-
BMJ Case Reports Oct 2020We present a case of azacitidine-induced pneumonitis which is a rare adverse drug reaction and reported in less than 0.1% of cases. Common side effects of azacitidine... (Review)
Review
We present a case of azacitidine-induced pneumonitis which is a rare adverse drug reaction and reported in less than 0.1% of cases. Common side effects of azacitidine are weakness, nausea, vomiting, constipation, injection site reactions, insomnia, among others. Our patient received azacitidine to treat her acute myeloid leukaemia and began to develop shortness of breath which progressed to dyspnoea at rest after completing a 7-day course of azacitidine and venetoclax. Initial chest X-ray revealed severe airspace disease for which the patient began receiving broad spectrum antibiotics, antifungals and antivirals therapy. Although infectious workup revealed invasive aspergillosis she did not clinically and radiologically improve despite being on isavuconazole until high-dose glucocorticoids were initiated. This case illustrates the importance of recognising and understanding the potential side effects of azacitidine and other chemotherapy agents as some adverse drug reactions can be life-threatening.
Topics: Aged; Azacitidine; Enzyme Inhibitors; Female; Humans; Invasive Fungal Infections; Lung; Pneumonia; Radiography, Thoracic; Tomography, X-Ray Computed
PubMed: 33122228
DOI: 10.1136/bcr-2020-236349 -
Current Opinion in Microbiology Aug 2021The occurrence of invasive pulmonary aspergillosis (IPA) in critically ill patients with viral pneumonitis has increasingly been reported in recent years.... (Review)
Review
The occurrence of invasive pulmonary aspergillosis (IPA) in critically ill patients with viral pneumonitis has increasingly been reported in recent years. Influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) are the two most common forms of this fungal infection. These diseases cause high mortality in patients, most of whom were previously immunocompetent. The pathogenesis of IAPA and CAPA is still not fully understood, but involves viral, fungal and host factors. In this article, we discuss several aspects regarding IAPA and CAPA, including their possible pathogenesis, the use of immunotherapy, and future challenges.
Topics: COVID-19; Critical Illness; Humans; Immunotherapy; Influenza, Human; Invasive Pulmonary Aspergillosis; Pneumonia, Viral
PubMed: 34034082
DOI: 10.1016/j.mib.2021.04.006 -
Journal For Immunotherapy of Cancer Jun 2020Pneumonitis from immune checkpoint inhibitors (ICI) is a potentially fatal immune-related adverse event (irAE) from antiprogrammed death 1/programmed death ligand 1...
BACKGROUND
Pneumonitis from immune checkpoint inhibitors (ICI) is a potentially fatal immune-related adverse event (irAE) from antiprogrammed death 1/programmed death ligand 1 immunotherapy. Most cases of ICI pneumonitis improve or resolve with 4-6 weeks of corticosteroid therapy. Herein, we report the incidence, clinicopathological features and management of patients with non-small cell lung cancer (NSCLC) and melanoma who developed chronic ICI pneumonitis that warrants ≥12 weeks of immunosuppression.
METHODS
Patients with ICI pneumonitis were identified from institutional databases of ICI-treated patients with advanced melanoma and NSCLC between January 2011 and July 2018. ICI pneumonitis was defined as clinical/radiographic evidence of lung inflammation without alternative diagnoses, adjudicated by a multidisciplinary team. Chronic ICI pneumonitis was defined as pneumonitis that persists or worsens with steroid tapering, and necessitates ≥12 weeks of immunosuppression, after ICI discontinuation. Serial chest CT was used to assess radiological features, and tumor response by Response EvaluationCriteria for Solid Tumors V.1.1. Bronchoalveolar lavage fluid (BALF) samples were assessed by cell differential. Lung biopsy samples were evaluated by H&E staining and multiplex immunofluorescence (mIF), where available.
RESULTS
Among 299 patients, 44 developed ICI pneumonitis (NSCLC: 5/205; melanoma: 1/94), and of these, 6 experienced chronic ICI pneumonitis. The overall incidence of chronic ICI pneumonitis was thus 2%. Of those who developed chronic ICI pneumonitis: the majority had NSCLC (5/6), all sustained disease control from ICIs, and none had other concurrent irAEs. Timing of chronic ICI pneumonitis development was variable (range: 0-50 months), and occurred at a median of 12 months post ICI start. Recrudescence of ICI pneumonitis occurred at a median of 6 weeks after initial steroid start (range: 3-12 weeks), with all patients requiring steroid reintroduction when tapered to ≤10 mg prednisone/equivalent. The median total duration of steroids was 37 weeks (range: 16-43+weeks). Re-emergence of radiographic ICI pneumonitis occurred in the same locations on chest CT, in most cases (5/6). All patients who developed chronic ICI pneumonitis had BALF lymphocytosis on cell differential and organising pneumonia on lung biopsy at initial ICI pneumonitis presentation, with persistent BALF lymphocytosis and brisk CD8+ infiltration on mIF at pneumonitis re-emergence during steroid taper.
CONCLUSIONS
A subset of patients who develop pneumonitis from ICIs will develop chronic ICI pneumonitis, that warrants long-term immunosuppression of ≥12 weeks, and has distinct clinicopathological features.
Topics: Aged; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Pneumonia; Retrospective Studies
PubMed: 32554618
DOI: 10.1136/jitc-2020-000840 -
The Journal of Infectious Diseases Jun 2021
Review
Topics: Anti-Infective Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Humans; Lung; Microbiota; Pneumonia
PubMed: 33330898
DOI: 10.1093/infdis/jiaa702 -
Frontiers in Immunology 2023Immune checkpoint inhibitor (ICI)-related pneumonitis (IRP) is a common and potentially fatal clinical adverse event. The identification and prediction of the risk of...
BACKGROUND
Immune checkpoint inhibitor (ICI)-related pneumonitis (IRP) is a common and potentially fatal clinical adverse event. The identification and prediction of the risk of ICI-related IRP is a major clinical issue. The objective of this study was to apply a machine learning method to explore risk factors and establish a prediction model.
METHODS
We retrospectively analyzed 48 patients with IRP (IRP group) and 142 patients without IRP (control group) who were treated with ICIs. An Elastic Net model was constructed using a repeated k-fold cross-validation framework (repeat = 10; k = 3). The prediction models were validated internally and the final prediction model was built on the entire training set using hyperparameters with the best interval validation performance. The generalizability of the final prediction model was assessed by applying it to an independent test set. The overall performance, discrimination, and calibration of the prediction model were evaluated.
RESULTS
Eleven predictors were included in the final predictive model: sindillizumab, number of ≥2 underlying diseases, history of lung diseases, tirelizumab, non-small cell lung cancer (NSCLC), percentage of CD4 lymphocytes, body temperature, KPS score ≤70, hemoglobin, cancer stage IV, and history of antitumor therapy. The external validation of the risk prediction model on an independent test set of 37 patients and showed good discrimination and acceptable calibration ability: with AUC of 0.81 (95% CI 0.58-0.90), AP of 0.76, scaled Brier score of 0.31, and Spiegelhalter-z of -0.29 (P-value:0.77). We also designed an online IRP risk calculator for use in clinical practice.
CONCLUSION
The prediction model of ICI-related IRP provides a tool for accurately predicting the occurrence of IRP in patients with cancer who received ICIs.
Topics: Humans; Immune Checkpoint Inhibitors; Carcinoma, Non-Small-Cell Lung; Retrospective Studies; Lung Neoplasms; Pneumonia; Machine Learning
PubMed: 37457722
DOI: 10.3389/fimmu.2023.1138489 -
Journal of the National Comprehensive... Nov 2023Immune checkpoint inhibitors (ICIs) are a first-line and perioperative treatment for lung cancer. Pneumonitis is a potentially life-threatening complication of ICI...
BACKGROUND
Immune checkpoint inhibitors (ICIs) are a first-line and perioperative treatment for lung cancer. Pneumonitis is a potentially life-threatening complication of ICI treatment in 2% to 5% of patients; however, risk factors for developing ICI pneumonitis (ICI-p) remain undefined.
METHODS
We conducted a retrospective cohort study of consecutive patients with lung cancer who received at least one dose of ICI from 2015 through 2020 at The Ohio State University. Pneumonitis cases were documented by the treating oncologist and retrospectively evaluated for agreement between an oncologist and a pulmonologist. Patient demographic and clinical characteristics were recorded and summarized between those with and without pneumonitis for the overall cohort. Univariate and multivariable survival analyses using the Fine-Gray competing risk model were used to examine the associations.
RESULTS
A total of 471 patients with lung cancer were included, of which 402 had non-small cell lung cancer and 69 had small cell lung cancer; 39 (8%) patients in the overall cohort developed ICI-p. Preexisting interstitial abnormalities and prior chest radiation were both significantly associated with ICI-p on univariate analysis (hazard ratio [HR], 8.91; 95% CI, 4.69-16.92; P<.001; and HR, 2.81; 95% CI, 1.50-5.28; P=.001). On multivariable analyses, interstitial abnormalities remained a strong independent risk factor for ICI-p when controlling for chest radiation and type of immunotherapy (HR, 9.77; 95% CI, 5.17-18.46; P<.001). Among patients with ICI-p (n=39), those with severe (grade 3-5) pneumonitis had worse overall survival compared with those with mild (grade 1 or 2) pneumonitis (P=.001). Abnormal pulmonary function test results at both 12 and 18 months prior to ICI initiation were not significantly associated with ICI-p.
CONCLUSIONS
Preexisting interstitial abnormalities on chest CT and prior chest radiation are independent risk factors that are strongly associated with ICI-p in patients with lung cancer. These findings highlight a potential need for closer observation for ICI-p among patients with these risk factors.
Topics: Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Retrospective Studies; Pneumonia
PubMed: 37935100
DOI: 10.6004/jnccn.2023.7059 -
Expert Review of Clinical Pharmacology 2023Serious phosphatidylinositol 3 kinase (PI3K) inhibitor-related pneumonitis has raised clinical concerns, and integrated data for this condition are lacking. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Serious phosphatidylinositol 3 kinase (PI3K) inhibitor-related pneumonitis has raised clinical concerns, and integrated data for this condition are lacking.
METHODS
Randomized controlled trials (RCTs) comparing PI3K inhibitor therapy with control treatments from electronic databases and registrations were searched from inception to 1 April 20231 April 2023seven1 April 2023. The outcomes of our study were the incidence and risk of all-grade and grade ≥ 3 PI3K inhibitor-associated pneumonitis compared with controls.
RESULTS
The meta-analysis included 13 studies comprising 3916 patients. The incidence of all-grade and grade ≥ 3 pneumonitis was 3.7% (82/2210) and 3.0% (35/1162) in patients treated with PI3K inhibitors. PI3K inhibitors significantly increased the risk of all-grade and grade ≥ 3 pneumonitis compared with controls (RR 5.63, 95% CI [2.97, 10.65], < 0.00001; RR 6.85, 95% CI [2.45, 19.11], = 0.0002, respectively) with no significant heterogeneity across studies. In terms of different PI3K inhibitors, copanlisib and idelalisib significantly increased the risk of pneumonitis compared to controls (RR 4.99, 95% CI [1.19, 21.01], = 0.03; RR 5.53, 95% CI [2.35, 13.01], < 0.0001, respectively).
CONCLUSION
PI3K inhibitors significantly increased the risk of pneumonitis compared with controls, and most cases are severe or even life-threatening.
PROSPERO REGISTRATION NUMBER
CRD42022318878.
Topics: Humans; Pneumonia; Phosphoinositide-3 Kinase Inhibitors; Incidence; Phosphatidylinositol 3-Kinases
PubMed: 37489925
DOI: 10.1080/17512433.2023.2238602 -
Pediatric Radiology Apr 2024Pediatric lung infections continue to be a leading cause of pediatric morbidity and mortality. Although both pediatric and general radiologists are familiar with typical... (Review)
Review
Pediatric lung infections continue to be a leading cause of pediatric morbidity and mortality. Although both pediatric and general radiologists are familiar with typical lung infections and their imaging findings in children, relatively rare lung infections continue to present a diagnostic challenge. In addition, the advances in radiological imaging and emergence of several new lung infections in recent years facilitated the need for up-to-date knowledge on this topic. In this review article, we discuss the imaging findings of pediatric lung infections caused by unusual/uncommon and new pathogens. We review the epidemiological, clinical, and radiological imaging findings of viral (coronavirus disease 2019, Middle East respiratory syndrome, bird flu), bacterial (Streptococcus anginosus, Francisella tularensis, Chlamydia psittaci), and parasitic lung infections (echinococcosis, paragonimiasis, amoebiasis). Additional disorders whose clinical course and imaging findings may mimic lung infections in children (hypersensitivity pneumonitis, pulmonary hemorrhage, eosinophilic pneumonia) are also presented, to aid in differential diagnosis. As the clinical presentation of children with new and unusual lung infections is often non-specific, imaging evaluation plays an important role in initial detection, follow-up for disease progression, and assessment of potential complications.
Topics: Child; Humans; Lung; Pneumonia; COVID-19; Lung Diseases; Thorax
PubMed: 38097820
DOI: 10.1007/s00247-023-05818-z -
Frontiers in Immunology 2020Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by biallelic mutations in the gene, has historically been defined... (Review)
Review
Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by biallelic mutations in the gene, has historically been defined by the development of chronic mucocutaneous candidiasis together with autoimmune endocrinopathies, primarily hypoparathyroidism and adrenal insufficiency. Recent work has drawn attention to the development of life-threatening non-endocrine manifestations such as autoimmune pneumonitis, which has previously been poorly recognized and under-reported. In this review, we present the clinical, radiographic, autoantibody, and pulmonary function abnormalities associated with APECED pneumonitis, we highlight the cellular and molecular basis of the autoimmune attack in the AIRE-deficient lung, and we provide a diagnostic and a therapeutic roadmap for patients with APECED pneumonitis. Beyond APECED, we discuss the relevance and potential broader applicability of these findings to other interstitial lung diseases seen in secondary AIRE deficiency states such as thymoma and RAG deficiency or in common polygenic autoimmune disorders such as idiopathic Sjögren's syndrome.
Topics: Animals; Autoimmune Diseases; Central Tolerance; Humans; Lung; Pneumonia; Polyendocrinopathies, Autoimmune; Transcription Factors; AIRE Protein
PubMed: 33584685
DOI: 10.3389/fimmu.2020.609253 -
Clinical Oncology (Royal College of... Oct 2023Pneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced...
AIMS
Pneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). In this study we sought to identify the risk factors for pneumonitis with CRT-ICI therapy in LA-NSCLC cases and determine its impact on survival.
MATERIALS AND METHODS
We conducted a retrospective chart review of 140 patients with LA-NSCLC who underwent curative-intent CRT-ICI with durvalumab between 2018 and 2021. Pneumonitis was diagnosed by a multidisciplinary team of clinical experts. We used multivariable cause-specific hazard models to identify risk factors associated with grade ≥2 pneumonitis. We constructed multivariable Cox proportional hazard models to investigate the impact of pneumonitis on all-cause mortality.
RESULTS
The median age of the cohort was 67 years; most patients were current or former smokers (86%). The cumulative incidence of grade ≥2 pneumonitis was 23%. Among survivors, 25/28 patients had persistent parenchymal scarring. In multivariable analyses, the mean lung dose (hazard ratio 1.14 per Gy, 95% confidence interval 1.03-1.25) and interstitial lung disease (hazard ratio 3.8, 95% confidence interval 1.3-11.0) increased the risk for pneumonitis. In adjusted models, grade ≥2 pneumonitis (hazard ratio 2.5, 95% confidence interval 1.0-6.2, P = 0.049) and high-grade (≥3) pneumonitis (hazard ratio 8.3, 95% confidence interval 3.0-23.0, P < 0.001) were associated with higher all-cause mortality.
CONCLUSIONS
Risk factors for pneumonitis in LA-NSCLC patients undergoing CRT-ICI include the mean radiation dose to the lung and pre-treatment interstitial lung disease. Although most cases are not fatal, pneumonitis in this setting is associated with markedly increased mortality.
Topics: Humans; Aged; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Retrospective Studies; Chemoradiotherapy; Pneumonia; Radiation Pneumonitis
PubMed: 37507279
DOI: 10.1016/j.clon.2023.07.003