Edgar Delgado-Eckert1, Anna James2, Delphine Meier-Girard1, Maciej Kupczyk3, Lars I Andersson2, Apostolos Bossios4, Maria Mikus2, Junya Ono5, Kenji Izuhara6, Roelinde Middelveld2, Barbro Dahlén4, Mina Gaga7, Nikos M Siafakas8, Alberto Papi9, Bianca Beghe10, Guy Joos11, Klaus F Rabe12, Peter J Sterk13, Elisabeth H Bel13, Sebastian L Johnston14, Pascal Chanez15, Mark Gjomarkaj16, Peter H Howarth17, Ewa Niżankowska-Mogilnicka18, Sven-Erik Dahlén19, Urs Frey1. 1. University of Basel, University Children's Hospital, Basel, Switzerland. 2. Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden. 3. Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Lodz, Poland. 4. Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Huddinge and Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. 5. Shino-Test Corporation Ltd, Sagamihara, Japan. 6. Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan. 7. University of Athens, Athens, Greece. 8. University of Crete, Crete, Greece. 9. University of Ferrara, Ferrara, Italy. 10. University of Modena and Reggio Emilia, Italy. 11. University of Ghent, Ghent, Belgium. 12. Christian Albrechts University Kiel, Kiel, Germany. 13. Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 14. The Imperial College of Science and Technology, London, United Kingdom. 15. University of Marseilles, Marseilles, France. 16. Italian Research Council, Palermo, Italy. 17. University of Southampton, Southampton, United Kingdom. 18. The Jagellonian University, Krakow, Poland. 19. Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden. Electronic address: Sven-Erik.Dahlen@ki.se.
Abstract
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.
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.
Authors: Maria Sparreman Mikus; Johan Kolmert; Lars I Andersson; Jörgen Östling; Richard G Knowles; Cristina Gómez; Magnus Ericsson; John-Olof Thörngren; Payam Emami Khoonsari; Barbro Dahlén; Maciej Kupczyk; Bertrand De Meulder; Charles Auffray; Per S Bakke; Bianca Beghe; Elisabeth H Bel; Massimo Caruso; Pascal Chanez; Bo Chawes; Stephen J Fowler; Mina Gaga; Thomas Geiser; Mark Gjomarkaj; Ildikó Horváth; Peter H Howarth; Sebastian L Johnston; Guy Joos; Norbert Krug; Paolo Montuschi; Jacek Musial; Ewa Niżankowska-Mogilnicka; Henric K Olsson; Alberto Papi; Klaus F Rabe; Thomas Sandström; Dominick E Shaw; Nikolaos M Siafakas; Mathias Uhlén; John H Riley; Stewart Bates; Roelinde J M Middelveld; Craig E Wheelock; Kian Fan Chung; Ian M Adcock; Peter J Sterk; Ratko Djukanovic; Peter Nilsson; Sven-Erik Dahlén; Anna James Journal: Eur Respir J Date: 2022-02-17 Impact factor: 16.671