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

Abstract

BackgroundStudies 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.MethodsPatients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, 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.ResultsOf 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 post-bronchodilator FEV1/FVC <lower limit of normal.Symptoms and exacerbations increased with greater physician-assessed severity, and were higher in asthma+COPD, but 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/severity groups, but blood neutrophil counts increased with severity across all diagnoses.ConclusionThis 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.

ACO (Asthma–COPD Overlap) Is Independent from COPD: The Case Against

“…The distribution of blood eosinophils in COPD populations is not different from that seen in healthy patients without the disease [ 98 ], suggesting that the coexistence of a higher count and COPD occurs by chance rather than due to a specific causal mechanism. As noted already, the blood eosinophil count in the large observational NOVELTY study was not different between patients with an ACO diagnosis and those thought to have usual COPD [ 51 ], a finding that held true across the clinician-determined range of disease severity ( Figure 3 ). The diagnostic classification did have some significance as ACO patients were more likely to receive ICS treatment in disease perceived to be mild or moderately severe than was the case if COPD alone was diagnosed.…”

“…Further work on well characterised cohorts preferably with appropriate CT imaging should help clarify these relationships. However, the largest comparative cohort study to date, NOVELTY, found no difference in blood eosinophil counts between the asthma, COPD and asthma-COPD overlap groups that they recruited [ 51 ], suggesting that blood eosinophils are not useful discriminants in routine clinical practice in identifying what physicians felt constituted ACO.…”

“…In many ways the most powerful argument for the existence of an overlap state between asthma and COPD comes from genetics. By combining data from several pathological studies in asthma and COPD, Christenson et al found that genes associated with a Th2 phenotype in asthmatics were also expressed in patients with COPD and that blood eosinophil counts and airway responsiveness were increased when this was the case [ 51 ]. They argue that these genes might be involved in the earlier stages of the development of COPD.…”

“… Mean absolute eosinophil count (cells/µL) in 11,243 patients who participated in the NOVELTY study which included 5940 with a physician diagnosis of asthma, 3907 with a physician diagnosis of COPD and 1396 with a physician diagnosis of asthma and COPD. The physician also assessed disease severity as mild, moderate or severe [ 51 ]. …”

Comparison of Clinical Characteristics and Short-Term Prognoses Within Hospitalized Chronic Obstructive Pulmonary Disease Patients Comorbid With Asthma, Bronchiectasis, and Their Overlaps: Findings From the ACURE Registry

“…Patients with chronic obstructive pulmonary disease (COPD), comorbid with asthma (asthma-COPD overlap, ACO) or bronchiectasis (bronchiectasis-COPD overlap, BCO) as well as their coexistence (ABCO), are commonly seen phenotypes, which have been broadly discussed whether they were distinct disease entities, but there is no concluded consensus yet (1). The concept of "ACO" or "asthma + COPD" appeals as a great interest to investigators (2)(3)(4)(5)(6)(7)(8)(9)(10)(11), and similar discussion applies to the research of bronchiectasis and COPD overlap (12)(13)(14)(15)(16). Few data was reported on the ABCO phenotype.…”