# ASO (Asthma-COPD Overlap) Is Independent from COPD, a Case in Favor: A Systematic Review
## 3 Results
### Characteristics of Selected Studies and Risk of Bias
#### 3.2.3 Serum IgE Elevation and Atopic Background for COPD and ACO  
Atopy refers to a genetic tendency to produce IgE typically for common and environmental allergens including inhaled allergens and food allergens. The presence of IgE specific for inhaled allergens, such as dust mites, cockroach and animal dander, is known to be a risk factor for asthma [102; 103]. Serum total IgE levels were significantly correlated in pairs of siblings for bronchial hyperresponsiveness to histamine, which is implicated as a coinherited trait [104]. In addition, symptoms and exacerbations of asthma were significantly associated with an elevation of serum total IgE, which was independent of specific IgE [105]. This intriguing role of total, non-specific IgE in the association with asthma may be explained by the ability of IgE to enhance mast cell survival via Fc receptor I cross-linking [106]. Serum levels of total IgE, IL-4 and leukotriene B4 were increased in ACO compared to COPD [107]. These observational and translational studies suggest that the mast cell activation pathway is upregulated in ACO as with asthma. This hypothesis was further supported by at least two clinical studies indicating that omalizumab, a humanized monoclonal antibody for IgE, markedly improved asthma control and health-related quality of life in ACO and this observed improvement in ACO was as large as that in asthma [108; 109]. Given the evidence regarding IgE biology in atopic asthma overlapping COPD, it may be sensible to evaluate asthma complications in COPD patients with atopy.  
\begin{table}
\begin{tabular}{c c c c c c} \hline
**References** & **Study Design** & **Subject Numbers** & **Severity of Airflow** & **Intervention or** & **Results** \\  & & & & **Limitation** & **Measurement** & **Results** \\ \hline \multicolumn{6}{l}{_Studies for biomarkers of induced sputum differentiating ACO from COPD_} \\ \hline \multirow{6}{*}{[PERSON], et al. [98]} & \multirow{2}{*}{Cross-sectional} & Discovery cohort: 14 & \multirow{2}{*}{Post-bronodilator} & \multirow{2}{*}{Only sputum NGAL levels could} \\  & & never smoker, 24 & & & \\  & & healthy smoker, 24 & & & \\  & asthma, 20 COPD, 18 & & (never smoker), 98.5 \(\pm\) & IL-13, MPO, NGAL, & \\  & & ACO, & 15.5\% (healthy smoker), & YKL-40, IL-6 protein & from asthma (\(p<0.001\)) and \\  & & Replication cohort: 22 & 78.8 \(\pm\) 14.0\% (asthma), & levels in induced & & \\  & & never smoker, 40 & 58.3 \(\pm\) 19.1\% (COPD), & sputum & COPD (\(p<0.05\) and \(p=p\)) \\  & & healthy smoker, 21 & 51.6 \(\pm\) 13.7\% (ACO) in & 0.002) in the discovery & and replication cohorts. \\  & & asthma, 35 COPD, 17 & & & \\  & ACO & & & & \\ \hline \multicolumn{6}{l}{_Studies for radiographical analyses differentiating ACO from COPD_} \\ \hline \multirow{6}{*}{[PERSON], et al. [99]} & \multirow{2}{*}{Retrospective} & \multirow{2}{*}{COPD 55, asthma 39, ACO 18} & FEV\({}_{1}\) 54.1 \(\pm\) 12.1\% (COPD), \(\mathcal{D}_{0.00}\) 13.8\% (asthma), \(55.8\pm\) 12.4\% (Acom) & Radiographical evidence of sinonasal inflammation (Lund-Mackay staging, LMs) & In patients with ACO and COPD, total and ethomal LMS scores were significantly lower than those in patients with asthma. \\ \hline \multirow{6}{*}{[PERSON], et al. [100]} & \multirow{2}{*}{Cross-sectional} & \multirow{2}{*}{COPD 123, ACO 106} & Post-bronodilator & \multirow{2}{*}{Sagittal-lung CT measurements were significantly larger in} \\  & & FEV\({}_{1}\) 54.7 \(\pm\) 20.8\% (Acom) & & & \\  & & & (COPD), 64.4 \(\pm\) 15.7\% (Acom) & & \\