Biomarker Profiles in Asthma With High vs Low Airway Reversibility and Poor Disease Control

Busse, William W.; Holgate, Stephen T.; Wenzel, Sally E.; Klekotka, Paul; Chon, Yun; Feng, JingYuan; Ingenito, Edward P.; Nirula, Ajay

doi:10.1378/chest.14-2457

Cited by 65 publications

(50 citation statements)

References 9 publications

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“…We did not observe an association to FE NO levels, a marker easily suppressed by compliance with ICS therapy. This is in contrast to a smaller study by Kupczyk and coworkers (9) showing a link between EPA status and elevated FE NO levels, but consistent with a larger retrospective biomarker analysis of two recent clinical trials (28). Additionally, adults in the SARP-3 cohort seem to have an inverse relationship between exacerbations and IgE levels ( Figure 3) or degree of allergen polysensitization (Table 3, Figures 3 and 4).…”

Section: Discussionsupporting

confidence: 84%

“…Prior studies have shown a lack of association between IgE levels and measures of asthma control, and lower levels of IgE in patients with poor bronchodilator responsiveness (15,28). Collectively, although patients with high levels of type 2 inflammatory biomarkers are at increased risk of exacerbation, those with frequent exacerbation may or may not have high levels of type 2 inflammation at the time of assessment.…”

Section: Number Of Exacerbations In the Lastmentioning

confidence: 99%

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Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations

Denlinger

Phillips

Ramratnam

et al. 2017

Am J Respir Crit Care Med

370

267

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Rationale: Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.Objectives: To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.Methods: Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (>3). Replication of a multivariable model was performed with data from the SARP-1 1 2 cohort.Measurements and Main Results: Of 709 subjects in the SARP-3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP-3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP-3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval],

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Section: Discussionsupporting

confidence: 84%

Section: Number Of Exacerbations In the Lastmentioning

confidence: 99%

Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations

Denlinger

Phillips

Ramratnam

et al. 2017

Am J Respir Crit Care Med

370

267

View full text Add to dashboard Cite

show abstract

“…This finding is in contrast to a previous review, which found a higher rate of atopic conditions such as sinusitis in patients with uncontrolled asthma, albeit in an elderly population (36). Conversely, T helper 2 inflammation, which is associated with uncontrolled asthma, has been observed independent of atopic status in some SA populations (37,38). These previous findings support the possibility that, in this population of patients with SA, atopic conditions such as eczema and sinusitis may not have increased in prevalence with uncontrolled disease, but were associated with a lower risk of uncontrolled disease.…”

Section: Discussioncontrasting

confidence: 96%

Clinical characteristics and burden of illness among adolescent and adult patients with severe asthma by asthma control: the IDEAL study

Müllerová¹,

Cockle

Gunsoy

et al. 2020

Journal of Asthma

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Objectives: Severe asthma (SA) can be uncontrolled despite guideline-directed treatment. We described SA characteristics and identified factors associated with uncontrolled disease and frequent exacerbations. Methods: Post hoc analysis of the observational IDEAL study (201722/NCT02293265) included patients with SA aged !12 years receiving high-dose inhaled corticosteroids plus additional controller(s) for !12 months. Uncontrolled SA was defined by Asthma Control Questionnaire (ACQ)-5 scores !1.5 or !1 exacerbations (prior year), and further stratified by exacerbation frequency (no/infrequent [0-1] vs frequent [!2]; prior year); associated factors were determined using multivariate logistic regression. Results: Of 670 patients with SA, 540 (81%) were uncontrolled (ACQ-5 scores !1.5: 80%; !1 exacerbations [prior year]: 71%). Uncontrolled patients had lower lung function and worse health-related quality of life (HRQoL) than controlled patients; 197/540 (37%) experienced frequent exacerbations (prior year). Worse St George's Respiratory Questionnaire (SGRQ) total score, comorbid sinusitis, or eczema were significantly associated with uncontrolled SA; younger age, never smoker status, exacerbation requiring hospitalization (previous year), worse SGRQ symptom score, comorbid nasal polyps, COPD, or osteoporosis were significantly associated with uncontrolled SA with frequent exacerbations. Conclusions: In IDEAL, one-fifth of patients with SA were controlled, based on symptoms. Uncontrolled, exacerbating SA was associated with specific comorbidities, frequent exacerbations, a lower lung function, and compromised HRQoL, although inference from this analysis is limited by the selective cross-sectional nature of the cohort. Nonetheless, these data highlight the need for more effective precision treatments in this population.

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“…Bronchodilator response has been reported to inversely correlate with the degree of hyperresonsiveness to adenosine 5 0monophosphate (AMP) during bronchial challenge [11], which is known to reflect the persistence of underlying bronchial inflammation in asthma [12]. Moreover, there is evidence of correlation between bronchodilator response and other markers of airway inflammation such as exhaled nitric oxide [13,14], eosinophils in bronchial biopsy specimens [15] or a combination of serum IgE, blood eosinophils and exhaled nitric oxide [16].…”

Section: Patients With Airway Obstruction (N ¼ 76)mentioning

confidence: 99%

Bronchodilator response as a marker of poor asthma control

Heffler

Crimi

Campisi

et al. 2016

Respiratory Medicine

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Biomarker Profiles in Asthma With High vs Low Airway Reversibility and Poor Disease Control

Abstract: BACKGROUND: High bronchodilator reversibility in adult asthma is associated with distinct clinical characteristics. Th is analysis compares lung function, biomarker profi les, and disease control in patients with high reversibility (HR) and low reversibility (LR) asthma.

Cited by 65 publications

References 9 publications

Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations

Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations

Clinical characteristics and burden of illness among adolescent and adult patients with severe asthma by asthma control: the IDEAL study

Bronchodilator response as a marker of poor asthma control

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