Abstract
Original language | English |
---|---|
Pages (from-to) | 407-419 |
Number of pages | 13 |
Journal | Journal of allergy and clinical immunology |
Volume | 148 |
Issue number | 2 |
Early online date | 2021 |
DOIs | |
Publication status | Published - Aug 2021 |
Keywords
- Asthma
- chronic obstructive pulmonary disease
- cluster analysis
- phenotyping
- remodeling
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In: Journal of allergy and clinical immunology, Vol. 148, No. 2, 08.2021, p. 407-419.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation
AU - Delgado-Eckert, Edgar
AU - James, Anna
AU - Meier-Girard, Delphine
AU - Kupczyk, Maciej
AU - Andersson, Lars I.
AU - Bossios, Apostolos
AU - Mikus, Maria
AU - Ono, Junya
AU - Izuhara, Kenji
AU - Middelveld, Roelinde
AU - Dahlén, Barbro
AU - Gaga, Mina
AU - Siafakas, Nikos M.
AU - Papi, Alberto
AU - Beghe, Bianca
AU - Joos, Guy
AU - Rabe, Klaus F.
AU - Sterk, Peter J.
AU - Bel, Elisabeth H.
AU - Johnston, Sebastian L.
AU - Chanez, Pascal
AU - Gjomarkaj, Mark
AU - Howarth, Peter H.
AU - Niżankowska-Mogilnicka, Ewa
AU - Dahlén, Sven-Erik
AU - Frey, Urs
N1 - Funding Information: Disclosure of potential conflict of interest: A. Papi reports grants, personal fees, and nonfinancial support from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, TEVA, and Menarini, as well as personal fees and nonfinancial support from Mundipharma, Zambon, Novartis, and Sanofi/Regeneron; in addition, he has also received personal fees from Roche and Edmondpharma and grants from Fondazione Maugeri and Fondazione Chiesi outside the submitted work. B. Dahlén reports personal fees from AstraZeneca, Teva, and Sanofi and grants from Novartis and GSK outside the submitted work. B. Beghe reports personal fees from AstraZeneca, Chiesi, and from GSK outside the submitted work. E. H. Bel reports grants and personal fees from AstraZeneca, GSK, Novartis, Teva, Sanofi/Regeneron, Sterna, and Chiesi. G. Joos reports grants from AstraZeneca, Bayer, and Chiesi; personal fees from Eureca vzw and Teva; and grants and personal fees from GlaxoSmithKline (all of which were paid to his department) outside the submitted work. J. Ono is an employee of Shino-Test Corporation. K. Izuhara reports grants from Shino-test Co Ltd during the conduct of the study, as well as grants from AstraZeneca and Sanofi outside the submitted work; in addition, he has a licensed patent. K. Rabe reports grants and personal fees from Boehringer Ingelheim and Astra Zeneca and personal fees from Novartis, Chiesi Pharmaceuticals, Regeneron, Sanofi, and Roche. M. Gaga reports grants and personal fees from Novartis, BMS, and Menarini; grants from Galapagos and Elpen; and personal fees from MSD and Roche outside the submitted work. P. Howarth reports employment by GSK. P. Sterk reports being a scientific advisor and having a formally nonsubstantial interest in the startup company Breathomix BV outside the submitted work. R. Middelveld reports grants from the Swedish Strategic Research Foundation, AstraZeneca, the Swedish Heart Lung Foundation, and the Swedish Asthma and Allergy Association outside the submitted work. S. Johnston reports personal fees from Virtus Respiratory Research, Myelo Therapeutics GmbH, Concert Pharmaceuticals, Bayer, Synairgen, Novartis, Boehringer Ingelheim, Chiesi, Gerson Lehrman Group, resTORbio, Bioforce Materia Medical Holdings, PrepBio Pharma, Pulmotect, Virion Health, Lallemand Pharma, and AstraZeneca outside the submitted work; in addition, he has 3 patents (Antivirus Therapy for Respiratory Diseases, UK patent application No. GB 0405634.7; Interferon-Beta for Anti-Virus Therapy for Respiratory Diseases, International Patent Application No. PCT/ GB05/50031; and Interferon Lambda Therapy for the Treatment of Respiratory Disease, UK patent application No.6779645.9). S. E. Dahlén reports personal fees from AstraZeneca, Cayman Chemicals, GSK, Novartis, Sanofi-Regeneron, and TEVA outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: Funding for this project was provided by the Swiss National Science Foundation (grant 3200-B0-112099). The Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease (BIOAIR) study was supported by The Fifth Framework Programme of the European Union (contract number QLG1-CT-2000-01185) and several national funding bodies (the Swedish Heart-Lung Foundation, Asthma and Allergy Foundation and the Stockholm County Council), and it received unconditional support from Vitalograph. The ChAMP (the Centre for Allergy Research Highlights Asthma Markers of Phenotype) consortium is supported by the Swedish Strategic Research Foundation and an unconditional and competitive grant donated by AstraZeneca. M.K. and A.J. were supported by the Bernard Osher Initiative for Severe Asthma Research. Disclosure of potential conflict of interest: A. Papi reports grants, personal fees, and nonfinancial support from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, TEVA, and Menarini, as well as personal fees and nonfinancial support from Mundipharma, Zambon, Novartis, and Sanofi/Regeneron; in addition, he has also received personal fees from Roche and Edmondpharma and grants from Fondazione Maugeri and Fondazione Chiesi outside the submitted work. B. Dahl?n reports personal fees from AstraZeneca, Teva, and Sanofi and grants from Novartis and GSK outside the submitted work. B. Beghe reports personal fees from AstraZeneca, Chiesi, and from GSK outside the submitted work. E. H. Bel reports grants and personal fees from AstraZeneca, GSK, Novartis, Teva, Sanofi/Regeneron, Sterna, and Chiesi. G. Joos reports grants from AstraZeneca, Bayer, and Chiesi; personal fees from Eureca vzw and Teva; and grants and personal fees from GlaxoSmithKline (all of which were paid to his department) outside the submitted work. J. Ono is an employee of Shino-Test Corporation. K. Izuhara reports grants from Shino-test Co Ltd during the conduct of the study, as well as grants from AstraZeneca and Sanofi outside the submitted work; in addition, he has a licensed patent. K. Rabe reports grants and personal fees from Boehringer Ingelheim and Astra Zeneca and personal fees from Novartis, Chiesi Pharmaceuticals, Regeneron, Sanofi, and Roche. M. Gaga reports grants and personal fees from Novartis, BMS, and Menarini; grants from Galapagos and Elpen; and personal fees from MSD and Roche outside the submitted work. P. Howarth reports employment by GSK. P. Sterk reports being a scientific advisor and having a formally nonsubstantial interest in the startup company Breathomix BV outside the submitted work. R. Middelveld reports grants from the Swedish Strategic Research Foundation, AstraZeneca, the Swedish Heart Lung Foundation, and the Swedish Asthma and Allergy Association outside the submitted work. S. Johnston reports personal fees from Virtus Respiratory Research, Myelo Therapeutics GmbH, Concert Pharmaceuticals, Bayer, Synairgen, Novartis, Boehringer Ingelheim, Chiesi, Gerson Lehrman Group, resTORbio, Bioforce Materia Medical Holdings, PrepBio Pharma, Pulmotect, Virion Health, Lallemand Pharma, and AstraZeneca outside the submitted work; in addition, he has 3 patents (Antivirus Therapy for Respiratory Diseases, UK patent application No. GB 0405634.7; Interferon-Beta for Anti-Virus Therapy for Respiratory Diseases, International Patent Application No. PCT/ GB05/50031; and Interferon Lambda Therapy for the Treatment of Respiratory Disease, UK patent application No.6779645.9). S. E. Dahl?n reports personal fees from AstraZeneca, Cayman Chemicals, GSK, Novartis, Sanofi-Regeneron, and TEVA outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: Funding for this project was provided by the Swiss National Science Foundation (grant 3200-B0-112099 ). The Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease (BIOAIR) study was supported by The Fifth Framework Programme of the European Union (contract number QLG1-CT-2000-01185 ) and several national funding bodies (the Swedish Heart-Lung Foundation , Asthma and Allergy Foundation and the Stockholm County Council ), and it received unconditional support from Vitalograph. The ChAMP (the Centre for Allergy Research Highlights Asthma Markers of Phenotype) consortium is supported by the Swedish Strategic Research Foundation and an unconditional and competitive grant donated by AstraZeneca. M.K. and A.J. were supported by the Bernard Osher Initiative for Severe Asthma Research . Publisher Copyright: © 2021
PY - 2021/8
Y1 - 2021/8
N2 - Background: In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success. Objective: We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics. Methods: We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV1 measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort. Results: Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin). Conclusion: FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring.
AB - Background: In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success. Objective: We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics. Methods: We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV1 measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort. Results: Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin). Conclusion: FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring.
KW - Asthma
KW - chronic obstructive pulmonary disease
KW - cluster analysis
KW - phenotyping
KW - remodeling
UR - http://www.scopus.com/inward/record.url?scp=85102043368&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jaci.2020.12.652
DO - https://doi.org/10.1016/j.jaci.2020.12.652
M3 - Article
C2 - 33548398
SN - 0091-6749
VL - 148
SP - 407
EP - 419
JO - Journal of allergy and clinical immunology
JF - Journal of allergy and clinical immunology
IS - 2
ER -