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Background: Inflammation in chronic obstructive pulmonary disease (COPD) is characterised by increased neutrophilic infiltration of the airways. Cilomilast, a navel selective phosphodiesterase 4 inhibitor in clinical development for COPD treatment, [...]

ABSTRACT: The aim of this study was to evaluate the role of ageing on variability of airflow obstruction and on the specific pattern of nocturnal exacerbations ('morning dipping' of peak [...]

BACKGROUND AND AIM: Endothelin has bronchoconstrictive, vasoactive, and inflammatory properties and may be involved in the pathogenesis of asthma. We have studied the involvement of endothelin in asthma by examining its expression and release by mononuclear phagocytes obtained from 56 patients with asthma and 32 control subjects and the activation of mononuclear phagocytes by endothelin. METHODS: Endothelin immunoreactivity was studied by using immunocytochemistry on monocytes and alveolar macrophages. Spontaneous and lipopolysaccharide-induced endothelin release from monocytes and alveolar macrophages was studied by radioimmunoassay. The proportion of intracellular endothelin was assessed after cell disruption by Triton (Union Carbide Corp., Bound Brook, N.J.). The release of fibronectin and tumor necrosis factor-@a induced by endothelin was studied in alveolar macrophages by enzyme immunoassay. RESULTS: Endothelin immunoreactivity was significantly increased in cells from patients with asthma in comparison with those from the control group, but its release by alveolar macrophages was similar in both groups. Levels in the cell lysates and supernatants were similar for patients with asthma and normal subjects. Endothelin significantly increased the release of tumor necrosis factor-@a and fibronectin by alveolar macrophages from normal subjects and patients with stable asthma, but it significantly decreased their release in patients with unstable asthma. CONCLUSION: This study suggests a role for endothelin in airway inflammation in asthma. Endothelin may act in a different fashion on alveolar macrophages, depending on the degree of stability of the disease. (J ALLERGY CLIN IMMUNOL 1996;98:412-20.)

It has been suggested that hyperosmolarity may be one of the stimuli that provoke exercise-induced asthma and rhinitis. We investigated whether changes in osmolarity could result in increased levels of mediator release from nasal cells. Cells were dispersed from nasal polyps by enzymatic digestion and were incubated for 15 minutes with solutions of varying osmolarity obtained by the addition of mannitol to Hanks' balanced salt solution. After incubation was performed, cell supernatants were removed, and the release of 15-hydroxyeicosatetraenoic acid, prostaglandin "2 leukotriene B "4, and fibronectin was measured. Lactate dehydrogenase was measured to assess cell viability. Epithelial cells made up 40% to 60% of cells and mononuclear cells 40% to 65%. At 900 mOsm/kg H "2O, which has been suggested as the osmolarity of the fluid lining the airways during exercise, we observed a significant increase (Wilcoxon W test) in the release of 15-hydroxyeicosatetraenoic acid (p < 0.008), leukotriene B "4 (p < 0.008), and prostaglandin "2 (p < 0.008), but no significant increase in the release of fibronectin was seen. No significant increase was seen between lactate dehydrogenase and 15-hydroxyeicosatetraenoic acid release, suggesting that the increase in mediator levels was not caused by cell death. These results show that hyperosmolar solutions can induce activation of nasal cells, which may at least partly explain rhinitis caused by exercise. (J ALLERGY CLIN IMMUNOL 1995;96:980-5.)

Background: Urinary leukotriene E"4 (LTE"4) is a marker of the body's production of cysteinyl LTs, important mediators of airway inflammation. The role of the latter in nocturnal asthma is a topic of increasing interest. Objective: This investigation was aimed at determining whether nighttime attacks are associated with increased release of LTs, expressed by urinary LTE"4, and the relationship between the two phenomena. Methods: Three groups were studied: group A, seven control subjects; group B, nine asthmatic patients without nocturnal attacks; and group C, nine asthmatic patients with a comparable daytine FEV"1 but who were experiencing nocturnal exacerbations (morning dips in peak expiratory flow >20%). Urine was collected over 24 hours in three samples (9:00 am to 3:00 pm; 3:00 pm to 9:00 pm; and 9:00 pm to 9:00 am). LTE"4 was measured by high-performance liquid chromatography and radioimmunoassay and expressed as nanograms per millimole of creatinine. Results: No significant differences between urinary LTE"4 were noticed within groups A and B. Conversely, in group C urinary LTE"4 at night (geometric mean with 95% confidence interval: 35.16 with 28.77-42.85) was significantly higher than that of the other samples (respectively 23.12 with 17.78-30.06, p<0.05; and 25.18 with 21.03-30.13, p<0.02); it was also significantly higher than in all the samples of other groups. A significant (p<0.02) linear correlation was observed between morning dip in peak expiratory flow and the log urinary LTE"4 in the nocturnal sample. Conclusion: These results indicate the role of LTs in nocturnal asthma and suggest that urinary LTE"4 may be a useful marker of this condition.

BackgroundInduced sputum and methacholine inhalation challenge are routinely used for the assessment of airway inflammation and airway hyperresponsiveness, respectively. This study investigates whether a methacholine challenge performed one hour before sputum induction alters the cellular and biochemical constituents of sputum. Methods Sixteen stable asthmatic patients with lung function within the normal range underwent two sputum inductions within one week. One hour before one of the sputum inductions a methacholine challenge was performed. Results There were no significant differences in total cell count, macrophages, neutrophils, eosinophils, lymphocytes, epithelial cells, ECP, and albumin between the two challenges. The repeatability of cell counts was good for all cells, ECP and albumin, but poor for total cells. Conclusions In patients with stable asthma a methacholine challenge carried out one hour before sputum induction does not significantly alter the cellular and biochemical constituents of sputum.