**1. Introduction**

Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling due to chronic inflammation and subsequent airflow limitation that should be considered most to be associated with chronic symptoms such as shortness of breath and dyspnea [1]. Inhaled bronchodilators of long-acting beta-2 agonist/muscarinic antagonist have been introduced to treat symptomatic COPD [2]. Recently, more focus on the inflammation as a background condition of COPD is growing attention to a therapeutic factor to be considered [3]. In this regard, an

inhaled corticosteroid (ICS) has been involved in the standard therapy for moderate to severe COPD. However, using ICS raises the concern of an increased risk of pneumonia [4]. Thus, another class of anti-inflammatory therapeutic options would be awaited. In line with this concept, experimental anti-inflammatory therapy using heme oxygenase (HO)-1 administration or induction in murine lung disease model including emphysema has been reported with successful amelioration of disease progression [5, 6]. HO catalyzes the degradation of heme to biliverdin, carbon monoxide (CO), and iron [7]. Thus, the by-products of biliverdin and CO act as anti-inflammatory and antioxidative agents [8, 9]. The results showing that the serum levels of HO-1 in patients with COPD having significantly lower compared to those in healthy adults could support the benefits of HO-1 adminitration/induction in the lungs of COPD [10]. A recent report indicates that the HO-1 could regulate lung inflammatory/oxidtative stress status by modulating mitogen-activated protein kinase (MAPK) pathway especially for extracellular signal-regulated kinase (ERK) [11].

There are several ways of induction and/or upregulation of HO-1 in the lungs by 1) chemical induction using hemin or CoPP [10, 12] and 2) local/systemic administration of recombinant HO-1 [5, 6, 13].

Especially, the use of generally recognized as safe (GRAS) materials such as lactic acid bacteria (LAB) for producing/delivering the therapeutics for human diseases such as inflammatory bowel disease and colorectal cancer has been gaining growing attention [14–17]. In addition, exploring the conceptional use of GRAS materials for lung diseases has been planned and tried for an experimental COPD model [13, 18].

This chapter summarizes the detailed experimental approach of the intratracheal administration of GRAS microbes for producing/delivering therapeutics in the COPD model.
