BackgroundInterstitial lung disease (ILD) is one of the most serious complications associated with connective tissue diseases (CTD). Patients with ILD have increased mortality and limited treatment options. Lung transplant has been recognized as an option for patients with end-stage CTD-ILD. However, rheumatic diseases are still sometimes considered a contraindication for lung transplant because of concerns for worse outcomes.ObjectivesOur aims were to: a) assess long-term post-transplant survival in patients with CTD-ILD and b) compare post post-transplant survival of patients with CTD-ILD with patients with idiopathic pulmonary fibrosis (IPF).MethodsSingle center study in a referral center for lung transplant of all patients who underwent lung transplantation for CTD-ILD between 1998 and 2017. This cohort was compared with patients with IPF (group-matched for age, transplant year and basiliximab induction). Cumulative survival rates after transplantation were estimated by the Kaplan-Meier method and compared between groups using the log-rank test.ResultsWe studied 26 patients with CTD-ILD matched to 26 patients with IPF. The underlying diseases of patients with CTD-ILD were: Rheumatoid arthritis (n=9), Scleroderma (n=6), Sjögren syndrome (n= 4), ANCA-vasculitis (n=3), Anti synthetase syndrome (n=2), Dermatomyositis (n=1), Systemic lupus erythematosus (n=1). The comparative study of baseline characteristics between both groups is shown in the TABLE. All of RA patients undergoing transplantation in our study had the histologic subtype of usual interstitial pneumonia (UIP) whereas non-specific interstitial pneumonia (NSIP) was the most common histologic subtype of ILD associated with the rest of CTD. Cumulative survival rates at 5 year post-transplant did no differ significantly between CTD-ILD and IFP [42.4% vs 65.8% (p=0.075)] (FIGURE 1).ConclusionOur retrospective analysis showed a trend to lower long-term post-transplant survival than in those with IPF, however no statistical differences were found in cumulative survival rates at 5-years post-transplant. These data support that lung transplantation should be considered in patients with end-stage CTD-ILD.Disclosure of InterestsD. Prieto-Peña: None declared, Monica Calderón-Goercke: None declared, Amaya Martínez-Meñaca: None declared, Victor Manuel Mora-Cuesta: None declared, Sonia Fernández-Rozas: None declared, David Iturbe-Fernández: None declared, Jose Manuel Cifrián-Martínez: None declared, Miguel A González-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen
Patients undergoing lung transplantation (LTx) need administration of immunosuppressive therapy following the procedure to prevent graft rejection. However, these drugs are not exempt from potential risks. The development of cardiovascular risk factors and impaired renal function in the post-transplantation period are conditions that may be favoured by the use of calcineurin inhibitor (CNI) drugs which could have repercussions on the quality of life and the post-transplantation evolution. To evaluate the cardiovascular and renal toxicity following the administration of CNI as maintenance immunosuppression in lung transplant recipients (LTRs) we reviewed a total number of 165 patients undergoing LTx between 01/01/2015 and 08/12/2018. They were divided into two groups according to the CNI drug administrated: cyclosporine (CsA-group) with 11 patients or tacrolimus (Tac-group), with 154 patients. We evaluated the de novo occurrence of arterial hypertension (HTN), diabetes mellitus (DM), hyperlipidemia and impaired renal function after initiation of CNI administration. In addition to that, the time until each of these events was assessed. A higher rate for developing HTN (p < 0.001) and impaired renal function (p = 0.047) was observed within the CsA-group. The new onset of hyperlipidemia was similar between both CNI groups and de novo appearance of DM was only documented in those LTRs receiving tacrolimus. In this LTRs retrospective study, it was observed that having ≥ 4 tacrolimus trough levels above the upper limit of the proposed interval for each specific post-LTx period was associated with an increased risk for developing renal impairment. No other statistically significant association was found between supratherapeutic CNIs blood levels and the evaluated toxicities.
BackgroundPleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease (ILD) that can be idiopathic or associated with a variety of different conditions, including connective tissue diseases (CTD)[1-2]. In this regard, the presence of PPFE has been reported as an independent predictor of worse prognosis in CTD-ILD patients[3]. Approximately one third of the patients with ILD meet criteria for a CTD[4].ObjectivesA) To determine the prevalence of PPFE in a cohort of Spanish patients with CTD-ILD, andB) to compare the characteristics between CTD-ILD patients with and without PPFE.MethodsA total of 99 patients with CTD-ILD (31 rheumatoid arthritis (RA), 31 systemic sclerosis (SSc), 21 idiopathic inflammatory myositis (IIM), 6 primary Sjögren’s syndrome (SS), 4 systemic lupus erythematosus (SLE) and 6 with other CTDs) from the Hospital Universitario Marqués de Valdecilla (Santander, Spain) were included in this study. The presence of PPFE was confirmed by experienced radiologists evaluating chest high-resolution computed tomography images from all patients. In addition, demographic, clinical and radiological characteristics were collected.ResultsThe presence of PPFE was found in 9 (9.1%) of the 99 CTD-ILD patients, whereas the remaining 90.9% had no signs of PPFE. In particular, it was confirmed in 4 patients with RA (12.9%), 2 with SSc (6.5%), 1 with IIM (4.8%), 1 with primary SS (16.7%) and 1 with SLE (25.0%) (Figure 1). The prevalence of bronchial dilation was statistically higher in CTD-ILD patients with PPFE compared to those without PPFE (44.4%versus6.74%, respectively, p=0.006,Table 1). There were no significant differences in age at CTD or ILD diagnosis, sex, smoking history, body mass index and pulmonary function tests at ILD diagnosis between both groups (Table 1).ConclusionWe provide the prevalence and clinical data of PPFE in patients with CTD-ILD from a national referral centre. Approximately 1 out of 10 of our patients presented associated PPFE, closely correlated to bronchial dilation. The identification of this condition in CTD-ILD patients should be considered routinely since it may worsen their prognosis.References[1]Chua F, et al. Ann Am Thorac Soc. 2019 Nov;16(11):1351-1359. doi: 10.1513/AnnalsATS.201902-181CME[2]Bonifazi M, et al. Eur Respir J. 2020 Jul 9;56(1):1902135. doi: 10.1183/13993003.02135-2019[3]Orlandi M, et al. Rheumatology (Oxford). 2020 Dec 1;59(12):3645-3656. doi: 10.1093/rheumatology/keaa451[4]Atienza-Mateo B, et al. J Clin Med. 2020 May 26;9(6):1606. doi: 10.3390/jcm9061606Table 1.Demographic, clinical and radiological characteristics between CTD-ILD patients with and without PPFE.CharacteristicsCTD-ILD patients with PPFECTD-ILD patients without PPFEpAge at CTD diagnosis (years), mean ± SD57.4 ± 11.353.0 ± 12.60.35Age at ILD diagnosis (years), mean ± SD54.9 ± 12.656.4 ± 12.50.73Sex (men/women), n (%)3/6 (37.5/62.5)43/47 (47.8/52.2)0.50Smoking history, n (%)4 (50.0)52 (62.7)0.48Body mass index23.5 ± 5.526.2 ± 4.60.14PFTs at ILD diagnosisFVC ml, mean ± SD2196 ± 12682740 ± 945.30.16FVC (% predicted), mean ± SD71.3 ± 38.184.1 ± 25.40.22DLCO (% predicted), mean ± SD36.2 ± 19.347.0 ± 16.00.15DLCO/VA (% predicted), mean ± SD66.8 ± 18.872.9 ± 23.20.57Radiological featuresAny bronchial dilatation, n (%)4 (44.4)6 (6.74)0.006CTD: connective-tissue disease; DLCO: diffusing capacity of the lung for carbon monoxide; FEV1: forced expiratory volume in one second; FVC: forced vital capacity; ILD: interstitial lung disease; PFTs: pulmonary function tests; PPFE: pleuroparenchymal fibroelastosis; SD: standard deviation; VA: alveolar volume.Significant results are highlighted in bold.Figure 1.Prevalence of PPFE in each CTD-ILD.AcknowledgementsVP-C is supported by funds of PI18/00042 from Instituto de Salud Carlos III (ISCIII), co-funded by European Regional Development Fund; RL-M is a recipient of a Miguel Servet type II Program fellowship from ISCIII, co-funded by the European Social Fund, `Investing in your future ́ (CPII21/00004).Disclosure of InterestsBelén Atienza-Mateo: None declared, Sara Remuzgo Martinez: None declared, Verónica Pulito-Cueto: None declared, Diego Ferrer: None declared, Gerardo Blanco: None declared, Sheila Izquierdo: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, Raquel López-Mejías: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Lilly, Bristol-Myers, Janssen, Galapagos and MSD, Consultant of: Abbvie, Pfizer, Roche, Lilly, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD, Novartis and Roche, Jose Manuel Cifrián-Martínez: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Grant/research support from: Abbvie, MSD, Jansen and Roche.
BackgroundInterstitial lung disease (ILD) is one of the main causes of death in patients with rheumatoid arthritis (RA), constituting itsearly diagnosis in these patients a challenge for the clinicians [1]. In this sense, pulmonary endothelial activation is one of the essential steps to the development of lung lesions [2,3]. In this regard, endothelin-1 (ET-1), the most potent endogenous vasoconstrictor, has been described as a profibrotic molecule [3]. Accordingly, it is plausible to think that ET-1 is involved in the pathophysiology of RA-ILD+.ObjectivesTo explore the role of ET-1 as a biomarker of pulmonary fibrosis in RA-ILD+.MethodsPeripheral venous blood was collected from 21 RA-ILD+patients and two comparative groups: 25 RA-ILD-patients and 21 idiopathic pulmonary fibrosis (IPF) patients. All the subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Serum levels of ET-1 were determined by ELISA.ResultsRA-ILD+patients showed increased levels of ET-1 compared to those with RA-ILD-(p<0.01,Figure 1A). Interestingly, the ability of serum ET-1 levels to discriminate patients with RA-ILD+from those with RA-ILD-was further confirmed by receiver operating characteristic curves (area under the curve: 0.77, p<0.01,Figure 1B). The optimal cutoff value for ET-1 showing the best sensitivity and specificity was 1.02 pg/mL. Moreover, patients with RA-ILD+presented similar levels of ET-1 than those with IPF (p=0.50,Figure 1A). Additionally, a negative correlation between ET-1 serum levels and both forced vital capacity and forced expiratory volumen at first second was disclosed in patients with RA-ILD+(r=-0.56, p=0.04 and r=-0.65, p=0.01, respectively).Figure 1.ET-1 for the diagnosis of RA-ILD+. Differences in serum levels of ET-1 between patients with RA-ILD+and those with RA-ILD-and IPF (A), as well as ROC curves analysis of ET-1 for the discrimination of RA-ILD+from RA-ILD-(B). ET-1: endothelin 1; RA: rheumatoid arthritis; ILD: interstitial lung disease; IPF: idiopathic pulmonary fibrosis;. Significant results are highlighted inbold.ConclusionOur study suggests that ET-1 levels are linked to lung injury and worse lung function, supporting its role as a potential blood biomarker of ILD in RA patients.References[1]Expert Rev Clin Immunol. 2021;17(5):485-497;[2]JCI Insight. 2021;6(22):e125635;[3]Am J Respir Cell Mol Biol. 2010;42(1):16-20.AcknowledgementsVP-C is supported by funds of PI18/00042 from Instituto de Salud Carlos III (ISCIII), co-funded by European Regional Development Fund; MSM-G is financed by funds of TRANS-VAL 22/01 from IDIVAL; RL-M is a recipient of a Miguel Servet type II Program fellowship from ISCIII, co-funded by the European Social Fund, `Investing in your future´ (CPII21/00004).Disclosure of InterestsVerónica Pulito-Cueto: None declared, Sara Remuzgo Martinez: None declared, Belén Atienza-Mateo: None declared, Fernanda Genre Romero: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, María Sebastián Mora-Gil: None declared, Virginia Portilla: None declared, Alfonso Corrales: None declared, Iván Ferraz-Amaro: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Grant/research support from: Abbvie, MSD, Jansen and Roche.
Background. Lung transplantation remains the treatment of choice for end-stage lung diseases, and recipient selection is currently based on clinical urgency, ABO compatibility, and donor size. The risk of allosensitization is classically based on HLA mismatch, but eplet mismatch load is increasingly seen to be important in long-term outcomes in solid organ transplantation. Chronic lung allograft dysfunction (CLAD) is relatively common and relevant, affecting almost 50% of patients 5 y after transplantation and being the first cause of death from the first year after transplantation. The overall class-II eplet mismatch load has been associated with CLAD development. Methods. Based on clinical data, 240 lung transplant recipients were eligible for CLAD, and HLA and eplet mismatch was analyzed using the HLAMatchmaker 3.1 software. Results. A total of 92 (38.3%) lung transplant recipients developed CLAD. The time free-of-CLAD was significantly decreased in patients with presence of DQA1 eplet mismatches (P = 0.015). Furthermore, when other previously described CLAD risk factors were studied in a multivariate analysis, the presence of DQA1 eplet mismatches was found to be independently associated with the early onset of CLAD. Conclusions. The concept of epitope load has arisen as a new tool to better define donor–recipient immunologic compatibility. The presence of DQA1 eplet mismatches potentially would increase the likelihood of developing CLAD.
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