Pneumocystis Pneumonia in Patients with Autoimmune Diseases: A Retrospective Study Focused on Clinical Characteristics and Prognostic Factors Related to Death

<div><p>Background</p><p>With the increasing use of immunosuppressive agents, the number of opportunistic infections has risen in patients with autoimmune diseases. Pneumocystis pneumonia (PCP) is one of these opportunistic infections that have a high mortality rate. However, only a few studies have described PCP in these patients, and these studies are limited in scope. We conducted this retrospective study to describe the clinical characteristics and factors associated with outcomes of PCP in patients with autoimmune diseases.</p><p>Methods</p><p>A retrospective study was performed in laboratory diagnosed PCP patients with autoimmune diseases in an academic hospital over a 10-year period. Patients with human immunodeficiency virus (HIV) infection were not included. Clinical characteristics were collected and the factors related to death were analysed.</p><p>Results</p><p>A total of 69 patients with PCP during the study period were included. Common clinical features included fever (81%), cough (56%), and dyspnea (35%). Ground glass opacity (81%) and reticulation (52%) were the most common radiological findings. Concurrent pulmonary infections including bacterium, aspergillus and cytomegalovirus were found in 34% of the patients. The overall in-hospital mortality rate was 32%. High mortality was associated with lower PaO₂/FiO₂ ratios and albumin levels. The lymphocyte count, CD4+ T cell count, previous usage of immunosuppressive agents, the duration and dose of glucocorticoids did not affect the outcome.</p><p>Conclusions</p><p>The mortality rate in PCP patients with autoimmune diseases is high. Low PaO₂/FiO₂ ratios and albumin levels are independent prognostic factors of mortality.</p></div

Univariate analyses of risk factors among PCP patients determining survival rates.

<p>* Corticosteroids doses were expressed as the prednisolone equivalent dose</p><p>Univariate analyses of risk factors among PCP patients determining survival rates.</p

Demographical details, underlying diseases, and diagnostic procedures of the patients.

<p>* Vasculitis: Behcet’s disease, microscopic polyangiitis, granulomatosis with polyangiitis</p><p>** Other CTDs: Sjogren syndrome (SS), undifferentiated connective tissue disease (UCTD), mixed connective tissue disease, scleroderma</p><p># Immunosuppressive agents: cyclophosphamide, cyclosporin A, mycophenlatemofetil, and tripterygium glycosides</p><p>& Biological agents: ritaximab, and antitumor necrosis factor α(infliximab, entanercept)</p><p>Demographical details, underlying diseases, and diagnostic procedures of the patients.</p

Clinical manifestations, Radiologic characters and laboratory findings of the patients.

<p>* Included <i>pseudomonas aeruginosa</i> in three specimens, <i>Acinetobacter baumannii</i> in one specimen, <i>Klebsiella pneumonia</i> in one specimen</p><p>Clinical manifestations, Radiologic characters and laboratory findings of the patients.</p

Kaplan-Meier survival curve for the patients with pneumocystis pneumonia.

<p>Kaplan-Meier survival curve for the patients with pneumocystis pneumonia.</p

Image_1_Peripheral Blood Lymphocyte Subsets Predict the Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer.tif

BackgroundNon–small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients’ response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy.MethodsTo explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs.ResultsThe two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4+CD45RA− T cell (HR = 0.644, P = 0.047) and CD8+ T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4+CD45RA− T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4+CD45RA− T cell >311.3 × 106/L as the threshold. In contrast, CD8+ T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4+ T cell and its subsets were significantly higher in patients with mild (grades 1–2) immune-related adverse events (irAEs) than those without irAEs. CD8+CD38+ T cell was associated with total irAEs and severe (grades 3–4) irAEs but was not suitable to be a predictive biomarker.ConclusionPeripheral blood CD4+CD45RA− T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8+CD38+ T cell was associated with irAEs and severe irAEs.</p

Image_4_Peripheral Blood Lymphocyte Subsets Predict the Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer.tif

BackgroundNon–small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients’ response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy.MethodsTo explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs.ResultsThe two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4+CD45RA− T cell (HR = 0.644, P = 0.047) and CD8+ T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4+CD45RA− T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4+CD45RA− T cell >311.3 × 106/L as the threshold. In contrast, CD8+ T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4+ T cell and its subsets were significantly higher in patients with mild (grades 1–2) immune-related adverse events (irAEs) than those without irAEs. CD8+CD38+ T cell was associated with total irAEs and severe (grades 3–4) irAEs but was not suitable to be a predictive biomarker.ConclusionPeripheral blood CD4+CD45RA− T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8+CD38+ T cell was associated with irAEs and severe irAEs.</p

Image_3_Peripheral Blood Lymphocyte Subsets Predict the Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer.tif

BackgroundNon–small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients’ response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy.MethodsTo explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs.ResultsThe two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4+CD45RA− T cell (HR = 0.644, P = 0.047) and CD8+ T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4+CD45RA− T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4+CD45RA− T cell >311.3 × 106/L as the threshold. In contrast, CD8+ T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4+ T cell and its subsets were significantly higher in patients with mild (grades 1–2) immune-related adverse events (irAEs) than those without irAEs. CD8+CD38+ T cell was associated with total irAEs and severe (grades 3–4) irAEs but was not suitable to be a predictive biomarker.ConclusionPeripheral blood CD4+CD45RA− T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8+CD38+ T cell was associated with irAEs and severe irAEs.</p

Table_1_Peripheral Blood Lymphocyte Subsets Predict the Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer.xlsx

BackgroundNon–small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients’ response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy.MethodsTo explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs.ResultsThe two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4+CD45RA− T cell (HR = 0.644, P = 0.047) and CD8+ T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4+CD45RA− T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4+CD45RA− T cell >311.3 × 106/L as the threshold. In contrast, CD8+ T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4+ T cell and its subsets were significantly higher in patients with mild (grades 1–2) immune-related adverse events (irAEs) than those without irAEs. CD8+CD38+ T cell was associated with total irAEs and severe (grades 3–4) irAEs but was not suitable to be a predictive biomarker.ConclusionPeripheral blood CD4+CD45RA− T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8+CD38+ T cell was associated with irAEs and severe irAEs.</p

Image_5_Peripheral Blood Lymphocyte Subsets Predict the Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer.tif

BackgroundNon–small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients’ response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy.MethodsTo explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs.ResultsThe two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4+CD45RA− T cell (HR = 0.644, P = 0.047) and CD8+ T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4+CD45RA− T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4+CD45RA− T cell >311.3 × 106/L as the threshold. In contrast, CD8+ T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4+ T cell and its subsets were significantly higher in patients with mild (grades 1–2) immune-related adverse events (irAEs) than those without irAEs. CD8+CD38+ T cell was associated with total irAEs and severe (grades 3–4) irAEs but was not suitable to be a predictive biomarker.ConclusionPeripheral blood CD4+CD45RA− T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8+CD38+ T cell was associated with irAEs and severe irAEs.</p