**1. Introduction**

Since its recognition in 1989, *Chlamydia pneumoniae* has been extensively studied for its role as a widespread respiratory pathogen and its potential consequences for both children and adults. Its ability to evade the human immune system, biphasic development cycle, and capacity to spread throughout the host has made it a suspect in many chronic inflammatory diseases, including asthma.

Asthma is the most common chronic disease in childhood [1] and it is a major global health problem, affecting an estimated 300 million people of all ages worldwide [2].

Asthma is characterized by chronic airway inflammation. The pathogenetic mechanisms leading to asthma are likely to be diverse and influenced by multiple genetic polymorphisms as well as environmental factors, including respiratory tract infections. Chlamydia pneumonia is of particular interest among the various infections associated with new-onset asthma, asthma severity, and treatment resistance. This chapter aims to provide an overview of the association between Chlamydia pneumonia and childhood asthma and to summarize the most recent evidence on this topic.

#### **1.1 Asthma**

Asthma is an umbrella term for heterogeneous diseases with similar clinical manifestations, but different underlying pathophysiological mechanisms and prognoses. The Global Initiative for Asthma (GINA) defines asthma as "the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity, together with variable expiratory airflow limitation" [1]. These symptoms can be triggered by respiratory irritants, exercise, respiratory infections, and exposure to allergens in susceptible individuals.

Asthma symptoms and airflow limitation may resolve with or without treatment, and patients may remain asymptomatic for weeks or months. While many patients with classic asthma symptoms respond well to conventional treatments, some do not. These cases may be related to different underlying mechanisms.

#### **1.2 Asthma phenotypes**

Asthma phenotypes define clinically observable characteristics and are classified according to different elements (e.g., the age of onset, triggers, comorbidities, etc.). Besides, asthma endotypes define the underlying biological mechanisms making the clinical characteristics. Detailing the differences in the phenotypes and pathological or molecular characteristics of the content of the inflammation are trying to be explained by genotypes [3–5].

In order to achieve a more personalized medicine, especially for those with severe, treatment-resistant asthma, it seems future research will target classifying phenotypes based on endotypes (pathophysiological mechanisms) and the biomarkers associated with them. Additionally, exploring the etiology and mechanisms of the disease would help to more accurately predict the persistence of childhood asthma and its prognosis.

Several key elements, such as the age of onset, triggering factors, characteristics of symptoms, and biomarkers, have been taken into consideration when determining phenotypes of asthma [6].

*Phenotypes by age of onset*: This group consists of patients who were diagnosed with asthma at the age of 12 or older, with no definite upper age limit [7]. Typically, this group consists of adults, particularly women, who exhibit asthma that requires high doses of inhaled corticosteroids or is relatively resistant to corticosteroids [8].

*Phenotypes by biomarkers*: Asthma phenotyping can be conducted on biomarkers found in bronchial biopsy specimens, induced sputum, and peripheral blood, such as eosinophils and neutrophils (and the associated cytokines) that are involved in the Th-2 and non-Th-2 pathways, respectively [5, 9, 10].

A. Type 2 asthma can be further divided into two subtypes: allergic asthma and eosinophilic asthma [11]. (a) Allergic asthma is typically seen in children and is characterized by a history of eczema, allergic rhinitis, or food-drug allergies. This phenotype usually responds well to inhaled corticosteroids. (b) Eosinophilic asthma is identified when a patient's blood eosinophil count is >150/μl, and the eosinophil rate is higher than 2% in the sputum. Features of this phenotype include high eosinophil count, increased asthma severity, late-onset, and steroid resistance.

B. Non-Type 2 asthma refers to a group of patients who do not exhibit biomarkers of type-2 inflammation, such as epidermal prick test-compatible allergic comorbidities or eosinophils in blood/sputum. Their airway inflammation is either neutrophilic or paucigranulocytic (with few inflammatory cells). This non-allergic asthma group does not respond well to inhaled corticosteroid treatment. Neutrophil-derived inflammation, Chlamydia pneumoniae *and Childhood Asthma DOI: http://dx.doi.org/10.5772/intechopen.111711*

which may be associated with disorganized airway microbiota, appears to be linked to the most severe forms of asthma, typically seen in very young children and teenagers [12].

Asthma severity and asthma control were often used interchangeably. Today, asthma severity is evaluated retrospectively and defined as a condition where high doses and/or multiple medications are required to control the disease. Uncontrolled/ difficult asthma is now considered a condition where symptoms persist despite treatment, and patients experience frequent exacerbations or attacks [2, 6, 13, 14].
