Impact of the New Definition of Pulmonary Hypertension on the Prevalence of Primary Graft Dysfunction in Lung Transplant Recipients.

BACKGROUND & AIM: Pulmonary hypertension (PH) secondary to lung disease (Group-3 PH) is the second leading cause of PH. The role of PH as a risk factor for primary graft dysfunction (PGD) following lung transplant (LT) is controversial. OBJECTIVE: To assess the impact that the new definition of PH had on the prevalence of PH in patients with advanced lung disease-candidate for LT, and its association with the occurrence of PGD. METHOD: A retrospective study was performed in all patients undergoing cardiac catheterisation referred for consideration as candidates to LT in a centre between 1 January 2017 and 31 December 2022. The baseline and haemodynamic characteristics of patients were analysed, along with the occurrence of PGD and post-transplant course in those who ultimately underwent transplantation. RESULTS: A total of 396 patients were included. Based on the new 2022 European Society of Cardiology/European Respiratory Society definitions, as many as 70.7% of patients met PH criteria. Since the introduction of the 2022 definition, a significant reduction was observed in the frequency of severe Group-3 PH (41.1% vs 10.3%; p<0.001), with respect to the 2015 definition. As many as 236 patients underwent transplantation. None of the variables associated with PH was identified as a risk factor for PGD. CONCLUSION: The new classification did not have any impact on the prevalence of PGD after transplantation. These results exclude that any significant differences exist in the baseline characteristics or post-transplant course of patients with Group-3 PH vs unclassified PH.

Long-term survival of lung transplantation for interstitial lung disease associated with connective tissue diseases: a study of 26 cases from a referral centre.

OBJECTIVES: Interstitial lung disease (ILD) is a leading cause of mortality in patients with connective tissue diseases (CTD). Lung transplantation has become a viable option for patients with end-stage CTD-ILD. However, patients with CTD are often considered suboptimal candidates for lung transplantation because of concerns of worse outcomes. We assessed post-transplant survival of patients with CTD-ILD compared to patients with idiopathic pulmonary fibrosis (IPF). METHODS: Medical records of patients who underwent lung transplantation for CTD-ILD at a single referral centre for lung transplantation in Northern Spain between 1998 and 2018 were reviewed. This cohort was compared with patients with IPF (group-matched for age ±3.3 years, transplant year and use of basiliximab induction previous to transplant). Cumulative survival rates after transplantation were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. RESULTS: We studied 26 patients with CTD-ILD and 26 patients with IPF. The underlying diseases of CTD-ILD patients were rheumatoid arthritis (n=9), scleroderma (n=6), Sjögren's syndrome (n=4), ANCA-associated vasculitis (n=3), anti-synthetase syndrome (n=2), and dermatomyositis, systemic lupus erythematosus (1 each). Baseline characteristics were similar in both groups. CTD-ILD patients experienced acute graft rejection less commonly than those with IPF (32.0% vs. 62.5%; p=0.032). However, a non-statistically significant increased frequency of chronic graft rejection was observed in CTD-ILD patients (20.0% vs. 8.3%; p=0.417). In this regard, the 5-year cumulative survival rates after transplantation was reduced in CTD-ILD (42.4% vs. 65.8%) but the difference did not achieve statistical significance (p=0.075). CONCLUSIONS: Long-term post-transplant survival in Northern Spanish patients with CTD-ILD is reduced compared with IPF.

The impact of time from ILD diagnosis to referral to the transplant center on the probability of inclusion in the transplant waiting list.

BACKGROUND: Lung transplant is a therapeutic option for patients with progressive interstitial lung disease (ILD). OBJECTIVES: The objective of this study was to determine whether time from ILD diagnosis to referral to a transplant center influences the probability of being included in the transplant waiting list. METHODS: We performed a retrospective cohort study including all ILD patients evaluated as lung transplantation (LT) candidates at a lung transplant center between 01/01/2017 and 31/12/2022. The primary endpoint was the probability of being included in the lung transplant waiting list according to the time elapsed from diagnosis to referral to the transplant center. RESULTS: A total of 843 lung transplant requests were received, of which 367 (43.5%) were associated with ILD. Thirteen patients were excluded because they did not attend the first visit, whereas another 11 were excluded because some information was missing. As a result, our final sample was composed of 343 patients. The median time from diagnosis to referral was 29.4 (10.9 - 61.1) months. The overall probability of inclusion in the waiting list was 29.7%. By time from diagnosis to referral, the probability of inclusion in the waiting list was 48.1% for the patients referred 〈 6 months from diagnosis; 27.5% for patients referred 6 to 24 months from diagnosis; and 25.8% for patients referred 〉 24 months from diagnosis (p = 0.007). CONCLUSIONS: Early referral to a lung transplant center seemed to increase the probability of being included in the lung transplant waiting list. Further research is needed in this topic.

Evaluating Sensitization-associated, Neuropathic-like Symptoms and Psychological Factors in Patients With Interstitial Lung Disease.

The aims of this study were to phenotype pain in patients with interstitial lung disease (ILD) by investigating the association between sensitization-associated symptoms with quality of life, anxiety/depression, pain catastrophizing, and kinesiophobia levels and identifying those risk factors explaining the variance of quality of life in individuals with ILD and pain. One hundred and thirty-two (38.6% women, mean age: 70, standard deviation: 10.5 years) patients with ILD completed clinical (age, sex, height, weight), psychological (Hospital Anxiety and Depression Scale [HADS] and the Pittsburgh Sleep Quality Index), and health-related quality of life (EQ-5D-5L) variables, as well as the Central Sensitization Inventory (CSI), the Self-Report Leeds Assessment of Neuropathic Symptoms (S-LANSS), Pain Catastrophizing Scale, and Tampa Scale for Kinesiophobia (TSK-11) questionnaires. The prevalence of sensitization-associated symptomatology (CSI), neuropathic-like features (S-LANSS), anxiety symptoms, depressive symptoms, or poor sleep was 20.5%, 23.5%, 23.6%, 22.9%, or 51.6%. Significant associations between CSI, S-LANSS, HADS-A, HADS-D, Pain Catastrophizing Scale, TSK-11, and EQ-5D-5L (.220 < r < .716) were found. The regression analysis revealed that CSI, TSK-11, and HADS-D explained 44.8% of the variance of EQ-5D-5L (r2 adjusted: .448). This study found the presence of sensitization-associated and neuropathic-like symptoms as well as other central nervous system-derived symptoms, such as anxiety, depression, poor sleep, pain catastrophizing, and kinesiophobia in 25% of ILD patients with pain. Sensitization-associated symptoms, depression, and kinesiophobia were associated with a worse quality of life. These findings would support that individuals with ILD can exhibit different pain phenotypes, including nociplastic-like pain phenotype based on self-reported measurements. PERSPECTIVE: Pain in patients with ILD can fulfill features of different phenotypes, including nociplastic pain, when sensory, emotional, and cognitive mechanisms are involved at the same time.

Osteopontin as a Biomarker in Interstitial Lung Diseases.

Osteopontin (OPN) is a glycoprotein involved in Th1 and Th17 differentiation, and inflammation and tissue remodeling. OPN is a biomarker of disease activity in patients with autoimmune inflammatory conditions. This study aimed to assess the diagnostic and prognostic value of OPN in interstitial lung diseases (ILDs). Between May 2016 and October 2019, 344 patients with ILD were recruited at the Hospital Universitario Marqués de Valdecilla (Spain) and were prospectively followed-up. This study involved the determination of OPN serum levels by ELISA and OPN RNA expression quantified using qPCR. Six genetic polymorphisms in OPN (rs28357094, rs2853749, rs2853750, rs11728697, rs7695531, and rs1126616) were genotyped using TaqMan assays. OPN serum levels were also assessed in 140 healthy controls. OPN serum levels (median [interquartile range]) were significantly higher in ILD patients than in controls (1.05 [0.75-1.51] ng/mL versus 0.81 [0.65-0.98] ng/mL in healthy controls; p < 0.01). OPN serum levels were inversely correlated with the forced vital capacity. OPN serum levels were also higher in ILD patients who died or underwent lung transplantation when compared with the remaining ILD patients (1.15 [0.80-1.72] ng/mL versus 0.99 [0.66-1.32] ng/mL; p = 0.05). Survival worsened in ILD patients with OPN > 1.03 ng/mL at 1, 3, and 5 years. No statistically significant differences in the genetic frequencies of OPN polymorphisms or the RNA expression were found among the different ILD groups. Elevated levels of OPN in the serum may be a useful indicator in identifying patients with ILD who are more likely to experience poor outcomes.

Bronchial Stenosis After Lung Transplantation From cDCD Donors Using Simultaneous Abdominal Normothermic Regional Perfusion: A Single-center Experience.

BACKGROUND: Controlled donation after circulatory death (cDCD) has increased the number of lung donors significantly. The use of abdominal normothermic regional perfusion (A-NRP) during organ procurement is a common practice in some centers due to its benefits on abdominal grafts. This study aimed to assess whether the use of A-NRP in cDCD increases the frequency of bronchial stenosis in lung transplant (LT) recipients. METHODS: A single-center, retrospective study including all LTs was performed between January 1, 2015, and August 30, 2022. Airway stenosis was defined as a stricture that leads to clinical/functional worsening requiring the use of invasive monitoring and therapeutic procedures. RESULTS: A total of 308 LT recipients were included in the study. Seventy-six LT recipients (24.7%) received lungs from cDCD donors using A-NRP during organ procurement. Forty-seven LT recipients (15.3%) developed airway stenosis, with no differences between lung recipients with grafts from cDCD (17.2%) and donation after brain death donors (13.3%; P = 0.278). A total of 48.9% of recipients showed signs of acute airway ischemia on control bronchoscopy at 2 to 3 wk posttransplant. Acute ischemia was an independent risk factor for airway stenosis development (odds ratio = 2.523 [1.311-4.855], P = 0.006). The median number of bronchoscopies per patient was 5 (2-9), and 25% of patients needed >8 dilatations. Twenty-three patients underwent endobronchial stenting (50.0%) and each patient needed a median of 1 (1-2) stent. CONCLUSIONS: Incidence of airway stenosis is not increased in LT recipients with grafts obtained from cDCD donors using A-NRP.

Exacerbation of chronic renal failure because of inhaled tobramycin in a lung transplant patient.

61-year-old man, with a history of years of unknown etiology bronchiectasis, with chronic bronchial infection by Burkholderia multivorans, who received treatment with a double lung transplant on 08/20/2020. Persistent positive cultures of Burkholderia multivorans after transplant in respiratory samples was observed, and treatment with inhaled tobramycin 300 mg/12 hours was started. One month after treatment, a significant worsening of renal function was observed, which was already altered, and toxic levels of tobramycin were measured in blood samples 12 hours after the last inhaled administration. After stopping treatment, kidney function returned to its baseline values.