Asthma: Symptoms, Causes, Risk Factors and Triggers

Asthma is chronic disease and it is widespread amon different ages. Prevalence studies have focused on the demand for an history of intermittent wheezing and, on this basis, the prevalence of childhood asthma has been reported up to 40%. Although most acute attacks are reversible and improve spontaneously or in minutes or hours with treatment without intermediate intervals, many asthma patients develop chronic airflow limitation. This affects diagnosis, management (Managing asthmatic attacks) and attempts to prevent acute exacerbations

Definition of Asthma

Asthma is a chronic inflammatory airway disease in the lungs. This inflammation occasionally causes the airways to narrow, producing wheezing and difficulty breathing sometimes to the point where the patient is panting for air. This obstruction of the air flow stops spontaneously or responds to a wide range of treatments. Continuous inflammation makes asthmatics hypersensitive to stimuli such as cold air, exercise, dust, air pollutants and even stress or anxiety

Changes in the lungs of asthmatics make their airways (the smallest bronchi and bronchioles) hyper-reactive to many different types of stimuli that do not affect healthy lungs. During an asthma attack, Mucus secretion occurs in the air spaces due to spasm to  the muscle tissue in the walls of the bronchi and the cells that line the airways swell. Both actions cause the bronchi to shrink, a change called bronchoconstriction. Consequently, an asthmatic person must make a much greater effort to breathe

Pathophysiology

Asthma is associated with specific chronic inflammation of the mucosa of the lower airways. One of the main goals of treatment is to reduce this inflammation. The pathophysiological sign of asthma is a reduction in the diameter of the airways caused by the contraction of smooth muscle, vascular congestion, edema of the bronchial wall and thick secretions. These changes are reflected in changes in lung function, increased respiratory work and abnormal distribution of pulmonary blood flow

The airways contain plugs made up of mucus, serum proteins, inflammatory cells and cellular debris. At a microscopic level, the airways are infiltrated with eosinophils and mononuclear cells. Evidence of microvascular leakage, epithelial changes and vasodilation are often observed. The smooth muscle of the airways is hypertrophic and characterized by the formation of new vessels, by the increase in the number of goblet epithelial cells and by the deposition of interstitial collagen under the epithelium. Inflammation affects all bronchial lung structures

Many different cell types have been implicated in the pathogenesis of asthma, such as eosinophils, lymphocytes, dendritic cells, smooth muscle, epithelial cells and endothelial cells. In severe asthma or with some comorbidities, neutrophils can also play an important role. For example, asthma patients tend to develop eosinophilic infiltrations into the respiratory tract. Furthermore, the recruitment of T helper 2 (TH2) cells appears to play an important role in initiating and maintaining airway inflammation. Variations in corticosteroid T cell reactivity may be related to steroid resistant clinical asthma. Dendritic cells play a central role in the development of the asthma phenotype, particularly in extrinsic asthma and also the role of the dendritic cell in providing a link between innate and adaptive immunity. These cells (dendritic cells) appear to help direct the type of adaptive immune response (TH1 vs. TH2). In asthma, a TH2 response is favored

Symptoms of Asthma

Symptoms of asthma include wheezing and coughing. Many, but not all, patients will carry the history of asthma in the presentation. At the start of the attack, patients will complain from

• Feeling of tightness and pain in chest 
• Shortness of breath
• Trouble sleeping, especially at night
• Coughing, when laughing, or doing an exercise or sports activity
• Difficulty talking
• Fatigue
• Anxiety or panic

Signs that asthma is probably getting worse include:

• Signs and Symptoms of Acute exacerbation of asthma
• Increased difficulty in breathing and the need to use a quick relief inhaler, measured with a device used to check lung function (peak flow meter)

As the disease worsens, wheezing becomes evident. A full history can be helpful in guiding the treatment of asthma exacerbations. Acute exacerbations of asthma are classified by clinical characteristics

Causes and Risk Factors of Asthma 

Atopy

Atopy is the main risk factor for asthma and non-atopic people have a very low risk of developing asthma. Asthmatic patients commonly suffer from other atopic diseases, in particular allergic rhinitis, which can be found in> 80% of asthmatic patients and atopic dermatitis (eczema). It can be found atopic in 40-50% of the population in rich countries, but only a proportion of atopic individuals who become asthmatic

Some environmental or genetic factors predispose to the development of asthma in atopic individuals. The allergens  are usually proteins that have protease activity, that lead to sensitization and the most common allergens are derived from house dust mites, cat and dog fur, cockroaches (in cities), tree and grass pollen and rodents (in laboratory workers). Atopy is due to the genetically determined production of specific IgE antibodies and many patients have a family history of allergic diseases

Genetic Predisposition

The family association of asthma and a high degree of concordance for asthma in identical twins indicate a genetic predisposition to the disease; however, it is not yet clear whether the genes that predispose to asthma are similar or in addition to those that predispose to asthma. Now it seems likely that several genes may also contribute specifically to asthma and there is growing evidence that the severity of asthma is also genetically determined

Epigenetic mechanisms

There is growing evidence that epigenetic mechanisms may be important, particularly in the early development of asthma. DNA methylation and histone modification patterns can be influenced by diet, exposure to cigarette smoke and air pollution and can influence the genes involved in the pathogenesis of asthma. These epigenetic changes can occur in the fetus following maternal environmental exposure

Diet

The role of dietary factors is controversial. Observational studies have shown that diets low in antioxidants such as vitamin C and vitamin A, magnesium, selenium and omega-3 polyunsaturated fats (fish oil) or rich in sodium and omega-6 polyunsaturated fats are associated with an increased risk of asthma. Vitamin D deficiency can also predispose to the development of asthma

Overweight

Studies have shown that, obesity is among the factors that cause asthma at various ages

Asthma Triggers

In most cases, asthma is caused by the inhalation of an allergen that triggers the chain of biochemical and tissue changes that lead to airway inflammation, bronchoconstriction and wheezing. Since avoiding (or at least minimizing) exposure is the most effective way to treat asthma, it is essential to identify which allergen or irritant is causing the symptoms in a particular patient. The most important inhalation allergens that lead to asthma attacks are:

• Animal hair

• Dust mites

• Fungi (molds) that grow indoors

• cockroach allergens

• Pollens generally cause allergic rhinitis rather than asthma, but in thunderstorms the pollen grains are disturbed and the particles that can be released can trigger severe exacerbations of asthma (temporal asthma)

• Professional exposure to chemicals, fumes or particles of industrial materials, hairdressing 

• Tobacco smoke

• Air pollutants, increased environmental levels of sulfur dioxide, ozone, diesel particulate matter and nitrogen oxides are associated with an increase in asthma symptoms

• Food preservatives called sulfites

• Inhaling cold air (cold-induced asthma), many patients report worsening asthma in the hot season and when the weather changes. Some asthmatics get worse when exposed to strong smells or perfumes, but the mechanism of this response is uncertain

• Exercise-induced asthma (in some children, asthma attacks are simply caused by exercise), exercise is a common trigger for asthma, particularly in children. The mechanism is related to hyperventilation, which causes an increase in osmolality in the fluid of the lining of the airways and triggers the release of the mediator from the mast cells, with consequent bronchoconstriction. Exercise-induced asthma (EIA) generally begins after the end of the exercise and spontaneously recovers in about 30 minutes. The EIA is worse in cold and dry climates than in hot and humid ones

• Stress or high level of anxiety, many asthmatics report a worsening of symptoms with stress . Psychological factors can lead to bronchoconstriction through cholinergic reflex pathways. Paradoxically, very severe stress, such as pain, generally does not get worse and can even improve asthma symptoms

• Once asthma is present, symptoms can start or worsen if the patient also has rhinitis (inflammation of the lining of the nose) or sinusitis. When, for some reason, stomach acid returns to the esophagus in a reaction called acid reflux or gastroesophageal reflux disease (GERD), it is common in asthma patients, as it increases with bronchodilators

Although acid reflux can trigger reflex bronchoconstriction, it rarely causes asthma symptoms and anti-reflux therapy generally does not reduce asthma symptoms in most patients. This condition can also worsen asthma

• Additionally, a viral respiratory tract infection can inflame an asthmatic reaction, upper respiratory tract virus infections such as rhinovirus, respiratory syncytial virus and coronavirus are the most common trigger factors for severe acute exacerbations and can also invade the epithelial cells of the fundus . like the upper airways

The mechanism by which these viruses cause exacerbations is poorly understood, but there is an increase in inflammation of the respiratory tract with an increase in the number of eosinophils and neutrophils. There is evidence of a reduced production of type I interferons by the epithelial cells of asthmatic patients, with a consequent increase in susceptibility to these viral infections and an increase in the inflammatory response

• Aspirin and drugs called beta blockers, often used to treat high blood pressure, can also worsen asthma symptoms, beta-adrenergic blockers often worsen asthma acutely and their use can be fatal. The mechanisms are unclear, but are probably mediated by an increase in cholinergic bronchoconstriction 

All beta-blockers should be avoided and also selective β, β2 blockers or topical application (eg Timolol eye drops) can be dangerous. Angiotensin converting enzyme inhibitors are theoretically harmful since they inhibit the degradation of kines, which are bronchoconstrictors; however, asthma rarely worsens and characteristic cough is not more common in asthmatics than in non-asthmatics

• Hormones, some women show premenstrual worsening of asthma, which can sometimes be very serious. The mechanisms are not fully understood, but are related to a drop in progesterone and, in severe cases, can be improved by treatment with high doses of progesterone or gonadotropin releasing factors. Thyrotoxicosis and hypothyroidism can worsen asthma, although the mechanisms are uncertain