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6 52 A further strength of our study was the wide range of clinically relevant conditions examined in the context of disease staging, TAK-632 with higher prevalence of respiratory symptoms, respiratory and cardiovascular diseases, breathlessness and poor self-rated health among participants in the tightest definitions of FT and LLN obstruction, confirming similar findings in the USA.53 54 While recent guidelines13 46 55 recommend adopting multidimensional definitions of respiratory disease, our study outcomes were defined only using spirometry. While we acknowledge the merits of a multidimensional approach, and agree that neither spirometric cut-off is able to fully characterise the complex diagnostic Ipatasertib concentration features of COPD,56 our primary aim was to use up-to-date survey data to evaluate differences in prevalence according to FT and LLN thresholds, to provide baseline data for monitoring purposes in the UK, and promote comparability with international studies. Current recommendations regarding symptom criteria are less specific than those for spirometry. We chose, therefore, to examine the associations between disease staging assessed only using spirometry and presence of respiratory symptoms, rather than broaden the definition of disease. Implications Recent UK studies used administrative primary care databases to report the number of diagnosed and treated patients, thereby missing undiagnosed cases. Such studies have reported prevalence below 2%.57 58 The disparity in prevalence from clinical versus epidemiological studies led to the development of the COPD prevalence model, with the HSE 2001 used as input data, to more accurately estimate prevalence.59 In accordance with previous NICE recommendations,44 COPD is currently defined in the model as FT stage II+ (FEV1/FVC IWR-1 our study shows that the strength of association between risk factors and airflow obstruction varies according to spirometric criterion, with age and sex differences in risk being more marked for FT, and for FT stage II+, than LLN. In the absence of agreement among experts, policymakers, clinicians and researchers building the COPD epidemiological database, it is important to appreciate the sensitivity of estimates of the disease burden, and its distribution across sociodemographic groups, to differences in methods, including spirometric cut-offs. The prevalence of reported physician-diagnosed COPD in our study was 2.8%, considerably lower than spirometry-based estimates, possibly indicating considerable under-recognition by participants and physicians.