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Antifibrotic drugs are the standard treatments for patients with idiopathic pulmonary fibrosis (IPF). This study aims to assess the safety of antifibrotic treatment in IPF patients undergoing lung transplantation.Patients with a diagnosis of IPF who received a lung transplant between January 2015 and June 2019 at four Spanish hospitals specialized in lung transplantation were retrospectively recruited. Cases were defined as patients receiving antifibrotic treatments at time of transplant. Each case was matched with a control who did not receive antifibrotic treatment.A total of 164 patients were included in the study cohort (103 cases and 61 controls). There were no statistically significant differences between the cases and controls in any of the items studied related to transplantation except the time until the appearance of chest wall dehiscence: although there were no differences in the incidence of wall dehiscence in either group (12.3% vs. 13.7%; p = 0.318), the patients on antifibrotic drugs experienced it earlier (21 days [IQR = 12.5-41.5] vs. 63 days [IQR = 46.75-152.25]; p = 0.012). There were no differences in overall post-transplant survival between the two groups (p = 0.698) or in conditional survival at 30 days, 90 days, 3 years or 5 years. However, 1 year survival was significantly greater among controls (80.6% vs. 93.3%; p = 0.028).There was evidence that chest wall dehiscences appeared earlier post-transplant in patients using antifibrotics, even though this factor did not significantly impact survival.

The outcomes of heart-lung transplant (HLT) are worse than those of heart transplant (HT) and lung transplant alone; this and the availability of mechanical assistance have meant that the indications for HLT have been changing. This study aims to analyze the evolution of indications for HLT in a country of 47 million inhabitants.We performed a retrospective observational study of all HLTs performed in Spain (performed in 2 centers) from 1990 to 2020. The total number of patients included was 1751 (HT 1673 and HLT 78). After clinical adjustment, overall survival was compared between the 2 groups. Seven etiological subgroups were considered within the HLT group: (1) cardiomyopathy with pulmonary hypertension (CM + PH);, (2) Eisenmenger syndrome, (3) congenital heart disease without Eisenmenger syndrome, (4) idiopathic pulmonary arterial hypertension (IPAH), (5) cystic fibrosis, (6) chronic obstructive pulmonary disease (COPD) and/or emphysema), and (7) diffuse interstitial lung disease.There were a large number of differences between patients with HLT vs HT. HLT had a 2.69-fold increased probability of death in the first year compared with HT. The indications for HLT have changed over the years. In the recent period the indications are mainly congenital heart disease and Eisenmenger syndrome, with some cases of CM + PH. Other indications for HLT have virtually disappeared, mainly lung diseases (IPAH, COPD, cystic fibrosis). Median survival was low in CM + PH (18 days), diffuse interstitial lung disease (29 days), and ischemic heart disease (114 days); intermediate in Eisenmenger syndrome (600 days); and longer in IPAH, COPD and/or emphysema, and cystic fibrosis.HLT is a procedure with high mortality. This and mechanical assists mean that the indications have changed over the years. Etiological analysis is of utmost interest to take advantage of organs and improve survival.

In cystic fibrosis (CF), there is a predisposition to bronchial colonization by potentially pathogenic microorganisms, such as fungi. Our aims were to describe the dynamics of respiratory mycobiota in patients with CF and to evaluate the geographic, age and gender variability in its distribution.Cohort study in which 45 patients with CF from four hospitals in three Spanish cities were followed up during a 1-year period, obtaining spontaneous sputum samples every 3 to 6 months. Fungal microbiota were characterized by Internal Transcribed Spacer sequencing and Pneumocystis jirovecii was identified by nested PCR in a total of 180 samples.The presence of fungi were detected in 119 (66.11%) of the 180 samples and in 44 (97.8%) of the 45 patients: 19 were positive and 1 negative throughout all follow-ups and the remaining 25 presented alternation between positive and negative results. A total of 16 different genera were identified, with Candida spp. (50/180, 27.78%) and Pneumocystis spp. (44/180, 24.44%) being the most prevalent ones. The distribution of fungal genera was different among the evaluated centres (p 0.05), by age (non-adults aged 6-17 years vs. adults aged ≥18 years) (p 0.05) and by gender (p 0.05).A high prevalence of fungal respiratory microbiota in patients with CF was observed, whose dynamics are characterized by the existence of multiple cycles of clearance and colonization, reporting the existence of geographic, age and gender variability in the distribution of fungal genera in this disease.

Background Respiratory syncytial virus (RSV) can cause severe respiratory infection and is a risk factor for development of bronchiolitis obliterans syndrome (BOS) in patients who have undergone lung transplantation (LT). The treatment options are limited in this population. We assessed the efficacy of oral administration for the treatment of RSV infection after LT. Methods A retrospective case-control was conducted in LT patients who documented RSV infection. Demographic, clinical, and efficacy variables (resolution infection, recovery of lung function, incidence of BOS, mortality) was compared between the oral ribavirin (RBV) group and the control group. Results Thirty-six LT patients were included (19 RBV group, 17 control group). Significant differences were found for age, sex and coinfections. However, no differences of immunosuppressive level and baseline forced expiratory volume in the first second of expiration (FEV1) were found. RSV clearance was evident in 5 patients (26.3%) of the RBV group vs 2 patients (11.8%) in the control group (odds ratio [OR], 0.37; P = .282). At 3 months, FEV1 remained stable in 12 patients (80%) of the RBV group vs 13 patients (81.3%) of the control group (OR, 0.92; P = .321). At 6 months, FEV1 remained stable in 11 patients (73.3%) of the RBV group and 12 patients (75%) of the control group (OR, 1.25; P = .779), and BOS appeared in 6 patients (31.6%) vs 4 patients (23.5%) of the control group (OR, 1.50; P = .591). Mortality rates were 26% (5 patients) in the RBV group vs 29.4% (5 patients) in the control group (OR, 1.40; P = .637). Conclusions No significant differences in efficacy parameters were found between groups; however, stabilization without worsening of respiratory function was observed at 3 and 6 months. Because of the variability in the treatment regimen and the heterogeneity of groups, a protocol was developed to standardize and evaluate the use of oral RBV as treatment for RSV in LT.

Purpose The purpose of this research was to identify diagnostic volatile organic compounds (VOCs) in exhaled breath condensate (EBC) from lung transplant recipients (LTR) colonized or infected by Aspergillus spp., Staphylococcus aureus and Pseudomonas aeruginosa, in order to develop a cheap, accurate and quick non-invasive diagnostic test. To this end we performed metabolomic analysis in EBC using gas chromatography-time-of-flight mass spectrometry (GC-QTOF) in the high-resolution mode. Methods Between January 2018-June 2019, 40 LTR were recruited in the Lung Transplant Unit, from whom 71 EBC and respiratory samples (sputum, bronchoalveolar lavage or oropharyngeal swabs) were obtained. Bacteria and fungi identification were performed according to routine laboratory standards for respiratory samples. The ECOScreen2 device was used for EBC collection at -20 °C during 15 minutes, and samples were stored at −80°C in 200 μL and 500 μL aliquots until analysis. EBC samples from patients colonized either with P. aeruginosa, S. aureus, Aspergillus spp. or none of the above (controls) where selected for headspace Solid Phase Micro Extraction (SPME) with DVBP fibres in order to concentrate VOCs before their injection in the Agilent GCMS 7200 Accurate Mass Q-TOF equipment for the metabolomic analysis. GC-QTOF untargeted analysis (deconvolution, alignment, and recursive analysis) was performed with the MassHunter and Mass Profiler Software, and statistical analysis with R software. Results We selected 27 samples for SPME-GC/QTOF analysis: nine controls, seven from patients colonized by Aspergillus spp., six with P. aeruginosa, three with S. aureus and two with both P. aeruginosa and S. aureus. The PLS-DA analysis clearly differentiated patients colonized with S. aureus or P. aeuruginosa from those who were not, with a very little overlap in patients colonized with A. fumigatus from the controls. Volcano plot analysis found two possible biomarkers for Aspergillus spp. detection, six for S. aureus and none for P. aeruginosa, may be because of the small n in our study. Conclusion SPME-GC/QTOF in EBC is a promising tool for non-invasive diagnosis of fungal and bacterial infections in LTR. However, the presumptive identification of these biomarkers needs to be confirmed with targeted metabolomic studies and their sensitivity and specificity should be studied in future research.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection. J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III.

Fundamento y objetivo Describir la incidencia de complicaciones perioperatorias de los pacientes trasplantados de pulmon por enfisema pulmonar y estudiar los factores de riesgo asociados a la morbimortalidad en el postoperatorio inmediato. Pacientes y metodo Estudio retrospectivo que incluye a 69 pacientes trasplantados de pulmon por enfisema pulmonar durante los anos 1994-2002. Se realizo un analisis univariante para identificar las variables asociadas con la incidencia de la mortalidad en la Unidad de Reanimacion o con el aumento de complicaciones postoperatorias. Las variables que presentaron significacion estadistica se sometieron a analisis multivariante mediante el modelo de regresion logistica. Resultados Se incluyo a 65 pacientes. Diecisiete recibieron un trasplante unipulmonar (TUP) y 48 un transplante bilateral secuencial (TBP). Las complicaciones intraoperatorias fueron mas habituales en el grupo del trasplante bipulmonar (35,3% en el TBP frente a 72,9% en el TUP, p Conclusiones Los pacientes con TUP tienen menor numero de complicaciones en el perioperatorio, lo que condiciona una mayor supervivencia durante la estancia en reanimacion. La ventilacion mecanica durante mas de 48 h y la hemorragia posquirurgica fueron las variables que mejor predijeron la mortalidad en el postoperatorio inmediato.

Fundamentos Describir en pacientes hospitalizados por sospecha de neoplasia pulmonar la proporcion de ingresos y estancias inadecuadas, las causas de inadecuacion y los tiempos de demora diagnostica; analizar la relacion entre caracteristicas del paciente, duracion de la estancia y utilizacion inadecuada de la hospitalizacion, y valorar la asociacion entre solicitud de pruebas diagnosticas, prolongacion de la estancia y utilizacion innecesaria de la hospitalizacion. Metodos Cohorte prospectiva de 118 pacientes hospitalizados por sospecha de neoplasia broncopulmonar en un hospital universitario en la que se analizo la duracion de la estancia, estancias inadecuadas y demoras en la realizacion de pruebas diagnosticas. Resultados La duracion media de la estancia fue de 16,3 dias, con un 74,2% de estancias innecesarias e importantes demoras diagnosticas intrahospitalarias, que superaron los 5 dias para la realizacion de una radiografia de torax, casi 7 para la realizacion de una tomografia computarizada y 8 para disponer de los resultados de la anatomia patologica. La proporcion de estancias inadecuadas se asocio al numero y tipo de pruebas solicitadas. Conclusiones Los resultados de este estudio sugieren amplias posibilidades para mejorar la calidad de la atencion a los pacientes con sospecha de neoplasia pulmonar, tanto evitando ingresos innecesarios como acortando las demoras diagnosticas, a la par que se reducen los costes de la atencion y se reservan las camas hospitalarias para aquellos casos en que la situacion clinica realmente lo requiera.

a b s t r a c t Thrombotic microangiopathy (TMA) is a rare complication associated with the use of calcineurin inhi- bitors in lung transplantation, irrespective of the underlying disease of the graft recipient. It usually occurs in incomplete forms, complicating and delaying diagnosis until damage is already irreversible. It is unrelated to time from transplantation and often presents with concomitant infection, which tends to confound diagnosis. The cases discussed here have a common causative agent and all present with con- comitant infection. Treatment recommendations have changed in recent years with the introduction of plasmapheresis or, more recently, the availability of the antibody eculizumab. Notwithstanding, the most cost-effective measure is withdrawal or switching of the calcineurin inhibitor. TMA is an underdiagnosed clinical entity that should be considered in the management of transplantation patients.

Background Therapeutic monitoring of everolimus is necessary to determine an optimal dosage regimen in lung transplantation patients to prevent graft rejection due to the narrow therapeutic window. The area under the concentration-time curve (AUC –12 ) is the best strategy for pharmacokinetic study because it reflects total drug exposure in the body, especially in cystic fibrosis (CF) patients who have abnormalities in the gastrointestinal system. Purpose The aim of this study was to evaluate the absorption profile of everolimus in patients with CF after lung transplantation in order to optimise immunosuppressive therapy. Material and methods A pharmacokinetic, descriptive and cross sectional study was conducted in lung transplant patients with determination of AUC –12 of everolimus at less than 4 months post-transplantation. All patients were taking combined immunosuppressive treatment with everolimus. After a minimum of 7 days of receiving the same dose, nine blood samples were collected at predose, and at 0.5, 1, 2, 3, 4, 6, 8 and 12 h post-morning dose. Everolimus concentrations were measured by QMS immunoassay. Results 7 full pharmacokinetic analyses were performed in bilateral lung transplant patients. All were women with a median age of 26 years (range 13–40) and median weight of 47 kg (range 28–67). A C max of 6.40 ng/mL (range 5.64–18.51) was reached at 2 h (range 1–6). When target trough levels were achieved (3–8 ng/mL), median everolimus exposure was 53.10 ng.h/mL (range 30.81–113.31). Two patients showed a normal absorption profile of everolimus and 5 patients showed a low overall exposure to everolimus because the value C min and AUC were below the normal range. All patients underwent dose/interval modification of everolimus after the results. Following adjustments, all patients reached levels within the therapeutic range. Conclusion The pharmacokinetic variability of everolimus is very high. Monitoring everolimus levels could optimise immunosuppressive therapy. The AUC can be calculated in any CF patient regardless of the time after transplantation as long as they do not have trough levels in the therapeutic range. No conflict of interest.

Background We present a retrospective study of 9 years of experience in the management of graft dysfunction in the early postoperative period after lung transplantation (LT) and heart lung transplantation (HLT). Material and Methods There were 190 LT and HLT (22.63% single LT, 71.05% bilateral sequential LT, and 7.36% HLT) performed from 1993 to 2002. Hemodynamic and respiratory parameters were monitored during the operative technique and critical care for the first 24 hours. We analyzed ischemic time, bypass need, and type of transplant. Results Lung graft dysfunction occurred in 37.2% of patients, but only in 12.2% was it severe. Nearly all patients were ventilated on a 50% fraction of inspired oxygen during the first 24–48 hours; 61.56% of patients were extubated before the first 5 postoperative day and 38.43% thereafter. The mean ischemia time for the first lung was 220 ± 28 minutes: for the second lung, it was 378 ± 31 minutes. The anesthetic time was 500–600 minutes. The variables associated with a significantly increased graft dysfunction were as follows: bilateral LT, and cardiopulmonary bypass requirement. The residence in the intensive care unit (ICU) was longer for patients with graft dysfunction than for those without that problem. Mortality directly related to graft dysfunction was only 4.07%. Conclusions A correlation among graft ischemia and early postoperative morbidity and duration of ICU stay did not have a significant impact on mortality.

Our goal was to analyze the incidence of perioperative complications in patients with pulmonary emphysema who underwent lung transplantation and to identify variables associated with the incidence of morbidity and mortality during the immediate postoperative period.We undertook a retrospective study of 65 pulmonary emphysema patients who received lung transplants from 1994 through 2002 with the aim of determining the most common intra- and early postoperative complications in the ICU. An univariate analysis was carried out in order to identify variables associated with the incidence of mortality and postoperative complications. Those variables showing statistical significance underwent a multivariate analysis, by means of a pattern of logistic regression, in order to calculate the odds ratio and confidence interval.Seventeen patients received single-lung transplants (SLT) and 48 patients received sequential double-lung transplants (DLT). Intraoperative complications appeared more frequently in the DLT group. Most frequent complications during surgery were reperfusion syndrome (44.6%) and pulmonary hypertension (16.9%). The intraoperative survival was 100%. Fifty-five patients had some type of postoperative complication. Commonest postoperative complications were infection (56.9%) and primary graft failure (36.6%). In the early postoperative period the mortality rate was 16.9%. Main cause of death in the ICU was sepsis (54.5%). A time of mechanical ventilation48 hours and postoperative hemorrhage were the variables with a higher predictive value for mortality in the early postoperative period.Patients with SLT had a lower rate of perioperative complications and a higher survival during their stay in the ICU. Time of mechanical ventilation48 hours and postoperative hemorrhage were the variables that best predicted death in the early postoperative period following lung transplantation. Despite our experience, however, perioperative mortality in lung transplantation remains high up to this day.

To report among hospitalised patients the proportion of admissions and inappropriate stays, causes for inappropriateness and length in diagnosis delay. To analyse the relationship between patient's characteristics, length of stay and inappropriate use of hospitalization; to evaluate the association between requesting diagnostic tests, stay prolongation and unnecessary use of hospitalization.Prospective cohort of 118 admitted patients because of bronchopulmonary cancer at a university teaching hospital. Length of stay, inappropriate stays and delays in diagnostic tests were analysed.The mean hospital stay was 16.3 days, with 74.2% of unnecessary stays and relevant intrahospital diagnostic delays, with over five days for obtaining a chest X-ray, almost seven for a computerized tomography, and eight to have pathology results available. The proportion of inappropriate stays was associated with the number and type of requested tests.The results of this study suggest a number of possibilities to improve care quality to patients with suspect of lung cancer, both avoiding unnecessary admissions and shortening diagnostic delays. Also, care costs are reduced and hospital beds are reserved for those patients whose clinical status warrant hospital admission.

To study the initial respiratory effects and those observed 18 months later after the inhalation of toxic and irritant substances in textile aerography workers.Seventeen patients (14 women and 3 men), with a mean age of 21 years (range: 18-38).Initially, pulmonary effects were assessed by pathological (transbronchial biopsy and/or video-thoracoscopy) and functional findings [spirometry with lung volumes and study of diffusion capacity of CO (DLCO)]. Eighteen months later a challenge bronchial test with histamine was performed.Forty-one per cent of patients had pathologic lesions with intraalveolar fibrin, 35% had minimal non-specific lesions, 18% bronchiolitis obliterans with organized pneumonia (BOOP) and 6% pulmonary fibrosis and BOOP. Functional respiratory test showed two patients with a slight restrictive pattern, one patient with very severe restriction and six patients with low DLCO. The challenge tests was positive for 59% of patients.After the massive inhalation of irritant and/or toxic substances, patients presented different types of pathological response at pulmonary level. In our workers histological repairing lesions--of high or low degree--were found, BOOP being the lesions observed most frequently, and different patterns of functional involvement. Fifty-nine per cent of cases developed non-specific bronchial hyperreactivity consistent with a reactive airways dysfunction syndrome.

The purpose of this study has been to prove if the lung is the target organ of an allergen against which a biological hypersensitivity, by means of skin test and RAST, has been found; comparing score Foucard diagnostic with inhalatory test result. At the same time, checking test specificity and reproductibility. Fourty children, both sexes aged between 6 and 14 years diagnosed of bronchial asthma divided in two groups were studied. First group included 31 children with hypersensitivity to dermatophagoides and second group was control group including 9 children. The test with dermatophagoides was performed in both groups according to Cockcroft method. The parameters which indicated test positivity were 20% fall in FEV1 for early response and 40% fall in PERF for late response. The results obtained show 83.9% positive tests with 80.6% early responses and 45.2% positive late response. The specificity and reproductibility were of 100%.

Antecedentes: Existen avances importantes en el manejo de la infección bacteriana en pacientes con fibrosis quística (FQ), pero hay muchas lagunas en el campo de las infecciones fúngicas. Objetivos: El objetivo del estudio fue analizar si la colonización respiratoria crónica por hongos filamentosos tenía impacto clínico y si el tratamiento antifúngico modificaba la enfermedad. Métodos: Estudio prospectivo, bicéntrico y descriptivo con un seguimiento de 3 años y controles médicos cuatrimestrales. Se incluyeron pacientes adultos de dos Unidades de Fibrosis Quística de hospitales terciarios. Se recogieron datos de variables clínicas, microbiológicas, analíticas y espirométricas; en un subgrupo se evaluó la calidad de vida mediante el cuestionario específico para FQ (CFQ-R). Para analizar estadísticamente la evolución a lo largo del tiempo del volumen espiratorio máximo en el primer segundo (FEV1) y la capacidad vital forzada (FVC) se realizaron modelos lineales mixtos. Resultados: De los 98 pacientes incluidos en el estudio, 40 presentaron colonización crónica por hongos filamentosos. La presencia de hongos filamentosos en la vía aérea se asoció a una caída anual del FEV1 y FVC de 0,029 y 0,017 litros, respectivamente (p