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Association between glucose intolerance and chemotherapy-induced lung injury in patients with lung cancer and interstitial lung disease

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Abstract

Purpose

Cytotoxic chemotherapy-induced lung injury is a fatal complication in patients with lung cancer and interstitial lung disease (ILD). We aimed to evaluate the association between hyperglycemia and this form of lung injury in patients with lung cancer concomitant with ILD.

Methods

From 1147 patients with advanced lung cancer, we retrospectively enrolled 98 patients with ILD whose hemoglobin A1c (HbA1c) levels were measured, and investigated the association between HbA1c levels and cytotoxic chemotherapy-induced lung injury. In 73 patients whose serum samples were retained, we measured serum levels of advanced glycation end products (AGE) and assessed the association of AGE levels with HbA1c levels and cytotoxic chemotherapy-induced lung injury.

Results

The incidence of cytotoxic chemotherapy-induced lung injury was significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8%, but not in those with HbA1c levels ≥ 6.5% than in those with HbA1c levels < 6.5%. The multivariate logistic regression model revealed that HbA1c level ≥ 5.8% was a significant risk factor for this complication [odds ratio 3.178 (95% confidence interval 1.057–9.556), P = 0.040]. In addition, serum AGE levels were significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8% [median (interquartile range); 0.129 (0.023–0.290) and 0.474 (0.213–1.109) μg/mL, P = 0.001].

Conclusion

Glucose intolerance (e.g., HbA1c level ≥ 5.8%) may be a risk factor of cytotoxic chemotherapy-induced lung injury, which might be associated with elevated AGE production due to hyperglycemia.

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

Funding

This work was supported by JSPS KAKENHI (grant number 18K15951).

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Authors and Affiliations

  1. Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Toshihito Otani, Kakuhiro Yamaguchi, Shinjiro Sakamoto, Yasushi Horimasu, Takeshi Masuda, Shintaro Miyamoto, Taku Nakashima, Hiroshi Iwamoto, Kazunori Fujitaka & Noboru Hattori

  2. Department of Internal Medicine, Mitsugi General Hospital, 124, Ichi, Mitsugi-cho, Onomichi, Hiroshima, 722-0393, Japan

    Satoshi Nakao

  3. Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Hironobu Hamada

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  1. Toshihito Otani
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Contributions

TO: validation, formal analysis, investigation, resources, data curation, writing—original draft, visualization. KY: conceptualization, methodology, formal analysis, resources, writing—review and editing. NS: validation, formal analysis, investigation, resources, data curation, writing—review and editing. SS: resources, writing—review and editing. YH: resources, writing—review and editing. TM: resources, writing—review and editing. SM: resources, writing—review and editing. TN: resources, writing—review and editing. HI: resources, writing—review and editing. KF: resources, writing—review and editing. HH: resources, writing—review and editing, supervision. NH: resources, writing—review and editing, supervision, project administration.

Corresponding author

Correspondence to Kakuhiro Yamaguchi.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of Hiroshima University Hospital (E-2242 and M326).

Consent to participate

The opt-out method was used to obtain participant’s consent. The participants who provided stored serum samples also provided written informed consent before the samples were obtained.

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Data will be made available on reasonable request.

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Otani, T., Yamaguchi, K., Nakao, S. et al. Association between glucose intolerance and chemotherapy-induced lung injury in patients with lung cancer and interstitial lung disease. Cancer Chemother Pharmacol 88, 857–865 (2021). https://doi.org/10.1007/s00280-021-04341-y

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