Fungal microbiota dynamics and its geographic, age and gender variability in patients with cystic fibrosis.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.

Evolving Indications for Heart-Lung Transplant in Spain.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Antifibrotics and lung transplantation: A Spanish multicentre case-controlled study.

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: There was evidence that chest wall dehiscences appeared earlier post-transplant in patients using antifibrotics, even though this factor did not significantly impact survival.

Geographic distribution and phenotype of European people with cystic fibrosis carrying A1006E mutation.

BACKGROUND: A1006E is a Cystic Fibrosis (CF) mutation that is still not widely known. We report phenotypic features and geographic distribution of the largest cohort of people with CF (pwCF) carrying A1006E to date. METHODS: Study of European pwCF carrying A1006E mutation, included in the European CF Society Patient Registry (ECFSPR). Genotype, ancestries and all variables recorded were compared to a cohort of F508del/F508del patients. Rate of decline in percentage-of-predicted FEV1 (ppFEV1) was also analyzed using the 2010-2017 ECFSPR. RESULTS: 44 pwCF carrying A1006E were reported (59% males), median age 33 years old (3-58), 54.5% Spanish and 40.9% Italian, most with ancestry in Murcia (Spain) and Lazio (Italy) regions. Compared to F508del homozygous, A1006E-pwCF were significantly older (75% vs. 52.5% ≥ 18 years old) and diagnosed at later median age (6.98 vs. 0.29 years); showed lower rates of meconium ileus (2.33% vs. 17.7%), pancreatic insufficiency (27.91% vs. 99.26%), diabetes (2.33% vs. 21.98%), liver disease (6.98% vs. 36.72%) and Pseudomonas aeruginosa chronic colonization (30.95% vs. 42.51%); and presented better nutrition (BMI z-score 0.44 vs. -0.43) and ppFEV1 (90.8% vs. 78.6%), with 18.9% (most >40 years old) having a ppFEV1<70%. Additional ppFEV1 decline (0.96% per year) was attributed to F508del/F508del genotype (p = 0.0007). None died or needed organ transplantation during the study period. CONCLUSIONS: A1006E-pwCF are mainly of Western Mediterranean Spanish and Italian descent. When compared with F508del/F508del-pwCF, they usually have a milder form of the disease, associated with pancreatic sufficiency and slower FEV1 decline. However, some will develop progressive respiratory impairment during adulthood.

Oral Ribavirin for Treatment of Respiratory Syncytial Virus in Lung Transplantation Recipients.

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.

Impact of SARS-CoV-2 infection in patients with cystic fibrosis in Spain: Incidence and results of the national CF-COVID19-Spain survey.

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 is detailed. METHODS: Retrospective descriptive observational study, for which a Spanish CF Patients with Confirmed COVID-19 Registry is created, requesting information on number of people affected between 8 March-16 May 2020 and their clinical-demographic characteristics from the CF Units participating in the European Cystic Fibrosis Society Patient Registry (ECFSPR). The accumulated incidence is calculated, compared with that of the general population. Additionally, a survey (CF-COVID19-Spain) is carried out on prevention of SARS-CoV-2 infection, workings of CF Units and possible reasons for the incidence observed. RESULTS: COVID-19 was diagnosed in eight CF patients, one of whom had received a lung transplant. The accumulated incidence was 32/10000 in CF patients and 49/10000 in the general population. General death rate was 5.85/10000 while no CF patients included in the ECFSPR died. The characteristics of those affected and the results of the survey are described. CONCLUSIONS: Despite being considered a disease at high risk of severe COVID-19, the low incidence and mortality in CF patients in Spain contrasts with the figures for the general population. The possible factors that would explain such findings are discussed, with the help of the results of the CF-COVID19-Spain survey.

[Lung transplantation for emphysema: retrospective study of 65 patients]. / Trasplante pulmonar por enfisema: análisis retrospectivo de 65 pacientes.

BACKGROUND AND OBJECTIVE: 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. PATIENTS AND METHOD: 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. RESULTS: 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 ventilation > 48 hours and postoperative hemorrhage were the variables with a higher predictive value for mortality in the early postoperative period. CONCLUSIONS: Patients with SLT had a lower rate of perioperative complications and a higher survival during their stay in the ICU. Time of mechanical ventilation > 48 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.