The Role of Hypertension and Renin-angiotensin-aldosterone System Inhibitors in Bleomycin-induced Lung Injury

Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):e321-e327. doi: 10.1016/j.clml.2020.10.004. Epub 2020 Oct 9.

Abstract

Introduction: The risk factors for bleomycin-induced lung injury (BLI), a fatal complication of cancer chemotherapy, are not well-established. The renin-angiotensin-aldosterone system (RAAS) has recently been suggested to play a role in the development of lung injury. This study clarified the impact of hypertension (HTN) and the administration of RAAS inhibitors on BLI occurrence in patients treated with bleomycin-containing regimens.

Patients and methods: We retrospectively analyzed the data of 190 patients treated with a bleomycin-containing regimen for Hodgkin lymphoma or germ cell tumors at our institutions from 2004 to 2018.

Results: Overall, 190 patients received bleomycin, and symptomatic BLI occurred in 21 (11.1%) cases. In the multivariate analysis, age ≥ 65 years (odd ratio, 10.90; 95% confidence interval, 3.72-32.20; P < .001) and history of HTN (odds ratio, 3.32; 95% confidence interval, 1.07-10.30; P = .04) were found to be significant risk factors for BLI onset. BLI occurred in 3.6% (n = 5) of patients with no risk, 11.8% (n = 2) of those whose only risk factor was HTN, 31.6% (n = 6) of those whose only risk factor was age ≥ 65 years, and 57.1% (n = 8) of those with both risk factors (P < .001). BLI-induced mortality rates in each group were 0.0% (n = 0), 5.9% (n = 1), 10.5% (n = 2), and 42.9% (n = 6) (P < .001), respectively. Among 31 patients with HTN, BLI incidence was 12.5% in patients who were administered RAAS inhibitors and 53.3% in those who were not (P = .02).

Conclusion: Older age and history of HTN were independent risk factors for the development of BLI, and the administration of RAAS inhibitors might reduce the onset of BLI.

Keywords: Germ cell tumors; Hodgkin lymphoma; Mediastinal tumor; Ovarian tumor; Testicular tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 2 Receptor Blockers / pharmacology
  • Angiotensin II Type 2 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Bleomycin / administration & dosage
  • Bleomycin / adverse effects*
  • Child
  • Female
  • Hodgkin Disease / drug therapy
  • Humans
  • Hypertension / drug therapy
  • Hypertension / epidemiology*
  • Incidence
  • Lung Injury / chemically induced
  • Lung Injury / epidemiology*
  • Lung Injury / prevention & control
  • Male
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / drug therapy
  • Renin-Angiotensin System / drug effects
  • Retrospective Studies
  • Risk Assessment / statistics & numerical data
  • Risk Factors
  • Young Adult

Substances

  • Angiotensin II Type 2 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Bleomycin