Lymphocytic pneumonitis as the manifestation of acute graft‐versus‐host disease of the lung

Bolaños-Meade, Javier; Ioffe, Olga B.; Hey, Jamie C.; Vogelsang, Georgia B.; Akpek, Görgün

doi:10.1002/ajh.20315

Cited by 13 publications

(9 citation statements)

References 16 publications

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“…In a study of HCT recipients with bloodstream infections, postengraftment events were associated with worse outcomes, including death (62). "Late onset" noninfectious PCs, which may be subjected to diagnostic inaccuracy (63), have been associated with acute and chronic GVHD (35,64,65) and mortality (66). Many subjects in our study had multiple PCs, suggesting susceptibility to recurrent lung injury, incomplete resolution, and/or misdiagnosis and treatment of a previous PC.…”

Section: Discussionmentioning

confidence: 99%

“…Ninety-four of 112 (83.8%) PCs were first diagnosed by chest CT, and 71.4% (80 of 112) of radiographic findings were described as multifocal (35) or diffuse (20). Thirty-three PCs (29.2%) occurred during the first 30 days, and 86 (76.8%) occurred by the end of the first post-transplantation year.…”

Section: Pulmonary Complications Mortality and Other Clinical Outcomesmentioning

confidence: 99%

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Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation

Harris

Morjaria

Littmann

et al. 2016

Am J Respir Crit Care Med

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Rationale: Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown.Objectives: To investigate whether changes in gut microbiota are associated with PCs after HCT.Methods: A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota. The primary endpoint, PC, was defined by new abnormal parenchymal findings on chest imaging in the setting of respiratory signs and/or symptoms. Outcomes were collected up to 40 months after transplant. Clinical and microbiota risk factors for PCs and mortality were evaluated using survival analysis.Measurements and Main Results: One hundred twelve PCs occurred in 66 (70.2%) subjects. A high comorbidity index (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.30-4.00; P = 0.004), fluoroquinolones (HR, 2.29, 95% CI, 1.32-3.98; P = 0.003), low baseline diversity (HR, 2.63; 95% CI, 1.22-5.32; P = 0.015), and g-proteobacteria domination of fecal microbiota (HR, 2.64; 95% CI, 1.10-5.65; P = 0.031), which included common respiratory pathogens, predicted PCs. In separate analyses, low baseline diversity was associated with PCs that occurred preengraftment (HR, 6.30; 95% CI, 1.42-31.80; P = 0.016), whereas g-proteobacteria domination predicted PCs postengraftment (HR, 3.68; 95% CI, 1.49-8.21; P = 0.006) and overall mortality (HR, 3.52; 95% CI, 1.28-9.21; P = 0.016). Postengraftment PCs were also independent predictors of death (HR, 2.50; 95% CI, 1.25-5.22; P = 0.009).Conclusions: This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and g-proteobacteria domination were predictive of mortality. This suggests an adverse relationship between the graft and lung, which is perhaps mediated by bacterial composition in the gut. Further study is warranted.Keywords: stem cell transplantation; microbiota; pulmonary disease Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative therapy for many blood disorders and malignancies. Advances in transplant management have greatly improved outcomes (1). However, pulmonary complications (PCs) are associated with high morbidity and mortality. Although PCs have been reported in up to 70% of HCT recipients (2-4), the epidemiology is poorly defined in this heterogeneous population.Lung injury after HCT can occur early or late, present as acute or chronic, and involve one or more anatomic

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Section: Discussionmentioning

confidence: 99%

Section: Pulmonary Complications Mortality and Other Clinical Outcomesmentioning

confidence: 99%

Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation

Harris

Morjaria

Littmann

et al. 2016

Am J Respir Crit Care Med

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“…Cooke et al [9] first found that lung injury was encountered in the process of aGVHD. Many animal experiments of aGVHD also confirmed that early non-infectious diffused lung injury was associated with aGVHD [1,10−12] and this was also supported by clinical studies [13,14] , but whether the lung is one of the target organs of aGVHD remains undetermined [1,2,10,15] .…”

Section: Discussionmentioning

confidence: 68%

Effect and mechanism of acute graft versus host disease on early diffuse murine lung injury following allogeneic stem cell transplantation

et al. 2009

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To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C(57)BL/6-->BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor alpha (TNFalpha) and Interferon (IFNgamma) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFalpha were lower on day +7 than on day +3. In group B, the levels of TNFalpha attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFalpha were highest on day +7 and there was a significant difference between those on days +7 and +14 (P=0.816). In group A, the levels of IFNgamma on day +7 were higher than on day +3. In group B, the levels of IFNgamma increased progressively, but the comparison of IFNgamma levels in different times had no statistical significance (P=0.521, 0.118, 0.340). In group C, the levels of IFNgamma attained a peak by day +7 and decreased on day +14. aGVHD is the main cause of early non-infectious lung injury. T lymphocytes and TNFalpha are possibly implicated in the pathogenesis of acute GVHD-induced lung injury. The decreased levels of IFNgamma in lung tissues following transplantation might be associated with pulmonary fibrosis in late non-infectious pulmonary complications.

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“…LIP is a rare late-onset, non-infectious pulmonary complication of chronic GVHD 10–12. LIP is better described in the non-transplant setting where it is often associated with adult autoimmune or paediatric immunodeficiency disorders 10.…”

Section: Discussionmentioning

confidence: 99%

Pleuropericarditis, obliterative bronchiolitis and lymphocytic interstitial pneumonitis after allogeneic haematopoietic stem cell transplantation

Alousi¹,

Ghosh

Rice

et al. 2011

Case Reports

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SummaryChronic graft-versus-host disease (GVHD) is a common complication of allogeneic haematopoietic cell transplantation, with pulmonary involvement occurring in 5-10% of cases. Obliterative bronchiolitis (OB) is recognised as a diagnostic manifestation of chronic GVHD, whereas lymphocytic interstitial pneumonitis (LIP) has been reported but is not considered diagnostic, and pleuritis is not clearly associated. The authors describe a transplant patient who simultaneously manifested three distinct pulmonary processes: OB, patchy LIP and pleuropericarditis. The onset of these entities along with other manifestations of chronic GVHD, their resolution with increased immunosuppression and their recurrence upon tapering support all three entities as manifestations of GVHD in the lungs.

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Lymphocytic pneumonitis as the manifestation of acute graft‐versus‐host disease of the lung

Cited by 13 publications

References 16 publications

Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation

Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation

Effect and mechanism of acute graft versus host disease on early diffuse murine lung injury following allogeneic stem cell transplantation

Pleuropericarditis, obliterative bronchiolitis and lymphocytic interstitial pneumonitis after allogeneic haematopoietic stem cell transplantation

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