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Immunosuppressive therapy reduces the risk for allograft rejection but leaves recipients susceptible to infections. Cytomegalovirus (CMV) is one of the most frequent causes for infection after transplantation and increases the risk for allograft rejection. As lung transplant recipients (LTRs) need to be under immunosuppression for life, they are a vulnerable group. To determine the potential association between the development of CMV infection and the calcineurin inhibitor (CNI) blood levels within previous 90 days, a retrospective review of LTRs was performed. Data from recipients who underwent a lung transplantation (LTx) at our center from January 2011 to December 2018 were collected. The studied recipients, after case/control matching, included 128 CMV-infection cases. The median time from the transplant to the first positive CMV viral load was 291.5 days. In our study, more patients were treated with tacrolimus (91.9%) than with cyclosporine (8.1%). Drug blood levels at selected timepoints showed no statistically significant difference between cases and controls. However, we found that CMV infection was more frequent in the donor-seropositive/recipient-seronegative group, interstitial lung disease (ILD) recipients, LTRs who underwent basiliximab induction, cyclosporine treated recipients, and LTRs with lymphopenia (at the time of CMV infection and 90 days before). In this review of LTRs, no association between the CNI blood level and CMV infection was seen, although other immunity-related factors were found to be influencing, i.e., basiliximab induction, cyclosporine treatment, and lymphopenia.

The most critical forms of coronavirus disease 2019 (COVID-19) are associated with excessive activation of the inflammasome. Despite the COVID-19 impact on public health, we still do not fully understand the mechanisms by which the inflammatory response influences disease prognosis. Accordingly, we aimed to elucidate the role of polymorphisms in the key genes of the formation and signaling of the inflammasome as biomarkers of COVID-19 severity. For this purpose, a large and well-defined cohort of 377 COVID-19 patients with mild (n = 72), moderate (n = 84), severe (n = 100), and critical (n = 121) infections were included. A total of 24 polymorphisms located in inflammasome-related genes (NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, IL18, NFKB1, ATG16L1, and MIF) were genotyped in all of the patients and in the 192 healthy controls (HCs) (who were without COVID-19 at the time of and before the study) by RT-qPCR. Our results showed that patients with mild, moderate, severe, and critical COVID-19 presented similar allelic and genotypic distribution in all the variants studied. No statistically significant differences in the haplotypic distribution of NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, and ATG16L1 were observed between COVID-19 patients, who were stratified by disease severity. Each stratified group of patients presented a similar genetic distribution to the HCs. In conclusion, our results suggest that the inflammasome polymorphisms studied are not associated with the worsening of COVID-19.

A simplified 4‐strata risk stratification approach based on three variables is widespread in pulmonary arterial hypertension (PAH) at follow‐up. This study aimed to assess the impact of replacing the 6‐min walk test (6MWT) with the peak 02 uptake evaluated by the cardiopulmonary exercise test (CPET) on risk stratification by this scale. We included 180 prevalent patients with PAH from two reference hospitals in Spain, followed up between 2006 and 2022. Patients were included if all the variables of interest were available within a 3‐month period on the Spanish Registry of Pulmonary Arterial Hypertension (REHAP): functional class (FC); NT‐proBNP; 6MWT; and CPET. The original 4‐strata model (NT‐proBNP, 6MWT, FC) identified most patients at low or intermediate‐low risk (36.7% and 51.1%, respectively). Notably, the modified scale (NT‐proBNP, CPET, FC) improved the identification of patients at intermediate‐high risk up to 18.9%, and at high risk up to 1.1% in comparison with the previous 12.2% and 0.0% in the original scale. This new model increased the number of patients correctly classified into higher‐risk strata (positive NRI of 0.06), as well as classified more patients without events in lower‐risk strata (negative NRI of 0.04). The proposed score showed a slightly superior prognostic capacity compared with the original model (Harrel's C‐index 0.717 vs. 0.709). Using O2 uptake instead of distance walked in the 6MWT improves the identification of high‐risk patients using the 4‐strata scale. This change could have relevant prognostic implications and lead to changes in the specific treatment of PAH.

This work was supported by the Spanish Society of Pneumology (SEPAR Nº 1383/23; Nº 1616/24) and the Spanish Ministry of Science and Innovation (Project PID2020-114787RBI00, funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe”).

Inflammatory cell activation in asthma may lead to reactive oxygen species (ROS) overproduction with an imbalance between oxidant levels and antioxidant capacity, called oxidative stress (OS). Since particulate matter (PM) airborne exposure may also contribute to ROS generation, it is unclear whether PM contributes more to OS than inflammatory cell activation. In our ASTHMA-FENOP study, which included 44 asthma patients and 37 matched controls, we aimed to characterize OS using five serum markers: total ROS content, protein carbonyl content, oxidized low-density lipoprotein (OxLDL), 8-hydroxydeoxyguanosine, and glutathione. Volunteers wore personal samplers for 24 h, collecting fine and coarse PM fractions separately, and the oxidative potential (OP) was determined using two methods. We observed differences between asthmatic and non-asthmatic volunteers in some OS markers, such as OxLDL, with an adjusted mean difference of 50,059.8 ng/mL (p < 0.001). However, we did not find an association between higher PM-OP and increased systemic OS. This suggests that at our PM-OP exposure levels, OS generated by the inflammatory cells themselves is more relevant than that generated by airborne PM. This supports the idea that asthma is a heterogeneous disease at the molecular level, mediated by inflammatory cell activation, and that OS may have potential clinical implications.

Patients undergoing lung transplantation (LTx) need administration of immunosuppressive therapy following the procedure to prevent graft rejection. However, these drugs are not exempt from potential risks. The development of cardiovascular risk factors and impaired renal function in the post-transplantation period are conditions that may be favoured by the use of calcineurin inhibitor (CNI) drugs which could have repercussions on the quality of life and the post-transplantation evolution. To evaluate the cardiovascular and renal toxicity following the administration of CNI as maintenance immunosuppression in lung transplant recipients (LTRs) we reviewed a total number of 165 patients undergoing LTx between 01/01/2015 and 08/12/2018. They were divided into two groups according to the CNI drug administrated: cyclosporine (CsA-group) with 11 patients or tacrolimus (Tac-group), with 154 patients. We evaluated the de novo occurrence of arterial hypertension (HTN), diabetes mellitus (DM), hyperlipidemia and impaired renal function after initiation of CNI administration. In addition to that, the time until each of these events was assessed. A higher rate for developing HTN ( p  < 0.001) and impaired renal function ( p  = 0.047) was observed within the CsA-group. The new onset of hyperlipidemia was similar between both CNI groups and de novo appearance of DM was only documented in those LTRs receiving tacrolimus. In this LTRs retrospective study, it was observed that having ≥ 4 tacrolimus trough levels above the upper limit of the proposed interval for each specific post-LTx period was associated with an increased risk for developing renal impairment. No other statistically significant association was found between supratherapeutic CNIs blood levels and the evaluated toxicities.

Niemann-Pick disease is a rare autosomal recessive disease characterized by an abnormal intracellular lipid accumulation. Type B is later in onset and a less severe form of the disease, so affected people may survive in adulthood. Storage of sphingomyelin in pulmonary macrophages can lead to interstitial lung disease. There are very few published cases of lung transplantation in patients with Niemann-Pick disease, all of them described in the last 2 years. We present here one case of a 57-year-old man successfully treated with a double-lung transplant.

Background Macitentan is the latest endothelin-receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), presenting enhanced properties over previous ERAs. Objective We describe the clinical and echocardiographic evolution of patients with PAH who started macitentan after discontinuing bosentan/ambrisentan. Methods This was a retrospective series of patients with different etiologies who started macitentan after the suspension of other ERAs under routine clinical practice at five Spanish hospitals. World Health Organization functional class (WHO-FC), 6-min walk distance (6MWD), levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and cardiac imaging data were collected and described at baseline (before macitentan initiation) and after 3, 6, and 12 months, when available. Results In total, 12 patients (ten women; mean age 65.63 ± 13.27 years) were observed. At baseline, most patients were receiving concomitant PAH medications, and five patients were classed as WHO-FC III. After 3 months of macitentan treatment, WHO-FC had improved in four patients, 6MWD increased in eight patients, and NT-proBNP levels and right atrial area were lowered in seven and eight patients, respectively. Similar results were observed after 6 and 12 months. Macitentan was well-tolerated, with no PAH hospitalizations, septostomies, transplants, or deaths registered. Conclusions Our results suggest that switching to macitentan in patients with PAH who discontinued bosentan/ambrisentan was well-tolerated and effective. Further studies are needed to confirm these observations.

In pulmonary arterial hypertension (PAH) patients it is essential to perform a prognostic assessment to optimize the treatment. The aim of this study is to evaluate the risk stratification concordance assessed with different exercise test variables in a cohort of PAH patients. A retrospective analysis was performed using patient data registered in the PAH unit. Only those patients in whom the mean time elapsed between the 6‐min walking test (6MWT) and the cardiopulmonary exercise test (CPET) was a maximum of 6 months were selected. A total of 140 records from 40 patients were finally analyzed. When it came to assessing the concordance between the two exercise tests in the guidelines (CPET and 6MWT), up to 84.3% of the records did not coincide in terms of the risk stratification. Exclusively considering the CPET parameters, most of the records (75%) failed to include all three variables in the same risk category. When analyzing the VO2 alone, up to 40.7% of the tests yielded different risk classifications depending on whether the parameter was expressed. In conclusion, there is a low concordance between the two proposed exercise tests. These results should be a call for reflection on whether the cut‐off points set for the exercise tests proposed for the current risk stratification are adequate to achieve a correct risk stratification or whether they require an appropriate revision.

The aim of this study was to determine the role of endothelin-1 (ET-1), a molecule involved in multiple vascular and fibrosing abnormalities, as a biomarker of interstitial lung disease (ILD), as well as its use for the differential diagnosis between idiopathic pulmonary fibrosis (IPF) and ILD associated with autoimmune diseases (AD-ILD), using a large and well-defined cohort of patients with ILD. A total of 112 patients with IPF, 91 patients with AD-ILD (28 rheumatoid arthritis (RA), 26 systemic sclerosis, 20 idiopathic inflammatory myositis and 17 interstitial pneumonia with autoimmune features) and 44 healthy controls were included. ET-1 serum levels were determined by enzyme-linked immunosorbent assay. A significant increase in ET-1 levels was found in patients with IPF compared to controls. Likewise, AD-ILD patients also showed higher ET-1 levels than controls when the whole cohort was stratified by the type of AD. Similar ET-1 levels were found in IPF and AD-ILD patients, regardless of the underlying AD. Interestingly, increased ET-1 levels were correlated with worse lung function in IPF and RA-ILD patients. Our study supports that serum ET-1 may be useful as a biomarker of ILD, although it could not help in the differential diagnosis between IPF and AD-ILD. Moreover, ET-1 levels may be associated with ILD severity.