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Frontiers in Immunology 2023Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is...
Heterogenous lung inflammation CT patterns distinguish pneumonia and immune checkpoint inhibitor pneumonitis and complement blood biomarkers in acute myeloid leukemia: proof of concept.
BACKGROUND
Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is time-consuming and challenging. To fill this gap, we build an image-based tool, and further evaluate it clinically alongside relevant blood biomarkers.
MATERIALS AND METHODS
We studied CT images from 97 patients with pneumonia and 29 patients with pneumonitis from acute myeloid leukemia treated with ICIs. We developed a CT-derived signature using a habitat imaging algorithm, whereby infected lungs are segregated into clusters ("habitats"). We validated the model and compared it with a clinical-blood model to determine whether imaging can add diagnostic value.
RESULTS
Habitat imaging revealed intrinsic lung inflammation patterns by identifying 5 distinct subregions, correlating to lung parenchyma, consolidation, heterogenous ground-glass opacity (GGO), and GGO-consolidation transition. Consequently, our proposed habitat model (accuracy of 79%, sensitivity of 48%, and specificity of 88%) outperformed the clinical-blood model (accuracy of 68%, sensitivity of 14%, and specificity of 85%) for classifying pneumonia versus pneumonitis. Integrating imaging and blood achieved the optimal performance (accuracy of 81%, sensitivity of 52% and specificity of 90%). Using this imaging-blood composite model, the post-test probability for detecting pneumonitis increased from 23% to 61%, significantly ( = 1.5 - 9) higher than the clinical and blood model (post-test probability of 22%).
CONCLUSION
Habitat imaging represents a step forward in the image-based detection of pneumonia and pneumonitis, which can complement known blood biomarkers. Further work is needed to validate and fine tune this imaging-blood composite model and further improve its sensitivity to detect pneumonitis.
Topics: Humans; Immune Checkpoint Inhibitors; Pneumonia; Tomography, X-Ray Computed; Inflammation; Biomarkers; Leukemia, Myeloid, Acute
PubMed: 37841255
DOI: 10.3389/fimmu.2023.1249511 -
The Oncologist Jun 2018Substantial improvements in the early detection and treatment of breast cancer have led to improvements in survival, but breast cancer remains a significant cause of... (Review)
Review
UNLABELLED
Substantial improvements in the early detection and treatment of breast cancer have led to improvements in survival, but breast cancer remains a significant cause of morbidity and mortality in women. In 2012, the mammalian target of rapamycin (mTOR) inhibitor everolimus was approved by the U.S. Food and Drug Administration for the treatment of advanced breast cancer in patients resistant to endocrine therapy. Although everolimus is generally well tolerated, mTOR inhibitor-associated pneumonitis is one of the most common adverse drug events leading to treatment discontinuation. To date, the underlying pathophysiology of this toxicity is unclear, and this uncertainty may hinder the optimization of management strategies. However, experiences from breast cancer and renal cell carcinoma clinical trials indicate that mTOR inhibitor-associated pneumonitis can be effectively managed by early detection, accurate diagnosis, and prompt intervention that generally involves everolimus dose reductions, interruptions, or discontinuation. Management can be achieved by a multidisciplinary approach that involves the collaborative efforts of nurses, oncologists, radiologists, infectious disease specialists, pulmonologists, clinical pharmacists, and pathologists. Comprehensive education must be provided to all health care professionals involved in managing patients receiving everolimus therapy. Although general recommendations on the management of mTOR inhibitor-associated pneumonitis have been published, there is a lack of consensus on the optimal management of this potentially serious complication. This article provides an overview of mTOR inhibitor-associated pneumonitis, with a focus on the detection, accurate diagnosis, and optimal management of this class-related complication of mTOR inhibitor therapy.
IMPLICATIONS FOR PRACTICE
This article summarizes the pathogenesis, clinical presentation, incidence, detection, and optimal management of everolimus-related noninfectious pneumonitis in breast cancer. In particular, this article provides a detailed overview of the important aspects of the detection, accurate diagnosis, and appropriate management of mammalian target of rapamycin inhibitor-associated pneumonitis. In addition, this article emphasizes that effective management of this adverse drug event in patients with breast cancer will require a multidisciplinary approach and collaboration among various health care professionals.
Topics: Breast Neoplasms; Female; Humans; Pneumonia; TOR Serine-Threonine Kinases
PubMed: 29487226
DOI: 10.1634/theoncologist.2017-0343 -
Internal Medicine (Tokyo, Japan) 2012
Topics: Acyclovir; Adult; Antiviral Agents; Chickenpox; Female; Humans; Incidental Findings; Pneumonia, Viral; Radiography
PubMed: 22449689
DOI: 10.2169/internalmedicine.51.6409 -
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 2023Immune checkpoint inhibitors (ICIs) modulate the body's immune function to treat tumors but may also induce pneumonitis. Immune checkpoint inhibitor-related pneumonitis... (Review)
Review
Immune checkpoint inhibitors (ICIs) modulate the body's immune function to treat tumors but may also induce pneumonitis. Immune checkpoint inhibitor-related pneumonitis (ICIP) is a serious immune-related adverse event (irAE). Immunotherapy is currently approved as a first-line treatment for non-small cell lung cancer (NSCLC), and the incidence of ICIP in NSCLC patients can be as high as 5%-19% in clinical practice. ICIP can be severe enough to lead to the death of NSCLC patients, but there is a lack of a gold standard for the diagnosis of ICIP. Radiomics is a method that uses computational techniques to analyze medical images (e.g., CT, MRI, PET) and extract important features from them, which can be used to solve classification and regression problems in the clinic. Radiomics has been applied to predict and identify ICIP in NSCLC patients in the hope of transforming clinical qualitative problems into quantitative ones, thus improving the diagnosis and treatment of ICIP. In this review, we summarize the pathogenesis of ICIP and the process of radiomics feature extraction, review the clinical application of radiomics in ICIP of NSCLC patients, and discuss its future application prospects.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Immunotherapy
PubMed: 37799725
DOI: 10.3389/fimmu.2023.1251645 -
BMJ Case Reports Jul 2021Pembrolizumab is a selective anti-PD-L1 humanised monoclonal antibody approved by the Food and Drug Administration for treating multiple cancers, including cervical...
Pembrolizumab is a selective anti-PD-L1 humanised monoclonal antibody approved by the Food and Drug Administration for treating multiple cancers, including cervical cancer, non-small cell lung cancer (NSCLC), renal cell carcinoma, bladder cancer, and squamous head and neck cancer. Pneumonitis is a rare but known complication of pembrolizumab treatment for NSCLC. The median time frame of its appearance is 2.8 months. However, we present a case of pneumonitis appearing within 48 hours. The patient presented with rapidly progressive respiratory failure, and imaging demonstrated diffuse bilateral patchy involvement of the upper lung lobe and pre-hilar regions, which likely indicate pneumonitis. Because of likely grade 3 pneumonitis, he was treated with steroids and showed immediate improvement of symptoms. Repeated CT imaging showed resolution of bilateral patchy infiltrates. He was discharged to the rehabilitation unit. Rapid recognition of pneumonitis as a side effect of pembrolizumab is important because early treatment can help prevent respiratory failure and possible death.
Topics: Antibodies, Monoclonal, Humanized; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Male; Pneumonia
PubMed: 34266820
DOI: 10.1136/bcr-2021-242493 -
The Oncologist Jan 2024Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable outcomes, they are associated with a unique set of toxicities termed as immune-related adverse events (irAEs). Among the toxicities, ICI-related pneumonitis has poor outcomes with little understanding of its risk factors. This retrospective study aimed to investigate whether pre-existing interstitial lung abnormality (ILA) is a potential risk factor for ICI-related pneumonitis.
MATERIALS AND METHODS
Patients with non-small cell lung cancer, malignant melanoma, renal cell carcinoma, and gastric cancer, who was administered either nivolumab, pembrolizumab, or atezolizumab between September 2014 and January 2019 were retrospectively reviewed. Information on baseline characteristics, computed tomography findings before administration of ICIs, clinical outcomes, and irAEs were collected from their medical records. Pre-existing ILA was categorized based on previous studies.
RESULTS
Two-hundred-nine patients with a median age of 68 years were included and 23 (11.0%) developed ICI-related pneumonitis. While smoking history and ICI agents were associated with ICI-related pneumonitis (P = .005 and .044, respectively), the categories of ILA were not associated with ICI-related pneumonitis (P = .428). None of the features of lung abnormalities were also associated with ICI-related pneumonitis. Multivariate logistic analysis indicated that smoking history was the only significant predictor of ICI-related pneumonitis (P = .028).
CONCLUSION
This retrospective study did not demonstrate statistically significant association between pre-existing ILA and ICI-related pneumonitis, nor an association between radiologic features of ILA and ICI-related pneumonitis. Smoking history was independently associated with ICI-related pneumonitis. Further research is warranted for further understanding of the risk factors of ICI-related pneumonitis.
Topics: Humans; Aged; Carcinoma, Non-Small-Cell Lung; Retrospective Studies; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Kidney Neoplasms; Lung
PubMed: 37590388
DOI: 10.1093/oncolo/oyad187 -
Cancer Medicine Jul 2023Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) have shown remarkable clinical activity in patients with non-small-cell lung cancer (NSCLC). However,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) have shown remarkable clinical activity in patients with non-small-cell lung cancer (NSCLC). However, pneumonitis is a serious side effect of ALK TKIs in NSCLC patients. In this meta-analysis, we aimed to determine the incidence of ALK-TKI-associated pneumonitis.
MATERIALS AND METHODS
We searched electronic databases to identify relevant studies published until August 2022. The incidence of pneumonitis was calculated using a fixed-effects model when no substantial heterogeneity was observed. Otherwise, a random-effects model was used. Subgroup analyses of different treatment groups were performed. Statistical analyses were conducted using STATA 17.0.
RESULTS
Twenty-six clinical trials involving 4752 patients were eligible for analysis. All-grade pneumonitis incidence was 2.92% (95% confidence interval [CI]: 1.79%-4.27%), high-grade (Grade 3-4) pneumonitis incidence was 1.42% (95% CI: 0.84%-2.12%) and Grade 5 pneumonitis incidence was 0.09% (95% CI: 0.00%-0.28%). The subgroup analysis showed that brigatinib was associated with the highest incidence of both all-grade and high-grade pneumonitis (7.09% and 3.06%, respectively). ALK TKI treatment after chemotherapy was associated with a higher incidence of all-grade and high-grade pneumonitis than first-line ALK TKI treatment (7.73% vs. 2.26% and 3.64% vs. 1.26%, respectively). Cohorts from Japanese trials had a higher incidence of all-grade and high-grade pneumonitis.
CONCLUSION
Our study provides precise data on the incidence of pneumonitis in patients receiving treatment with ALK TKIs. Overall, ALK TKIs have tolerable pulmonary toxicity. Early pneumonitis identification and treatment are required to prevent further deterioration in patients receiving treatment with brigatinib and in those who received prior chemotherapy, particularly in the Japanese population.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Protein-Tyrosine Kinases; Anaplastic Lymphoma Kinase; Tyrosine Kinase Inhibitors; Incidence; Protein Kinase Inhibitors; Pneumonia; Drug-Related Side Effects and Adverse Reactions
PubMed: 37017467
DOI: 10.1002/cam4.5913 -
Canadian Respiratory Journal 2009Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodinecontaining compound that tends to... (Review)
Review
Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodinecontaining compound that tends to accumulate in several organs, including the lungs. It has been associated with a variety of adverse events. Of these events, the most serious is amiodarone pulmonary toxicity. Although the incidence of this complication has decreased with the use of lower doses of amiodarone, it can occur with any dose. Because amiodarone is widely used, all clinicians should be vigilant of this possibility. Pulmonary toxicity usually manifests as an acute or subacute pneumonitis, typically with diffuse infiltrates on chest x-ray and high-resolution computed tomography. Other, more localized, forms of pulmonary toxicity may occur, including pleural disease, migratory infiltrates, and single or multiple nodules. With early detection, the prognosis is good. Most patients diagnosed promptly respond well to the withdrawal of amiodarone and the administration of corticosteroids, which are usually given for four to 12 months. It is important that physicians be familiar with amiodarone treatment guidelines and follow published recommendations for the monitoring of pulmonary as well as extrapulmonary adverse effects.
Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Dose-Response Relationship, Drug; Humans; Pneumonia; Risk Factors; Ventricular Dysfunction
PubMed: 19399307
DOI: 10.1155/2009/282540 -
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