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

• Published in: Cancer chemotherapy and pharmacology Vol. 88; no. 5; pp. 857 - 865
• Main Authors: Otani, Toshihito, Yamaguchi, Kakuhiro, Nakao, Satoshi, Sakamoto, Shinjiro, Horimasu, Yasushi, Masuda, Takeshi, Miyamoto, Shintaro, Nakashima, Taku, Iwamoto, Hiroshi, Fujitaka, Kazunori, Hamada, Hironobu, Hattori, Noboru
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2021; Springer Nature B.V
• Subjects: Advanced glycosylation end products; Aged; Antineoplastic Agents - adverse effects; Cancer Research; Chemotherapy; Confidence intervals; Cytotoxicity; Female; Glucose; Glucose Intolerance - chemically induced; Glucose tolerance; Glycated Hemoglobin A - analysis; Glycation End Products, Advanced - blood; Glycosylation; Hemoglobin; Humans; Hyperglycemia; Hyperglycemia - chemically induced; Hyperglycemia - physiopathology; Injuries; Intolerance; Lung cancer; Lung diseases; Lung Diseases, Interstitial - complications; Lung Diseases, Interstitial - drug therapy; Lung Diseases, Interstitial - physiopathology; Lung Injury - chemically induced; Lung Neoplasms - drug therapy; Lung Neoplasms - physiopathology; Male; Medicine; Medicine & Public Health; Oncology; Original Article; Pharmacology/Toxicology; Retrospective Studies; Risk analysis; Risk factors; Serum levels; Statistical analysis; Vital Capacity; Glucose intolerance; Interstitial lung disease; Hemoglobin A1c; Diabetes mellitus; Lung cancer; Advanced glycation end product
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-021-04341-y

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.