Amparo Solé

Hospital Universitari i Politècnic la Fe · Research Center

Background Chronic lung allograft dysfunction (CLAD) is defined by a progressive loss of FEV1 and is associated with premature mortality. The aim of this study was to investigate the direct association between FEV1 decline and risk of mortality in patients after lung transplantation (LTx).Methods10-year follow up data from lung transplant recipient...

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 l...

Introduction Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. Methods A multicenter prospective observational study of 92 patient...

Background: Scedosporium species and Lomentospora prolificans (Sc/Lp) are emerging molds that cause invasive disease associated with a high mortality rate. After Aspergillus, these molds are the second filamentous fungi recovered in lung transplant (LT) recipients. Aims: Our objective was to evaluate the incidence, risk factors and outcome of Sc...

Background: There are important advances in the management of bacterial infection in patients with cystic fibrosis (CF), but there are many gaps in the field of fungal infections. Aims: The aim of this study was to analyse whether chronic respiratory filamentous fungal colonization had clinical impact and whether antifungal treatment can change...

Long‐term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L‐CsA‐i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double‐blind, placebo‐controlled,...

Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the Internat...

Patients with connective tissue disease (CTD) and advanced lung disease are often considered suboptimal candidates for lung transplantation (LTx) due to their underlying medical complexity and potential surgical risk. There is substantial variability across LTx centers regarding the evaluation and listing of these patients. The International Societ...

Background . In CLEAR-108—a phase 3, randomised, open-label study—once-daily amikacin liposome inhalation suspension (ALIS) was noninferior to twice-daily tobramycin inhalation solution (TIS) in improving lung function in patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection after 3 treatment cycles (28 days on/28 days off...

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 I...

Purpose Chronic lung allograft dysfunction (CLAD) is the main limiting factor for long-term survival after lung transplantation (LT). However, there is a small number of LT patients which are long-term survivors with good allograft function (LTS). The aim of the present study was to compare the gene expression profile of CLAD and LTS patients and p...

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...

Background Tezacaftor–ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8–24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOL...

Introduction: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. Methods: A multicenter prospective observational study of 92 patien...

The clinical course of lung transplantation (LT) is diverse: some patients present chronic lung allograft dysfunction (CLAD) and progressive decline in pulmonary function but others, maintain normal spirometric values and active live. Objectives to elucidate whether long-term LT survivors with normal spirometry achieve normal exercise capacity, an...

Background Tuberculosis (TB) represents a diagnostic and therapeutic challenge for solid organ transplant recipients, particularly after lung transplant (LT). Our aim was to determine the impact of TB in LT patients in Spain, considering prevalence, clinical presentation, prevention and therapeutic management. In addition, differences in outcome be...

Background Given the high incidence of confirmed infection by SARS-CoV-2 and mortality by COVID-19 in the Spanish population, its impact was analysed among persons with Cystic Fibrosis (CF) as a group at risk of a worse evolution. The possible causes of the incidence observed in them are explained and how CF Units have faced this health challenge i...

Purpose Chronic lung allograft dysfunction (CLAD) is the main limiting factor for long-term survival after lung transplantation (LT). However, there is a small number of LT patients which are long-term survivors with good allograft function (LTS). The aim of the present study was to compare the gene expression profile of CLAD and LTS patients and p...

Background: Tuberculosis (TB) represents a diagnostic and therapeutic challenge for solid organ transplant recipients, particularly after lung transplant (LT). Our aim was to determine the impact of TB in LT patients in Spain, considering prevalence, clinical presentation, prevention and therapeutic management. In addition, differences in outcome...

Background: Long-term survival with good allograft function (LTS) after lung transplantation (LT) is mainly limited by the development of chronic lung allograph dysfunction (CLAD). The objective of this study was to identify genes and miRNAs which might contribute to a better understanding of the molecular mechanisms influencing LTS after LT. Meth...

Background: The development of chronic lung allograph dysfunction (CLAD) is the leading limitation of long-term survival with good allograft function (LTS) after lung transplantation (LT). The aim of this study was to identify leukocyte subpopulations and to develop a gene model which allows the discrimination of LTS patients. Methods: The cell ma...

Background: Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. Methods: Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of pred...

Background: Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung-transplant recipients. Methods: We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a lar...

Background: Bronchiolitis obliterans syndrome (BOS) is a major limitation in the long-term survival of lung transplant recipients (LTRs). However, the risk factors in the development of BOS remain undetermined. We conducted an international cohort study of LTRs to assess whether Aspergillus colonization with large or small conidia is a risk factor...

Introduction and objectives To examine the impact of TEZ/IVA on disease-related symptoms, functioning, and well-being as measured by Cystic Fibrosis Questionnaire–Revised (CFQ-R) in patients with cystic fibrosis (CF) homozygous for F508del-CFTR (F508del/F508del). Improvement in the respiratory domain of CFQ-R, the only domain for which the minimal...

Post-transplant lymphoproliferative disorders (PTLD) are a rare complication after both solid organ (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this single center retrospective study, we compared clinical, biological, and histological features, and outcomes of PTLD after both types of transplant. We identified 82 PT...

Background: Invasive aspergillosis (IA) is a frequent complication in lung transplant recipients (LTRs). Clinical risk factors for IA have not been fully characterized, especially in the era of extensive anti-fungal prophylaxis. The primary objective of this study was to evaluate the clinical risk factors associated with IA in LTRs. The secondary...

Background Infection is still a leading cause of death during the first year after lung transplantation. Objectives We performed a multicenter study to assess monitoring of early humoral immunity as a means of identifying lung recipients at risk of serious infections. Setting Teaching hospitals. Methods We prospectively analyzed 82 adult lung re...

Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows for the entrapment of airborne bacteria and fungal spores and provides a suitable environment for growth of microorganisms, including numerous yeast and filamentous fungal species....

Cystic fibrosis (CF) is a chronic lethal multi-system condition; however, most of the morbidity and mortality is dependent on the status of the respiratory system. Progressive respiratory decline is mediated by chronic infection and inflammation, punctuated by important acute events known as pulmonary exacerbations which can lead to accelerated dec...

Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplant, but it rarely causes invasive infection. Treatment remains challenging, particularly due to the inherent resistance to multiple antifungal agents. We present three complicated invasive tracheobronchial and lung Scedosporium apiospermum infections following lung trans...

Background: The Cystic Fibrosis Questionnaire-Revised (CFQ-R+14) is a disease-specific, health-related quality of life instrument for cystic fibrosis (CF) patients ≥14years. We have developed a Spanish electronic version of the CFQ-R (e-CFQ-R+14 Spain). Our aim was to compare the paper and electronic versions and to validate the electronic version...

This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung trans...

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 availabl...

Background: The optimal length of cytomegalovirus (CMV) prophylaxis in lung transplantation according to CMV serostatus is not well established. Methods: We have performed a prospective, observational, multicenter study in order to determine the incidence of CMV infection and disease in 92 CMV-seropositive lung transplant recipients (LTR), their...

Background and aims To specify the prevalence of patients diagnosed with CF at age of ≥60 year-old and to analyze their characteristics. Patients and methods Observational study of CF patients which were diagnosed at age ≥60 year-old. The analyzed variables were: age, sex, nationality, lung function parameters, conditions present at diagnosis, mic...

Our aim in this chapter is to present the state of the art, including our own group research, in the field of immunosuppressant pharmacogenetics in the four main types of solid organ transplantation: kidney, heart, lung, and liver. The main focus will be on those findings in the field that have been widely investigated and then in those that are cl...

Appropriate post-transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppres...

Epidemiology and relationship between RVs and lung function, acute rejection (AR), and opportunistic infections in lung transplant recipients (LuTR) in not well known. We performed a prospective cohort study (2009-2014) by collecting nasopharyngeal swabs (NPS) from asymptomatic LuTR during seasonal changes and from LuTR with upper respiratory tract...

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,...

Background: Despite well-known risk factors and predictive survival models, many patients with cystic fibrosis (CF) die while on the waiting list for lung transplant. We evaluated whether specific Cystic Fibrosis Questionnaire (CFQ-R) scales provide additional benefit to conventional tools in identifying referral timing and waitlist mortality. Me...

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering m...

Nebulized antibiotic therapy is an attractive therapeutic option given the high concentration obtained from the drug at the site of infection, minimizing the adverse effects and possible drug interactions. Inhalation of drugs as treatment of cystic fibrosis (CF) related lung disease has been proven to be highly effective. Consequently, an increasin...

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 fr...

Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CY...

Chronic renal dysfunction (CRD) after lung transplantation (LT) is a common and noteworthy complication associated with increased morbidity and mortality rates. The study objectives were to determine the prevalence of CRD according to different diagnostic criteria and describe its therapeutic management. This observational, multicenter, retrospecti...

Objective Interim analysis to evaluate safety, tolerability, and efficacy of LAI, a novel amikacin formulation, in CF patients with chronic P aeruginosa infection previously treated with LAI or tobramycin inhalation solution (TIS). Methods In the CLEAR-108 trial, patients were randomized 1:1 to 3 treatment cycles (28 days on/28 days off) of LAI 59...

Pseudomonas aeruginosa is the main pathogen in bronchopulmonary infections in cystic fibrosis (CF) patients. It can only be eradicated at early infection stages while reduction of its bacterial load is the therapeutic goal during chronic infection or exacerbations. Neonatal screening and pharmacokinetic/pharmacodynamic knowledge has modified the ma...

Pulmonary exacerbation (PEx) is a hallmark of cystic fibrosis. Although several criteria have been proposed for the definition of PEx, no consensus has yet been reached. Very often, many PEx cases go unreported. A standardized and validated definition is needed to reduce variability in clinical practice. The pathophysiology of recurrent episodes re...

Pseudomonas aeruginosa is the main pathogen in bronchopulmonary infections in cystic fibrosis (CF) patients. It can only be eradicated at early infection stages while reduction of its bacterial load is the therapeutic goal during chronic infection or exacerbations. Neonatal screening and pharmacokinetic/pharmacodynamic knowledge has modified the ma...

The best investigational drug to treat cystic fibrosis (CF) patients with the most common CF-causing mutation (F508del) is VX-809 (lumacaftor) which recently succeeded in Phase III clinical trial in combination with ivacaftor. This corrector rescues F508del-CFTR from its abnormal intracellular localization to the cell surface, a traffic defect shar...

Estimates of the incidence and prevalence of serious fungal infections, based on epidemiological data, are essential in order to inform public health priorities given the lack of resources dedicated to the diagnosis and treatment of these serious fungal diseases. However, epidemiology of these infections is largely unknown, except for candidaemia a...