Heterogeneity within and between physician-diagnosed asthma and/or COPD: NOVELTY cohort

Abstract

Background: Studies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort.

Methods: Patients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis.

Results: Of 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1 s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12 months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses.

Conclusion: This analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications.

Trial registration: ClinicalTrials.gov NCT02760329.

Conflict of interest statement

Conflict of interest: H.K. Reddel reports grants, personal fees and non-financial support from AstraZeneca, during the conduct of the study; grants and personal fees for data monitoring committee work, advisory board work and providing independent medical education from AstraZeneca and GlaxoSmithKline, personal fees for data monitoring committee work from Merck, personal fees for data monitoring committee work, advisory board work and grant for registry from Novartis, personal fees for providing independent medical education from Teva, personal fees for advisory board work and providing independent medical education from Boehringer Ingelheim, and personal fees for advisory board work from Sanofi Genzyme and Chiesi, outside the submitted work; and is Chair of the GINA Scientific Committee and a member of the GINA Board. Conflict of interest: J. Vestbo reports personal fees for steering committee work from AstraZeneca, during the conduct of the study; and personal fees for consultancy and lectures from GlaxoSmithKline, Chiesi Pharmaceuticals, Novartis and AstraZeneca, and grants and personal fees for consultancy and lectures from Boehringer Ingelheim, outside the submitted work. Conflict of interest: A. Agusti reports personal fees for scientific committee work from AstraZeneca, during the conduct of the study; and grants and personal fees for lectures and advisory board work from GlaxoSmithKline and Menarini, and personal fees for lectures and advisory board work from Chiesi, outside the submitted work. Conflict of interest: G.P. Anderson reports personal fees for consultancy and share options from Pieris Pharmaceuticals, ENA Therapeutics and ENA Respiratory, personal fees for scientific committee work from AstraZeneca, and personal fees for lectures from GlaxoSmithKline, AstraZeneca, Menarini and Novartis, outside the submitted work; and has US Patent 7,455,836 licensed to MorphoSys, sublicensed to GlaxoSmithKline. Conflict of interest: A.T. Bansal has nothing to disclose. Conflict of interest: R. Beasley reports personal fees for steering committee work from AstraZeneca, during the conduct of the study; and grants and personal fees from AstraZeneca and GlaxoSmithKline, personal fees from Avillion and Theravance, and grants from Genentech, outside the submitted work. Conflict of interest: E.H. Bel reports grants and personal fees from AstraZeneca, GlaxoSmithKline, Novartis and Teva, and personal fees from Sanofi/Regeneron, Sterna and Chiesi, outside the submitted work. Conflict of interest: C. Janson reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva, outside the submitted work. Conflict of interest: B. Make reports grants, non-financial support and other (advisory board and presentations) from AstraZeneca, grants, non-financial support and other from GlaxoSmithKline, non-financial support for data monitoring committee work from Spiration, grants, non-financial support and other (advisory board) from Sunovion, other (CME activity) from Mt. Sinai, Web MD, National Jewish Health, Novartis, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, Medscape, Ultimate Medical Academy, Eastern Pulmonary Society, Catamount Medical, Eastern VA Medical Center, Academy Continued Health Care Learning and Wolters Kluwer Health, grants from Pearl Research and NHLBI, other (advisory board) from Verona, Boehringer Ingelheim, Theravance and Science 24/7, non-financial support and other (advisory board) from Circassia and Phillips, personal fees and non-financial support for consultancy from Third Pole, non-financial support and other (data monitoring committee) from Shire, and personal fees for data monitoring committee work from Takeda, outside the submitted work. Conflict of interest: I.D. Pavord reports personal fees for lectures, advisory board work, meeting attendance and organising educational events from AstraZeneca, personal fees for lectures, advisory board work and meeting attendance from Boehringer Ingelheim and GlaxoSmithKline, personal fees for lectures from Aerocrine and Chiesi, personal fees for lectures and advisory board work from Almirall and Novartis, personal fees for advisory board work from Genentech, Regeneron, Sanofi, Circassia and Knopp, personal fees for lectures, meeting attendance and organising educational events from Teva, and grants from NIHR, outside the submitted work. Conflict of interest: D. Price reports study funding from AstraZeneca, during the conduct of the study; personal fees for advisory board work and consultancy from Amgen, grants and personal fees for advisory board work, lectures, consultancy and travel/accommodation/meeting expenses from AstraZeneca and Boehringer Ingelheim, grants and personal fees for advisory board work, lectures and consultancy from Chiesi, Mylan and Teva, grants and personal fees for advisory board work from Circassia, personal fees for lectures from Cipla and Kyorin, personal fees for consultancy and lectures from GlaxoSmithKline, grants and personal fees for advisory board work, lectures, consultancy, travel/accommodation/meeting expenses and educational activities from Mundipharma and Novartis, grants and personal fees for consultancy from Pfizer and Theravance, grants and personal fees for advisory board work and lectures from Regeneron Pharmaceuticals and Sanofi Genzyme, grants from Respiratory Effectiveness Group and UK National Health Service, personal fees for advisory board work and travel/accommodation/meeting expenses from ThermoFisher, non-financial support for grant committee reviewing from Efficacy and Evaluation Mechanism Programme and Health Technology Assessment, outside the submitted work; has stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; and is part owner of the social enterprise Optimum Patient Care Ltd (Australia and UK) and of the Observational and Pragmatic Research Institute Pte Ltd (Singapore). Conflict of interest: E. Rapsomaniki is an employee of AstraZeneca (UK). Conflict of interest: N. Karlsson is an employee of AstraZeneca. Conflict of interest: D.K. Finch was an employee of AstraZeneca at the time of authorship. Conflict of interest: J. Nuevo is an employee of AstraZeneca. Conflict of interest: A. de Giorgio-Miller has nothing to disclose. Conflict of interest: M. Alacqua has nothing to disclose. Conflict of interest: R. Hughes reports personal fees from GlaxoSmithKline, Novartis, Boehringer Ingelheim and AstraZeneca, outside the submitted work; and is an employee of AstraZeneca. Conflict of interest: H. Müllerová is an employee of AstraZeneca. Conflict of interest: M. Gerhardsson de Verdier is an employee of AstraZeneca.

Copyright ©The authors 2021.

Figures

FIGURE 1

a) Respiratory and b) non-respiratory comorbidities in the NOVELTY population, by physician-assigned diagnosis. COPD: chronic obstructive pulmonary disease; CAD: coronary artery disease; MI: myocardial infarction. #: from an electronic case report form entry under “Respiratory Comorbidities” and/or from a record of abnormal computed tomography findings; ¶: any cardiovascular disease other than hypertension, CAD, MI or congestive heart failure.

FIGURE 2

Variability in a) modified Medical Research Council (mMRC) dyspnoea grade (available for 96.5% of patients), b) St George's Respiratory Questionnaire (SGRQ) total score (available for 69.3% of patients) and c) Chronic Airways Assessment Test (CAAT#) total score (available for 70.0% of patients) by physician-assigned diagnosis and severity.¶ For b and c, boxes represent the median (interquartile range (Q1–Q3); whiskers extend to 1.5 times the interquartile range, with circles representing individual outliers. COPD: chronic obstructive pulmonary disease. #: the CAAT is a trademark of the GlaxoSmithKline group of companies. © 2009 GlaxoSmithKline. All rights reserved. It has been modified from the COPD Assessment Test, with permission, by replacement of the term “COPD” with “chronic airways” and “pulmonary disease” in the questionnaire title and instruction, respectively. ¶: recruitment was stratified by diagnosis/severity with the aim of achieving similar numbers of patients in each group; for patients with asthma+COPD, the severity category is the worse of the two physician-assessed severity classifications, and patients with COPD classified as “very severe” were included in the “severe” group.

FIGURE 3

Frequency distribution by a) the number of exacerbations# and b) the mean number of exacerbations (among all patients, including those with no exacerbations) in the past 12 months, by physician-assigned diagnosis and severity.¶ In b, data are presented as mean+sd. COPD: chronic obstructive pulmonary disease. #: exacerbations include mild, moderate and severe exacerbations, from the following question in the electronic case report form: “During the past 12 months, on how many occasions has your patient experienced an exacerbation of their asthma or COPD beyond the patient's usual day-to-day variance?”; ¶: recruitment was stratified by diagnosis/severity with the aim of achieving similar numbers of patients in each group; for patients with asthma+COPD, severity was based on the more severe of the physician's assessed severity for asthma and for COPD, and patients with COPD classified as “very severe” were included in the “severe” group.

FIGURE 4

Heterogeneity in a–i) post-bronchodilator forced expiratory volume in 1 s (FEV1), j–r) post-bronchodilator FEV1/forced vital capacity (FVC) and s–aa) bronchodilator responsiveness, by physician-assigned diagnosis and severity. For continuous data, density is calculated as frequency divided by category width. The solid black lines show the median values. Grey shading shows the spirometric thresholds used in asthma/chronic obstructive pulmonary disease (COPD) diagnostic criteria [2, 3]. See supplementary table S3 for the number of patients with post-bronchodilator spirometry data. Global Lung Function Initiative multi-ethnic reference equations were used to calculate % predicted values [13].

FIGURE 4

Heterogeneity in a–i) post-bronchodilator forced expiratory volume in 1 s (FEV1), j–r) post-bronchodilator FEV1/forced vital capacity (FVC) and s–aa) bronchodilator responsiveness, by physician-assigned diagnosis and severity. For continuous data, density is calculated as frequency divided by category width. The solid black lines show the median values. Grey shading shows the spirometric thresholds used in asthma/chronic obstructive pulmonary disease (COPD) diagnostic criteria [2, 3]. See supplementary table S3 for the number of patients with post-bronchodilator spirometry data. Global Lung Function Initiative multi-ethnic reference equations were used to calculate % predicted values [13].