Effects of Medication Use on Small Airway Function and Airway Inflammation in Patients with Clinically Controlled Asthma

Abstract

Objective

To observe effects of medication use on small airway function, airway inflammation and acute exacerbations in patients with clinically controlled asthma.

Methods

Forced expiratory flow over the middle half of the forced expiratory curve (FEF_25%–75%), percentage of eosinophil, concentrations of eosinophil cationic protein (ECP) and interleukin (IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone. Subsequently, acute exacerbations were compared between two groups during the 24-week follow-up period.

Results

FEF_25%–75% in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone. Meanwhile, the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone. Additionally, the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period.

Conclusion

Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations, presumably secondary to reduction in airway inflammation.

Keywords

asthma / clinical control / small airways / airway inflammation / acute exacerbation

References

[1] TulicMK, HamidQ. New insights into the pathophysiology of the small airways in asthma. Clin Chest Med, 2006, 27(1): 41-52

[2] HamidQ, SongY, KotsimbosTC, et al.. Inflammation of small airways in asthma. J Allergy Clin Immunol, 1997, 100(1): 44-51

[3] HowarthP. Small airway inflammation and asthma. Int J Clin Pract Suppl, 1998, 96: 15-22

[4] CorrenJ. Small airways disease in asthma. Curr Allergy Asthma Rep, 2008, 8(6): 533-539

[5] BatemanED, HurdSS, BarnesPJ, et al.. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J, 2008, 31(1): 143-178

[6] BatemanED, BousheyHA, BousquetJ, et al.. Can guideline-defined asthma control be achieved?. The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med, 2004, 170(8): 836-844

[7] RabeKF, AdachiM, LaiCK, et al.. Worldwide severity and control of asthma in children and adults: the global asthma insights and reality surveys. J Allergy Clin Immunol, 2004, 114(1): 40-47

[8] JacksonDJ, SykesA, MalliaP, et al.. Asthma exacerbations: origin, effect, and prevention. J Allergy Clin Immunol, 2011, 128(6): 1165-1174

[9] CastilloJR, PetersSP, BusseWW. Asthma Exacerbations: Pathogenesis, Prevention, and Treatment. J Allergy Clin Immunol Pract, 2017, 5(4): 918-927

[10] LeachCL. Improved delivery of inhaled steroids to the large and small airways. Respir Med, 1998, 92(Suppl A): 3-8

[11] VirchowJC, MehtaA, LjungbladL, et al.. Add-on montelukast in inadequately controlled asthma patients in a 6-month open-label study: the MONtelukast In Chronic Asthma (MONICA) study. Respir Med, 2010, 104(5): 644-651

[12] VirchowJCJr., PrasseA, NayaI, et al.. Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids. Am J Respir Crit Care Med, 2000, 162(2): 578-585 Pt 1

[13] PinI, GibsonPG, KolendowiczR, et al.. Use of induced sputum cell counts to investigate airway inflammation in asthma. Thorax, 1992, 47(1): 25-29

[14] PavordID, PizzichiniMM, PizzichiniE, et al.. The use of induced sputum to investigate airway inflammation. Thorax, 1997, 52(6): 498-501

[15] PizzichiniE, PizzichiniMM, EfthimiadisA, et al.. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med, 1996, 154(2): 308-317 Pt 1

[16] RingdalN, ElirazA, PruzinecR, et al.. The salmeterol/fluticasone combination is more effective than fluticasone plus oral montelukast in asthma. Respir Med, 2003, 97(3): 234-241

[17] TulicMK, ChristodoulopoulosP, HamidQ. Small airway inflammation in asthma. Respir Res, 2001, 2(6): 333-339

[18] ShawRJ, DjukanovicR, TashkinDP, et al.. The role of small airways in lung disease. Respir Med, 2002, 96(2): 67-80

[19] van VeenIH, SterkPJ, SchotR, et al.. Alveolar nitric oxide versus measures of peripheral airway dysfunction in severe asthma. Eur Respir J, 2006, 27(5): 951-956

[20] BergeronC, HauberHP, GotfriedM, et al.. Evidence of remodeling in peripheral airways of patients with mild to moderate asthma: effect of hydrofluoroalkane-flunisolide. J Allergy Clin Immunol, 2005, 116(5): 983-989

[21] MondinoC, CiabattoniG, KochP, et al.. Effects of inhaled corticosteroids on exhaled leukotrienes and prostanoids in asthmatic children. J Allergy Clin Immunol, 2004, 114(4): 761-767

[22] BarnesPJ. Cytokines as mediators of chronic asthma. Am J Respir Crit Care Med, 1994, 150(5): S42-49 Pt 2

[23] GrootendorstDC, SontJK, WillemsLN, et al.. Comparison of inflammatory cell counts in asthma: induced sputum vs bronchoalveolar lavage and bronchial biopsies. Clin Exp Allergy, 1997, 27(7): 769-779

[24] LeachCL, DavidsonPJ, HasselquistBE, et al.. Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers. Chest, 2002, 122(2): 510-516