Effects of indacaterol on the LPS-evoked changes in fluid secretion rate and pH in swine tracheal membrane.

An acquired dysregulation of airway secretion is likely involved in the pathophysiology of chronic bronchitis and chronic obstructive pulmonary disease (COPD). Nowadays, it is widely known that several kinds of long-acting bronchodilators reduce the frequency of COPD exacerbations. However, limited data are available concerning the complementary additive effects on airflow obstruction. Using an optical method and a selective pH indicator, we succeeded in evaluating the gland secretion rate and the pH in swine tracheal membrane. A physiologically relevant concentration of acetylcholine (ACh) 100 nM induced a gradual increase in the amount of gland secretion. Lipopolysaccharides (LPS) accelerated the ACh-induced secretory responses up to around threefold and lowered the pH level significantly. Long-acting ß2-agonists (LABAs) including indacaterol (IND), formoterol, and salmeterol restored the LPS-induced changes in both the hypersecretion and acidification. The subsequent addition of the long-acting muscarine antagonist, glycopyrronium, further increased the pH values. Two different inhibitors for cystic fibrosis transmembrane conductance regulator (CFTR), NPPB and CFTRinh172, abolished the IND-mediated pH normalization in the presence of both ACh and ACh + LPS. Both immunofluorescence staining and western blotting analysis revealed that LPS downregulated the abundant expression of CFTR protein. However, IND did not restore the LPS-induced decrease in CFTR expression on Calu-3 cells. These findings suggest that the activation of cAMP-dependent HCO3- secretion through CFTR would be partly involved in the IND-mediated pH normalization in gland secretion and may be suitable for the maintenance of airway defense against exacerbating factors including LPS.

The Clinical Features of Patients with Sarcoidosis and Malignant Diseases in Japan.

Objective Recent studies suggest a significant association between sarcoidosis and malignancy, although the results have remained controversial. The aim of this study is to evaluate the clinical features of patients with sarcoidosis associated with malignant diseases in Japan. Patients We conducted a medical record review of all sarcoidosis patients in Tohoku University Hospital between January 1, 1981, and May 31, 2017. Methods The clinical records and pathology reports for each patient were screened, and the clinical characteristics of malignancies as well as sarcoidosis were reviewed. Results A total of 52 (18.8%) patients with malignancy were identified among 277 patients with sarcoidosis. Among those 52 patients, we identified 62 with malignant diseases. These patients were older and more likely to be women than the remaining 225 (81.2%) sarcoidosis patients without malignancy. The most prevalent malignant disease was breast cancer (14 cases, 22.6%), followed by stomach cancer (8 cases, 12.9%) and lung cancer (7 cases, 11.3%). Among the 14 patients with both sarcoidosis and breast cancer, 8 (57.1%) were diagnosed with breast cancer before sarcoidosis. All of these eight cases had undergone surgical resection of the cancer. Conclusion This study showed a higher incidence of patients with both sarcoidosis and malignancy in Japan than in some western countries. Breast cancer is the most prevalent malignant disease. The high frequency of sarcoidosis after surgical resection of breast cancer may suggest a causative association between malignancy and the development of sarcoidosis.