Sandrine Hirschi

Disseminated Trichosporon mycotoxinivorans, Aspergillus fumigatus, and Scedosporium apiospermum coinfection after lung and liver transplantation in a cystic fibrosis patient.

ABSTRACT Trichosporon mycotoxinivorans is a novel pathogen recently found in cystic fibrosis patients. We report the first case of a disseminated fatal infection with T. mycotoxinivorans associated with invasive Aspergillus fumigatus and Scedosporium apiospermum infection after lung and liver transplantation in a cystic fibrosis patient.

Severe hematologic complications after lung transplantation in patients with telomerase complex mutations

BACKGROUND Mutations in the telomerase complex (TERT and TR) are associated with pulmonary fibrosis and frequent hematologic manifestations. The aim of this study was to characterize the prognosis of lung transplantation in patients with TERT or TR mutations. METHODS Patients with documented TERT or TR mutations who received a lung transplant between 2007 and 2013 in France were identified via an exhaustive search of the lung transplantation network, one expert genetic laboratory, and the clinical research network on rare pulmonary diseases. RESULTS There were 9 patients (7 men) with TERT (n = 6) or TR (n = 3) mutations who received a single (n = 8) or a double (n = 1) lung transplant for pulmonary fibrosis. Median age was 50 years (range, 35-61 years) at diagnosis and 52 years (range, 37-62 years) at the time of lung transplantation. Thrombocytopenia was present in 7 patients before lung transplantation. After lung transplantation, 6 patients developed myelodysplasia and/or bone marrow failure, directly contributing to death in 4 cases. Anemia was observed in 9 patients, and neutropenia was observed in 3 patients. The median survival after lung transplantation was 214 days (range, 59-1,709 days). CONCLUSIONS Patients with mutations of the telomerase complex are at high risk of severe hematologic complications after lung transplantation, in particular, bone marrow failure. Specific recommendations should be developed for appropriate guidance regarding hematologic risk assessment before transplantation and management of the post-transplantation immunosuppressive regimen.

Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss) ☆: A study of 157 patients by the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires and the European Respiratory Society Taskforce on eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

OBJECTIVE To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA. METHODS Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease. RESULTS The study population included 157 patients (mean age 49.4±14.1), with a follow-up of 7.4±6.4years. Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glomerulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic vasculitis (p=0.005) and with the presence of ANCA (p<0.001). Overall, 59% of patients had polyangiitis as defined by definite vasculitis, strong surrogate of vasculitis, mononeuritis multiplex, and/or ANCA with at least one systemic manifestation other than ENT or respiratory. Patients with polyangiitis had more systemic manifestations including arthralgias (p=0.02) and renal disease (p=0.024), had higher peripheral eosinophilia (p=0.027), and a trend towards less myocarditis (p=0.057). Using predefined criteria of vasculitis and surrogates of vasculitis, ANCA alone were found to be insufficient to categorise patients with vasculitis features. CONCLUSION We suggest a revised nomenclature and definition for EGPA and a new proposed entity referred to as hypereosinophilic asthma with systemic (non vasculitic) manifestations.

Clinical usefulness of oral immunoglobulins in lung transplant recipients with norovirus gastroenteritis: a case series.

Viral gastroenteritis causing diarrhea is a common complication observed in lung transplant recipients. Differently from the mild and typically self-limited disease seen in immunocompetent subjects, immunocompromised patients frequently have a more severe course. Norovirus and rotavirus are among the leading causes of severe gastroenteritis in transplant recipients. Specific treatment is unavailable, although good supportive treatment can significantly reduce morbidity. Previous studies have suggested that oral immunoglobulins may be used for the treatment of acute viral gastroenteritis after solid-organ transplantation. Herein, we conducted a retrospective chart review of 12 lung transplant recipients with norovirus-induced gastroenteritis who were treated with oral immunoglobulins for 2 days. Eleven patients were successfully treated, whereas 1 subject was only mildly improved. Four patients had at least 1 recurrence. No significant adverse effects were observed. We conclude that oral immunoglobulins may be clinically useful for lung transplant recipients with norovirus-induced gastroenteritis.

Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

The respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) have not been studied in detail. In this retrospective multicentre study, EGPA was defined by asthma, eosinophilia and at least one new onset extra-bronchopulmonary organ manifestation of disease. The study population included 157 patients (mean±sd age 49.4±14.1 years), with a mean±sd blood eosinophil count of 7.4±6.4×109 L−1 at diagnosis. There was a mean±sd of 11.8±18.2 years from the onset of asthma to the diagnosis of EGPA, of 1.4±8.4 years from the first onset of peripheral eosinophilia to the diagnosis of EGPA, and of 7.4±6.4 years from EGPA diagnosis to the final visit. Despite inhaled and oral corticosteroid treatment, the severity of asthma increased 3–6 months before the onset of the systemic manifestations. Asthma was severe in 57%, 48%, and 56% of patients at diagnosis, at 3 years, and at the final visit, respectively. Persistent airflow obstruction was present in 38%, 30%, and 46% at diagnosis, at 3 years, and at the final visit, respectively. In EGPA, asthma is severe, antedates systemic manifestations by a mean of 12 years, and progresses to long-term persistent airflow obstruction despite corticosteroids in a large proportion of patients, which affects long-term management and morbidity. In EGPA, asthma is severe and progresses to persistent airflow obstruction despite corticosteroids in many patients http://ow.ly/8uf8301KSoT

Mass Spectrometry–based Proteomic Analysis: A Good Diagnostic Tool for Cystic Lung Light Chain Deposition Disease

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Dichotomy in pulmonary graft-versus-host disease evident among allogeneic stem-cell transplant recipients undergoing lung transplantation

Allogeneic haematopoietic stem-cell transplantation (HSCT) has become a life-saving treatment option for numerous benign and malignant diseases, with more than 14 500 procedures being performed annually in Europe alone [1]. Late-onset noninfectious pulmonary complications (NIPCs) have emerged as the main hurdle to long-term survival, affecting up to 26% of HSCT recipients and conferring 2- and 5-year survival rates of 44% and 13%, respectively [2, 3]. Interstitial lung disease is a common, largely unrecognised feature of pulmonary GvHD after stem cell transplant http://ow.ly/DWP4307mO3i

Lung Transplantation for Advanced Cystic Lung Disease Due to Nonamyloid Kappa Light Chain Deposits

RATIONALE Cystic lung light chain deposition disease (LCDD) is a severe and rare form of nonamyloid kappa light chain deposits localized in the lung, potentially leading to end-stage respiratory insufficiency. OBJECTIVES To assess the outcome after lung transplantation (LT) in this setting with particular attention to disease recurrence. METHODS We conducted a retrospective multicenter study of seven patients who underwent LT for cystic lung LCDD in France between September 1992 and June 2012 in five centers. MEASUREMENTS AND MAIN RESULTS In total, five females and two males (mean age, 39.1 ± 5.3 yr) underwent one single LT or seven double LT (one retransplantation). Before LT, the patients showed a constant obstructive ventilatory pattern with low carbon monoxide diffusing capacity and resting hypoxemia. Lung computed tomography revealed widespread cysts with occasional micronodulations. No extrapulmonary disease or plasma cell neoplasm was detected. The serum-free kappa/lambda light chain ratio was increased in three cases. The median follow-up after LT was 56 months (range, 1-110 mo). Kaplan-Meier survival was 85.7, 85.7, and 64.3% at 1, 3, and 5 years, respectively. Three patients died from multiorgan failure (n = 1), chronic rejection (n = 1), and breast cancer (n = 1) at 23 days, 56 months, and 96 months, respectively. At the end of follow-up, no patients showed recurrence on imaging or histopathology. CONCLUSIONS This small case series confirms that cystic lung LCDD is a severe disease limited to the lung, affecting mostly young females. LT appears to be a good therapeutic option allowing for satisfactory long-term survival. We found no evidence of recurrence of the disease after LT.

Gastric distension is a contributing factor to pneumonia after pulmonary resection

OBJECTIVES The literature concerning relations between thoracic surgery and digestive motility is poor. The aim of our study was two-fold: (i) to show a link between thoracic surgery and gastric distension and (ii) between post-operative pneumoniae and gastric distension. METHODS A retrospective analysis was conducted in 262 patients who had undergone a thoracotomy for lung resection between January and December 2007. Transverse diameter of the stomach was measured on chest X-rays performed on Day 0 and on Day 1. Gastric distension was defined as a ratio (R) D1/D0 higher than 1.3 (min: 0.5; max: 4.1). Three groups were defined: Group 1 (absence of distension) R < 1.3; Group 2 (moderate distension) 1.3 ≤ R < 2.3; Group 3 (major distension) R ≥ 2.3. International criteria of the Center of Disease Control were used to define pneumonia. Appropriate statistical tests were carried out. RESULTS There were 73 women (27.9%) and 189 men (72.1%), ages ranged from 20 to 83 years (average: 59.9 years). As for gastric distension, 194 patients (74.04%) constituted Group 1, 53 (20.23%) Group 2 and 15 (5.73%) Group 3. Pneumonectomy significantly increased the incidence of gastric distension on Day 1 (P = 0.04). The side, mediastinal lymphadenectomy and personal medical past history of upper gastro-intestinal tract surgery had no statistically significant influence on the incidence of gastric distension. Univariate analysis showed that patients with gastric distension on D1 had significantly more infectious pneumonia on Day 5 (P < 0.0001): 16 (8.25%) patients in Group 1, vs 14 (26.41%) in Group 2 and 7 (46.67%) in Group 3. Furthermore, on Day 5, 33.33% (n = 8) of pneumectomies had pneumonia, against 12.18% (n = 29) of patients who had undergone another type of surgery (P = 0.01). On multivariate analysis, gastric distension was an independent predictive factor of infectious pneumonia on Day 5 (Group 3: odds ratio = 16.127 [4.267; 60 959], P < 0.0001). CONCLUSIONS We established, in our cohort of patients, a link between pneumonectomy and gastric distension on Day 1 and infectious pneumonia on Day 5. A prospective multicentre study would be desirable to verify these data.

Early and Late Atrial Arrhythmias After Lung Transplantation - Incidence, Predictive Factors and Impact on Mortality -

BACKGROUND Atrial arrhythmias (AAs) are frequent after lung transplantation (LT) and late postoperatively. Several predictive factors of early postoperative AAs after LT have been identified but those of late AAs remain unknown. Whether AA after LT affects mortality is still being debated. This study assessed in a large cohort of LT patients the incidence of AAs early and late after surgery, their predictive factors and their effect on mortality.Methods and Results:We studied 271 consecutive LT patients over 9 years. Mean follow-up was 2.9±2.4 years. 33% patients developed postoperative AAs. Age (odds ratio (OR) 2.35; confidence interval (CI) [1.31-4.24]; P=0.004) and chronic obstructive pulmonary disease (OR 2.13; CI [1.12-4.03]; P=0.02) were independent predictive factors of early AAs. Late AAs occurred 2.2±2.7 years after transplant in 8.8% of the patients. Pretransplant systolic pulmonary arterial pressure (PTsPAP) was the only independent predictive factor of late AA (OR 1.028; CI [1.001-1.056]; P=0.04). Double LT was associated with long-term freedom from atrial fibrillation (AF) but not from atrial flutter (AFL). Early and late AAs after surgery had no effect on mortality. Double LT was associated with better survival. CONCLUSIONS Early AA following LT is common in contrast with the low occurrence of late, often organized, AA. Early and late AAs do not affect mortality. PTsPAP is an independent predictor of late AA. Double LT protects against late AF but not AFL.