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. 2022 Nov;27(11):929-940.
doi: 10.1111/resp.14325. Epub 2022 Jul 21.

Treatable traits in the NOVELTY study

Alvar Agustí  1   2   3   4 , Eleni Rapsomaniki  5 , Richard Beasley  6 , Rod Hughes  7 , Hana Müllerová  8 , Alberto Papi  9   10 , Ian D Pavord  11 , Maarten van den Berge  12 , Rosa Faner  3   4 ; NOVELTY Study Investigators
Collaborators, Affiliations

Treatable traits in the NOVELTY study

Alvar Agustí et al. Respirology. 2022 Nov.

Erratum in

  • Corrigendum.
    [No authors listed] [No authors listed] Respirology. 2022 Dec;27(12):1095. doi: 10.1111/resp.14406. Epub 2022 Nov 6. Respirology. 2022. PMID: 36336467 Free PMC article. No abstract available.

Abstract

Background and objective: Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent and complex diseases that require personalized management. Although a strategy based on treatable traits (TTs) has been proposed, the prevalence and relationship of TTs to the diagnostic label and disease severity established by the attending physician in a real-world setting are unknown. We assessed how the presence/absence of specific TTs relate to the diagnosis and severity of 'asthma', 'COPD' or 'asthma + COPD'.

Methods: The authors selected 30 frequently occurring TTs from the NOVELTY study cohort (NOVEL observational longiTudinal studY; NCT02760329), a large (n = 11,226), global study that systematically collects data in a real-world setting, both in primary care clinics and specialized centres, for patients with 'asthma' (n = 5932, 52.8%), 'COPD' (n = 3898, 34.7%) or both ('asthma + COPD'; n = 1396, 12.4%).

Results: The results indicate that (1) the prevalence of the 30 TTs evaluated varied widely, with a mean ± SD of 4.6 ± 2.6, 5.4 ± 2.6 and 6.4 ± 2.8 TTs/patient in those with 'asthma', 'COPD' and 'asthma + COPD', respectively (p < 0.0001); (2) there were no large global geographical variations, but the prevalence of TTs was different in primary versus specialized clinics; (3) several TTs were specific to the diagnosis and severity of disease, but many were not; and (4) both the presence and absence of TTs formed a pattern that is recognized by clinicians to establish a diagnosis and grade its severity.

Conclusion: These results provide the largest and most granular characterization of TTs in patients with airway diseases in a real-world setting to date.

Keywords: COPD; airways; allergy; asthma; bronchitis; chronic obstructive pulmonary disease; emphysema; smoking.

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Conflict of interest statement

Alvar Agustí has received payments in his role as a member of the scientific committee of NOVELTY; received research grants from AstraZeneca, Chiesi, GSK, Menarini, MSD and Zambon; consulting fees from AstraZeneca, Chiesi, GSK, Menarini, MSD and Zambon; and payment or honoraria from AstraZeneca, Chiesi, GSK, Menarini, MSD and Zambon. Eleni Rapsomaniki and Rod Hughes are employees of AstraZeneca. Hana Müllerová is an employee and shareholder of AstraZeneca. Richard Beasley received research grants from AstraZeneca, Cure Kids (NZ), Genentech, GSK and HRC (NZ); consulting fees from AstraZeneca, Avillion and Theravance; payment or honoraria from AstraZeneca, Cipla and Asthma and Respiratory Foundation NZ; support for attending meetings from AstraZeneca and Theravance; and is the Chair of the adult asthma guidelines group for the Asthma and Respiratory Foundation of NZ. Alberto Papi received research grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Pfizer, Sanofi and Teva; consulting fees from AstraZeneca, Avillion, Chiesi, Elpen Pharmaceuticals, GSK, IQVIA, Novartis and Sanofi; and payment or honoraria from AstraZeneca, Avillion, Boehringer Ingelheim, Chiesi, Edmond Pharma, Elpen Pharmaceuticals, GSK, IQVIA, Menarini, MSD, Mundipharma, Novartis, Sanofi, Teva and Zambon. Ian D. Pavord received research grants from Chiesi; consulting fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Dey Pharma, Genentech, GSK, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, Novartis, Regeneron Pharmaceuticals Inc., Respivert, Schering‐Plough and Teva; payment or honoraria from Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Regeneron Pharmaceuticals Inc., Sanofi and Teva; support for attending meetings from AstraZeneca, Chiesi, GSK, Regeneron Pharmaceuticals Inc., Sanofi, Teva and Napp Pharmaceuticals; and other financial or non‐financial interests from AstraZeneca, Boehringer Ingelheim, GSK, Regeneron Pharmaceuticals Inc., Sanofi and Teva. Maarten van den Berge received research grants from Genentech, GSK, Novartis, Roche and Sanofi. Rosa Faner received research grants from AstraZeneca, GSK, Instituto de Salud Carlos III—Spanish National Health Service and Menarini; consulting fees from GSK; and payment or honoraria from Chiesi.

Figures

FIGURE 1
FIGURE 1
Prevalence of the investigated TTs in the entire study population (A) and by geographical region (B). Non‐evaluable traits due to missing data were adjusted by weighting for the proportion of positive traits among those evaluable in a patient. EOS, eosinophilic; PRISm, preserved ratio impaired spirometry; Th2, type‐2 airway inflammation; TT, treatable trait
FIGURE 2
FIGURE 2
(A) Heat map of fold changes in prevalence of TTs across the three diagnostic labels considered (columns from left to right: ‘asthma’ vs. ‘COPD’, ‘asthma + COPD’ vs. ‘COPD’ and ‘asthma + COPD’ vs. ‘asthma’). The final column highlights (x) those TTs with a ≥2‐ (orange cells) or ≤0.5‐ (blue cells) fold change between diagnostic labels. (B) Heat map of statistically significant p‐values (ANOVA) associated with differences in prevalence of a given TT by disease severity in patients with ‘asthma’, ‘asthma + COPD’ and ‘COPD’. TTs are ordered by p‐value in patients with ‘asthma’. Darkest shading, p ≤ 0.001; mid‐shading, p ≤ 0.01; light shading, p ≤ 0.05; no shading, p > 0.05. ANOVA, analysis of variance; COPD, chronic obstructive pulmonary disease; EOS, eosinophilic; PRISm, preserved ratio impaired spirometry; Th2, type‐2 airway inflammation; TT, treatable trait
FIGURE 3
FIGURE 3
Network of TT co‐occurrence (i.e., the proportion of patients presenting two given TTs) by disease label. Colour node indicates their pulmonary, extra‐pulmonary or behavioural/environmental origin. Node size is proportional to its prevalence, and the width of the edge (links) indicates the proportion of patients in whom a given TT pair co‐occur. COPD, chronic obstructive pulmonary disease; PRISm, preserved ratio impaired spirometry; Th2, type‐2 airway inflammation; TT, treatable trait
FIGURE 4
FIGURE 4
Pattern recognition heat map in relation to diagnostic label (left three columns) and severity assessment (right three columns). For this analysis, TTs were dichotomized as binary variables (present/absent) and their associations with diagnostic labels and severity of disease were explored using chi‐square tests. Coloured cells indicate statistically significant associations (p < 0.05), where cell colour (orange or blue) corresponds to an OR > 1 (i.e., presence of the TT) or an OR < 1 (i.e., absence of the TT), respectively. COPD, chronic obstructive pulmonary disease; EOS, eosinophilic; PRISm, preserved ratio impaired spirometry; Th2, type‐2 airway inflammation; TT, treatable trait
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