Abstract
Asthma is a chronic disease that may cause remodeling of the airways. We aimed to observe the effects of the combined use of inhaled budesonide and formoterol on both the reversibility of remodeling and structural changes in the airways. Thirty-six male patients (age range, 20–31) with mild-to-moderate persistent asthma were given inhaled formoterol and budesonide treatment for three months. Bronchial diameter (BD) and bronchial wall thickness (BWT), as measured by high-resolution computerized tomography, and reticular basement membrane thickness (RBMT), assessed in bronchoscopic biopsy specimens, were compared with pretreatment findings. Twenty-two age-matched male controls were also enrolled. BDs of the patients were significantly smaller than in the controls, whereas BWT and RBMT were greater. After three months BWT and RBMT of the subsegmental airways significantly decreased and BD increased. There was a prominent eosinophilic and lymphocytic infiltration in the bronchial mucosa of the asthmatics, and the eosinophilic infiltration significantly improved with treatment. Both serum total IgE and eosinophil counts were related to eosinophilic infiltration in the biopsy samples (r = 0.494 and r = 0.463, respectively). FEV1 was positively correlated with the diameters of the segmental and subsegmental airways (r = 0.491 and r = 0.265, respectively) and negatively correlated with BWT of the subsegmental airways (r = −0.293) and with the RBMT of both the segmental and subsegmental airways (r = −0.597 and r = −0.590, respectively). We suggest that treatment with inhaled formoterol and budesonide may reverse increased RBMT and BWT as part of remodeling in patients with asthma.
Similar content being viewed by others
References
Adcock IM, Maneechotesuwan K, Usmani O (2002) Molecular interactions between glucocorticoids and long-acting beta-2 agonists. J Allergy Clin Immunol 110:S261–S268
Awadh N, Muller NL, Park CS, Abboud RT, FitzGerald JM (1998) Airway wall thickness in patients with near fatal asthma and control groups: assessment with high resolution computed scanning. Thorax 53:248–253
Barbato A, Turato G, Baraldo S, et al. (2003) Airway inflammation in childhood asthma. Am J Respir Crit Care Med 168:798–803
Boulet LP, Turcotte H, Laviolette M, et al. (2000) Airway hyperresponsiveness, inflammation and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma. Am J Respir Crit Care Med 162:1308–1313
Bousquet J, Jeffery PK, Busse WW, et al. (2000) Asthma: from bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 161:1720–1745
Bumbacea D, Campbell D, Nguyen L, et al. (2004) Parameters associated with persistent airflow obstruction in chronic severe asthma. Eur Respir J 24:8–10
Chetta A, Foresi A, Del Donno M, et al. (1997) Airways remodeling is a distinctive feature of asthma and is related to severity of disease. Chest 111:852–857
Djukanovic R, Wilson JW, Britten KM, et al. (1992) Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis 145:669–674
Eickelberg O, Roth M, Lorx R, et al. (1999) Ligand-independent activation of the glucocorticoid receptor by the beta-2 adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem 274:1005–1010
Fish JE, Peters SP (1999) Asthma severity: histopathologic correlations. Drugs Today 35:585–594
Gono H, Fujimoto K, Kawakami S, Kubo K (2003) Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma. Eur Respir J 22:965–971
Hadcock JR, Wang H-Y, Malbon CC. (1989) Agonist-induced destabilization of beta adrenergic receptor mRNA: attenuation of glucocorticoid-induced up-regulation of beta-adrenergic receptors. J Biol Chem 264:19928–19933
Hoshino M, Nakamura Y, Sim JJ, et al. (1998) Inhaled corticosteroid reduced lamina reticularis of the basement membrane by modulation of insulin-like growth factor (IGF)-1 expression in bronchial asthma. Clin Exp Allergy 28:568–577
Hoshino M, Takahashi M, Takai Y, et al. (1999) Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma. J Allergy Clin Immunol 104:356–363
Hudon C, Turcotte H, Laviolette M, Carrier C, Boulet LP (1997) Characteristics of bronchial asthma with incomplete reversibility of airflow obstruction. Ann Allergy Asthma Immunol 78:195–202
James AL, Maxwell PS, Pearce-Pinto G, Elliot JG, Carrol NG (2002) The relationship of reticular basement membrane thickness to airway wall remodeling in asthma. Am J Respir Crit Care Med 166:1590–1595
Jeffery PK, Godfrey RW, Adelroth E, et al. (1992) Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma: a quantitative light and electron microscopic study. Am Rev Respir Dis 145:890–899
Kasahara K, Shiba K, Ozawa T, et al. (2002) Correlation between the bronchial subepithelial layer and whole airway wall thickness in patients with asthma. Thorax 57:242–246
King GG, Muller NL, Whittal KP, Xiang QS, Pare PD (2000) An analysis algorithm for measuring airway lumen and wall areas from high-resolution computed tomographic data. Am J Respir Crit Care Med 161: 574–580
Koshak EA, Alamoudi OS (1999) Do eosinophil counts correlate differently with asthma severity by symptoms versus peak flow rate? Ann Allergy Asthma Immunol 83:567–571
Koto HM, Mak JCW, Haddad E-B, et al. (1996) Mechanisms of impaired beta-adrenoceptor-induced airway relaxation by interleukin-1-beta in vivo in the rat. J Clin Invest 98:1780–1787
Laitinen A, Karjalainen E-M, Altraja A, et al. (2000) Histopathologic features of early and progressive asthma. J Allergy Clin Immunol 105(2 Pt 2):S509–S513
Laprise C, Laviolette M, Boutet M, et al. (1999) Asymptomatic airway hyperesponsiveness: relationships with airway inflammation and remodelling. Eur Respir J 14:63–73
Lee YM, Park JS, Hwang JH, et al. (2004) High resolution CT findings in patients with near-fatal asthma. Comparison of patients with mild-to-severe asthma and normal control subjects and changes in airway abnormalities following steroid treatment. Chest 126:1840–1848
Lloyd CM, Gonzalo JA, Nguyen T, et al. (2001) Resolution of bronchial hyperresponsiveness and pulmonary inflammation is associated with IL-3 and tissue leukocyte apoptosis. J Immunol 166:2033–2040
Louis R, Lau LCK, Bron AO, et al. (2000) The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med 161:9–16
Lundgren R, Soderberg M, Horstedt P, et al. (1988) Morphological studies of bronchial mucosal biopsies from asthmatics before and after ten years of treatment with inhaled steroids. Eur Respir J 1:883–889
Mak JCW, Nishikawa M, Shirasaki H, Miyayasu K, Barnes PJ (1995) Protective effect of a glucocorticoid on downregulation of pulmonary beta-2 adrenergic receptors in vivo. J Clin Invest 96:99–106
McMillan SJ, Xanthout G, Lloyd CM (2005) Therapeutic administration of budesonide ameliorates allergen-induced airway remodeling. Clin Exp Allergy 35:388–396
Nakano Y, Müller NL, King GG, et al. (2002) Quantitative assessment of airway remodeling using high-resolution CT. Chest 122:271–275
Neville RG, Pearson MG, Richards N, et al. (1999) A cost analysis on the pattern of asthma prescribing in the UK. Eur Respir J 14:605–609
Olivieri D, Chetta A, Del Donno M, et al. (1997) Effects of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlled study. Am J Respir Crit Care Med 155:1864–1871
Overbeek SE, Mulder PG, Baelemans SM, Hoogsteden HC, Prins JB (2005) Formoterol added to low-dose budesonide has no additional antiinflammatory effect in asthmatic patients. Chest 128:1121–1127
Paganin F, Seneterre E, Chanez P, et al. (1996) Computed tomography of the lungs in asthma: influence of disease severity and etiology. Am J Respir Crit Care Med 153: 110–114
Saetta M, Maestrelli P, Turato G, et al. (1995) Airway wall remodeling after cessation of exposure to isocyanates in sensitized asthmatic subjects. Am J Respir Crit Care Med 151:489–494
Serrano J, Plaza V, Sanchis J (1999) Hospital admission from asthma. A descriptive study and analysis of factors related to prognosis after release. Arch Bronchopneumol 35:372–378
Sont JK, Willems LNA, Bel EH, et al. (1999) Clinical control and histopathologic outcome of asthma when using airway hyperesponsiveness as an additional guideline to long-term treatment. Am J Respir Crit Care Med 159:1043–1051
Trigg CJ, Manolitsas ND, Wang J, et al. (1994) Placebo-controlled immunopathologic study of 4 months of inhaled corticosteroids in asthma. Am J Respir Crit Care Med 150:17–22
Usmani OS, Maneechotesuwan K, Adcock IM, Barnes PJ (2002) Glucocorticoid receptor activation following inhaled fluticasone and salmeterol (abstract). Am J Respir Crit Care Med 165:A616
Vignola AM, Paganin F, Capieu L, et al. (2004) Airway remodeling assessed by sputum and high-resolution computed tomography in asthma and COPD. Eur Respir J 24:893–894
Vignola AM, Riccobono L, Profita M, et al. (2005) Effects of low doses of inhaled fluticasone propionate on inflammation and remodeling in persistent-mild asthma. Allergy 60:1511–1517
Wallin A, Sandstrom T, Soderberg M, et al. (1999) The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma. Am J Respir Crit Care Med 159:79–86
Ward C, Pais M, Bish R, et al. (2002) Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma. Thorax 57:309–316
Ward C, Walters H (2005) Airway remodeling: the influence of corticosteroids. Curr Opin Allergy Clin Immunol 5: 43–48
Wilson JW, Li X (1997) The measurement of reticular basement membrane and submucosal collagen in the asthmatic airway. Clin Exp Allergy 27:363–371
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Capraz, F., Kunter, E., Cermik, H. et al. The Effect of Inhaled Budesonide and Formoterol on Bronchial Remodeling and HRCT Features in Young Asthmatics. Lung 185, 89–96 (2007). https://doi.org/10.1007/s00408-006-0007-2
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00408-006-0007-2