Paucigranulocytic asthma: Do sputum macrophages matter?

2021 ◽  
Vol 42 (6) ◽  
pp. 530-536
Author(s):  
Muge Olgac ◽  
Semra Dolek Guler ◽  
Semra Demir ◽  
Derya Unal ◽  
Belkıs Ertek ◽  
...  
Keyword(s):  
Vital Capacity ◽  
Forced Expiratory Volume ◽  
Induced Sputum ◽  
Blood Eosinophil ◽  
Inhaled Corticosteroid ◽  
Uncontrolled Asthma ◽  
Asthma Control Test ◽  
Eosinophilic Asthma ◽  
Cell Counts ◽  
Eosinophil Counts

Background: Although paucigranulocytic asthma (PGA) is the most common phenotype of stable asthma, its features have not been adequately studied. In this study, we aimed to display the characteristics of PGA. Method: A total of 116 non-smoking adult patients with asthma (80% women; mean ± standard deviation age, 39 ± 12.9 years) admitted to three tertiary centers were included. Their demographic and clinical features, allergy status, biochemical results, scores of Asthma Control Test (ACT), spirometry, and exhaled nitric oxide (FeNO) measurements were obtained. Induced sputum cytometry was performed. Results: Four phenotypes, according to induced sputum cell counts, were detected: eosinophilic asthma (EA) (22.4%), mixed granulocytic asthma (MGA) (6.9%), neutrophilic (NA) (7.8%), and PGA (62.9%). In the sputum, macrophages were higher in the PGA group compared with the other groups (PGA versus NA and PGA versus MGA, p < 0.001; and PGA versus EA, p =0 .030). The atopy rate between phenotypes was the same. Although the forced expiratory volume in the first second of expiration (FEV1) was similar in four groups, the ratio of FEV1 to the forced vital capacity ratio was higher (p = 0.013) and FEV1 reversibility was lower in the patients with PGA than the corresponding values in other phenotypes (p = 0.015). Low reversibility was comparable both in patients with PGA who were inhaled corticosteroid (ICS) naive and in patients on ICS treatment. Although insignificant, the FeNO values and blood eosinophil counts were higher in the MGA and EA groups, whereas these were the lowest in the PGA group. The uncontrolled asthma ratio was low in PGA (16%), whereas it was 11% for NA, 25% for MG, and 23% in EA. Conclusion: Macrophages are predominant in sputum of patients with PGA. Besides a lower uncontrolled asthma ratio, lower FEV1 reversibility is a prominent characteristic of this phenotype.

scholarly journals Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1822
Author(s):  
Corrado Pelaia ◽  
Claudia Crimi ◽  
Santi Nolasco ◽  
Giovanna Elisiana Carpagnano ◽  
Raffaele Brancaccio ◽  
...  
Keyword(s):  
Life Experience ◽  
Symptom Control ◽  
Real Life ◽  
Forced Expiratory Volume ◽  
Blood Eosinophil ◽  
Asthma Control Test ◽  
Biologic Treatment ◽  
Eosinophilic Asthma ◽  
Exacerbation Rate ◽  
Severe Eosinophilic Asthma

Background. The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. Patients and methods. Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. Results. In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV1) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). Conclusion. The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

scholarly journals Effectiveness of mepolizumab in a real-life cohort of patients with severe refractory eosinophilic asthma and multiple comorbidities

2020 ◽  
Author(s):  
Claudia Crimi ◽  
Raffaele Campisi ◽  
Giulia Cacopardo ◽  
Rossella Intravaia ◽  
Santi Nolasco ◽  
...  
Keyword(s):  
Treatment Response ◽  
Real Life ◽  
Forced Expiratory Volume ◽  
Blood Eosinophil ◽  
Asthma Control Test ◽  
Eosinophilic Asthma ◽  
Life Effectiveness ◽  
Blood Eosinophil Count ◽  
Severe Eosinophilic Asthma ◽  
Act Score

AbstractBACKGROUNDPatients with severe asthma often suffer from comorbidities whose impact on the course of biological therapy has not been elucidated yet.OBJECTIVETo evaluate real-life effectiveness and the presence/absence of predictors of treatment response in patients with one or more comorbidities who received mepolizumab (MEPO) for the treatment of severe eosinophilic asthma (EA).METHODSHealth records of 31 patients were retrospectively analyzed. Asthma control test (ACT) score, blood eosinophil count, forced expiratory volume in 1 second (FEV1), FEV1% of predicted and FEV1/FVC (Forced Vital Capacity) ratio, oral corticosteroid (OCS) dosage and exacerbations were recorded at baseline (T0), after 3 (T1), 6 (T3), nine (T6) and 12 months (T12). A clinical response was defined as: i) 30% exacerbation decrease; ii) 80% blood eosinophilia reduction; iii) 3 point ACT increase; iv) FEV1 increase ≥ 200 mL.RESULTSAt T12 blood eosinophil level decreased by 89.89% (p>0.0001), an improvement in ACT of 3 points from baseline was recorded in 80.65% of patients (p>0.0001) and 96.77% of patients reduced by minimum 30% the number of exacerbations (p>0.0001). 84% of patients discontinued OCS (p>0.0001). FEV1 increased by 0.22 (p=0.0224) while FEV1/FVC was statistically significant only at T1. No significant differences were generally found among patients with a specific comorbidity. The number of comorbidities did not influence treatment response. Neither the comorbidities nor other characteristics (sex, BMI, age, smoking, baseline eosinophil level) influenced treatment response.CONCLUSIONSMEPO in patients with severe EA is effective regardless of the presence of one or more comorbidities.

scholarly journals Clinical and economic consequences of switching from omalizumab to mepolizumab in uncontrolled severe eosinophilic asthma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giovanna Elisiana Carpagnano ◽  
Emanuela Resta ◽  
Massimiliano Povero ◽  
Corrado Pelaia ◽  
Mariella D’Amato ◽  
...  
Keyword(s):  
Disease Onset ◽  
National Health System ◽  
Healthcare Spending ◽  
Blood Eosinophil ◽  
Asthma Control Test ◽  
Eosinophilic Asthma ◽  
Exacerbation Rate ◽  
Serum Ige ◽  
Asthmatic Patients ◽  
Severe Eosinophilic Asthma

AbstractSevere asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS), which worsen patients’ health and increase healthcare spending. The aim of this study was to assess the clinical and economic impact of switching from omalizumab (OMA) to mepolizumab (MEP) in patients eligible for both biologics, but not optimally controlled by omalizumab. We retrospectively enrolled uncontrolled severe asthmatic patients who switched from OMA to MEP during the last two years. Information included blood eosinophil count, asthma control test (ACT), spirometry, serum IgE, fractional exhaled nitric oxide (FeNO), OCS intake, drugs, exacerbations/hospitalizations, visits and diagnostic exams. Within the perspective of Italian National Health System, a pre- and post-MEP 12-month standardized total cost per patient was calculated. 33 patients were enrolled: five males, mean age 57 years, disease onset 24 years. At OMA discontinuation, 88% were OCS-dependent with annual mean rate of 4.0 clinically significant exacerbations, 0.30 exacerbations needing emergency room visits or hospitalization; absenteeism due to disease was 10.4 days per patient. Switch to MEP improved all clinical outcomes, reducing total exacerbation rate (RR = 0.06, 95% CI 0.03–0.14), OCS-dependent patients (OR = 0.02, 95% CI 0.005–0.08), and number of lost working days (Δ = − 7.9, 95% CI − 11.2 to − 4.6). Pulmonary function improved, serum IgE, FeNO and eosinophils decreased. Mean annual costs were €12,239 for OMA and €12,639 for MEP (Δ = €400, 95% CI − 1588–2389); the increment due to drug therapy (+ €1,581) was almost offset by savings regarding all other cost items (− €1,181). Patients with severe eosinophilic asthma, not controlled by OMA, experienced comprehensive benefits by switching to MEP with only slight increases in economic costs.

scholarly journals Associations between blood eosinophils and decline in lung function among adults with and without asthma

2018 ◽  
Vol 51 (4) ◽  
pp. 1702536 ◽  
Author(s):  
Robert J. Hancox ◽  
Ian D. Pavord ◽  
Malcolm R. Sears
Keyword(s):  
Lung Function ◽  
Vital Capacity ◽  
Airflow Obstruction ◽  
Population Based ◽  
Forced Expiratory Volume ◽  
Lung Function Decline ◽  
Characteristic Features ◽  
Predicted Values ◽  
Blood Eosinophils ◽  
Eosinophil Counts

Eosinophilic inflammation and airway remodelling are characteristic features of asthma, but the association between them is unclear. We assessed associations between blood eosinophils and lung function decline in a population-based cohort of young adults.We used linear mixed models to analyse associations between blood eosinophils and spirometry at 21, 26, 32 and 38 years adjusting for sex, smoking, asthma and spirometry at age 18 years. We further analysed associations between mean eosinophil counts and changes in spirometry from ages 21 to 38 years.Higher eosinophils were associated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratios and lower FEV1 % predicted values for both pre- and post-bronchodilator spirometry (all p-values ≤0.048). Although eosinophil counts were higher in participants with asthma, the associations between eosinophils and spirometry were similar among participants without asthma or wheeze. Participants with mean eosinophil counts >0.4×109 cells·L−1 between 21 and 38 years had greater declines in FEV1/FVC ratios (difference 1.8%, 95% CI 0.7–2.9%; p=0.001) and FEV1 values (difference 3.4% pred, 95% CI 1.5–5.4% pred); p=0.001) than those with lower counts.Blood eosinophils are associated with airflow obstruction and enhanced decline in lung function, independently of asthma and smoking. Eosinophilia is a risk factor for airflow obstruction even in those without symptoms.

scholarly journals Switching from omalizumab to mepolizumab: real-life experience from Southern Italy

2020 ◽  
Vol 14 ◽  
pp. 175346662092923 ◽  
Author(s):  
Giovanna Elisiana Carpagnano ◽  
Corrado Pelaia ◽  
Maria D’Amato ◽  
Nunzio Crimi ◽  
Nicola Scichilone ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Severe Asthma ◽  
Southern Italy ◽  
Life Experience ◽  
Real Life ◽  
Forced Expiratory Volume ◽  
Asthma Control Test ◽  
Eosinophilic Asthma ◽  
Life Study ◽  
First Choice

Background: Current availability of several biologic treatments for severe asthma makes it possible to choose the most appropriate for each patient. Sometimes a good percentage of patients with severe asthma may be eligible for biologics that target either the allergic phenotype or the eosinophilic one, but not all respond to that selected as first choice. The aim of our real-life study was to assess whether, for patients with severe eosinophilic allergic asthma, not previously controlled by the anti-IgE omalizumab, the shift to another biologic targeting interleukin-5, such as mepolizumab, may represent a good therapeutic choice. Methods: A total of 41 consecutive patients with severe, persistent allergic, eosinophilic asthma, uncontrolled despite treatment with omalizumab, were enrolled in seven certified Clinical Respiratory Units of Southern Italy (Catania, Catanzaro, Foggia, Bari, Palermo, and two University Respiratory Units of Naples) and shifted to mepolizumab without a wash-out period. Data at baseline, after at least 12 months of therapy with omalizumab, and after at least 12 months of treatment with mepolizumab were collected. Results: After at least 12 months of therapy with mepolizumab, patients experienced a significant decrease in the number of exacerbations/year (5.8 ± 1.8 versus 0.7 ± 0.9, p < 0.0001), an increment of asthma control test score (12 ± 2.7 versus 21.9 ± 2.7, p < 0.0001), an increase in pre-bronchodilator forced expiratory volume in 1 s (1.56 ± 0.45 l versus 1.86 ± 0.52 l, p < 0.0001), and a reduction of blood eosinophils (584 ± 196 cells/µl versus 82 ± 56 cells/µl, p < 0.0001). The percentage of patients who were dependent on corticosteroids significantly decreased from 46% at baseline to 5% during treatment with mepolizumab. Conclusion: Results of our real-life multicentric experience confirms that the shift to mepolizumab could be a good therapeutic strategy in severe eosinophilic allergic asthma not previously controlled by omalizumab. The reviews of this paper are available via the supplemental material section.

scholarly journals Effects of the first three doses of benralizumab on symptom control, lung function, blood eosinophils, oral corticosteroid intake, and nasal polyps in a patient with severe allergic asthma

2020 ◽  
Vol 8 ◽  
pp. 2050313X2090696 ◽  
Author(s):  
Corrado Pelaia ◽  
Maria Teresa Busceti ◽  
Alessandro Vatrella ◽  
Marco Ciriolo ◽  
Eugenio Garofalo ◽  
...  
Keyword(s):  
Nasal Polyps ◽  
Oral Corticosteroid ◽  
Inhaled Corticosteroids ◽  
Symptom Control ◽  
Serum Levels ◽  
Forced Expiratory Volume ◽  
High Serum ◽  
Asthma Control Test ◽  
Eosinophilic Asthma ◽  
Blood Eosinophils

Severe allergic eosinophilic asthma can be characterized by inadequate control, despite the regular use of high dosages of inhaled corticosteroids/long-acting β2-adrenergic agonists combinations, and the very frequent utilization of oral corticosteroids. Therefore, under these circumstances, an add-on biological treatment with monoclonal antibodies directed against suitable molecular targets, involved in the pathobiology of type-2 airway inflammation, is very useful. Within such a context, our case report refers to a 46-year-old woman with severe allergic eosinophilic asthma and relapsing nasal polyps, not eligible to add-on biological therapy with omalizumab because of her very high serum levels of immunoglobulins E (IgE). She is currently under treatment with the humanized monoclonal antibody benralizumab (30 mg subcutaneous injection, administered every 4 weeks for the first three doses, and every 8 weeks thereafter), an eosinophil-depleting anti-interleukin-5-receptor biologic. Our patient experienced relevant clinical and functional improvements already after the first dose, and subsequently striking changes were recorded after the second and third doses, including remarkable increases in asthma control test scores and forced expiratory volume in 1 s values, associated with a complete depletion of blood eosinophils and the interruption of oral corticosteroid intake, as well as with the concomitant disappearance of nasal polyps after the second dose. In conclusion, this case study suggests that benralizumab can exert a very rapid and effective therapeutic action in patients with severe eosinophilic asthma and nasal polyposis.

scholarly journals NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Gene Colice ◽  
Janet M. Griffiths ◽  
Gun Almqvist ◽  
Sandhia Ponnarambil ◽  
...  
Keyword(s):  
Blood Eosinophil ◽  
Health Related Quality ◽  
Uncontrolled Asthma ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Related Quality ◽  
Health Related ◽  
Eosinophil Counts

Abstract Background Patients with severe, uncontrolled asthma have a significant unmet need for new treatments that have broader effects on airway inflammation, and that provide greater improvements in asthma outcomes than currently approved biologics and standard-of-care therapies. Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. In the PATHWAY phase 2b study (NCT02054130), tezepelumab significantly reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline disease phenotype. This article reports the design and objectives of the pivotal phase 3 NAVIGATOR study. Methods NAVIGATOR (NCT03347279) is an ongoing randomized, double-blind, placebo-controlled trial in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids (N = 1061). The study population includes approximately equal proportions of patients with high (≥ 300 cells/μL) and low (< 300 cells/μL) blood eosinophil counts. The study comprises a 5–6-week screening period, a 52-week treatment period and a 12-week post-treatment follow-up period. All patients will receive their prescribed controller medications without change throughout the study. The primary efficacy endpoint is the annualized asthma exacerbation rate during the 52-week treatment period. Key secondary endpoints include the effect of tezepelumab on lung function, asthma control and health-related quality of life. Discussion NAVIGATOR is evaluating the effect of tezepelumab in patients with a broad range of severe asthma phenotypes at baseline, including those with low blood eosinophil counts. The target sample size for NAVIGATOR (N = 1060) was achieved, and it is the largest clinical study of tezepelumab in severe, uncontrolled asthma to date. NAVIGATOR aims to further investigate the effect of tezepelumab on exacerbations and build on observations from the phase 2b PATHWAY study, and to demonstrate further the potential of tezepelumab to provide patients with severe, uncontrolled asthma with improvements in lung function, asthma control and health-related quality of life. Trial registration NCT03347279 (ClinicalTrials.gov). Registered 20 November 2017.

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