Asthma
Template:TOC-right 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
Prognosis
Treatment
Treatment of acute exacerbations
The U.S. National Asthma Education and Prevention Program defines exacerbations as:[3]
- 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.
In order to comply with ozone protection, these medicines must not use chlorofluorocarbons (CFC) for a chlorofluorocarbon by January 1, 2009.[4][5] Inhalers using hydrofluoroalkane (HFA) propellants are CFC-free. The HFA based inhalers are brand name and more expensive. They are Ventolin by GlaxoSmithKline, ProAir by Ivax, Proventil by Schering-Plough and Xopenex by Sepracor. The first three use albuterol whereas Xopenex uses levalbuterol. Financial assistance is available for patients available through the Partnership for Prescription Assistance (1-888-477-2669).[5] As of November, 2007, the prices costs in American dollars were Ventolin 36.12, ProAir 36.72, Proventil 42.20 and Xopenex 49.75.[6]
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
Methylxanthines
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.[3]
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.
- ↑ 3.0 3.1 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).
- ↑ Anonymous (2008). Information on the Elimination of Chlorofluorocarbon-containing (CFC) Albuterol MDIs and Other Ozone-Depleting Drug Products. Food and Drug Administration.
- ↑ 5.0 5.1 Tarkan L (May 13, 2008). Rough Transition to a New Asthma Inhaler. New York Times. Retrieved on 2008-05-13.
- ↑ Drugs for Chronic Obstructive Pulmonary Disease (pdf) 95. Medical Letter (Novmber, 2007).
- ↑ 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]