Inflammation and corticosteroid responsiveness in ex-, current- and never-smoking asthmatics

Abstract

BackgroundIt has been suggested that smoking asthmatics benefit less from corticosteroid treatment than never-smoking asthmatics. We investigated differences in blood and sputum inflammatory profiles between ex-, current-, and never-smokers and assessed their ICS treatment response after 2-week and 1-year treatment.MethodsWe analyzed FEV1, PC20 methacholine and PC20 AMP, (differential) cell counts in sputum and blood in ex-, current- and never-smokers at baseline (n=114), after 2-week treatment with fluticasone 500 or 2000 μg/day (n=76) and after 1-year treatment with fluticasone 500 μg/day or a variable dose of fluticasone based on a self-management plan (n=64).ResultsA total of 114 patients were included (29 ex-, 30 current- and 55 never-smokers. At baseline, ex- and current-smokers had less eosinophils in sputum and blood than never-smokers. Blood neutrophil counts were higher in current- than in never-smokers. A higher number of cigarettes smoked daily was associated with lower blood and sputum eosinophils. After 2-week ICS treatment, FEV1 %predicted improved less in current-smokers than never-smokers (2.4% versus 8.1%, p=0.010) and ex-smokers tended to improve less than never-smokers (4.1%, p=0.067). In contrast, no differences in ICS treatment response in lung function or inflammatory cells were found between the three groups after 1 year.ConclusionsEx- and current-smokers have less eosinophils and more neutrophils in their sputum and blood than never-smokers. Although ex- and current-smokers have a reduced short-term corticosteroid treatment response, we did not find a difference in their long-term treatment response.

Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study

“…2628 Similarly, lower BMI and non-smoking status as predictors are not unexpected, because the obesity-related asthma phenotype is typically noneosinophilic, 1,2 and current and ex-smokers have lower blood eosinophils than never-smokers. 2729 The proportion of patients with peripheral eosinophilia (16%) in the present study was similar to the 18-26% prevalence found among adults with asthma in three recent observational studies using a similar cut-point (<400/µL vs. ≥400/µL). 15,17, 19 Zeiger et al 17 in a study of 2392 adults with asthma found that blood eosinophil count ≥400/µL was a risk factor for asthma exacerbation the following year as well as for excessive SABA use (≥4 puffs/day, equivalent to ≥400 µg/day in this study).…”

Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study

“…We also saw an increase in absolute numbers of neutrophils in the blood and a decrease in FeNO in the SAs/ex group compared with the SAn group. These effects are also reported in milder asthma [30][31][32]. Other inflammatory changes observed in response to smoking in milder asthma include a reduction in blood [30] and sputum eosinophils [30,33], increases in sputum neutrophils [29], and increased submucosal CD8 + lymphocytes and macrophages in bronchial biopsies [34]; however, we did not see these differences in our severe asthma subjects.…”

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

“…From a pragmatic, clinical perspective, phenotypic traits can be used in the daily clinical care to target-specific treatments: eosinophilia combined with exacerbations predicts effect of anti-IL5 [27] and patients with fixed airflow obstruction and exacerbations may benefit from tiotropium [28]. Furthermore, perennial allergic sensitization, airflow obstruction (FEV1 < 80%) and exacerbations predict effect of anti-IgE [5].…”