Validation of a diagnosis-agnostic symptom questionnaire for asthma and/or COPD

Abstract

Background: The Respiratory Symptoms Questionnaire (RSQ) is a novel, four-item patient-reported diagnosis-agnostic tool designed to assess the frequency of respiratory symptoms and their impact on activity, without specifying a particular diagnosis. Our objective was to examine its validity in patients with asthma and/or chronic obstructive pulmonary disease (COPD).

Methods: Baseline data were randomly sampled from patients who completed the RSQ in the NOVELTY study (ClinicalTrials.gov: NCT02760329). The total sample (n=1530) comprised three randomly selected samples (n=510 each) from each physician-assigned diagnostic group (asthma, asthma+COPD and COPD). The internal consistency and structural validity of the RSQ were evaluated using exploratory and confirmatory factor analyses; psychometric performance was observed using Classical Test Theory and Item Response Theory analyses.

Results: For the total sample, the mean±sd RSQ score was 5.6±4.3 (range 0-16). Irrespective of diagnosis, the internal consistency of items was uniformly adequate (Cronbach's α=0.76-0.80). All items had high factor loadings and structural characteristics of the measure were invariant across groups. Using the total sample, RSQ items informatively covered the θ score range of -2.0 to 2.8, with discrimination coefficients for individual items being high to very high (1.7-2.6). Strong convergent correlations were observed between the RSQ and the St George's Respiratory Questionnaire (0.77, p<0.001).

Conclusions: The RSQ is a valid, brief, patient-reported tool for assessing respiratory symptoms in patients across the whole spectrum of asthma and/or COPD, rather than using different questionnaires for each diagnosis. It can be used for monitoring respiratory symptoms in clinical practice, clinical trials and real-world studies.

Conflict of interest statement

Conflict of interest: N. Karlsson is an employee of AstraZeneca. Conflict of interest: M.J. Atkinson reports payment as an independent consultant to Evidera for activities contracted by AstraZeneca associated with the psychometric evaluation of the Respiratory Symptoms Questionnaire; he has provided analytic direction and unbiased interpretation of the RSQ findings. Conflict of interest: H. Müllerová is an employee of AstraZeneca. Conflict of interest: M. Alacqua is an employee of AstraZeneca. Conflict of interest: C. Keen is an employee of AstraZeneca. Conflict of interest: R. Hughes is an employee of AstraZeneca. Conflict of interest: C. Janson reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva Pharmaceuticals, outside the submitted work. Conflict of interest: B. Make reports grants (with funds provided to, and controlled by, National Jewish Health) from AstraZeneca, GlaxoSmithKline, National Heart, Lung, and Blood Institute, Pearl Research and Sunovion; personal fees from Takeda and Third Pole; nonfinancial support from AstraZeneca, Circassia, GlaxoSmithKline, Phillips, Shire, Spiration, Sunovion and Third Pole; and other support from Academy Continued Health Care Learning, American College of Chest Physicians, AstraZeneca, Boehringer Ingelheim, Catamount Medical, Circassia, Eastern Pulmonary Society, Eastern VA Medical Center, GlaxoSmithKline, Hybrid Communications, Medscape, Mount Sinai Medical Center, National Jewish Health, Novartis, Phillips, Projects in Knowledge, Science 24/7, Shire, Sunovion, Theravance, Ultimate Medical Academy, Verona, WebMD and Wolters Kluwer Health, all outside the submitted work. Conflict of interest: D. Price received funding for the conduct of this study from AstraZeneca and discloses board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mundipharma, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals and Thermofisher; consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma, Mylan, Novartis, Pfizer, Teva Pharmaceuticals and Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mundipharma, Mylan, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva Pharmaceuticals, Theravance and the UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mundipharma, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme and Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma and Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis and Thermofisher; funding for patient enrolment or completion of research from Novartis; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp, which develops adherence monitoring technology; is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. Conflict of interest: H.K. Reddel reports that this study is funded by AstraZeneca. She received reimbursement from AstraZeneca for time spent working on the study but not for manuscript preparation. She also reports advisory boards for AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Sanofi-Genzyme; data and safety monitoring boards for AstraZeneca, GlaxoSmithKline, Merck and Novartis; honoraria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Teva Pharmaceuticals for independent medical educational presentations; and independent research funding from AstraZeneca, GlaxoSmithKline and Novartis, all outside the submitted work.

Copyright ©ERS 2021.

Figures

FIGURE 1

The Respiratory Symptoms Questionnaire (RSQ), response options and scoring. Responses to each of the four RSQ questions (items 1–4) are scored 0–4, with higher scores indicative of more frequent or worse symptoms. Total score ranges from 0 to 16. The RSQ is available for free use for legitimate scientific and clinical care reasons; AstraZeneca retains licensing rights through RWS Life Sciences (for further details, contact: astrazeneca@rws.com).

FIGURE 2

Distribution of physician-assessed severity (mild, moderate or severe) in the total sample for Respiratory Symptoms Questionnaire (RSQ) items, by response score: a) item 1 (frequency of daytime symptoms), b) item 2 (frequency of rescue inhaler use), c) item 3 (degree of activity limitation) and d) item 4 (frequency of night-time awakenings due to symptoms). The total sample (n=1530) comprised patients with physician-assigned diagnoses of asthma (n=510), asthma+COPD (n=510) and COPD (n=510). See figure 1 for full details of the RSQ questions and response options. Physicians were not aware of a patient's RSQ responses when they assigned the severity category. Percentages within columns may not total 100% due to rounding.

FIGURE 3

Distribution of physician-assessed severity (mild, moderate or severe) in the total sample, by Respiratory Symptoms Questionnaire (RSQ) score. The total sample (n=1530) comprised patients with physician-assigned diagnoses of asthma (n=510), asthma+COPD (n=510) and COPD (n=510). Percentages within columns may not total 100% due to rounding.