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. 2021 Feb 4;57(2):2001836.
doi: 10.1183/13993003.01836-2020. Print 2021 Feb.

Instability of sputum molecular phenotypes in U-BIOPRED severe asthma

Nazanin Z Kermani  1 , Stelios Pavlidis  1   2 , Jiaxing Xie  2 , Kai Sun  1 , Matthew Loza  3 , Fred Baribaud  3 , Steve J Fowler  4 , Dominic E Shaw  5 , Louise J Fleming  2 , Peter H Howarth  6 , Ana R Sousa  7 , Julie Corfield  8   9 , Charles Auffray  10 , Bertrand De Meulder  10 , Peter J Sterk  11 , Yike Guo  1 , Mohib Uddin  12 , Ratko Djukanovic  6 , Ian M Adcock  1   2 , Kian Fan Chung  1   2 ; U-BIOPRED study group
Affiliations

Instability of sputum molecular phenotypes in U-BIOPRED severe asthma

Nazanin Z Kermani et al. Eur Respir J. .

Abstract

At 1 year, 45% of severe asthma change molecular phenotype as determined by sputum transcriptomic analysis. Together with concomitant shift in sputum granulocytic markers, this may indicate variability of driving mechanisms in this unstable group. https://bit.ly/35aj489

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Conflict of interest statement

Conflict of interest: N.Z. Kermani has nothing to disclose. Conflict of interest: S. Pavlidis has nothing to disclose. Conflict of interest: J. Xie has nothing to disclose. Conflict of interest: K. Sun has nothing to disclose. Conflict of interest: M. Loza is an employee and shareholder of Janssen R&D, Pharmaceutical Companies of Johnson & Johnson. Conflict of interest: F. Baribaud is an employee and shareholder of Janssen R&D, Pharmaceutical Companies of Johnson & Johnson. Conflict of interest: S.J. Fowler reports grants from Innovative Medicines Initiative (IMI), during the conduct of the study; personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim and Novartis, outside the submitted work. Conflict of interest: D.E. Shaw reports personal fees from GSK, AstraZeneca, Teva and Boehringer Ingelheim, outside the submitted work. Conflict of interest: L.J. Fleming reports personal fees for advisory board membership from Novartis, Vectura and Boehringer Ingelheim; grants for research from Asthma UK and BLF; personal fees for lectures from Novartis, outside the submitted work. Conflict of interest: P.H. Howarth reports part time employment by GSK as Global Medical Expert. Conflict of interest: A.R. Sousa has nothing to disclose. Conflict of interest: J. Corfield has nothing to disclose. Conflict of interest: C. Auffray has nothing to disclose. Conflict of interest: B. De Muelder has nothing to disclose. Conflict of interest: P.J. Sterk reports grants from Innovative Medicines Initiative (IMI), during the conduct of the study. Conflict of interest: Y. Guo has nothing to disclose. Conflict of interest: M. Uddin is an employee of AstraZeneca and holds shares in the company. Conflict of interest: R. Djukanovic reports personal fees from TEVA, grants and personal fees from Novartis, and personal fees and other support from Synairgen outside the submitted work. Conflict of interest: I.M. Adcock reports personal fees for advisory board membership from GSK, AstraZeneca, Novartis, Boehringer Ingelehim and Vectura; grants from Pfizer, GSK, MRC, EU, Boehringer Ingelheim and Innovative Medicines Initiative (IMI); and personal fees for lectures, outside the submitted work. Conflict of interest: K.F. Chung has received honoraria for participating on advisory board meetings of GSK, AstraZeneca, Novartis, Merck, Boehringer Ingelheim, Roche and TEVA regarding treatments for asthma and COPD and on the scientific advisory board of the Clean Breathing Institute supported by GSK Health Care Consumer Products; and has also been remunerated for speaking engagements by AstraZeneca, Novartis and Merck, outside the submitted work.

Figures

FIGURE 1
FIGURE 1
a) Pie charts showing the distribution of granulocytic inflammation measured in sputum cells in 38 patients with severe asthma at first visit and at follow-up at 1 year. Eosinophilia defined as eosinophil count ≥1.5%; neutrophilia as neutrophil count ≥74%; mixed as neutrophilic and eosinophilic; and paucigranulocytic as neither neutrophilic nor eosinophilic. b) Sankey plot showing the flow of transcription-associated cluster (TAC) membership and sputum granulocyte inflammation at baseline and at 1 year. Eos: eosinophilic; neu: neutrophilic; mix: mixed eosinophilic and neutrophilic; pauci: paucigranulocytic. c) Dot plot relative enrichment scores with box and whisker plots showing median and interquartile range for six pathway signatures assessed at baseline (upper panels), and at 1 year follow-up (lower panels) on sputum transcriptomics using gene set variation analysis. Patient samples are colour-based according to baseline cluster membership in the TACs. ILC2: innate lymphoid cell type 2; IL-13/Th2: interleukin-13/T-helper type 2; OXPHOS: oxidative phosphorylation.
See this image and copyright information in PMC

References

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