Neutrophilic inflammation is associated with small airway function in older people with asthma

Keulers, L.A.B. (2013) Neutrophilic inflammation is associated with small airway function in older people with asthma. thesis, Medicine.

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Abstract

Background: Small airway function makes an important contribution to asthma control. The multiple breath nitrogen washout test measures ventilation heterogeneity in convection-dependent (Scond) and the more peripheral diffusion-dependent (Sacin) airways. Airway hyperresponsiveness (AHR) is a feature of asthma that is associated with inflammation. Severity of AHR is predicted by Scond in younger asthmatics and by Sacin in elderly asthmatics. The effect of airway inflammation on small airway function is unknown. In contrast to eosinophilic inflammation, a characteristic feature of asthma, neutrophil numbers increase with age. This might implicate an association of the type of airway inflammation and the localisation of small airway function. Aim: The study aim was to determine the association between sputum inflammatory cells and the site of small airway dysfunction in younger and older adult patients with asthma. Methods: Fifty three (20-67 years) subjects with asthma were divided into two groups (< 40 or ≥ 40 years) and had measures of atopy, spirometry, lung volumes, fraction of exhaled nitric oxide (FeNO) as an inflammatory biomarker, severity of AHR measured by dose response slope (DRS) to mannitol, ventilation heterogeneity measured by Scond and Sacin, and induced sputum differential cell counts. Backward multiple regressions were used to determine the predictors of Scond and Sacin in the different age groups. Results: Subjects ≥ 40 had significantly less atopy and longer disease duration than subjects < 40. Sacin and Scond were higher in subjects ≥ 40 (P = 0.01 and P = 0.051, respectively). In multiple regression analysis, Sacin was best predicted by % predicted FEV1/FVC and % neutrophils in subjects ≥ 40 (model r2 = 0.466, P = 0.001) and by % predicted RV/TLC in subjects < 40 (model r2 = 0.336, P < 0.001). Scond was predicted by % predicted FEV1/FVC and FeNO in subjects ≥ 40 (model r2 = 0.464, P = 0.002) and by % predicted RV/TLC and DRS in subjects < 40 (model r2 = 0.380, P < 0.001). FeNO positively correlated with (r = 0.473, P = 0.006), but did not significantly predict Scond in subjects < 40. Conclusion: Eosinophilic inflammation, reflected by FeNO, affects the conducting airways in both younger and older asthmatics. Neutrophilic inflammation additionally affects the peripheral airways in older asthmatics. Since neutrophilic inflammation is difficult to treat, these findings may have clinical implications for older asthmatics.

Item Type:	Thesis (Thesis)
Supervisor name:	Postma, Prof. Dr. D.S.
Supervisor name:	King, Prof. G.G. and Airway Physiology and Imaging Research Group and Woolcock Institute of Medical Research and Sydney, Australia
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:45
Last Modified:	25 Jun 2020 10:45
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/667

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