Type-2 Biomarkers Research Articles

Blood eosinophils, fractional exhaled nitric oxide and the risk of asthma attacks in randomised controlled trials: protocol for a systemic review and control arm patient-level meta-analysis for clinical prediction modelling

IntroductionThe reduction of the risk of asthma attacks is a major goal of guidelines. The fact that type-2 inflammatory biomarkers identify a higher risk, anti-inflammatory responsive phenotype is potentially relevant...

Dupilumab Efficacy in LIBERTY ASTHMA QUEST Patients With Uncontrolled, Moderate-to-Severe Asthma By Allergen Sensitization Status

Many patients with asthma, including asthma with an allergic phenotype, also have type 2 (T2) inflammation. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4/13, key and central drivers of T2 inflammation in multiple diseases. In QUEST (NCT02414854), add-on dupilumab 200 or 300mg q2w vs placebo significantly reduced severe exacerbations, improved pre-bronchodilator FEV1, and was well tolerated in patients with uncontrolled, moderate-to-severe asthma, with greater effects in patients with elevated T2 biomarkers at baseline (blood eosinophils ≥150cells/μL or FeNO ≥25ppb).

15LO1 dictates glutathione redox changes in asthmatic airway epithelium to worsen type 2 inflammation.

Altered redox biology challenges all cells, with compensatory responses often determining a cell’s fate. When 15 lipoxygenase 1 (15LO1), a lipid-peroxidizing enzyme abundant in asthmatic human airway epithelial cells (HAECs), binds phosphatidylethanolamine-binding protein 1 (PEBP1), hydroperoxy-phospholipids, which drive ferroptotic cell death, are generated. Peroxidases, including glutathione peroxidase 4 (GPX4), metabolize hydroperoxy-phospholipids to hydroxy derivatives to prevent ferroptotic death, but consume reduced glutathione (GSH). The cystine transporter SLC7A11 critically restores/maintains intracellular GSH. We hypothesized that high 15LO1, PEBP1, and GPX4 activity drives abnormal asthmatic redox biology, evidenced by lower bronchoalveolar lavage (BAL) fluid and intraepithelial cell GSH:oxidized GSH (GSSG) ratios, to enhance type 2 (T2) inflammatory responses. GSH, GSSG (enzymatic assays), 15LO1, GPX4, SLC7A11, and T2 biomarkers (Western blot and RNA-Seq) were measured in asthmatic and healthy control (HC) cells and fluids, with siRNA knockdown as appropriate. GSSG was higher and GSH:GSSG lower in asthmatic compared with HC BAL fluid, while intracellular GSH was lower in asthma. In vitro, a T2 cytokine (IL-13) induced 15LO1 generation of hydroperoxy-phospholipids, which lowered intracellular GSH and increased extracellular GSSG. Lowering GSH further by inhibiting SLC7A11 enhanced T2 inflammatory protein expression and ferroptosis. Ex vivo, redox imbalances corresponded to 15LO1 and SLC7A11 expression, T2 biomarkers, and worsened clinical outcomes. Thus, 15LO1 pathway–induced redox biology perturbations worsen T2 inflammation and asthma control, supporting 15LO1 as a therapeutic target.

Biomarcadores tipo 2 são de alguma ajuda para distinguir rinossinusite crônica com pólipos nasais de rinossinusite crônica sem pólipos nasais?

Biomarcadores tipo 2 são de alguma ajuda para distinguir rinossinusite crônica com pólipos nasais de rinossinusite crônica sem pólipos nasais?

D010 CAPTAIN STUDY: EFFECTS OF BASELINE IGE LEVELS ON TRIPLE THERAPY RESPONSE IN INADEQUATELY CONTROLLED ASTHMA

CAPTAIN showed that adding umeclidinium (UMEC) to fluticasone furoate/vilanterol (FF/VI) improved lung function and symptom control in uncontrolled asthma; treatment response varied by baseline type-2 inflammatory biomarkers. As IgE may also influence treatment response, we evaluated the impact of adding UMEC and/or increasing FF dose in subgroups defined by baseline IgE levels.

P066 DUPILUMAB EFFICACY IN PATIENTS WITH TYPE 2 ASTHMA WITH/WITHOUT ALLERGIC PHENOTYPE RECEIVING HIGH-DOSE INHALED CORTICOSTEROIDS

Dupilumab blocks the shared receptor component for IL-4/IL-13, key and central drivers of type 2 (T2) inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), add-on dupilumab 200/300mg every 2 weeks, vs placebo, significantly reduced severe exacerbations, improved pre-bronchodilator FEV1, and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma. Treatment effects were greater in patients with elevated baseline T2 biomarkers (blood eosinophils ≥150cells/μL or FeNO ≥25ppb). This post hoc analysis assessed dupilumab efficacy in patients with T2 asthma on high-dose inhaled corticosteroids (ICS) with/without an allergic phenotype.

Effectiveness of benralizumab in severe eosinophilic asthma: Distinct sub-phenotypes of response identified by cluster analysis.

BackgroundBenralizumab is effective in severe eosinophilic asthma (SEA), but suboptimal responses are observed in some patients. Although several factors have been associated with benralizumab response, no cluster analysis has yet been undertaken to identify different responsiveness sub‐phenotypes.ObjectiveTo identify SEA sub‐phenotypes with differential responsiveness to benralizumab.MethodsOne hundred and five patients diagnosed with SEA who had completed 6 months of benralizumab treatment were included in a hierarchical cluster analysis based on a set of clinical variables that can be easily collected in routine practice (age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV1% predicted, nasal polyposis, bronchiectasis).ResultsFour clusters were identified: Clusters 2 and 3 included patients with high levels of both IgE and eosinophils (type‐2 biomarkers high), whereas Clusters 1 and 4 included patients with only one type‐2 biomarker at a high level: IgE in Cluster 1 and eosinophils in Cluster 4. Clusters 2 and 3 (both type‐2 biomarkers high) showed the highest response rate to benralizumab in terms of elimination of exacerbations (79% and 80% respectively) compared to Clusters 1 and 4 (52% and 60% respectively). When super‐response (the absence of exacerbation without oral corticosteroid use) was assessed, Cluster 2, including patients with more preserved lung function than the other clusters, but comparable exacerbation rate, oral corticosteroid use and symptom severity, was the most responsive cluster (87.5% of patients).ConclusionsOur cluster analysis identified benralizumab differential response sub‐phenotypes in SEA, with the potential of improving disease treatment and precision management.

Relationship between longitudinal changes in type-2 inflammation, immunoglobulin E sensitization, and clinical outcomes in young asthmatics.

BackgroundAsthma is a heterogeneous condition where biomarkers may be of considerable advantage in diagnosis and therapy monitoring. However, the changes in asthma biomarkers and immunoglobulin E (IgE) over the course of life has not been extensively investigated.ObjectiveTo study longitudinal changes in type‐2 inflammatory biomarkers, IgE, and clinical outcomes, and the association between these changes, in young asthmatics.MethodsAsthmatics (age 10–35 years, n = 253) were examined at baseline and at a follow‐up visit, 43 [23–65] (median [range]) months later. Subjects were analyzed using the multi‐allergen tests Phadiatop and fx5 (ImmunoCAP) and grouped based on the baseline allergen‐specific IgE antibody (sIgE) concentration: <0.10, 0.10–0.34, and ≥0.35 kUA/L. The relationship between changes (Δ values) in type‐2 biomarkers (individualized fraction of exhaled nitric oxide [FeNO%], blood eosinophil [B‐Eos] count, total IgE [tIgE] and sIgE, lung function [% predicted forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC)], and Asthma Control Test [ACT]) score were determined.ResultsAt follow up, FEV1 and FEV1/FVC had decreased (93.6% vs. 95.8%, and 93.4% vs. 94.7% of predicted, respectively [p < 0.001 both]), whereas ACT score had increased (21.6 vs. 20.6, p = 0.001). A significant decline in lung function was seen in subjects with sIgE ≥ 0.10 kUA/L, but not in those with undetectable sIgE (<0.10 kUA/L). Furthermore, tIgE and sIgE declined over time (p < 0.001 all) whereas FeNO% and B‐Eos count were not significantly changed. In univariate analysis, significant negative correlations between ∆B‐Eos count and ∆FeNO%, on one hand, and changes in lung function, on the other hand, were seen, and multivariate analysis showed an independent relationship between ΔFeNO%, and ΔFEV1 (p < 0.05) and ΔFEV1/FVC% (p < 0.01). Sex‐specific analysis showed that the independent association between ΔFeNO%, and ΔFEV1 remained only in females (p = 0.005), and there was a significant interaction with sex (p = 0.02).ConclusionIn young asthmatics, IgE levels declined over 43 months, whereas FeNO and B‐Eos remained unchanged. In spite of improved asthma control, an accelerated lung function decline was seen in patients with detectable sIgE at baseline, and the decline correlated with changes in type‐2 biomarkers. Particularly, the increase in individualized FeNO associated independently with decline in FEV1 in females.

An asthma plan

An asthma plan

Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps

Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) is a common disease that is characterized by multiple inflammatory endotypes. However, the molecular mechanisms in CRSsNP are poorly understood compared with those of polypoid CRS. Our aim was to identify mechanisms and biomarkers associated with inflammatory endotypes underpinning CRSsNP. Ethmoid tissues and nasal lavage fluids (NLFs) were obtained from control patients and patients with CRS. The gene expression profiles were determined by microarray analysis and quantitative RT-PCR, and expression of proteins was measured by ELISA and Luminex analysis. Microarray found that compared with their levels of expression in control tissue, the levels of expression of 126, 241, and 545 genes were more than 3-fold and significantly elevated in CRSsNP with type 1 (T1) endotype, type 2 (T2) endotype, and type 3 (T3) endotype, respectively. Selected identified genes were confirmed by RT-PCR. Gene set enrichment analysis suggested that T1 CRSsNP was associated with IFN-γ signaling and antiviral immunity controlled by T cells (TH1 and CD8+), natural killer cells, and antigen-presenting cells; T2 CRSsNP was associated with STAT6 signaling and IgE-mediated activation controlled by eosinophils, mast cells, TH2 cells, group 2 innate lymphoid cells, and antigen-presenting cells; and T3 CRSsNP was associated with IL-17 signaling, acute inflammatory response, complement-mediated inflammation, and infection controlled by neutrophils, TH17 cells, B cells, and antigen-presenting cells. The results suggest that T1 (CXCL9 and CXCL10), T2 (eosinophilic proteins and CCL26), and T3 (CSF3) endotypic biomarkers in NLF may be able to distinguish tissue endotypes in CRSsNP. Inflammatory endotypes in CRSsNP were controlled by different molecular mechanisms. NLF biomarker assays may allow for more precise and personalized medicaltreatments in CRS.

The Prevalence of Subtypes of Type 2 Inflammation in an Unselected Population of Patients with Severe Asthma

With the introduction of different targeted therapies for type 2 (T2)-high asthma, there is an urgent need for markers to guide the choice of treatment. T2-high asthma includes different clinical phenotypes of asthma, but the prevalence and impact of activation of different T2 inflammatory pathways is unknown. To describe the level of coexpression of clinically available T2 inflammatory markers in patients with severe asthma, and the relationship with clinical characteristics and comorbidities. Patients with severe asthma according to European Respiratory Society/American Thoracic Society guidelines were examined prospectively including sputum induction and grouped according to T2 biomarkers: blood eosinophilia (≥0.3× 109/L), total IgE (≥150 U/mL), and fractional exhaled nitric oxide (≥25 parts per billion). We found 116 (70%) of the 166 patients to have at least 1 T2 biomarker elevated: 39% had 2 or more elevated biomarkers, whereas 31% had only 1 biomarker elevated. Concomitant airway and systemic eosinophilia was present in 28% of all patients, corresponding to half (53%) of the patients with either. Expression patterns of the T2 biomarkers were associated with differences in allergic sensitization and the coexistence of nasal polyposis. Most patients with severe asthma showed at least 1 T2 inflammatory trait. Coexpression of T2 biomarkers was highly heterogeneous, and different expression patterns were associated with distinct clinical characteristics.

Ne 2 tipo sunkios astmos diagnostikos ir gydymo galimybės

Įrodyta, jog 2 tipo astma bei eozinofilinis kvėpavimo takų uždegimas nustatomas dviem trečdaliams sergančių sunkia astma pacientų. Jam būdinga padidėjęs eozinofilų skaičius kraujyje, didesnė serumo imunoglobulino E (IgE) ir frakcinė iškvepiamo azoto oksido (FeNO) koncentracijos. Tačiau trečdaliui sergančiųjų sunkia astma vis dėlto stebimi ne 2 tipo astmai būdingi požymiai.Nepaisant to, kad klinikinėje praktikoje vartojami vis nauji vaistai sunkiai astmai gydyti ir dažnai pabrėžiama individualaus sunkios astmos gydymo parinkimo svarba, šiuo metu specifinis sunkios astmos gydymas biologiniais vaistais yra galimas tik esant 2 tipo astmai (eozinofiliniam fenotipui). Deja, ne 2 tipo astmai būdingiems fenotipams (neutrofilinei ir paucigranuliocitinei astmai) patvirtinto veiksmingo medikamentinio gydymo kol kas nėra.

The effects of oral corticosteroids on lung function, type-2 biomarkers and patient-reported outcomes in stable asthma: A systematic review and meta-analysis

BackgroundSeveral studies have investigated the physiological effect of OCS in stable asthma, however these have included heterogeneous populations and outcomes. This paper is the first to combine their results. MethodsWe searched Medline, Embase and Web of Science databases for studies reporting the impact of OCS on FEV1, FVC, blood eosinophils, fractional exhaled nitric oxide (FeNO), Asthma Control Questionnaire (ACQ) score or Asthma Quality Of Life Questionnaire (AQLQ) score in stable asthma. We extracted data on the correlates of OCS response. Results61 studies, comprising 1608 patients, were included. FEV1 was improved by 9% (95% CI: 7, 11). There were stronger increases in FEV1 among those with a mean baseline FEV1<60% predicted (19%, 95% CI: 13, 24). Despite these improvements, substantial residual impairment remained after treatment. Blood eosinophils were reduced by 76% (95% CI: 63, 88) with larger decreases in studies of corticosteroid-naïve patients (93%, 95% CI: 73,100). Sputum eosinophils were reduced by 89% (95% CI: 79, 98) while FeNO was decreased by 35% (95% CI: 28, 41). ACQ scores were reduced by 20% (95% CI: 11, 29). Patients with higher baseline lung function impairment, sputum eosinophils, blood eosinophils and FeNO had improved OCS response. InterpretationOCS consistently improves lung function, reduces markers of type-2 inflammation, and alleviates asthma symptoms. However, substantial residual impairment remained following treatment and mean improvements were below the minimally important clinically difference. Patients with increased markers of type-2 inflammation are more responsive to treatment, suggesting these should be used to better target OCS use.

Composite type-2 biomarker strategy versus a symptom–risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial

SummaryBackgroundAsthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide [FENO], blood eosinophils, and serum periostin) with a standardised symptom–risk-based algorithm (control).MethodsWe did a single-blind, parallel group, randomised controlled trial in adults (18–80 years of age) with severe asthma (at treatment steps 4 and 5 of the Global Initiative for Asthma) and FENO of less than 45 parts per billion at 12 specialist severe asthma centres across England, Scotland, and Northern Ireland. Patients were randomly assigned (4:1) to either the biomarker strategy group or the control group by an online electronic case-report form, in blocks of ten, stratified by asthma control and use of rescue systemic steroids in the previous year. Patients were masked to study group allocation throughout the entirety of the study. Patients attended clinic every 8 weeks, with treatment adjustment following automated treatment-group-specific algorithms: those in the biomarker strategy group received a default advisory to maintain treatment and those in the control group had their treatment adjusted according to the steps indicated by the trial algorithm. The primary outcome was the proportion of patients with corticosteroid dose reduction at week 48, in the intention-to-treat (ITT) population. Secondary outcomes were inhaled corticosteroid (ICS) dose at the end of the study; cumulative dose of ICS during the study; proportion of patients on maintenance oral corticosteroids (OCS) at study end; rate of protocol-defined severe exacerbations per patient year; time to first severe exacerbation; number of hospital admissions for asthma; changes in lung function, Asthma Control Questionnaire-7 score, Asthma Quality of Life Questionnaire score, and T2 biomarkers from baseline to week 48; and whether patients declined to progress to OCS. A secondary aim of our study was to establish the proportion of patients with severe asthma in whom T2 biomarkers remained low when corticosteroid therapy was decreased to a minimum ICS dose. This study is registered with ClinicalTrials.gov, NCT02717689 and has been completed.FindingsPatients were recruited from Jan 8, 2016, to July 12, 2018. Of 549 patients assessed, 301 patients were included in the ITT population and were randomly assigned to the biomarker strategy group (n=240) or to the control group (n=61). 28·4% of patients in the biomarker strategy group were on a lower corticosteroid dose at week 48 compared with 18·5% of patients in the control group (adjusted odds ratio [aOR] 1·71 [95% CI 0·80–3·63]; p=0·17). In the per-protocol (PP) population (n=121), a significantly greater proportion of patients were on a lower corticosteroid dose at week 48 in the biomarker strategy group (30·7% of patients) compared with the control group (5·0% of patients; aOR 11·48 [95% CI 1·35–97·83]; p=0·026). Patient choice to not follow treatment advice was the principle reason for loss to PP analysis. There was no difference in secondary outcomes between study groups and no loss of asthma control among patients in the biomarker strategy group who reduced their corticosteroid dose.InterpretationBiomarker-based corticosteroid adjustment did not result in a greater proportion of patients reducing corticosteroid dose versus control. Understanding the reasons for patients not following treatment advice in both treatment strategies is an important area for future research. The prevalence of T2 biomarker-low severe asthma was low.FundingThis study was funded, in part, by the Medical Research Council UK.

Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease.

Airway inflammation in chronic obstructive pulmonary disease (COPD) is typically thought to be driven by Type1 immune responses, while Type2 inflammation appears to be present in definite proportions in the stable state and during exacerbations. In fact, some COPD patients showed gene expression of Type2 inflammation in the airway, and this subset was associated with the inhaled corticosteroid (ICS) response. Interestingly enough, the relationship between COPD and diseases associated with Type2 inflammation from the perspective of impaired lung development is increasingly highlighted by recent epidemiologic studies on the origin of COPD. Therefore, many researchers have shown an interest in the prevalence and the role of existent Type2 biomarkers such as sputum and blood eosinophils, exhaled nitric oxide fraction, and atopy, not only in asthma but also in COPD. Although the evidence about Type2 biomarkers in COPD is inconsistent and less robust, Type2 biomarkers have shown some potential when analyzing various clinical outcomes or therapeutic response to ICS. In this article, we review the existent and emerging Type2 biomarkers with clinically higher applicability in the management of COPD.

Type 2 Inflammatory Biomarker Response After Exercise Challenge Testing.

IntroductionExercise-induced bronchoconstriction is due to osmotic stimulus of the airway epithelium and leads to a cascade of biomarker release from several inflammatory cells. Several type 2 (T2) mediators have been linked to exercise-induced bronchoconstriction, but the T2 response per se has not been described during exercise. The aim of this study was therefore to investigate T2 biomarkers in plasma and urine from subjects with asthma and healthy controls before and after an exercise challenge.MethodsTwenty-two subjects with mild asthma and 18 healthy controls performed an exercise challenge test on a treadmill, and fractional exhaled NO (FeNO) was measured at baseline. Blood and urine samples were collected repeatedly during 60 min after the test and Interleukin-13 (IL-13), thymus and activation-related chemokine (TARC), periostin and leukotrienes were measured.ResultsAsthmatics and controls showed similar levels of IL-13, TARC, periostin and Cys-LT in plasma at baseline, and there were no differences in baseline levels between subjects with a negative and positive exercise challenge. After exercise, there was an overall increase in interleukin-13 (IL-13) in plasma in all subjects (p<0.001), with a peak at 10 min after the exercise challenge in both the asthmatic and control group. An increase in TARC in plasma was also seen (p<0.001), but only in the control subjects. In contrast, Cys-LT in plasma showed an overall decrease in all subjects (p<0.001), while periostin in plasma did not change. In conjunction with plasma, the level of IL-13 was increased in urine 30 min after the exercise challenge (p=0.002) and decreased again at 60 min (p=0.004). Similarly, leukotriene E4 (LTE4) was increased in urine samples, with a peak at 60 min and most pronounced in asthmatic subjects (p<0.001) but was seen also in controls (p=0.008).DiscussionIn conclusion, circulating levels of IL-13 are increased after exercise to the same extent in asthmatics and healthy control subjects, which indicates a physiological rather than a pathophysiological response. Also, the levels of TARC and leukotrienes were affected after exercise.

Are type-2 biomarkers of any help in asthma diagnosis?

T2 biomarkers lack the accuracy to make an asthma diagnosis in patients with suggestive symptoms https://bit.ly/3hYnnHu

Detection of type2 biomarkers for response in COPD

Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory lung disease. It is important to identify patients who would respond to anti-inflammatory treatment. This prospective study aims to determine how inflammatory biomarkers could be used to predict the potential effect of inhaled corticosteroids (ICS) in terms of symptoms and lung function. We evaluated the levels of blood eosinophils, exhaled nitric oxide fraction at a flow rate of 50 ml s−1 (FeNO), alveolar nitric oxide concentration (Calv), immunoglobulin E and atopy in 43 patients with symptomatic COPD and correlated these expression levels with the changes in the COPD Assessment Test (CAT) and lung function by 12 weeks of add-on therapy with ciclesonide 400 μg d−1 on bronchodilators. The mean changes in the CAT score and FEV1 were −1.4 points and +90 ml, respectively, with significant variation in the levels of change. The area under the receiver’s operating characteristic curve (AUC) for FeNO in predicting improvements in both the CAT score and FEV1 was 0.92. The AUC for Calv and blood eosinophils was 0.82 and 0.65. Two cutoffs were chosen, one corresponding to a high value of FeNO associated with certainty for response inclusion (FeNO = 35 ppb; sensitivity = 0.67, specificity = 0.94; positive predictive value = 0.80) and the other with certainty for response exclusion (FeNO = 20 ppb; sensitivity = 1.00, specificity = 0.58, negative predictive value = 1.00). Baseline FeNO values were significantly correlated with changes in FEV1 and CAT (all p < 0.0001). FeNO could be a valuable biomarker for identifying individuals who respond to steroid therapy among patients with symptomatic COPD in terms of symptoms and airflow limitation. The study was prospectively registered with the University Hospital Medical Information Network (UMIN) in Japan (protocol ID 000010711).

Change in type-2 biomarkers and related cytokines with prednisolone in uncontrolled severe oral corticosteroid dependent asthmatics: an interventional open-label study

Type-2 biomarkers and related cytokines (IL-5, IL-13), lung function and asthma symptoms were measured in 44 poorly-controlled severe oral corticosteroid (OCS)-dependent asthmatics for up to 88 days after a 7-day...

EFFECTS OF OMALIZUMAB ON MARKERS OF TYPE 2 INFLAMMATION: RESULTS FROM THE EXTRA STUDY

Introduction Targeting type 2 (T2) inflammation in moderate-to-severe asthma with omalizumab improves asthma control and reduces exacerbations. Whether omalizumab impacts T2 inflammatory biomarkers has not been fully elucidated. We examined the impact of omalizumab on T2 inflammatory biomarkers. Methods Post-hoc analyses of moderate-to-severe, uncontrolled allergic asthmatics (12-75 years) from the prospective, randomized, placebo-controlled trial of omalizumab, EXTRA were conducted. Changes from baseline in fractional exhaled nitric oxide (FeNO), blood eosinophils (EOS) and serum interleukin-13 (IL-13) with omalizumab versus placebo were evaluated. FeNO was measured at Weeks 4, 8, 16, 32, and 48, EOS at Weeks 16, 32 and 48, and IL-13 at Week 16. FeNO was further analyzed using dichotomized baseline subgroups with cutoff points at 25ppb or 50ppb. Results Compared with placebo, omalizumab-treated patients had larger decreases in all T2 biomarkers throughout treatment. At Week 48, median [IQR]% changes of -13.1 [-43.9, 26.6]% versus 0 [-28.9, 40]% and -11.1 [-48.5, 36.2]% versus 0.0 [-36.0, 40.0]% were observed in the omalizumab and placebo-treated groups for EOS and FeNO, respectively. FeNO reductions were observed by Week 4 and were greater in omalizumab-treated patients with higher baseline FeNO (-60.2 [-71.6, -26.8]% versus -4.6 [-34.2, 42.3]% in ≥50 versus Conclusions Omalizumab treatment reduced T2 inflammatory biomarkers. Reductions were more pronounced in patients with higher baseline levels. These findings highlight the anti-inflammatory effects of omalizumab. FeNO percent change upon omalizumab treatment by baseline levels.