Vildagliptin‐induced ground‐glass nodules mimicking lung metastases in a cancer patient receiving Lactobacillus probiotic supplementation

Abstract

The association between gut microbiota and the lung immune system has been attracting increasing interest. Here, we report a case of pancreatic cancer in which the dipeptidyl peptidase-4 inhibitor vildagliptin induced unusual manifestations of interstitial pneumonia, possibly under the influence of Lactobacillus paraplantarum probiotic supplementation. Chest computed tomography and positron emission tomography showed multiple ground-glass nodules (GGNs) mimicking metastatic lung cancer. Transbronchial biopsy specimens showed mild fibrosis and infiltration of lymphocytes consisting of more CD4 + than CD8 + cells. The CD4 + cells did not include FOXP3 + regulatory T cells. Bronchoalveolar lavage confirmed lymphocytosis with a markedly increased CD4 + /CD8 + ratio of 7.4. The nodules disappeared shortly after vildagliptin and probiotics were withheld. If unusual interstitial pneumonia is observed in some cancer patients, physicians should pay careful attention to their medication history, including probiotic supplements.

Is DPP4 inhibition a comrade or adversary in COVID-19 infection

“…Several case reports have been published of vildagliptin induced interstitial pneumonia and ground glass changes in lung postulated to mimic anti TNF-alpha treatment and is postulated to be secondary to reduced TNF-alpha. In one such case, these lesions had lymphocytosis with markedly increased CD4+/ CD8+ ratio which is similar to what is seen in COVID-19 infection [13,14]. Hence, it is possible that baseline DPP-4 inhibition may increase the risk of fibrotic lesions in the lungs in COVID-19 infection wherein T cell immunity is affected.…”

DPP-4 Inhibitors as a Savior for COVID-19 Patients with Diabetes

“…Using a mouse model, it was found that the DPP-4 inhibitor drug vildagliptin also induces natural killer (NK) cell activity, which leads to reduced lung cancer growth [ 64 ]. Although, few studies suggest that vildagliptin induces pneumonitis, which may increase the chances of fibrotic lesions in the lungs during SARS-CoV-2 infection and increase the severity of COVID-19 disease [ 65 ]. DPP-4 inhibition is also associated with some degree of immune suppression, and long-term suppression of the immune system could lead to undesirable side effects [ 66 ].…”

“…Because DPP-4 inhibitors can suppress immunity by altering the T cells activity [ 62 ], this has led to some suggestions that DPP-4 inhibitors might increase the risk of infections such as nasopharyngitis and interstitial pneumonitis in patients [ 65 ]. However meta-analyses and also large-scale patient studies performed by Clinical Practice Research Datalink of United Kingdom (CPRD) found no such increased risk of infections in DPP-4 inhibitor users in comparison to other anti-diabetic drugs [ 76 ].…”

Lactobacilli Infection Case Reports in the Last Three Years and Safety Implications

“…One study reported just Gram staining as the method of identification [ 54 ]. In the case of interstitial pneumonia published in 2020 ( Table 2 ) cultures were not carried out, but it was assumed that the Lactiplantibacillus paraplantarum strain present in the probiotic yogurt consumed by the patient was the cause, since ground-glass nodules (GGNs) formed in the lungs disappeared after discontinuing the assumption of the probiotic and vildagliptin [ 50 ].…”