ObjectivesA meta-analysis suggested that the use of varenicline, which is a partial agonist of nicotinic acetylcholine receptors and is effective in smoking cessation, increases the risk of cardiovascular events within 52 weeks of starting treatment. Defining these events as occurring during drug treatment (usually for 12 weeks) or within 30 days of discontinuation, another meta-analysis showed that the risk was statistically insignificant. In the present study, we aimed to clarify the effect of varenicline-assisted smoking cessation on vascular endothelial function assessed by flow-mediated vasodilation (FMD).DesignBefore–after and time-series.SettingTochigi Prefecture, Japan.ParticipantsData of 85 participants who visited nicotine-dependent outpatient services were reviewed. FMD was repeatedly measured in 33 of the 85 participants. Inclusion criteria: 20 years and older, Brinkman index ≥200, Tobacco Dependence Screener ≥5 and stated motivation to quit smoking.InterventionsEach participant was treated with varenicline titrated up to 1.0 mg twice daily (for 12 weeks in total).Primary and secondary outcome measuresParticipants were evaluated by FMD prior to, and 3 months after, complete smoking cessation. Follow-up FMD measurements were carried out every 3 months if possible. Changes in FMD during varenicline use were also evaluated.ResultsFMD was significantly increased from 4.0±1.8% to 5.5±2.2% (p<0.01, n=22) 3 months after complete cessation. Although the timecourse of FMD in most of the cases showed an increase with fluctuations, there was an exceptional case where FMD decreased over the 9 months following complete cessation. Although statistically insignificant, FMD also increased during varenicline use (from 3.7±2.7% to 4.3±2.8%, n=11).ConclusionsOur observations suggest that in ceasing smokers, varenicline and smoking cessation do not lead to a worsening of the vascular endothelial function.Trial registrationFK-79 (International University of Health and Welfare).

Serum levels of sialyl SSEA-1 antigen, a carbohydrate antigen, were measured by radioimmunoassay in 142 patients with nonmalignant lung diseases. In 20 of 41 patients with fibrosing lung disease, either idiopathic or associated with collagen disease, the serum sialyl SSEA-1 levels were abnormally elevated. In patients with other lung diseases, the serum levels were almost within normal limits, less than 38.0 units/ml. In fibrosing lung disease the serum levels ranged from 13.8 to 147.0 units/ml and were largely concurrent with the degree of disease activity. The therapeutic effects of corticosteroid, which were evaluated with clinical-radiographic-physiologic scores and survivals in the patients with elevated serum levels, were significantly lower than those of the patients with the normal range of antigen levels. An immunohistochemical study performed on autopsied lungs from five patients with fibrosing lung disease indicated that the antigen was selectively expressed in the pulmonary epithelial cells that covered the remodeling alveolar septi in the lungs. No antigen was detectable by immunostaining in normal pulmonary epithelium among five normal lungs. From these findings, it is thought that the elevated levels of serum sialyl SSEA-1 may be derived from proliferating epithelial cells that were dominant in the late stage of fibrosing lung disorders. The measurements of serum sialyl SSEA-1 in patients with fibrosing lung disease may be clinically useful in establishing the degree of disease activity that has an influence on patient prognosis and therapeutic response.

Lymphocytes obtained by bronchoalveolar lavage (BAL) in hypersensitivity pneumonitis (HP) and pulmonary sarcoidosis (PS) are believed to be derived from interstitial inflammatory lesions of the lung in which lymphocytes have migrated from the blood. Because cellular motility is one of the important factors in lymphocyte migration, we investigated the motility of BAL lymphocytes from 12 patients with HP and 12 with PS, as well as their responsiveness to chemoattractants in vitro by modified Boyden chamber method. Motility was evaluated by the number of migrated cells and the migration distance. The numbers of migrated BAL lymphocytes from patients with HP and PS in albumin-containing medium were 318.3 +/- 93.0 (mean +/- SD) and 207.6 +/- 35.5, respectively, and were greater than those of BAL lymphocytes from normal control subjects (133.3 +/- 40.9) and blood lymphocytes, and comparable with those of mitogen-activated blood lymphocytes. The motility of BAL lymphocytes in these diseases compared with blood lymphocytes was also increased in protein-free medium. In addition, the culture supernatants of alveolar macrophages (AM) enhanced the motility of BAL, mitogen-activated, and blood lymphocytes. These results suggest that BAL lymphocytes in these diseases are functionally motile, and their enhanced motility, as well as mediators from AM, may facilitate the accumulation of lymphocytes at the epithelial surface.

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Our previous studies have suggested a role for complement fragments presumably activated by immune complexes in patients with hypersensitivity pneumonitis. The present study has shown that circulating complement depletion by cobra venom factor resulted in the reduction in severity of immune-complex-mediated pulmonary inflammation. The activity of chemotactic factors for neutrophils generated in bronchoalveolar lavage fluids in complement-depleted animals was significantly diminished to 61.2% compared to the undepleted animals. In addition, reduced activity of chemotactic factors resulted in a marked reduction of accumulation of neutrophils in bronchoalveolar lavage fluids indicating that chemotactic factors play an important role in the sequestration of neutrophils on the alveolar side of the lung. In conclusion, chemotactic factors in bronchoalveolar lavage fluids which preceded the accumulation of polymorphonuclear cells are partially derived from complement.