Eosinophil Inflammation and Hyperresponsiveness in the Airways as Phenotypes of COPD, and Usefulness of Inhaled Glucocorticosteroids

The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway hyperresponsiveness may develop in some cases with chronic obstructive lung disease (COPD), independent of asthma. However, little is known about clinical significance...

Full description

Saved in:
Bibliographic Details
Published inFrontiers in Pharmacology Vol. 10; p. 765
Main Authors Kume, Hiroaki, Hojo, Masayuki, Hashimoto, Naozumi
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media SA 25.07.2019
Frontiers Media S.A
Subjects
Online AccessGet full text

Cover

Loading…
Abstract The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway hyperresponsiveness may develop in some cases with chronic obstructive lung disease (COPD), independent of asthma. However, little is known about clinical significance of these phenotypes of COPD in detail. This clinical study was designed to examine prevalence of airway eosinophilia and airway hyperresponsiveness in COPD who have no symptom and no past history of asthma, and to examine involvement of these pathophysiological features of asthma in the management and therapy for COPD. Sputum examination qualitative and quantitative procedures was performed in stable COPD (GOLD 1-3). When sputum eosinophils were qualitatively (≥+) or quantitatively assessed (≥3%), ciclesonide (inhaled glucocorticosteroids) was added on bronchodilators. In cases with FEV ≥ 70% of predicted values, acetylcholine provocation test was examined for assessment of airway hyperresponsiveness. Therapeutic effect was evaluated using spirometry and COPD assessment test (CAT). Sputum eosinophils were observed in 65 (50.4%) of 129 subjects using qualitative analysis; in contrast, lower grade (>0%) and higher grade (≥3%) were observed in 15 (20.3%) and 25 (33.8%) of 74 subjects using quantitative analysis. Airway hyperresponsiveness developed in 46.9% of these subjects with sputum eosinophils. Exacerbations occurred much more frequently in lower-grade airway eosinophilia without ciclesonide than in higher-grade airway eosinophilia with ciclesonide. Airway hyperresponsiveness significantly increased frequency of exacerbations in COPD with both lower and higher grade in airway eosinophilia. Addition of ciclesonide to indacaterol markedly improved lung function (FEV , IC), CAT score, and reliever use in these subjects with airway eosinophilia determined by qualitative analysis. However, ciclesonide was less effective in improving these values in subjects with airway hyperresponsiveness than in those without airway hyperresponsiveness. Airway eosinophilia and airway hyperresponsiveness are complicated with 25-50% of COPD that have no symptom and history for asthma. These phenotypes of COPD are closely related to symptom stability and reactivity to glucocorticosteroids. These phenotypes may play key roles for advancement of the management and therapy of this disease.
AbstractList Background: The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway hyperresponsiveness may develop in some cases with chronic obstructive lung disease (COPD), independent of asthma. However, little is known about clinical significance of these phenotypes of COPD in detail.Aims and objectives: This clinical study was designed to examine prevalence of airway eosinophilia and airway hyperresponsiveness in COPD who have no symptom and no past history of asthma, and to examine involvement of these pathophysiological features of asthma in the management and therapy for COPD.Methods: Sputum examination via qualitative and quantitative procedures was performed in stable COPD (GOLD 1–3). When sputum eosinophils were qualitatively (≥+) or quantitatively assessed (≥3%), ciclesonide (inhaled glucocorticosteroids) was added on bronchodilators. In cases with FEV1 ≥ 70% of predicted values, acetylcholine provocation test was examined for assessment of airway hyperresponsiveness. Therapeutic effect was evaluated using spirometry and COPD assessment test (CAT).Results: Sputum eosinophils were observed in 65 (50.4%) of 129 subjects using qualitative analysis; in contrast, lower grade (>0%) and higher grade (≥3%) were observed in 15 (20.3%) and 25 (33.8%) of 74 subjects using quantitative analysis. Airway hyperresponsiveness developed in 46.9% of these subjects with sputum eosinophils. Exacerbations occurred much more frequently in lower-grade airway eosinophilia without ciclesonide than in higher-grade airway eosinophilia with ciclesonide. Airway hyperresponsiveness significantly increased frequency of exacerbations in COPD with both lower and higher grade in airway eosinophilia. Addition of ciclesonide to indacaterol markedly improved lung function (FEV1, IC), CAT score, and reliever use in these subjects with airway eosinophilia determined by qualitative analysis. However, ciclesonide was less effective in improving these values in subjects with airway hyperresponsiveness than in those without airway hyperresponsiveness.Conclusions: Airway eosinophilia and airway hyperresponsiveness are complicated with 25–50% of COPD that have no symptom and history for asthma. These phenotypes of COPD are closely related to symptom stability and reactivity to glucocorticosteroids. These phenotypes may play key roles for advancement of the management and therapy of this disease.
Background: The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway hyperresponsiveness may develop in some cases with chronic obstructive lung disease (COPD), independent of asthma. However, little is known about clinical significance of these phenotypes of COPD in detail. Aims and objectives: This clinical study was designed to examine prevalence of airway eosinophilia and airway hyperresponsiveness in COPD who have no symptom and no past history of asthma, and to examine involvement of these pathophysiological features of asthma in the management and therapy for COPD. Methods: Sputum examination via qualitative and quantitative procedures was performed in stable COPD (GOLD 1-3). When sputum eosinophils were qualitatively (≥+) or quantitatively assessed (≥3%), ciclesonide (inhaled glucocorticosteroids) was added on bronchodilators. In cases with FEV1 ≥ 70% of predicted values, acetylcholine provocation test was examined for assessment of airway hyperresponsiveness. Therapeutic effect was evaluated using spirometry and COPD assessment test (CAT). Results: Sputum eosinophils were observed in 65 (50.4%) of 129 subjects using qualitative analysis; in contrast, lower grade (>0%) and higher grade (≥3%) were observed in 15 (20.3%) and 25 (33.8%) of 74 subjects using quantitative analysis. Airway hyperresponsiveness developed in 46.9% of these subjects with sputum eosinophils. Exacerbations occurred much more frequently in lower-grade airway eosinophilia without ciclesonide than in higher-grade airway eosinophilia with ciclesonide. Airway hyperresponsiveness significantly increased frequency of exacerbations in COPD with both lower and higher grade in airway eosinophilia. Addition of ciclesonide to indacaterol markedly improved lung function (FEV1, IC), CAT score, and reliever use in these subjects with airway eosinophilia determined by qualitative analysis. However, ciclesonide was less effective in improving these values in subjects with airway hyperresponsiveness than in those without airway hyperresponsiveness. Conclusions: Airway eosinophilia and airway hyperresponsiveness are complicated with 25-50% of COPD that have no symptom and history for asthma. These phenotypes of COPD are closely related to symptom stability and reactivity to glucocorticosteroids. These phenotypes may play key roles for advancement of the management and therapy of this disease.Background: The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway hyperresponsiveness may develop in some cases with chronic obstructive lung disease (COPD), independent of asthma. However, little is known about clinical significance of these phenotypes of COPD in detail. Aims and objectives: This clinical study was designed to examine prevalence of airway eosinophilia and airway hyperresponsiveness in COPD who have no symptom and no past history of asthma, and to examine involvement of these pathophysiological features of asthma in the management and therapy for COPD. Methods: Sputum examination via qualitative and quantitative procedures was performed in stable COPD (GOLD 1-3). When sputum eosinophils were qualitatively (≥+) or quantitatively assessed (≥3%), ciclesonide (inhaled glucocorticosteroids) was added on bronchodilators. In cases with FEV1 ≥ 70% of predicted values, acetylcholine provocation test was examined for assessment of airway hyperresponsiveness. Therapeutic effect was evaluated using spirometry and COPD assessment test (CAT). Results: Sputum eosinophils were observed in 65 (50.4%) of 129 subjects using qualitative analysis; in contrast, lower grade (>0%) and higher grade (≥3%) were observed in 15 (20.3%) and 25 (33.8%) of 74 subjects using quantitative analysis. Airway hyperresponsiveness developed in 46.9% of these subjects with sputum eosinophils. Exacerbations occurred much more frequently in lower-grade airway eosinophilia without ciclesonide than in higher-grade airway eosinophilia with ciclesonide. Airway hyperresponsiveness significantly increased frequency of exacerbations in COPD with both lower and higher grade in airway eosinophilia. Addition of ciclesonide to indacaterol markedly improved lung function (FEV1, IC), CAT score, and reliever use in these subjects with airway eosinophilia determined by qualitative analysis. However, ciclesonide was less effective in improving these values in subjects with airway hyperresponsiveness than in those without airway hyperresponsiveness. Conclusions: Airway eosinophilia and airway hyperresponsiveness are complicated with 25-50% of COPD that have no symptom and history for asthma. These phenotypes of COPD are closely related to symptom stability and reactivity to glucocorticosteroids. These phenotypes may play key roles for advancement of the management and therapy of this disease.
The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway hyperresponsiveness may develop in some cases with chronic obstructive lung disease (COPD), independent of asthma. However, little is known about clinical significance of these phenotypes of COPD in detail. This clinical study was designed to examine prevalence of airway eosinophilia and airway hyperresponsiveness in COPD who have no symptom and no past history of asthma, and to examine involvement of these pathophysiological features of asthma in the management and therapy for COPD. Sputum examination qualitative and quantitative procedures was performed in stable COPD (GOLD 1-3). When sputum eosinophils were qualitatively (≥+) or quantitatively assessed (≥3%), ciclesonide (inhaled glucocorticosteroids) was added on bronchodilators. In cases with FEV ≥ 70% of predicted values, acetylcholine provocation test was examined for assessment of airway hyperresponsiveness. Therapeutic effect was evaluated using spirometry and COPD assessment test (CAT). Sputum eosinophils were observed in 65 (50.4%) of 129 subjects using qualitative analysis; in contrast, lower grade (>0%) and higher grade (≥3%) were observed in 15 (20.3%) and 25 (33.8%) of 74 subjects using quantitative analysis. Airway hyperresponsiveness developed in 46.9% of these subjects with sputum eosinophils. Exacerbations occurred much more frequently in lower-grade airway eosinophilia without ciclesonide than in higher-grade airway eosinophilia with ciclesonide. Airway hyperresponsiveness significantly increased frequency of exacerbations in COPD with both lower and higher grade in airway eosinophilia. Addition of ciclesonide to indacaterol markedly improved lung function (FEV , IC), CAT score, and reliever use in these subjects with airway eosinophilia determined by qualitative analysis. However, ciclesonide was less effective in improving these values in subjects with airway hyperresponsiveness than in those without airway hyperresponsiveness. Airway eosinophilia and airway hyperresponsiveness are complicated with 25-50% of COPD that have no symptom and history for asthma. These phenotypes of COPD are closely related to symptom stability and reactivity to glucocorticosteroids. These phenotypes may play key roles for advancement of the management and therapy of this disease.
Background: The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway hyperresponsiveness may develop in some cases with chronic obstructive lung disease (COPD), independent of asthma. However, little is known about clinical significance of these phenotypes of COPD in detail. Aims and objectives: This clinical study was designed to examine prevalence of airway eosinophilia and airway hyperresponsiveness in COPD who have no symptom and no past history of asthma, and to examine involvement of these pathophysiological features of asthma in the management and therapy for COPD. Methods: Sputum examination via qualitative and quantitative procedures was performed in stable COPD (GOLD 1–3). When sputum eosinophils were qualitatively (≥+) or quantitatively assessed (≥3%), ciclesonide (inhaled glucocorticosteroids) was added on bronchodilators. In cases with FEV 1 ≥ 70% of predicted values, acetylcholine provocation test was examined for assessment of airway hyperresponsiveness. Therapeutic effect was evaluated using spirometry and COPD assessment test (CAT). Results: Sputum eosinophils were observed in 65 (50.4%) of 129 subjects using qualitative analysis; in contrast, lower grade (>0%) and higher grade (≥3%) were observed in 15 (20.3%) and 25 (33.8%) of 74 subjects using quantitative analysis. Airway hyperresponsiveness developed in 46.9% of these subjects with sputum eosinophils. Exacerbations occurred much more frequently in lower-grade airway eosinophilia without ciclesonide than in higher-grade airway eosinophilia with ciclesonide. Airway hyperresponsiveness significantly increased frequency of exacerbations in COPD with both lower and higher grade in airway eosinophilia. Addition of ciclesonide to indacaterol markedly improved lung function (FEV 1 , IC), CAT score, and reliever use in these subjects with airway eosinophilia determined by qualitative analysis. However, ciclesonide was less effective in improving these values in subjects with airway hyperresponsiveness than in those without airway hyperresponsiveness. Conclusions: Airway eosinophilia and airway hyperresponsiveness are complicated with 25–50% of COPD that have no symptom and history for asthma. These phenotypes of COPD are closely related to symptom stability and reactivity to glucocorticosteroids. These phenotypes may play key roles for advancement of the management and therapy of this disease.
Author Hiroaki Kume
Naozumi Hashimoto
Masayuki Hojo
AuthorAffiliation 4 Department of Respiratory Medicine, Nagoya University Graduate School of Medicine , Nagoya , Japan
1 Department of Respiratory Medicine, Rinku General Medical Center , Izumisano , Japan
3 Division of Respiratory Medicine, National Center for Global Health and Medicine , Tokyo , Japan
2 Department of Respiratory Medicine and Allergology, Faculty of Medicine, Kindai University , Osakasayama , Japan
AuthorAffiliation_xml – name: 1 Department of Respiratory Medicine, Rinku General Medical Center , Izumisano , Japan
– name: 3 Division of Respiratory Medicine, National Center for Global Health and Medicine , Tokyo , Japan
– name: 2 Department of Respiratory Medicine and Allergology, Faculty of Medicine, Kindai University , Osakasayama , Japan
– name: 4 Department of Respiratory Medicine, Nagoya University Graduate School of Medicine , Nagoya , Japan
Author_xml – sequence: 1
  givenname: Hiroaki
  surname: Kume
  fullname: Kume, Hiroaki
– sequence: 2
  givenname: Masayuki
  surname: Hojo
  fullname: Hojo, Masayuki
– sequence: 3
  givenname: Naozumi
  surname: Hashimoto
  fullname: Hashimoto, Naozumi
BackLink https://cir.nii.ac.jp/crid/1873398392946463616$$DView record in CiNii
https://www.ncbi.nlm.nih.gov/pubmed/31404293$$D View this record in MEDLINE/PubMed
BookMark eNp9Us1vFCEUn5gaW2vvngwHDx7cdfgYBi4mzVrbTZq0B3smwLzp0LAwwmxN7_7hsrOtaT3IAcjj9_HC-72tDkIMUFXvcb2kVMgv_TjotCQ1lsu6bnnzqjrCnNOFFJgcPLsfVic539VlUSkpZ2-qQ4pZzYikR9Xvs5hdiOPgPFqH3uvNRk8uBqRDhy4eRkgJ8hhDdvcQIGfkApoGQKcu_dIPGemMrgcIcSrQjGKPVlfX3z7P7JsM_dbPpFJfh0F76NC539poY5qcjXmCFF2X31Wve-0znDyex9XN97Mfq4vF5dX5enV6ubBMtNPC4MZQKlvd2caSrtONsByIabSxBlivDW5Nayi00DEjtGgo5qRA25oYyig9rtZ73S7qOzUmt9HpQUXt1FyI6VbpXWMelCTW2J7jWkrMuGFCGFw-syFUAFgmi9bXvda4NRvoLIQpaf9C9OVLcIO6jfeK85ZTumvm06NAij-3kCe1cdmC9zpA3GZFSEtaSlnDC_TDc6-_Jk9jLAC-B9gUc07QK-umeY7F2nmFa7WLjJojo3aRUXNkCrH-h_ik_R_Kxz0lOFdsdjsWpVEpqCSSccYpx5z-AaWB0hc
CitedBy_id crossref_primary_10_1136_bmjopen_2022_066354
crossref_primary_10_12677_ACM_2022_125621
crossref_primary_10_3390_biom15020182
crossref_primary_10_4252_wjsc_v16_i2_70
crossref_primary_10_1016_j_csbj_2021_04_014
crossref_primary_10_36604_1998_5029_2021_81_115_125
crossref_primary_10_3389_fimmu_2025_1501898
crossref_primary_10_1155_2022_4427637
crossref_primary_10_3390_antiox12010142
crossref_primary_10_1016_j_lfs_2020_118973
crossref_primary_10_1136_bmjopen_2020_038874
crossref_primary_10_30629_0023_2149_2024_102_7_510_517
crossref_primary_10_1016_j_pulmoe_2019_10_006
crossref_primary_10_1186_s12931_024_02780_8
crossref_primary_10_2147_COPD_S366126
Cites_doi 10.3390/ijms17091590
10.15036/arerugi.33.167
10.1183/09031936.06.00072105
10.1080/15412555.2018.1445213
10.1513/pats.200512-125SF
10.1183/09031936.00169711
10.1016/j.pharmthera.2015.09.004
10.2147/COPD.S61854
10.1136/thx.2009.120741
10.1164/ajrccm.165.3.2104066
10.1016/S1081-1206(10)62140-0
10.2174/9781681083377118030005
10.3390/ijms19071999
10.1164/ajrccm/145.2_Pt_1.301
10.2147/COPD.S80992
10.2147/COPD.S119908
10.1136/thx.2004.032516
10.5772/60969
10.1016/j.pharmthera.2009.06.004
10.1016/j.rmed.2011.09.006
10.1183/09031936.05.00047504
10.1183/09031936.00146306
10.1164/ajrccm/143.1.109
10.1164/ajrccm.154.2.8756799
10.1016/j.coph.2018.03.011
10.1164/ajrccm.153.6.8665038
10.1136/thx.2005.052241
10.1186/s12931-017-0559-0
10.1183/13993003.00436-2016
10.1136/thoraxjnl-2013-203602
10.1186/1465-9921-10-24
10.1016/j.jaci.2009.06.029
10.1136/thoraxjnl-2014-206740
10.1136/thx.2008.108027
10.1016/S1081-1206(10)60858-7
10.1136/thx.54.5.403
10.2147/COPD.S113484
10.1016/0091-6749(81)90132-9
10.1016/j.jaci.2012.02.025
10.1016/j.rmed.2015.10.004
10.1378/chest.11-2535
10.1164/rccm.201104-0597OC
10.1164/ajrccm.161.2.9903097
10.1016/j.jaci.2016.04.022
ContentType Journal Article
Copyright Copyright © 2019 Kume, Hojo and Hashimoto 2019 Kume, Hojo and Hashimoto
Copyright_xml – notice: Copyright © 2019 Kume, Hojo and Hashimoto 2019 Kume, Hojo and Hashimoto
DBID RYH
AAYXX
CITATION
NPM
7X8
5PM
DOA
DOI 10.3389/fphar.2019.00765
DatabaseName CiNii Complete
CrossRef
PubMed
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
PubMed
MEDLINE - Academic
DatabaseTitleList
MEDLINE - Academic
PubMed

Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Pharmacy, Therapeutics, & Pharmacology
EISSN 1663-9812
ExternalDocumentID oai_doaj_org_article_92cbcf61099146b488b19815238eec49
PMC6676333
31404293
10_3389_fphar_2019_00765
Genre Journal Article
GroupedDBID 53G
5VS
9T4
AAFWJ
AAKDD
ACGFO
ACGFS
ACXDI
ADBBV
ADRAZ
AENEX
AFPKN
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAWUL
BCNDV
DIK
EMOBN
GROUPED_DOAJ
GX1
HYE
KQ8
M48
M~E
O5R
O5S
OK1
P2P
PGMZT
RNS
RPM
RYH
AAYXX
CITATION
IAO
IEA
IHR
IHW
IPNFZ
NPM
RIG
7X8
5PM
ID FETCH-LOGICAL-c487t-b15b3397adc5c2dda58c6e2b5abcbe4fab17b7b3e7ed4b8a8531625c2702b3433
IEDL.DBID M48
ISSN 1663-9812
IngestDate Wed Aug 27 01:25:08 EDT 2025
Thu Aug 21 13:59:26 EDT 2025
Fri Jul 11 01:05:58 EDT 2025
Thu Jan 02 23:01:14 EST 2025
Tue Jul 01 03:27:22 EDT 2025
Thu Apr 24 23:03:31 EDT 2025
Thu Jun 26 22:01:06 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Keywords bronchial hyperreactivity
airway eosinophil inflammation
asthma-COPD overlap
LABA
sputum examination
Language English
License This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c487t-b15b3397adc5c2dda58c6e2b5abcbe4fab17b7b3e7ed4b8a8531625c2702b3433
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Present address: Hiroaki Kume, Center for Allergy and Respiratory Medicine, Nogami Hospital, Sennan, Japan
This article was submitted to Respiratory Pharmacology, a section of the journal Frontiers in Pharmacology
Edited by: Paolo Montuschi, Catholic University of the Sacred Heart, Italy
Reviewed by: Mohib Uddin, AstraZeneca (Sweden), Sweden; Sabina Antonela Antoniu, Grigore T. Popa University of Medicine and Pharmacy, Romania
OpenAccessLink http://journals.scholarsportal.info/openUrl.xqy?doi=10.3389/fphar.2019.00765
PMID 31404293
PQID 2272733456
PQPubID 23479
ParticipantIDs doaj_primary_oai_doaj_org_article_92cbcf61099146b488b19815238eec49
pubmedcentral_primary_oai_pubmedcentral_nih_gov_6676333
proquest_miscellaneous_2272733456
pubmed_primary_31404293
crossref_citationtrail_10_3389_fphar_2019_00765
crossref_primary_10_3389_fphar_2019_00765
nii_cinii_1873398392946463616
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2019-07-25
PublicationDateYYYYMMDD 2019-07-25
PublicationDate_xml – month: 07
  year: 2019
  text: 2019-07-25
  day: 25
PublicationDecade 2010
PublicationPlace Switzerland
PublicationPlace_xml – name: Switzerland
PublicationTitle Frontiers in Pharmacology
PublicationTitleAlternate Front Pharmacol
PublicationYear 2019
Publisher Frontiers Media SA
Frontiers Media S.A
Publisher_xml – name: Frontiers Media SA
– name: Frontiers Media S.A
References Sin (B35) 2016; 48
Gao (B13) 2016; 11
Donohue (B10) 2017; 12
Fukunaga (B12) 2016; 17
Kume (B21) 2018
Brown (B5) 2009; 10
Leigh (B26) 2006; 27
Sumino (B37) 2012; 130
De Meer (B9) 2002; 165
Porsbjerg (B31) 2007; 98
Brutsche (B6) 2006; 61
Gibson (B14) 2015; 70
Tkacova (B41) 2016; 138
Rossi (B32) 2012; 106
Tashkin (B39) 1996; 153
Kume (B23) 2015; 156
Hargreave (B17) 1981; 68
van Veen (B45) 2009; 124
Landis (B25) 2014; 9
Vanfleteren (B46) 2014; 69
van Rensen (B44) 1999; 54
Wurst (B47) 2016; 110
Bel (B2) 1991; 143
Miravitlles (B28) 2017
Siva (B36) 2007; 29
Fujimoto (B11) 2005; 25
Simpson (B34) 2009; 124
B16
Uddin (B42) 2010; 65
Currie (B8) 2003; 90
Tashkin (B38) 1992; 145
Kume (B22) 2017
van den Berge (B43) 2012; 40
Bafadhel (B1) 2011; 184
Makino (B27) 1984; 33
Kostikas (B19) 2018; 15
Pizzichini (B30) 1996; 154
Calzetta (B7) 2018; 40
Belda (B3) 2000; 161
Zanini (B48) 2015; 10
Brightling (B4) 2005; 60
Gibson (B15) 2009; 64
Scherr (B33) 2012; 142
Kolsum (B18) 2017; 18
Papi (B29) 2006; 3
Kume (B24) 2018; 19
B40
Kume (B20) 2015
References_xml – volume: 17
  year: 2016
  ident: B12
  article-title: Involvement of Ca2+ signaling in the synergistic effects between muscarinic receptor antagonists and β₂-adrenoceptor agonists in airway smooth muscle
  publication-title: Int. J. Mol. Sci.
  doi: 10.3390/ijms17091590
– volume: 33
  start-page: 167
  year: 1984
  ident: B27
  article-title: Clinical evaluation of standard method of acetylcholine inhalation test in bronchial asthma
  publication-title: Arerugi
  doi: 10.15036/arerugi.33.167
– volume: 27
  start-page: 964
  year: 2006
  ident: B26
  article-title: Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment
  publication-title: Eur. Respir. J.
  doi: 10.1183/09031936.06.00072105
– volume: 15
  start-page: 185
  year: 2018
  ident: B19
  article-title: Early Changes in eDiary COPD symptoms predict clinically relevant treatment response at 12 weeks: analysis from the CRYSTAL Study
  publication-title: COPD
  doi: 10.1080/15412555.2018.1445213
– volume: 3
  start-page: 245
  year: 2006
  ident: B29
  article-title: Pathophysiology of exacerbations of chronic obstructive pulmonary disease
  publication-title: Proc. Am. Thorac. Soc.
  doi: 10.1513/pats.200512-125SF
– volume: 40
  start-page: 1098
  year: 2012
  ident: B43
  article-title: Clinical and inflammatory determinants of bronchial hyperresponsiveness in COPD
  publication-title: Eur. Respir. J.
  doi: 10.1183/09031936.00169711
– volume: 156
  start-page: 75
  year: 2015
  ident: B23
  article-title: Research and development of bronchodilators for asthma and COPD with a focus on G protein/KCa channel linkage and β2-adrenergic intrinsic efficacy
  publication-title: Pharmacol. Ther.
  doi: 10.1016/j.pharmthera.2015.09.004
– volume: 9
  start-page: 597
  year: 2014
  ident: B25
  article-title: Continuing to confront COPD international patient survey: methods, COPD prevalence, and disease burden in 2012-2013
  publication-title: Int. J. Chron. Obstruct. Pulmon. Dis.
  doi: 10.2147/COPD.S61854
– volume: 65
  start-page: 684
  year: 2010
  ident: B42
  article-title: Prosurvival activity for airway neutrophils in severe asthma
  publication-title: Thorax
  doi: 10.1136/thx.2009.120741
– volume: 165
  start-page: 327
  year: 2002
  ident: B9
  article-title: Bronchial responsiveness to adenosine 5′-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV(1)
  publication-title: Am. J. Respir. Crit. Care Med.
  doi: 10.1164/ajrccm.165.3.2104066
– start-page: 49
  volume-title: Eur. Respir. J.
  year: 2017
  ident: B28
  article-title: Diagnosis of asthma–COPD overlap: the five commandments
– volume: 90
  start-page: 194
  year: 2003
  ident: B8
  article-title: Dose response of inhaled corticosteroids on bronchial hyperresponsiveness: a meta-analysis
  publication-title: Ann. Allergy Asthma Immunol.
  doi: 10.1016/S1081-1206(10)62140-0
– start-page: 116
  volume-title: Frontiers in clinical drug research - anti allergy agents
  year: 2018
  ident: B21
  article-title: Research and development for anti-asthmatic agents with a focus on phenotype changing by Ca2+ signaling in airway smooth muscle cells
  doi: 10.2174/9781681083377118030005
– volume: 19
  year: 2018
  ident: B24
  article-title: Involvement of allosteric effect and KCa channels in crosstalk between β₂-adrenergic and muscarinic M₂ receptors in airway smooth muscle
  publication-title: Int. J. Mol. Sci.
  doi: 10.3390/ijms19071999
– volume: 145
  start-page: 301
  year: 1992
  ident: B38
  article-title: The lung health study: airway responsiveness to inhaled methacholine in smokers with mild to moderate airflow limitation. The Lung Health Study Research Group
  publication-title: Am. Rev. Respir. Dis.
  doi: 10.1164/ajrccm/145.2_Pt_1.301
– volume: 10
  start-page: 1155
  year: 2015
  ident: B48
  article-title: Bronchial hyperresponsiveness, airway inflammation, and reversibility in patients with chronic obstructive pulmonary disease
  publication-title: Int. J. Chron. Obstruct. Pulmon. Dis.
  doi: 10.2147/COPD.S80992
– volume: 12
  start-page: 367
  year: 2017
  ident: B10
  article-title: Comparative efficacy of long-acting β2-agonists as monotherapy for chronic obstructive pulmonary disease: a network meta-analysis
  publication-title: Int. J. Chron. Obstruct. Pulmon. Dis.
  doi: 10.2147/COPD.S119908
– volume: 60
  start-page: 193
  year: 2005
  ident: B4
  article-title: Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease
  publication-title: Thorax
  doi: 10.1136/thx.2004.032516
– ident: B16
– start-page: 289
  volume-title: Muscle Cell and Tissue
  year: 2015
  ident: B20
  article-title: Ca2+ dynamics and Ca2+ sensitization in the regulation of airway smooth muscle tone
  doi: 10.5772/60969
– volume: 124
  start-page: 86
  year: 2009
  ident: B34
  article-title: Inflammatory mechanisms and treatment of obstructive airway diseases with neutrophilic bronchitis
  publication-title: Pharmacol. Ther.
  doi: 10.1016/j.pharmthera.2009.06.004
– volume: 106
  start-page: 84
  year: 2012
  ident: B32
  article-title: Acute effects of indacaterol on lung hyperinflation in moderate COPD: a comparison with tiotropium
  publication-title: Respir. Med.
  doi: 10.1016/j.rmed.2011.09.006
– volume: 25
  start-page: 640
  year: 2005
  ident: B11
  article-title: Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease
  publication-title: Eur. Respir. J.
  doi: 10.1183/09031936.05.00047504
– volume: 29
  start-page: 906
  year: 2007
  ident: B36
  article-title: Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial
  publication-title: Eur. Respir. J.
  doi: 10.1183/09031936.00146306
– volume: 143
  start-page: 109
  year: 1991
  ident: B2
  article-title: The effect of inhaled corticosteroids on the maximal degree of airway narrowing to methacholine in asthmatic subjects
  publication-title: Am. Rev. Respir. Dis.
  doi: 10.1164/ajrccm/143.1.109
– volume: 154
  start-page: 308
  year: 1996
  ident: B30
  article-title: Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements
  publication-title: Am. J. Respir. Crit. Care Med.
  doi: 10.1164/ajrccm.154.2.8756799
– volume: 40
  start-page: 95
  year: 2018
  ident: B7
  article-title: Pharmacological mechanisms leading to synergy in fixed-dose dual bronchodilator therapy
  publication-title: Curr. Opin. Pharmacol.
  doi: 10.1016/j.coph.2018.03.011
– volume: 153
  start-page: 1802
  year: 1996
  ident: B39
  article-title: Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. The Lung Health Study Research Group
  publication-title: Am. J. Respir. Crit. Care Med.
  doi: 10.1164/ajrccm.153.6.8665038
– volume: 61
  start-page: 671
  year: 2006
  ident: B6
  article-title: Bronchial hyperresponsiveness and the development of asthma and COPD in asymptomatic individuals: SAPALDIA cohort study
  publication-title: Thorax
  doi: 10.1136/thx.2005.052241
– ident: B40
– volume: 18
  start-page: 73
  year: 2017
  ident: B18
  article-title: Clinical characteristics of eosinophilic COPD versus COPD patients with a history of asthma
  publication-title: Respir. Res.
  doi: 10.1186/s12931-017-0559-0
– volume: 48
  start-page: 664
  year: 2016
  ident: B35
  article-title: What is asthma–COPD overlap syndrome? Towards a consensus definition from a round table discussion
  publication-title: Eur. Respir. J.
  doi: 10.1183/13993003.00436-2016
– volume: 69
  start-page: 72
  year: 2014
  ident: B46
  article-title: Moving from the Oslerian paradigm to the post-genomic era: are asthma and COPD outdated terms
  publication-title: Thorax
  doi: 10.1136/thoraxjnl-2013-203602
– volume: 10
  start-page: 24
  year: 2009
  ident: B5
  article-title: Dysregulated apoptosis and NFkappaB expression in COPD subjects
  publication-title: Respir. Res.
  doi: 10.1186/1465-9921-10-24
– volume: 124
  start-page: 2
  year: 2009
  ident: B45
  article-title: Consistency of sputum eosinophilia in difficult-to-treat asthma: A 5-year follow-up study
  publication-title: J. Allergy Clin. Immunol.
  doi: 10.1016/j.jaci.2009.06.029
– volume: 70
  start-page: 683
  year: 2015
  ident: B14
  article-title: Asthma–COPD overlap 2015: now we are six
  publication-title: Thorax
  doi: 10.1136/thoraxjnl-2014-206740
– volume: 64
  start-page: 728
  year: 2009
  ident: B15
  article-title: The overlap syndrome of asthma and COPD: what are its features and how important is it
  publication-title: Thorax
  doi: 10.1136/thx.2008.108027
– volume: 98
  start-page: 44
  year: 2007
  ident: B31
  article-title: Association of airway hyperresponsiveness with reduced quality of life in patients with moderate to severe asthma
  publication-title: Ann. Allergy Asthma Immunol.
  doi: 10.1016/S1081-1206(10)60858-7
– volume: 54
  start-page: 403
  year: 1999
  ident: B44
  article-title: Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma
  publication-title: Thorax
  doi: 10.1136/thx.54.5.403
– volume: 11
  start-page: 2457
  year: 2016
  ident: B13
  article-title: Characterization of sputum biomarkers for asthma–COPD overlap syndrome
  publication-title: Int. J. Chron. Obstruct. Pulmon. Dis.
  doi: 10.2147/COPD.S113484
– volume: 68
  start-page: 347
  year: 1981
  ident: B17
  article-title: Bronchial responsiveness to histamine or methacholine in asthma: Measurement and clinical significance
  publication-title: J. Allergy Clin. Immunol.
  doi: 10.1016/0091-6749(81)90132-9
– volume: 130
  start-page: 69
  year: 2012
  ident: B37
  article-title: Methacholine challenge test: diagnostic characteristics in asthmatic patients receiving controller medications
  publication-title: J. Allergy Clin. Immunol.
  doi: 10.1016/j.jaci.2012.02.025
– start-page: 41
  volume-title: Potassium Channels in Health and Disease
  year: 2017
  ident: B22
  article-title: Role of large-conductance calcium-activated potassium channels on airway smooth muscle in physiological and pathological conditions
– volume: 110
  start-page: 1
  year: 2016
  ident: B47
  article-title: Understanding asthma–chronic obstructive pulmonary disease overlap syndrome
  publication-title: Respir. Med.
  doi: 10.1016/j.rmed.2015.10.004
– volume: 142
  start-page: 919
  year: 2012
  ident: B33
  article-title: Response to add-on inhaled corticosteroids in COPD based on airway hyperresponsiveness to mannitol
  publication-title: Chest
  doi: 10.1378/chest.11-2535
– volume: 184
  start-page: 662
  year: 2011
  ident: B1
  article-title: Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers
  publication-title: Am. J. Respir. Crit. Care Med.
  doi: 10.1164/rccm.201104-0597OC
– volume: 161
  start-page: 475
  year: 2000
  ident: B3
  article-title: Induced sputum cell counts in healthy adults
  publication-title: Am. J. Respir. Crit. Care Med.
  doi: 10.1164/ajrccm.161.2.9903097
– volume: 138
  start-page: 1571
  year: 2016
  ident: B41
  article-title: Airway hyperresponsiveness in chronic obstructive pulmonary disease: a marker of asthma–chronic obstructive pulmonary disease overlap syndrome
  publication-title: J. Allergy Clin. Immunol.
  doi: 10.1016/j.jaci.2016.04.022
SSID ssj0000399364
Score 2.277369
Snippet The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway hyperresponsiveness may...
Background: The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway...
Background: The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway...
SourceID doaj
pubmedcentral
proquest
pubmed
crossref
nii
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 765
SubjectTerms airway eosinophil inflammation
asthma-COPD overlap
bronchial hyperreactivity
LABA
Pharmacology
RM1-950
sputum examination
Therapeutics. Pharmacology
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Li9swEBZlT72Uvuu2W1QoC4WYVJZlOcftdrfZQtscNrA3oScxBDnECSX3_eE7I2ezSSntpRcfLMmMNSN_M_LMJ0I-WMN4ABjOhXAYoHADS-pTnddaBy2Ck1JjvfP3H9V4Wn67Ftd7R31hTlhPD9xP3HBUWGMDkoKPYFEbsDcDcTKgDq-9t2Uq3QPM2wum0jcYcbcq-_-SEIWNhmEx08j_yZCfUiKW7OFQousHdIlN8ydP8_eEyT0EunhMHm1dR3rai_yEPPDxKTmZ9NzTmwG9ui-l6gb0hE7uWak3z8jNeds1sV3Mmjm9jAEMoS9apDo6OoZoFE_pSOmy_eePNpGCc0hPm-Uvvemo7uCBPra4Z9vRNtCzn5MvgzR62vmwnqdBcP8yzgB0HP2KyfAQ24I4WEiybBvXPSfTi_Ors3G-PYIhtxDJrHLDhOHgsmhnhS2c06K2lS-M0MYaXwZtmDTScC-9K02tAfwZRFQWq9wMLzl_QY5iG_0rQh00lALbAysdM3qkGQwOri6kDMJnZHinEGW3_OR4TMZcQZyCKlRJhQpVqJIKM_JxN2LRc3P8pe9n1PGuH7Jqpxtga2pra-pftpaRY7AQkA6vrJYwM8m_LCukXWNVRt7f2Y6CVYq_XnT07bpTRYF-IgdvNSMve1vaicKR4Qi8rozIAys7kPWwJTazxASOCcqc89f_4-XekIc4XbhvXYi35Gi1XPtjcLhW5l1aW7eXTym3
  priority: 102
  providerName: Directory of Open Access Journals
Title Eosinophil Inflammation and Hyperresponsiveness in the Airways as Phenotypes of COPD, and Usefulness of Inhaled Glucocorticosteroids
URI https://cir.nii.ac.jp/crid/1873398392946463616
https://www.ncbi.nlm.nih.gov/pubmed/31404293
https://www.proquest.com/docview/2272733456
https://pubmed.ncbi.nlm.nih.gov/PMC6676333
https://doaj.org/article/92cbcf61099146b488b19815238eec49
Volume 10
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV3db9MwELdgvPCC-CbAJiOhSUgtw3Ecpw8IjbHRIQ36sEp7i_xJgyqnNK2g7_zh3DlZS1EFL32Ic5Xlu_P9zvH9jpCXRjPuIQz3hbCYoHANLvWm6BdKeSW8lVJhvfPF53w4zj5diatNeXS3gM3O1A77SY3n09c_v6_egcO_xYwT4u2Rn00UUnsypJ6UubhJbkFcktjP4KID-3FfxlicZ-23yp2CW7EpUvhDxAlVtQt9_n2J8o-odHaX3OngJD1u9X-P3Pim7pPDUctHverRy015VdOjh3S0YapePSC_TuumCvVsUk3pefBgHG0hI1XB0iFkqNi5I16hbbdEWgUKgJEeV_MfatVQ1cAfulDjOW5Da09Pvow-9KL0uHF-OY1C8Pw8TCAQWfoRL8hDvgvTweKSeV3Z5iEZn51engz7XVuGvoHsZtHXTGgOMEZZI0xqrRKFyV2qhdJGu8wrzaSWmjvpbKYLBYCAQZZlsPJN84zzR2Qv1ME9IdTCQCZw3LPMMq0GioGwt0UqpRcuIUfXCilNx1mOrTOmJeQuqMIyqrBEFZZRhQl5tZaYtXwd_3j3Pep4_R4ybccH9fxr2TluOUiNNh5J6QcQVDTsd5oNCkA9vHDOZIOE7IOFwOzwlxUSViZizixHKjaWJ-TFte2U4Ln4OUYFVy-bMk0RO3JAsAl53NrSeiocWY8AiSVEblnZ1ly3R0I1iezgeGmZc_70P_N6Rm7jSuAxdSqek73FfOn2AV8t9EE8lziIzvMbn1gk8A
linkProvider Scholars Portal
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Eosinophil+Inflammation+and+Hyperresponsiveness+in+the+Airways+as+Phenotypes+of+COPD%2C+and+Usefulness+of+Inhaled+Glucocorticosteroids&rft.jtitle=Frontiers+in+Pharmacology&rft.au=Hiroaki+Kume&rft.au=Masayuki+Hojo&rft.au=Naozumi+Hashimoto&rft.date=2019-07-25&rft.pub=Frontiers+Media+SA&rft.eissn=1663-9812&rft.volume=10&rft_id=info:doi/10.3389%2Ffphar.2019.00765
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1663-9812&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1663-9812&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1663-9812&client=summon