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Cancer Medicine Feb 2024Immune-related pneumonitis is a rare and potentially fatal adverse event associated with sintilimab. We aimed to develop and validate a nomogram for predicting the risk...
BACKGROUND
Immune-related pneumonitis is a rare and potentially fatal adverse event associated with sintilimab. We aimed to develop and validate a nomogram for predicting the risk of immune-related pneumonitis in patients treated with sintilimab.
METHODS
The least absolute shrinkage and selection operator (LASSO) regression was used to determine risk factors. Multivariable logistic regression was used to establish a prediction model. Its clinical validity was evaluated using calibration, discrimination, decision, and clinical impact curves. Internal validation was performed against the validation set and complete dataset.
RESULTS
The study included 632 patients; 59 were diagnosed with immune-related pneumonitis. LASSO regression analysis identified that the risk factors for immune-related pneumonitis were pulmonary metastases (odds ratio [OR], 4.015; 95% confidence interval [CI]: 1.725-9.340) and metastases at >3 sites (OR, 2.687; 95% CI: 1.151-6.269). The use of combined antibiotics (OR, 0.247; 95% CI: 0.083-0.738) and proton pump inhibitors (OR, 0.420; 95% CI: 0.211-0.837) were protective factors. The decision and clinical impact curves showed that the nomogram had clinical value for patients treated with sintilimab.
CONCLUSIONS
We have developed and validated a practical nomogram model of sintilimab-associated immune-related pneumonitis, which provides clinical value for determining the risk of immune-related pneumonitis and facilitating the safe administration of sintilimab therapy.
Topics: Humans; Nomograms; Pneumonia; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized
PubMed: 38214102
DOI: 10.1002/cam4.6708 -
The Netherlands Journal of Medicine Aug 2018Hydroxycarbamide is used in the treatment of myeloproliferative neoplasms. Hydroxycarbamide is known for its relative lack of severe side effects. Here we present a... (Review)
Review
Hydroxycarbamide is used in the treatment of myeloproliferative neoplasms. Hydroxycarbamide is known for its relative lack of severe side effects. Here we present a 66-year-old man with a severe pneumonitis within three weeks after starting him on hydroxycarbamide. He developed life-threatening respiratory failure and was admitted to an intensive care unit. Extensive testing of blood and cultures from sputum and bronchoalveolar lavage fluid did not reveal a pathogenic microorganism. Discontinuation of the drug and treatment with prednisolone resulted in clinical improvement within 2 days. Radiological resolution was confirmed after one month. The clinical course suggests that the pneumonitis was induced by hydroxycarbamide. We want to alert physicians that, in spite of the common assumption that the use of hydroxycarbamide is relatively safe, patients can develop a severe pneumonitis with detrimental outcome and that hydroxycarbamide should be considered a causative agent in the differential diagnosis of pneumonitis.
Topics: Administration, Oral; Aged; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Humans; Hydroxyurea; Male; Myeloproliferative Disorders; Netherlands; Pneumonia; Prednisolone; Respiratory Insufficiency; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 30152396
DOI: No ID Found -
Journal For Immunotherapy of Cancer Jul 2020Pneumonitis is a rare but serious adverse event caused by cancer immunotherapy. The diagnosis between COVID-19-induced pneumonia and immunotherapy-induced pneumonitis...
Pneumonitis is a rare but serious adverse event caused by cancer immunotherapy. The diagnosis between COVID-19-induced pneumonia and immunotherapy-induced pneumonitis may be challenging in the era of COVID-19 outbreak. Some clinical symptoms and radiological findings of pneumonitis can be attributed to the coronavirus infection as well as to an immune-related adverse event. Identifying the exact cause of a pneumonitis in patients on treatment with immunotherapy is crucial to promptly start the most appropriate treatment. The proper management of immune checkpoint inhibitors for the risk of pneumonia must take into account a series of parameters. Accurate attention should be payed to symptoms like cough, fever and dyspnea during immunotherapy.
Topics: Antineoplastic Agents, Immunological; Betacoronavirus; COVID-19; COVID-19 Testing; CTLA-4 Antigen; Clinical Laboratory Techniques; Coronavirus Infections; Diagnosis, Differential; False Negative Reactions; Glucocorticoids; Humans; Immunosuppressive Agents; Lung; Neoplasms; Pandemics; Pneumonia; Pneumonia, Viral; Programmed Cell Death 1 Receptor; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 32699182
DOI: 10.1136/jitc-2020-000952 -
Journal For Immunotherapy of Cancer Apr 2019Pneumonitis is a potential consequence of both lung-directed radiation and immune checkpoint blockade (ICB), particularly treatment with PD-1/PD-L1 inhibitors....
BACKGROUND
Pneumonitis is a potential consequence of both lung-directed radiation and immune checkpoint blockade (ICB), particularly treatment with PD-1/PD-L1 inhibitors. Significant morbidity and mortality can result, and severe pneumonitis attributed to ICB precludes continued therapy. Thus, discriminating between radiation- and ICB- related pneumonitis is of importance for the increasing number of patients receiving both treatments. Furthermore, data are limited regarding the interplay between radiation- and ICB-induced lung injury, and which biomarkers might be associated with toxicity.
CASE PRESENTATION
We report longitudinal clinical and radiologic data, and circulating biomarkers in a melanoma patient treated with axillary radiation followed by ICB who developed consolidation and ground glass opacities (GGO) within the radiation field suggestive of radiation-pneumonitis followed by consolidation outside of the radiation field suggestive of ICB-related pneumonitis. Of note, symptomatic radiation-pneumonitis developed despite a low radiation dose to the lung (V20 < 8%), and ICB-related pneumonitis was limited to the ipsilateral lung, suggesting additive effect of radiation and ICB in the development of lung injury. Circulating biomarker analyses demonstrated increases in CXCR2, IL1ra and IL2ra that coincided with the development of symptomatic pneumonitis.
CONCLUSIONS
These data highlight the imaging findings associated with radiation and ICB-related lung toxicity, and anecdotally describe a clinical course with circulating biomarker correlates. This information can help guide clinical evaluation and future research investigations into the toxicity of combined radiation immunotherapy approaches.
Topics: Antineoplastic Agents, Immunological; Biomarkers; Cytokines; Humans; Inflammation Mediators; Male; Melanoma; Middle Aged; Pneumonia; Radiography, Thoracic; Radiotherapy; Tomography, X-Ray Computed
PubMed: 31014385
DOI: 10.1186/s40425-019-0583-3 -
The American Journal of Case Reports Aug 2020BACKGROUND Rifampicin-induced pneumonitis is an infrequent occurrence, with only a few cases reported in the literature. Furthermore, this condition constitutes a...
BACKGROUND Rifampicin-induced pneumonitis is an infrequent occurrence, with only a few cases reported in the literature. Furthermore, this condition constitutes a diagnostic challenge, particularly in the era of COVID-19 infection. Here, we report a case of rifampicin-induced pneumonitis with clinical, imaging, and histological features of acute respiratory distress syndrome (ARDS), which required severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to exclude a diagnosis of coronavirus disease 2019 (COVID-19) pneumonia. CASE REPORT A 43-year-old man on anti-TB treatment for TB meningitis developed new-onset fever, fatigue, hypoxemic respiratory failure, and bilateral pulmonary opacities. His clinical, chest X-ray, and CT thorax findings of ARDS were similar to both rifampicin-induced pneumonitis and severe COVID-19 pneumonia. However, reverse transcription polymerase chain reaction (RT-PCR) testing from a nasopharyngeal swab and bronchoalveolar lavage (BAL) via the GeneXpert system was negative for SARS-CoV-2. A detailed workup, including lung biopsy, revealed drug-induced pneumonitis as the cause of his presentation. His pneumonitis improved after discontinuation of rifampicin and recurred following the rifampicin challenge. CONCLUSIONS This case highlights the importance of early, rapid, and accurate testing for SARS-CoV-2 during the COVID-19 pandemic for patients presenting with acute respiratory symptoms, so that accurate diagnosis and early patient management are not delayed for patients with treatable causes of acute and severe lung diseases. Timely identification of rifampicin-induced pneumonitis via a high clinical suspicion, detailed workup, and histopathological analysis is required to avoid permanent damage to the lungs.
Topics: Adult; Antibiotics, Antitubercular; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Male; Pandemics; Pneumonia; Pneumonia, Viral; Rifampin; SARS-CoV-2; Tomography, X-Ray Computed; Tuberculosis, Meningeal
PubMed: 32840240
DOI: 10.12659/AJCR.927586 -
Science Translational Medicine Jun 2019Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by mutations, presents with several autoimmune diseases. Among...
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by mutations, presents with several autoimmune diseases. Among these, endocrine organ failure is widely recognized, but the prevalence, immunopathogenesis, and treatment of non-endocrine manifestations such as pneumonitis remain poorly characterized. We enrolled 50 patients with APECED in a prospective observational study and comprehensively examined their clinical and radiographic findings, performed pulmonary function tests, and analyzed immunological characteristics in blood, bronchoalveolar lavage fluid, and endobronchial and lung biopsies. Pneumonitis was found in >40% of our patients, presented early in life, was misdiagnosed despite chronic respiratory symptoms and accompanying radiographic and pulmonary function abnormalities, and caused hypoxemic respiratory failure and death. Autoantibodies against BPIFB1 and KCNRG and the homozygous c.967_979del13 mutation are associated with pneumonitis development. APECED pneumonitis features compartmentalized immunopathology, with accumulation of activated neutrophils in the airways and lymphocytic infiltration in intraepithelial, submucosal, peribronchiolar, and interstitial areas. Beyond APECED, we extend these observations to lung disease seen in other conditions with secondary AIRE deficiency (thymoma and RAG deficiency). Aire-deficient mice had similar compartmentalized cellular immune responses in the airways and lung tissue, which was ameliorated by deficiency of T and B lymphocytes. Accordingly, T and B lymphocyte-directed immunomodulation controlled symptoms and radiographic abnormalities and improved pulmonary function in patients with APECED pneumonitis. Collectively, our findings unveil lung autoimmunity as a common, early, and unrecognized manifestation of APECED and provide insights into the immunopathogenesis and treatment of pulmonary autoimmunity associated with impaired central immune tolerance.
Topics: Adolescent; Adult; Autoantibodies; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Lymphocytes; Male; Middle Aged; Pneumonia; Prospective Studies; T-Lymphocytes; Young Adult
PubMed: 31167928
DOI: 10.1126/scitranslmed.aav5597 -
Pulmonology 2023
Topics: Humans; Leukemia, Myeloid, Acute; Pneumonia
PubMed: 35963829
DOI: 10.1016/j.pulmoe.2022.06.010 -
Histopathology Dec 2022To improve understanding of the pathology of immune check-point inhibitor (ICI)-related pneumonitis, clinical, radiographic and histopathological features and outcomes...
AIMS
To improve understanding of the pathology of immune check-point inhibitor (ICI)-related pneumonitis, clinical, radiographic and histopathological features and outcomes were investigated in a cohort of patients who were treatment-naive before receiving ICI inhibition, who underwent lung biopsy, and in whom other potential causes of lung injury were excluded.
METHODS
Patients were retrospectively identified via searches of institutional pathology and clinical records. Patients treated with other modalities for cancer and patients with lung infections or other aetiologies that could cause pneumonitis were excluded. Clinical records were reviewed by pulmonologists. Imaging studies at presentation and follow-up were reviewed by a thoracic radiologist. Pathology was reviewed by thoracic pathologists.
RESULTS
Six patients with ICI-related pneumonitis were identified. Two patients presented with respiratory failure requiring mechanical ventilation, diffuse ground glass opacities (GGOs) on chest computed tomography (CT) and acute lung injury (ALI) pattern on transbronchial lung biopsies and had fatal outcomes, despite treatment. The remaining four patients presented with less severe symptoms, predominantly consolidations and patchy ground glass and part solid opacities on chest CT, organising pneumonia (OP) or chronic interstitial inflammation histologically, and showed favourable responses to treatment and remission within months.
CONCLUSIONS
This study highlights two radiological-pathological patterns of ICI-related pneumonitis with different behaviour: (1) severe respiratory symptoms and diffuse GGOs on imaging correlating with ALI pattern histologically and poor prognosis; and (2) mild respiratory symptoms and consolidations or patchy subsolid opacities on imaging correlating histologically with OP or chronic interstitial inflammation and good outcomes.
Topics: Humans; Retrospective Studies; Pneumonia; Tomography, X-Ray Computed; Acute Lung Injury; Inflammation; Lung
PubMed: 35775853
DOI: 10.1111/his.14704 -
Italian Journal of Pediatrics Apr 2020Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species,... (Review)
Review
Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.
Topics: Betacoronavirus; Breast Feeding; COVID-19; Coronavirus Infections; Humans; Infant; Infant, Newborn; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32349772
DOI: 10.1186/s13052-020-0820-x -
In Vivo (Athens, Greece) 2021It is important to identify radiation pneumonitis above Common Terminology Criteria for Adverse Events Grade 2 (G2) in order to safely continue durvalumab maintenance...
BACKGROUND/AIM
It is important to identify radiation pneumonitis above Common Terminology Criteria for Adverse Events Grade 2 (G2) in order to safely continue durvalumab maintenance after chemoradiotherapy for advanced lung cancer. The aim of this study was to discover factors that predict pneumonitis above G2.
PATIENTS AND METHODS
A follow-up computed tomography (CT) image was superimposed on the planning CT image using deformable image registration (DIR). The pneumonitis area was contoured on follow-up CT after DIR and the dose-volume histogram parameters of the contoured pneumonitis area were calculated.
RESULTS
V5 (Percentage of total volume receiving ≥5 Gy) to V50 of pneumonitis were significantly lower in patients with G2 pneumonitis than in those with G1 pneumonitis. The pneumonitis V15 was the most significant. The group with pneumonitis V15 <87.10% had significantly more G2 pneumonitis than the group with pneumonitis V15 ≥87.10%.
CONCLUSION
Pneumonitis V15 <87.10% was a risk factor for G2 pneumonitis.
Topics: Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Humans; Lung Neoplasms; Pneumonia; Radiation Pneumonitis; Radiotherapy Dosage
PubMed: 34697180
DOI: 10.21873/invivo.12644