**1. Introduction**

There are usually multiple risk factors that could exacerbate patients with asthma and other respiratory diseases. There are some risk factors that can be recognized

#### **Figure 1.**

 *Host factors contributing to asthma exacerbations.* 


#### **Figure 2.**

 *External environmental and occupational factors.* 

quickly such as family history, smoking history and animals. There are Host factors contributing that contribute to asthma exacerbations ( **Figure 1** ), and external risk factors ( **Figure 2** ). further recognized other not so clear risk factors good understanding of asthma pathophysiology needs to be study. Asthma is a heterogeneous disease, characterized by airway hyperresponsiveness, chronic airway inflammation, reversible

### *Environmental and Occupational Factors; Contribution and Perspectives on Difficult to Treat… DOI: http://dx.doi.org/10.5772/intechopen.108605*

airway obstruction and remodeling of the lung, leading to respiratory symptoms, which includes shortness of breath, wheezes, chest tightness and cough [1]. These symptoms vary over time in intensity and are present with variable expiratory airflow limitation [2]. However, airflow limitation may become persistent later in the course of the disease, making this condition difficult to treat [3]. Diagnosing asthma in the setting of multiple environmental factors is a challenging work, however at some point patients will lead the physician for specific factors that worsens the disease. Irritant's exposures will lead to asthma symptoms in specific situations which makes this heterogenous disease sometimes a predictable one [4]. Uncontrolled asthma is when patient has either poor symptom control (frequent symptoms or increased use of rescue therapy, when have limited activity due to asthma, night waking due to asthma or have frequent exacerbation, defined as more than 2 exacerbations a year requiring oral corticosteroids or serious exacerbations (> 1/year) requiring hospitalization [3]. Difficult to treat asthma is when there is poor symptom control, despite patient been on optimal therapy. Optimal therapy includes maintenance treatment with medium or high dose inhaled corticosteroids (ICS) or oral corticosteroids with a second controller, which is usually a long-acting beta agonist (LABA) or with maintenance of oral corticosteroids.

It is known that asthma is a multifactorial condition that includes a combination of genetic and environmental factors [5]. Early recognition is critical in the proper management of asthma, as well as to prevent exacerbations and complications [6].

Environmental factors induce airway inflammation that leads to an exaggerated hypersensitivity that cause airway obstruction [5]. This response is the result of an increased presence of eosinophils, lymphocytes, and mast cells leading to airway inflammation and damage to the bronchial epithelium. The most common cause is IgE-mediated type I allergen exposure response [7]. Environmental factors that contribute to asthma symptoms and severity include viral infection, allergens (cockroaches, dust mites, pollens, animal dander and molds), indoor and outdoor air pollution, tobacco smoke (passive and active smoker), occupational sensitizers (isocyanates, platinum salts, animal biological products), and other causes such as exercise food allergies, GERD, Aspirin or NSAID sensitivity, among others. Occupational asthma is an important part of the environmental factors that contribute to difficult to treat asthma. Occupational exposures are a major cause of lung disease and disability worldwide [8, 9]. It is estimated that work related exposures account for as much as 15–25% of the asthma burden in the United States [10]. Work-related asthma may cause functional impairment and disability and tends to cause higher morbidity than general asthma [11]. In new cases of asthma presentation in adults with an unknown trigger, work-related asthma should be considered.

### **1.1 Work-related asthma (WRA)**

Early recognition of this entity and control of exposures are important in work-related induced asthma, because low-molecular-weight chemical sensitizers, also cause asthma in a similar mechanism of allergens [7]. WRA is divided into 2 categories: (1) Occupational asthma (OA), which is define as the asthma that is caused by exposition of an agent at work and (2) Work exacerbated asthma (WEA), with is defined as pre-existing asthma that is exacerbated by exposure to an agent at work. OA is suggested by a correlation between asthma symptoms and work, as well as with improvement when away from work for several days. It is cause by agents that are classified depending on their molecular weight; high-molecular-weight (HMW) or low molecular weight (LMW) agents [12]. The HMW antigens consist of animal and plant proteins, fungi, and other large organic molecules. The LMW antigens consist of chemicals and some metal salts [13].


#### **Figure 3.**

 *Inorganic occupational exposures contributing to difficult to treat asthma.* 

#### **Figure 4.**

 *Organic occupational exposures contributing to difficult to treat asthma.* 

 It is thought that the LMW act through type I hypersensitivity mechanism, producing specific IgE antibodies, but the entire mechanisms are not well understood [ 12 ]. It is know that offending agents can cause an acute inflammatory response inducing reactive *Environmental and Occupational Factors; Contribution and Perspectives on Difficult to Treat… DOI: http://dx.doi.org/10.5772/intechopen.108605*


#### **Figure 5.**

*Major occupational asthma causes divided by molecular weight into low molecular weight irritant and high molecular weight irritant. \*\*Rosenman KD, Beckett WS. Web based listing of agents associated with new onset work-related asthma. Respir med. 2015 may; 109(5):625–31.*

airways dysfunction syndrome, if exposure is repeated a chronic inflammation is produced that leads to persistent or permanent changes consistent with asthma [12]. It is important to recognize this offending agent as early as possible to prevent these changes. The most frequent causes of OA are Flour (31%) Isocyanates (17%), Persulfates (7%), Metals (4%), Wood (3%), Latex (3%), Acylates (3%), Quaternary ammonium (3.2%), Others (28%) [13], this factors can be divided into inorganic (**Figure 3**) and organic (**Figure 4**) risk factors, high molecular and low molecular weight (**Figure 5**).

\*\*Torén K, Brisman J, Olin AC, Blanc PD. Asthma on the job: work-related factors in new onset-asthma and in exacerbations of pre-existing asthma. Respir Med. 2000 Jun;94(6):529–35.
