Dataset Information

Clinician Attitudes to Using Low-Dose Radiation Therapy to Treat COVID-19 Lung Disease.

ABSTRACT:

Purpose

Current treatments for coronavirus disease 2019 (COVID-19) lung disease have limited efficacy. Low-dose radiation therapy (LDRT) has received both interest and criticism as a potential treatment for this condition. In this qualitative study we explored clinicians' perspectives to identify barriers to testing LDRT in clinical trials and implementing it in clinical practice.

Methods and materials

Semistructured interviews were undertaken with 6 clinicians from 3 medical disciplines. Interviews were recorded, transcribed verbatim, and analyzed thematically, using a framework approach. Common themes regarding barriers to using LDRT for COVID-19 lung disease were identified from the data.

Results

Three categories of barriers emerged: (1) the potential to do harm to the patient, including difficulty in predicting harm and lack of existing data to inform quantification of risks; (2) the feasibility of trialing this novel treatment strategy in the clinical setting, in particular trial design and recruitment, patient selection and buy-in from relevant clinician groups; and (3) the logistics of delivering the treatment, in particular risks of transmission to other patients and resources required for patient transfer.

Conclusions

This study identified several barriers that may impede the evaluation and subsequent implementation of LDRT as a treatment for COVID-19 lung disease, from the perspectives of clinicians in 3 relevant specialties. By documenting and articulating these concerns, we hope to enhance discussion of why these barriers exist, and enable them to be addressed in a proactive manner to facilitate research into the potential benefits of radiation treatment for patients with COVID-19 lung disease going forward.

SUBMITTER: Hanna CR

PROVIDER: S-EPMC7726525 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeLow-dose whole lung radiation therapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection, and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling, and mechanisms of action.Methods and materialsFemale C57BL/6 mice were treated with intranasal bleomycin sulfate (7.5 or 11.25 units/kg, day 0) and then exposed to whole lung radiation therapy (0.5, 1.0, or 1.5 Gy, or sham; day 3). Bodyweight was measured daily, and lung tissue was harvested for histology and flow cytometry on day 10. Computed tomography lung imaging was performed before radiation (day 3) and pre-endpoint (day 10).ResultsBleomycin caused pneumonitis of variable severity, which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight, and a proportion of these mice exhibited less severe histopathologic lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. In addition, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells (DCs), and neutrophil-DC hybrids. Overall, bleomycin-treated mice exhibited significantly higher percentages of nonaerated lung in left than right lungs, and LDLR (1.0 Gy) limited further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not improve bodyweight, flow cytometric, or radiologic readouts of bleomycin-induced pneumonitis.ConclusionsOur data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose, and provide evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ DCs, and neutrophil-DC hybrids.