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Drug-Induced Interstitial Pneumonitis In Children
Published in Lourdes R. Laraya-Cuasay, Walter T. Hughes, Interstitial Lung Diseases in Children, 2019
Marina I. Liscano, Lawrence J. Ettinger
Interstitial pneumonitis and pulmonary fibrosis are the major pulmonary toxicities, resulting in abnormal pulmonary function manifested by a restrictive pattern and a decrease in diffusing capacity (DLCO).2 The pathophysiology has not been defined in man, but has been described in mice following bleomycin administration.1 Ad described by Adamson and Bowden3 the first pathologic finding is the development of endothelial blebs in the alveolar capillary endothelium. This is followed by the development of interstitial fibrinous edema, a mononuclear cell response, and hyaline membranes. Electron microscopic studies in man have shown a decrease in type I pneumocytes and a subsequent change in type II pneu-mocytes, including proliferation, delamellation, and migration into alveolar sacs. Finally, the alveolar septae become thickened, collagen fibers are noted adjacent to fibroblasts, and a dense proliferation of fibrous tissue and a decrease in the number of alveolar septae occur. In several animal species, these changes have been observed initially in the subpleural region with later extension into the bronchiolar areas. Pleural thickening may accompany the pneumonitis.1 Although pulmonary toxicity is thought to be the result of a direct toxic effect in most cases, immunologic and hypersensitivity mechanisms may also play a role in certain cases.2,4,5 These toxicities may occur during therapy or following discontinuation of the implicated drug.
Understanding the role of co-morbidities in interstitial lung diseases
Published in Muhunthan Thillai, David R Moller, Keith C Meyer, Clinical Handbook of Interstitial Lung Disease, 2017
Adrian Shifren, Tonya Russell, Adam L Anderson, Steven D Nathan
Pulmonary toxicity remains an important consideration in the differential diagnosis of patients treated for ILD who present with progressive respiratory symptoms or worsening infiltrates. Prognosis varies depending on the type and severity of pulmonary toxicity; however, in the face of already compromised lung function, drug-induced pulmonary disease may result in significant patient morbidity and mortality.
A strategy for interpretation of pulmonary function tests
Published in Jonathan Dakin, Mark Mottershaw, Elena Kourteli, Making Sense of Lung Function Tests, 2017
Jonathan Dakin, Mark Mottershaw, Elena Kourteli
There is a reduction of FVC, with a Kco which is normal or impaired. Suspect interstitial lung disease (ILD). TLco should also be examined, as reduction of TLco is more sensitive in detection of abnormality than reduction in Kco. Fine inspiratory crepitations are usually present on auscultation, though they may be absent in patients with sarcoidosis. Are there any risk factors for ILD e.g. connective-tissue disease, antigen or occupational exposure, treatment with drugs known to cause pulmonary toxicity? Consider a high-resolution CT scan of the thorax.
Acute hazard assessment of silver nanoparticles following intratracheal instillation, oral and intravenous injection exposures
Published in Nanotoxicology, 2021
Ali Kermanizadeh, Nicklas R. Jacobsen, Agnieszka Mroczko, David Brown, Vicki Stone
Despite the many insights offered in this study and the comprehensive toxicological assessment in the extra-pulmonary organs, there is a major limitation in the study design that needs to be mentioned and considered in the interpretation of findings. In all reality, any realistic NP-induced adverse effects to extra-pulmonary organs in man would only occur following long-term exposure (with the exception of intentional IV administration of nanomedicines). Hence in an ideal in vivo hazard assessment, studies should to be carried out with low intermittent repeated dosing and to incorporate recovery periods to allow for the assessment of clearance of NPs, manifestation of adverse effects and potential for organ recovery to be identified. That being said, this study is valuable in allowing for a direct comparison to be made between the different routes of toxicity and how this important variable affects the toxicity observed extra-pulmonary tissues. Any upcoming studies might also investigate a wider range of time points post material exposure to identify the optimum peak for certain endpoints (e.g. acute-phase response, cytokine production). It is also important to state that this is the first of two independent studies investigating NP-induced extra-pulmonary toxicity following different routes of exposure. In this paper, Ag NPs was selected as a high solubility material, while TiO2 is utilized in the second study as a low solubility NP (manuscript in preparation).
Impact of unfavorable factors on outcomes among inoperable stage II-IV Nonsmall cell lung cancer patients treated with proton therapy
Published in Acta Oncologica, 2019
He J. Zhu, Romaine C. Nichols, Randal H. Henderson, Christopher G. Morris, Stella Flampouri, Dat C. Pham, Christopher L. Klassen, Vandana Seeram, James D. Cury, Lisa Jones, Lisa McGee, Bradford S. Hoppe
Both acute and late toxicities potentially associated with PT or chemotherapy were prospectively recorded during on-treatment and follow-up visits (Table 3). Toxicity assessments on the first treatment day indicate patients’ baseline pulmonary issues. Overall, no significant difference in either acute or late toxicities was observed between the two risk groups. Both groups reported a high rate of grade 2 acute esophagitis (70% and 48%) with subtle differences attributed to lower use of concurrent chemoradiation and more stage II patients in the unfavorable cohort, but only 4% and 3% developed grade 3 esophagitis in the favorable and unfavorable groups, respectively. Late esophageal toxicities more than 6 months after treatment were similar between the two groups with 1 grade 3 or higher event in both groups. Symptomatic (grade 2 or higher) radiation pneumonitis within 6 months of treatment occurred in 14% of unfavorable-risk patients and 13% of favorable-risk patients, including 4 patients with grade 3 toxicity, 3 of whom had a prior history of lung surgery. Maximum late pulmonary toxicity reflects that only a couple of patients developed the majority of the grade 3 or higher pulmonary toxicities. In fact, only 1 favorable patient developed a grade 3 or higher late pulmonary complication, while 6 complained of a grade 2 or higher late complication under the setting of 3 having complained at baseline. Among the unfavorable patients, 6 complained of a late grade 3 toxicity (4 complained at baseline) and 24 complained of grade 2 toxicity (14 complained at baseline).
Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage III or IV classical Hodgkin lymphoma
Published in Journal of Medical Economics, 2019
Thomas E. Delea, Arati Sharma, Aaron Grossman, Caitlin Eichten, Keenan Fenton, Neil Josephson, Akshara Richhariya, Alison J. Moskowitz
The long-term absolute excess mortality associated with exposure to frontline chemotherapy was estimated based on results of a study of 1,261 patients treated for Hodgkin lymphoma between 1965 and 1987 and followed until October 200024. Because absolute excess mortality in this study increased approximately linearly by time since frontline therapy, absolute excess mortality in the model was estimated by fitting a linear regression equation to these data. The long-term relative risk of death for patients with pulmonary toxicity was based on a retrospective study by Martin et al.3 of 141 patients who were treated with bleomycin-containing chemotherapy for newly-diagnosed Hodgkin lymphoma between 1986 and 2003. The long-term relative risk of death with grade 3 or higher pulmonary toxicity was estimated to be 2.5 by comparing the reported Kaplan Meier estimated OS after 5 years for patients with vs without pulmonary toxicity.