Role of VEGF polymorphisms in the susceptibility and severity of interstitial lung disease

The search for biomarkers that can help to establish an early diagnosis and prognosis of interstitial lung disease (ILD) is of potential interest. VEGF polymorphisms have been implicated in the development of several lung disorders. Consequently, we assessed, for the first time, the role of VEGF polymorphisms in the susceptibility and severity of ILD. A total of 436 Caucasian ILD patients (244 with idiopathic interstitial pneumonias (IIPs) and 192 with non-IIP) and 536 ethnically-matched healthy controls were genotyped for VEGF rs833061, rs1570360, rs2010963, rs3025020, and rs3025039 polymorphisms by TaqMan assays. Pulmonary function tests were collected from all the patients. VEGF serum levels were determined by ELISA in a subgroup of patients. No VEGF genotype, allele, carrier, or haplotype differences were found between ILD patients and controls as well as between IIP and non-IIP patients. However, an association of rs1570360 with IIP in women and also with lung function in IIP patients was found. None of the VEGF polymorphisms were associated with VEGF levels. In conclusion, our results suggest that VEGF does not seem to play a relevant role in ILD, although rs1570360 may influence the severity of ILD in women and a worse outcome in IIP patients.Funding: This research was partially supported by a grant from Spanish Society of Pulmonology and Thoracic Surgery (SEPAR 474-2017). S.R.-M. was supported by funds of the RETICS Program (RD16/0012/0009) from the “Instituto de Salud Carlos III” (ISCIII), co-funded by the European Regional Development Fund. V.P.-C. was supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). B.A.-M. was recipient of a “López Albo” post-residency program funded by Servicio Cántabro de Salud. L.L.-G. was supported by funds from IDIVAL (INNVAL 20/06). O.G. was beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10. R.L.-M. was a recipient of a Miguel Servet type I program fellowship from the ISCIII, co-funded by the ESF, “Investing in your future” (grant CP16/00033)

Influence of MUC5B gene on antisynthetase syndrome

ABSTRACT: MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was partially supported by grants from the Foundation for Research in Rheumatology (FOREUM). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ‘Instituto de Salud Carlos III’ (ISCIII), co-funded by the European Social Fund (ESF, ‘Investing in your future’) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009), co-funded by the European Regional Development Fund (ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ESF). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF). OG is Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). OG,is member of RETICS Programme, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. The work of OG (PI17/00409), was funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Programme (Project number 734899). OG is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10

Sarcoidosis pulmonar y síndrome antifosfolipídico

La sarcoidosis pulmonar es una enfermedad granulomatosa de etiología desconocida que puede cursar con un cuadro clínico de disnea, tos, dolor torácico y alteraciones radiológicas características. Presentamos el primer caso descrito en toda la bibliografía revisada en PubMed, entre los años 1990 y 2002, en revistas de lenguas inglesa y española, de sarcoidosis pulmonar asociada a síndrome antifosfolipídico primario, en un paciente de 35 años, que cursó con trombosis venosa y desarrolló posteriormente sarcoidosis pulmonar que, a pesar de presentar factores considerados de buen pronóstico, evolucionó de forma poco favorable. Concluimos que la asociación de ambas entidades clínicas es poco frecuente y que la presencia de un síndrome antifosfolipídico asociado podría condicionar una mayor morbimortalidad

Trasplante pulmonar en enfermedades supurativas

Objetivo: El trasplante pulmonar es una opción terapéutica válida para pacientes con bronquiectasias. El objetivo de nuestro trabajo ha sido analizar nuestra experiencia en estos pacientes y comparar los resultados entre los pacientes con fibrosis quística y bronquiectasias de otra etiología. Pacientes y método: Se ha realizado un estudio retrospectivo de los pacientes trasplantados por bronquiectasias para analizar las características demográficas, funcionales y aspectos microbiológicos antes y después del trasplante, así como la supervivencia. Resultados: Entre 1991 y 2002 trasplantamos a 171 pacientes, de los cuales 44 presentaban enfermedad pulmonar supurativa (27 fibrosis quística y 17 bronquiectasias de otras etiologías). No había diferencias significativas en las variables demográficas entre ambos grupos. En el momento del trasplante la función pulmonar mostraba grave obstrucción bronquial (volumen espiratorio forzado en el primer segundo: 808 ± 342 ml; capacidad vital forzada: 1.390 ± 611 ml) e insuficiencia respiratoria (presión arterial de oxígeno: 52 ± 10 mmHg; presión arterial de anhídrido carbónico: 48 ± 9 mmHg). Sólo la presión arterial de oxígeno fue significativamente inferior en los pacientes con bronquiectasias de etiología diferente de la fibrosis quística. El 91% de los pacientes presentaba colonización de la vía aérea; el germen más frecuente fue Pseudomona spp. (64%), que en un 9% de los casos fue multirresistente. En el postoperatorio inmediato se aislaron gérmenes en el 59% de los casos; la mitad de ellos eran los mismos que se habían aislado antes del trasplante. Un año después del trasplante pulmonar, un 34% de los pacientes seguían mostrando colonización bronquial. La supervivencia al año fue del 79% y a los 5 años del 49%, sin diferencias significativas entre los pacientes con fibrosis quística y el resto de las enfermedades supurativas, ni entre los pacientes con o sin colonización por Pseudomonas spp. Sólo 2 pacientes fallecieron por neumonía bacteriana en el primer mes del trasplante pulmonar. Conclusiones: A pesar de que la colonización de la vía aérea de los pacientes con enfermedad supurativa complica el manejo tras el trasplante pulmonar, los resultados en términos de supervivencia son buenos

Esophageal motor disorders are frequent during pre and post lung transplantation. Can they influence lung rejection?

ABSTRACT Background: lung transplantation (LTx) is a viable option for most patients with end-stage lung diseases. Esophageal motor disorders (EMD) are frequent in candidates for LTx, but there is very little data about changes in esophageal motility post-LTx. Aim: the aim of our study was to assess esophageal motor disorders by high resolution manometry (HRM) both pre-LTx and six months post-LTx in patients with and without organ rejection. Study: HRM (Manoscan(r)) was performed in 57 patients both pre-LTx and six months post-LTx. HRM plots were analyzed according to the Chicago classification 3.0. Results: EMD were found in 33.3% and in 49.1% of patients pre-LTx and post-LTx, respectively, and abnormal peristalsis was more frequently found post-LTx (p = 0.018). Hypercontractile esophagus was frequently found post-LTx (1.8% and 19.3% pre-LTx and post-LTx, respectively). Esophagogastric junction (EGJ) morphology changed significantly pre-LTx and post-LTx; type I (normal) was more frequent post-LTx (63-2% and 82.5% respectively, p = 0.007). EMD were more frequent post-LTx in both the non-rejection and rejection group, although particularly in the rejection group (43.2% and 69.2% respectively, p = 0.09). EMD such as distal spasm, hypercontractile esophagus and EGJ outflow obstruction were also observed more frequently post-LTx in the rejection group. Conclusion: significant changes in esophageal motility were observed pre-LTx and particularly post-LTx; hypercontractile esophagus was a frequent EMD found post-LTx. EMD were more frequent in the group of patients that experienced organ rejection compared to the non-rejection group. EMD leading to an impaired esophageal clearance should be considered as an additional factor that contributes to LTx failure