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Background: Induced sputum cytology and protein biomarkers can be used to assess airways infl ammation. Increases in sputum iron have been described in infl ammatory lung disease. We hypothesized that other sputum metals may be affected by airways infl ammation and investigated their potential value as biomarkers. Methods: Sputum was obtained from 20 healthy control subjects and from patients with infl ammatory pulmonary diseases (23 with cystic fi brosis [CF], 16 with bronchiectasis, 17 with asthma, and 23 with COPD), and iron, zinc, manganese, and copper were measured. Fourteen patients with CF were also studied through an exacerbation cycle. Results: Sputum zinc and iron were elevated in CF and non-CF bronchiectasis vs controls ( P , .001, zinc; P , .01 iron). Manganese was elevated in asthma ( P , .01) and bronchiectasis ( P , .05) vs controls. Copper was elevated in CF vs controls ( P , .05). Zinc decreased ( P , .01) following treatment of CF exacerbation. In subjects with CF zinc levels correlated with other biomarkers. Conclusions: These results suggest a relationship of high concentrations of total zinc and iron with airways infl ammation in CF and non-CF bronchiectasis, with longitudinal changes being observed in CF. Further work is required to elucidate potential infl ammatory mechanisms related to these observations. CHEST 2010; 137(3):635–641

Study objectives: To investigate whether differing airway interleukin (IL)-18 levels may be implicated in the pathogenesis of asthma and sarcoidosis. Setting: University teaching hospital. Patients and methods: IL-18 levels were measured in BAL fluid and in the supernatant of lipopolysaccharide (LPS)-stimulated alveolar macrophages obtained by BAL from 15 patients with sarcoidosis, 11 patients with asthma, and 13 healthy subjects. We also examined the relationship between IL-18 levels and macrophage and lymphocyte concentrations in BAL fluid. IL-18 was measured using an in-house enzyme-linked immunosorbent assay. Results: IL-18 levels were significantly lower in BAL fluid from patients with asthma (median, 0.0 pg/mL; interquartile range, 0.0 to 0.0 pg/mL) compared to patients with sarcoidosis (median, 222.0 pg/10 6 ; interquartile range, 110 to 340 pg/mL; p 0.009, Mann Whitney rank-sum test) and healthy control subjects (median, 162 pg/mL; interquartile range, 38 to 203 pg/mL; p 0.025, Mann Whitney rank-sum test). Individual analyses comparing IL-18 levels with BAL macrophage counts, and IL-18 with lymphocyte counts in the three groups showed no correlation between these indexes. The mean levels of IL-18 in unstimulated macrophage supernatants were 410 pg/10 6 cells for patients with asthma, 723.4 pg/10 6 cells for patients with sarcoidosis, and 734.8 pg/10 6 cells for healthy control subjects (p > 0.05). Stimulated macrophages from patients with sarcoidosis responded with increasing amounts of IL-18 at lower doses of LPS than macrophages from healthy control subjects or patients with asthma. Conclusion: Our findings suggest that inherently low levels of IL-18 may be associated with the pathogenesis of asthmatic airway inflammation. (CHEST 2002; 121:1421–1426)

STUDY OBJECTIVE: To examine whether atopy influences exhaled nitric oxide (NO) levels in adults with established asthma. SETTING: Specialist respiratory unit in a university teaching hospital. PATIENTS: Twenty-eight asthmatics (mean FEV(1), 85.7%) receiving short-acting inhaled bronchodilators and a range of inhaled steroids (0 to 4,000 microg/d). INTERVENTIONS: Subjects were studied on two occasions, 5 to 7 days apart, between September and March. MEASUREMENTS AND RESULTS: On the first day, FEV(1), exhaled NO, and histamine challenge were performed. On the second day, exhaled NO, total IgE, and skin-prick testing to six common allergens were conducted. Exhaled NO was measured with the single exhalation method. We found exhaled NO levels to correlate positively with total IgE (r = 0.43, p = 0.02) and number of positive skin-prick tests (p = 0. 002). By contrast, there was no significant correlation between exhaled NO and FEV(1) or the provocative concentration causing a 20% fall in FEV(1). Subanalyses of steroid-treated and steroid-naive patients in this group revealed the same findings. CONCLUSION: Exhaled NO levels in asthmatics correlate more closely with atopy than with bronchial hyperreactivity and lung function.