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Original Research: Asthma |

Omalizumab Treatment Response in a Population With Severe Allergic Asthma and Overlapping COPD FREE TO VIEW

Steven Maltby, PhD; Peter G. Gibson, MBBS; Heather Powell, MMedSc; Vanessa M. McDonald, PhD, B Nurs, RN
Author and Funding Information

FUNDING/SUPPORT: The Australian Xolair Registry was supported by Novartis Pharmaceuticals Australia Pty Ltd as an investigator-sponsored study. Preparation of this article was made possible through funding from the National Health and Medical Research Council (NHMRC) Centre of Excellence in Severe Asthma (APP1078579, www.severeasthma.org.au).

aNational Health and Medical Research Council Centre of Excellence in Severe Asthma, the University of Newcastle, Newcastle, Australia

bPriority Research Centre for Healthy Lungs, the University of Newcastle, Newcastle, Australia

cHunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia

dDepartment of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, Australia

CORRESPONDENCE TO: Vanessa M. McDonald, PhD, B Nurs, RN, Centre of Excellence in Severe Asthma, Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, Faculty of Health and Medicine, The University of Newcastle, Level 2 West Wing, Locked Bag 1000, Newcastle, New Lambton, NSW 2305, Australia


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(1):78-89. doi:10.1016/j.chest.2016.09.035
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Published online

Background  Asthma and COPD are common airway diseases. Individuals with overlapping asthma and COPD experience increased health impairment and severe disease exacerbations. Efficacious treatment options are required for this population. Omalizumab (anti-IgE) therapy is effective in patients with severe persistent asthma, but limited data are available on efficacy in populations with overlapping asthma and COPD.

Methods  Data from the Australian Xolair Registry were used to compare treatment responses in individuals with asthma-COPD overlap with responses in patients with severe asthma alone. Participants were assessed at baseline and after 6 months of omalizumab treatment. We used several different definitions of asthma-COPD overlap. First, we compared participants with a previous physician diagnosis of COPD to participants with no COPD diagnosis. We then made comparisons based on baseline lung function, comparing participants with an FEV1 < 80% predicted to those with an FEV1 > 80% predicted after bronchodilator use. In the population with an FEV1< 80%, analysis was further stratified based on smoking history.

Results  Omalizumab treatment markedly improved asthma control and health-related quality of life in all populations assessed based on the Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores. Omalizumab treatment did not improve lung function (FEV1, FVC, or FEV1/FVC ratio) in populations that were enriched for asthma-COPD overlap (diagnosis of COPD or FEV1 < 80%/ever smokers).

Conclusions  Our study suggests that omalizumab improves asthma control and health-related quality of life in individuals with severe allergic asthma and overlapping COPD. These findings provide real-world efficacy data for this patient population and suggest that omalizumab is useful in the management of severe asthma with COPD overlap.

Figures in this Article

Asthma and COPD are common obstructive airway diseases., These diseases may overlap, resulting in greater health impairment and more frequent and severe exacerbations than observed in individuals with asthma or COPD alone.,,,, The challenges related to the clinical management of patients with an overlap of asthma and COPD are increasingly recognized, prompting the development of a consensus-based document by the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease. Improving outcomes for this population and determining efficacious treatment options are high priorities.

Asthma-COPD overlap is an umbrella term that encompasses several different phenotypes, such as eosinophilic COPD, severe asthma with incomplete airflow reversibility, and asthma with smoking. This has prompted calls to further evaluate patients for specific mechanistic pathways (endotypes) and then to target specific treatments for each mechanistic pathway, rather than treating based on a disease label.

There are promising new targeted therapies for the treatment of severe treatment-refractory asthma that target the T-helper (Th)2/eosinophilic/allergic pathways in asthma. These pathways can also occur in COPD,,; however, a diagnosis of COPD is typically an exclusion criterion for clinical trials in asthma and vice versa., As a result, limited clinical data exist on the efficacy of these treatments in a population with overlapping asthma and COPD.

Omalizumab (Xolair) is an effective therapy for patients with severe persistent asthma,,,,,,,,,,,,,,,,,; it acts by binding to serum IgE, reducing mast cell, basophil, dendritic cell, and B-cell responses.,,,, To date, there are limited data available on the efficacy of omalizumab in populations with overlapping asthma and COPD.

The Australian Xolair Registry (AXR) was established to evaluate the real-world use of omalizumab for treatment-resistant severe allergic asthma in Australia. This registry captured a significant proportion of all Australians prescribed omalizumab (n = 177) and provides the opportunity to assess treatment response in patients with overlapping COPD. Analysis of the AXR population provides unbiased and structured insight into the real-world patient population receiving treatment.

The aim of this study was to determine the efficacy of omalizumab treatment in individuals with severe allergic asthma and overlapping COPD. Further, we aimed to compare treatment response in participants with asthma-COPD overlap and participants with severe allergic asthma alone. We hypothesized that response to omalizumab treatment would be similar in both populations.

Study Design

The AXR is an investigator-initiated and led multicenter noninterventional observational study that recruited patients with severe allergic asthma who were being assessed for eligibility and commencement of government-subsidized omalizumab through the Australian Pharmaceutical Benefits Scheme., Participants with severe allergic asthma were enrolled between October 2011 and June 30, 2014, and assessments were performed at baseline and after 6 months of omalizumab treatment. To be eligible for subsidized omalizumab through the Australian Pharmaceutical Benefits Scheme, and thus be part of the registry, participants needed to demonstrate that they had severe uncontrolled allergic asthma despite high-dose inhaled corticosteroids (ICS) and long-acting beta agonists, with optimal inhaler technique and adherence. This was determined using the following criteria: a confirmed diagnosis of asthma, being in the care of a respiratory physician or allergist for at least 12 months, a duration of asthma for at least 1 year, an FEV1 < 80%, an Asthma Control Questionnaire (ACQ-5) score ≥ 2, and treatment with 1,000 μg of a fluticasone propionate equivalent and at least salmeterol 50 μg bid or eformoterol 12 μg bid. Prior use of oral corticosteroids was also required. Inhaler technique and adherence were assessed and deemed optimal by the prescribing physicians.

The study was approved by the Hunter New England Human Research Ethics Committee (HNEHREC Ref: 11/10/19/5.03). Participants provided written informed consent on entry into the data registry.

Assessments

Data were collected prospectively at enrollment and at 6 months after initiating omalizumab therapy, as previously described. The baseline demographic and clinical variables collected included age, sex, duration of allergic asthma, comorbid disease profile (including atopy, rhinitis, eczema, and anaphylaxis), asthma therapy, and asthma control. FEV1, FVC, and the FEV1/FVC ratio were also collected, when possible both before and after bronchodilator (BD) use. Asthma control and health status was recorded using the five-item Asthma Control Questionnaire (ACQ-5) and the Asthma Quality of Life Questionnaire (AQLQ).

Asthma-COPD Overlap Definitions

We assessed the response to omalizumab treatment in an asthma-COPD overlap population, using several different definitions that have been reported in the literature. A total of 177 participants in the AXR cohort had baseline and 6-month follow-up data available for assessment. All participants were prescribed high-dose ICS and long-acting beta-agonists. We performed two primary comparisons of this data set. In the first analysis, we compared participants with a previous physician diagnosis of COPD (n = 17) and a population with no COPD diagnosis (n = 160). The second analysis involved a subpopulation of the AXR registry with post-BD spirometry data available at baseline (n = 72). Individuals with post-BD FEV1 > 80% predicted (n = 17) were compared with those with an FEV1 < 80% (n = 55). We further stratified the FEV1 < 80% group based on available smoking history (n = 47) and compared never smokers (n = 36) with ever smokers (n = 11).

Statistical Analysis

Statistical analysis was performed using Stata 13 (StataCorp LP). Baseline features for the first and second analyses were performed using the χ2 or Fisher exact test for categorical data and the Student t test or Wilcoxon rank sum test for continuous data, as appropriate. Further comparison of baseline features for the second analysis were performed using one-way analysis of variance or the Kruskal-Wallis test, as appropriate, with a Bonferroni correction for multiple comparisons. Paired analyses were conducted on baseline and follow-up clinical, quality of life, and medication data to determine response to omalizumab treatment, using the McNemar χ2 or exact test for categorical data or the Wilcoxon signed rank test for continuous data. A P value < .05 was considered significant.

Omalizumab in Physician-Diagnosed COPD

A higher prevalence of previous smoking was observed in the population with severe allergic asthma and concomitant physician-diagnosed COPD (66.7% vs 25.3%; P = .002). Participants with physician-diagnosed COPD were older (62.3 vs 50.3 years of age; P = .002) and had higher rates of eczema (29.4% vs 10.6%; P = .026), but there were no further differences in the baseline characteristics (Table 1).

Table Graphic Jump Location
Table 1 Baseline Participant Characteristics for Physician Diagnosis of COPD
a Data are presented as mean (SD); Student t test.
b Data are presented as No. (%); χ2 or Fisher exact test.
c Data are presented as median (quartile 1, quartile 3); Wilcoxon rank sum test.

Boldface indicates statistical significance (P < .05). ACQ-5 = Asthma Control Questionnaire; AQLQ = Asthma Quality of Life Questionnaire; BD = bronchodilator; BDP = beclometasone dipropionate equivalent; ICS = inhaled corticosteroids; OCS = oral corticosteroids.

Asthma control and health-related quality of life (HRQoL) significantly improved in those with severe allergic asthma and physician-diagnosed COPD (ACQ-5 score at baseline improved from 3.68 to 1.69 after omalizumab treatment; P < .0001; AQLQ score improved from 4.03 to 5.56; P < .016) (Fig 1A, B, e-Fig 1). A similar degree of improvement was observed in participants without physician-diagnosed COPD (ACQ-5 score from 3.49 to 1.99; P < .0001; AQLQ score from 3.47 to 4.61; P < .0001) (Fig 1A, B, e-Fig 1). Improvements were observed for all domains of the AQLQ in both populations, with the exception of the activity component in the COPD-diagnosed population (e-Table 1). All improvements exceeded the minimal clinically important difference (0.5-point improvement) for each assessment.

Figure 1
Figure Jump LinkFigure 1 Comparisons based on physician diagnosis of COPD. A, Asthma control (ACQ-5). B, Health-related quality of life (AQLQ) questionnaire scores. C and D, Pre-BD and post-BD FEV1/FVC results at baseline (red bars) and 6-month follow-up of omalizumab therapy (blue bars). Graphs represent mean ± SD. *P < .05, *** P < .001, ****P < .0001. ACQ-5 = Asthma Control Questionnaire; AQLQ= Asthma Quality of Life Questionnaire; BD = bronchodilator.Grahic Jump Location

At 6-month follow-up, improved lung function was observed after omalizumab treatment in the non-COPD diagnosed population, for pre-BD FEV1 (from 57.6% to 63.1%; P = .02) and the FEV1/FVC ratio (from 58.5% to 62.1%; P = .009) and the post-BD FEV1/FVC ratio (from 58.0% to 64.3%; P = .0003) (Fig 1C, D, e-Fig 1). No improvement was seen in lung function (pre-BD or post-BD FEV1, FVC, FEV1/FVC ratio) in the COPD-diagnosed population.

Omalizumab in COPD Determined by Spirometry

Participants with severe allergic asthma and a post-BD FEV1 > 80% predicted and those with a post-BD < 80% predicted were compared. Notably, all participants with a physician diagnosis of COPD were in the FEV1 < 80% population.

At baseline, participants with severe allergic asthma and a post-BD FEV1 < 80% had lower FEV1 (pre-BD, 49.3% vs 84.4%; P < .0001; post-BD, 54.6% vs 93.4%), FVC (pre-BD, 73.0% vs 98.1%; P < .0001; post-BD 78.6% vs 105.5%), and FEV1/FVC ratio (pre-BD, 53.5% vs 66.8%; P = .001; post-BD, 55.0% vs 69.1%) (Table 2), as expected based on the categorization of participants. The FEV1 < 80% group also had a significantly longer duration of asthma (26.4 vs 7.9 years; P = .046). When compared based on smoking history, never smokers with a post-BD FEV1 < 80% had a lower baseline pre-BD FEV1 compared with ever smokers (44.7% vs 60.1%) (Table 3). No further differences were observed in medication use or asthma control and HRQoL scores at baseline for either comparison (Tables 2, 3).

Table Graphic Jump Location
Table 2 Baseline Patient Characteristics Based on Post-BD FEV1
a Data are presented as mean (SD); Student t test, Wilcoxon rank sum test.
b Data are presented as No. (%); χ2 or Fisher exact test.
c Data are presented as median (quartile 1, quartile 3).

Boldface indicates statistical significance (P < .05). See Table 1 legend for expansion of abbreviations.

Table Graphic Jump Location
Table 3 Baseline Patient Characteristics Based on Post-BD FEV1 and Smoking History
a Data are presented as mean (SD); one-way analysis of variance.
b Data are presented as No. (%); χ2 or Fisher exact test.
c Data are presented as median (quartile 1, quartile 3); Kruskal-Wallis test.
d Post hoc significance vs post-BD FEV1 % ≥ 80%.
e Post hoc significance vs post-BD FEV1 % < 80% and never smoker.

Boldface indicates statistical significance (P < .05). NA = not available. See Table 1 legend for expansion of other abbreviations.

Again, all populations assessed (regardless of smoking history) had improved asthma control and HRQoL after omalizumab treatment, as measured by the ACQ-5 (Figs 2, 3A, e-Figs 2, 3) and the AQLQ (Figs 2, 3B, e-Figs 2, 3). Improvements in individual domains of the AQLQ questionnaire failed to reach statistical significance in the FEV1 > 80% population and ever smokers, likely due to limited availability of AQLQ data in these populations (FEV1 > 80% population, n = 5; ever smokers, n = 3) (e-Tables 2, 3). Improvements again exceeded the minimal clinically important difference for each assessment, and a similar degree of improvement was observed for each population.

Figure 2
Figure Jump LinkFigure 2 Comparisons based on baseline post-BD FEV1 assessment (> 80% predicted vs < 80%). A, Asthma control (ACQ-5) scores. B, Health-related quality of life (AQLQ) scores. C and D, Pre-BD and post-BD FEV1/FVC spirometry results at baseline (red bars) and 6-month follow-up of omalizumab therapy (blue bars). Graphs represent mean ± SD. ***P < .001, ****P < .0001. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Figure 3
Figure Jump LinkFigure 3 Comparisons based on smoking history (never vs ever smoker) in the post-BD FEV1 < 80% population. A, Asthma control (ACQ-5 questionnaire) scores. B, Health-related quality of life (AQLQ) questionnaire scores. C and D, Pre-BD and post-BD FEV1/FVC spirometry results at baseline (red bars) and 6-month follow-up of omalizumab therapy (blue bars). Graphs represent mean ± SD. *P < .05, ***P < .001, ****P < .0001. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location

At the 6-month follow-up, there was no significant improvement in FEV1, FVC, or the FEV1/FVC ratio in the FEV1 > 80% population after omalizumab treatment (Fig 2, e-Fig 2). In contrast, the FEV1 < 80% population had significant improvements in FEV1 (pre-BD, from 47.8% to 56.6%; P = .006; post-BD, from 55.4% to 65.5%; P = .004) and the FEV1/FVC ratio (pre-BD, from 52.9 to 59.2; P = .002; post-BD, from 53.3 to 60.6; P = .0007) following treatment (Fig 2, e-Fig 2). The FEV1 < 80% population also had a significant decrease in oral corticosteroid use (from 47.3% to 36.4%; P = .031 (e-Table 2). When compared based on smoking history, never smokers had significant improvements in lung function, assessed by FEV1 (pre-BD, from 43.8% to 56.7%; P = .001; post-BD, from 51.9% to 66.1%; P = .001) and the FEV1/FVC ratio (pre-BD, from 51.5 to 59.6; P = .002; post-BD, from 51.9 to 61.1; P = .001) and pre-BD FVC (from 68.8% to 76.3%; P = .04) (Fig 3, e-Fig 3). No improvements were observed in spirometry results (pre-BD or post-BD FEV1, FVC, FEV1/FVC ratio) in the ever smoker population (e-Table 3).

This study suggests that omalizumab improves asthma control and HRQoL in individuals with severe allergic asthma and overlapping COPD. When compared, similar improvements were seen between individuals with overlapping COPD and individuals with severe allergic asthma alone.

Data on the response to omalizumab treatment in asthma-COPD overlap populations are extremely limited. Clinical trials of omalizumab efficacy have typically excluded patients with a physician diagnosis of COPD, which would have excluded approximately 10% of the AXR population. Our assessment provides insights into real-life evaluation of patients with severe allergic asthma. These are important findings, as they contribute new knowledge for managing patients with severe allergic asthma who have an overlapping COPD phenotype—an estimated 20% of the population.

Identification of individuals with asthma-COPD overlap can be complex. The Global Initiative for Chronic Obstructive Lung Disease/GINA recommendations for asthma, COPD, and asthma-COPD overlap provide some guidance. However, adapting these recommendations to the severe treatment-refractory asthma population reveals the real-world difficulties in determining asthma-COPD overlap status in this patient group. Assessment based on lung function measures, such as post-BD FEV1/FVC < 0.7 or FEV1 < 80% predicted includes a large proportion of the population with severe asthma, and does not provide additional insight into patients with potential asthma-COPD overlap. Evidence of BD-mediated reversibility is also proposed as a diagnostic criterion to differentiate asthma from COPD but does not rule out asthma-COPD overlap. Further, reversibility may not be present in severe asthma.

In the AXR population, when assessed based on a preexisting physician diagnosis of COPD, only 17 of 177 participants (9.6%) were classified as having asthma-COPD overlap. This likely underestimates the true population when compared with published prevalence data. Comparison based on a post-BD FEV1 < 80% included 55 of 72 participants (76.4%), which likely overestimates the overlap population. Further stratification based on a smoking history resulted in 11 of 47 participants with a previous smoking history (23.4%). Interestingly, participants with a physician diagnosis of COPD fell within both never smoker and ever smoker categories in our analysis. Although none of these approaches can definitively confirm asthma-COPD overlap status, the use of several diagnostic criteria is a strength of this study, since it allows for assessment of omalizumab treatment effects across different populations. Our analyses represent the real-world situation in which differentiation between severe asthma, COPD, and asthma-COPD overlap is problematic.

Only two publications have previously reported on omalizumab treatment responses in patients with asthma-COPD overlap, with a total of 13 patients., An assessment of 59 patients with severe persistent allergic asthma who were treated with omalizumab identified three patients with asthma-COPD overlap and reported reduced asthma exacerbations and improved asthma control after treatment for 1 year, although no statistical comparisons were performed. A second study of 10 patients with asthma-COPD overlap (definition not provided) found that omalizumab treatment improved lung function (FEV1, peak expiratory flow, and FEV1/FVC) and asthma control. These studies provide support for the efficacy of omalizumab treatment in a small number of patients with both severe asthma and COPD. However, these findings are from a very small number of participants and provide no insight into how responses compare with a matched population of patients with severe asthma without overlapping COPD. These comparisons are a further strength of this present study.

Our data set provides insight into a further 17 patients (based on a physician diagnosis of COPD), as well as populations further enriched for asthma-COPD overlap based on post-BD FEV1 (n = 55) and smoking history (n = 11). Importantly, our findings provide direct comparisons to patients with severe allergic asthma lacking overlapping COPD features. This data set reflects the realities of the difficulty in diagnosing asthma-COPD overlap in this patient population and highlights beneficial response to treatment regardless of overlapping COPD.

Collectively our analyses provide consistent findings on the response to omalizumab treatment in an asthma-COPD overlap enriched population. Across all comparison groups, we observed significant improvements in asthma control and quality of life after treatment, regardless of COPD status. For all groups, these improvements exceeded the minimal clinically important difference, and a similar degree of improvement was seen in all patient populations. These findings indicate that omalizumab treatment has similar efficacy regardless of diagnostic phenotype.

However, no improvement in lung function was observed in populations enriched for asthma-COPD overlap (physician-diagnosed COPD or ever smokers with post-BD FEV1 < 80%). These results are not surprising because of the irreversible nature of COPD and are quite consistent with findings from the omalizumab clinical trials, in which asthma control, HRQoL, and exacerbation rates are consistently reduced, whereas improvement in lung function is quite variable. We did observe improvements in lung function in populations not enriched for asthma-COPD overlap (no physician-diagnosed COPD and never smokers with post-BD FEV1 < 80%). This finding is consistent with several real-life effectiveness studies documenting omalizumab response in individuals with asthma., Further, other targeted therapies such as the interleukin-5Rα monoclonal antibody benralizumab, may improve FEV1 in individuals with COPD.

A growing body of literature has demonstrated a functional role for IgE in some populations with COPD.,,,,,,, A subset of patients with COPD has increased Th2 cytokines and eosinophilic disease, and omalizumab treatment may be beneficial in this population. Indeed, monoclonal antibodies against Th2 cytokines are currently undergoing trials in this population (eg, mepolizumab [anti-interleukin-5] in NCT02105961, NCT02105948, NCT01463644).

Although these results are informative, we acknowledge some limitations. Nonrandom sampling was used to recruit participants for the registry, no placebo group was available to assess for placebo effects, and there are difficulties in defining asthma-COPD overlap. The first analysis was based on a physician diagnosis of COPD, which does not provide objective confirmation of disease. Objective documentation of emphysema (eg, high-resolution CT or diffusion capacity assessment) in this population could be assessed in future studies. Because of insufficient power, we could not assess the potential impact of asthma duration or age on treatment response or possible subphenotypes within the population. Further, our analyses still provide relatively small numbers of patients with overlapping asthma-COPD. Further real-world studies evaluating the effect of omalizumab in an asthma-COPD overlap population will provide additional insights for treatment.

Omalizumab treatment improves asthma control and quality of life in a population with severe allergic asthma and associated COPD. These findings provide real-world efficacy data for this patient population and suggest that omalizumab is useful for management of patients with asthma-COPD overlap.

Author contributions: P. G. is the guarantor of this paper, taking responsibility for the integrity of the work as a whole from inception to published article. H. P. had full access to all of the data in the study and takes responsibility for integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. S. M., P. G. G., H. P., and V. M. M. contributed substantially to the study design, data analysis and interpretation, and writing of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: S. M. has been supported by fellowships from the Canadian Institutes of Health Research (CIHR) and the University of Newcastle and is supported by the NHMRC Centre of Excellence in Severe Asthma. P. G. G. holds an NHMRC Practitioner Fellowship; has participated in educational symposia funded by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Novartis; and has participated in studies funded by GlaxoSmithKline and AstraZeneca. V. M. M. is supported by an NHMRC TRIP fellowship; has participated in educational symposia funded by GlaxoSmithKline, AstraZeneca, Menarini, Boehringer Ingelhiem, and Novartis; has participated in studies funded by GlaxoSmithKline; and is on the advisory boards of GlaxoSmithKline, Novartis, AstraZeneca, and Menarini. None declared (H. P.).

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Collaborators: Members of the Australian Xolair registry team are Peter G. Gibson, Helen Reddel, Vanessa M. McDonald, Guy Marks, Christine Jenkins, Andrew Gillman, John Upham, Michael Sutherland, Janet Rimmer, Frank Thien, Greg P. Katsoulotos, Matthew Cook, Ian Yang, Connie Katelaris, Simon Bowler, David Langton, Paul Robinson, Craig Wright, Veronica Yozghatlian, Scott Burgess, Pathmanathan Sivakumaran, Adam Jaffe, Jeff Bowden, Peter A.B. Wark, Kwok Y. Yan, Vicky Kritikos, Matthew Peters, Mark Hew, Ali Aminazad, Michael Bint, and Michael Guo.

Additional information: The e-Figures and e-Tables can be found in the Supplemental Materials section of the online article.

Reddel H.K. .Bateman E.D. .Becker A. .et al A summary of the new GINA strategy:a roadmap to asthma control. Eur Respir J. 2015;46:622-639 [PubMed]journal. [CrossRef] [PubMed]
 
Vestbo J. .Hurd S.S. .Agusti A.G. .et al Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187:347-365 [PubMed]journal. [CrossRef] [PubMed]
 
McDonald V.M. .Higgins I. .Gibson P.G. . Managing older patients with coexistent asthma and chronic obstructive pulmonary disease: diagnostic and therapeutic challenges. Drugs Aging. 2013;30:1-17 [PubMed]journal. [CrossRef] [PubMed]
 
Gibson P.G. .McDonald V.M. . Asthma-COPD overlap 2015: now we are six. Thorax. 2015;70:683-691 [PubMed]journal. [CrossRef] [PubMed]
 
Miravitlles M. .Soriano J.B. .Ancochea J. .et al Characterisation of the overlap COPD-asthma phenotype. Focus on physical activity and health status. Respir Med. 2013;107:1053-1060 [PubMed]journal. [CrossRef] [PubMed]
 
Hardin M. .Cho M. .McDonald M.L. .et al The clinical and genetic features of COPD-asthma overlap syndrome. Eur Respir J. 2014;44:341-350 [PubMed]journal. [CrossRef] [PubMed]
 
Menezes A.M. .Montes de Oca M. .Perez-Padilla R. .et al Increased risk of exacerbation and hospitalization in subjects with an overlap phenotype: COPD-asthma. Chest. 2014;145:297-304 [PubMed]journal. [CrossRef] [PubMed]
 
Global Initiative for Asthma/Global Initiative for Chronic Obstructive Lung Disease. Diagnosis of Diseases of Chronic Airflow Limitation: Asthma COPD and Asthma-COPD Overlap Syndrome (ACOS), 2015.
 
Agusti A. .Bel E. .Thomas M. .et al Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J. 2016;47:410-419 [PubMed]journal. [PubMed]
 
Grainge C.L. .Maltby S. .Gibson P.G. .Wark P.A. .McDonald V.M. . Targeted therapeutics for severe refractory asthma:monoclonal antibodies. Expert Rev Clin Pharmacol. 2016;9:927-941 [PubMed]journal. [CrossRef] [PubMed]
 
Jamieson D.B. .Matsui E.C. .Belli A. .et al Effects of allergic phenotype on respiratory symptoms and exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188:187-192 [PubMed]journal. [CrossRef] [PubMed]
 
Neves M.C. .Neves Y.C. .Mendes C.M. .et al Evaluation of atopy in patients with COPD. J Bras Pneumol. 2013;39:296-305 [PubMed]journal. [CrossRef] [PubMed]
 
Renkema T.E. .Kerstjens H.A. .Schouten J.P. .Vonk J.M. .Koeter G.H. .Postma D.S. . The importance of serum IgE for level and longitudinal change in airways hyperresponsiveness in COPD. Clin Exp Allergy. 1998;28:1210-1218 [PubMed]journal. [CrossRef] [PubMed]
 
Travers J. .Marsh S. .Caldwell B. .et al External validity of randomized controlled trials in COPD. Respir Med. 2007;101:1313-1320 [PubMed]journal. [CrossRef] [PubMed]
 
Travers J. .Marsh S. .Williams M. .et al External validity of randomised controlled trials in asthma: to whom do the results of the trials apply? Thorax. 2007;62:219-223 [PubMed]journal. [CrossRef] [PubMed]
 
Bardelas J. .Figliomeni M. .Kianifard F. .Meng X. . A 26-week, randomized, double-blind, placebo-controlled, multicenter study to evaluate the effect of omalizumab on asthma control in patients with persistent allergic asthma. J Asthma. 2012;49:144-152 [PubMed]journal. [CrossRef] [PubMed]
 
Chanez P. .Contin-Bordes C. .Garcia G. .et al Omalizumab-induced decrease of FcxiRI expression in patients with severe allergic asthma. Respir Med. 2010;104:1608-1617 [PubMed]journal. [CrossRef] [PubMed]
 
Busse W. .Corren J. .Lanier B.Q. .et al Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108:184-190 [PubMed]journal. [CrossRef] [PubMed]
 
Hanania N.A. .Alpan O. .Hamilos D.L. .et al Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med. 2011;154:573-582 [PubMed]journal. [CrossRef] [PubMed]
 
Busse W.W. .Morgan W.J. .Gergen P.J. .et al Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364:1005-1015 [PubMed]journal. [CrossRef] [PubMed]
 
Gevaert P. .Calus L. .Van Zele T. .et al Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013;131:110-116.e111 [PubMed]journal. [CrossRef] [PubMed]
 
Holgate S.T. .Chuchalin A.G. .Hebert J. .et al Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy. 2004;34:632-638 [PubMed]journal. [CrossRef] [PubMed]
 
Ohta K. .Miyamoto T. .Amagasaki T. .Yamamoto M. . 1304 Study Group Efficacy and safety of omalizumab in an Asian population with moderate-to-severe persistent asthma. Respirology. 2009;14:1156-1165 [PubMed]journal. [CrossRef] [PubMed]
 
Soler M. .Matz J. .Townley R. .et al The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18:254-261 [PubMed]journal. [CrossRef] [PubMed]
 
Vignola A.M. .Humbert M. .Bousquet J. .et al Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR. Allergy. 2004;59:709-717 [PubMed]journal. [CrossRef] [PubMed]
 
Massanari M. .Holgate S.T. .Busse W.W. .Jimenez P. .Kianifard F. .Zeldin R. . Effect of omalizumab on peripheral blood eosinophilia in allergic asthma. Respir Med. 2010;104:188-196 [PubMed]journal. [CrossRef] [PubMed]
 
Humbert M. .Beasley R. .Ayres J. .et al Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment):INNOVATE. Allergy. 2005;60:309-316 [PubMed]journal. [CrossRef] [PubMed]
 
Milgrom H. .Fick R.B. Jr..Su J.Q. .et al Treatment of allergic asthma with monoclonal anti-IgE antibody. rhuMAb-E25 Study Group. N Engl J Med. 1999;341:1966-1973 [PubMed]journal. [CrossRef] [PubMed]
 
Milgrom H. .Berger W. .Nayak A. .et al Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics. 2001;108:E36- [PubMed]journal. [CrossRef] [PubMed]
 
Lanier B. .Bridges T. .Kulus M. .Taylor A.F. .Berhane I. .Vidaurre C.F. . Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009;124:1210-1216 [PubMed]journal. [CrossRef] [PubMed]
 
Gibson P.G. .Taramarcaz P. .McDonald V.M. . Use of omalizumab in a severe asthma clinic. Respirology. 2007;12:S35-S44 [PubMed]journal. [CrossRef] [PubMed]
 
Abraham I. .Alhossan A. .Lee C.S. .Kutbi H. .MacDonald K. . “Real-life” effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review. Allergy. 2016;71:593-610 [PubMed]journal. [CrossRef] [PubMed]
 
Normansell R. .Walker S. .Milan S.J. .Walters E.H. .Nair P. . Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;:1CD003559- [PubMed]journal
 
Djukanovic R. .Wilson S.J. .Kraft M. .et al Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med. 2004;170:583-593 [PubMed]journal. [CrossRef] [PubMed]
 
Oliver J.M. .Tarleton C.A. .Gilmartin L. .et al Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during omalizumab therapy. Int Arch Allergy Immunol. 2010;151:275-284 [PubMed]journal. [CrossRef] [PubMed]
 
Schroeder J.T. .Bieneman A.P. .Chichester K.L. .et al Decreases in human dendritic cell-dependent T(H)2-like responses after acute in vivo IgE neutralization. J Allergy Clin Immunol. 2010;125:896-901.e896 [PubMed]journal. [CrossRef] [PubMed]
 
Chan M.A. .Gigliotti N.M. .Dotson A.L. .Rosenwasser L.J. . Omalizumab may decrease IgE synthesis by targeting membrane IgE+ human B cells. Clin Transl Allergy. 2013;3:29- [PubMed]journal. [CrossRef] [PubMed]
 
Gibson P.G. .Reddel H. .McDonald V.M. .et al Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry. Intern Med J. 2016;46:1054-1062 [PubMed]journal. [CrossRef] [PubMed]
 
Hew M, Gillman A, Sutherland M, et al. Real-life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria [published online ahead of print July 5, 2016].Clin Exp Allergy.http://dx.doi.org/10.1111/cea.12774.
 
Juniper E.F. .Svensson K. .Mork A.C. .Stahl E. . Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir Med. 2005;99:553-558 [PubMed]journal. [CrossRef] [PubMed]
 
Juniper E.F. .Buist A.S. .Cox F.M. .Ferrie P.J. .King D.R. . Validation of a standardized version of the Asthma Quality of Life Questionnaire. Chest. 1999;115:1265-1270 [PubMed]journal. [CrossRef] [PubMed]
 
Heaney L.G. .Brightling C.E. .Menzies-Gow A. .Stevenson M. .Niven R.M. . British Thoracic Society Difficult Asthma Network Refractory asthma in the UK: cross-sectional findings from a UK multicentre registry. Thorax. 2010;65:787-794 [PubMed]journal. [CrossRef] [PubMed]
 
Moore W.C. .Bleecker E.R. .Curran-Everett D. .et al Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119:405-413 [PubMed]journal. [CrossRef] [PubMed]
 
Yalcin A.D. .Celik B. .Yalcin A.N. . Omalizumab (anti-IgE) therapy in the asthma-COPD overlap syndrome (ACOS) and its effects on circulating cytokine levels. Immunopharmacol Immunotoxicol. 2016;38:253-256 [PubMed]journal. [CrossRef] [PubMed]
 
Tat T.S. .Cilli A. . Omalizumab treatment in asthma-COPD overlap syndrome. J Asthma. 2016;:1-3 [PubMed]journal
 
Korn S. .Thielen A. .Seyfried S. .Taube C. .Kornmann O. .Buhl R. . Omalizumab in patients with severe persistent allergic asthma in a real-life setting in Germany. Respir Med. 2009;103:1725-1731 [PubMed]journal. [CrossRef] [PubMed]
 
Brightling C.E. .Bleecker E.R. .Panettieri R.A. Jr..et al Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014;2:891-901 [PubMed]journal. [CrossRef] [PubMed]
 
Celedon J.C. .Speizer F.E. .Drazen J.M. .et al Bronchodilator responsiveness and serum total IgE levels in families of probands with severe early-onset COPD. Eur Respir J. 1999;14:1009-1014 [PubMed]journal. [CrossRef] [PubMed]
 
de Jong J.W. .van der Belt-Gritter B. .Koeter G.H. .Postma D.S. . Peripheral blood lymphocyte cell subsets in subjects with chronic obstructive pulmonary disease: association with smoking, IgE and lung function. Respir Med. 1997;91:67-76 [PubMed]journal. [CrossRef] [PubMed]
 
Jin J. .Liu X. .Sun Y. . The prevalence of increased serum IgE and Aspergillus sensitization in patients with COPD and their association with symptoms and lung function. Respir Res. 2014;:15130- [PubMed]journal
 
Masuko H. .Sakamoto T. .Kaneko Y. .et al Lower FEV1 in non-COPD, nonasthmatic subjects: association with smoking, annual decline in FEV1, total IgE levels, and TSLP genotypes. Int J Chron Obstruct Pulmon Dis. 2011;:6181-6189 [PubMed]journal
 
Sherrill D.L. .Lebowitz M.D. .Halonen M. .Barbee R.A. .Burrows B. . Longitudinal evaluation of the association between pulmonary function and total serum IgE. Am J Respir Crit Care Med. 1995;152:98-102 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 Comparisons based on physician diagnosis of COPD. A, Asthma control (ACQ-5). B, Health-related quality of life (AQLQ) questionnaire scores. C and D, Pre-BD and post-BD FEV1/FVC results at baseline (red bars) and 6-month follow-up of omalizumab therapy (blue bars). Graphs represent mean ± SD. *P < .05, *** P < .001, ****P < .0001. ACQ-5 = Asthma Control Questionnaire; AQLQ= Asthma Quality of Life Questionnaire; BD = bronchodilator.Grahic Jump Location
Figure Jump LinkFigure 2 Comparisons based on baseline post-BD FEV1 assessment (> 80% predicted vs < 80%). A, Asthma control (ACQ-5) scores. B, Health-related quality of life (AQLQ) scores. C and D, Pre-BD and post-BD FEV1/FVC spirometry results at baseline (red bars) and 6-month follow-up of omalizumab therapy (blue bars). Graphs represent mean ± SD. ***P < .001, ****P < .0001. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3 Comparisons based on smoking history (never vs ever smoker) in the post-BD FEV1 < 80% population. A, Asthma control (ACQ-5 questionnaire) scores. B, Health-related quality of life (AQLQ) questionnaire scores. C and D, Pre-BD and post-BD FEV1/FVC spirometry results at baseline (red bars) and 6-month follow-up of omalizumab therapy (blue bars). Graphs represent mean ± SD. *P < .05, ***P < .001, ****P < .0001. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Baseline Participant Characteristics for Physician Diagnosis of COPD
a Data are presented as mean (SD); Student t test.
b Data are presented as No. (%); χ2 or Fisher exact test.
c Data are presented as median (quartile 1, quartile 3); Wilcoxon rank sum test.

Boldface indicates statistical significance (P < .05). ACQ-5 = Asthma Control Questionnaire; AQLQ = Asthma Quality of Life Questionnaire; BD = bronchodilator; BDP = beclometasone dipropionate equivalent; ICS = inhaled corticosteroids; OCS = oral corticosteroids.

Table Graphic Jump Location
Table 2 Baseline Patient Characteristics Based on Post-BD FEV1
a Data are presented as mean (SD); Student t test, Wilcoxon rank sum test.
b Data are presented as No. (%); χ2 or Fisher exact test.
c Data are presented as median (quartile 1, quartile 3).

Boldface indicates statistical significance (P < .05). See Table 1 legend for expansion of abbreviations.

Table Graphic Jump Location
Table 3 Baseline Patient Characteristics Based on Post-BD FEV1 and Smoking History
a Data are presented as mean (SD); one-way analysis of variance.
b Data are presented as No. (%); χ2 or Fisher exact test.
c Data are presented as median (quartile 1, quartile 3); Kruskal-Wallis test.
d Post hoc significance vs post-BD FEV1 % ≥ 80%.
e Post hoc significance vs post-BD FEV1 % < 80% and never smoker.

Boldface indicates statistical significance (P < .05). NA = not available. See Table 1 legend for expansion of other abbreviations.

References

Reddel H.K. .Bateman E.D. .Becker A. .et al A summary of the new GINA strategy:a roadmap to asthma control. Eur Respir J. 2015;46:622-639 [PubMed]journal. [CrossRef] [PubMed]
 
Vestbo J. .Hurd S.S. .Agusti A.G. .et al Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187:347-365 [PubMed]journal. [CrossRef] [PubMed]
 
McDonald V.M. .Higgins I. .Gibson P.G. . Managing older patients with coexistent asthma and chronic obstructive pulmonary disease: diagnostic and therapeutic challenges. Drugs Aging. 2013;30:1-17 [PubMed]journal. [CrossRef] [PubMed]
 
Gibson P.G. .McDonald V.M. . Asthma-COPD overlap 2015: now we are six. Thorax. 2015;70:683-691 [PubMed]journal. [CrossRef] [PubMed]
 
Miravitlles M. .Soriano J.B. .Ancochea J. .et al Characterisation of the overlap COPD-asthma phenotype. Focus on physical activity and health status. Respir Med. 2013;107:1053-1060 [PubMed]journal. [CrossRef] [PubMed]
 
Hardin M. .Cho M. .McDonald M.L. .et al The clinical and genetic features of COPD-asthma overlap syndrome. Eur Respir J. 2014;44:341-350 [PubMed]journal. [CrossRef] [PubMed]
 
Menezes A.M. .Montes de Oca M. .Perez-Padilla R. .et al Increased risk of exacerbation and hospitalization in subjects with an overlap phenotype: COPD-asthma. Chest. 2014;145:297-304 [PubMed]journal. [CrossRef] [PubMed]
 
Global Initiative for Asthma/Global Initiative for Chronic Obstructive Lung Disease. Diagnosis of Diseases of Chronic Airflow Limitation: Asthma COPD and Asthma-COPD Overlap Syndrome (ACOS), 2015.
 
Agusti A. .Bel E. .Thomas M. .et al Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J. 2016;47:410-419 [PubMed]journal. [PubMed]
 
Grainge C.L. .Maltby S. .Gibson P.G. .Wark P.A. .McDonald V.M. . Targeted therapeutics for severe refractory asthma:monoclonal antibodies. Expert Rev Clin Pharmacol. 2016;9:927-941 [PubMed]journal. [CrossRef] [PubMed]
 
Jamieson D.B. .Matsui E.C. .Belli A. .et al Effects of allergic phenotype on respiratory symptoms and exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188:187-192 [PubMed]journal. [CrossRef] [PubMed]
 
Neves M.C. .Neves Y.C. .Mendes C.M. .et al Evaluation of atopy in patients with COPD. J Bras Pneumol. 2013;39:296-305 [PubMed]journal. [CrossRef] [PubMed]
 
Renkema T.E. .Kerstjens H.A. .Schouten J.P. .Vonk J.M. .Koeter G.H. .Postma D.S. . The importance of serum IgE for level and longitudinal change in airways hyperresponsiveness in COPD. Clin Exp Allergy. 1998;28:1210-1218 [PubMed]journal. [CrossRef] [PubMed]
 
Travers J. .Marsh S. .Caldwell B. .et al External validity of randomized controlled trials in COPD. Respir Med. 2007;101:1313-1320 [PubMed]journal. [CrossRef] [PubMed]
 
Travers J. .Marsh S. .Williams M. .et al External validity of randomised controlled trials in asthma: to whom do the results of the trials apply? Thorax. 2007;62:219-223 [PubMed]journal. [CrossRef] [PubMed]
 
Bardelas J. .Figliomeni M. .Kianifard F. .Meng X. . A 26-week, randomized, double-blind, placebo-controlled, multicenter study to evaluate the effect of omalizumab on asthma control in patients with persistent allergic asthma. J Asthma. 2012;49:144-152 [PubMed]journal. [CrossRef] [PubMed]
 
Chanez P. .Contin-Bordes C. .Garcia G. .et al Omalizumab-induced decrease of FcxiRI expression in patients with severe allergic asthma. Respir Med. 2010;104:1608-1617 [PubMed]journal. [CrossRef] [PubMed]
 
Busse W. .Corren J. .Lanier B.Q. .et al Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108:184-190 [PubMed]journal. [CrossRef] [PubMed]
 
Hanania N.A. .Alpan O. .Hamilos D.L. .et al Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med. 2011;154:573-582 [PubMed]journal. [CrossRef] [PubMed]
 
Busse W.W. .Morgan W.J. .Gergen P.J. .et al Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364:1005-1015 [PubMed]journal. [CrossRef] [PubMed]
 
Gevaert P. .Calus L. .Van Zele T. .et al Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013;131:110-116.e111 [PubMed]journal. [CrossRef] [PubMed]
 
Holgate S.T. .Chuchalin A.G. .Hebert J. .et al Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy. 2004;34:632-638 [PubMed]journal. [CrossRef] [PubMed]
 
Ohta K. .Miyamoto T. .Amagasaki T. .Yamamoto M. . 1304 Study Group Efficacy and safety of omalizumab in an Asian population with moderate-to-severe persistent asthma. Respirology. 2009;14:1156-1165 [PubMed]journal. [CrossRef] [PubMed]
 
Soler M. .Matz J. .Townley R. .et al The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18:254-261 [PubMed]journal. [CrossRef] [PubMed]
 
Vignola A.M. .Humbert M. .Bousquet J. .et al Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR. Allergy. 2004;59:709-717 [PubMed]journal. [CrossRef] [PubMed]
 
Massanari M. .Holgate S.T. .Busse W.W. .Jimenez P. .Kianifard F. .Zeldin R. . Effect of omalizumab on peripheral blood eosinophilia in allergic asthma. Respir Med. 2010;104:188-196 [PubMed]journal. [CrossRef] [PubMed]
 
Humbert M. .Beasley R. .Ayres J. .et al Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment):INNOVATE. Allergy. 2005;60:309-316 [PubMed]journal. [CrossRef] [PubMed]
 
Milgrom H. .Fick R.B. Jr..Su J.Q. .et al Treatment of allergic asthma with monoclonal anti-IgE antibody. rhuMAb-E25 Study Group. N Engl J Med. 1999;341:1966-1973 [PubMed]journal. [CrossRef] [PubMed]
 
Milgrom H. .Berger W. .Nayak A. .et al Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics. 2001;108:E36- [PubMed]journal. [CrossRef] [PubMed]
 
Lanier B. .Bridges T. .Kulus M. .Taylor A.F. .Berhane I. .Vidaurre C.F. . Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009;124:1210-1216 [PubMed]journal. [CrossRef] [PubMed]
 
Gibson P.G. .Taramarcaz P. .McDonald V.M. . Use of omalizumab in a severe asthma clinic. Respirology. 2007;12:S35-S44 [PubMed]journal. [CrossRef] [PubMed]
 
Abraham I. .Alhossan A. .Lee C.S. .Kutbi H. .MacDonald K. . “Real-life” effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review. Allergy. 2016;71:593-610 [PubMed]journal. [CrossRef] [PubMed]
 
Normansell R. .Walker S. .Milan S.J. .Walters E.H. .Nair P. . Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;:1CD003559- [PubMed]journal
 
Djukanovic R. .Wilson S.J. .Kraft M. .et al Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med. 2004;170:583-593 [PubMed]journal. [CrossRef] [PubMed]
 
Oliver J.M. .Tarleton C.A. .Gilmartin L. .et al Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during omalizumab therapy. Int Arch Allergy Immunol. 2010;151:275-284 [PubMed]journal. [CrossRef] [PubMed]
 
Schroeder J.T. .Bieneman A.P. .Chichester K.L. .et al Decreases in human dendritic cell-dependent T(H)2-like responses after acute in vivo IgE neutralization. J Allergy Clin Immunol. 2010;125:896-901.e896 [PubMed]journal. [CrossRef] [PubMed]
 
Chan M.A. .Gigliotti N.M. .Dotson A.L. .Rosenwasser L.J. . Omalizumab may decrease IgE synthesis by targeting membrane IgE+ human B cells. Clin Transl Allergy. 2013;3:29- [PubMed]journal. [CrossRef] [PubMed]
 
Gibson P.G. .Reddel H. .McDonald V.M. .et al Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry. Intern Med J. 2016;46:1054-1062 [PubMed]journal. [CrossRef] [PubMed]
 
Hew M, Gillman A, Sutherland M, et al. Real-life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria [published online ahead of print July 5, 2016].Clin Exp Allergy.http://dx.doi.org/10.1111/cea.12774.
 
Juniper E.F. .Svensson K. .Mork A.C. .Stahl E. . Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir Med. 2005;99:553-558 [PubMed]journal. [CrossRef] [PubMed]
 
Juniper E.F. .Buist A.S. .Cox F.M. .Ferrie P.J. .King D.R. . Validation of a standardized version of the Asthma Quality of Life Questionnaire. Chest. 1999;115:1265-1270 [PubMed]journal. [CrossRef] [PubMed]
 
Heaney L.G. .Brightling C.E. .Menzies-Gow A. .Stevenson M. .Niven R.M. . British Thoracic Society Difficult Asthma Network Refractory asthma in the UK: cross-sectional findings from a UK multicentre registry. Thorax. 2010;65:787-794 [PubMed]journal. [CrossRef] [PubMed]
 
Moore W.C. .Bleecker E.R. .Curran-Everett D. .et al Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119:405-413 [PubMed]journal. [CrossRef] [PubMed]
 
Yalcin A.D. .Celik B. .Yalcin A.N. . Omalizumab (anti-IgE) therapy in the asthma-COPD overlap syndrome (ACOS) and its effects on circulating cytokine levels. Immunopharmacol Immunotoxicol. 2016;38:253-256 [PubMed]journal. [CrossRef] [PubMed]
 
Tat T.S. .Cilli A. . Omalizumab treatment in asthma-COPD overlap syndrome. J Asthma. 2016;:1-3 [PubMed]journal
 
Korn S. .Thielen A. .Seyfried S. .Taube C. .Kornmann O. .Buhl R. . Omalizumab in patients with severe persistent allergic asthma in a real-life setting in Germany. Respir Med. 2009;103:1725-1731 [PubMed]journal. [CrossRef] [PubMed]
 
Brightling C.E. .Bleecker E.R. .Panettieri R.A. Jr..et al Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014;2:891-901 [PubMed]journal. [CrossRef] [PubMed]
 
Celedon J.C. .Speizer F.E. .Drazen J.M. .et al Bronchodilator responsiveness and serum total IgE levels in families of probands with severe early-onset COPD. Eur Respir J. 1999;14:1009-1014 [PubMed]journal. [CrossRef] [PubMed]
 
de Jong J.W. .van der Belt-Gritter B. .Koeter G.H. .Postma D.S. . Peripheral blood lymphocyte cell subsets in subjects with chronic obstructive pulmonary disease: association with smoking, IgE and lung function. Respir Med. 1997;91:67-76 [PubMed]journal. [CrossRef] [PubMed]
 
Jin J. .Liu X. .Sun Y. . The prevalence of increased serum IgE and Aspergillus sensitization in patients with COPD and their association with symptoms and lung function. Respir Res. 2014;:15130- [PubMed]journal
 
Masuko H. .Sakamoto T. .Kaneko Y. .et al Lower FEV1 in non-COPD, nonasthmatic subjects: association with smoking, annual decline in FEV1, total IgE levels, and TSLP genotypes. Int J Chron Obstruct Pulmon Dis. 2011;:6181-6189 [PubMed]journal
 
Sherrill D.L. .Lebowitz M.D. .Halonen M. .Barbee R.A. .Burrows B. . Longitudinal evaluation of the association between pulmonary function and total serum IgE. Am J Respir Crit Care Med. 1995;152:98-102 [PubMed]journal. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Supporting Data

e-Figures 1-3 and e-Tables 1-3

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