Serological Biomarkers in Individuals with Interstitial Lung Disease after SARS-CoV-2 Infection and Association with Post-COVID-19 Symptoms.

Patients with interstitial lung disease (ILD) represent a vulnerable population against an acute SARS-CoV-2 infection. It has been observed that up to 80% of patients with ILD can develop post-COVID-19 symptomatology one year after. This secondary analysis aimed to, 1, compare serological biomarkers before and after surpassing a SARS-CoV-2 infection in individuals with interstitial lung disease (ILD) and, 2, to compare serological biomarkers between ILD patients who develop and those who do not develop post-COVID-19 symptoms. Seventy-six patients with ILD (40.4% women, age: 69, SD: 10.5 years) who survived a SARS-CoV-2 infection participated. High-resolution computerized tomography (CT) of the lungs, two pulmonary function tests (forced vital capacity (FVC) and diffusion value of carbon monoxide (DLCO)) and fourteen serological biomarkers were collected before and after SARS-CoV-2 infection. Participants were asked for the presence of post-COVID-19 symptomatology a mean of twelve (SD: eight) months after infection. Sixty patients (79%) showed post-COVID-19 symptoms (mean: 3.5, SD 1.1), with fatigue (68.4%), dyspnea (31.5%), and concentration loss (27.6%) being the most prevalent. Creatine phosphokinase (CPK) was the only biomarker showing differences in our study. In fact, CPK levels were higher after the acute SARS-CoV-2 infection (mean difference: 41.0, 95%CI 10.1 to 71.8, p = 0.03) when compared to before the infection. Thus, CPK levels were also higher in ILD patients with post-COVID-19 fatigue (mean difference: 69.7, 95%CI 12.7 to 126.7, p = 0.015) or with post-COVID-19 dyspnea (mean difference: 34.8, 95%CI 5.2 to 64.4, p = 0.025) than those patients without these post-COVID-19 symptoms. No significant changes in CT or functional pulmonary tests were observed after COVID-19 in patients with ILD. In conclusion, patients with ILD exhibited an increase in CPK levels after SARS-CoV-2 infection, albeit no changes in other serological biomarkers were identified. Similarly, the presence of post-COVID-19 fatigue or dyspnea was also associated with higher CPK levels in ILD patients. Studies investigating long COVID mechanisms in vulnerable populations such as ILD are needed.

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.

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.

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.

Association of Kinesiophobia with Catastrophism and Sensitization-Associated Symptoms in COVID-19 Survivors with Post-COVID Pain.

Pain symptoms after the acute phase of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are present in almost 50% of COVID-19 survivors. The presence of kinesiophobia is a risk factor which may promote and perpetuate pain. This study aimed to investigate variables associated with the presence of kinesiophobia in a sample of previously hospitalized COVID-19 survivors exhibiting post-COVID pain. An observational study was conducted in three urban hospitals in Spain, including one hundred and forty-six COVID-19 survivors with post-COVID pain. Demographic (age, weight, height), clinical (intensity and duration of pain), psychological (anxiety level, depressive level, sleep quality), cognitive (catastrophizing), sensitization-associated symptoms, and health-related quality of life variables were collected in 146 survivors with post-COVID pain, as well as whether they exhibited kinesiophobia. Stepwise multiple linear regression models were conducted to identify variables significantly associated with kinesiophobia. Patients were assessed a mean of 18.8 (SD 1.8) months after hospital discharge. Kinesiophobia levels were positively associated with anxiety levels (r: 0.356, p < 0.001), depression levels (r: 0.306, p < 0.001), sleep quality (r: 0.288, p < 0.001), catastrophism (r: 0.578, p < 0.001), and sensitization-associated symptoms (r: 0.450, p < 0.001). The stepwise regression analysis revealed that 38.1% of kinesiophobia variance was explained by catastrophism (r2 adj: 0.329, B = 0.416, t = 8.377, p < 0.001) and sensitization-associated symptoms (r2 adj: 0.381, B = 0.130, t = 3.585, p < 0.001). Kinesiophobia levels were associated with catastrophism and sensitization-associated symptoms in previously hospitalized COVID-19 survivors with post-COVID pain. Identification of patients at a higher risk of developing a higher level of kinesiophobia, associated with post-COVID pain symptoms, could lead to better therapeutic strategies.

Early onset of azithromycin to prevent CLAD in lung transplantation: Promising results of a retrospective single centre experience.

INTRODUCTION: Azithromycin (AZI) may be an effective immune modulator in lung transplant (LT) recipients, and can decrease chronic lung allograft dysfunction (CLAD) rates, the leading cause of mortality after the 1st year post-LT. The aim of the study is to assess the effect of AZI initiation and its timing on the incidence and severity of CLAD in LT recipients. METHODS: Single-center retrospective study, including LT recipients from 01/01/2011 to 30/06/2020. Four groups were established: those who started AZI at the 3rd week post-LT (group A), those who received AZI later than the 3rd week post-LT and had preserved FEV1 (B), those who did not receive AZI (C) and those who started AZI due to a decline in FEV1 (D). The dosage of AZI prescribed was 250 mg three times per week. CLAD was defined and graduated according to the 2019 ISHLT criteria. RESULTS: We included 358 LT recipients: 139 (38.83%) were in group A, 94 (26.25%) in group B, 91 (25.42%) in group C, and 34 (9.50%) in group D. Group A experienced the lowest CLAD incidence and severity at 1 (p = .01), 3 (p < .001), and 5 years post-LT, followed by Group B. Groups C and D experienced a higher incidence and severity of CLAD (p = .015). Initiation of AZI prior to FEV1 decline (Groups A and B) proved to be protective against CLAD after adjusting for differences between the treatment groups. CONCLUSIONS: Early initiation of AZI in LT recipients could have a role in decreasing the incidence and severity of CLAD. In addition, as long as FEV1 is preserved, initiating AZI at any time could also be useful to prevent the incidence of CLAD and reduce its severity.

Lung transplantation for emphysema: only emphysema or something else?

Background: Some studies have reviewed lung explants histology to determine the frequency of pretransplant non-identified neoplasms or explore its diagnostic correlation with a previous diagnosis of interstitial lung disease (ILD). This study aims to review the histopathology of explants from patients who underwent lung transplantation (LT). Methods: A retrospective, single-center study that included patients who underwent LT for emphysema between 01 January 2011 and 31 October 2021. The control group was composed of patients with lung cancer who underwent a lung resection between 01 November 2011 and 31 December 2019 and had a previous diagnosis of chronic obstructive pulmonary disease (COPD) prior to lung resection surgery. A systematic review was performed of histological findings to compare the frequency of additional histological diagnoses. Results: The study sample included 160 patients (43.8%) who received a lung transplant for emphysema and 205 patients with COPD and lung cancer treated surgically. Although the patients in the cancer group were significantly older and had more comorbidities and higher cumulative tobacco consumption, transplant recipients received an additional significative histologic diagnosis more frequently (58.1% vs. 12.7%; P<0.001) including ILD, pneumoconiosis and others. Conclusions: Significant additional histological findings were more frequent in the group of lung transplant recipients with emphysema. Notably, these findings were not explained by tobacco use, and they were significantly more frequent in transplant recipients than in patients with a previous diagnosis of COPD and higher cumulative tobacco consumption but with a better respiratory functional status.

Sensitization-Associated Post-COVID-19 Symptoms at 6 Months Are Not Associated with Serological Biomarkers at Hospital Admission in COVID-19 Survivors: A Secondary Analysis of a Cohort Study.

Individuals who survived coronavirus disease, 2019 (COVID-19), often have symptoms of sensitization, but the extent to which these symptoms relate to serological biomarkers remains unclear. Therefore, this secondary analysis evaluated the association between serological biomarkers at hospital admission with sensitization-associated post-COVID-19 symptoms in a sample of previously hospitalized COVID-19 survivors. Sixty-seven individuals hospitalized due to SARS-CoV-2 infection in one urban hospital of Madrid (Spain) during the first wave of the pandemic were assessed a mean of 6.0 (SD 0.8) months after hospital discharge. The Central Sensitization Inventory (CSI) was used as rough tool to estimate the presence of sensitization-associated post-COVID-19 symptoms (≥40/100 points). Levels of 16 serological biomarkers collected at hospital admission were obtained from medical records. Twenty-four (35.8%) patients reported sensitization-associated post-COVID-19 symptoms (CSI ≥ 40 points). Subjects reporting sensitization-associated symptoms had lower ferritin and hemoglobin levels than those not reporting sensitization-associated post-COVID-19 symptoms; however, these differences were small. We observed significant but small negative associations of the CSI score with ferritin (r: -0.251, p = 0.04) and hemoglobin (r: -0.292, p = 0.017) levels. No other significant difference was found. In conclusion, this secondary analysis did not find significant associations between the investigated serological biomarkers at hospital admission and sensitization-associated post-COVID-19 symptoms at 6 months after hospitalization in COVID-19 survivors.