Drug Hypersensitivity Reactions in Patients with Cystic Fibrosis: Potential Value of the Lymphocyte Toxicity Assay to...

Cystic fibrosis (CF) is a genetic disease characterized by multi-system dysfunction resulting in recurrent lung infections and progressive pulmonary disease. CF patients are at a higher risk for drug hypersensitivity reactions (DHRs) compared to the general population, which has been attributed to the recurrent need for antibiotics and the inflammation associated with CF disease. In vitro toxicity tests such as the lymphocyte toxicity assay (LTA) offer the potential for risk assessment for DHRs. In the current study, we investigated the utility of the LTA test for diagnosis of DHRs in a cohort of CF patients.

Twenty CF patients with suspected DHRs to sulfamethoxazole, penicillins, cephalosporins, meropenem, vancomycin, rifampicin, and tobramycin were recruited to this study and tested using the LTA test along with 20 healthy control volunteers. Demographic data of the patients, including age, sex, and medical history, were obtained. Blood samples were withdrawn from patients and healthy volunteers, and the LTA test was performed on isolated peripheral blood monocytes (PBMCs) from those individuals.

Cells from CF patients with DHRs displayed a significant (p < 0.0001) concentration-dependent enhanced cell death upon incubation with the culprit drug compared to cells from healthy volunteers. The positivity rate of the LTA test was over 80% in patients with a medical history and clinical presentation consistent with DHRs.

This study is the first to evaluate the use of the LTA test for diagnosis of DHRs in CF patients. According to our results, the LTA test may be a useful tool for diagnosis and management of DHRs in CF patients. Identifying the culprit drug is essential for optimal healthcare for CF patients in the setting of a suspected DHR. The data also provide evidence that accumulation of toxic reactive metabolites could be an important component in the cascade of events leading to the development of DHRs in CF patients. A larger-scale study is needed to confirm the data.