Asthma

Asthma is characterized by a predisposition to chronic inflammation of the lungs in which the airways (bronchi) are reversibly narrowed. Asthma affects 7% of the population of the United States, 6.5% of British people and a total of 300 million worldwide. During asthma attacks (exacerbations of asthma), the smooth muscle cells in the bronchi constrict, the airways become inflamed and swollen, and breathing becomes difficult. This is often referred to as a tight chest and is a sign to immediately take medication.

Asthma causes 4,000 deaths a year in the United States. Medicines such as inhaled short-acting beta-2 agonists may be used to treat acute attacks. Attacks can also be prevented by avoiding triggering factors such as allergens or rapid temperature changes and through drug treatment such as inhaled corticosteroids and then long-acting beta-2 agonists if necessary. Leukotriene antagonists are less effective than corticosteroids, but have no side effects. Monoclonal antibodies, such as mepolizumab and omalizumab, are sometimes effective. Prognosis is good with treatment.

In contrast to chronic obstructive pulmonary disease and chronic bronchitis, the inflammation of asthma is reversible. In contrast to emphysema, asthma affects the bronchi, not the alveoli.

The National Heart, Lung and Blood Institute defines asthma as a common chronic disorder of the airways characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness (bronchospasm), and an underlying inflammation.

Public attention in the developed world has recently focused on the predisposition because of its rapidly increasing prevalence, affecting up to one quarter of urban children.

Signs and symptoms

Because of the spectrum of severity within the asthma, some people with asthma only rarely experience symptoms, usually in response to triggers, where as other more severe cases may have marked airflow obstruction at all times.

Asthma exists in two states: the steady-state of chronic asthma, and the acute state of an acute asthma exacerbation. The symptoms are different depending on what state the patient is in.

Common symptoms of asthma in a steady-state include: nighttime coughing, shortness of breath with exertion but no dyspnea at rest, a chronic 'throat-clearing' type cough, and complaints of a tight feeling in the chest. Severity often correlates to an increase in symptoms. Symptoms can worsen gradually and rather insidiously, up to the point of an acute exacerbation of asthma. It is a common misconception that all people with asthma wheeze—some never wheeze, and their disease may be confused with another chronic obstructive pulmonary disease such as emphysema or chronic bronchitis.

An acute exacerbation of asthma is commonly referred to as an asthma attack. The cardinal symptoms of an attack are shortness of breath (dyspnea), wheezing, and chest tightness. Although the former is often regarded as the primary symptom of asthma, some patients present primarily with coughing, and in the late stages of an attack, air motion may be so impaired that no wheezing may be heard. When present the cough may sometimes produce clear sputum. The onset may be sudden, with a sense of constriction in the chest, as breathing becomes difficult and wheezing occurs (primarily upon expiration, but sometimes in both respiratory phases). It is important to note inspiratory stridor without expiratory wheeze however, as an upper airway obstruction may manifest with symptoms similar to an acute exacerbation of asthma, with stridor instead of wheezing, and will remain unresponsive to bronchodilators.

Signs of an asthmatic episode include wheezing, prolonged expiration, a rapid heart rate (tachycardia), and rhonchous lung sounds (audible through a stethoscope). During a serious asthma attack, the accessory muscles of respiration (sternocleidomastoid and scalene muscles of the neck) may be used, shown as in-drawing of tissues between the ribs and above the sternum and clavicles, and there may be the presence of a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest.

During very severe attacks, an asthma sufferer can turn blue from lack of oxygen and can experience chest pain or even loss of consciousness. Just before loss of consciousness, there is a chance that the patient will feel numbness in the limbs and palms may start to sweat. The person's feet may become cold. Severe asthma attacks which are not responsive to standard treatments, called status asthmaticus, are life-threatening and may lead to respiratory arrest and death.

Though symptoms may be very severe during an acute exacerbation, between attacks a patient may show few or even no signs of the disease.

Cause

Asthma is caused by environmental and genetic factors, which can influence how severe asthma is and how well it responds to medication. Some environmental and genetic factors have been confirmed by further research, while others have not been. Underlying both environmental and genetic factors is the role of the upper airway in recognizing the perceived dangers and protecting the more vulnerable lungs by shutting down the airway. Profet <Profet M. “The function of allergy: immunological defense against toxins.” Q Rev Biol. 1991 Mar;66(1):23-62.> has argued that allergens look to our immune systems like significant threats. Asthma, in this view, is seen as an evolutionary defense. This view also suggests that removing or reducing airborne pollutants should be successful at reducing the problem.

Environmental

Many environmental risk factors have been associated with asthma development and morbidity in children, but a few stand out as well-replicated or that have a meta-analysis of several studies to support their direct association.

Environmental tobacco smoke, especially maternal cigarette smoking, is associated with high risk of asthma prevalence and asthma morbidity, wheeze, and respiratory infections. Low air quality, from traffic pollution or high ozone levels, has been repeatedly associated with increased asthma morbidity and has a suggested association with asthma development that needs further research. Recently many people have gotten asthma from being over weight at a very young age from nine to seventeen.

Recent studies show a relationship between exposure to air pollutants (e.g. from traffic) and childhood asthma. This research finds that both the occurrence of the disease and exacerbation of childhood asthma are affected by outdoor air pollutants.

Caesarean sections have been associated with asthma when compared with vaginal birth; a meta-analysis found a 20% increase in asthma prevalence in children delivered by Caesarean section compared to those who were not. It was proposed that this is due to modified bacterial exposure during Caesarean section compared with vaginal birth, which modifies the immune system (as described by the hygiene hypothesis).

Psychological stress has long been suspected of being an asthma trigger, but only in recent decades has convincing scientific evidence substantiated this hypothesis. Rather than stress directly causing the asthma symptoms, it is thought that stress modulates the immune system to increase the magnitude of the airway inflammatory response to allergens and irritants.

Viral respiratory infections at an early age, along with siblings and day care exposure, may be protective against asthma, although there have been controversial results, and this protection may depend on genetic context.

Antibiotic use early in life has been linked to development of asthma in several examples; it is thought that antibiotics make one susceptible to development of asthma because they modify gut flora, and thus the immune system (as described by the hygiene hypothesis). The hygiene hypothesis is a hypothesis about the cause of asthma and other allergic disease, and is supported by epidemiologic data for asthma. For example, asthma prevalence has been increasing in developed countries along with increased use of antibiotics, c-sections, and cleaning products. All of these things may negatively affect exposure to beneficial bacteria and other immune system modulators that are important during development, and thus may cause increased risk for asthma and allergy.

Recently scientists connected the rise in prevalence of asthma, to the rise in use of paracetamol, suggesting the possibility that paracetamol can cause asthma.

It has been suggested that viral infections such as HSV, VSV and CSV are correlated to asthma episodes.

Genetic

Over 100 genes have been associated with asthma in at least one genetic association study. However, such studies must be repeated to ensure the findings are not due to chance. Through the end of 2005, 25 genes had been associated with asthma in six or more separate populations.
Many of these genes are related to the immune system or to modulating inflammation. However, even among this list of highly replicated genes associated with asthma, the results have not been consistent among all of the populations that have been tested. This indicates that these genes are not associated with asthma under every condition, and that researchers need to do further investigation to figure out the complex interactions that cause asthma. One theory is that asthma is a collection of several diseases, and that genes might have a role in only subsets of asthma. For example, one group of genetic differences (single nucleotide polymorphisms in 17q21) was associated with asthma that develops in childhood.

Risk factors

Studying the prevalence of asthma and related diseases such as eczema and hay fever have yielded important clues about some key risk factors. The strongest risk factor for developing asthma is a family history of atopic disease; this increases one's risk of hay fever by up to 5x and the risk of asthma by 3-4x. In children between the ages of 3-14, a positive skin test for allergies and an increase in immunoglobulin E increases the chance of having asthma. In adults, the more allergens one reacts positively to in a skin test, the higher the odds of having asthma.

Because much allergic asthma is associated with sensitivity to indoor allergens and because Western styles of housing favor greater exposure to indoor allergens, much attention has focused on increased exposure to these allergens in infancy and early childhood as a primary cause of the rise in asthma. Primary prevention studies aimed at the aggressive reduction of airborne allergens in a home with infants have shown mixed findings. Strict reduction of dust mite allergens, for example, reduces the risk of allergic sensitization to dust mites, and modestly reduces the risk of developing asthma up until the age of 8 years old. However, studies also showed that the effects of exposure to cat and dog allergens worked in the converse fashion; exposure during the first year of life was found to reduce the risk of allergic sensitization and of developing asthma later in life.

The inconsistency of this data has inspired research into other facets of Western society and their impact upon the prevalence of asthma. One subject that appears to show a strong correlation is the development of asthma and obesity. In the United Kingdom and United States, the rise in asthma prevalence has echoed an almost epidemic rise in the prevalence of obesity. In Taiwan, symptoms of allergies and airway hyper-reactivity increased in correlation with each 20% increase in body-mass index.

Diagnosis

Asthma is defined simply as reversible airway obstruction. Reversibility occurs either spontaneously or with treatment. The basic measurement is peak flow rates and the following diagnostic criteria are used by the British Thoracic Society:

• 20% difference on at least three days in a week for at least two weeks;
• 20% improvement of peak flow following treatment, for example:
• 10 minutes of inhaled β-agonist (e.g., salbutamol);
• six weeks of inhaled corticosteroid (e.g., beclometasone);
• 14 days of 30 mg prednisolone.
• 20% decrease in peak flow following exposure to a trigger (e.g., exercise).

In many cases, a physician can diagnose asthma on the basis of typical findings in a patient's clinical history and examination. Asthma is strongly suspected if a patient suffers from eczema or other allergic conditions—suggesting a general atopic constitution—or has a family history of asthma. While measurement of airway function is possible for adults, most new cases are diagnosed in children who are unable to perform such tests.

In children, the key to asthma diagnosis is the sound of wheezing or a high-pitched sound upon exhalation. Other clues are recurrent wheezing, breathing difficulty, or chest tightness, or a history of coughing that is worse at night. The doctor should also know if the child's symptoms are worse with exercise, colds,or exposure to certain irritants such as smoke, emotional stress, or changes in the weather. nicotine smoke is enough to trigger wheezing so bad as to make the person diagnosed with asthma feel like they have to vomit.

Other information important to diagnosis is the age at which symptoms began and how they progressed, the timing and pattern of wheezing, when and how often a child had to visit a clinic or hospital emergency department because of symptoms, whether the child ever took bronchodilator medication for the symptoms and the nature of the response to medication.

Although pediatricians may tend to ask parents for information about their children's symptoms, studies suggest that children themselves are reliable sources as early as age 7 and perhaps even as early as age 6.

In adults and older children, diagnosis can be made with spirometry or a peak flow meter (which tests airway restriction), looking at both the diurnal variation and any reversibility following inhaled bronchodilator medication. The latest guidelines from the U.S. National Asthma Education and Prevention Program (NAEPP) recommend spirometry at the time of initial diagnosis, after treatment is initiated and symptoms are stabilized, whenever control of symptoms deteriorates, and every 1 or 2 years on a regular basis.

The NAEPP guidelines do not recommend testing peak expiratory flow as a regular screening method, because it is more variable than spirometry. However, testing peak flow at rest (or baseline) and after exercise can be helpful, especially in young patients who may experience only exercise-induced asthma. It may also be useful for daily self-monitoring and for checking the effects of new medications. Peak flow readings can be charted on graph paper charts together with a record of symptoms or use peak flow charting software. This allows patients to track their peak flow readings and pass information back to their doctor or nurse.

In the Emergency Department, doctors may use a capnography which measures the amount of exhaled carbon dioxide, along with pulse oximetry which shows the percentage of hemoglobin that is carrying oxygen, to determine the severity of an asthma attack as well as the response to treatment.

More recently, exhaled nitric oxide has been studied as a breath test indicative of airway inflammation in asthma.

Treatment

Perhaps the most important step in controlling asthma is establishing a partnership between doctor and patient (whether child or adult) to create a specific, customized plan for proactively monitoring and managing symptoms. It is essential to be certain that someone who has asthma understands (and takes an active part in deciding) what needs to be accomplished, including reducing exposure to allergens, taking medical tests to assess the severity of symptoms, and possibly using medications. The treatment plan should be written down, consulted at every visit, and adjusted according to changes in symptoms.

The most effective treatment for asthma is identifying triggers, such as pets or aspirin, and limiting or eliminating exposure to them. If trigger avoidance is insufficient, medical treatment is available. Desensitization has been suggested as a possible cure. Additionally, some trial subjects were able to remove their symptoms by retraining their breathing habits with the Buteyko method.

Other forms of treatment include relief medication, prevention medication, long-acting β2-agonists, and emergency treatment.
 

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