An Adjudication Protocol for Severe Bacterial and Viral Pneumonia

Abstract

Rationale: Clinical endpoints that constitute successful treatment in severe pneumonia are difficult to ascertain and vulnerable to bias. Utility of a protocolized adjudication procedure to determine meaningful endpoints in severe pneumonia is not well described. Objectives: To develop and validate a protocol for classification and adjudication of clinical endpoints in severe bacterial and viral pneumonia in a prospective cohort of critically ill, mechanically ventilated patients. Methods: Each episode of pneumonia was independently reviewed by two of six pulmonary and critical care physician adjudicators. If a discrepancy in at least one critical answer occurred between the two adjudicators, a third adjudicator reviewed the case and answered the specific question(s) for which there was a lack of agreement. If discrepancy remained after all three adjudications, consensus was achieved through committee review. Results: Evaluation of 784 pneumonia episodes during 593 hospitalizations achieved a 79% crude rate of interobserver agreement defined as agreement between 2 of 3 reviewers. Culture-negative pneumonia was associated with increased interobserver agreement. Multiple episodes of pneumonia and bacterial and viral co-infection in the initial episode of pneumonia were associated with decreased interobserver agreement. For bacterial pneumonia, patients with an adjudicated day 7-8 clinical impression of cure for the initial episode of pneumonia were more likely to be discharged alive compared to patients with a day 7-8 clinical impression of indeterminate (p < 0.01), superinfection (p = 0.03), or a combined impression of persistence and superinfection (p = 0.04). In viral pneumonia, patients with an adjudicated clinical impression of cure for an initial episode of viral pneumonia were more likely to be discharged alive compared to patients with an adjudicated clinical impression of persistence (p < 0.01), indeterminate (p < 0.01), or bacterial superinfection (p < 0.01). Conclusions: We developed and validated a protocol for classification and adjudication of clinical endpoints in severe pneumonia. This protocol can be applied to cohorts of patients with severe pneumonia to provide uniform assessment of patient-centered endpoints.

A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia

“…In contrast, T cell enrichment was associated with favorable clinical parameters, including respiratory system compliance, in patients with COVID-19. The resolution status of the pneumonia episode based on expert clinical adjudication (21) was linked to mortality in patients with severe SARS-CoV-2 pneumonia in our cohort ( Supplemental Figure 3M-N ), similar to our findings in the larger cohort of patients with severe pneumonia enrolled in the SCRIPT study (15).…”

“…Participants could re-enter the study under a new study identifier if they were discharged from the hospital and subsequently re-admitted to the ICU. The etiology of pneumonia (SARS-CoV-2, other viral pneumonia, other pneumonia, or non-pneumonia [intubated for reasons other than pneumonia]) and outcome of each pneumonia episode (cured, indeterminate, or not cured) were adjudicated by consensus of pulmonary and critical care medicine physicians using a validated procedure (15,21). The etiology of pneumonia was determined based on clinical and BAL fluid data obtained on the date of study enrollment.…”

“…The etiology of pneumonia was determined based on clinical and BAL fluid data obtained on the date of study enrollment. Detailed definitions of pneumonia episodes and resolution status are available in reference (21). In this study, patients who underwent lung transplantation for refractory respiratory failure and patients who were transferred to home or inpatient hospice were adjudicated as having died in the reported binary outcome (discharged from the hospital alive versus deceased).…”

“…In contrast, T cell enrichment was associated with favorable clinical parameters, including respiratory system compliance, in patients with COVID-19. The resolution status of the pneumonia episode based on expert clinical adjudication (21) was linked to mortality in patients with severe SARS-CoV-2 pneumonia in our cohort (Supplemental Figure 3M-N), similar to our findings in the larger cohort of patients with severe pneumonia enrolled in the SCRIPT study (15). Expression of CD127 (the interleukin-7 receptor) and HLA-DR on peripheral blood T cells has been associated with outcomes in SARS-CoV-2 pneumonia, with CD127 correlating with less severe disease and better outcomes and HLA-DR correlating with worsened disease severity and poorer outcomes (9,22,23).…”

An observational cohort study of bronchoalveolar lavage fluid galactomannan andAspergillusculture positivity in patients requiring mechanical ventilation

“…This multi-step/multi-blinded reviewer adjudication process is described in detail separately. 20 We examined results both at the level of each BAL and at the level of each patient admission. We examined patients and BAL samples that had BAL fluid GM ODI <0.5, BAL fluid GM ODI >0.5, BAL fluid GM ODI >0.8, and those who did or did not grow Aspergillus on culture.…”