**3.2 Asthma-COPD overlap**

The term asthma-COPD overlap (ACO), which is a phenotype of COPD, is used to identify patients with airway diseases that combine clinical features of both

*New Perspectives in Pharmacological Therapy for COPD: Phenotype Classification and… DOI: http://dx.doi.org/10.5772/intechopen.106949*

asthma and COPD [8, 95]. However, diagnosis of ACO may be unclear because COPD and asthma may be unclear because these two diseases are heterogeneous. It is also unclear to accurately distinguish between ACO and COPD with eosinophilia in peripheral blood. There is still disagreement with ACO; and the concept of ACO remains quite controversial [11, 96]. ACO is diagnosed for a patient who has characteristic of COPD, namely persistent airflow limitation as well as features of asthma [8]. Features of asthma develop in between approximately 15% of patients with COPD as well [8, 97]. ACO is not a single uniform entity but consists of multiple sub-phenotypes, such as asthma with irreversible airway obstruction due to structural changes, or smoke or predominantly neutrophilic inflammation, and COPD with eosinophilic inflammation [97]. It is generally considered that patients with ACO appear to have more symptoms, more frequent exacerbations, increased risk of hospitalization, and a worse quality of life [98]; on the other hand, patients with ACO appear to have a lower mortality [95]. The identification of ACO is important because corticosteroids are beneficial to patients with ACO, regardless of FEV1 or exacerbation frequency [99]. The responsiveness to corticosteroids is due to feature of asthma in ACO.

#### **3.3 Airway eosinophilia and airway hyperresponsiveness as phenotypes of COPD**

Since airway eosinophilia and AHR overlap between COPD and asthma, the differential diagnosis between COPD, asthma, and ACO can be unclear in cases with eosinophilia and AHR in the airways. It also still unclear to distinguish accurately between eosinophilic COPD and COPD with asthma [100]. A previous report that examined airway eosinophilic inflammation using sputum induction and examined AHR using methacholine provocation test in 21 cases of COPD has indicated that 41.4% had AHR, 31.0% had increased sputum eosinophils, and that cases with AHR had higher sputum eosinophils than cases without AHR and those with sputum eosinophils more than 3% had more exacerbations in the previous year [55]. In another study, 203 patients with COPD who have no symptoms and past history related to asthma were enrolled to examine role of eosinophilic inflammation and AHR in the airways as phenotypes of COPD [12]. These subjects were diagnosed as COPD based on lung function test and smoking history. Eosinophils in the sputum were observed in 65 (50.4%) of 129 subjects using qualitative analysis; in contrast, lower grade (more than 0%, less than 3%) and higher grade (3% or more) were observed in 15 (20.3%) and 25 (33.8%) of 74 subjects using quantitative analysis [12]. Exacerbations occurred much more frequently in lower-grade airway eosinophilia without inhaled corticosteroid than in higher-grade airway eosinophilia with inhaled corticosteroid [12]. Regulation of airway eosinophilia is associated with a reduction in exacerbations of COPD (**Figure 2**) [101]. AHR developed in 46.9% of these subjects with sputum eosinophils; but grade of airway eosinophilia was not associated with development of AHR. AHR also significantly increased frequency of exacerbations in COPD with both lower and higher grade in airway eosinophilia [12]. This clinical report demonstrates that airway eosinophilia and AHR cause in COPD, independent of asthma, and that these phenotypes of COPD are closely related to symptom stability (exacerbations). Moreover, AHR is associated with mortality in COPD [102–104]. These essential results derived from these clinical studies are summarized in **Figures 2**, **3** and **Table 1**.

**Figure 2.**

*Clinical characteristics caused by airway eosinophilia and airway hyperresponsiveness as phenotypes of COPD. Illustrated based on ref. [12, 55, 89, 101–109].*

#### **Figure 3.**

*Phenotypes of COPD classified into airway eosinophilia and airway hyperresponsiveness. Illustrated based on ref. [12, 55].*
