Impact of an increase in the inhaled corticosteroid dose on blood eosinophils in asthma

Lommatzsch, Marek; Klein, Maria; Stoll, Paul; Virchow, J. Christian

doi:10.1136/thoraxjnl-2018-212233

Cited by 40 publications

(32 citation statements)

References 10 publications

(7 reference statements)

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“…Finally, significantly greater reductions in asthma exacerbations were seen in patients with raised FeNO (≥19.5 ppb), eosinophils (≥260 cells/µL), and periostin (≥50 ng/mL) who were treated with omalizumab in the EXTRA phase 3 study, compared with placebo recipients 41 . Although elevated eosinophils in peripheral blood have been associated with type 2 asthma, their levels can be significantly influenced by the use of ICS 42 . Thus, peripheral blood eosinophilia as a type 2 inflammation marker should always be interpreted in view of the current dose of ICS.…”

Section: Discussionmentioning

confidence: 97%

Dupilumab is effective in type 2‐high asthma patients receiving high‐dose inhaled corticosteroids at baseline

Bourdin

Papi

Corren

et al. 2020

Allergy

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Background: Dupilumab blocks the shared receptor component for interleukin (IL)-4/ IL-13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre-BD) forced expiratory volume in 1 second (FEV 1) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate-to-severe (phase 3) asthma. Methods: In patients on high-dose inhaled corticosteroids (ICS) with type 2-high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre-BD FEV 1 and asthma control (5-item asthma control questionnaire [ACQ-5]) were analyzed. Results: In high-dose ICS type 2-high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%-69%/57%-60% (all P<.05) and 53%-69%/48%-66%

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Section: Discussionmentioning

confidence: 97%

Dupilumab is effective in type 2‐high asthma patients receiving high‐dose inhaled corticosteroids at baseline

Bourdin

Papi

Corren

et al. 2020

Allergy

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“…Oscillometric measures of SAD seem to be feasible tools in selecting appropriate patients qualifying for anti-T2 biological therapy beyond the rather crude measurement of baseline blood eosinophils count that is frequently influenced by a multitude of factors, e.g. dose of inhaled or oral steroids [22], diurnal variations [23] and atopic comorbidities [24]. Our observations on the improvements in SAD might be explained by the findings that in severe asthmatics, small airway function is significantly altered with type-2 inflammation (T cells and activated eosinophils infiltration) compared to large airways [25,26].…”

Section: Table 2 Area Under the Curve (Auc) Of Clinical Predictorsmentioning

confidence: 99%

Small airway dysfunction as predictor and marker for clinical response to biological therapy in severe eosinophilic asthma: a longitudinal observational study

et al. 2020

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Background Anti-T2 biological therapies have proven to effectively reduce acute exacerbations and daily doses of oral steroids in severe eosinophilic asthma. Despite the remarkable clinical efficacy, there are usually only moderate improvements in airflow limitation, suggesting that other measures of lung function like small airway dysfunction (SAD) might better reflect the clinical response. We aimed to investigate if measures of small airway function would predict and correlate with the clinical response to anti-T2 therapy. Methods We studied data of patients who were previously included in the German prospective longitudinal All Age Asthma Cohort (ALLIANCE) that recruits asthma patients of all severity grades and inflammatory phenotypes. The selection criteria for this analysis were adult patients with severe eosinophilic asthma under treatment with anti-T2 biological agents. Asthma control was assessed by asthma control test (ACT) and number of severe exacerbations. Small airway function was assessed by the frequency dependence of resistance (FDR, R5-20)) derived from impulse oscillometry (IOS) and the mean forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75). We also studied air trapping (RV and RV/TLC), blood eosinophils and FeNO. Patients were classified into responders and partial or non-responders. Clinical response was defined as at least 50% reduction in annualized severe exacerbations and daily oral steroid doses accompanied with a minimum increase of 3 points in the ACT score. We used a Receiver Operator Characteristic (ROC) to study the capacity of FDR in predicting clinical response compared to other clinical variable like blood eosinophils. We studied the correlation between FDR measures and clinical response, represented by the ACT score and number of exacerbations, using linear regressions. Results 20 patients were included (mean age, 59 ± 9 years; 60% female; mean body mass index (BMI), 27.6 ± 5.4 kg/m2; mean absolute blood eosinophils, 570 ± 389/µl; mean number of severe exacerbations 12 months prior to initiating the biological therapy, 5.0 ± 3; mean predicted FEV1, 76 ± 21%; mean predicted FDR, 224 ± 140%; mean daily prednisolone dose, 6.4 ± 4.9 mg; mean ACT score, 15 ± 5). Responders had significantly higher baseline FDR compared to partial or non-responders but similar FEV1, FEF25–75, RV and RV/TLC. ROC analysis showed that the combination of FDR and blood eosinophils had the best predictive capacity of the clinical response among all tested clinical markers (FeNO, FEV1, FDR, blood eosinophils) with an AUC of 85% [67–100%], (CI = 0.95, p = 0.01). Linear regressions indicated better associations between improvements in FDR and ACT score (R2 = 0.42, p = 0.001) than with FEV1 and ACT score (R2 = 0.25, p = 0.013). Likewise, we observed better associations between improvements in FDR and reduction of exacerbations (R2 = 0.41, p = 0.001) than with FEV1 (R2 = 0.20, p = 0.025). Conclusion Our data suggest that severe SAD may represent a distinct phenotype of eosinophilic asthma that substantially improves under anti-T2 biological therapy. Measures of small airway function might be useful in selecting appropriate patients qualifying for anti-T2 biological therapy in addition to blood eosinophil count.

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“…It has been postulated that high doses of ICS are comparable with a daily oral dose of up to 5 mg prednisolone per day [40]. This is probably the explanation for the strong reduction of eosinophil concentrations in peripheral blood (by nearly 50%) following an increase of the daily ICS treatment from a medium to a high dose [41]. Therefore, it is currently debated whether high doses of ICS are an acceptable long-term treatment option for asthma or whether other immune-modulating treatment strategies with less adverse effects should be preferred.…”

Section: Current and Potential Future Options Of Immune Modulation Inmentioning

confidence: 99%

Immune Modulation in Asthma: Current Concepts and Future Strategies

Lommatzsch¹

2020

Respiration

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Asthma treatment concepts have profoundly changed over the last 20 years, from standard therapeutic regimens for all patients with asthma towards individually tailored interventions targeting treatable traits ("precision medicine"). A precise and highly effective immune modulation with minimal adverse effects plays a central role in this new concept. Recently, there have been major advances in the treatment of asthma with immune-modulatory compounds. One example is the approval of several highly potent biologics for the treatment of severe asthma. New immune-modulatory strategies are expected to enter clinical practice in the future; these innovations will be especially important for patients with treatment-resistant asthma.

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Impact of an increase in the inhaled corticosteroid dose on blood eosinophils in asthma

Cited by 40 publications

References 10 publications

Dupilumab is effective in type 2‐high asthma patients receiving high‐dose inhaled corticosteroids at baseline

Dupilumab is effective in type 2‐high asthma patients receiving high‐dose inhaled corticosteroids at baseline

Small airway dysfunction as predictor and marker for clinical response to biological therapy in severe eosinophilic asthma: a longitudinal observational study

Immune Modulation in Asthma: Current Concepts and Future Strategies

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