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BACKGROUND: Antifibrotic agents (AFAs) are now standard-of-care for idiopathic pulmonary fibrosis (IPF). Concerns have arisen about the safety of these drugs in patients undergoing lung transplantation (LTx). METHODS: We performed a multi-centre, nationwide, retrospective, observational study of French IPF patients undergoing LTx between 2011 and 2018 to determine whether maintaining AFAs in the peri-operative period leads to increased bronchial anastomoses issues, delay in skin healing and haemorrhagic complications. We compared the incidence of post-operative complications and the survival of patients according to AFA exposure. RESULTS: Among 205 patients who underwent LTx for IPF during the study period, 58 (28%) had received AFAs within 4 weeks before LTx (AFA group): pirfenidone in 37 (18.0%) and nintedanib in 21 (10.2%). The median duration of AFA treatment before LTx was 13.8 (5.6-24) months. The AFA and control groups did not significantly differ in airway, bleeding or skin healing complications (p = 0.91, p = 0.12 and p = 0.70, respectively). Primary graft dysfunction was less frequent in the AFA than control group (26% vs. 43%, p = 0.02), and the 90-day mortality was lower (7% vs. 18%, p = 0.046). CONCLUSIONS: AFA therapy did not increase airway, bleeding or wound post-operative complications after LTx and could be associated with reduced rates of primary graft dysfunction and 90-day mortality.
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Fibrosis Pulmonar Idiopática , Trasplante de Pulmón , Disfunción Primaria del Injerto , Humanos , Antifibróticos , Estudios Retrospectivos , Disfunción Primaria del Injerto/tratamiento farmacológico , Disfunción Primaria del Injerto/etiología , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/cirugía , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Piridonas/efectos adversos , Resultado del TratamientoRESUMEN
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.
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Infecciones por Bordetella , Bordetella , Huésped Inmunocomprometido , Trasplante de Pulmón , Trasplante de Pulmón/efectos adversos , Humanos , Bordetella/aislamiento & purificación , Infecciones por Bordetella/microbiología , Infecciones por Bordetella/diagnóstico , Masculino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Receptores de TrasplantesRESUMEN
QUESTION ADDRESSED BY THE STUDY: Do three coronavirus disease 2019 (COVID-19) vaccine doses induce a serological response in lung transplant recipients? METHODS: We retrospectively included 1071 adults (551 (52%) males) at nine transplant centres in France. Each had received three COVID-19 vaccine doses in 2021, after lung transplantation. An anti-spike protein IgG response, defined as a titre >264â BAU·mL-1 after the third dose (median (interquartile range (IQR)) 3.0 (1.7-4.1)â months), was the primary outcome and adverse events were the secondary outcomes. Median (IQR) age at the first vaccine dose was 54 (40-63)â years and median (IQR) time from transplantation to the first dose was 64 (30-110)â months. RESULTS: Median (IQR) follow-up after the first dose was 8.3 (6.7-9.3)â months. A vaccine response developed in 173 (16%) patients. Factors independently associated with a response were younger age at vaccination, longer time from transplantation to vaccination and absence of corticosteroid or mycophenolate therapy. After vaccination, 51 (5%) patients (47 non-responders (47/898 (5%)) and four (4/173 (2%)) responders) experienced COVID-19, at a median (IQR) of 6.6 (5.1-7.3)â months after the third dose. No responders had severe COVID-19 compared with 15 non-responders, including six who died of the disease. CONCLUSIONS: Few lung transplant recipients achieved a serological response to three COVID-19 vaccine doses, indicating a need for other protective measures. Older age and use of mycophenolate or corticosteroids were associated with absence of a response. The low incidence of COVID-19 might reflect vaccine protection via cellular immunity and/or good adherence to shielding measures.
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Vacunas contra la COVID-19 , COVID-19 , Adulto , Masculino , Humanos , Femenino , Receptores de Trasplantes , COVID-19/prevención & control , Estudios Retrospectivos , PulmónRESUMEN
BACKGROUND: Respiratory infections are a major threat for lung recipients. We aimed to compare with a monocentric study the impact of late viral and bacterial respiratory infections on the graft function. METHODS: Patients, who survived 6 months or more following lung transplantation that took place between 2009 and 2014, were classified into three groups: a viral infection group (VIG) (without any respiratory bacteria), a bacterial infection group (BIG) (with or without any respiratory viruses), and a control group (CG) (no documented infection). Chronic lung allograft dysfunction (CLAD) and acute rejection were analysed 6 months after the inclusion in the study. RESULTS: Among 99 included lung recipients, 57 (58%) had at least one positive virological respiratory sample during the study period. Patients were classified as follows: 38 in the VIG, 25 in the BIG (among which 19 co-infections with a virus) and 36 in the CG. The BIG presented a higher initial deterioration in lung function (p = 0.05) than the VIG. But 6 months after the infection, only the VIG presented a median decrease of forced expiratory volume in 1 s; - 35 mL (IQR; - 340; + 80) in the VIG, + 140 mL (+ 60;+ 330) in the BIG and + 10 (- 84;+ 160) in the CG, p < 0.01. Acute rejection was more frequent in the VIG (n = 12 (32%)), than the BIG (n = 6 (24%)) and CG (n = 3 (8%)), p < 0.05, despite presenting no more CLAD (p = 0.21). CONCLUSIONS: Despite a less severe initial presentation, single viral respiratory infections seem to lead to a greater deterioration in lung function, and to more acute rejection, than bacterial infections.
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Infecciones Bacterianas/diagnóstico , Trasplante de Pulmón , Infecciones del Sistema Respiratorio/diagnóstico , Virosis/diagnóstico , Femenino , Volumen Espiratorio Forzado , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Picornaviridae/aislamiento & purificación , Pseudomonas aeruginosa/aislamiento & purificación , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virologíaRESUMEN
AIMS: Antibody-mediated rejection (AMR) is an emerging and challenging issue in transplantation. Endothelial deposition of C4d and microvascular inflammation (MI) are reliable markers of AMR in renal and cardiac transplantation, but remain controversial in the lung. Our aim was to assess C4d immunohistochemistry and histological patterns for the diagnosis of lung AMR. METHODS AND RESULTS: We reviewed 158 transbronchial biopsies (TBBs) (n = 85 clinically indicated, and n = 73 surveillance TBBs) from 48 recipients, blinded to clinical and serological data. C4d was scored as 0, 1+ (<10%), 2+ (10-50%) or 3+ (>50%). TBBs were reassessed for MI and acute lung injury (ALI). Donor-specific antibodies (DSAs), acute clinical graft dysfunction and chronic lung allograft graft dysfunction (CLAD) were recorded. C4d3+, C4d2+, C4d1+ and C4d0 occurred respectively in four (2.5%), six (3.8%), 28 (17.7%) and 120 (75.9%) TBBs. MI and ALI were rare but more frequent in C4d1-3+ TBBs than in the absence of C4d. C4d2+ was frequently observed with concomitant infection. Among the surveillance TBBs, only two (2.7%) showed MI. Neither ALI nor C4d3+ was diagnosed on surveillance TBBs. No significant association was found between histopathological findings and DSAs. All four patients with C4d3+ could retrospectively be diagnosed with AMR and developed CLAD. CONCLUSION: Although rare, diffuse C4d deposition appears to be a strong indication of acute clinical AMR in lung transplant patients, whereas intermediate C4d2+ requires more investigations. In stable patients, histopathology and C4d may lack the sensitivity to diagnose subclinical AMR. This emphasises the need for a multidisciplinary evaluation of each suspected AMR case, and the need for complementary diagnostic tools.
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Anticuerpos/inmunología , Complemento C4b/metabolismo , Rechazo de Injerto/etiología , Trasplante de Pulmón , Fragmentos de Péptidos/metabolismo , Adulto , Biopsia , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Humanos , Inmunohistoquímica , Pulmón/inmunología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Presence of anti-human leukocyte antigen donor-specific antibodies (DSAs) is associated with poor outcome after lung transplantation. Currently, DSAs are detected using the Luminex technique, which may be overly sensitive. The new C1q assay allows for the exclusive detection of complement (C1q)-binding antibodies, involved in antibody-mediated rejection. We investigated whether early detection of complement-binding DSAs is associated with chronic lung allograft dysfunction (CLAD) and survival.From 2009 to 2012, lung transplant recipients from three transplantation centres were screened for the presence of DSA and their complement-binding capacity during the 6-12â months post-transplantation in a stable condition.The analysis included 168 patients. The 3-year rates of freedom from CLAD and graft survival were lower for patients with complement-binding DSAs (33.6% and 53.7%, respectively), as compared with patients with non-complement-binding DSAs (61.9% and 77.4%, respectively) and patients without DSA (70% and 84.9%, respectively) (p<0.001 and p=0.001, respectively). Detection of complement-binding DSA was associated with a risk of graft loss that was nearly tripled after adjustment for clinical, functional, histological and immunological factors (hazard ratio 2.98, 95% CI 1.33-6.66; p=0.008).Assessment of the C1q-binding capacity of DSA appears to be useful in identifying stable lung transplant recipients at high risk of lung allograft loss.
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Complemento C1q/inmunología , Antígenos HLA/inmunología , Isoanticuerpos/inmunología , Trasplante de Pulmón , Donantes de Tejidos , Adulto , Aloinjertos , Femenino , Francia , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
OBJECTIVES: To assess the accuracy of reduced-dose, low-mA chest CT (RD-CT) reconstructed with model-based iterative reconstruction (MBIR) in detecting usual early complications following pulmonary transplantation, as compared to standard-dose chest CT (SD-CT) reconstructed with adaptative statistical iterative reconstruction (ASIR). METHODS: Our institutional review board approved this prospective study and patients provided written informed consent. Two thoracic radiologists independently evaluated 47 examinations performed routinely in 20 patients during 6 months following lung transplantation for the detection and/or evolution of usual pleuropulmonary complications and for subjective image quality. Each examination consisted of successive acquisition of unenhanced SD-CT (100-120 kV, noise index 45, ASIR) and RD-CT (100 kV, 16-24mAs/slice, MBIR). RESULTS: Mean CTDIvol was 4.12 ± 0.88 and 0.65 ± 0.09 mGy for SD-CT and RD-CT, respectively. Complications were found in 40/47 (85 %) examinations. Sensitivity and negative predictive value of RD-CT were 92-100 % for the detection of pneumonia, fungal infection, pleural effusion, pneumothorax, and bronchial dehiscence or stenosis, as compared to SD-CT. Image quality of RD-CT was graded good for 81 % of examinations. CONCLUSIONS: MBIR-RD-CT is accurate, as compared to SD-CT, for delineating most usual pleuropulmonary complications during the 6 months following pulmonary transplantation and might be used routinely for the early monitoring of pulmonary allografts. KEY POINTS: ⢠Early chest complications are frequent following a pulmonary transplantation ⢠CT has a key role for their detection and follow-up ⢠Low-mAMBIR CT is accurate for monitoring most lung allograft early pleuropulmonary complications ⢠MBIR chest CT allows a six-fold dose reduction compared to standard CT.
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Enfermedades Pulmonares/diagnóstico , Trasplante de Pulmón/efectos adversos , Pulmón/diagnóstico por imagen , Pleura/diagnóstico por imagen , Enfermedades Pleurales/diagnóstico , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Algoritmos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Estudios Prospectivos , Dosis de RadiaciónRESUMEN
Background: Human metapneumovirus (hMPV) is one of the leading respiratory viruses. This prospective observational study aimed to describe the clinical features and the outcomes of hMPV-associated lower respiratory tract infections in adult inpatients. Methods: Consecutive adult patients admitted to one of the 31 participating centers with an acute lower respiratory tract infection and a respiratory multiplex PCR positive for hMPV were included. A primary composite end point of complicated course (hospital death and/or the need for invasive mechanical ventilation) was used. Results: Between March 2018 and May 2019, 208 patients were included. The median age was 74 [62-84] years. Ninety-seven (47 %) patients were men, 187 (90 %) had at least one coexisting illness, and 67 (31 %) were immunocompromised. Median time between first symptoms and hospital admission was 3 [2-7] days. The two most frequent symptoms were dyspnea (86 %) and cough (85 %). The three most frequent clinical diagnoses were pneumonia (42 %), acute bronchitis (20 %) and acute exacerbation of chronic obstructive pulmonary disease (16 %). Among the 52 (25 %) patients who had a lung CT-scan, the most frequent abnormality was ground glass opacity (41 %). While over four-fifths of patients (81 %) received empirical antibiotic therapy, a bacterial coinfection was diagnosed in 61 (29 %) patients. Mixed flora (16 %) and enterobacteria (5 %) were the predominant documentations. The composite criterion of complicated course was assessable in 202 (97 %) patients, and present in 37 (18 %) of them. In the subpopulation of pneumonia patients (42 %), we observed a more complicated course in those with a bacterial coinfection (8/24, 33 %) as compared to those without (5/60, 8 %) (p = 0.02). Sixty (29 %) patients were admitted to the intensive care unit. Among them, 23 (38 %) patients required invasive mechanical ventilation. In multivariable analysis, tachycardia and alteration of consciousness were identified as risk factors for complicated course. Conclusion: hMPV-associated lower respiratory tract infections in adult inpatients mostly involved elderly people with pre-existing conditions. Bacterial coinfection was present in nearly 30 % of the patients. The need for mechanical ventilation and/or the hospital death were observed in almost 20 % of the patients.
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Lung transplantation (LTx) is a steadily expanding field. The considerable developments have been driven over the years by indefatigable work conducted at LTx centers to improve donor and recipient selection, combined with multifaceted efforts to overcome challenges raised by the surgical procedure, perioperative care, and long-term medical complications. One consequence has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. The Francophone Pulmonology Society (Société de Pneumology de Langue Française, SPLF) set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force examined the most recent literature and evaluated the risk factors that limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while also improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.
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Trasplante de Pulmón , Calidad de Vida , Humanos , Francia/epidemiología , Factores de Riesgo , ContraindicacionesAsunto(s)
Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias , Proteinosis Alveolar Pulmonar/complicaciones , Anciano , Lavado Broncoalveolar , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Humanos , Pulmón/inmunología , Pulmón/cirugía , Masculino , Persona de Mediana Edad , Proteinosis Alveolar Pulmonar/patología , Surfactantes Pulmonares , Transducción de SeñalRESUMEN
BACKGROUND: It is unknown whether pulmonary arterial hypertension (PAH) risk stratification instruments could be helpful to support the decision to list a patient for lung transplantation (LT). Our aim was to evaluate contemporary risk assessment tools in a cohort of PAH patients listed for LT. METHODS: Consecutive PAH patients (without pulmonary veno-occlusive disease or unrepaired congenital heart disease) listed for LT at the French Pulmonary Hypertension Reference Center between January 2006 and December 2018 were included. At the time of listing, risk stratification was assessed using the ESC/ERS criteria, the REVEAL Lite 2 score and the COMPERA 2.0 method. The primary end point was overall survival after LT listing. Secondary outcome measures were mortality on waiting list and posttransplant survival. RESULTS: One hundred and two patients were enrolled (mean age 38 ± 13 years, 69% females). Overall survival after listing was 72%, 58% and 46% at 1, 3 and 5 years respectively. Survival after LT listing was lower in "high-risk" patients according to the ESC/ERS criteria (p = 0.0001) and the REVEAL Lite 2 score (p = 0.04). The COMPERA 2.0 method discriminated post-listing survival of patients at high-risk, intermediate-high and intermediate-low risk (p = 0.04). The proportion of patients requiring urgent transplantation and extracorporeal life support as a bridge to transplantation was higher in the "high-risk" patients. Posttransplant survival was significantly lower in "high-risk" patients according to the ESC/ERS criteria (p = 0.0004). CONCLUSIONS: High-risk PAH patients at the time of LT listing have poor outcomes, suggesting that LT should be considered earlier in the course of PAH remaining refractory to triple combination therapy with a parenteral prostacyclin.
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Trasplante de Pulmón , Hipertensión Arterial Pulmonar , Adulto , Epoprostenol , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hipertensión Arterial Pulmonar/cirugía , Estudios Retrospectivos , Medición de RiesgoRESUMEN
Background: Targeted medical therapy and balloon pulmonary angioplasty (BPA) entered the field of chronic thromboembolic pulmonary hypertension (CTEPH) treatment in the early 2010's. Multimodal therapy is emerging as the new gold standard for CTEPH management. Whether this change of paradigm impacted early outcomes of pulmonary endarterectomy (PEA) remains unknown. Our aim is to report our surgical experience in the era of CTEPH multimodal management. Methods: Patients who underwent PEA between 2016 and 2020 were included in the study. Early outcomes were described and compared between three groups of patients: PEA alone, PEA after targeted medical therapy induction and PEA after BPA. Results: A total of 418 patients, 225 males and 193 females, with a mean age of 59±14 years were included in the study. 336 patients underwent PEA alone, 69 after medical targeted therapy induction and 13 after unilateral BPA. Baseline preoperative pulmonary vascular resistance [4.99 (IQR, 1.71-8.48), 6.21 (IQR, 4.37-8.1), 5.03 (IQR, 4.44-7.19) wood units (WU), P=0.230, respectively] and PEA effectiveness [% decrease mean pulmonary artery pressure (mPAP), 24 (IQR, 7-42), 25 (IQR, 7-35), 23 (IQR, 3-29), P=0.580] did not differ between groups. Compared to PEA alone and PEA+BPA, the medical therapy induction group represented the most challenging group with higher baseline mPAP (45±10 vs. 42±11 and 43±11 mmHg, P=0.047), longer circulatory arrest time (30.1±15 vs. 26.6±10 and 19.6±6 min, P=0.005), higher post-PEA extracorporeal membrane oxygenation use (20.6% vs. 8.7 and 9.1%, P=0.004), higher duration on mechanical ventilation [4 (IQR, 1-12) vs. 1 (IQR, 0.5-5) and 2 (IQR, 1-3) days, P=0.005], higher complication rate (85.5% vs. 74.6% and 76.9%, P=0.052) and higher 90-day mortality (13% vs. 3.9% and 0%, P=0.002). Compared to PEA and PEA+ medical therapy induction groups, patients in the BPA induction group were older [72 (IQR, 62-76) vs. 60 (IQR, 48-69) and 62 (IQR, 52-72) years, P=0.005], and underwent shorter cardiopulmonary bypass (191.9±47.9 vs. 222±107.2 and 236.8±46.4 min, P<0.001), aortic cross clamping (54.8±21 vs. 82.7±31.4 and 80.1±32.9 min, P=0.002) and circulatory arrest time (19.6±6.2 vs. 26.6±10.8 and 30.1±15.1 min, P=0.008). Conclusions: Multimodal therapy approach to CTEPH patients did not affect effectiveness of PEA. Medical therapy and BPA could act in synergy with surgery to treat more challenging patients.
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BACKGROUND: Survival after lung transplantation (LTx) still remains limited by chronic lung allograft dysfunction (CLAD), thought to represent a form of chronic rejection. We investigated whether the immune checkpoint HLA-G/ILT2 expressed by peripheral T-cell subpopulations could predict CLAD. METHODS: We used data for 150 LTx recipients from COLT (Cohort-For-Lung-Transplantation) cohort with ≥1 available blood sample at 1-, 6-, or 12-months post-Tx. Analysis of T cells by flow cytometry focused on the ILT2 receptor of HLA-G and other markers (CD57, CD25, CD127). T-cell subset analyses compared stable patients and those with CLAD at 3 years post-LTx. RESULTS: With data for 78 stable and 72 CLAD patients, among 21 T-cell subsets expressing ILT2, only CD4+CD57+ILT2+ T cells were associated with outcome. At 1-month post-Tx, low proportion of CD4+CD57+ILT2+ T cells was associated with reduced 3-year incidence of CLAD (CD4+CD57+ILT2+ T cells ≤ first IQR [25%] vs > first IQR, log-rank test, p = 0.028). Furthermore, the incidence of CLAD was higher with >2.6- vs ≤2.6-fold increased proportion of CD4+CD57+ILT2+ T cells over the first year post-LTx (3-year freedom frequencies: 27% [95%CI: 8-50] vs 64% [95%CI: 48-77] (log-rank test, p = 0.014). On multivariable analysis, increased proportion of CD4+CD57+ILT2+ T cells over the first year predicted CLAD (hazard ratio 1.25; 95%CI: 1.09-1.44; p = 0.001). Focusing on CD4+CD57+ILT2+ T cells, we demonstrated ex vivo that they are cytotoxic CD4+ T cells, selectively inhibited by HLA-G. CONCLUSIONS: Our data suggest that an early increase of CD4+CD57+ILT2+ T cells after LTx may be associated with CLAD onset.
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Antígenos HLA-G , Trasplante de Pulmón , Aloinjertos , Humanos , Pulmón , Linfocitos TRESUMEN
INTRODUCTION: Lung cancer is a frequent pathology for which the best curative treatment is pulmonary resection. Pulmonary arterial hypertension is a rare disease but pulmonary hypertension associated with parenchymal disease or left heart disease is frequently observed in these patients. The diagnosis of pulmonary hypertension before lung resection makes the perioperative management of these patients more difficult and sometimes leads to rejecting patients for surgery. AREAS COVERED: We performed a review of literature on PubMed on Pulmonary hypertension associated lung resection, preoperative assessment of lung resection and perioperative management of PH patients, including guidelines and clinical trials.In this review, we summarize the current state of knowledge regarding the pre and perioperative management of patients with suspected or confirmed PH who can benefit from surgical treatment of lung cancer. EXPERT OPINION: Management of PH patients before lung resection should include a very careful workup including at least right heart catheterization with evaluation of the targeted PH treatment in an expert center and evaluation of other comorbidities. Perioperative management must be carried out in a specialized center.
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Hipertensión Pulmonar , Neoplasias Pulmonares , Procedimientos Quirúrgicos Torácicos , Cateterismo Cardíaco , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/terapia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugíaRESUMEN
We sought to determine whether invasive aspergillosis (IA) during the first year after lung transplantation increased the risk of chronic lung allograft dysfunction (CLAD). METHODS: We retrospectively reviewed the records of 191 patients who underwent lung transplantation at our institution between January 2013 and December 2017. Screening for Aspergillus was with bronchial aspirates, bronchoalveolar lavage if indicated or during surveillance bronchoscopy, radiography, and computed tomography. We used Fine and Gray multivariable regression to identify potential risk factors for CLAD. RESULTS: During the first posttransplant year, 72 patients had at least 1 deep-airway sample positive for Aspergillus; 63 were classified as having IA and were included in the study. Median number of endoscopies per patient during the first year was 9 (range, 1-44). Median time from transplantation to first Aspergillus-positive sample was 121 d. Bronchial aspirate samples and bronchoalveolar lavage fluid were positive in 71 and 44 patients, respectively. Aspergillus fumigatus (n = 36, 50%) predominated; bacterial samples were also positive in 22 (31%) patients. IA within 4 mo after transplantation was independently associated with CLAD development (subdistribution hazard ratio, 3.75; 95% confidence interval [CI], 1.61-8.73; P < 0.01) by regression analysis. Survival at 3 and 5 y conditional on 1-y CLAD-free survival was 37% (95% CI, 24%-58%), and 24% (95% CI, 11%-52%) in the IA <4 mo group compared to 65% (95% CI, 57%-73%) and 54% (95% CI, 43%-66%) in the non-IA group and to 69% (95% CI, 58%-83%) and 54% (95% CI, 35%-82%) in the IA ≥4 mo group, respectively (P < 0.01, logrank test). CONCLUSIONS: Our evaluation of de novo IA showed that this infection was most strongly associated with CLAD when found within 4 mo after transplantation.
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PURPOSE: Pulmonary arterial hypertension (PAH) is rare but remains fatal in infants and children despite the advance of targeted therapies. Lung transplantation (LTx), first performed in pediatric patients in the 1980s, is, with the Potts shunt, the only potentially life-extending option in patients with end-stage PAH but is possible only in tightly selected patients. Size-matching challenges severely restrict the donor organ pool, resulting-together with peculiarities of PAH in infants-in high waitlist mortality. We aimed to investigate survival when using a high-priority allocation program (HPAP) in children with PAH listed for double-LTx or heart-LTx. METHODS: We conducted a single-center, retrospective, before-after study of consecutive children with severe Group 1 PAH listed for double-LTx or heart-LTx between 1988 and 2019. The HPAP was implemented in France in 2006 and 2007 for heart-LTx and double-LTx, respectively. RESULTS: Fifty-five children with PAH were listed for transplantation. Mean age at transplantation was 15.8±2.8 years and 72% had heart-lung transplantation. PAH was usually idiopathic (65%) or due to congenital heart disease (25%). HPAP implementation resulted in the following significant benefits: Decreased cumulative incidence of waitlist death within 1 and 2 years (p < 0.0001); increased cumulative incidence of transplantation within 6 months, from 44% to 67% (p < 0.01); and improved survival after listing (at 1, 3, and 5 years: 61%, 50%, and 44% vs. 92%, 84%, and 72% before and after HPAP implementation, respectively; pâ¯=â¯0.02). CONCLUSION: HPAP implementation was associated with significant improvements in access to transplantation and in survival after listing in children with end-stage PAH.
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Trasplante de Corazón-Pulmón/métodos , Trasplante de Pulmón/métodos , Hipertensión Arterial Pulmonar/cirugía , Presión Esfenoidal Pulmonar/fisiología , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adolescente , Niño , Toma de Decisiones , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Incidencia , Masculino , Selección de Paciente , Hipertensión Arterial Pulmonar/epidemiología , Hipertensión Arterial Pulmonar/fisiopatología , Estudios Retrospectivos , Listas de EsperaRESUMEN
BACKGROUND: A small proportion of patients with chronic obstructive pulmonary disease (COPD) patients present severe pulmonary hypertension (PH), defined by mean pulmonary artery pressure (mPAP) ≥35 mm Hg measured by right heart catheterization. Little is known about the characteristics of severe PH-COPD. The aim of the study based on a national registry was to describe this phenotype. METHODS: We prospectively included and followed patients with incident PH-COPD. Clinical, functional, hemodynamic data at inclusion and follow-up were retrieved. Survival assessed by Kaplan-Meier analysis was the primary end-point. RESULTS: From 2012 to 2016, 99 patients from 13 French centers were included in the study (82 males; median age 66.0 years [interquartile range 62.0-72.0]). At inclusion, most patients had marked dyspnea (55.6% and 22.2% New York Heart Association class III and IV, respectively). During 12 months before inclusion, 42.9% had an exacerbation requiring a hospitalization. Pulmonary function tests showed a moderate obstructive pattern with median (interquartile range) FEV1 50.0 [35.0-63.0] % predicted and low diffusing capacity for carbon monoxide, median 20.0 [16.5-30.6] % predicted. The median values for PaO2 and PaCO2 on room air were 50.0 [44.8-62.0] and 36.0 [31.1-43.0] mm Hg. Median values of mPAP, pulmonary artery occlusion pressure, cardiac index and pulmonary vascular resistance were 42.0 [37.0-48.0] mm Hg, 11.0 [9.0-14.0] mm Hg, 3.0 [2.4-3.6] L/min/m2, and 6.3 [4.2-7.9] WU, respectively. Mean restricted survival was 15.0 [13.9-16.0] months. CONCLUSIONS: Severe PH-COPD is characterized by moderate airway obstruction but marked dyspnea and marked hypoxemia, low DLCO and high mPAP. This phenotype is associated with poor prognosis.
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Hipertensión Pulmonar/etiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Presión Esfenoidal Pulmonar/fisiología , Resistencia Vascular/fisiología , Anciano , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/fisiopatología , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND: Patients with end-stage idiopathic pulmonary fibrosis (IPF) are increasingly having bilateral rather than single-lung transplantation. OBJECTIVE: To compare survival after single and bilateral lung transplantation in patients with IPF. DESIGN: Analysis of data from the United Network of Organ Sharing registry. SETTING: Transplantation centers in the United States. PATIENTS: 3327 patients with IPF who had single (2146 patients [64.5%]) or bilateral (1181 patients [35.5%]) lung transplantation between 1987 and 2009. MEASUREMENTS: Survival times and causes of death after lung transplantation. Selection bias was accounted for by multivariate risk adjustment, propensity score risk adjustment, and propensity-based matching. RESULTS: Median survival time was longer after bilateral lung transplantation than single-lung transplantation (5.2 years [CI, 4.3 to 6.7 years] vs. 3.8 years [CI, 3.6 to 4.1 years]; P < 0.001). However, survival times for the 2 procedures did not differ after adjustment for baseline differences, with adjusted hazard ratios (HRs) for mortality with bilateral transplantation ranging from 0.89 (95% CI, 0.79 to 1.02) to 0.96 (CI, 0.77 to 1.20) in different analyses. Bilateral lung transplantation seemed to result in harm within the first year (HR, 1.18 [CI, 0.98 to 1.42]) but survival benefit thereafter (HR, 0.72 [CI, 0.59 to 0.87]). Primary graft failure was a more common cause of death among patients who had bilateral rather than single-lung transplantation (3.7% vs. 1.9%; P = 0.002). Cancer was a more common cause of death among patients who had single rather than bilateral lung transplantation (unadjusted HR for death among single vs. bilateral transplant recipients, 3.60 [CI, 2.16 to 6.05]; P <0.001). LIMITATION: Causes of death were ascertained without an adjudication committee and must be interpreted cautiously. CONCLUSION: Survival did not differ between patients who had single and bilateral lung transplantation. Single-lung transplantation confers short-term survival benefit but long-term harm, whereas bilateral transplantation confers short-term harm but long-term survival benefit. PRIMARY FUNDING SOURCE: None.