastrophic anti-phospholipid syndrome in the absence of IgG anti-cardiolipin antibodies. Scand J Rheumatol 1995; 24 (06) 389-391
128 Kerr JE, Poe R, Kramer Z. Antiphospholipid antibody syndrome presenting as a refractory noninflammatory pulmonary vasculopathy. Chest 1997; 112 (06) 1707-1710
129 Argento A, DiBenedetto RJ. ARDS and adrenal insufficiency associated with the antiphospholipid antibody syndrome. Chest 1998; 113 (04) 1136-1138
130 Maddison PJ, Thorpe C, Seale JRC, Ahmed W, Whiteley GS. ‘Catastrophic’ antiphospholipid syndrome. Lupus 2000; 9 (07) 484-488
131 Wiedermann FJ, Mayr A, Schobersberger W. , et al. Acute respiratory failure associated with catastrophic antiphospholipid syndrome. J Intern Med 2000; 247 (06) 723-730
132 Starakis I, Mazokopakis E, Siagris D, Liossis S, Karatza C, Antonopoulos A. Catastrophic antiphospholipid syndrome presented with severe hypertension, adult respiratory distress syndrome and unilateral adrenal haemorrhagic infarction. Rheumatol Int 2007; 27 (08) 781-783
133 Suzuki Y, Hayakawa H, Murakami M. , et al. A case of antiphospholipid syndrome associated with acute respiratory distress syndrome [in Japanese]. Nihon Kokyuki Gakkai Zasshi 2008; 46 (11) 955-959
134 Kinjo K, Terabe H, Ogawa M. , et al. A case of catastrophic antiphospholipid syndrome presenting with acute respiratory distress syndrome as the initial manifestation. Rheumatol Int 2008; 29 (02) 211-216
135 Rodríguez-Pintó I, Moitinho M, Santacreu I. , et al; CAPS Registry Project Group (European Forum on Antiphospholipid Antibodies). Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of 500 patients from the International CAPS Registry. Autoimmun Rev 2016; 15 (12) 1120-1124
136 Maneta-Peyret L, Kitsiouli E, Lekka M, Nakos G, Cassagne C. Autoantibodies to lipids in bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. Crit Care Med 2001; 29 (10) 1950-1954
137 Bucciarelli S, Espinosa G, Asherson RA. , et al; Catastrophic Antiphospholipid Syndrome Registry Project Group. The acute respiratory distress syndrome in catastrophic antiphospholipid syndrome: analysis of a series of 47 patients. Ann Rheum Dis 2006; 65 (01) 81-86
138 Wiedermann FJ, Lederer W, Mayr AJ, Sepp N, Herold M, Schobersberger W. Prospective observational study of antiphospholipid antibodies in acute lung injury and acute respiratory distress syndrome: comparison with catastrophic antiphospholipid syndrome. Lupus 2003; 12 (06) 462-467
139 Holter JF, Weiland JE, Pacht ER, Gadek JE, Davis WB. Protein permeability in the adult respiratory distress syndrome. Loss of size selectivity of the alveolar epithelium. J Clin Invest 1986; 78 (06) 1513-1522
140 Howell MD, Davis AM. Management of ARDS in adults. JAMA 2018; 319 (07) 711-712
141 Matthay MA, McAuley DF, Ware LB. Clinical trials in acute respiratory distress syndrome: challenges and opportunities. Lancet Respir Med 2017; 5 (06) 524-534
142 Bellani G, Laffey JG, Pham T. , et al; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 2016; 315 (08) 788-800
143 Wynn TA. Integrating mechanisms of pulmonary fibrosis. J Exp Med 2011; 208 (07) 1339-1350
144 Savin H, Huberman M, Kott E. , et al. Fibrosing alveolitis associated with primary antiphospholipid syndrome. Br J Rheumatol 1994; 33 (10) 977-980
145 Kelion AD, Cockcroft JR, Ritter JM. Antiphospholipid syndrome in a patient with rapidly progressive fibrosing alveolitis. Postgrad Med J 1995; 71 (834) 233-235
146 Barnini T, Silvestri E, Emmi G. , et al. Pulmonary fibrosis and lymphocytic alveolitis associated with triple antiphospholipid antibody positivity: a diagnostic puzzle. Clin Exp Rheumatol 2012; 30 (05) 806
147 Magro CM, Allen J, Pope-Harman A. , et al. The role of microvascular injury in the evolution of idiopathic pulmonary fibrosis. Am J Clin Pathol 2003; 119 (04) 556-567
148 Kupferminc MJ, Lee MJ, Green D, Peaceman AM. Severe postpartum pulmonary, cardiac, and renal syndrome associated with antiphospholipid antibodies. Obstet Gynecol 1994; 83 (5, Pt 2): 806-807
149 Pego-Reigosa JM, Medeiros DA, Isenberg DA. Respiratory manifestations of systemic lupus erythematosus: old and new concepts. Best Pract Res Clin Rheumatol 2009; 23 (04) 469-480
150 Warrington KJ, Moder KG, Brutinel WM. The shrinking lungs syndrome in systemic lupus erythematosus. Mayo Clin Proc 2000; 75 (05) 467-472
151 Meena M, DeStephano CC, Watson WJ, Brost BC. Shrinking lung syndrome in pregnancy complicated by antiphospholipid antibody syndrome. Obstet Gynecol 2011; 117 (2, Pt 2): 506-508
152 Langenskiöld E, Bonetti A, Fitting JW. , et al. Shrinking lung syndrome successfully treated with rituximab and cyclophosphamide. Respiration 2012; 84 (02) 144-149
153 Borrell H, Narváez J, Alegre JJ. , et al. Shrinking lung syndrome in systemic lupus erythematosus: a case series and review of the literature. Medicine (Baltimore) 2016; 95 (33) e4626
154 Bertoli AM, Tabares AH, Casas JP, Saurit V, Caeiro F, Alvarellos A. Lung cavitation in primary antiphospholipid syndrome. Lupus 2002; 11 (01) 57-59
155 Torok N, Abu Malouh A, Kasmani R, Abusamieh M. Cavitary lung lesions in systemic lupus: an unusual presentation. Lupus 2010; 19 (08) 993-996
156 Humbert M, Sitbon O, Chaouat A. , et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med 2006; 173 (09) 1023-1030
157 Simonneau G, Azarian R, Brenot F, Dartevelle PG, Musset D, Duroux P. Surgical management of unresolved pulmonary embolism. A personal series of 72 patients. Chest 1995; 107 (1, Suppl): 52S-55S
158 Auger WR, Permpikul P, Moser KM. Lupus anticoagulant, heparin use, and thrombocytopenia in patients with chronic thromboembolic pulmonary hypertension: a preliminary report. Am J Med 1995; 99 (04) 392-396
159 Wolf M, Boyer-Neumann C, Parent F. , et al. Thrombotic risk factors in pulmonary hypertension. Eur Respir J 2000; 15 (02) 395-399
160 Sompradeekul S, Minipan M. Clinical features and management of chronic thromboembolic pulmonary hypertension in Thai. J Med Assoc Thai 2010; 93 (Suppl. 01) S79-S85
161 Wong CL, Szydlo R, Gibbs S, Laffan M. Hereditary and acquired thrombotic risk factors for chronic thromboembolic pulmonary hypertension. Blood Coagul Fibrinolysis 2010; 21 (03) 201-206
162 Park SY, Lee SM, Shin JW. , et al. Epidemiology of chronic thromboembolic pulmonary hypertension in Korea: results from the Korean registry. Korean J Intern Med (Korean Assoc Intern Med) 2016; 31 (02) 305-312
163 Crausman RS, Achenbach GA, Pluss WT, O'Brien RF, Jennings CA. Pulmonary capillaritis and alveolar hemorrhage associated with the antiphospholipid antibody syndrome. J Rheumatol 1995; 22 (03) 554-556
164 Al-Hajjaj MS. Massive pulmonary hemorrhage in a Saudi female with primary antiphospholipid syndrome. Saudi Med J 2000; 21 (08) 777-779
165 Marcos Rodríguez PJ, Montero Martínez C, Verea Hernando H. Pulmonary haemorrhage and primary antiphospholipid syndrome: case report and review [in Spanish]. Med Interna 2007; 24 (03) 125-128
166 Lafosse-Marin M, Marcq M, Diot P, Gruel Y, Diot E. Intra-alveolar pulmonary haemorrhage, an unusual manifestation of the primary antiphospholipid syndrome [in French]. Rev Med Interne 2009; 30 (03) 271-273