Asthma diagnosis and treatment
Effect of inhaled corticosteroids on symptom severity and sputum mediator levels in chronic persistent cough

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Background

Chronic cough often lasts for more than 1 year and is associated with airway inflammation. The effect of inhaled corticosteroids on symptom severity and inflammatory mediator levels in these patients is unknown.

Objective

We sought to determine whether inhaled corticosteroids reduce cough severity and sputum mediator concentrations in patients with chronic persistent cough.

Methods

We performed a double-blind, randomized, placebo-controlled crossover study with inhaled fluticasone, 500 μg twice daily, and placebo for 14 days in 88 patients with cough for more than 1 year, with normal chest radiography and spirometry results. Outcome measures were a daily cough visual analogue scale and induced sputum concentrations of eosinophilic cationic protein (ECP), myeloperoxidase, leukotriene B4 (LTB4), leukotrienes C4/D4/E4 (cysteinyl leukotrienes [Cys-LTs]), prostaglandin E2 (PGE2), IL-8, and TNF-α. Sputum cell counts, exhaled nitric oxide levels, and carbon monoxide levels were also measured.

Results

There was a significant improvement in the cough visual analogue scale after inhaled fluticasone compared with placebo (mean difference, 1.0; 95% CI, 0.4-1.5; P < .001). LTB4, Cys-LT, and PGE2 levels were increased in all causes of cough. Sputum ECP counts, exhaled nitric oxide levels, and carbon monoxide levels decreased significantly after inhaled fluticasone. There was no change in sputum cell counts and other mediator concentrations.

Conclusion

Cough severity and sputum ECP levels are modestly reduced by inhaled corticosteroids in patients with chronic cough persisting for more than 1 year. LTB4, Cys-LT, PGE2, IL-8, myeloperoxidase, and TNF-α levels are unaltered by this therapy. This raises the possibility that drugs targeted to reduce the effects of these mediators might be of benefit in chronic persistent cough.

Section snippets

Subjects

Adults with a cough for more than 1 year were recruited from hospital respiratory clinics and from responses to an advertisement in a local newspaper. No subject had evidence of any other lung disease on the basis of history, clinical examination, chest radiography, and spirometry. Exclusion criteria were treatment with inhaled or oral corticosteroids within 3 weeks of inclusion, upper respiratory tract infection within 6 weeks of inclusion, angiotensin-converting enzyme inhibitor treatment,

Baseline subject characteristics and investigations

We screened 120 subjects with cough, 93 of whom met all the inclusion criteria and were randomized; 88 completed all study visits. Of these, 52 were recruited from the community (general practitioner referrals and advertisement in a newspaper), and 36 were referred from hospital clinics. Five subjects dropped out because of inability to attend all study visits.

A final diagnosis for the cough was obtained in 78 (89%) of the 88 patients; 74% had a single diagnosis, 24% had 2 diagnoses, and 2% had

Discussion

This is the first randomized, placebo-controlled study to demonstrate an improvement in cough severity after inhaled fluticasone compared with after placebo in patients with chronic cough for more than 1 year. The decrease in cough severity score was accompanied by a decrease in sputum ECP, eNO, and CO levels, but there was no reduction in sputum mediator levels of LTB4, Cys-LT, PGE2, IL-8, MPO, and TNF-α.

Although there was a statistically significant decrease in the cough VAS, this

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