Blood eosinophils predict inhaled fluticasone response in bronchiectasis

Aliberti, Stefano; Sotgiu, Giovanni; Blasi, Francesco; Saderi, Laura; Posadas, Tomás; García, Miguel Ángel Martínez

doi:10.1183/13993003.00453-2020

Cited by 50 publications

(37 citation statements)

References 10 publications

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“…Symptom reduction using ICS has reported by one study by Martinez-Garcia and colleagues, 26 with reduced dyspnoea scores, sputum production and improved QoLperhaps dependent on eosinophil airway inflammation. 27 In the present study, and in contrast to previous neutral studies, 26,28 we have demonstrated increased prevalence of moderate and severe exacerbations in patients with BE using ICS, perhaps due to the study design with standardof-care of the present study.…”

Section: Bronchodilator and Inhaled Corticosteroid Treatment Of Bronchiectasiscontrasting

confidence: 87%

Inhaled Corticosteroid Therapy in Bronchiectasis is Associated with All-Cause Mortality: A Prospective Cohort Study

Håkansson¹,

Fjællegaard²,

Browatzki³

et al. 2021

COPD

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Background and Objective: Prescribing inhaled corticosteroids (ICS) for bronchiectasis (BE) in the absence of obstructive lung disease is controversial. Studies investigating ICS therapy and impact on morbidity and mortality in BE are sparse. Methods: This study comprises all patients with BE managed at respiratory outpatient clinics at two university hospitals in the Capital Region of Denmark 2014-2015. Baseline data were obtained from patient medical records, and patients were followed until April 2020. Results: Out of 264 patients, 122 (46%) were prescribed ICS with no demographic differences between users/non-users of ICS. Among patients prescribed ICS, 21% did not have a concomitant diagnosis of asthma or COPD. Patients prescribed ICS had lower lung function (median FEV 1 65.2 vs 80.9%pred, p<0.001) and a higher symptom burden in terms of cough (p 0.028), sputum production (p <0.001) and dyspnea (p <0.001). Pseudomonaspositive sputum cultures were more common in ICS-treated patients (6.5 vs 20%, p 0.010), as were previous severe exacerbations (41% vs 21%, p <0.001). In terms of mortality, highdose ICS use was associated with increased mortality in multivariable Cox regression adjusted for age, sex, FEV 1 and concomitant asthma/COPD .0], p 0.003). Conclusion:In this cohort, close to one out of five patients with BE were prescribed ICS despite having no concomitant diagnosis of asthma or COPD. Overall, ICS treatment was associated with higher morbidity and mortality, though causation is difficult to establish.

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Section: Bronchodilator and Inhaled Corticosteroid Treatment Of Bronchiectasiscontrasting

confidence: 87%

Inhaled Corticosteroid Therapy in Bronchiectasis is Associated with All-Cause Mortality: A Prospective Cohort Study

Håkansson¹,

Fjællegaard²,

Browatzki³

et al. 2021

COPD

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“…A decrease in the number of lymphocytes may also participate in the pathogenesis of bronchiectasis, as these cells play a major role in the host adaptive immune response [15]. Other inflammatory cell types such as eosinophils may also play a role in the prognosis and in the response to treatment in these patients [16][17][18][19]. For instance, non-CF bronchiectasis patients with high levels of blood eosinophils were shown to respond better to treatments with different biological agents [20,21] and to inhaled corticosteroids [17,22].…”

Section: Introductionmentioning

confidence: 99%

“…Other inflammatory cell types such as eosinophils may also play a role in the prognosis and in the response to treatment in these patients [16][17][18][19]. For instance, non-CF bronchiectasis patients with high levels of blood eosinophils were shown to respond better to treatments with different biological agents [20,21] and to inhaled corticosteroids [17,22]. Similarly, patients with COPD exhibiting blood eosinophil counts lower than 2% were also those showing an inadequate response to inhaled corticosteroids [23].…”

Section: Introductionmentioning

confidence: 99%

Phenotypic Clustering in Non-Cystic Fibrosis Bronchiectasis Patients: The Role of Eosinophils in Disease Severity

Wang

Villa

Dobarganes

et al. 2021

IJERPH

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Whether high blood eosinophil counts may define a better phenotype in bronchiectasis patients, as shown in chronic obstructive pulmonary disease (COPD), remains to be investigated. Differential phenotypic characteristics according to eosinophil counts were assessed using a biostatistical approach in a large cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 906 patients who met the inclusion criteria were clustered into two groups on the basis of their eosinophil levels. The potential differences according to the bronchiectasis severity index (BSI) score between two groups (Mann–Whitney U test and eosinophil count threshold: 100 cells/µL) showed the most balanced cluster sizes: above-threshold and below-threshold groups. Patients above the threshold exhibited significantly better clinical outcomes, lung function, and nutritional status, while showing lower systemic inflammation levels. The proportion of patients with mild disease was higher in the above-threshold group, while the below-threshold patients were more severe. Two distinct clinical phenotypes of stable patients with non-cystic fibrosis (CF) bronchiectasis of a wide range of disease severity were established on the basis of blood eosinophil counts using a biostatistical approach. Patients classified within the above-threshold cluster were those exhibiting a mild disease, significantly better clinical outcomes, lung function, and nutritional status while showing lower systemic inflammatory levels. These results will contribute to better characterizing bronchiectasis patients into phenotypic profiles with their clinical implications.

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“…Interleukin (IL)-4, IL-5, and IL-13 mediate the T2 inflammatory cascade but are not routinely evaluated [4]. Eosinophil counts in the peripheral blood and oral fractional exhaled nitric oxide (FeNO) are surrogates of the airway eosinophilic inflammation and of the T2-high endotype [5]. Monoclonal antibodies (e.g., mepolizumab and benralizumab, which block IL-5 and IL-5 receptor -IL5ra-, respectively) can reduce the exacerbation rate and improve the quality of life and are able to spare systemic corticosteroid in eosinophilic severe asthmatic patients with bronchiectasis [6].…”

Section: Introductionmentioning

confidence: 99%

“…High levels of FeNO in bronchiectasis are associated with blood eosinophilia, IL13-driven inflammation, and reduced lung function [7,8]. Furthermore, the level of blood eosinophils seems to identify the subgroup of bronchiectasis patients who can be effectively treated by inhaled corticosteroids (ICS) [5,9,10]. Finally, anti-IL5 or anti-IL5ra drugs result in successful outcomes in severe eosinophilic asthmatic patients with concomitant bronchiectasis [6,11].…”

Section: Introductionmentioning

confidence: 99%

T2-High Endotype and Response to Biological Treatments in Patients with Bronchiectasis

et al. 2021

Self Cite

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Although bronchiectasis pathophysiology has been historically understood around the presence of airway neutrophilic inflammation, recent experiences are consistent with the identification of a type 2 inflammation (T2) high endotype in bronchiectasis. In order to evaluate prevalence and clinical characteristics of bronchiectasis patients with a T2-high endotype and explore their response to biologicals, two studies were carried out. In a cross-sectional study, bronchiectasis adults without asthma underwent clinical, radiological, and microbiological assessment, along with blood eosinophils and oral fractional exhaled nitric oxide (FeNO) evaluation, during stable state. Prevalence and characteristics of patients with a T2- high endotype (defined by the presence of either eosinophils blood count ≥300 cells·µL−1 or oral FeNO ≥ 25 dpp) were reported. A case series of severe asthmatic patients with concomitant bronchiectasis treated with either mepolizumab or benralizumab was evaluated, and patients’ clinical data pre- and post-treatment were analyzed up to 2 years of follow up. Among bronchiectasis patients without asthma enrolled in the cross-sectional study, a T2-high endotype was present in 31% of them. These patients exhibited a more severe disease, high dyspnea severity, low respiratory function, and high impact on quality of life. Among the five patients with severe eosinophilic asthma and concomitant bronchiectasis included in the series, treatment with either mepolizumab or benralizumab significantly reduced the exacerbation rate with an effect that persists for up to 2 years of follow up. If validated across different settings, our data suggest the need to design randomized controlled trials on biological treatments targeting the T2-high endotype in bronchiectasis patients.

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Blood eosinophils predict inhaled fluticasone response in bronchiectasis

Abstract: Take home message6-month treatment with inhaled fluticasone propionate significantly improved QoL in bronchiectasis patients who show a blood eosinophil counts ≥3%

Cited by 50 publications

References 10 publications

Inhaled Corticosteroid Therapy in Bronchiectasis is Associated with All-Cause Mortality: A Prospective Cohort Study

Inhaled Corticosteroid Therapy in Bronchiectasis is Associated with All-Cause Mortality: A Prospective Cohort Study

Phenotypic Clustering in Non-Cystic Fibrosis Bronchiectasis Patients: The Role of Eosinophils in Disease Severity

T2-High Endotype and Response to Biological Treatments in Patients with Bronchiectasis

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