Association of upper and lower airway eosinophilic inflammation with response to omalizumab in patients with severe asthma

被引:8
作者
Kurokawa, Makoto [1 ]
Koya, Toshiyuki [1 ]
Takeuchi, Hiroyuki [1 ]
Hayashi, Masachika [1 ]
Sakagami, Takuro [1 ]
Ishioka, Kojiro [2 ]
Gon, Yasuhiro [3 ]
Hasegawa, Takashi [4 ]
Kikuchi, Toshiaki [1 ]
机构
[1] Niigata Univ, Grad Sch Med & Dent Sci, Dept Resp Med & Infect Dis, Niigata, Japan
[2] Niigata Univ, Grad Sch Med & Dent Sci, Dept Otolaryngol Head & Neck Surg, Niigata, Japan
[3] Nihon Univ Med, Dept Internal Med, Div Resp Med, Tokyo, Japan
[4] Niigata Univ Med & Dent Hosp, Dept Gen Med, Niigata, Japan
基金
日本学术振兴会;
关键词
Omalizumab; severe asthma; fraction of exhaled nitric oxide; nasal biopsy; major basic protein; EPSILON-RI EXPRESSION; EXHALED NITRIC-OXIDE; IGE; RHINITIS; THERAPY; SAFETY;
D O I
10.1080/02770903.2018.1541357
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: The anti-immunoglobulin E monoclonal antibody, omalizumab, is used to treat severe asthma and has the potential to ameliorate airway inflammation. However, the effect of omalizumab in ameliorating upper airway inflammation has not been fully elucidated. Objective: We investigated the association of upper and lower airway inflammation with the response to omalizumab treatment. Methods: We used the Global Evaluation of Treatment Effectiveness to assess the efficacy of omalizumab in treating 16 patients with severe asthma. We also investigated the symptom score, short-acting beta-agonist inhaler use, pulmonary function, biomarkers, computed tomography scans, and nasal mucosa pathology at omalizumab initiation and after four months of treatment. Results: When the fraction of exhaled nitric oxide (FeNO) and the percentage of sputum eosinophil were used as indicators of lower airway inflammation, positive correlations were found between CD20 B-cell, mast cell, and eosinophil counts in the nasal mucosa. Improved asthma symptoms were observed in 12 of the 16 severe asthma cases. The FeNO and eosinophil levels in the nasal tissue, prior to the administration of omalizumab were predictors of the response to asthma treatment. Conclusions: These findings suggest heterogeneity among people with severe asthma. In addition, the phenotype associated with response to omalizumab, leading to improvement in asthma symptoms, comprises upper airway eosinophilia and high FeNO levels.
引用
收藏
页码:71 / 78
页数:8
相关论文
共 24 条
[1]   ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005 [J].
American Thoracic Society ;
European Respiratory Society .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2005, 171 (08) :912-930
[2]   Omalizumab-induced reductions in mast cell FcεRI expression and function [J].
Beck, LA ;
Marcotte, GV ;
MacGlashan, D ;
Togias, A ;
Saini, S .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2004, 114 (03) :527-530
[3]   Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression [J].
Boudewijn, Ilse M. ;
Faiz, Alen ;
Steiling, Katrina ;
van der Wiel, Erica ;
Telenga, Eef D. ;
Hoonhorst, Susan J. M. ;
ten Hacken, Nick H. T. ;
Brandsma, Corry-Anke ;
Kerstjens, Huib A. M. ;
Timens, Wim ;
Heijink, Irene H. ;
Jonker, Marnix R. ;
de Bruin, Harold G. ;
Vroegop, J. Sebastiaan ;
Pasma, Henk R. ;
Boersma, Wim G. ;
Wielders, Pascal ;
van den Elshout, Frank ;
Mansour, Khaled ;
Spira, Avrum ;
Lenburg, Marc E. ;
Guryev, Victor ;
Postma, Dirkje S. ;
van den Berge, Maarten .
RESPIRATORY RESEARCH, 2017, 18
[4]   Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen) [J].
Bousquet, J. ;
Khaltaev, N. ;
Cruz, A. A. ;
Denburg, J. ;
Fokkens, W. J. ;
Togias, A. ;
Zuberbier, T. ;
Baena-Cagnani, C. E. ;
Canonica, G. W. ;
van Weel, C. ;
Agache, I. ;
Ait-Khaled, N. ;
Bachert, C. ;
Blaiss, M. S. ;
Bonini, S. ;
Boulet, L. -P. ;
Bousquet, P. -J. ;
Camargos, P. ;
Carlsen, K. -H. ;
Chen, Y. ;
Custovic, A. ;
Dahl, R. ;
Demoly, P. ;
Douagui, H. ;
Durham, S. R. ;
van Wijk, R. Gerth ;
Kalayci, O. ;
Kaliner, M. A. ;
Kim, Y. -Y. ;
Kowalski, M. L. ;
Kuna, P. ;
Le, L. T. T. ;
Lemiere, C. ;
Li, J. ;
Lockey, R. F. ;
Mavale-Manuel, S. ;
Meltzer, E. O. ;
Mohammad, Y. ;
Mullol, J. ;
Naclerio, R. ;
Hehir, R. E. O. ;
Ohta, K. ;
Ouedraogo, S. ;
Palkonen, S. ;
Papadopoulos, N. ;
Passalacqua, G. ;
Pawankar, R. ;
Popov, T. A. ;
Rabe, K. F. ;
Rosado-Pinto, J. .
ALLERGY, 2008, 63 :8-+
[5]   Predicting and evaluating response to omalizumab in patients with severe allergic asthma [J].
Bousquet, J. ;
Rabe, K. ;
Humbert, M. ;
Chung, K. F. ;
Berger, W. ;
Fox, H. ;
Ayre, G. ;
Chen, H. ;
Thomas, K. ;
Blogg, M. ;
Holgate, S. .
RESPIRATORY MEDICINE, 2007, 101 (07) :1483-1492
[6]   Persistency of response to omalizumab therapy in severe allergic (IgE-mediated) asthma [J].
Bousquet, J. ;
Siergiejko, Z. ;
Swiebocka, E. ;
Humbert, M. ;
Rabe, K. F. ;
Smith, N. ;
Leo, J. ;
Peckitt, C. ;
Maykut, R. ;
Peachey, G. .
ALLERGY, 2011, 66 (05) :671-678
[7]  
Busse William W., 2000, Journal of Allergy and Clinical Immunology, V106, P1033
[8]   International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma [J].
Chung, Kian Fan ;
Wenzel, Sally E. ;
Brozek, Jan L. ;
Bush, Andrew ;
Castro, Mario ;
Sterk, Peter J. ;
Adcock, Ian M. ;
Bateman, Eric D. ;
Bel, Elisabeth H. ;
Bleecker, Eugene R. ;
Boulet, Louis-Philippe ;
Brightling, Christopher ;
Chanez, Pascal ;
Dahlen, Sven-Erik ;
Djukanovic, Ratko ;
Frey, Urs ;
Gaga, Mina ;
Gibson, Peter ;
Hamid, Qutayba ;
Jajour, Nizar N. ;
Mauad, Thais ;
Sorkness, Ronald L. ;
Teague, W. Gerald .
EUROPEAN RESPIRATORY JOURNAL, 2014, 43 (02) :343-373
[9]   Exhaled nitric oxide and nasal tryptase are associated with wheeze, rhinitis and nasal allergy in primary school children [J].
De Prins, Sofie ;
Marcucci, Francesco ;
Sensi, Laura ;
Van de Mieroop, Els ;
Nelen, Vera ;
Nawrot, Tim S. ;
Schoeters, Greet ;
Koppen, Gudrun .
BIOMARKERS, 2014, 19 (06) :481-487
[10]   Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma [J].
Djukanovic, R ;
Wilson, SJ ;
Kraft, M ;
Jarjour, NN ;
Steel, M ;
Chung, KF ;
Bao, WB ;
Fowler-Taylor, A ;
Matthews, J ;
Busse, WW ;
Holgate, ST ;
Fahy, JV .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 170 (06) :583-593