Nonasthmatic chronic cough: No effect of treatment with an inhaled corticosteroid in patients without sputum eosinophilia.

BACKGROUND: Inhaled corticosteroids are effective in suppressing a chronic cough without asthma associated with sputum eosinophilia. OBJECTIVE: To investigate the inflammatory characteristics in the induced sputum of patients with a chronic cough without asthma or known cause and the effects of budesonide treatment on chronic cough in those patients. PATIENTS AND METHODS: Forty-four adults (mean [minimu, maximum] age of 45 years [20,75], 28 women, 17 atopic subjects and 32 nonsmokers], with a daily bothersome cough for at least one year and who had no evidence of asthma or other known cause for the cough, were consecutively enrolled. The trial was a randomized, double-blind, controlled parallel group trial of budesonide 400 mg twice daily for two weeks versus placebo. Patients then received open administration of the same dose of budesonide for a further two weeks. Sputum was induced before and at the end of each treatment period. Cough severity was documented by a visual analogue scale. RESULTS: Thirty-nine (89%) patients produced mucoid sputum after induction on at least one study visit. At baseline, the majority (59%) had a mild elevation in the median proportion of neutrophils (65%). All had elevated fluid phase levels of fibrinogen (3200 mg/L) and albumin (880 mg/L), and high levels of interleukin-8 and substance P. Interleukin-8 correlated with neutrophils (rho=0.72, P<0.001), fibrinogen (rho=0.65, P<0.001), albumin (rho=0.67, P=0. 001) and eosinophil cationic protein (rho=0.60, P=0.001). Substance P correlated with albumin (rho=0.60, P=0.006). No subject had an increase in eosinophils. Treatment with budesonide did not affect cough or sputum measurements. CONCLUSIONS: Patients with nonasthmatic chronic cough enrolled in this study had evidence of a mild neutrophilia and/or microvascular leakage. Chronic cough did not respond to treatment with budesonide, perhaps because the cause was not associated with sputum eosinophilia.

Diagnosing occupational asthma: use of induced sputum.

The diagnosis of occupational asthma (OA) needs to be made with as much objective evidence as possible. If there is airway inflammation, measurement of this should be an asset. The objective of this study was to investigate whether there is an increase in induced sputum and blood eosinophils and eosinophil cationic protein (ECP) in OA after work exposure. Patients were assessed after a 2-4 week period at work and away from work with cell counts and ECP assays performed blind to the clinical data. They were considered to have OA if symptoms were worse at work and there was a fall in forced expiratory volume in one second (FEV1) > or =20% or in the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) of four-fold or more compared with away from work. Patients whose symptoms were worse at work but had a change in FEV1 of <20% and in methacholine PC20 of less than four-fold were considered as controls. Sixteen patients were studied. Ten had OA and six were controls. Patients with OA had a significant increase in median (interquartile range) sputum eosinophils and ECP when at work compared with the periods out of work, 10.0 (17.05) versus 0.8 (1.6)% (p=0.007) and 3,840 (6,076) versus 116 (180) microg x L(-1) (p=0.01). They also had a higher blood eosinophil count, 0.3 (0.5) x 10(9) versus 0.2 (0.1) x 10(9) x L(-1) (p=0.013), and a trend towards higher serum ECP levels, 44.0 (20.0) versus 32.0 (18.5) microg x L(-1) (p=0.07). In conclusion, the proportion of eosinophils and levels of eosinophil cationic protein in sputum are particularly high at work in patients with occupational asthma, suggesting that the measurement of these factors can supplement other physiological outcomes in establishing the diagnosis of occupational asthma.

Prednisone-dependent asthma: inflammatory indices in induced sputum.

The kinetics of changes in inflammatory indices in induced sputum from eight prednisone dependent asthmatics whose minimum clinical maintenance and exacerbation doses were known were investigated. The study began on the last day of a course of 30 mg prednisone daily for one week. Thereafter, the daily prednisone was reduced in a structured way to below the maintenance dose. This treatment was continued until a clinical exacerbation occurred. Prednisone 30 mg daily was then given again for one week. The mean duration of prednisone reduction was 7.4 weeks and the median dose was 7.5 mg x day(-1). Increases in sputum eosinophils preceded increases in blood eosinophils by 4 weeks and worsening of symptoms and forced expiratory volume in one second by 6 weeks. The clinical exacerbation was also accompanied by sputum neutrophilia and increases in sputum eosinophil cationic protein (ECP), fibrinogen and interleukin (IL)-5. Treatment with prednisone suppressed median sputum eosinophilia (from 16.3 to 0%, p<0.001), decreased sputum ECP (from 7,480 to 700 microg x L(-1), p = 0.01), but did not improve neutrophil numbers, fibrinogen or IL-5. The results show that the reduction of prednisone treatment in prednisone-dependent asthmatics evokes a severe airway eosinophilic inflammatory response. Clinical and blood indices deteriorate later than those in sputum suggesting that sputum examination may be useful to identify the minimum regular dose of prednisone required in these patients.

Markers of inflammation in induced sputum in acute bronchitis caused by Chlamydia pneumoniae.

Little is known of the inflammatory characteristics of acute infections of the respiratory tract caused by virus and unusual bacteria such as Chlamydia pneumoniae. A case is reported in whom inflammatory indices in sputum were used to investigate, for the first time, the airway inflammation during an episode of acute bronchitis caused by C pneumoniae. The patient presented with a dry cough of five days duration. C pneumoniae was identified by polymerase chain reaction (PCR) in a nasopharyngeal swab collected on day 5. Virological studies were negative. Clinical and inflammatory indices in induced sputum were measured on days 6, 8, and 11. The cough cleared spontaneously by day 11. Forced expiratory volume in one second was normal throughout. Sputum findings identified intense airway inflammation characterised by increased total cell and lymphocyte counts followed by an increase in neutrophils and a decrease in the CD4/CD8 ratio, activation of CD8 lymphocytes, and exudation as indicated by an increase in fluid phase fibrinogen. These observations suggest that sputum might be useful to monitor an inflammatory/immune response of the airway in acute infections.

Sputum in severe exacerbations of asthma: kinetics of inflammatory indices after prednisone treatment.

We have investigated the time-course of symptoms, forced expiratory volume in one second (FEV1), and the airway inflammatory changes in sputum selected from saliva and blood of 10 patients with severe exacerbation of asthma betwen presentation and after 1, 2, 3, 7, and 21 days of treatment. The sputum was induced by a modified standard protocol, and we examined its safety. The severe exacerbation of asthma was defined by the presence of nocturnal symptoms disturbing sleep and/or the need for inhaled short acting beta2-agonist > or = 8 puffs/d and an FEV1 after bronchodilator < 60% of predicted. The treatment consisted of additional prednisone 30 mg daily for 5 d followed by reduction to zero by day 10. Abnormal findings [median (interquartile range)] in spontaneous and induced sputum included low viability of cells [52.0 (34.0)%]; eosinophilia [20.0 (16.4)%]; many free eosinophil granules; and increased levels of fluid-phase ECP [1960 (9204) microg/L], fibrinogen [6045 (10720) microg/L], and IL-5 [160 (212) pg/ml]. Peripheral blood eosinophils [10.4 (7.6)%] and ECP levels [34.0 (35.0) microg/L] were increased. After treatment, symptoms, FEV1, blood eosinophilia, and serum ECP improved in the first 24 h. Sputum eosinophils and ECP did not improve until 48 h and fibrinogen not until 7 d. The improvement in sputum eosinophils and ECP levels was correlated with improvement of FEV1 and in fluid-phase IL-5. Thirty sputum inductions were performed safely in the majority with inhaled isotonic or 3% saline (23.3% or 63.3%, respectively) over a short duration (mean 8.4 min). The patients who had a fall in FEV1 of > or = 10% (10 occasions) after induction differed from those with a fall of < 10% only in the amount of inhaled beta2-agonist used by the patients in the preceding 24 h [8.0 (5.0) versus 4.0 (3.0) puffs/d, p = 0.01]. The results suggest that spontaneous or induced sputum can be used safely to follow the kinetics of effects of antiinflammatory treatment in a severe exacerbation of asthma. The clinical and blood indices improve before those in sputum, raising the possibility that examination of sputum is a better guide in these patients to follow the effects of treatment.