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We investigated the time course of change of type-2 asthma biomarkers after a severe asthma exacerbation. Blood eosinophils were lowest immediately after treatment was initiated (0.07 vs 0.33×10 9 /L, p<0.001) while serum IgE levels were at their highest (339 vs 249 U/L, p<0.001). Fractional exhaled Nitric Oxide levels were lowest 2 weeks after treatment (23 vs 33 ppb, p=0.06) and serum periostin levels were lowest 1 week after treatment (45·9 vs 50·9 ng/mL, p<0.001). A delay of 4-8 weeks following a severe exacerbation is required if these biomarkers are used to guide the ongoing management of patients with asthma. TRIAL REGISTRATION NUMBER: Post-results; The Australia New Zealand Trial Registry, >ACTRN12614000443695., Competing Interests: Competing interests: CH and JM are employees of Genentech Inc., a member of the Roche group. RB reports grants from Genentech during the conduct of the study; personal fees from Health Research Council of New Zealand, Glaxo Smith Kline, AstraZeneca, and Novartis outside the submitted work; grants from AstraZeneca, Chiese, Cephalon, Genentech, Novartis and Sanofi Aventis outside the submitted work. Other authors have no competing interests to declare., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Type 2 biomarkers that predict both likelihood of future severe exacerbations and response to mAb therapy in asthma would be useful clinically in identifying patients both at greater risk of hospitalization and most likely to benefit from mAb therapy., Objective: To describe the association between type 2 biomarkers, blood eosinophils, fractional exhaled nitric oxide (Feno), serum periostin, and serum IgE, and time to severe exacerbation in a broad asthma population., Methods: Participants from 2 adult asthma cohorts with baseline measurements of blood eosinophils, Feno, serum periostin, and serum IgE were reviewed after at least 12 months to obtain an exacerbation history, corroborated with general practitioner and hospital medical records. The association between baseline type 2 biomarkers and time to exacerbation was described by Cox proportional hazard ratios (HRs) using multivariate models., Results: A total of 212 participants were followed for a median (range) 3.8 (1.1-5.3) years; 67 of 212 (32%) had at least 1 severe exacerbation. The HRs (95% CI) of baseline type 2 biomarkers and time to exacerbation were as follows: blood eosinophils per 0.1 × 10 9 /L increase, 0.89 (0.76-1.05), P = .17; log Feno per 0.693 increase, 0.65 (0.52-0.81), P < .001; log serum periostin per 0.693 increase, 0.62 (0.35-1.09), P = .10; log serum IgE per 0.693 increase, 0.89 (0.80-1.00), P = .05., Conclusions: The positive association between type 2 biomarkers and risk of severe exacerbations in populations with severe refractory asthma does not extend to mild and moderate asthma. Non-type 2 asthma may represent a phenotype associated with an increased risk of severe exacerbations in a broad asthma population., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Different ages of asthma onset can lead to similar clinical symptoms but have different underlying mechanisms that may influence treatment response. This post-hoc analysis assessed response to omalizumab in relation to the age of asthma onset. Using pooled data from two phase III studies (patients 12–75 years), changes in exacerbation rates, forced expiratory volume in 1 second (FEV1) and inhaled corticosteroids (ICS) were assessed by age of asthma onset (<18 [n = 574], 18– 40 [n = 360], >40 years [n = 136]). Exacerbations (week 16) were reduced with omalizumab versus placebo in all subgroups (relative rate reduction [95% confidence interval]: <18, (53.1% [–73.6,–16.6]; 18–40, (68.3% [–85.5,–31.0]; >40, (38.4% [–77.3,67.4]). FEV1 increased with omalizumab in all subgroups; increases were sustained in <18 and 18–40 years subgroups, but not in >40 years subgroup. ICS dose reductions (week 28) were greater with omalizumab versus placebo, regardless of age of asthma onset, as were percentages of patients with ICS doses reduced by at least 50% and 100%. In conclusion, omalizumab-treated patients had lower exacerbation rates and were more frequently able to reduce/ discontinue ICS versus placebo, regardless of age of asthma onset, therefore omalizumab may be beneficial to all eligible patients with allergic asthma. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with variable underlying pathophysiologies. Numerous patient factors have been linked to differences in disease severity, control, and response to treatment, including asthma status, aspirin sensitivity, previous sinonasal surgery, and blood eosinophil levels. Objective: The present study examines the efficacy of the anti-immunoglobulin E therapy, omalizumab, versus placebo in patients with CRSwNP from the replicate POLYP 1 (NCT03280550) and POLYP 2 (NCT03280537) trials, grouped by inherent patient characteristics to determine the response to therapy. Methods: Patients in prespecified subgroups from POLYP 1 and POLYP 2 (studies pooled for analysis) were examined. Subgroups included blood eosinophil count at baseline (>300 or ≤300 cells/μL), previous sinonasal surgery (yes or no), asthma status (yes or no), and aspirin sensitivity status (yes or no). Subgroups were examined for subgroup-specific adjusted mean difference (95% confidence interval [CI]) (omalizumab–placebo) in change from baseline at week 24 in Nasal Congestion Score (NCS), Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), Total Nasal Symptom Score (TNSS), and University of Pennsylvania Smell Identification Test (UPSIT). Results: Adjusted mean difference (95% CI) (omalizumab–placebo) in NCS, NPS, SNOT-22, TNSS, and UPSIT change from baseline at week 24 consistently favored omalizumab treatment over placebo in patients with blood eosinophil count >300 and ≤300 cells/μL, with or without previous sinonasal surgery, asthma, and aspirin sensitivity. Conclusion: Together, these data suggest broad efficacy of omalizumab across clinical and patient-reported outcomes in patients with CRSwNP, independent of the underlying patient factors examined, including those with high eosinophil levels and those who have undergone previous surgery, which are associated with high recurrence. Clinical Trial Registration: ClinicalTrials.gov identifiers: POLYP 1: ClinicalTrials.gov identifier NCT03280550 (https://clinicaltrials.gov/ct2/show/NCT03280550); POLYP 2: ClinicalTrials.gov identifier NCT03280537 (https://clinicaltrials.gov/ct2/show/NCT03280537). [ABSTRACT FROM AUTHOR]

Background: Current biologic therapies target allergic, eosinophilic or type 2 inflammation phenotypic asthma. However, frequency and degree of overlap among these subtypes is unclear. Objective: To characterize overlap among allergic, eosinophilic and type 2 asthma phenotypes. Methods: Post hoc analyses of baseline data were performed in two adult populations: (a) not selected for any asthma subtype (N = 935) and (b) selected for allergic asthma (N = 1049). Degree of overlap was examined using commonly accepted phenotypic definitions to guide treatment for allergic asthma (skin prick–positive and/or positive serum–specific immunoglobulin E > 0.35 kU/L) and eosinophilic asthma (blood eosinophil high count ≥ 300 cells/µL; low cut‐off ≥ 150 cells/µL). Consistent with previous studies, fractional exhaled nitric oxide high level of ≥ 35 ppb and low cut‐off of ≥ 25 ppb were selected as local markers of type 2 inflammation and to prevent overlap with the systemic eosinophilic asthma definition. Results: In the non‐subtype–selected population, 78.0% had allergic asthma; of these, 39.5% had eosinophilic asthma and 29.5% had type 2 asthma. Within patients with eosinophilic asthma (40.6% of total), 75.8% had allergic asthma and 41.3% had type 2 asthma. Within patients with type 2 asthma (28.3% of total), 81.1% had allergic asthma and 59.2% had eosinophilic asthma. In the allergic asthma–selected population, 38.3% had eosinophilic asthma and 29.2% had type 2 asthma. Within patients with eosinophilic asthma, 46.3% had type 2 asthma. Within patients with type 2 asthma, 60.8% had eosinophilic asthma. Overlaps among subtypes increased at low cut‐off values. Conclusions and clinical relevance: In this post hoc analysis in adults with moderate‐to‐severe asthma, allergic asthma was the most prevalent phenotype, followed by eosinophilic and type 2 asthma. Despite observed overlaps, a considerable proportion of patients had only a predominantly allergic subtype. Understanding the degree of overlap across phenotypes will help patient management and guide treatment options. [ABSTRACT FROM AUTHOR]