Clinical and Inflammatory Features of Exacerbation-Prone Asthma: A Cross-Sectional Study Using Multidimensional Assessment

Abstract

<b><i>Background:</i></b> Reducing asthma exacerbations is a major target of current clinical guidelines, but identifying features of exacerbation-prone asthma (EPA) using multidimensional assessment (MDA) is lacking. <b><i>Objective:</i></b> To systemically explore the clinical and inflammatory features of adults with EPA in a Chinese population. <b><i>Methods:</i></b> We designed a cross-sectional study using the Severe Asthma Web-based Database from the Australasian Severe Asthma Network (ASAN). Eligible Chinese adults with asthma (<i>n</i> = 546) were assessed using MDA. We stratified patients based on exacerbation frequency: none, few (1 or 2), and exacerbation prone (≥3). Univariate and multivariable negative binomial regression analyses were performed to investigate features associated with the frequency of exacerbations. <b><i>Results:</i></b> Of 546 participants, 61.9% had no exacerbations (<i>n</i> = 338), 29.6% had few exacerbations (<i>n</i> = 162), and 8.4% were exacerbation prone (<i>n</i> = 46) within the preceding year. EPA patients were characterized by elevated blood and sputum eosinophils but less atopy, with more controller therapies but worse asthma control and quality of life (all <i>p</i> < 0.05). In multivariable models, blood and sputum eosinophils (adjusted rate ratio = 2.23, 95% confidence interval = [1.26, 3.84] and 1.67 [1.27, 2.21], respectively), FEV<sub>1</sub> (0.90 [0.84, 0.96]), bronchodilator responsiveness (1.16 [1.05, 1.27]), COPD (2.22 [1.41, 3.51]), bronchiectasis (2.87 [1.69, 4.89]), anxiety (2.56 [1.10, 5.95]), and depression (1.94 [1.20, 3.13]) were found. Further, upper respiratory tract infection (1.83 [1.32, 2.54]) and food allergy (1.67 [1.23, 2.25]) were at high risk of asthma symptom triggers. <b><i>Conclusion:</i></b> EPA is a clinically recognizable phenotype associated with several recognizable traits that could be addressed by targeted treatment.

Assessment of bronchodilator responsiveness to salbutamol or ipratropium using different criteria in treatment-naïve patients with asthma and COPD

“…The rate of BD responsiveness shows a direct dose-response relationship with long-term mortality in patients with asthma [ 25 ]. Moreover, bronchial responsiveness is a risk factor for exacerbation-prone asthma in a Chinese cohort [ 26 ]. In this regard, our findings show that administering only salbutamol does not identify all treatment-naïve patients with BDR, and patients showing reversibility to ipratropium could be undetected and misclassified as non-reversible.…”

Modelling ASthma TrEatment Responses (MASTER): Effect of individual patient characteristics on the risk of exacerbation in moderate or severe asthma: A time‐to‐event analysis of randomized clinical trials

“…Consequently, guidelines for the clinical management of asthma patients with moderate or severe symptoms continue to overlook the effect of individual patient characteristics as potential contributors or determinants of future risk. In fact, previous investigations have shown that inflammatory mediators, including eosinophilia and increased airflow limitation, are associated with a higher risk of exacerbation in severe and refractory asthma 26–28 . However, none of these studies attempted to assess, in a parametric manner, how inflammatory markers and phenotypical characteristics correlate with symptom control (ACQ‐5) and other clinical and demographic characteristics.…”

“…In fact, previous investigations have shown that inflammatory mediators, including eosinophilia and increased airflow limitation, are associated with a higher risk of exacerbation in severe and refractory asthma. [26][27][28] However, none of these studies attempted to assess, in a parametric manner, how inflammatory markers and phenotypical characteristics correlate with symptom control (ACQ-5) and other clinical and demographic characteristics. F I G U R E 6 Heat map showing the probability of at least one exacerbation within the first year of treatment for patients receiving monotherapy or combination therapy.…”

Acute exacerbations of chronic rhinosinusitis: The current state of knowledge

“…In a similar vein to study of the asthma exacerbation‐prone phenotype, work has been done to study CRS patients who have frequent AECRS or an exacerbation‐prone phenotype 27 . We have previously proposed that AECRS‐prone be defined as having at least 4 AECRS episodes in a 12 months period 18 based on previous guidelines indicating that at least 1 rescue medication in 3 months was an indication of uncontrolled CRS 1 .…”

“…26 In a similar vein to study of the asthma exacerbation-prone phenotype, work has been done to study CRS patients who have frequent AECRS or an exacerbation-prone phenotype. 27 We have previously proposed that AECRS-prone be defined as having at least 4 AECRS episodes in a 12 months period 18 based on previous guidelines indicating that at least 1 rescue medication in 3 months was an indication of uncontrolled CRS. 1 In a retrospective review of over 3000 patients with CRS, 19.3% were found to have meet this criteria for exacerbation-prone CRS, with at least 4 AECRS (defined by an antibiotic course prescribed for worsening sinus symptoms) over a 12 months period.…”