Clinical features and allograft failure rates of pulmonary antibody-mediated rejection categories.

BACKGROUND: Pulmonary antibody-mediated rejection (AMR) consensus criteria categorize AMR by diagnostic certainty. This study aims to define the clinical features and associated outcomes of these recently defined AMR categories. METHODS: Adjudication committees reviewed clinical data of 335 lung transplant recipients to define clinical or subclinical AMR based on the presence of allograft dysfunction, and the primary endpoints, time from transplant to allograft failure, a composite endpoint of chronic lung allograft dysfunction and/or death. Clinical AMR was subcategorized based on diagnostic certainty as definite, probable or possible AMR if 4, 3, or 2 characteristic features were present, respectively. Allograft injury was assessed via plasma donor-derived cell-free DNA (ddcfDNA). Risk of allograft failure and allograft injury was compared for AMR categories using regression models. RESULTS: Over the 38.5 months follow-up, 28.7% of subjects developed clinical AMR (n = 96), 18.5% developed subclinical AMR (n = 62) or 58.3% were no AMR (n = 177). Clinical AMR showed higher risk of allograft failure and ddcfDNA levels compared to subclinical or no AMR. Clinical AMR included definite/probable (n = 21) or possible AMR (n = 75). These subcategories showed similar clinical characteristics, ddcfDNA levels, and risk of allograft failure. However, definite/probable AMR showed greater measures of AMR severity, including degree of allograft dysfunction and risk of death compared to possible AMR. CONCLUSIONS: Clinical AMR showed greater risk of allograft failure than subclinical AMR or no AMR. Subcategorization of clinical AMR based on diagnostic certainty correlated with AMR severity and risk of death, but not with the risk of allograft failure.

The ISHLT chronic lung allograft dysfunction consensus criteria are applicable to pulmonary chronic graft-versus-host disease.

Pulmonary chronic graft-versus-host disease (PcGVHD) is a devastating complication of allogeneic hematopoietic stem cell transplant (HCT). The 2014 National Institutes of Health cGVHD consensus criteria (NIH criteria) only captures bronchiolitis obliterans syndrome (BOS). In this study, we adapted the 2019 International Society for Heart and Lung Transplantation (ISHLT) criteria of chronic lung allograft dysfunction (CLAD) to define novel phenotypes of PcGVHD and compared the performance of this criteria with the NIH criteria to identify patients with high-risk PcGVHD. We reviewed consecutive patients in a cGVHD natural history protocol (#NCT00092235) and adapted the 2019 CLAD criteria (the adapted criteria) to define PcGVHD as post-HCT forced expiratory volume at 1 second < 80% predicted value, with 4 phenotypes: obstructive, restrictive, mixed obstructive/restrictive, and undefined. An independent adjudication committee evaluated subjects for diagnosis and phenotyping. We identified 166 (47.4%) patients who met the adapted criteria, including obstruction (n = 12, 3.4%), restriction (n = 67, 19.1%), mixed obstruction/restriction (n = 47, 13.4%), and undefined (n = 40, 11.4%). In these patients, less than half (n = 78) met the NIH criteria for BOS (NIH+); the rest (n = 88) did not (NIH-). The NIH- subjects showed increased risk of death compared with those without PcGVHD (hazard ratio = 1.88, 95% confidence interval = 1.20-2.95; P = .006) that was similar to NIH+ subjects (P = .678). Our study demonstrated the potential of the adapted criteria in identifying patients with high-risk PcGVHD that have been missed by the NIH criteria. The adapted criteria could become a valuable tool to better phenotype and study lung disease in cGVHD.

Management of life-threatening hemoptysis in the ICU.

Life-threatening hemoptysis is commonly encountered in the ICU and its management can be challenging even for experienced clinicians. Depending on the etiology and severity, one can tailor the treatment modality and therapeutic intervention(s). The grading of severity of hemoptysis varies greatly in the literature; however, unlike hemorrhage in other scenarios, small amounts of blood can significantly impair oxygenation and ventilation leading to cardiovascular collapse. Importantly, the initial evaluation and management should focus on airway and hemodynamic stabilization along with maintenance of oxygenation and ventilation. In this review, we discuss commonly encountered etiologies, vascular anatomy, diagnostic evaluation, and therapeutic interventions. We examine the evolving trends in etiologies of life-threating hemoptysis over the years. The role of flexible and rigid bronchoscopy as both a diagnostic and therapeutic modality is explored, as well as the use and indications of several bronchoscopic techniques, such as topical hemostatic agents, endobronchial tamponade, and tranexamic acid (TXA). In addition, we assess the use of multi-row detector computed tomography as the initial rapid diagnostic method of choice and its use in planning for definitive treatment. The efficacy and long-term results of bronchial artery embolization (BAE) are evaluated, as well as indications for surgical intervention. Furthermore, the importance of a multidisciplinary approach is emphasized. The necessary interplay between intensivists, consultative services, and radiologists is described in detail and an algorithmic management strategy incorporating the above is outlined. Given the complexity in management of life-threatening hemoptysis, this paper aims to summarize the available diagnostic and therapeutic methods and provide a standardized approach for the management of patients with this often difficult to treat condition.