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Frontiers in Immunology 2023Pneumonitis is one of the most common adverse events induced by the use of immune checkpoint inhibitors (ICI), accounting for a 20% of all ICI-associated deaths. Despite... (Review)
Review
BACKGROUND
Pneumonitis is one of the most common adverse events induced by the use of immune checkpoint inhibitors (ICI), accounting for a 20% of all ICI-associated deaths. Despite numerous efforts to identify risk factors and develop predictive models, there is no clinically deployed risk prediction model for patient risk stratification or for guiding subsequent monitoring. We believe this is due to systemic suboptimal approaches in study designs and methodologies in the literature. The nature and prevalence of different methodological approaches has not been thoroughly examined in prior systematic reviews.
METHODS
The PubMed, medRxiv and bioRxiv databases were used to identify studies that aimed at risk factor discovery and/or risk prediction model development for ICI-induced pneumonitis (ICI pneumonitis). Studies were then analysed to identify common methodological pitfalls and their contribution to the risk of bias, assessed using the QUIPS and PROBAST tools.
RESULTS
There were 51 manuscripts eligible for the review, with Japan-based studies over-represented, being nearly half (24/51) of all papers considered. Only 2/51 studies had a low risk of bias overall. Common bias-inducing practices included unclear diagnostic method or potential misdiagnosis, lack of multiple testing correction, the use of univariate analysis for selecting features for multivariable analysis, discretization of continuous variables, and inappropriate handling of missing values. Results from the risk model development studies were also likely to have been overoptimistic due to lack of holdout sets.
CONCLUSIONS
Studies with low risk of bias in their methodology are lacking in the existing literature. High-quality risk factor identification and risk model development studies are urgently required by the community to give the best chance of them progressing into a clinically deployable risk prediction model. Recommendations and alternative approaches for reducing the risk of bias were also discussed to guide future studies.
Topics: Humans; Japan; Pneumonia; Risk Factors; Systematic Reviews as Topic
PubMed: 37818359
DOI: 10.3389/fimmu.2023.1228812 -
Respirology (Carlton, Vic.) Sep 2021article
article
Topics: COVID-19; Humans; Lung; Pneumonia; Pulmonary Embolism; SARS-CoV-2
PubMed: 34322959
DOI: 10.1111/resp.14123 -
Journal of Postgraduate Medicine 2022Methotrexate leading to hypercalcaemia is a rarely reported adverse event. We present three elderly patients with inflammatory arthritis who developed hypercalcemia...
Methotrexate leading to hypercalcaemia is a rarely reported adverse event. We present three elderly patients with inflammatory arthritis who developed hypercalcemia probably due to methotrexate-induced granulomatous pneumonitis. All patients presented with worsening non-productive cough with dyspnea, nausea, loss of appetite, and confusion. Their clinical and radiologic features were consistent with methotrexate-induced pneumonitis. On evaluation, all patients concurrently had hypercalcemia with normal 25OH D3, and low PTH with markedly elevated levels of 1,25OH D3 seen in two patients. In all three patients, hypercalcemia and pneumonia responded to hydration, corticosteroids, and methotrexate withdrawal. There was no relapse of symptoms on long term follow-up. In these three patients with inflammatory arthritis, methotrexate-induced pneumonitis led to symptomatic hypercalcemia. Unless hypercalcemia is looked for and treated in this setting, the morbidity can be high.
Topics: Adrenal Cortex Hormones; Aged; Arthritis; Humans; Hypercalcemia; Methotrexate; Pneumonia
PubMed: 35975343
DOI: 10.4103/jpgm.jpgm_1180_21 -
Journal of Cancer Research and Clinical... Aug 2023As immune checkpoint inhibitors (ICIs) are widely used, a series of immune-related adverse events (irAEs) have been reported, including immune checkpoint... (Review)
Review
As immune checkpoint inhibitors (ICIs) are widely used, a series of immune-related adverse events (irAEs) have been reported, including immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis). The incidence of ICI-pneumonitis is higher in reality than in clinical trials. The diagnosis is challenging, mainly based on clinical and imaging features, and requires the exclusion of other causes. The data on the biological mechanisms of ICI-pneumonitis are scarce, resulting in little knowledge of the best treatment for ICI-pneumonitis. Bronchoalveolar lavage (BAL) may be helpful to identify the biological differences or find predictive biomarkers, and may in turn help to develop phenotype-specific targeted drugs to treat ICI-pneumonitis. Herein, we outline the characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for ICI-pneumonitis. Through careful sorting and literature review, we find crosstalk between pathogenic Th17/Th1 cells (i.e., Th17.1) and pro-inflammatory monocytes, and activation of Th17(/Th1)/IL-17A (/IFN-γ) pathways may play a key role in the pathogenesis of ICI-pneumonitis. Disruption of the interaction between pathogenic Th17/Th1 cells and pro-inflammatory monocytes (such as, anti-IL-23) may be a potential treatment for ICI-pneumonitis. We first describe the possible pathophysiological mechanisms of ICI-pneumonitis, hoping to contribute to the optimization of diagnosis and treatment, as well as provide readers with research inspiration.
Topics: Humans; Immune Checkpoint Inhibitors; Bronchoalveolar Lavage Fluid; Pneumonia
PubMed: 36944820
DOI: 10.1007/s00432-023-04696-0 -
Frontiers in Immunology 2022Radiation recall pneumonitis (RRP) is described as an unpredictable acute inflammatory reaction within the previously irradiated lung site during the administration of... (Review)
Review
Radiation recall pneumonitis (RRP) is described as an unpredictable acute inflammatory reaction within the previously irradiated lung site during the administration of systematic therapy after radiotherapy. Here, we reported a case of a 54-year-old woman with non-small lung cancer (NSCLC), who had pneumonitis at 3 and 10 months after radiotherapy regarded as radiation pneumonitis (RP) and RRP induced by anti-PD-1 sintilimab, respectively. This unique patient with double pneumonitis (RP and RRP) has drawn attention to the identification of immune or radiation pneumonitis, its potential mechanism, and further treatment strategy after the emergence of RRP.
Topics: Antibodies, Monoclonal, Humanized; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Middle Aged; Pneumonia; Radiation Pneumonitis
PubMed: 35280981
DOI: 10.3389/fimmu.2022.823767 -
La Radiologia Medica Feb 2023To compare the radiological findings of immune checkpoint inhibitor-related pneumonitis (IRP) and COVID-19 pneumonia, evaluating the potential of the CO-RADS score to...
OBJECTIVES
To compare the radiological findings of immune checkpoint inhibitor-related pneumonitis (IRP) and COVID-19 pneumonia, evaluating the potential of the CO-RADS score to differentiate between them.
METHODS
Two readers blindly reviewed chest CTs from age- and sex-matched groups of 33 patients with IRP and 33 patients with COVID-19 pneumonia. Each examiner evaluated the presence of 13 CT features, semiquantitatively scored lung involvement, and assigned a CO-RADS score. Inter-reader reliability in the assessment of CT features and CO-RADS categories was evaluated with Cohen's κ. Distribution differences between groups were evaluated with the χ, Fisher's, and Mann-Whitney U tests.
RESULTS
Substantial or higher inter-reader reliability was found in CO-RADS assignments (κ = 0.664) and in the evaluation of CT features (κ ≥ 0.638), among which the sole feature found to significantly differentiate IRP from COVID-19 pneumonia was unilateral presentation (p < 0.001). Lung involvement semiquantitative scores and CO-RADS scores were significantly higher (p < 0.001) in COVID patients (median involvement score 4, IQR 4-6; median CO-RADS score 5, IQR 4-5) than in IRP patients (median involvement score 2.5, IQR 2-4; median CO-RADS score 3, IQR 3-4) but exploratory analysis of CO-RADS specificity revealed comparatively low values, ranging between 51.5% (Reader 1) and 54.6% (Reader 2).
CONCLUSIONS
CT features of IRP and COVID-19 pneumonia frequently overlap, save for the extent of lung involvement and bilaterality. In the current SARS-CoV-2 pandemic, the low specificity of the CO-RADS score for the differential diagnosis of COVID-19 pneumonia and IRP may prompt to reconsider the role of imaging in IRP work-up.
Topics: Humans; COVID-19; Immune Checkpoint Inhibitors; SARS-CoV-2; Reproducibility of Results; Tomography, X-Ray Computed; Pneumonia; Retrospective Studies
PubMed: 36680711
DOI: 10.1007/s11547-023-01598-6 -
Frontiers in Immunology 2023Checkpoint inhibitor-related pneumonitis (CIP) is a complication of immunotherapy for malignant tumors that severely limits the treatment cycles as well as endangers... (Review)
Review
Checkpoint inhibitor-related pneumonitis (CIP) is a complication of immunotherapy for malignant tumors that severely limits the treatment cycles as well as endangers patients' health. The chest CT imaging features or typing of CIP and the application of radiomics will contribute to the precise prevention, early diagnosis and instant treatment of CIP. This article reviews the advances in the CT features and the application of radiomics in CIP.
Topics: Humans; Neoplasms; Pneumonia; Immunotherapy; Tomography, X-Ray Computed
PubMed: 36756121
DOI: 10.3389/fimmu.2023.1082980 -
Clinical Lung Cancer Sep 2020Approximately one third of patients with non-small-cell lung cancer (NSCLC) present with stage III or locally advanced NSCLC. These patients have historically been... (Review)
Review
Approximately one third of patients with non-small-cell lung cancer (NSCLC) present with stage III or locally advanced NSCLC. These patients have historically been managed with chemoradiotherapy. However, outcomes for these patients remain poor, with a 5-year survival rate between 15% and 32%. Immune checkpoint inhibitors have revolutionized the treatment of patients with NSCLC. One such agent, durvalumab, a selective high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 binding to programmed cell death protein 1 and cluster of differentiation 80, was recently approved in the consolidation setting after completion of definitive platinum-based chemoradiotherapy and has become the current standard of care for patients with stage III locally advanced NSCLC. Immune checkpoint blockade is associated with increased risk of immunotherapy-related adverse events, which can be managed most effectively when detected early, ideally in the context of a multidisciplinary approach. Pneumonitis represents the potentially most severe and life-threatening of all reported immunotherapy-related adverse events, but it is further complicated in the context of recent prior therapies also known to cause pulmonary toxicity, such as radiotherapy. However, there are major gaps in our ability to identify immunotherapy-related pneumonitis and distinguish it from radiation pneumonitis. This review aims to define the key steps in the detection, diagnosis, and treatment of immunotherapy-related pneumonitis.
Topics: Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Prognosis
PubMed: 32576443
DOI: 10.1016/j.cllc.2020.02.025 -
Thorax Feb 1977Thirty human lung biopsy specimens have been diagnoses as desquamative interstitial pneumonitis. Six cases had intraalveolar lesions, believed to be early, while 20 had... (Review)
Review
Thirty human lung biopsy specimens have been diagnoses as desquamative interstitial pneumonitis. Six cases had intraalveolar lesions, believed to be early, while 20 had advanced disease characterised by intraalveolar cellular clumps, alveolar wall fibrosis, distortion, and loss of pulmonary parenchyma. Electron microscopy, high resolution light microscopy, and cytological examination have shown that the characteristic clumps in the alveolar air spaces are formed predominantly by enlarged and aggregated macrophages. Lymphocytes and eosinophils are also present in the intraalveolar clumps and in alveolar walls. Inflammation and immunological mechanisms are suggested as causes of the cellular clumping. Interstitial pneumonitis, alveolar wall fibrosis, changes in the alveolar epithelium, and loss of lung parenchyma are believed to be secondary events.
Topics: Adult; Aged; Chronic Disease; Diagnosis, Differential; Female; Humans; Lung; Male; Microscopy, Electron; Middle Aged; Pneumonia; Pulmonary Fibrosis
PubMed: 320710
DOI: 10.1136/thx.32.1.7 -
Frontiers in Immunology 2022Whilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high...
PURPOSE
Whilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high risk of treatment-related pneumonitis remains a concern. Asians may be more sensitive to lung toxicity than other races. This retrospective study intended to provide a comprehensive pneumonitis profile of TRT followed by ICI and investigate the risk factors from a Chinese cohort of lung cancer.
METHODS AND MATERIALS
From January 2016 to July 2021, 196 patients with lung cancer who received TRT prior to ICI were retrospectively analyzed. Treatment-related pneumonitis, including checkpoint inhibitor pneumonitis (CIP), radiation pneumonitis (RP), and radiation recall pneumonitis (RRP), were recorded and graded through medical records and chest computed tomography. Characteristics predictive of pneumonitis were assessed using logistic regression models, and the receiver operating characteristic analyses were performed to identify optimal cut points for quantitative variables.
RESULTS
With a median follow-up of 18 months, a total of 108 patients (55.1%) developed treatment-related pneumonitis during ICI therapy, with an incidence of 25.5% for grade 2 or higher (G2+) and 4.1% for G3+. The overall rates of CIP, RP and RRP were 8.2% (n=16), 46.9% (n=92) and 7.1% (n=14), respectively. With a total mortality rate of 1.5%, vast majority of the patients recovered from pneumonitis or remained stable. No patients died of RRP. Half of the patients with G2+ RP who withheld ICI therapy restarted ICI safely after resolution of RP. The history of chronic pulmonary diseases (=0.05), mean lung dose (MLD, =0.038), percent volume of lung receiving ≥5 Gy (V5, =0.012) and percent volume of lung receiving ≥20 Gy (V20, =0.030) predicted the occurrence of RRP in univariate analyses. Interval between TRT and ICI less than 3 months was an independent predictor for G2+ treatment-related pneumonitis in a multivariate model (Odds ratio OR=2.787, =0.004).
CONCLUSIONS
Treatment-related pneumonitis, especially RRP, is acceptable and manageable in the setting of TRT followed by ICI in this Asian population. Dosimetric parameters MLD, V5 and V20 may improve the predictions of RRP in clinical practice.
Topics: Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Radiation Pneumonitis; Retrospective Studies; Risk Factors
PubMed: 35795657
DOI: 10.3389/fimmu.2022.918787