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Biomedical subjects

W Maziak

Publications and source records attributed to W Maziak.

4 recordsLinked to original sources

Neutrophilic inflammation in severe persistent asthma.

Airway inflammation in severe asthma is not well characterized but may involve neutrophils. We have compared induced sputum profiles in patients with asthma of varying severity and normal control subjects. We have also measured exhaled nitric oxide (NO) as a noninvasive marker of inflammation. Asthma severity was based on clinical features before treatment and the minimum medication required to maintain asthma control at the time of sputum induction, and classified as (1) mild: treated with inhaled beta(2)-agonist occasionally (n = 23; FEV(1), 91%; peak expiratory flow (PEF) variability, 10.5%), (2) moderate: requiring medium dose inhaled steroids to maintain control (n = 16; FEV(1), 88%; PEF variability, 9.1%), and (3) severe: despite using inhaled and oral steroids (n = 16; FEV(1), 61%; PEF variability, 36.2%). The asthmatic patients were nonsmokers with evidence of airway hyperresponsiveness or reversible airway obstruction, and free of respiratory tract infection for at least 6 wk. Sputum revealed significantly increased neutrophil numbers in severe asthma (53.0 [38.4- 73.5]%, p < 0.05) compared with mild asthma (35.4 [29.8-46.1]%) and normal control subjects (27.7 [20.6-42.2]%). Interleukin-8 (IL-8) and neutrophil myeloperoxidase (MPO) levels were increased in asthmatic patients, with the highest levels in severe asthma. Eosinophil numbers were increased in both mild and severe asthma, but interleukin-5 (IL-5) levels were highest in mild asthma, whereas eosinophil cationic protein (ECP) levels were highest in severe asthma. Exhaled NO levels were highest in asthmatic untreated with corticosteroids, but there was no significant difference between asthmatics using corticosteroids (Groups 2 and 3), regardless of clinical asthma severity. This confirms the role of eosinophils in asthma but suggests a potential role of neutrophils in more severe asthma.

Adult

Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.

Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease (COPD), despite lack of proven efficacy. Because COPD involves airway inflammation and probable protease-antiprotease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients with COPD were treated with fluticasone propionate (500 microg twice a day) for 4 wk, delivered via MDI and spacer, in a double-blind crossover study. There was no clinical benefit in terms of lung function or symptom scores, and induced sputum inflammatory cells, percentage neutrophils, and IL-8 levels were unchanged. Sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD. Furthermore, inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction.

Administration, Inhalation

Exhaled nitric oxide in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and a neutrophilic inflammation. Exhaled nitric oxide (NO) may be a marker of disease activity in a variety of lung diseases. We measured exhaled NO in patients with documented COPD and investigated whether the concentration of exhaled NO is related to the severity of disease as defined by lung function. We also investigated whether concentration of exhaled NO was different in COPD patients who received inhaled steroids compared with steroid-naive patients. We studied 13 current smokers with COPD, eight exsmokers with COPD, 12 patients with unstable COPD (exacerbation or severe disease), and 10 smokers with chronic bronchitis without airflow limitation. Exhaled NO levels were significantly higher in patients with unstable COPD (12.7 +/- 1.5 ppb) than in other groups (p < 0.01). Exhaled NO levels were significantly higher in smokers with COPD than in smokers with chronic bronchitis (4.3 +/- 0.5 versus 2.5 +/- 0.5 ppb, p < 0.05), and were even higher in patients with COPD who had stopped smoking (6.3 +/- 0.6 ppb, p < 0.01). Exhaled NO levels showed a significant negative correlation with their lung function assessed by % predicted FEV1 values (r = -0.6, p < 0.001). Exhaled NO levels in patients treated with inhaled steroids were significantly higher compared with steroid-naive patients (8.2 +/- 1.2 ppb versus 5 +/- 0.4 ppb, p < 0.05), but the first group included more severe patients as assessed by lung function. We conclude that exhaled NO could serve as a useful, practical marker for monitoring disease activity in COPD.

Administration, Inhalation