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2.
Transpl Int ; 37: 12816, 2024.
Article in English | MEDLINE | ID: mdl-39015153

ABSTRACT

Night work is frequently associated with sleep deprivation and is associated with greater surgical and medical complications. Lung transplantation (LT) is carried out both at night and during the day and involves many medical healthcare workers. The goal of the study was to compare morbidity and mortality between LT recipients according to LT operative time. We performed a retrospective, observational, single-center study. When the procedure started between 6 AM and 6 PM, the patient was allocated to the Daytime group. If the procedure started between 6 PM and 6 AM, the patient was allocated to the Nighttime group. Between January 2015 and December 2020, 253 patients were included. A total of 168 (66%) patients were classified into the Day group, and 85 (34%) patients were classified into the Night group. Lung Donors' general characteristics were similar between the groups. The 90-day and one-year mortality rates were similar between the groups (90-days: n = 13 (15%) vs. n = 26 (15%), p = 0.970; 1 year: n = 18 (21%) vs. n = 42 (25%), p = 0.499). Daytime LT was associated with more one-year airway dehiscence (n = 36 (21%) vs. n = 6 (7.1%), p = 0.004). In conclusion, among patients who underwent LT, there was no significant association between operative time and survival.


Subject(s)
Lung Transplantation , Operative Time , Humans , Lung Transplantation/adverse effects , Lung Transplantation/mortality , Male , Female , Retrospective Studies , Middle Aged , Adult , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Sleep Deprivation/complications , Aged
3.
Transpl Int ; 37: 12445, 2024.
Article in English | MEDLINE | ID: mdl-38962472

ABSTRACT

While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field's incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.


Subject(s)
Biomarkers , Graft Rejection , Heart Transplantation , Lung Transplantation , Humans , Biomarkers/blood , Biopsy , Cell-Free Nucleic Acids/blood , Consensus , Europe , Gene Expression Profiling , Graft Rejection/diagnosis , Lung Transplantation/adverse effects , Societies, Medical
4.
Article in English | MEDLINE | ID: mdl-38972753

ABSTRACT

PURPOSE: This meta-analysis aimed to examine the prognosis of patients with acute exacerbation of interstitial lung disease (AE-ILD) treated with lung transplantation compared to those with stable interstitial lung disease (ILD). METHODS: We conducted a detailed search in PubMed, Embase, Web of Science, and the Cochrane Library, with the primary outcomes being overall survival (OS), acute cellular rejection (ACR), primary graft dysfunction (PGD), and length of stay (LOS). RESULTS: Five cohort studies were included in this meta-analysis, with 183 patients enrolled in the AE-ILD group and 337 patients in the stable-ILD group. The results showed that in regard to perioperative outcomes, the AE-ILD group did not differ from the stable-ILD group in the incidence of ACR (relative risks [RR] = 0.34, p = 0.44) and the incidence of PGD Ⅲ (RR = 0.53, p = 0.43), but had a longer LOS (mean difference = 9.15, p = 0.02). Regarding prognosis, the two also did not differ in 90-day OS (RR = 0.97, p = 0.59), 1-year OS (RR = 1.05, p = 0.66), and 3-year OS (RR = 0.91, p = 0.76). CONCLUSION: Our study concluded that the efficacy of lung transplantation in patients with AE-ILD is not inferior to that of patients with stable ILD. Lung transplantation is one of the potential treatments for patients with AE-ILD.


Subject(s)
Disease Progression , Graft Rejection , Length of Stay , Lung Diseases, Interstitial , Lung Transplantation , Adult , Aged , Female , Humans , Male , Middle Aged , Graft Rejection/mortality , Graft Rejection/diagnosis , Lung Diseases, Interstitial/mortality , Lung Diseases, Interstitial/surgery , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/physiopathology , Lung Transplantation/mortality , Lung Transplantation/adverse effects , Primary Graft Dysfunction/mortality , Primary Graft Dysfunction/diagnosis , Primary Graft Dysfunction/etiology , Primary Graft Dysfunction/physiopathology , Risk Factors , Time Factors , Treatment Outcome
5.
J Med Virol ; 96(7): e29770, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38949200

ABSTRACT

Donor and recipient human cytomegalovirus (HCMV) seropositive (D+R+) lung transplant recipients (LTRs) often harbor multiple strains of HCMV, likely due to transmitted donor (D) strains and reactivated recipient (R) strains. To date, the extent and timely occurrence of each likely source in shaping the post-transplantation (post-Tx) strain population is unknown. Here, we deciphered the D and R origin of the post-Tx HCMV strain composition in blood, bronchoalveolar lavage (BAL), and CD45+ BAL cell subsets. We investigated either D and/or R formalin-fixed paraffin-embedded blocks or fresh D lung tissue from four D+R+ LTRs obtained before transplantation. HCMV strains were characterized by short amplicon deep sequencing. In two LTRs, we show that the transplanted lung is reseeded by R strains within the first 6 months after transplantation, likely by infiltrating CD14+ CD163+/- alveolar macrophages. In three LTRs, we demonstrate both rapid D-strain dissemination and persistence in the transplanted lung for >1 year post-Tx. Broad inter-host diversity contrasts with intra-host genotype sequence stability upon transmission, during follow-up and across compartments. In D+R+ LTRs, HCMV strains of both, D and R origin can emerge first and dominate long-term in subsequent episodes of infection, indicating replication of both sources despite pre-existing immunity.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Lung Transplantation , Tissue Donors , Transplant Recipients , Humans , Lung Transplantation/adverse effects , Cytomegalovirus/genetics , Cytomegalovirus/classification , Cytomegalovirus Infections/virology , Male , Middle Aged , Female , Adult , Genotype , Lung/virology , Bronchoalveolar Lavage Fluid/virology
6.
Respir Res ; 25(1): 262, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951782

ABSTRACT

BACKGROUND: Donor-specific antibodies (DSAs) are common following lung transplantation (LuTx), yet their role in graft damage is inconclusive. Mean fluorescent intensity (MFI) is the main read-out of DSA diagnostics; however its value is often disregarded when analyzing unwanted post-transplant outcomes such as graft loss or chronic lung allograft dysfunction (CLAD). Here we aim to evaluate an MFI stratification method in these outcomes. METHODS: A cohort of 87 LuTx recipients has been analyzed, in which a cutoff of 8000 MFI has been determined for high MFI based on clinically relevant data. Accordingly, recipients were divided into DSA-negative, DSA-low and DSA-high subgroups. Both graft survival and CLAD-free survival were evaluated. Among factors that may contribute to DSA development we analyzed Pseudomonas aeruginosa (P. aeruginosa) infection in bronchoalveolar lavage (BAL) specimens. RESULTS: High MFI DSAs contributed to clinical antibody-mediated rejection (AMR) and were associated with significantly worse graft (HR: 5.77, p < 0.0001) and CLAD-free survival (HR: 6.47, p = 0.019) compared to low or negative MFI DSA levels. Analysis of BAL specimens revealed a strong correlation between DSA status, P. aeruginosa infection and BAL neutrophilia. DSA-high status and clinical AMR were both independent prognosticators for decreased graft and CLAD-free survival in our multivariate Cox-regression models, whereas BAL neutrophilia was associated with worse graft survival. CONCLUSIONS: P. aeruginosa infection rates are elevated in recipients with a strong DSA response. Our results indicate that the simultaneous interpretation of MFI values and BAL neutrophilia is a feasible approach for risk evaluation and may help clinicians when to initiate DSA desensitization therapy, as early intervention could improve prognosis.


Subject(s)
Graft Rejection , Lung Transplantation , Pseudomonas Infections , Pseudomonas aeruginosa , Lung Transplantation/adverse effects , Lung Transplantation/mortality , Humans , Female , Male , Middle Aged , Pseudomonas Infections/immunology , Pseudomonas Infections/diagnosis , Pseudomonas Infections/mortality , Adult , Pseudomonas aeruginosa/immunology , Graft Rejection/immunology , Graft Rejection/diagnosis , Tissue Donors , Retrospective Studies , Graft Survival , Cohort Studies , Isoantibodies/blood , Aged
7.
Exp Clin Transplant ; 22(5): 381-385, 2024 May.
Article in English | MEDLINE | ID: mdl-38970281

ABSTRACT

OBJECTIVES: Lung transplant is the ultimate treatment of many end-stage lung diseases. Calcineurin inhibitors, crucial in immunosuppression for lung transplant recipients, are linked to secondary hypertension, necessitating antihypertensive treatment. In addition, lung transplant recipients frequently experience orthostatic hypotension, occasionally stemming from autonomic dysfunction, but also commonly attributed as a negative side effect of antihypertensive treatment. Our study aimed to evaluate the frequency of orthostatic blood pressure irregularities and investigate the involvement of antihypertensive treatment as a potential risk factor in the occurrence among lung transplant recipients. MATERIALS AND METHODS: Fifty-six consecutive lung transplant recipients, both inpatient and outpatient, at the University Hospital Zurich (Switzerland) were monitored from 1999 to 2013. Transplant recipients underwent a Schellong test (an active standing test). Our evaluation encompassed their initial traits, such as the existence of supine hypertension. We computed the odds ratio for the comparison of the likelihood of experiencing orthostatic hypotension while using a minimum of 1 type of antihypertensive medication versus absence of antihypertensive drugs. RESULTS: Of the lung transplant recipients, 25% showed a positive Schellong test. Within this group, 64% had supine hypertension, and 29% displayed symptoms of orthostatic hypotension. Among the patients, 71% were using at least 1 type of antihypertensive medication. The odds ratio for showing orthostatic hypotension while taking at least 1 type of antihypertensive drug versus the absence of antihypertensive medications was 1.64 (95% exact CI, 0.39-6.90) with P = .50. This finding remained consistent regardless of age, sex, inpatient or outpatient status, and the duration since transplant. CONCLUSIONS: Orthostatic blood pressure dysregulation is prevalent among lung transplant recipients, frequently without noticeable symptoms. In our cohort, the use of antihypertensive medications did not elevate the risk of orthostatic hypotension.


Subject(s)
Antihypertensive Agents , Blood Pressure , Hypotension, Orthostatic , Lung Transplantation , Humans , Lung Transplantation/adverse effects , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/physiopathology , Hypotension, Orthostatic/epidemiology , Female , Male , Cross-Sectional Studies , Middle Aged , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Risk Factors , Adult , Treatment Outcome , Blood Pressure/drug effects , Odds Ratio , Aged , Hypertension/drug therapy , Hypertension/diagnosis , Hypertension/physiopathology , Hypertension/epidemiology , Hospitals, University , Retrospective Studies
8.
Immunol Lett ; 268: 106886, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38906482

ABSTRACT

OBJECTIVE: Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2 protecting individuals, especially the immunocompromised, from COVID-19. Still, it remains largely unknown how solid organ transplant and different immunosuppressive medications affect development of vaccine-induced immunity. METHODS: In this work, we monitored humoral and cellular memory responses after mRNA SARS-CoV-2 two-doses and booster doses vaccination in cystic fibrosis lung transplanted patients (CFT) and compared them with both cystic fibrosis patients without lung transplant (CF) and with kidney transplant recipients (KT). In particular, we investigated the effects of immunosuppressive regimens on immune memory to SARS-CoV-2 after mRNA SARS-CoV-2 vaccine in transplanted patients. RESULTS: Our results showed that immunocompromised transplanted patients displayed a weak cellular and humoral memory to SARS-CoV-2 mRNA vaccination. In addition, obtained data clearly demonstrate that immunosuppressive therapy regimen including antimetabolites, further reduces patients' ability to respond to vaccination at both humoral and cell-mediated level. Notably, patient treated with antimetabolites showed a lower humoral and cellular response also after a booster dose vaccination. CONCLUSION: These results, even if obtained on a small patient's cohort, question whether immunocompromised patients need interventions to improve vaccine SARS-CoV-2 mRNA vaccine response such as additional jab or modulation of immunosuppressive therapy.


Subject(s)
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunity, Cellular , Immunity, Humoral , Immunocompromised Host , Immunosuppressive Agents , SARS-CoV-2 , Transplant Recipients , Humans , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Male , Female , Immunosuppressive Agents/therapeutic use , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Antibodies, Viral/immunology , Antibodies, Viral/blood , Adult , Vaccination , Middle Aged , Cystic Fibrosis/immunology , Immunologic Memory , Organ Transplantation/adverse effects , Kidney Transplantation/adverse effects , Lung Transplantation/adverse effects , Immunization, Secondary
9.
J Int Med Res ; 52(6): 3000605241259442, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38867540

ABSTRACT

OBJECTIVE: To investigate the association between driving pressure (ΔP) and 90-day mortality in patients following lung transplantation (LTx) in patients who developed primary graft dysfunction (PGD). METHODS: This prospective, observational study involved consecutive patients who, following LTx, were admitted to our intensive care unit (ICU) from January 2022 to January 2023. Patients were separated into two groups according to ΔP at time of admission (i.e., low, ≤15 cmH2O or high, >15 cmH2O). Postoperative outcomes were compared between groups. RESULTS: In total, 104 patients were involved in the study, and of these, 69 were included in the low ΔP group and 35 in the high ΔP group. Kaplan-Meier analysis of 90-day mortality showed a statistically significant difference between groups with survival better in the low ΔP group compared with the high ΔP group. According to Cox proportional regression model, the variables independently associated with 90-day mortality were ΔP and pneumonia. Significantly more patients in the high ΔP group than the low ΔP group had PGD grade 3 (PGD3), pneumonia, required tracheostomy, and had prolonged postoperative extracorporeal membrane oxygenation (ECMO) time, postoperative ventilator time, and ICU stay. CONCLUSIONS: Driving pressure appears to have the ability to predict PGD3 and 90-day mortality of patients following LTx. Further studies are required to confirm our results.


Subject(s)
Lung Transplantation , Humans , Lung Transplantation/mortality , Lung Transplantation/adverse effects , Male , Female , Prospective Studies , Middle Aged , Adult , Primary Graft Dysfunction/mortality , Primary Graft Dysfunction/etiology , Intensive Care Units , Kaplan-Meier Estimate , Postoperative Complications/mortality , Pressure , Extracorporeal Membrane Oxygenation/mortality , Risk Factors
10.
Clin Exp Med ; 24(1): 123, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856777

ABSTRACT

Lung transplant (LTx) recipients face a significant risk from coronavirus disease 2019 (COVID-19), with elevated hospitalization mortality rates even post-vaccination. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) typically induces pneumonia in even healthy individuals, it can also infect the transplanted lungs of LTx recipients, potentially leading to graft dysfunction. Despite the prevalence of COVID-19 pneumonia in LTx recipients, data on its characteristics and associated risk factors remain limited. This retrospective study analyzed data from LTx recipients at Tohoku University Hospital between January 2001 and November 2023. COVID-19 cases were identified, and patient records, including thoracic computed tomography (CT) evaluations, were reviewed. Patient characteristics, vaccination history, immunosuppressant use, and comorbidities were assessed. Descriptive analysis was utilized for data presentation. Among 172 LTx recipients, 39 (22.7%) contracted COVID-19, with 9 (23%) developing COVID-19 pneumonia. COVID-19 incidence in LTx recipients aligned with national rates, but pneumonia risk was elevated. Delayed antiviral therapy initiation was noted in pneumonia cases. Remdesivir was uniformly administered and remained the primary treatment choice. LTx recipients are susceptible to COVID-19 pneumonia, warranting vigilance and tailored management strategies. Pre-transplant vaccination and prompt COVID-19 diagnosis and treatment are imperative for optimizing outcomes in this population.


Subject(s)
Antiviral Agents , COVID-19 , Lung Transplantation , Humans , COVID-19/epidemiology , COVID-19/complications , COVID-19/therapy , Male , Female , Japan/epidemiology , Middle Aged , Lung Transplantation/adverse effects , Risk Factors , Retrospective Studies , Aged , Adult , Antiviral Agents/therapeutic use , SARS-CoV-2/isolation & purification , Transplant Recipients , Treatment Outcome , COVID-19 Drug Treatment , Incidence , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives
11.
Transpl Int ; 37: 12512, 2024.
Article in English | MEDLINE | ID: mdl-38887494

ABSTRACT

Brain death triggers a systemic inflammatory response. Whether systemic inflammation is different in lung donors after brain- (DBD) or circulatory-death (DCD) is unknown, but this may potentially increase the incidence of primary graft dysfunction (PGD) after lung transplantation. We compared the plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-α in BDB and DCD and their respective recipients, as well as their relationship with PGD and mortality after LT. A prospective, observational, multicenter, comparative, cohort-nested study that included 40 DBD and 40 DCD lung donors matched and their respective recipients. Relevant clinical information and blood samples were collected before/during lung retrieval in donors and before/during/after (24, 48 and 72 h) LT in recipients. Incidence of PGD and short-term mortality after LT was recorded. Plasma levels of all determined cytokines were numerically higher in DBD than in DCD donors and reached statistical significance for IL-6, IL-10 and IL-8. In recipients with PGD the donor's plasma levels of TNF-α were higher. The post-operative mortality rate was very low and similar in both groups. DBD is associated with higher systemic inflammation than DCD donors, and higher TNF-α plasma levels in donors are associated with a higher incidence of PGD.


Subject(s)
Brain Death , Inflammation , Lung Transplantation , Primary Graft Dysfunction , Tissue Donors , Humans , Lung Transplantation/adverse effects , Female , Male , Middle Aged , Prospective Studies , Adult , Inflammation/blood , Primary Graft Dysfunction/etiology , Primary Graft Dysfunction/blood , Tumor Necrosis Factor-alpha/blood , Interleukin-10/blood , Interleukin-6/blood , Interleukin-8/blood , Transplant Recipients , Cytokines/blood , Aged
12.
Int Immunopharmacol ; 137: 112381, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-38865754

ABSTRACT

A major cause of death for lung transplant recipients (LTRs) is the advent of chronic lung allograft dysfunction (CLAD), which has long plagued the long-term post-transplant prognosis and quality of survival of transplant patients. The intricacy of its pathophysiology and the irreversibility of its illness process present major obstacles to the clinical availability of medications. Immunotherapeutic medications are available, but they only aim to slow down the course of CLAD rather than having any therapeutic impact on the disease's development. For this reason, understanding the pathophysiology of CLAD is essential for both disease prevention and proven treatment. The immunological response in particular, in relation to chronic lung allograft dysfunction, has received a great deal of interest recently. Innate immune cells like natural killer cells, eosinophils, neutrophils, and mononuclear macrophages, as well as adaptive immunity cells like T and B cells, play crucial roles in this process through the release of chemokines and cytokines. The present review delves into changes and processes within the immune microenvironment, with a particular focus on the quantity, subtype, and characteristics of effector immune cells in the peripheral and transplanted lungs after lung transplantation. We incorporate and solidify the documented role of immune cells in the occurrence and development of CLAD with the advancements in recent years.


Subject(s)
Lung Transplantation , Humans , Lung Transplantation/adverse effects , Animals , Allografts/immunology , Graft Rejection/immunology , Chronic Disease , Lung/immunology , Lung/pathology , Immunity, Innate , Adaptive Immunity
13.
HLA ; 103(6): e15544, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38924641

ABSTRACT

HLA (HLA) are a major barrier to transplant success, as HLA-A and -B molecules are principal ligands for T-cells, and HLA-C for Killer cell Immunoglobulin-like Receptors (KIR), directing Natural Killer (NK) cell function. HLA-C molecules are designated "C1" or "C2" ligands based on residues 77 and 80, which determine the NK cell responses. Here, we investigated donor/recipient HLA-C mismatch associations with the development of chronic lung allograft dysfunction (CLAD) following lung transplantation (LTx). 310 LTx donor/recipient pairs were Next Generation Sequenced and assessed for C1 and C2 allotypes. PIRCHE scores were used to quantify HLA mismatching between donor/recipients at amino acid level and stratify recipients into low, moderate or highly mismatched groups (n = 103-104). Associations between C ligands and freedom from CLAD was assessed with Cox regression models and survival curves. C2/C2 recipients (n = 42) had less CLAD than those with C1/C1 (n = 138) or C1/C2 genotypes (n = 130) (p < 0.05). Incidence of CLAD was lower in C2/C2 recipients receiving a mismatched C1/C1 allograft (n = 14), compared to matched (n = 8) or heterozygous (n = 20) allografts. Furthermore, ~80% of these recipients (C2/C2 recipients receiving C1/C1 transplants) remained CLAD-free for 10 years post-LTx. Recipients with higher HLA-C mismatching had less CLAD (p < 0.05) an observation not explained by linkage disequilibrium with other HLA loci. Our data implicates a role for HLA-C in CLAD development. HLA-C mismatching was not detrimental to LTx outcome, but potentially beneficial, representing a paradigm shift in assessing donor/recipient matching. This may inform better selection of donor/recipient pairs and potentially more targeted approaches to treating CLAD.


Subject(s)
HLA-C Antigens , Histocompatibility Testing , Lung Transplantation , Humans , Lung Transplantation/adverse effects , HLA-C Antigens/genetics , HLA-C Antigens/immunology , Male , Female , Middle Aged , Adult , Genotype , Tissue Donors , Graft Rejection/immunology , Killer Cells, Natural/immunology , Aged , Primary Graft Dysfunction/immunology
14.
Ann Ital Chir ; 95(3): 294-298, 2024.
Article in English | MEDLINE | ID: mdl-38918958

ABSTRACT

AIM: Aspergillosis is the most common invasive fungal infection among lung transplant recipients (LTRs). Although its incidence is lower than that of bacterial or viral infections, it poses a similar or even higher mortality rate due to challenges in early diagnosis, limited treatment options, and various complications. Therefore, we aimed to evaluate the pulmonary aspergillosis cases in our tertiary lung transplant center. METHODS: A retrospective analysis of 146 LTRs was performed. The demographic data, microbiological and histopathological test results, and radiological findings used for Aspergillus identification were recorded. RESULTS: Aspergillus spp. was detected in 13 of 146 LTRs (9%), mean age 42.5 ± 14.06 years, an average of 18.9 months after lung transplantation. 3 cases (23%) had Aspergillus growth in tissue culture, and 2 (15.4%) showed fungal elements with septal hyaline fibrils in tissue pathology. Aspergillus spp Polymerase chain reaction (PCR) was positive in bronchoalveolar lavage of 8 (61.5%) cases. In addition, 4 (30.7%) cases had relevant tomography findings. The most common pathogens were A. Terreus (21%), A. Fumigatus (14%), and A. Flavus (14%). The mortality rate was 15%. CONCLUSIONS: LTRs are at high risk of Aspergillus spp infections. Early diagnosis with microbiological, histopathological, and radiological tests, in addition to well-established prevention strategies, prophylaxis, and treatment will provide a better survival rate for patients.


Subject(s)
Invasive Pulmonary Aspergillosis , Lung Transplantation , Tertiary Care Centers , Humans , Retrospective Studies , Lung Transplantation/adverse effects , Adult , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/mortality , Male , Female , Middle Aged , Postoperative Complications/microbiology
15.
Int J Mol Sci ; 25(9)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38731927

ABSTRACT

Bordetella hinzii (B. hinzii), a Gram-negative bacillus commonly associated with respiratory infections in animals, has garnered attention for its sporadic cases in humans, particularly in immunocompromised individuals. Despite its opportunistic nature, there remains limited understanding regarding its pathogenicity, diagnostic challenges, and optimal treatment strategies, especially in the context of immunosuppression. Herein, we present the first documented case of acute bronchitis caused by B. hinzii in an immunocompromised patient following double-lung transplantation. The patient, a former smoker with sarcoidosis stage IV, underwent transplant surgery and subsequently developed a febrile episode, leading to the identification of B. hinzii in broncho-alveolar lavage samples. Antimicrobial susceptibility testing revealed resistance to multiple antibiotics, necessitating tailored treatment adjustments. Our case underscores the importance of heightened awareness among clinicians regarding B. hinzii infections and the imperative for further research to elucidate its epidemiology and optimal management strategies, particularly in immunocompromised populations.


Subject(s)
Bordetella Infections , Bordetella , Immunocompromised Host , Lung Transplantation , Lung Transplantation/adverse effects , Humans , Bordetella/isolation & purification , Bordetella Infections/microbiology , Bordetella Infections/diagnosis , Male , Middle Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Transplant Recipients
16.
Transpl Int ; 37: 12751, 2024.
Article in English | MEDLINE | ID: mdl-38800671

ABSTRACT

Airway complications following lung transplantation remain an important cause of morbidity and mortality. We aimed to identify the incidence, risk factors and outcomes associated with clinically significant airway ischemia (CSAI) in our center. We reviewed 217 lung transplants (386 airway anastomoses) performed at our institution between February 2016 and December 2020. Airway images were graded using the 2018 ISHLT grading guidelines modified slightly for retrospective analysis. Airways were considered to have CSAI if they developed ischemia severity >B2, stenosis >50%, and/or any degree of dehiscence within 6-months of transplant. Regression analyses were used to evaluate outcomes and risk factors for CSAI. Eighty-two patients (37.8%) met criteria for CSAI. Of these, twenty-six (32%) developed stenosis and/or dehiscence, and 17 (21%) required interventions. Patients with CSAI had lower one-year (80.5% vs. 91.9%, p = 0.05) and three-year (67.1% vs. 77.8%, p = 0.08) survival than patients without CSAI. Factors associated with CSAI included younger recipient age, recipient diabetes, single running suture technique, performance of the left anastomosis first, lower venous oxygen saturation within 48-h, and takeback for major bleeding. Our single-center analysis suggests that airway ischemia remains a major obstacle in contemporary lung transplantation. Improving the local healing milieu of the airway anastomosis could potentially mitigate this risk.


Subject(s)
Ischemia , Lung Transplantation , Humans , Male , Risk Factors , Middle Aged , Female , Retrospective Studies , Incidence , Lung Transplantation/adverse effects , Ischemia/etiology , Adult , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Aged , Lung/blood supply
17.
Microbiol Spectr ; 12(6): e0379123, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38747583

ABSTRACT

The upper and lower respiratory tract may share microbiome because they are directly continuous, and the nasal microbiome contributes partially to the composition of the lung microbiome. But little is known about the upper and lower airway microbiome of early postoperative lung transplant recipients (LTRs). Using 16S rRNA gene sequencing, we compared paired nasal swab (NS) and bronchoalveolar lavage fluid (BALF) microbiome from 17 early postoperative LTRs. The microbiome between the two compartments were significantly different in Shannon diversity and beta diversity. Four and eight core NS-associated and BALF-associated microbiome were identified, respectively. NS samples harbored more Corynebacterium, Acinetobacter, and Pseudomonas, while BALF contained more Ralstonia, Stenotrophomonas, Enterococcus, and Pedobacter. The within-subject dissimilarity was higher than the between-subject dissimilarity, indicating a greater impact of sampling sites than sampling individuals on microbial difference. There were both difference and homogeneity between NS and BALF microbiome in early postoperative LTRs. High levels of pathogens were detected in both samples, suggesting that both of them can reflect the diseases characteristics of transplanted lung. The differences between upper and lower airway microbiome mainly come from sampling sites instead of sampling individuals. IMPORTANCE: Lung transplantation is the only therapeutic option for patients with end-stage lung disease, but its outcome is much worse than other solid organ transplants. Little is known about the NS and BALF microbiome of early postoperative LTRs. Here, we compared paired samples of the nasal and lung microbiome from 17 early postoperative LTRs and showed both difference and homogeneity between the two samples. Most of the "core" microbiome in both NS and BALF samples were recognized respiratory pathogens, suggesting that both samples can reflect the diseases characteristics of transplanted lung. We also found that the differences between upper and lower airway microbiome in early postoperative LTRs mainly come from sampling sites instead of sampling individuals.


Subject(s)
Bacteria , Bronchoalveolar Lavage Fluid , Lung Transplantation , Microbiota , RNA, Ribosomal, 16S , Transplant Recipients , Lung Transplantation/adverse effects , Humans , Microbiota/genetics , Bronchoalveolar Lavage Fluid/microbiology , Male , Female , Middle Aged , RNA, Ribosomal, 16S/genetics , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , Adult , Lung/microbiology , Postoperative Period , Aged , Respiratory System/microbiology
19.
J Surg Res ; 299: 129-136, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38754251

ABSTRACT

INTRODUCTION: Cytomegalovirus (CMV) infection is associated with a poor prognosis after lung transplantation, and donor and recipient CMV serostatus is a risk factor for reactivation. CMV prophylaxis is commonly administered in the first year following transplantation to reduce CMV infection; however, the risk factors for long-term reactivation remain unclear. We investigated the timing and risk factors of CMV infection after prophylactic administration. METHODS: This study was a retrospective review of the institutional lung transplantation database from June 2014 to June 2022. Data on patient characteristics, pretransplantation laboratory values, postoperative outcomes, and CMV infection were collected. Donor CMV-IgG-positive and recipient CMV-IgG-negative groups were defined as the CMV mismatch group. RESULTS: During the study period, 257 patients underwent lung transplantation and received a prophylactic dose of valganciclovir hydrochloride for up to 1 y. CMV infection was detected in 69 patients (26.8%): 40 of 203 (19.7%) in the non-CMV mismatch group and 29 of 54 (53.7%) in the CMV mismatch group (P < 0.001). CMV infection after prophylaxis occurred at a median of 425 and 455 d in the CMV mismatch and non-CMV mismatch groups, respectively (P = 0.07). Multivariate logistic regression analysis revealed that preoperative albumin level (odds ratio [OR] = 0.39, P = 0.04), CMV mismatch (OR = 15.7, P < 0.001), and donor age (OR = 1.05, P = 0.009) were significantly associated with CMV infection. CONCLUSIONS: CMV mismatch may have increased the risk of CMV infection after lung transplantation, which decreased after prophylaxis. In addition to CMV mismatch, low preoperative albumin level and donor age were independent predictors of CMV infection.


Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Lung Transplantation , Humans , Cytomegalovirus Infections/prevention & control , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/diagnosis , Male , Female , Retrospective Studies , Middle Aged , Lung Transplantation/adverse effects , Adult , Risk Factors , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , Recurrence , Valganciclovir/therapeutic use , Valganciclovir/administration & dosage , Aged , Cytomegalovirus/immunology , Cytomegalovirus/isolation & purification , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology
20.
J Surg Res ; 299: 303-312, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38788467

ABSTRACT

INTRODUCTION: Early extubation has been adopted in many settings within cardiothoracic surgery, with several advantages for patients. We sought to determine the association of timing of extubation in lung transplant recipients' short- and long-term outcomes. METHODS: Adult, primary lung transplants were identified from the United Network for Organ Sharing database. Recipients were stratified based on the duration of postoperative ventilation: 1) None (NV); 2) <5 Days (<5D); and 3) 5+ Days (5+D). Comparative statistics were performed, and both unadjusted and adjusted survival were analyzed with Kaplan-Meier Methods and a Cox proportional hazard model. A multivariable model including recipient, donor, and transplant characteristics was created to examine factors associated with NV. RESULTS: 28,575 recipients were identified (NV = 960, <5D = 21,959, 5+D = 5656). The NV group had shorter median length of stay (P < 0.01) and lower incidence of postoperative dialysis (P < 0.01). The NV and <5D groups had similar survival, while 5+D recipients had decreased survival (P < 0.01). The multivariable model demonstrated increased donor BMI, center volume, ischemic time, single lung transplant, and transplantation between 2011 and 2015 were associated with NV (P < 0.01 for all). Use of donation after cardiac death donors and transplantation between 2016 and 2021 was associated with postoperative ventilator use. CONCLUSIONS: Patients extubated early after lung transplantation have a shorter median length of stay without an associated increase in mortality. While not all patients are appropriate for earlier extubation, it is possible to extubate patients early following lung transplant. Further efforts are necessary to help expand this practice and ensure its' success for recipients.


Subject(s)
Airway Extubation , Lung Transplantation , Humans , Lung Transplantation/statistics & numerical data , Lung Transplantation/mortality , Lung Transplantation/adverse effects , Airway Extubation/statistics & numerical data , Female , Male , Middle Aged , Adult , Time Factors , Length of Stay/statistics & numerical data , Retrospective Studies , Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Kaplan-Meier Estimate
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