Asthma

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Asthma is a chronic inflammatory disorder of the airways, closely associated with an overexpression of immunoglobulin E (IgE). ^[1] At the cellular level, it is associated with an inflammatory response including infiltration of cells including neutrophils, eosinophils and lymphocytes; mast cell activation; and injury to epithelial cells.

"Inflammation contributes to airway hyperresponsiveness, airflow limitation, respiratory symptoms, and disease chronicity. In some patients, persistent changes in airway structure occur, including sub-basement fibrosis, mucus hypersecretion, injury to epithelial cells, smooth muscle hypertrophy, and angiogenesis."

Atopy, or genetic predisposition to an IgE response to common allergens, is the strongest known predisposing factors. Viral respiratory infections exacerbate existing disease and may contribute to the development of asthma.

Epidemiology[edit]

Etiology[edit]

According to the USA's National Heart, Lung, and Blood Institute of the National Institutes of Health, "atopy, the genetic predisposition for the development of an immunoglobulin E (IgE)-mediated response to common aeroallergens, is the strongest identifiable predisposing factor for developing asthma".

Atopy, although genetically predetermined, is exacerbated by environmental factors. Diesel gas emissions were shown to increase atopy in asthma in the same way as allergen exposure itself. As was emphasised by the researchers who isolated this effect, the demonstration of such a modification in the expression of genetic predispositions, which was achieved through epigenetic mechanisms, urges researchers to adopt a "new paradigm" in asthma and atopy management.^[2]

Pathophysiology[edit]

Diagnosis[edit]

Asthma may be overdiagnosed.^[3]

Prognosis[edit]

Many patients do well in spite of stopping their medications.^[4][5]

Clinical practice guidelines recommend stepping down treatment for patients with asthma after symptoms have been controlled for at least three months.^[6][7]

Treatment[edit]

Treatment of acute exacerbations[edit]

United States of America National Health Lung and Blood Institute's recommendations for the management of asthma exacerbations .

Classification[edit]

The U.S. National Asthma Education and Prevention Program defines exacerbations as:^[8]

• Mild. "Dyspnea only with activity (assess tachypnea in young children)"; peak expiratory flow rate ≥70 percent predicted or personal best
• Moderate. "Dyspnea interferes with or limits usual activity"; peak expiratory flow rate 40−69 percent predicted or personal best
• Severe. "Dyspnea at rest; interferes with conversation"; peak expiratory flow rate <40 percent predicted or personal best
  • Life threatening. "Too dyspneic to speak; perspiring"; peak expiratory flow rate <25 percent predicted or personal best

Drug therapy[edit]

Beta-adrenergic agonists[edit]

Albuterol, a beta-adrenergic agonists may be given 0.5 mg/kg/hour by continuous nebulization, although this may not reduce rates of hospitalization^[9]. In children albuteral may be given as 0.3 mg/kg/hour by continuous nebulization.^[10]

As opposed to short-acting beta-adrenergic blockers such as albuterol, which have both prophylactic and treatment roles, the long-acting variants, such as salmeterol, have no place in an acute attack.

Beta-adrenergic agonists[edit]

It is not clear whether adding ipratropium helps.^[11]

Corticosteroids[edit]

Regarding corticosteroids, a systematic review concluded:^[12]

"There is no evidence that corticosteroid doses greater than standard doses (prednisone 50-100 mg equivalent) are beneficial. Oral and intravenous corticosteroids, as well as intramuscular and oral corticosteroid regimens, seem to be similarly effective. A nontapered 5- to 10-day course of corticosteroid therapy seems to be sufficient for most discharged patients. Combinations of oral and inhaled corticosteroids on emergency department/hospital discharge might minimize the risk of relapse."

At the first signs of an attack, quadrupling^[13] but not doubling^[14], the dose of inhaled corticosteroid may reduce the risk of an exacerbation of asthma requiring treatment with oral corticosteroids.

Patients that have been prescribed inhalers that combine a corticosteroid with a long-acting beta-adrenergic blocker, however, must understand that they cannot increase the use of that inhaler to get more corticosteroid. To do so could give a dangerous overdose of the beta-agonist.

Leukotriene antagonists[edit]

Leukotriene antagonists, montelukast or zafirlukast, may help.

Magnesium[edit]

Magnesium sulfate 2 grams in 50 mL of normal saline intranvenously over 15 minutes may help.^[15]

Chronic treatment[edit]

Chronic asthma is an inflammatory disease. The core of modern treatment is preventing the inflammation, and using bronchodilators only when the inflammation goes out of control and causes bronchospasm.

Drug therapy[edit]

Many drugs beneficial for managing asthma are need to be inhaled into the bronchi and lungs. The simplest device for administering them is a metered-dose inhaler (MDI), which, in its basic form, produces a puff of aerosol to be inhaled with a single breath. Unfortunately, it takes a certain amount of dexterity to actuate the inhaler and take a simultaneous breath. By inserting a spacer chamber between the MDI and the mouthpiece, so the dose can be taken with several nonsynchronized breaths, administration becomes much more reliable. Spacers are a standard of care for children and animals, unless a nebulizer is used to deliver an aerosol using a powered pump that takes no special effort of inhalation.

Beta-adrenergic agonists[edit]

For more information, see: Adrenergic beta-agonist.

These are bronchodilators. They may be administered in metered-dose inhaler, nebulizer, or oral and parenteral forms.

Short acting beta-agonist agents are the initial treatment.

Long-acting adrenergic beta-agonists may help^[16]; however, they should not be used without corticosteroids and maybe should not be used in African American patients.^[17] As opposed to short-acting beta-adrenergic blockers such as albuterol, which have both prophylactic and treatment roles, the long-acting variants, such as salmeterol, have no place in an acute attack but may provide better overall control. Nevertheless, a higher death rate has been associated with the long-acting drugs.

They might be safe in asthma as long as corticosteroids are used; however they should be stopped if possible once asthma is controlled^[18]. Single-nucleotide polymorphisms of the ADBR2 subtype of adrenergic receptor may affect response to adrenergic beta-agonists. According to a meta-analyses by the Cochrane Collaboration, when used with corticosteroids the relative risk for asthma-related death is increased at 1.34 although this increase was not statistically significant with a confidence interval of 0.30 to 5.97.^[16][19] One meta-analysis found increased death even if corticosteroids are used; however, this meta-analysis excluded trials in which no deaths or intubations occurred.^[20] A meta-analysis found not increased risk among patients taking salmeterol and corticosteroids.^[21]

Corticosteroids[edit]

Inhaled corticosteroids have little if any systemic absorption, and have become a mainstay of the antiinflammatory component of asthma management.

Oral corticosteroids may be necessary in the management of severe asthma, but their many side effects offset their undoubted value. They are, however, fairly safe when used in short courses for exacerbations. For more severe disease, a specialist should be involved in finding ways to minimize their dose and adverse effects. These include such things as alternate-day dosing, or combining them with low-dosages of antimetabolites such as methotrexate.

Intravenous corticosteroids are part of the emergency treatment of asthma, along with nebulized bronchodilators. The intravenous route does not provide an appreciably faster onset of action than oral administration, but, of course, can be given to a patient who cannot swallow.

Methylxanthines[edit]

Theophylline is an orally administered bronchodilator, generally relegated to third-line status. It has a narrow therapeutic index and many drug interactions, usually because one or the other up- or down-regulates a Cytochrome P450 excretory pathway. Especially when used with other drugs, frequent blood level monitoring is wise to avoid toxicity.

Mast cell stabilizers[edit]

Leukotriene antagonists[edit]

Leukotriene antagonists may help.^[22]

Environmental management[edit]

High-efficiency particulate air (HEPA) cleaners may help.^[23]

Monitoring[edit]

A systematic review by the Cochrane Collaboration found that monitoring sputum eosinophils can guide treatment^[24] The review identified three randomized controlled trials that found that benefit from adjusting anti-inflammatory medications to maintain less than 2 to 8% eosinophils in sputum.

Regarding peak expiratory flow rate monitoring, according to a meta-analysis of randomized controlled trials by the Cochrane Collaboration, peak flow monitoring is equivalent to symptom monitoring.^[25] The U.S. National Asthma Education and Prevention Program recommends peak expiratory flow rate monitoring for selected patients.^[8] A more recent trial, with improved methods of symptom monitoring and education, found that peak flow monitoring did not improvement asthma control.^[26]

More recently, studies have examined graphical display of peak flow monitoring and reported improved outcomes by increasing routing use of inhaled corticosteroids^[27] and in a second study, no benefit^[28] in information.

References[edit]