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The recognition that there are some patients with features of asthma and chronic obstructive pulmonary disease (COPD) has highlighted the need to develop more specific treatments for these clinical phenotypes.

Some patients with COPD have predominantly eosinophilic inflammation and might respond to high doses of inhaled corticosteroids and newly developed specific antieosinophil therapies, including blocking antibodies against IL-5, IL-13, IL-33, and thymic stromal lymphopoietin, as well as oral chemoattractant receptor-homologous molecule expressed on TH2 cells antagonists. Other patients have severe asthma or are asthmatic patients who smoke with features of COPD-induced inflammation and might benefit from treatments targeting neutrophils, including macrolides, CXCR2 antagonists, phosphodiesterase 4 inhibitors, p38 mitogen-activating protein kinase inhibitors, and antibodies against IL-1 and IL-17. Other patients appear to have largely fixed obstruction with little inflammation and might respond to long-acting bronchodilators, including long-acting muscarinic antagonists, to reduce hyperinflation. Highly selected patients with severe asthma might benefit from bronchial thermoplasty. Some patients with overlap syndromes can be conveniently treated with triple fixed-dose combination inhaler therapy with an inhaled corticosteroid, long-acting β2-agonist, and long-acting muscarinic antagonist, several of which are now in development.

Corticosteroid resistance is a feature of asthma-COPD overlap syndrome, and understanding the various molecular mechanisms of this resistance has identified novel therapeutic targets and presented the prospect of therapies that can restore corticosteroid responsiveness.

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In their most typical forms, asthma and chronic obstructive pulmonary disease (COPD) are clearly distinguishable, but many patients with chronic airflow limitation demonstrate features of both conditions and have worse health outcomes than those with either disease alone. This has been called the asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS), but as yet, it lacks a precise definition. However, given the different pathways by which a patient can come to demonstrate features of both asthma and COPD, ACOS is not thought to represent a single disease but to include several heterogeneous phenotypes with different underlying mechanisms.

These issues have important implications for guidelines because some existing treatment recommendations for asthma and COPD are in conflict, and patients with both asthma and COPD have specifically been excluded from major pharmacologic trials. As a result, there is little evidence at present to support specific treatment recommendations for ACOS on the basis of efficacy or effectiveness, yet these patients continue to present for diagnosis and management, mainly in primary care. This article highlights the need for clinical guidance about ACOS, summarizes recommendations about its diagnosis and treatment from a sample of national asthma and COPD guidelines, and proposes a way forward, as suggested in a collaborative Global Initiative for Asthma/Global Initiative for Chronic Obstructive Lung Disease report, to provide health professionals with interim recommendations about syndromic recognition and initial treatment based on both potential effectiveness and potential risk.

Additional research in broad populations is urgently needed to develop a precise definition for ACOS, characterize its phenotypes, and identify opportunities for targeted treatment.

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Although it is currently recognized that bronchial asthma is not a single disease but a syndrome, we have not yet made use of our new understanding of this heterogeneity as we treat asthma patients. To increase the efficacy of anti-asthma drugs and to decrease costs, it is important to stratify asthma patients into subgroups and to develop therapeutic strategies for each subgroup.

Periostin has recently emerged as a biomarker for bronchial asthma, unique in that it is useful not in diagnosis but in categorizing asthma patients. We first found that periostin is a novel component of subepithelial fibrosis in bronchial asthma downstream of IL-13 signals. Thereafter, it was shown that periostin can be a surrogate biomarker of type 2 immune responses, the basis of the notion that a detection system of serum periostin is potentially a companion diagnostic for type 2 antagonists.

Furthermore, we have recently shown that serum periostin can predict resistance or hyporesponsiveness to inhaled corticosteroids, based on its contribution to tissue remodeling or fibrosis in bronchial asthma. Thus, serum periostin has two characteristics as a biomarker for bronchial asthma: it is both a surrogate biomarker of type 2 immune responses and a biomarker reflecting tissue remodeling or fibrosis.

We can take advantage of these characteristics to develop stratified medicine in bronchial asthma.

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