Nintedanib Treatment for Idiopathic Pulmonary Fibrosis Patients Who Have Been Switched from Pirfenidone Therapy: A Retrospective Case Series Study.

BACKGROUND: The efficacy and effectiveness of nintedanib as a first-line therapy in idiopathic pulmonary fibrosis (IPF) patients have been demonstrated by clinical trials and real-life studies. Our aim was to examine the safety profile and effectiveness of nintedanib when it is utilized as a second-line treatment in subjects who have discontinued pirfenidone. METHODS: The medical charts of 12 patients who were switched from pirfenidone to nintedanib were examined retrospectively. The drug's safety was defined by the number of adverse events (AEs) that were reported; disease progression was evaluated based on the patient's vital status and changes in forced vital capacity (FVC) at 12-month follow-up. RESULTS: The numbers of patients experiencing AEs and of the AEs per patient in our study group didn't significantly differ with respect to a group of 56 individuals who were taking nintedanib as a first-line therapy during the study period (5/12 vs. 22/56; p = 0.9999, and 0.00 (0.00-1.00) vs. 0.00 (0.00-3.00); p = 0.517, respectively). Two out of the 3 patients who had been switched to nintedanib due to a rapid disease progression showed stabilized FVC values. CONCLUSIONS: Nintedanib was found to have an acceptable safety profile in the majority of the IPF patients switched from pirfenidone. Prospective studies are warranted to determine if the drug can effectively delay disease progression in these patients.

miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation.

RATIONALE: Alveolar type II (ATII) cells act as adult stem cells contributing to alveolar type I (ATI) cell renewal and play a major role in idiopathic pulmonary fibrosis (IPF), as supported by familial cases harbouring mutations in genes specifically expressed by these cells. During IPF, ATII cells lose their regenerative potential and aberrantly express pathways contributing to epithelial-mesenchymal transition (EMT). The microRNA miR-200 family is downregulated in IPF, but its effect on human IPF ATII cells remains unproven. We wanted to 1) evaluate the characteristics and transdifferentiating ability of IPF ATII cells, and 2) test whether miR-200 family members can rescue the regenerative potential of fibrotic ATII cells. METHODS: ATII cells were isolated from control or IPF lungs and cultured in conditions promoting their transdifferentiation into ATI cells. Cells were either phenotypically monitored over time or transfected with miR-200 family members to evaluate the microRNA effect on the expression of transdifferentiation, senescence and EMT markers. RESULTS: IPF ATII cells show a senescent phenotype (p16 and p21), overexpression of EMT (ZEB1/2) and impaired expression of ATI cell markers (AQP5 and HOPX) after 6 days of culture in differentiating medium. Transfection with certain miR-200 family members (particularly miR-200b-3p and miR-200c-3p) reduced senescence marker expression and restored the ability to transdifferentiate into ATI cells. CONCLUSIONS: We demonstrated that ATII cells from IPF patients express senescence and EMT markers, and display a reduced ability to transdifferentiate into ATI cells. Transfection with certain miR-200 family members rescues this phenotype, reducing senescence and restoring transdifferentiation marker expression.

Lung cancer requires multidisciplinary treatment to improve patient survival: A case report.

The present study reports two cases of lung cancer with the involvement of the pleura. The diagnosis of adenocarcinoma with epidermal growth factor receptor (EGFR) mutation was made following repeated thoracentesis with cytology of pleural fluid and thoracoscopy with pleural biopsies. Talc pleurodesis was successfully performed in both cases subsequent to diagnosis. Following talc pleurodesis, the first patient (62 years old; male; non-smoker) underwent 3 cycles of cisplatin/vinorelbine chemotherapy, with a poor response. Concurrently, due to the presence of an EGFR mutation, treatment with gefitinib was initiated, with the patient achieving a good response for ~12 months. The residual tumor was treated with stereotactic radiotherapy and the patient continued gefitinib treatment. The patient is presently in good health, has not exhibited any signs of relapse and is continuing gefitinib treatment without side effects. The second patient (53 years old; male ex-smoker) underwent treatment with gefitinib subsequent to talc pleurodesis for a total of 15 months. In addition, radiotherapy (60 Gy) on the residual lesion was performed. Subsequently, second-line therapy with cisplatin/premetrexed was prescribed and followed by maintenance treatment with premetrexed. Three years after diagnosis, the patient did not exhibit any signs of recurrence. These two cases highlight the difficulty in treating advanced stage lung cancer, despite the presence of EGFR mutation. Each lung cancer is different and requires the physician to possess a wide range of knowledge of the therapeutic options available, in addition to careful monitoring in order to adjust the treatment over time. A multidisciplinary approach, involving surgeons, radiation oncologists, pulmonologists and oncologists, is required to optimize the survival and quality of life of patients with lung cancer.