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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.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.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 (p0.0001); increased cumulative incidence of transplantation within 6 months, from 44% to 67% (p0.01); 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; p = 0.02).HPAP implementation was associated with significant improvements in access to transplantation and in survival after listing in children with end-stage PAH.

BACKGROUND Restrictive allograft syndrome (RAS) after lung transplantation (LTx) is associated with the poorer graft survival in patients with chronic lung allograft dysfunction (CLAD). Nevertheless, its diagnostic criteria have not been clearly defined after single-LTx (SLTx). Hence, we studied an SLTx cohort with CLAD to investigate the utility of both computed tomography (CT)-score/volume measures and functional spirometric criteria for the early identification of RAS in this population. METHODS We included 51 patients with SLTx (17 RAS, 17 bronchiolitis obliterans syndrome [BOS], and 17 stable condition). The criteria for RAS diagnosis in SLTx included forced vital capacity (FVC) 0.7 and persistent CT-scan-lung opacities. We defined 4 time points (T): T-baseline, T-onset (first CT-scan-opacities), T-follow-up, and T-last. RESULTS In patients with RAS, the spirometric criteria for RAS at T-onset were reached in only 47% (FVC decline 0.7 [41%]), whereas at the same T-onset date, the graft CT-score increased to 5 (4-6) vs 1 (0-2) at baseline (p < 0.001) (CT - score ≥2 at T-onset in 100% and ΔCT - score ≥2 in 74% of patients with RAS), and the median CT-scan graft volume decreased to 1,722 ml (vs 1,796 ml at T-baseline, p = 0.003) (decreased CT-graft - volume

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+ ( 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.

SARS‐Cov2 outbreak has deeply impacted French lung transplant programs by the decreased number of lung donors, the scarcity of intensive care unit (ICU) beds and most importantly, the assumed worse prognosis of Covid‐19 in recipients during perioperative period. Despite no evidence has been published to suggest that lung transplant recipients were at high‐risk of acquiring the virus or developing severe Covid‐19, immunosuppression may worsen the prognosis of such infection in patient transplanted for end‐staged lung diseases.

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.

Summary Background Coronaviruses can induce the production of interleukin (IL)-1β, IL-6, tumour necrosis factor, and other cytokines implicated in autoinflammatory disorders. It has been postulated that anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19. We aimed to assess the off-label use of anakinra in patients who were admitted to hospital for severe forms of COVID-19 with symptoms indicative of worsening respiratory function. Methods The Ana-COVID study included a prospective cohort from Groupe Hospitalier Paris Saint-Joseph (Paris, France) and a historical control cohort retrospectively selected from the Groupe Hospitalier Paris Saint-Joseph COVID cohort, which began on March 18, 2020. Patients were included in the prospective cohort if they were aged 18 years or older and admitted to Groupe Hospitalier Paris Saint-Joseph with severe COVID-19-related bilateral pneumonia on chest x-ray or lung CT scan. The other inclusion criteria were either laboratory-confirmed SARS-CoV-2 or typical lung infiltrates on a lung CT scan, and either an oxygen saturation of 93% or less under oxygen 6 L/min or more, or aggravation (saturation ≤93% under oxygen 3 L/min) with a loss of 3% of oxygen saturation in ambient air over the previous 24 h. The historical control group of patients had the same inclusion criteria. Patients in the anakinra group were treated with subcutaneous anakinra (100 mg twice a day for 72 h, then 100 mg daily for 7 days) as well as the standard treatments at the institution at the time. Patients in the historical group received standard treatments and supportive care. The main outcome was a composite of either admission to the intensive care unit (ICU) for invasive mechanical ventilation or death. The main analysis was done on an intention-to-treat basis (including all patients in the anakinra group who received at least one injection of anakinra). Findings From March 24 to April 6, 2020, 52 consecutive patients were included in the anakinra group and 44 historical patients were identified in the Groupe Hospitalier Paris Saint-Joseph COVID cohort study. Admission to the ICU for invasive mechanical ventilation or death occurred in 13 (25%) patients in the anakinra group and 32 (73%) patients in the historical group (hazard ratio [HR] 0·22 [95% CI 0·11–0·41; p

Idiopathic pulmonary fibrosis (IPF) is characterized by relentlessly progressive lung function impairment that is consistently fatal in the absence of lung transplantation, as no curative pharmacological treatment exists. The pace of progression varies across patients, and acute life-threatening exacerbations occur unpredictably, causing further sharp drops in lung function. Recently introduced antifibrotic agents slow the pace of disease progression and may improve survival but fail to stop the fibrotic process. Moreover, the magnitude and kinetics of the response to these drugs cannot be predicted in the individual patient. These characteristics require that lung transplantation be considered early in the course of the disease. However, given the shortage of donor lungs, lung transplantation must be carefully targeted to those patients most likely to benefit. Current guidelines for lung transplantation listing may need reappraisal in the light of recent treatment advances. Patients with IPF often have multiple comorbidities such as coronary heart disease, frailty, and gastro-oesophageal reflux disease (GERD). Consequently, extensive screening for and effective treatment of concomitant conditions is crucial to appropriate candidate selection and outcome optimisation. A multidisciplinary approach is mandatory. Pulmonologists with expertise in IPF must work closely with lung transplant teams. Careful consideration must be given to preoperative optimisation, surgical technique, and pulmonary rehabilitation to produce the best post-transplantation outcomes.

Background. 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

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).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).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.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.• 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.

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 6-12 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) (p0.001 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.

Early acute renal failure (ARF) is a common complication after lung transplantation (LTx), and is associated with higher long-term mortality. Calcineurins inhibitors (CNIs) toxicity play a major role in ARF in the early phase post-LTx, and alternate nonnephrotoxic immunosuppressive (IS) regimen are needed in LTx. Belatacept, a novel immunosuppressant that blocks a T-cell costimulation pathway, is a nonnephrotoxic drug indicated as an alternative to CNIs in kidney Tx. In LTx, a few cases of CNI-belatacept conversion have been reported so far, only in the late long-term follow-up (>3 years post-LTx). We here report a single-center series of 4 LTx recipients converted to a belatacept primary IS-regimen in the early-postoperative period after LTx (month [M] 2, M2, M2, M5). Causes of conversion were persistent severe renal failure, due to: [1] thrombotic microangiopathy; [2] CNI toxicity/acute tubular necrosis (ATN); [3] ATN/FSglomerulosclerosis; [4] CNI toxicity. Following belatacept-conversion, acute rejection (AR) episodes occurred in 2 high immunologic risk recipients, with detection of donor-specific antibodies (asymptomatic AR both in patient 1 [graded A2B0] and patient 2 [A2Bx], which were both resolved with pulsed steroids). All 4 recipients remained with stable pulmonary function and significant renal function improvement at last available follow-up postbelatacept (M2, M3, M3, and M4). Outcome at 9 months postbelatacept, including incidence of AR and chronic lung allograft dysfunction, graft survival, and renal function outcome will be presented at the ERS 2017 congress.

Belatacept is increasingly used in lung transplant (LTx) recipients intolerant to calcineurin inhibitors (CNIs), with satisfactory outcome.1 We describe a case of fatal acute respiratory distress syndrome (ARDS) that developed in a single LTx recipient after starting a belatacept-based immunosuppres

BACKGROUND New methods of solid-phase assays, such as Luminex assay, with high sensitivity in detecting anti-human leukocyte antigen (HLA) antibodies (Abs), have increased the proportion of sensitized candidates waiting for lung transplantation (LTx). However, how to apply these results clinically during graft allocation is debated: strict exclusion of candidates with Luminex-positive results can lead to lost opportunities for Tx. We retrospectively analyzed the clinical impact of pre-LTx Luminex-detected Abs on post-LTx outcomes for patients who underwent LTx before the availability of Luminex assay. METHODS We analyzed data for 56 successive patients who underwent LTx before 2008 and were considered to not have anti-HLA Abs by then-available methods of detection at the date of their LTx. Pre-LTx sera from these patients were retested by Luminex assay. Using log-rank test, freedom from bronchiolitis obliterans syndrome (BOS) and graft survival were compared between patients with and without pre-LTx Luminex-detected anti-HLA Abs classes I and II and donor-specific Abs (DSA) classes I and II. RESULTS Freedom from bronchiolitis obliterans syndrome was lower, and mortality was higher for patients with than those without pre-LTx Luminex-detected DSA class II (P=0.004 and P=0.007, respectively) but did not differ for patients with and without DSA class I or anti-HLA Abs class I or II. CONCLUSIONS It suggests to avoid attributing graft with forbidden antigens to sensitized candidates with Luminex-detected DSA class II and to evaluate the role of specific posttransplantation protocols for LTx candidates who require emergency LTx.

Poor sleep quality is reported by candidates and recipients of lung transplantation (LTX) patients, but sleep pathologies are often unrecognized. High prevalence of sleep disordered breathing (SDB) in end-stage chronic respiratory diseases is reported. Aim: to describe sleep metrics and evaluate SDB-prevalence and characteristics in a french monocentric cohort of pre-LTX patients. Methods: Prospective, observational and analytical study of sleep and SDB in pre-LTX patients by polysomnography. Anthropometric, clinical, and pharmacological data were collected. Comparizons were performed by t-test and Chi2, significant p Results: 51 patients had a polysomnography (01/2013-12/2014), 21 patients had COPD, 27 lung fibrosis, 3 bronchietasis or asthma. Mean age (±SD) was 52.3 ± 9.6 y; BMI 24.8 ± 5.8 kg/M2. Mean TST was 378 ± 80 minutes; sleep efficiency 85 ± 13%; sleep stage N3 108 ± 51 min; REM sleep 17 ± 10%; aurousal-awakening index 17 ± 10 /h. AHI was 9.1 ± 11.0 /h. No patient had a history of SDB but moderate-severe SDB (AHI≥15/h) was found in 16% patients. SDB was obstructive. Prevalence of SDB was significantly higher in fibrosis (22%) compared to COPD (9%), maybe explained by significantly higher BMI and higher proportion of male. Conclusions: Objective sleep quality in pre-LTX transplant patients is poor with low TST, low sleep efficiency, and decreased REM sleep. SDB is less prevalent in our cohort than in previous, but still higher than in the general population, with significantly higher prevalence in fibrosis than in COPD.

Three weeks after single-lung transplantation for pulmonary fibrosis, a patient with high serum levels of de novo donor-specific antibodies received high-dose intravenous immunoglobulin (IVIG) infusion (scheduled dose: 2 g/kg on 2 days) to prevent antibody-mediated rejection. Within the first hours after completion of infusions, he experienced acute lung injury involving the transplanted lung. Given the clinical evolution and the absence of an alternative diagnosis, transfusion-related acute lung injury (TRALI) was diagnosed. The IVIG administered on each day was from the same batch. At day 110, because of an increase in the serum titers of donor-specific antibodies, IVIG therapy was reintroduced but from a different batch, with excellent clinical tolerance. The lung injury was explored biologically, but no mechanism was revealed. Given the increasing use of IVIG in solid-organ recipients, clinicians should be aware of possible TRALI after IVIG infusion.

International audience; Background. Lymphangioleiomyomatosis (LAM) is a rare disease, leading in some cases to end-stage respiratory failure. Lung transplantation (LT) represents a therapeutic option in advanced pulmonary LAM. Methods. We conducted a retrospective multicenter study of 44 patients who underwent LT for LAM at 9 centers in France between 1988 and 2006. Results. All patients were women with a mean age of 41 +/- 10 years at LT. There were 34 single-lung transplants and 11 bilateral transplants (one retransplantation). Prior clinical events related to LAM were present in 75% of the patients and previous thoracic surgical procedures were noted in 86.6% of cases. At the latest preoperative evaluation, 30 patients had an obstructive pattern (mean forced expiratory volume in 1 second: 26% 14% of predicted) and 15 had a combined restrictive and obstructive pattern, with a mean KCO=27%+/- 8.8% of predicted, PaO2=52.8 +/- 10.4 and PaCO2=42.6 +/- 9.8 mm Hg. Intraoperative cardiopulmonary bypass was required in 13 cases. The length of mechanical ventilation was 7.5 +/- 12.8 days. The median duration of follow-up was 37 months. The 1, 2, 5, and 10 years survival rates were 79.6%, 74.4%, 64.7%, and 52.4%, respectively. Extensive pleural adhesions were found in 21 patients leading to severe intraoperative hemorrhage. Postoperative LAM-related complications were pneumothorax in the native lung in five patients, chylothorax in six, bronchial dehiscence or stenosis in seven. There were two cases of recurrence of LAM. Conclusion. Despite a high morbidity mainly caused by previous surgical interventions and disease-related complications, LT is a satisfactory therapeutic option for end-stage respiratory failure in LAM.

Background. Thrombotic microangiopathy may develop after solid organ transplantation, but it is usually not associated with severe deficiency in von Willebrand factor-cleaving metalloprotease (ADAMTS 13) activity. Methods. We present the cases of two lung transplant recipients who experienced a thrombotic microangiopathy associated with an acquired severe (

Summary Background Initial management of primary spontaneous pneumothorax (PSP) remains a topic of debate. Recent guidelines recommend needle aspiration as the initial strategy for large PSP, but chest tube drainage is still widely used. Methods Over a six-year period, we used needle aspiration in all cases of large PSP at our center to assess this technique's efficacy in real-life clinical practice. Our prospective study in the pulmonary intensive care unit of a 680-bed university hospital included patients with a PSP greater than 20%, as estimated by the Light's index. Needle aspiration, performed after local anesthesia, used a plastic intravenous catheter. If it failed, we performed thoracic drainage. Results The study included 35 patients. The initial success rate of needle aspiration was 69% (n=24/35), the one-week success rate 63% (n=22/35), and the one-year rate 51% (n=18/35). Tolerance of needle aspiration was good except for transient vagal reaction in four patients. No risk factors (age, body mass index, delay before hospitalization, previous pneumothorax, or Light index at inclusion) predicted initial failure of needle aspiration. Conclusion Our results confirmed that needle aspiration is an attractive therapeutic option for patients with large PSP: success was observed in approximately two thirds of cases.

Lung volume reduction surgery (LVRS) has been shown to improve lung function and exercise tolerance in patients with severe emphysema. Some predictors of poor outcome have been described but the role of alpha1-antitrypsin (alpha1-AT) deficiency is still not well known. The aim of this study was to analyze the results of unilateral LVRS in our center according to the alpha1-AT status. The results of LVRS in 17 deficient patients and 35 nondeficient patients were analyzed at 3-6 months and 1 year after surgery. Compared with baseline, a significant improvement of FEV1, partial pressure in arterial blood (PaO2), dyspnea score and walking distance was observed in the two groups at 3-6 months after surgery and the studied parameters remained significantly improved at 1 year in the nondeficient group. By contrast, PaO2 and walking distance returned towards baseline in the deficient group at 1 year whereas improvement of FEV1 and dyspnea score was persistent. Mean values of FEV, at baseline, 3-6 months, and 1 year were 22 +/- 6%, 29 +/- 11%, and 26 +/- 9% and 28 +/- 12%, 38 +/- 17%, and 40 +/- 17% predicted in the deficient group and in the non-deficient group, respectively. In conclusion, the functional benefit is short-lasting in alpha1-AT deficient patients after unilateral LVRS.

Lung transplantation has been developed over the last fifteen years as a therapeutic option for different forms of advanced-stage lung disease. Idiopathic pulmonary fibrosis is a good indication. For these patients, single lung transplantation is usually preferred, bilateral lung transplantation to a lesser extent. Survival is similar for these two types of transplantation. The post-transplantation survival in patients with pulmonary fibrosis is about 65-70% at one year and 40% at five years. This rate is lower than observed for COPD or cystic fibrosis. If there are no complications, the patient can recover nearly normal lifestyle. Among the different complications, reimplantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict.

Study objectives: To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). Design: Retrospective study. Setting: One center in France. Patients: Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. Results: Mean age was 54.6 years. Pulmonary function test results were as follows: FEV1, 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to PaO2 and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV1, 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean PaO2, 46.2 mm Hg). Conclusion: While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators. (CHEST 2005; 127:1531–1536)

Several types of primary disease may recur after lung transplantation, but recurrence of pulmonary emphysema has so far never been published. We report the case of a 49-year-old white male who underwent single lung transplantation for emphysema related to alpha-1 antitrypsin deficiency and to superimposed smoking. The postoperative course was complicated by several rejection episodes. Subsequently, the patient remained stable without evidence of graft dysfunction for more than 10 years, but he resumed light smoking at 8 years after transplant. At 11 years after transplant, although the patient was still asymptomatic and had a stable lung function, recurrence of emphysema on the grafted side was diagnosed on computerized tomography of the thorax. One year later, the patient began to experience a moderate decline in lung function. Two separate bronchoalveolar lavages performed after the onset of the recurrence disclosed a significant elastolytic activity related to neutrophil serine-elastase in lavage fluid. In summary, we describe a case of recurrence of pulmonary emphysema in a patient with alpha-1 antitrypsin deficiency. The resumption of smoking has probably played a central role in the presence of elastolytic activity in lavage fluid and in the recurrence of emphysema.

Background Although lung retransplantation is the only definitive therapeutic option in lung recipients with bronchiolitis obliterans syndrome (BOS), its value remains a considerable source of controversy. We report our experience of retransplantation for BOS performed in our center since 1988. Methods Between 1988 and 2002, 15 lung retransplantations for BOS were performed. Patient survival, causes of death, long-term functional status, and BOS recurrence rate were reviewed. Results The retransplantation procedure was single-lung transplantation (SLT) in all cases (ipsilateral SLT, n = 4; contralateral SLT, n = 9; SLT after previous double-lung transplantation, n = 2). The median time between primary lung transplantation and retransplantation was 31 months (range, 12 to 39 months). The median follow-up duration of the 10 patients surviving beyond 6 months was 49.5 months (range, 16.5 to 105 months), and 5 patients were followed up for > 5 years. Actuarial survival rates at 1 year, 2 years, and 5 years after retransplantation were 60%, 53%, and 45%, respectively. Ten patients died during long-term follow-up, 6 of them from infection (60%). The retained graft was the initial site of the fatal infection in four of these six patients (66%). Two other patients with a retained graft experienced disabling chronic purulent expectoration arising from the old graft. In the 10 patients surviving beyond 6 months, mean best FEV 1 was 58 ± 13% of predicted (± SD), and actuarial freedom from BOS (stage 1, 2, or 3) at 1 year, 3 years, and 5 years was 90%, 72%, and 66%, respectively. Conclusion Lung retransplantation offered a viable therapeutic option for selected lung recipients with BOS. Given the morbidity and mortality related to the retained graft, we now favor replacement of the primary graft when retransplantation is considered.

Pulmonary alveolar proteinosis may occur after lung transplantation and may be a cause of respiratory deterioration http://ow.ly/tlrl307KlKY

Several cases of non-traumatic pulmonary haematoma have been reported in the literature. However, very few of them are related to anticoagulation therapy. The authors report two cases of pulmonary haematoma caused by oral anticoagulant therapy without any underlying pathological lesion. The evolution was fatal in the first case, whereas a slow spontaneous resolution of the haematoma was noted in the second. Non-traumatic pulmonary haematoma can be a complication of oral anticoagulation and should be considered in the differential diagnosis of pulmonary densities in this setting.

Breathing is maintained and controlled by a network of automatic neurons in the brainstem that generate respiratory rhythm and receive regulatory inputs. Breathing complexity therefore arises from respiratory central pattern generators modulated by peripheral and supra-spinal inputs. Very little is known on the brainstem neural substrates underlying breathing complexity in humans. We used both experimental and theoretical approaches to decipher these mechanisms in healthy humans and patients with chronic obstructive pulmonary disease (COPD). COPD is the most frequent chronic lung disease in the general population mainly due to tobacco smoke. In patients, airflow obstruction associated with hyperinflation and respiratory muscles weakness are key factors contributing to load-capacity imbalance and hence increased respiratory drive. Unexpectedly, we found that the patients breathed with a higher level of complexity during inspiration and expiration than controls. Using functional magnetic resonance imaging (fMRI), we scanned the brain of the participants to analyze the activity of two small regions involved in respiratory rhythmogenesis, the rostral ventro-lateral (VL) medulla (pre-Botzinger complex) and the caudal VL pons (parafacial group). fMRI revealed in controls higher activity of the VL medulla suggesting active inspiration, while in patients higher activity of the VL pons suggesting active expiration. COPD patients reactivate the parafacial to sustain ventilation. These findings may be involved in the onset of respiratory failure when the neural network becomes overwhelmed by respiratory overload We show that central neural activity correlates with airflow complexity in healthy subjects and COPD patients, at rest and during inspiratory loading. We finally used a theoretical approach of respiratory rhythmogenesis that reproduces the kernel activity of neurons involved in the automatic breathing. The model reveals how a chaotic activity in neurons can contribute to chaos in airflow and reproduces key experimental fMRI findings.

Mycobacterium genavense is recognized as a life-threatening pathogen in severely immunocompromised patients, mostly in those with advanced human immunodeficiency virus infection. We report a case of M. genavense infection in a lung-transplant recipient with late-onset death occurring from disseminated infection. In human immunodeficiency virus-negative patients, there exist only about 10 reports of disseminated M. genavense infection in immunocompromised hosts; and to our knowledge, this is a first reported case of M. genavense infection after a lung transplant. Diagnosis of M. genavense was obtained only with nucleic acid-based identification technique, as frequently observed in a few cases of human immunodeficiency virus-negative patients. A striking feature was the recurrence of this infection in our patient after a seemingly infection-free period of 3 years. Because M. genavense infection can be life-threatening, clinicians must be aware of the frequent requirement for nucleic-acid-based identification for its diagnosis.

Pulmonary hypertension (PH) carries a poor prognosis in interstitial lung diseases (ILDs). Its prevalence depends on the underlying condition, the most common being idiopathic pulmonary fibrosis, connective tissue disease-related ILD, sarcoidosis, and pulmonary Langerhans cell histiocytosis (PLCH). Although hypoxic vasoconstriction and loss of pulmonary capillaries are important in the pathogenesis of ILD-associated PH, other mechanisms may play a role, including the release of diverse cytokines and growth factors during fibrogenesis which induce vascular remodeling. This intrinsic vasculopathy may prevail in the venous side in sarcoidosis and PLCH. As a result, a small proportion of ILD patients may exhibit ‘out of proportion’ PH, i.e. more severe than expected from functional impairment (mean pulmonary artery pressure > 35–40 mm Hg). The accuracy of echocardiography for the detection of PH is weak in ILDs. Management of ILD-associated PH mainly relies on supplemental oxygen and lung transplantation in otherwise eligible patients. Treatments targeted to the underlying ILD do not usually affect the course of PH, with the exception of rare cases of nonfibrotic sarcoidosis responding to corticosteroids. Data on the efficacy and safety of pulmonary arterial hypertension-specific agents are lacking. Further controlled trials are warranted and should integrate the concept of disproportionate PH in their design.

Objective: This study aimed to describe and to analyze early severe digestive complications (ESDC) after lung transplantation (LT) in our center. Methods: A retrospective study included 351 patients, who underwent LT without cardiopulmonary bypass (CPB) at our center between March 1988 and December 2009. There were 86 double LTs and 265 single LTs. ESDCs were defined as complications (1) occurring during the first 30 days after transplantation or during initial hospitalization if longer; (2) involving the gastrointestinal tract; and (3) jeopardizing survival or requiring invasive therapeutic procedure. Patients’ characteristics, associated risk factors, and influence of ESDC on early outcome have been analyzed. Results: During the first 30 days after LT or initial hospitalization if longer, 26 ESDCs occurred in 26 patients (rate 7.4%, sex ratio M/F 66%, mean age 56 6 years). This included 10 acute cholecystitis (38%), four angiocholitis (15%), three perforated gastroduodenal ulcers (11%), three digestive perforations (11%), two intestinal occlusions (8%), two mesenteric ischemia (8%), and two acute pancreatitis (8%). ESDC occurred after a mean postoperative follow-up of 14 days (5—46), required emergency surgical treatment in 20 cases (77%), significantly prolonged the mean duration of hospitalization (96 days with ESDC vs 55 days without ESDC, p < 0.0001), and was responsible for death in five cases (19%). Surgical treatment included cholecystectomy (n = 11), bowel resection (n = 3), ulcer surgery (n = 2), subtotal colectomy (n = 2), Hartmann procedure (n = 1), and open coelioscopy (n = 1). Age and bilateral LTwere found to be significant risk factors for ESDC in both uni- and multivariate analyses. Conclusion: ESDC occurred in 7.4% of patients after LTwithout CPB, and was responsible for longer in-hospital stay. Relevant risk factors included older age and bilateral LT, interfering with current debate regarding recipients’ selection and procedure’s choice. # 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Bronchovascular fistula is a rare complication after lung transplantation, which usually has a fatal outcome. We describe the case of successful surgical treatment of bronchovascular fistula of the left upper pulmonary vein and the left main bronchus.

We report the case of a man who underwent a left-lung transplantation for pulmonary fibrosis and who developed deterioration of his respiratory condition at Day 16 post-operatively, with marked hypoxemia not explained by the usual early respiratory complications of lung transplantation. Contrast-enhanced transthoracic echocardiography identified a patent foramen ovale with massive spontaneous right-to-left shunting. As for the pathogenesis of this right-to-left shunting, we found no evidence supporting an elevation of right-side pressures, with the redirection of the inferior vena cava flow toward the patent foramen ovale being the suspected mechanism. We conclude that delayed reopening of the patent foramen ovale leading to massive right-to-left shunting is a possible complication after lung transplantation.

International audience; Background: Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other sotid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time. Methods: In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients. Results: Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes. Conclusions: We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.

Background There is no recognized medical treatment for chronic pulmonary aspergillosis (CPA) apart from surgery in patients with simple aspergilloma. To evaluate the efficacy of voriconazole in this setting, we conducted a retrospective multicenter study over a 3-year period. Methods For inclusion in the study, patients had to have received voriconazole for treatment of confirmed or probable CPA with a follow-up of at least 6 months. Clinical, radiologic, and mycologic data were collected at baseline, every 2 to 3 months, and at the end of treatment or at the date point. Results Twenty-four patients were included in the study, among which 9 patients presented with chronic cavitary pulmonary aspergillosis and 15 presented with chronic necrotizing pulmonary aspergillosis (CNPA). Voriconazole was given as a first-line treatment to 13 patients. The median duration of treatment and follow-up were 6.5 and 10 months, respectively. Three patients had to stop treatment with voriconazole because of toxicity. Symptoms and imagery findings were improved in 16 of 24 patients and 17 of 24 patients, respectively, at the end of follow-up. Mycology, which was positive at baseline in 21 of 23 patients, was negative in 18 of 19 patients at the end of follow-up; serologic test results were also negative in 6 of 19 evaluable patients, all of whom had CNPA. Improved radioclinical findings and mycologic eradication were observed at the end of follow-up in 11 of 19 patients (58%). Patients in whom the disease was controlled had a significantly longer median duration of treatment than patients in whom it was uncontrolled (9 vs 6 months, respectively; p=0.04). Conclusion Voriconazole provides effective treatment of CPA with an acceptable level of toxicity.

In patients presenting with idiopathic pulmonary fibrosis (IPF), modifications of pulmonary vessels are well defined in fibrotic areas but have not been accurately assessed in the intervening patches of preserved lung. Moreover, the relation between pulmonary vessel lesions and pulmonary hemodynamics is not well known. We therefore designed a retrospective study on lung explant specimens from 26 patients with a firm diagnosis of IPF who had undergone lung transplantation. Our aim was to (1) describe the vascular lesions, especially in preserved lung areas, and (2) correlate them with pulmonary hemodynamics. In dense fibrotic zones, thickening of the arterial and venous wall with severe luminal narrowing was present in each patient. In architecturally preserved lung zones, occlusion of venules and small pulmonary veins was observed in 65% of the patients, although there were only mild changes of muscular pulmonary arteries. We found a significant positive correlation between the macroscopic extent of lung fibrosis and mean pulmonary artery pressure, but we failed to find a relation between mean pulmonary artery pressure and venous/venular lesions in nonfibrotic areas. Our study points out that in many patients with IPF, nonfibrotic lung areas demonstrate an occlusive venopathy, the signification of which remains undetermined.

International audience; Background. Lung transplantation (LT) may represent a therapeutic option in case of advanced pulmonary Langerhans' cell histiocytosis (PLCH). Little is known however about the characteristics of the patients considered for LT or its results. Methods. We conducted a retrospective multicenter study by questionnaire on 39 patients who underwent LT for end-stage PLCH at seven centers in France. Results. Of the 39 patients, 15 received single lung transplantation, 15 double lung transplantation and 9 heart-lung transplantation. At evaluation, extrapulmonary involvement was present in 31% of the patients, pulmonary hypertension (PAPm > 25 mm Hg) was observed in 92% of cases and was moderate-to-severe (PAPm >= 35 mm Hg) in 72.5%. The survival was 76.9% at 1 year, 63.6% at 2 years, 57.2% at 5 years, and 53.7% at 10 years. Recurrence of the disease occurred in eight cases (20.5%) with no impact on the survival rate. The sole risk factor for recurrence of the disease was the presence of preoperative extrapulmonary involvement. Conclusion. Severe pulmonary hypertension is a common feature in patients with end-stage PLCH. Given the good postransplant survival rate and despite a recurrence rate of the disease of approximately 20% after LT, we conclude that LT is a therapeutic option in this setting.

iloprost has shown vasodilating potency similar to that of inhaled NO in secondary PHT, and it actually appears to be superior in primary PHT. The intraoperative use of aerosolized prostanoids has been reported in only a few surgical cases, probably because of concerns regarding impaired platelet function. Both inhaled prostacyclin and NO are associated with impaired platelet aggregation in vitro but are without signs of platelet dysfunction in vivo. Increases in mediastinal drainage or transfusion requirements were not observed in any of our cases. In conclusion, the intraoperative use of aerosolized iloprost is a clinical alternative to NO that warrants further comparative studies. References

Of the different respiratory disorders that complicate the course of polymyositis, diaphragmatic weakness is one that is seldom described and most often suspected rather than confirmed. We report a case of severe diaphragmatic weakness as a cause of acute respiratory failure revealing a polymyositis. The diaphragmatic involvement was proven by a very low esophageal pressure in response to cervical magnetic stimulation of the phrenic nerve. Corticosteroids and intravenous gammaglobulin, combined with mechanical ventilation, achieved a progressive recovery of diaphragmatic weakness.

Patients with end-stage idiopathic pulmonary fibrosis (IPF) are increasingly having bilateral rather than single-lung transplantation. In this study, after adjustment for baseline differences, surv...