Asthma: Difference between revisions
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=====Corticosteroids===== | =====Corticosteroids===== | ||
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===== | =====Methylxanthines===== | ||
[[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. | [[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. | ||
Revision as of 09:01, 5 December 2009
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 the epithelium.
"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
Etiology
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
Diagnosis
Asthma may be overdiagnosed.[3]
Prognosis
Treatment
Treatment of acute exacerbations
At the first signs of an attack, quadrupeling[4] but not doubling[5], the dose of inhaled corticosteroid may reduce the risk of an exacerbation of asthma requiring treatment with oral corticosteroids .
The U.S. National Asthma Education and Prevention Program defines exacerbations as:[6]
- 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
Chronic treatment
Drug therapy
Beta-adrenergic agonists
These drugs may be administered by inhaler, nebulizer, or oral and parenteral forms.
Short acting beta-agonist agents are the initial treatment.
Long-acting adrenergic beta-agonists may help[7]; however, they should not be used without corticosteroids and maybe should not be used in African American patients.[8] They might be safe in asthma as long as corticosteroids are used. 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.[7][9]
Corticosteroids
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
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
Leukotriene antagonists
Monitoring
A systematic review by the Cochrane Collaboration found that monitoring sputum eosinophils can guide treatment[10] 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.[11] The U.S. National Asthma Education and Prevention Program recommends peak expiratory flow rate monitoring for selected patients.[6]
References
- ↑ National Asthma Education and Prevention Program (2002), Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma, Expert Panel Report 2: Guidelines for the diagnosis and management of asthma., National Institutes of Health
- ↑ Liu J, Ballaney M, Al-alem U, et al (March 2008). "Combined inhaled diesel exhaust particles and allergen exposure alter methylation of T helper genes and IgE production in vivo". Toxicol. Sci. 102 (1): 76-81. DOI:10.1093/toxsci/kfm290. PMID 18042818. Research Blogging.
- ↑ Aaron, Shawn D.; Katherine L. Vandemheen, Louis-Philippe Boulet, R. Andrew McIvor, J. Mark FitzGerald, Paul Hernandez, Catherine Lemiere, Sat Sharma, Stephen K. Field, Gonzalo G. Alvarez, Robert E. Dales, Steve Doucette, Dean Fergusson, for the Canadian Respiratory Clinical Research Consortium (2008-11-18). "Overdiagnosis of asthma in obese and nonobese adults". CMAJ 179 (11): 1121-1131. DOI:10.1503/cmaj.081332. Retrieved on 2008-11-25. Research Blogging.
- ↑ Oborne J, Mortimer K, Hubbard RB, Tattersfield AE, Harrison TW (2009). "Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial.". Am J Respir Crit Care Med 180 (7): 598-602. DOI:10.1164/rccm.200904-0616OC. PMID 19590019. Research Blogging.
- ↑ Harrison TW, Oborne J, Newton S, Tattersfield AE (2004). "Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial.". Lancet 363 (9405): 271-5. PMID 14751699. Review in: ACP J Club. 2004 Sep-Oct;141(2):37
- ↑ 6.0 6.1 National Asthma Education and Prevention Program: Expert Panel Report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD. National Heart, Lung, and Blood Institute, 2007. (NIH publication no. 08-4051). Available from www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. (Accessed September 1, 2008).
- ↑ 7.0 7.1 Walters EH, Gibson PG, Lasserson TJ, Walters JA (2007). "Long-acting beta2-agonists for chronic asthma in adults and children where background therapy contains varied or no inhaled corticosteroid". Cochrane Database Syst Rev (1): CD001385. DOI:10.1002/14651858.CD001385.pub2. PMID 17253458. Research Blogging.
- ↑ Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE (2006). "Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths". Ann. Intern. Med. 144 (12): 904-12. PMID 16754916. [e]
- ↑ Cates CJ, Cates MJ (2008). "Regular treatment with salmeterol for chronic asthma: serious adverse events". Cochrane Database Syst Rev (3): CD006363. DOI:10.1002/14651858.CD006363.pub2. PMID 18646149. Research Blogging.
- ↑ Petsky H, Kynaston J, Turner C, et al (2007). "Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults". Cochrane database of systematic reviews (Online) (2): CD005603. DOI:10.1002/14651858.CD005603.pub2. PMID 17443604. PMID 17443604. Research Blogging.
- ↑ Powell H, Gibson PG (2003). "Options for self-management education for adults with asthma". Cochrane Database Syst Rev (1): CD004107. PMID 12535511. [e]