Background
Asthma is the most common chronic disease of childhood, affecting 5-10% of children and resulting in approximately 400,000 hospitalizations annually. In 1997, the National Heart, Lung, and Blood Institute defined asthma as a chronic inflammatory disorder of the airways that involves many different cells, including mast cells, eosinophils, and T lymphocytes. This inflammation causes recurrent episodes of wheezing, dyspnea, and cough. Episodes are associated with obstruction that occurs in predominantly small-to-medium airways and that reverses partially or completely, either spontaneously or with treatment. Asthma is also associated with increased airway hyperresponsiveness to various stimuli.
Status asthmaticus is an acute exacerbation of asthma that remains unresponsive to initial treatment with bronchodilators. Status asthmaticus can vary from a mild form to a severe form with bronchospasm, airway inflammation, and mucus plugging that can cause difficulty breathing; carbon dioxide retention; hypoxemia; and respiratory failure. The typical clinical presentation involves persistent wheezing with retractions. However, not all children with severe asthma wheeze; some may present with cough, dyspnea, or emesis. Alternatively, not all patients who present with wheezing have asthma; some may have one of various other causes of obstructed airways.
Pathophysiology
Exposure to an allergen or trigger causes a characteristic form of airway inflammation in susceptible individuals, exemplified by mast cell degranulation, release of inflammatory mediators, infiltration by eosinophils, and activated T lymphocytes. Multiple inflammatory mediators may be involved, including interleukin (IL)–3, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-13; leukotrienes; and granulocyte-macrophage colony-stimulating factors (GM-CSFs). These, in turn, incite involvement of mast cells, neutrophils, and eosinophils.
Figure depicting antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms. Physiologically, acute asthma has 2 components: an early acute bronchospastic aspect marked by smooth muscle bronchoconstriction and a later inflammatory component resulting in airway swelling and edema.
Early bronchospastic response
Within minutes of exposure to an allergen, mast cell degranulation is observed along with the release of inflammatory mediators, including histamine, prostaglandin D2, and leukotriene C4. These substances cause airway smooth muscle contraction, increased capillary permeability, mucus secretion, and activation of neuronal reflexes. Early asthmatic response is characterized by bronchoconstriction that is generally responsive to bronchodilators, such as beta2-agonist agents.
Later inflammatory response
Release of inflammatory mediators prime adhesion molecules in the airway epithelium and capillary endothelium, which then allows inflammatory cells, such as eosinophils, neutrophils, and basophils, to attach to the epithelium and endothelium and subsequently migrate into the tissues of the airway. Eosinophils release eosinophilic cationic protein (ECP) and major basic protein (MBP). Both ECP and MBP induce desquamation of the airway epithelium and expose nerve endings. This interaction promotes further airway hyperresponsiveness in asthma. This inflammatory component may even occur in individuals with mild asthma exacerbation.
Bronchospasm, mucus plugging, and edema in the peripheral airways result in increased airway resistance and obstruction. Air trapping results in lung hyperinflation, ventilation/perfusion (V/Q) mismatch, and increased dead space ventilation. The lung becomes inflated near the end-inspiratory end of the pulmonary compliance curve, with decreased compliance and increased work of breathing. The increased pleural and intra-alveolar pressures that result from obstruction and hyperinflation, together with the mechanical forces of the distended alveoli, eventually lead to a decrease in alveolar perfusion. The combination of atelectasis and decreased perfusion leads to V/Q mismatch within lung units. The V/Q mismatch and resultant hypoxemia trigger an increase in minute ventilation.
In the early stages of acute asthma, hyperventilation may result in respiratory alkalosis. This is because obstructed lung units (slow compartment) are relatively less numerous than unobstructed lung units (fast compartment). Hyperventilation allows carbon dioxide removal via the fast compartment. However, as the disease progresses and more lung units become obstructed, an increase in the slow compartments occurs with decreased ability for carbon dioxide removal, eventually resulting in hypercarbia.
Epidemiology
Frequency
United States
Asthma affects up to 10% of the US population. Prevalence has increased by 60% in all ages in the past 2 decades, with an approximate 40% increase in children. A significant rise in hospitalization and asthma mortality rates, especially in children aged 0-4 and 9-16 years, has accompanied the increased incidence. Asthma, including status asthmaticus that requires hospitalization,[1] is the leading cause of school absenteeism among children with chronic illness. Factors associated with the increase in asthma include indoor pollution, overcrowding, increased incidence of viral infections, allergens, cockroach allergy, and, possibly, a decrease in breastfeeding.
In addition, some researchers have described the hygiene hypothesis, which suggests that the public health success in reducing early childhood infections through vaccination and hygiene reduces early autoimmunization and increases the likelihood of allergies and asthma. This hypothesis remains controversial.
International
Worldwide incidence is unclear but is estimated to be about 20 million cases, 15% of which occur in children. The dramatic rise in the worldwide incidence of asthma has been attributed, in part, to pollution and industrialization. Under the hygiene hypothesis, improved immunization and public health measures would contribute to the increase in asthma.
Mortality/Morbidity
The mortality rate from asthma has increased at an alarming rate. From 1993-1995, the overall annual age-adjusted death rate for asthma increased 40%. The rise in the mortality rate is even higher among blacks, among people living in poverty, and among children aged 0-4 and 9-16 years.
Race
Although asthma affects people of all races, in the United States, Hispanic children seem to have a higher incidence. The mortality rate in the United States is highest among blacks.
Sex
In infants, males generally have more severe disease than females. In older children, males and females are equally affected. Asthma has a higher incidence among adult females.
Age
Asthma is well distributed among people of all age groups. Children who have asthma in the first year of life and those aged 9-16 years tend to have much more severe disease.
Gorelick M, Scribano PV, Stevens MW, Schultz T, Shults J. Predicting need for hospitalization in acute pediatric asthma. Pediatr Emerg Care. Nov 2008;24(11):735-44. [Medline].
National Asthma Education and Prevention Program (NAEPP) Expert Panel. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. 2007. National Heart, Lung, and Blood Institute; August 28, 2007. [Full Text].
[Best Evidence] Andrews T, McGintee E, Mittal MK, et al. High-dose continuous nebulized levalbuterol for pediatric status asthmaticus: a randomized trial. J Pediatr. Aug 2009;155(2):205-10.e1. [Medline].
[Best Evidence] Castro-Rodriguez JA, Rodrigo GJ. Efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing and asthma: a systematic review with meta-analysis. Pediatrics. Mar 2009;123(3):e519-25. [Medline].
Ciarallo L, Brousseau D, Reinert S. Higher-dose intravenous magnesium therapy for children with moderate to severeacute asthma. Arch Pediatr Adolesc Med. Oct 2000;154(10):979-83. [Medline].
Stephanopoulos DE, Monge R, Schell KH, et al. Continuous intravenous terbutaline for pediatric status asthmaticus. Crit Care Med. Oct 1998;26(10):1744-8. [Medline].
Chiang VW, Burns JP, Rifai N, Lipshultz SE, Adams MJ, Weiner DL. Cardiac toxicity of intravenous terbutaline for the treatment of severe asthma in children: a prospective assessment. J Pediatr. Jul 2000;137(1):73-7. [Medline].
Kalyanaraman M, Bhalala U, Leoncio M. Serial cardiac troponin concentrations as marker of cardiac toxicity in children with status asthmaticus treated with intravenous terbutaline. Pediatr Emerg Care. Oct 2011;27(10):933-6. [Medline].
Ream RS, Loftis LL, Albers GM, et al. Efficacy of IV theophylline in children with severe status asthmaticus. Chest. May 2001;119(5):1480-8. [Medline]. [Full Text].
Wheeler DS, Jacobs BR, Kenreigh CA, et al. Theophylline versus terbutaline in treating critically ill children with statusasthmaticus: a prospective, randomized, controlled trial. Pediatr Crit Care Med. Mar 2005;6(2):142-7. [Medline].
[Best Evidence] Kim IK, Phrampus E, Venkataraman S, Pitetti R, Saville A, Corcoran T. Helium/oxygen-driven albuterol nebulization in the treatment of children with moderate to severe asthma exacerbations: a randomized, controlled trial. Pediatrics. Nov 2005;116(5):1127-33. [Medline].
Kudukis TM, Manthous CA, Schmidt GA, Hall JB, Wylam ME. Inhaled helium-oxygen revisited: effect of inhaled helium-oxygen during the treatment of status asthmaticus in children. J Pediatr. Feb 1997;130(2):217-24. [Medline].
Anderson M, Svartengren M, Bylin G, Philipson K, Camner P. Deposition in asthmatics of particles inhaled in air or in helium-oxygen. Am Rev Respir Dis. Mar 1993;147(3):524-8. [Medline].
Hebbar KB, Petrillo-Albarano T, Coto-Puckett W, et al. Experience with use of extracorporeal life support for severe refractory status asthmaticus in children. Crit Care. Mar 2 2009;13(2):R29. [Medline].
Elias JA, Zhu Z, Chupp G, Homer RJ. Airway remodeling in asthma. J Clin Invest. Oct 1999;104(8):1001-6. [Medline]. [Full Text].
Pearlman DS. Pathophysiology of the inflammatory response. J Allergy Clin Immunol. Oct 1999;104(4 Pt 1):S132-7. [Medline].
Asthma. In: Fuhrman B, Zimmerman J, eds. Pediatric Critical Care. 2nd ed. St. Louis, MO: Mosby; 1998:473-5.
Scarfone RJ, Loiselle JM, Joffe MD, et al. A randomized trial of magnesium in the emergency department treatment of childrenwith asthma. Ann Emerg Med. Dec 2000;36(6):572-8. [Medline].
Schuh S, Johnson DW, Callahan S, et al. Efficacy of frequent nebulized ipratropium bromide added to frequent high-dosealbuterol therapy in severe childhood asthma. J Pediatr. Apr 1995;126(4):639-45. [Medline].
Schwarz AJ, Lubinsky PS. Acute severe asthma. In: Levin DL, Morriss FC, eds. Essentials of Pediatric Intensive Care. Vol 1. 2nd ed. 1997:143-56.
Werner HA. Status asthmaticus in children: a review. Chest. Jun 2001;119(6):1913-29. [Medline]. [Full Text].
Yung M, South M. Randomised controlled trial of aminophylline for severe acute asthma. Arch Dis Child. Nov 1998;79(5):405-10. [Medline]. [Full Text].
Zorc JJ, Pusic MV, Ogborn CJ, et al. Ipratropium bromide added to asthma treatment in the pediatric emergency department. Pediatrics. Apr 1999;103(4 Pt 1):748-52. [Medline]. [Full Text].
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