Maria Isabel Prieto Barrio

Risk factors for bronchiolitis, recurrent wheezing, and related hospitalization in preterm infants during the first year of life

Airway diseases are highly prevalent in infants and cause significant morbidity. We aimed to determine the incidence and risk factors for respiratory morbidity in a Spanish cohort of moderate‐to‐late preterm (MLP) infants prospectively followed during their first year of life.

Antibiotic resistance and population structure of cystic fibrosis Pseudomonas aeruginosa isolates from a Spanish multi-centre study

The first Spanish multi-centre study on the microbiology of cystic fibrosis (CF) was conducted from 2013 to 2014. The study involved 24 CF units from 17 hospitals, and recruited 341 patients. The aim of this study was to characterise Pseudomonas aeruginosa isolates, 79 of which were recovered from 75 (22%) patients. The study determined the population structure, antibiotic susceptibility profile and genetic background of the strains. Fifty-five percent of the isolates were multi-drug-resistant, and 16% were extensively-drug-resistant. Defective mutS and mutL genes were observed in mutator isolates (15.2%). Considerable genetic diversity was observed by pulsed-field gel electrophoresis (70 patterns) and multi-locus sequence typing (72 sequence types). International epidemic clones were not detected. Fifty-one new and 14 previously described array tube (AT) genotypes were detected by AT technology. This study found a genetically unrelated and highly diverse CF P. aeruginosa population in Spain, not represented by the epidemic clones widely distributed across Europe, with multiple combinations of virulence factors and high antimicrobial resistance rates (except for colistin).

Bronchopulmonary infection–colonization patterns in Spanish cystic fibrosis patients: Results from a national multicenter study

BACKGROUND Clinical and demographical knowledge on Spanish cystic fibrosis (CF) patients is incomplete as no national registry exists. CF-microbiology has not been studied at national level. The results of the first Spanish multicenter study on CF microbiology are presented. METHODS 24 CF-Units for adult (n=12) and pediatric (n=12) patients from 17 hospitals provided sputa and clinical data from 15 consecutive patients. Cultures and susceptibility testing were performed. Colonization impact on pulmonary function was assessed. RESULTS 341 patients [mean (SD) age 21 (11) years, 180≥18years, mean (SD) FEV1=68 (25)%] were included. Pseudomonas aeruginosa was reported as chronic, intermittent or absent in 46%, 22% and 32% of patients, respectively. The annual prevalence was 62%. Positive P. aeruginosa and methicillin-resistant Staphylococcus aureus cultures were significantly associated with lower FEV1 (p<0.001 and p=0.003, respectively). CONCLUSIONS The representative subset of the Spanish CF-population which has been clinically, demographically and microbiologically characterized will serve as a reference for future CF studies in Spain.

Pacientes con fibrosis quística atendidos en las unidades de fibrosis quística de la Comunidad de Madrid: estudio transversal de 387 casos

Fundamento y objetivo: Establecer las caracteristicas clinicas y geneticas de los pacientes con fibrosis quistica (FQ) de la Comunidad de Madrid. Pacientes y metodo: Estudio descriptivo y transversal de los pacientes con FQ atendidos regularmente durante el ano 2001. Se recogieron datos demograficos, geneticos, antropometricos, presencia de insuficiencia pancreatica, diabetes mellitus y colonizacion por Pseudomonas aeruginosa, valores espirometricos y de indice de masa corporal (puntuacion Z), y se compararon con los del registro americano del mismo ano. Resultados: Se incluyo a 387 pacientes ?209 varones (54%)?, la mayoria residentes en Madrid (n = 247 [63%]), con una edad media (DE) de 15,15 (10,42) anos (menores de 18 anos, 248 [64,24%]). La mutacion mas frecuente fue la F508del (52,8% de los cromosomas), con 104 homocigotos (28,5%). Presentaron insuficiencia pancreatica 310 (80,1%); diabetes mellitus, 30 (7,8%), y colonizacion por P. aeruginosa, 126 (33,1%). La funcion pulmonar se midio en 309 pacientes. La media del porcentaje predicho del volumen espiratorio forzado en el primer segundo fue de 82,5 (27,11) y la de la capacidad vital forzada de 89,32 (21,89). La media de la puntuacion Z del indice de masa corporal fue de ?0,0796 (1,18). La peor funcion pulmonar correspondio a los pacientes colonizados por P. aeruginosa, con peor estado de nutricion y de mayor edad. La insuficiencia pancreatica, la edad y la peor funcion respiratoria (volumen espiratorio forzado en el primer segundo) determinaron el peor estado nutricional. Conclusiones: Los pacientes con FQ de nuestra comunidad tienen buen estado nutricional, menos colonizacion por P. aeruginosa e insuficiencia pancreatica y mejor funcion pulmonar que los pacientes del registro americano. La menor presencia de la mutacion F508del en homocigosis podria ser la causa, al menos en parte, de estos resultados.

178* Assessment of pulmonary inflammation in cystic fibrosis patients by calprotectin determination in induced sputum

Introduction: A20 is a negative regulator of TLR driven NF-uB signalling. This regulatory function is reliant on the formation of a ubiquitin editing complex comprising A20, Ring Finger protein (RNF)11, Itch (E3 ligase) and the adaptor protein TAX1BP1 [1]. In CF epithelial cells LPS reduces the expression of all complex members. Moreover, A20 does not interact with other complex members or target proteins [2,3]. Here we sought to determine the role of CFTR in the down-regulation of A20 ubiquitin editing genes. Methods: 16HBE41obronchial epithelial cells were transfected with CFTR siRNA. Primary nasal epithelial cells (NECs) from CF patients [F508del homozygous (n = 6), or R117H/F508del heterozygous (n = 5)] and age-matched controls (n = 6) were fully differentiated at air-liquid interface and treated with LPS (P. aeruginosa, Sigma) for 24h. A20, RNF11, Itch and TAX1BP1 mRNA expression was assessed by qPCR and analysed by ANOVA. Results: Following CFTR knockdown (transfection efficiency 72%±5.34%, n = 3) A20 mRNA was reduced by 43% (P < 0.01). This would indicate that A20 expression may be regulated by CFTR. In line with this, expression of A20, RNF11, Itch and TAX1BP1 was significantly reduced (P < 0.01–0.001) in NECs from both CF groups compared with controls. Moreover, the reduction in A20, RNF11 and TAX1BP1 (P < 0.05) expression was more pronounced in the F508del than R117H group. Conclusion: Expression of the A20 ubiquitin editing complex reflects CF disease severity and may prove a novel predictor of inflammation. The CF Trust UK (PJ541) supported this work