Advertisement

Clinical Features and Outcomes of Combined Pulmonary Fibrosis and Emphysema After Lung Transplantation

      Background

      Combined pulmonary fibrosis and emphysema (CPFE) is recognized as a characteristic syndrome of smoking-related interstitial lung disease that has a worse prognosis than idiopathic pulmonary fibrosis (IPF). However, outcomes after lung transplantation for CPFE have not been reported. The aim of this study is to describe the clinical features and outcomes of CPFE after lung transplantation.

      Research Question

      What are the clinical features and outcomes of CPFE after lung transplantation?

      Study Design and Methods

      This is a single-center retrospective cohort study of patients with CPFE and IPF who underwent lung transplantation at our center between January 2011 and December 2016. We defined CPFE as ≥10% emphysema in the upper lung fields combined with fibrosis on high-resolution CT scan. We characterized the clinical features of patients with CPFE and compared their outcomes after lung transplantation with those with IPF.

      Results

      Twenty-seven of 172 (16%) patients with IPF met criteria for CPFE. Severe pulmonary hypertension was present in 16 of 27 (59%) patients with CPFE. On logistic regression analysis, CPFE was significantly associated with primary graft dysfunction (PGD) grade 3 (OR, 3.14; 95% CI, 1.18-8.37; P = .02). On competing risk regression analysis, CPFE was associated with acute cellular rejection (ACR) grade ≥ A2, and chronic lung allograft dysfunction (CLAD) (hazard ratio [HR], 1.89; 95% CI, 1.10-3.25; P = .02; HR, 1.96; 95% CI, 1.02-3.77; P = .04, respectively). Five-year survival was 79.0% for the CPFE group and 75.4% for the IPF group (log-rank P = .684).

      Interpretation

      After transplantation, patients with CPFE were more likely to develop PGD, ACR, and CLAD compared with those with IPF. However, survival was not significantly different between the two groups.

      Graphical Abstract

      Key Words

      Abbreviations:

      ACR (acute cellular rejection), CLAD (chronic lung allograft dysfunction), CPFE (combined pulmonary fibrosis and emphysema), IPF (idiopathic pulmonary fibrosis), ISHLT (International Society for Heart and Lung Transplantation), PAH (pulmonary arterial hypertension), PGD (primary graft dysfunction)
      To read this article in full you will need to make a payment
      Subscribe to CHEST
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Raghu G.
        • Remy-Jardin M.
        • Myers J.L.
        • et al.
        Diagnosis of idiopathic pulmonary fibrosis: an official ATS / ERS / JRS / ALAT clinical practice guideline.
        Am J Respir Crit Care Med. 2018; 198: e44-e68
        • King T.E.
        • Bradford W.Z.
        • Castro-Bernardini S.
        • et al.
        A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis.
        N Engl J Med. 2014; 370: 2083-2092
        • Richeldi L.
        • du Bois R.M.
        • Raghu G.
        • et al.
        Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis.
        N Engl J Med. 2014; 370: 2071-2082
        • Ryerson C.J.
        • Hartman T.
        • Elicker B.M.
        • et al.
        Clinical features and outcomes in combined pulmonary fibrosis and emphysema in idiopathic pulmonary fibrosis.
        Chest. 2013; 144: 234-240
        • Cottin V.
        • Nunes H.
        • Briller P.Y.
        • et al.
        Groupe d’Etude et de Recherche sur les Maladies Orphelines Pulmonaries (GERM O P): combined pulmonary fibrosis and emphysema: a distinct underrecognized entity.
        Eur Respir J. 2005; 26: 586-593
        • Cottin V.
        • Le Pavec J.
        • Prévot G.
        • et al.
        GERM”O”P. Pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema syndrome.
        Eur Respir J. 2010; 35: 105-111
        • Mejía M.
        • Carrillo G.
        • Rojas-Serrano J.
        • et al.
        Idiopathic pulmonary fibrosis and emphysema: decreased survival associated with severe pulmonary arterial hypertension.
        Chest. 2009; 136: 10-15
        • Snell G.I.
        • Yusen R.D.
        • Weill D.
        • et al.
        Report of the ISHLT working group on primary graft dysfunction, part I: definition and grading-A 2016 consensus group statement of the International Society for Heart and Lung Transplantation.
        J Heart Lung Transplant. 2017; 36: 1097-1103
        • Stewart S.
        • Fishbein M.C.
        • Snell G.I.
        • et al.
        Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection.
        J Heart Lung Transplant. 2007; 26: 1229-1242
        • Verleden G.M.
        • Glanville A.R.
        • Lease E.D.
        • et al.
        Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatment—a consensus report from the Pulmonary Council of the ISHLT.
        J Heart Lung Transplant. 2019; 38: 493-503
        • Glanville A.R.
        • Verleden G.M.
        • Todd J.L.
        • et al.
        Chronic lung allograft dysfunction: definition and update of restrictive allograft syndrome—a consensus report from the Pulmonary Council of the ISHLT.
        J Heart Lung Transplant. 2019; 38: 483-492
        • Kanda Y.
        Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics.
        Bone Marrow Transpl. 2013; 48: 452-458
        • Jankowich M.D.
        • Rounds S.I.S.
        Combined pulmonary fibrosis and emphysema syndrome: a review.
        Chest. 2012; 141: 222-231
        • Raghu G.
        • Weycker D.
        • Edelsberg J.
        • Bradford W.Z.
        • Oster G.
        Incidence and prevalence of idiopathic pulmonary fibrosis.
        Am J Respir Crit Care Med. 2006; 174: 810-816
        • Zhang L.
        • Zhang C.
        • Dong F.
        • et al.
        Combined pulmonary fibrosis and emphysema: a retrospective analysis of clinical characteristics, treatment and prognosis.
        BMC Pulm Med. 2016; 16: 137
        • Jiang C.G.
        • Fu Q.
        • Zheng C.M.
        Prognosis of combined pulmonary fibrosis and emphysema: comparison with idiopathic pulmonary fibrosis alone.
        Ther Adv Respir Dis. 2019; 13 (1753466619888119)
        • Kumar A.
        • Cherian S.V.
        • Vassallo R.
        • Yi E.
        • Ryu J.H.
        Current concepts in pathogenesis, diagnosis, and management of smoking-related interstitial lung diseases.
        Chest. 2018; 154: 394-408
        • Cottin V.
        • Azuma A.
        • Raghu G.
        • et al.
        Therapeutic effects of nintedanib are not influenced by emphysema in the Inpulsis trials.
        Eur Respir J. 2019; 53: 4
        • Koo H.J.
        • Do K.H.
        • Lee J.B.
        • Alblushi S.
        • Lee S.M.
        Lung cancer in combined pulmonary fibrosis and emphysema: a systematic review and meta-analysis.
        PLoS One. 2016; 11e0161437
        • Li C.
        • Wu W.
        • Chen N.
        • et al.
        Clinical characteristics and outcomes of lung cancer patients with combined pulmonary fibrosis and emphysema: a systematic review and meta-analysis of 13 studies.
        J Thorac Dis. 2017; 9: 5322-5334
        • Khuder S.A.
        Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis.
        Lung Cancer. 2001; 31: 139-148
        • Fang A.
        • Studer S.
        • Kawut S.M.
        • et al.
        Elevated pulmonary artery pressure is a risk factor for primary graft dysfunction following lung transplantation for idiopathic pulmonary fibrosis.
        Chest. 2011; 139: 782-787
        • Christie J.D.
        • Bavaria J.E.
        • Palevsky H.I.
        • et al.
        Primary graft failure following lung transplantation.
        Chest. 1998; 114: 51-60
        • Christie J.D.
        • Kotloff R.M.
        • Pochettino A.
        • et al.
        Clinical risk factors for primary graft failure following lung transplantation.
        Chest. 2003; 124: 1232-1241
        • Whitson B.A.
        • Nath D.S.
        • Johnson A.C.
        • et al.
        Risk factors for primary graft dysfunction after lung transplantation.
        J Thorac Cardiovasc Surg. 2006; 131: 73-80
        • Bando K.
        • Keenan R.J.
        • Paradis I.L.
        • et al.
        Impact of pulmonary hypertension on outcome after single-lung transplantation.
        Ann Thorac Surg. 1994; 58: 1336-1342