Chronic inflammation induces lymphangiogenesis and blood vessel remodelling. Since aged pneumonia patients often have repeated episodes of aspiration pneumonia, the pathogenesis may involve chronic inflammation. For lymphangiogenesis, VEGFR-3 and its ligand VEGF-C are key factors. No previous studies have examined chronic inflammation or vascular changes in aspiration pneumonia or its mouse models. In lung inflammation, little is known about the effect of blocking VEGFR-3 on lung lymphangiogenesis and, moreover, its effect on the disease condition. This study aimed to establish a mouse model of aspiration pneumonia, examine the presence of chronic inflammation and vascular changes in the model and in patients, and evaluate the effect of inhibiting VEGFR-3 on the lymphangiogenesis and disease condition in this model. To induce aspiration pneumonia, we repeated inoculation of pepsin at low pH and LPS into mice for 21-28 days, durations in which bronchioalveolar lavage and plasma leakage in the lung suggested the presence of exaggerated inflammation. Conventional and immunohistochemical analysis of tracheal whole mounts suggested the presence of chronic inflammation, lymphangiogenesis, and blood vessel remodelling in the model. Quantitative RT-PCR of the trachea and lung suggested the involvement of lymphangiogenic factor VEGF-C, VEGFR-3, and pro-inflammatory cytokines. In the lung, the aspiration model showed the presence of chronic inflammation and exaggerated lymphangiogenesis. Treatment with the VEGFR inhibitor axitinib or the VEGFR-3 specific inhibitor SAR131675 impaired lymphangiogenesis in the lung and improved oxygen saturation in the aspiration model. Since the lung is the main site of aspiration pneumonia, the changes were intensive in the lung and mild in the trachea. Human lung samples also showed the presence of chronic inflammation and exaggerated lymphangiogenesis, suggesting the relevance of the model to the disease. These results suggest lymphatics in the lung as a new target of analysis and therapy in aspiration pneumonia.

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The study suggests that smoking has a differential effect on cough responses between TRPV1 and TRPA1 stimulations.

BackgroundThe effect of aging on the cognitive aspect of cough has not been studied yet. The purpose of this study is to investigate the aging effect on the perception of urge-to-cough in healthy individuals.MethodsFourteen young, female, healthy never-smokers were recruited via public postings. Twelve elderly female healthy never-smokers were recruited from a nursing home residence. The cough reflex threshold and the urge-to-cough were evaluated by inhalation of citric acid. The cough reflex sensitivities were defined as the lowest concentration of citric acid that elicited two or more coughs (C2) and five or more coughs (C5). The urge-to-cough was evaluated using a modified the Borg scale.ResultsThere was no significant difference in the cough reflex threshold to citric acid between young and elderly subjects. The urge-to-cough scores at the concentration of C2 and C5 were significantly smaller in the elderly than young subjects. The urge-to-cough log-log slope in elderly subjects (0.73 ± 0.71 point · L/g) was significantly gentler than those of young subjects (1.35 ± 0.53 point · L/g, p < 0.01). There were no significant differences in the urge-to-cough threshold estimated between young and elderly subjects.ConclusionsThe cough reflex threshold did not differ between young and elderly subjects whereas cognition of urge-to-cough was significantly decreased in elderly subjects in female never-smokers. Objective monitoring of cough might be important in the elderly people.

BackgroundAlthough cigarette smoking has been implicated as an important risk factor for the development of respiratory symptoms, the perceptional aspects of two symptoms in smokers have not been fully elucidated. Therefore, we simultaneously evaluated the cough reflex sensitivity, the cognition of urge-to-cough and perception of dyspnea in both healthy smokers and non-smokers.MethodsFourteen male healthy never-smokers and 14 age-matched male healthy current-smokers were recruited via public postings. The cough reflex sensitivity and the urge-to-cough were evaluated by the inhalation of citric acid. The perception of dyspnea was evaluated by Borg scores during applications of external inspiratory resistive loads.ResultsThe cough reflex threshold to citric acid, as expressed by the lowest concentration of citric acid that elicited two or more coughs (C2) and the lowest concentration of citric acid that elicited five or more coughs (C5) in smokers was significantly higher than in non-smokers. The urge-to-cough log-log slope in smokers was significantly milder than that of non-smokers. There were no significant differences in the urge-to-cough threshold between non-smokers and smokers. There were no significant differences in perceptions of dyspnea between non-smokers and smokers.ConclusionsThe study showed that decreased cough reflex sensitivity in healthy smokers was accompanied by a decreased cognition of urge-to-cough whereas it was not accompanied by the alternation of perception of dyspnea. Physicians should pay attention to the perceptual alterations of cough in smokers.