Failure of montelukast to reduce sputum eosinophilia in high-dose corticosteroid-dependent asthma.

Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment. Montelukast is a cysteinyl leukotriene antagonist, which also reduces sputum and blood eosinophils. The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant. A total of 14 clinically stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone, with baseline sputum eosinophilia (> or =5%), were randomised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial. The primary outcome was the effect of treatment on the percentage of sputum eosinophils. Secondary outcomes were changes in the blood eosinophil count, symptoms, forced expiratory volume in one second, peak expiratory flow and the need for salbutamol. The median (interquartile range, i.e. 75th-25th centile) for sputum eosinophils at baseline was 15.7% (22). The effect of adding montelukast was not significantly different from that of placebo, sputum eosinophils being 9.3% (18.9) after montelukast and 11.3% (22.8) after placebo. No difference was detected on secondary outcomes. No crossover interactions were observed. In conclusion, the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia.

Sputum cell counts and exhaled nitric oxide in patients with gastroesophageal reflux, and cough or asthma.

BACKGROUND: Gastroesophageal reflux (GER) is commonly associated with chronic cough and asthma, but there is little or no information on the nature of any associated airway inflammation. OBJECTIVE: To observe whether the association with GER worsens airway inflammation in patients with chronic cough or asthma. PATIENTS AND METHODS: The airway inflammatory indexes in induced sputum and exhaled air were examined in a cross-sectional study of 11 patients with cough and GER, nine patients with mildly symptomatic asthma and GER, nine patients with mildly symptomatic asthma without GER and nine normal, healthy control subjects. GER was shown objectively by 24 h ambulatory pH recording. RESULTS: The sputum total cell count, the proportion of neutrophils and macrophages, and the fibrinogen level were normal in all four groups, with no significant differences among the groups. The sputum eosinophil and metachromatic cell percentages, and eosinophil cationic protein levels were normal in patients with cough and GER. They were significantly increased in patients with asthma compared with healthy subjects (P<0.01) and patients with cough (P<0.01), but were not different between groups with and without GER. Exhaled nitric oxide levels showed similar results (P<0.01). The correlations between the number of episodes of reflux and the proportion of sputum eosinophils, neutrophils or exhaled nitric oxide were modest but not significant. CONCLUSIONS: GER, when associated with cough or mildly symptomatic asthma, does not cause or aggravate existing airway inflammation as measured by induced sputum cell counts and fibrinogen level, or by exhaled nitric oxide.

A comparison of exhaled nitric oxide and induced sputum as markers of airway inflammation.

BACKGROUND: Exhaled nitric oxide (ENO) has been proposed as a noninvasive marker of airway inflammation in asthma. OBJECTIVE: We investigated the relationships among ENO, eosinophilic airway inflammation as measured by induced sputum, and physiologic parameters of disease severity (spirometry and methacholine PC(20)). We also examined the effect of corticosteroid treatment and atopy on ENO levels and eosinophil counts in induced sputum. METHODS: Measurements were taken on one day in 22 healthy nonatopic subjects, 28 healthy atopic subjects, 38 asthmatic subjects not taking inhaled steroids, 35 asthmatic subjects taking inhaled steroids, and 8 subjects with eosinophilic bronchitis without asthma. RESULTS: ENO levels showed significant but weak correlations with eosinophil differential counts in the steroid-naive asthmatic and healthy atopic groups (r (s) < 0.05). ENO levels were significantly lower in the asthmatic subjects taking steroids compared with the asthmatic subjects not taking steroids, despite there being no difference in the sputum cell counts, and a tendency to increased airflow limitation. ENO levels and sputum eosinophil counts were equally good at differentiating from steroid-naive asthmatic subjects. ENO levels were consistently raised in subjects with eosinophilic bronchitis without asthma. Atopy had no effect on ENO levels in the healthy subjects. CONCLUSION: We conclude that ENO is likely to have limited utility as a surrogate clinical measurement for either the presence or severity of eosinophilic airway inflammation, except in steroid-naive subjects.

Induced sputum examination: diagnosis of pulmonary involvement in Fabry's disease.

Fabry's disease is a rare inherited metabolic disorder caused by a deficiency in the enzyme alpha-galactosidase A. It can affect almost every organ, including the lungs. Confirmation of lung involvement has depended on invasive bronchial biopsy specimens or brushings to confirm the presence of typical lamellar inclusion bodies within bronchial epithelial cells. We report a patient with known Fabry's disease in whom these inclusion bodies were identified by examination of induced sputum.

Lipid-laden macrophages in induced sputum are a marker of oropharyngeal reflux and possible gastric aspiration.

The diagnostic properties of a "lipid index" of macrophages in induced sputum as a noninvasive marker of aspiration of acidic gastric contents were evaluated. In a cross-sectional study, 33 subjects (17 with symptoms suggestive of gastrooesophageal reflux) with normal chest radiographs and no symptoms of aspiration or sinus disease, underwent dual-channel 24-h ambulatory oesophageal pH recording and sputum induction. Oropharyngeal reflux, defined as at least one episode of a fall in pH to <4 at the upper oesophageal electrode, was considered indicative of aspiration of acidic gastric contents ("gold standard"). An index for the presence of intracellular lipid in sputum macrophages, detected by oil red O stain, was obtained. The sensitivity, specificity and predictive values of this "lipid index" were calculated. The "lipid index" could be calculated in 29 of 33 samples with high interobserver repeatability (intraclass correlation coefficient 0.96). Twenty subjects showed oropharyngeal reflux and nine did not. The median "lipid index" in subjects with oropharyngeal reflux (24.5) was significantly greater than that in those without reflux (1.0) (p<0.001). A "lipid index" of 7.0 had a sensitivity of 90%, a specificity of 89%, a positive predictive value of 95% and a negative predictive value of 80%. A "lipid index" of 7.0 in the macrophages of induced sputum is a good marker of oropharyngeal reflux.