Alternatively, WLL can be performed in a hyperbaric chamber [9]

Alternatively, WLL can be performed in a hyperbaric chamber [9]. The prognosis of solid organ transplant recipients with PAP remains largely unknown. reveals patchy, ground-glass opacities with interlobular septal thickening in a characteristic crazy paving pattern [1]. Open lung biopsy has historically been the gold standard for PAP diagnosis; however, up to 75% of cases can be diagnosed via BAL [1]. To date, 9 reports have described 11 solid organ recipients who developed PAP. Of these, 3 were lung transplant recipients [2, 3] and 8 were kidney transplant recipients [4C10]. Nine of FGF21 these patients were on immunosuppressive regimens that included mammalian target of rapamycin- (mTOR-) inhibitors (8 were treated with sirolimus [2, 5C7, 9] and 1 was treated with everolimus [4]), while 2 were on mTOR-inhibitor sparing regimens that included prednisone, a calcineurin inhibitor, and mycophenolate mofetil (MMF) [3, 10]. Here we report our experience with a lung transplant recipient treated with prednisone, MMF, and tacrolimus who developed PAP that worsened when MMF was replaced with everolimus. 2. Case Presentation The patient was a 67-year-old man who underwent bilateral lung transplantation for smoking-related chronic obstructive lung disease. His posttransplant course was complicated by mildly reduced left ventricular systolic function with an ejection fraction of 40%, impaired left ventricular relaxation with diastolic dysfunction, prostate cancer with radiation proctitis, and calcineurin inhibitor-induced renal insufficiency. He was maintained on a standard three-drug immunosuppressive regimen of prednisone, tacrolimus, and MMF for 35 months after transplant but was ultimately transitioned to a combination of prednisone, lower-dose tacrolimus, and everolimus to minimize the risk of prostate cancer recurrence and to slow the progression of Pyrazofurin calcineurin inhibitor-induced renal insufficiency. The patient experienced good allograft function for 3.5 years after transplant as evidenced by stable spirometry and absence of respiratory symptoms. Radiographically, he developed diffuse, centrilobular ground-glass nodules and small pleural effusions 25 months after transplant (Figure 1). The etiology of these nodules and effusions was unknown, despite multiple bronchoscopies with BAL fluid analysis and transbronchial biopsies, all of which showed normal lung parenchyma and no evidence of infection. At 41 months after lung transplant (16 months after onset of ground-glass nodules and 6 months after initiation of everolimus therapy), the patient returned to our clinic with worsening dyspnea; declines of 16% and 20% in FEV1 and FVC, respectively; and a crazy paving pattern on HRCT (Figure 2). Open in a separate window Figure 1 High-resolution axial computed tomography scan of the chest shows ground-glass centrilobular nodules before initiation of everolimus therapy. Open in a separate window Figure 2 High-resolution axial computed tomography scan of the chest shows diffuse ground-glass abnormalities with interlobular septal Pyrazofurin thickening in the characteristic crazy paving pattern after initiation of everolimus therapy. The patient was hospitalized and underwent bronchoscopy with BAL, which returned milky fluid characteristic of PAP. A right middle lobe biopsy via video-assisted thoracic surgery revealed pink proteinaceous material filling the air spaces with diastase-resistant periodic acid-Schiff (PAS) stain-positive globular inclusions consistent with PAP (Figure 3). Cultures and special stains (i.e., gram stain and methenamine fungal stain) showed no evidence of infection. Everolimus therapy was halted and the patient was treated with granulocyte-macrophage colony stimulating factor (GM-CSF), with some symptomatic and radiographic improvement. Serum lactate dehydrogenase was not measured and although anti-GM-CSF antibody titers were sent for testing, the results were never available. The patient’s hospital course was further complicated by serotonin syndrome with hemodynamic instability that prohibited whole-lung lavage (WLL), nonoliguric renal failure requiring hemodialysis, and sepsis due Pyrazofurin to acalculous cholecystitis that ultimately led to his death after a month-long hospitalization. Postmortem reanalysis of transbronchial biopsies obtained before initiation of everolimus therapy revealed scattered diastase-resistant PAS-positive globular inclusions within a background of pink granular material in 1 of 5 biopsies, consistent with PAP in the absence of mTOR-inhibitor therapy (Figure 4). Open in a separate window Figure.He may have suffered from immunosuppression-induced macrophage dysfunction and resultant mild PAP that worsened significantly with the addition of an mTOR-inhibitor. Although the exact mechanism of mTOR-inhibitor-associated PAP is unclear, an association between this drug class and development of PAP likely exists, as our case is the seventh report of this complication in solid organ transplant recipients treated with mTOR-inhibitors. been the gold standard for PAP diagnosis; however, up to 75% of cases can be diagnosed via BAL [1]. To date, 9 reports have described 11 solid organ recipients who developed PAP. Of these, 3 were lung transplant recipients [2, 3] and 8 were kidney transplant recipients [4C10]. Nine of these patients were on immunosuppressive regimens that included mammalian target of rapamycin- (mTOR-) inhibitors (8 were treated with sirolimus [2, 5C7, 9] and 1 was treated with everolimus [4]), while 2 were on mTOR-inhibitor sparing regimens that included prednisone, a calcineurin inhibitor, and mycophenolate mofetil (MMF) [3, 10]. Here we report our experience with a lung transplant recipient treated with prednisone, MMF, and tacrolimus who developed PAP that worsened when MMF was replaced with everolimus. 2. Case Presentation The patient was a 67-year-old man who underwent bilateral lung transplantation for smoking-related chronic obstructive lung disease. His posttransplant course was complicated by mildly reduced left ventricular systolic function with an ejection fraction of 40%, impaired left ventricular relaxation with diastolic dysfunction, prostate cancer with radiation proctitis, and calcineurin inhibitor-induced renal insufficiency. He was maintained on a standard three-drug immunosuppressive regimen of prednisone, tacrolimus, and MMF for 35 months after transplant but was ultimately transitioned to a combination of prednisone, lower-dose tacrolimus, and everolimus to minimize the risk of prostate cancer recurrence and to slow the progression of calcineurin inhibitor-induced renal insufficiency. The patient experienced good allograft function for 3.5 years after transplant as evidenced by stable spirometry and absence of respiratory symptoms. Radiographically, he developed diffuse, centrilobular ground-glass nodules and small pleural effusions 25 months after transplant (Figure 1). The etiology of these nodules and effusions was unknown, despite multiple bronchoscopies with BAL fluid analysis and transbronchial biopsies, all of which showed normal lung parenchyma and no evidence of infection. At 41 months after lung transplant (16 months after onset of ground-glass nodules and 6 months after initiation of everolimus therapy), the patient returned to our clinic with worsening dyspnea; declines of 16% and 20% in FEV1 and FVC, respectively; and a crazy paving pattern on HRCT (Figure 2). Open in a separate window Figure 1 High-resolution axial computed tomography scan of the chest shows ground-glass centrilobular nodules before initiation of everolimus therapy. Open in a separate window Figure 2 High-resolution axial computed tomography scan of the chest shows diffuse ground-glass abnormalities with interlobular septal thickening in the characteristic crazy paving design after initiation of everolimus therapy. The individual was hospitalized and underwent bronchoscopy with BAL, which came back milky fluid quality of PAP. The right middle lobe biopsy via video-assisted thoracic medical procedures revealed red proteinaceous material filling up the air areas with diastase-resistant regular acid-Schiff (PAS) stain-positive globular inclusions in keeping with PAP (Amount 3). Civilizations and special discolorations (i.e., gram stain and methenamine fungal stain) demonstrated no proof an infection. Everolimus therapy was halted and the individual was treated with granulocyte-macrophage colony rousing aspect (GM-CSF), with some symptomatic and radiographic improvement. Serum lactate dehydrogenase had not been measured and even though anti-GM-CSF antibody titers had been sent for examining, the results had been never obtainable. The.