Overview and Risk Factors
Asthma is a chronic respiratory disease in which bronchial obstruction and bronchospasm lead to dyspnea, wheezing, chest tightness, and/or cough. Key to its pathogenesis is inflammation of the airways. Inflammatory cells, including mast cells, eosinophils, T lymphocytes, plasma cells, and basophils, release histamine, various kinins, leukotrienes, prostaglandins, lipid mediators, tumor necrosis factor a (TNF-a), neuropeptides, substance P, and a host of other inflammatory mediators. Other features are smooth muscle hypertrophy, edema, basement membrane thickening, and mucous accumulation in airways.
The inflammatory process is triggered by allergens, which play a central role in approximately 60% of asthma patients. Other triggers include respiratory infections; inhaled irritants (particularly occupational exposures); stress; exercise; cold temperatures; medications such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and beta-blockers. Asthma is also caused by agents to which a person has specific sensitivity, such as aspirin and tartrazine, which is a petroleum-derived colorant.1
The prevalence of asthma in the United States is approximately 5%. Although the disease commonly begins in childhood, up to 40% of patients develop asthma as adults. Among adult patients, 10% to 20% have occupational asthma. An increase in the global prevalence of asthma over the past 30 years has been attributed to climate change, allergen exposure, urbanization, and air pollution, among other factors, but the precise pathogenesis of the observed increase is not clear. Asthma is more prevalent in affluent countries, leading to the question of whether overuse of antibiotics has led to reduced bacterial antigen exposure and a shift of the immune system to a more atopic phenotype. While air pollution is known to exacerbate asthma, it is not clear whether it can cause the disease.2,3
In children, asthma occurs more commonly in boys. Among adults, however, the disease is most prevalent in women over 40. Both mortality and morbidity are greater in African Americans, compared with whites. These differences are attributed in part to socioeconomic factors.4
Other risk factors include:
- Family history. About 75% of children with 2 asthmatic parents also have asthma.
- Environmental and occupational factors. These factors include tobacco smoke, animal dander, dust mites, plants, pollen, mold, enzymes, chemicals, and metals.
- Obesity. A large cohort, the Nurses' Health Study II, revealed a linear relation between body mass index (BMI) and risk of asthma, with a relative risk of 2.7 for the most obese group.5 Another study showed improvement in objective measures of asthma severity and control for those who lost weight.6
Diagnosis and Treatment
A characteristic history of periodic bronchospasm and variable airflow obstruction, occurring with or without stimuli that provoke an attack, is usually present. During acute attacks, symptoms such as tachypnea, chest tightness, wheezing, shortness of breath, and cough, with or without sputum production, are common. Difficulty taking deep breaths, difficulty finishing sentences, and/or lethargy indicate greater severity, and, possibly, status asthmaticus.
Physical examination often reveals use of accessory respiratory muscle, a prolonged expiratory phase with diffuse wheezing, and sometimes hyper-resonant lung fields with diminished breath sounds due to air trapping. Severe attacks may have less wheezing (due to reduced air flow), cyanosis, and signs of mental obtundation.
Routine pulmonary function tests during asymptomatic periods may be entirely normal. During exacerbations or in patients who have had asthma for many years, spirometry typically shows reduced FEV1 (forced expiratory volume in 1 second), a reduced FEV1/FVC (forced vital capacity) ratio, and/or reduced peak flows, and may also demonstrate increased total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC).
Blood testing may reveal eosinophilia and elevated serum IgE levels in asthma patients with atopy.
Skin testing can identify allergens that may be environmentally controlled.
With optimal asthma management, patients should have no symptoms or exercise limitation, no exacerbations or need for oral steroids, no albuterol requirement, and, overall, minimal medications and side effects.
Types of Asthma
Mild intermittent asthma is treated on an as-needed basis with inhaled beta-2-selective agonists, such as albuterol. Beta-adrenergic medications are bronchodilators and can be used before exercise or when symptoms occur; these are sometimes called "rescue medications".7 An alternative for exercise-induced asthma is cromolyn, a mast cell stabilizer. It is beneficial only if taken before exercise.
Mild persistent asthma usually requires daily inhalation of a corticosteroid, along with a short-acting beta-agonist for breakthrough symptoms. Inhaled corticosteroids decrease the risk of exacerbations and reduce the need for rescue medication. Common steroid preparations include budesonide, fluticasone, triamcinalone, beclomethasone, and flunisolide.
Moderate persistent asthma calls for an increased dose of inhaled corticosteroid and/or the addition of a long-acting beta agonist or leukotriene antagonist. Examples of leukotriene antagonists are zileuton, montelukast, pranlukast, and zafirlukast. Sustained-release theophylline or cromolyn preparations are alternatives. Failure to control symptoms with the use of 2 of the above medications suggests the patient may have severe asthma or perhaps another diagnosis.
Severe asthma requires high-dose inhaled corticosteroids or oral corticosteroids, along with other controller medicines.
Leukotriene antagonists are no substitute for inhaled corticosteroids,8 but in patients who make an excess of leukotrienes, they may complement the above therapies. Patients with exercise-induced bronchoconstriction, nasal polyposis, and aspirin sensitivity (triad asthma) tend to respond well to leukotriene antagonists.
Long-acting beta-agonists, such as salmeterol, are not to be used as monotherapy,9 as they have no significant anti-inflammatory effects. Indeed, they cause prolonged bronchodilation, which may mask a progressive inflammatory process that may eventually lead to a severe attack.
A recent study showed a small increase in risk of death among patients, particularly for African Americans, using salmeterol in addition to typical asthma drugs.10
Cromolyn and theophylline are rarely considered as first-line agents. However, in combination with inhaled corticosteroids, any of the above may be beneficial.
Omalizumab is a new monoclonoal antibody directed to human IgE. For patients with refractory asthma or for whom inhaled and/or oral steroids cause major side effects, anti-IgE therapy may reduce steroid requirements and side effects, and provide improved control for allergic asthmatics.
Immediate bronchodilation with inhaled albuterol is the mainstay of emergency treatment. In the emergency room, the delivery method for albuterol is most often continuous nebulization (approximately 10 mg/hr), or 2.5 mg every 20 minutes for 3 doses. However, data show that using a metered-dose inhaler (with a spacer) for 4 to 6 successive inhalations is approximately equal to 1 nebulizer. This method has the advantages of reducing the total amount of albuterol administered and shortening the length of stay in the emergency department, without increasing hospital admissions.11
Systemic corticosteroids, such as prednisone, prednisolone, and methylprednisolone, should be started concurrently in a patient who does not adequately respond to albuterol therapy. Their effect is often delayed up to 6 hours. Inhaled ipratropium bromide (an anticholinergic agent) is indicated if a person has moderate to severe airway obstruction that is unresponsive to beta agonists alone.
Heliox can benefit patients with severe airflow obstruction and mild hypoxemia in the acute setting. In patients with severe hypoxemia, the helium concentration needs to be decreased to a level less than what has been shown to be effective for improving airflow obstruction (70-80% helium) in order to deliver oxygen concentrations needed to maintain normoxia. Therefore heliox is contraindicated in severe hypoxemia.
The following factors are under investigation for their roles in asthma:
Maintenance of ideal body weight. Studies have found that a higher body weight increases the risk of asthma in both children and adults.12
Modifying fatty acid intake. Recent reviews13 and prospective studies14,15 have implicated omega-6 fatty acids (found in animal products and in margarine and other vegetable oils) as a possible risk factor for asthma. Consumption of these fatty acids has increased in Westernized societies along with a rise in asthma incidence, possibly due to their being precursors of leukotrienes with bronchoconstrictive effects. Studies have implicated margarine consumption as a risk factor for current asthma in both young adults16 and an older adult population.17 Also, a high ratio of omega-6 to omega-3 fatty acid intake was significantly associated with the risk for asthma in a pediatric population.14
Clinical interventions have not consistently demonstrated a benefit of adjustment in fatty acid intake in asthmatic patients. Increasing dietary intake of the omega-6 fat linoleic acid did not result in asthma exacerbation in 1 study,18 possibly indicating that animal sources of omega-6 fat (ie, arachidonic acid) may be responsible for these effects. Although fish intake has been associated with a lower risk for childhood asthma in certain studies,19 others have found associations between greater fish intake and an increase in asthma risk.20,21 In spite of some data revealing improvement in exercise-induced asthma symptoms in individuals given omega-3 fatty acid supplements,22 intervention trials have not yet definitively established the benefit of this approach in asthmatic patients.23
Controlled clinical trials have not yet established that a reduction in the intake of fat from margarine, other sources of omega-6 fatty acids, or fish is an effective treatment for asthma. Nevertheless, other reasons exist for limiting dietary fat intake in asthma patients, such as the current obesity epidemic. Obese patients may be at risk for acquiring asthma.24 As mentioned in the Obesity chapter, the worldwide prevalence of overweight is directly related to the percentage of fat in the diet, and low-fat diets have been consistently shown to promote moderate weight loss.25 For individuals who are underweight or may not benefit from a low-fat diet, the use of judicious amounts of monounsaturated fat from olive or canola oil may be a healthier alternative to vegetable oils, due to the latter's inconvertibility to pro-inflammatory leukotrienes.
Avoidance of salty foods. Pulmonary function improves with low-salt diets.26 In persons with exercise-induced asthma, following a low-salt diet (1,500 mg/day sodium restriction, equivalent to about 3.7 g NaCl/day) reduces post-exercise asthma severity to below the diagnostic limit of a 10% fall in FEV1.27
Fruits, vegetables, and other foods high in antioxidants. Several studies have found relationships between higher fruit and vegetable intakes and reduced risk for asthma.13,28 In some studies, patients with asthma were found to have lower dietary intakes or blood levels of antioxidants.29,30 Elevated levels of lipid peroxides indicative of oxidative stress have been found in these patients31 and appear to correlate with symptom severity.32 The Nurses' Health Study, a prospective study in adults, found that women in the highest quintile of vitamin E intake from food (not from supplements) had a 47% lower risk of adult-onset asthma than those in the lowest quintile. Studies have also found that supplemental antioxidants in the form of carotenoids (high-dose beta-carotene, lycopene, and other carotenoids) or combinations of vitamin C and vitamin E significantly improved exercise-induced asthma.27
Avoidance of allergenic foods, beverages, and preservatives. Food-induced bronchospasm occurs with the intake of certain foods in 2% to 24% of persons with asthma. Foods implicated most often as a cause include peanuts, milk, eggs, tree nuts, soy, wheat, legumes, beans, and turkey.33 The presence of both sulfating agents and histamine in wine may aggravate asthma,34 and several studies have found that asthma may be induced by green tea.35 Avoidance of trigger foods improves peak expiratory flow rate in asthmatic children.36,37
When dairy products are omitted from the diet, calcium may be obtained from calcium-fortified soymilk or juices, green leafy vegetables, beans, and calcium-precipitated tofu. Allergy testing should be considered in patients who appear to experience exacerbation of asthma in relation to certain foods or food groups.
Alternatively, patients can attempt to determine if a food triggers asthma by eliminating all common potentially allergenic foods and then reintroducing them one at a time. Patients should keep careful records of food intake and any change in symptom frequency to confirm that a given food is provoking an exacerbation of asthma.
Vegetarian and vegan diets. In a study of 27,766 Seventh-day Adventists,38 vegetarian women reported a lower incidence of asthma, compared with women on nonvegetarian diets.38 The theoretical basis for the value of vegan diets is the absence of potential triggers, particularly dairy products and eggs, as well as a relative lack of arachidonic acid. Observational studies have produced conflicting results, including some that suggest a protective effect of dairy product use in relation to asthma.39 However, in a clinical trial of a vegan diet, 22 of 24 asthma patients noted significant improvements in vital capacity, FEV1, and physical working capacity after 1 year on a vegan diet.40 Additional clinical trials are required to investigate the role of vegetarian and vegan diets.
Preventive measures. Measures recommended to decrease the risk for developing asthma include breast-feeding for the first 4 to 6 months of life and avoiding the following foods until children reach the specified ages: dairy products until at least 1 year old; eggs until at least 2 years old; and peanuts, nuts, and fish until at least 3 years old.41
Avoid allergenic foods per patient history.
Vegetarian diet, nondairy, may be tried on a prospective basis.
What to Tell the Family
Asthma can generally be well managed with diet and medications. Family members can help by encouraging a diet high in fruits, vegetables, and whole grains, and by minimizing fats and oils. Adopting such a diet themselves may help protect family members from later health problems, as well as make it easier for the patient to adhere to the dietary changes.
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