**2. Asthma treatment**

The goal of asthma treatment is to achieve daily symptom relief, reduce the risk of future exacerbations, and keep medication use within safe limits in terms of side effects. Asthma treatments fall into three categories: controller drugs (such as inhaled corticosteroids and leukotriene antagonists), symptom-relief/rescue medications (such as fast-acting bronchodilators and inhaled/systemic corticosteroids), and additional therapies (such as long-acting inhaled anticholinergics, low-dose corticosteroids, biologic agents, and immunotherapy) that are utilized when the patient's symptoms remain unchanged despite the use of high-dose controller drugs in settings where the risk factors are controlled [6]. The role of macrolides in the treatment of asthma has been a topic of interest for decades. The use of these medications will be discussed in more detail later in this chapter.

#### **2.1 Childhood asthma**

Asthma is the most common chronic disease in children, with a current prevalence ranging from 6–9% [15]. Preschool-aged children are particularly susceptible to symptoms similar to those of asthma, such as acute bronchiolitis and wheezing, making it crucial to predict if they will eventually develop asthma. Follow-up studies have revealed that remission of the disease is possible during adolescence, with rates varying from 15 to 64% [16]. Individuals with a milder onset and lower allergic susceptibility have a higher probability of remission [6].

Allergic asthma is the most common phenotype in childhood and is characterized by a history of atopic dermatitis, allergic rhinitis, food allergies, and IgE mediation. Eosinophilic infiltration marks airway inflammation in these patients. Nonallergic asthma is the second most common phenotype, which is marked by neutrophilic inflammation and lacks an atopic component [17].

Research suggests that multiple genetic and environmental factors interact to influence clinical manifestation, bronchial hyperresponsiveness, and the presence of atopy. It is now acknowledged that asthma has an integral relationship with the immune system. Atopy and asthma are related, although it is not a direct correlation since not all atopic people develop asthma, and not all asthmatics have detectable allergic sensitivity. Increased levels of IgE, the release of allergens from mast cells, the growth of eosinophils in the lungs, inflammation in the airways, and an imbalance of Th1 and Th2 responses indicate that a dysregulated immune system contributes to the development of asthma.

#### **2.2 Asthma and hygiene hypothesis**

Epidemiological studies have provided evidence for a rise in asthma and allergic illnesses in industrialized countries over recent decades, leading to the development of the "hygiene hypothesis." This hypothesis proposes that a lack of early childhood exposure to infectious agents, symbiotic microorganisms (e.g., probiotics), and parasites increases susceptibility to allergic diseases by altering the immune system. Evidence suggests that populations with greater exposure to infectious agents, such as in developing countries or families with more children, have a lower prevalence of allergic diseases. It is thought that decreased exposure to the microbial environment in more developed countries results in an immune system that is more likely to elicit allergic responses, rather than the protective immune responses that exposure to these organisms could elicit.

However, recent studies have suggested that the hygiene hypothesis may not be applicable to asthma, but instead, asthma may be connected to infections experienced during the life cycle [18–20]. The immune response generated from these infections is dependent on the route, duration, dose, and a person's genetic makeup [21].

#### **2.3 The microbiome of the airway**

Recent studies have suggested that the "microbiome of the respiratory tract" may play a role in the development of asthma [22]. This is supported by two studies that revealed notable variations between the quantity and variety of microbial populations in healthy individuals and asthmatics [23, 24]. Microbiomes, also known as microbial flora, are generally not considered to be a threat to human health since they are usually present in the lungs and other small environments in the body. However, as our understanding of these organisms and their effects on diseases such as atopy and asthma increases, their impact should be taken into account.

Research into the microbiome of the gut has established that the airways also contain a typical flora, with varying numbers, diversity, and distribution of prokaryotic species. Early research into this new field has suggested that various types of bacteria that are present in increased numbers in asthmatic airways may be contributing to the chronic airway inflammation and hyperreactivity that characterize asthma. A study with a relatively small sample size found that treatment with clarithromycin improved patients with increased bacterial populations and diversity [23].

Moreover, the microbial populations of the gastrointestinal tract are also being studied, and early antibiotic exposure has been linked to the development of atopy and asthma by altering the gastrointestinal tract flora [25–27]. The significance of these differences is yet to be fully determined.

#### **2.4 Asthma and infection**

For more than 20 years, researchers have been investigating whether asthma is an infectious disease, but a definitive answer has yet to be found [28]. Investigating the origins of asthma is challenging because it is difficult to collect samples from the lungs of children. It is now believed that a combination of genetic mutations and environmental conditions is responsible for the various pathways of asthma, making it a syndrome with a typical clinical presentation but with a myriad of potential pathogenic mechanisms.

Recent research suggests that the prolonged presence of certain microorganisms in the bronchi may be linked to the development of asthma. Acute viral infections are well-known triggers of asthma exacerbations in both adults and children. In contrast, little is known about the role of chronic infections in the pathogenesis of the disease itself.

#### Chlamydia pneumoniae *and Childhood Asthma DOI: http://dx.doi.org/10.5772/intechopen.111711*

Asthma can be caused by a variety of factors, including atopy, respiratory infections, genetic predisposition, and a Th2-biased immune response. Polymorphisms in host defense genes can also influence the host's innate immune response. The effect of infectious agents on asthma can vary depending on the type of asthma, such as childhood- or adult-onset, atopic or nonatopic, and neutrophilic, eosinophilic, or paucigranulocytic leukocyte airway predominance.

Numerous studies suggest that early-life lower respiratory tract infections, especially those caused by viruses such as Rhinoviruses (RV) and Respiratory Syncytial Virus (RSV), are linked to an increased risk of school-age asthma [29]. Additionally, atypical bacteria, such as *Mycoplasma pneumoniae* and *C. pneumoniae*, may also contribute to persistent infections and be involved in the development of asthma [30–33]. Of particular interest is the role of *C. pneumoniae*, an obligate intracellular respiratory pathogen, in both asthma severity and treatment resistance [34].
