eMedicine Specialties > Allergy and Immunology > Asthma

Allergic and Environmental Asthma

Author: William F Kelly III, MD, Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Staff Physician, Division of Pulmonary/Critical Care Medicine, Department of Medicine, Walter Reed Army Medical Center
Coauthor(s): John J Oppenheimer, MD, Clinical Associate Professor, University of Medicine and Dentistry of New Jersey; Director Clinical Research, Pulmonary and Allergy Associates, PA; Gregory J Argyros Col, MD, Chief, Graduate Medical and Dental Education, J7/Joint Task Force, National Capital Region Medical; Professor of Medicine, Uniformed Services University of the Health Sciences
Contributor Information and Disclosures

Updated: Jun 17, 2009

Introduction

Background

Asthma is a clinical syndrome characterized by episodic reversible airway obstruction, increased bronchial reactivity, and airway inflammation. Asthma results from complex interactions among inflammatory cells, their mediators, airway epithelium and smooth muscle, and the nervous system. In genetically susceptible individuals, these interactions can lead the patient with asthma to symptoms of breathlessness, wheezing, cough, and chest tightness.

Risk factors for asthma include a family history of allergic disease, the presence of allergen-specific immunoglobulin E (IgE), viral respiratory illnesses, exposure to aeroallergens, cigarette smoke, obesity, and lower socioeconomic status.

Environmental exposure in sensitized individuals is a major inducer of airway inflammation, which is a hallmark finding in the asthmatic lung. Although triggers induce inflammation through different pathways, the resulting effects all lead to increased bronchial reactivity.

The importance of allergy in asthma has been well established. Exposure to dust mites within the first year of life is associated with later development of asthma and, possibly, atopy. Mite and cockroach antigens are common, and exposure and sensitization has been shown to increase asthma morbidity. Allergies trigger asthma attacks in 60-90% of children and in 50% of adults. Approximately 75-85% of patients with asthma have positive (immediate) skin test results. In children, this sensitization is associated with disease activity.

Although most people with asthma have aeroallergen-induced symptoms, some individuals manifest symptoms with nonallergic triggers. About 3-10% of people with asthma are sensitive to nonsteroidal antiinflammatory drugs (NSAIDs). Approximately 5-10% of people with asthma have occupation- or industry-induced airway disease. Many individuals develop symptoms after viral respiratory tract infections.

Allergen avoidance and other environmental control efforts are feasible and effective. Symptoms, pulmonary function test findings, and airway hyperreactivity (AHR) improve with avoidance of environmental allergens. Removing even one of many allergens can result in clinical improvement. However, patients frequently are not compliant with such measures.

Pathophysiology

The allergic response in the airway is the result of a complex interaction of mast cells, eosinophils, T lymphocytes, macrophages, dendritic cells, and neutrophils. Inhalation-challenge studies with allergens reveal an early allergic response (EAR), which occurs within minutes and peaks at 20 minutes following inhalation of the allergen. Clinically, the manifestations of the EAR in the airway include bronchial constriction, airway edema, and mucus plugging. These effects are the result of mast cell–derived mediators. Four to ten hours later, a late allergic response may occur, which is characterized by infiltration of inflammatory cells into the airway and is most likely caused by cytokine-mediated recruitment and activation of lymphocytes and eosinophils.

Antigen-presenting cells (ie, macrophages, dendritic cells) in the airway capture, process, and present antigen to helper T cells, which, in turn, become activated and secrete cytokines. Helper T cells can be induced by cytokines to develop into TH 1 (ie, by interferon-gamma, interleukin [IL]–2) or TH 2 (ie, by IL-4, IL-5, IL-9, IL-13). Regulatory T cells (Treg) appear to play an important role in TH 2 cell response to allergens. Allergens drive the cytokine pattern toward TH 2, which promotes B-cell IgE production and eosinophil recruitment. Subsequently, IgE binds to the high-affinity receptor for IgE, Fc-epsilon-RI, on the surface of mast cells and basophils; with subsequent exposure to the allergen, the IgE is cross-linked. This leads to degranulation of the mast cell and basophil. Preformed mast cell mediators, such as histamine and proteases, are released, leading to the EAR.

Newly formed mediators such as leukotriene C4 and prostaglandin D2 also contribute to the EAR. Proinflammatory cytokines (IL-3, IL-4, IL-5, tumor necrosis factor-alpha [TNF-α]) are released from mast cells and are generated de novo after mast cell activation. These cytokines contribute to the late allergic response by attracting neutrophils and eosinophils. The eosinophils release major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase into the airway, causing epithelial denudation and exposure of nerve endings. The lymphocytes that are attracted to the airway continue to promote the inflammatory response by secreting cytokines and chemokines, which further potentiate the cellular infiltration into the airway.

The ongoing inflammatory process eventually results in hypertrophy of smooth muscles, hyperplasia of mucous glands, thickening of basement membranes, and continuing cellular infiltration. These long-term changes of the airway, referred to as airway remodeling, can ultimately lead to fibrosis and irreversible airway obstruction in some, but not most, patients.

Frequency

United States

Prevalence is difficult to determine because definitions and survey methods vary, but the prevalence of asthma appears to be on the rise. Asthma has a prevalence of 10.9%, affecting more than 22 million people, including more than 6 million children.1,2

International

Global Initiative for Asthma (GINA) researchers note an increase in prevalence, morbidity, mortality, and economic burden over the past 40 years, especially in children.1 Asthma affects more than 300 million people worldwide, and some reports suggest asthma prevalence is increasing by 50% every decade.1 The highest recorded prevalences outside North America are in the United Kingdom (>15%), New Zealand (15.1%), and Australia (14.7%).3

Mortality/Morbidity

  • In the United States, mortality has increased, especially in children who live in inner-city areas, despite advances in disease understanding and therapy. The number of deaths annually decreased from 5067 (1960-1962) to a low of 1870 (1975-1978) and then increased to 5429 (1993-1995). Worldwide, approximately 180,000 deaths annually are attributed to asthma; most deaths occur in those older than 45 years.
  • In the United States, asthma is annually responsible for 1.5 million emergency department (ED) visits; 500,000 hospital admissions (third leading preventable cause); and 100 million days of restricted activity. Medical expenses as well as lost work and productivity cost an estimated $12.7 billion in 1998. In Western countries, the financial burden on patients ranges from $300 to $1,300 per patient year, increasing with more severe disease.
  • Increased morbidity is multifactorial; morbidity may be increased by increased exposure to indoor allergens, less exposure to viral infections early in life, more environmental pollution, overuse of short-acting beta-2 agonists, underuse of anti-inflammatory medications, and limited access to or education about health care.
  • Worldwide, economic costs for asthma are more than costs for tuberculosis and AIDS combined. Cost is associated with disease severity;4 more than half of all expenditures are attributed to the 10-20% of patients with the most severe disease.

Race

  • Genetic differences may alter susceptibility to asthma as well as responsiveness to asthma medications.2 Significant genetic variation exists between and within racial and ethnic groups, but the issue is confounded by important coexisting economic, cultural, and environmental differences, including geography (place of birth).5 Associations have been suggested between polymorphisms in the B2-adrenergic receptor (ADRB2) and reduced responsiveness and increased adverse effects with long-acting beta-agonist bronchodilators. More recent studies suggest this is not the case.6
  • Females, ethnic minorities, people with a low annual family income (<$20,000/y in the United States), and persons with poor access to or education about health care have worse outcomes than other individuals.
  • Hospitalization and death rates are 50% higher for African American adults than white adults and 150% higher in children.
  • Asthma is rare in Eskimos.

Sex

  • Boys have been shown to be at greater risk for asthma than girls. In children younger than 14 years, the prevalence is twice as high in boys than in girls.
  • The difference narrows with age, and women aged 40 years have a greater prevalence than men of the same age.

Age

  • Disease onset can occur in people of any age, but children often present when younger than 6 years. Asthma is one of the most common chronic diseases of childhood.
  • Many young children “outgrow” asthma, especially boys who have no personal or family history of atopy. However, clinical experience shows that many teenagers who become asthma-free may experience asthma again in their 20s and 30s. Perinatal exposure to allergens or passive smoke has been postulated to make outgrowing asthma less likely.

Clinical

History

The classic history consists of wheeze, cough, and dyspnea. The predictive value of any single parameter is approximately 30% but is much higher when parameters are combined. Chest discomfort (eg, pain, tightness, congestion, inability to take a full breath) is also common. Some patients may have cough without other symptoms. Refractory chest colds may also suggest the diagnosis.

  • Record the following:
    • Age of onset
    • Frequency and severity of daytime and nocturnal symptoms
    • Symptom triggers, such as exercise, animals, irritants (smoke), and occupation (worse on workdays)
    • Seasonal and geographic variation, including presence of symptoms indoors and outdoors
    • Limits on activity, lost work or school days, and quality of life
    • Number of emergency department and urgent clinic visits, hospital admissions, intensive care unit (ICU) stays, and need for mechanical ventilation
    • Past treatments, including oral and inhaled steroids, frequency of rescue inhaler use, immunotherapy, and environmental avoidance
    • Family history of asthma
    • Personal or family history of atopy, allergy, rhinitis (including nonallergic rhinitis), or sinusitis
    • Gastroesophageal reflux symptoms
    • Food allergy
    • Growth (children)
    • Atopic dermatitis
  • All patients should be asked about or should undergo assessment regarding exacerbation of symptoms, as follows:
    • Allergic
      • Perennial symptoms - Pet in the home (especially in the bedroom, bed, or both), school, day care, or work environment; moisture, dampness, and humidifier use; mold and musty odors in any part of the home; cockroaches in the home; worsening of symptoms after vacuuming rugs (typical of dust mite allergen)
      • Seasonal symptoms (may extend beyond one season in temperate or tropical climates) - Early spring (trees), late spring and summer (grasses), summer and fall (dry molds), and fall (weeds)
    • Environmental
      • Personal or secondary tobacco smoke exposure in or out of the home
      • Gas-burning stoves, fireplaces, or heaters used in home
      • Sprays or chemical agents at work, home, or with hobbies
      • Symptoms only at one place (ie, at work during week with no symptoms on weekends)
      • School or business associates with similar problems
      • Symptoms after eating (dried, canned, or processed food)
      • Medications such as beta-blockers (including eye drops), aspirin, or other NSAIDs

Physical

Physical examination findings are often normal.

  • Head and neck: Nasal mucosal swelling, discharge, polyps, or sinus percussion tenderness may suggest associated allergic rhinitis or sinusitis. Wheezing heard only or mostly over the neck may suggest vocal cord dysfunction (VCD) or other laryngeal abnormality, though VCD can be present without a localizing wheeze. Increased jugular venous distension may point to an alternative explanation, such as heart failure, for the patient’s dyspnea and wheezing. Similarly, palpation of cervical or supraclavicular adenopathy would suggest malignancy, sarcoidosis, or infection.
  • Cardiac: Findings are normal. Patients with status asthmaticus may have a pulsus paradoxus greater than 10 mm Hg. A murmur, S3 gallop, or rub suggests a cardiac problem and not asthma.
  • Respiratory: During an acute asthma exacerbation, lung examination findings may include wheezing, rhonchi, hyperinflation, or prolonged expiratory phase. With severe disease, lung auscultation may reveal absent breath sounds (indicating poor air movement) or signs of respiratory distress and failure (eg, nasal flaring, grunting, accessory muscle use, cyanosis). Focal wheezing may indicate foreign body or other airway obstruction such as a tumor.
  • Skin: Check the patient for atopic dermatitis.
  • Extremities: Digital clubbing should not be present. Edema should also not be present. If edema is found, this suggests right- or left-sided heart failure.

Causes

The etiology of asthma is likely multifactorial. Genetic factors may control individual predispositions to asthma. Genetics may also be associated with responses to medications. Variation in the beta-adrenergic receptor gene of the Arg-Arg type has been associated with adverse responses to inhaled short-acting beta-agonist inhalers. Genetics alone cannot account for the significant increases in prevalence, as genetic factors take several generations to develop, and asthma and atopy are not always co-inherited. Several environmental or lifestyle factors have been implicated.

  • The hygiene hypothesis proposes that cleaner environments have led to less immunological stress, reducing the development of an asthma-protective TH 1 cytokine phenotype.
  • Measles infection, BCG vaccine administration, hepatitis A seropositivity, and other stimuli that increase production of interferon-gamma and IL-12 may inhibit the TH 2 allergic response.
  • In selected series, vaccinations, fewer childhood infections, liberal use of antibiotics, more processed food in diets, smaller families, and less exposure to day care environments have been associated with increased atopy and asthma. This is exemplified in western versus eastern Germany; asthma, atopy, and AHR are more prevalent in western Germany, while bronchitis is more common in eastern Germany.
  • One theory to explain the increased prevalence of allergic disease is that with fewer infectious stimuli in the environment, the in utero TH 2 allergic cytokine state never switches to the TH 1 state.
  • Causes or triggers of asthma can be divided as follows:
    • Allergic: Aeroallergens can include seasonal pollen, mold spores, dust mites, animal allergens, and food (especially in children). Monosodium glutamate does not appear to be an allergen.7
    • Nonallergic: These may include smoke, odors, cold air and weather, chemicals, medications (eg, aspirin, other NSAIDs, beta-blockers), exercise, hormonal changes (eg, pregnancy, menstrual cycle), and bisulfite food additives.

More on Allergic and Environmental Asthma

Overview: Allergic and Environmental Asthma
Differential Diagnoses & Workup: Allergic and Environmental Asthma
Treatment & Medication: Allergic and Environmental Asthma
Follow-up: Allergic and Environmental Asthma
References
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References

  1. Braman SS. The global burden of asthma. Chest. Jul 2006;130(1 Suppl):4S-12S. [Medline].

  2. Expert panel-3. NHLBI NIH; AUG 2007. 440. [Full Text].

  3. Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med. Nov 23 2006;355(21):2226-35. [Medline].

  4. Marcus P. Incorporating anti-IgE (omalizumab) therapy into pulmonary medicine practice: practice management implications. Chest. Feb 2006;129(2):466-74. [Medline].

  5. Scirica CV, Celedon JC. Genetics of asthma: potential implications for reducing asthma disparities. Chest. Nov 2007;132(5 Suppl):770S-781S. [Medline].

  6. Bleecker ER, Postma DS, Lawrance RM, Meyers DA, Ambrose HJ, Goldman M. Effect of ADRB2 polymorphisms on response to longacting beta2-agonist therapy: a pharmacogenetic analysis of two randomised studies. Lancet. Dec 22 2007;370(9605):2118-25. [Medline].

  7. Woessner KM, Simon RA, Stevenson DD. Monosodium glutamate sensitivity in asthma. J Allergy Clin Immunol. Aug 1999;104(2 Pt 1):305-10. [Medline].

  8. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J. Nov 2005;26(5):948-68. [Medline].

  9. Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. Mar 2008;100(3 Suppl 3):S1-148. [Medline].

  10. Irwin RS. Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines. Chest. Jan 2006;129(1 Suppl):80S-94S. [Medline].

  11. Juniper EF, Kline PA, Vanzieleghem MA, et al. Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Am Rev Respir Dis. Oct 1990;142(4):832-6. [Medline].

  12. The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med. Oct 12 2000;343(15):1054-63. [Medline].

  13. Pauwels RA, Lofdahl CG, Postma DS, et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med. Nov 13 1997;337(20):1405-11. [Medline].

  14. Suissa S, Ernst P, Benayoun S, Baltzan M, Cai B. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med. Aug 3 2000;343(5):332-6. [Medline].

  15. [Best Evidence] Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM,. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. Jan 2006;129(1):15-26. [Medline].

  16. Rabe KF, Pizzichini E, Stallberg B, Romero S, Balanzat AM, Atienza T. Budesonide/formoterol in a single inhaler for maintenance and relief in mild-to-moderate asthma: a randomized, double-blind trial. Chest. Feb 2006;129(2):246-56. [Medline].

  17. Woolcock A, Lundback B, Ringdal N, Jacques LA. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit Care Med. May 1996;153(5):1481-8. [Medline].

  18. Currie GP, Lee DK, Srivastava P. Long-acting bronchodilator or leukotriene modifier as add-on therapy to inhaled corticosteroids in persistent asthma?. Chest. Oct 2005;128(4):2954-62. [Medline].

  19. [Best Evidence] Sheikh A, Hurwitz B, Shehata Y. House dust mite avoidance measures for perennial allergic rhinitis. Cochrane Database Syst Rev. Jan 24 2007;CD001563. [Medline].

  20. Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2003;CD001186.

  21. Bruggenjurgen B, Reinhold T, Brehler R, et al. Cost-effectiveness of specific subcutaneous immunotherapy in patients with allergic rhinitis and allergic asthma. Ann Allergy Asthma Immunol. Sep 2008;101(3):316-24. [Medline].

  22. Cox G, Thomson NC, Rubin AS, et al. Asthma control during the year after bronchial thermoplasty. N Engl J Med. Mar 29 2007;356(13):1327-37. [Medline].

  23. Aaron SD, Fergusson D, Dent R, Chen Y, Vandemheen KL, Dales RE. Effect of weight reduction on respiratory function and airway reactivity in obese women. Chest. Jun 2004;125(6):2046-52. [Medline].

  24. Hallstrand TS, Bates PW, Schoene RB. Aerobic conditioning in mild asthma decreases the hyperpnea of exercise and improves exercise and ventilatory capacity. Chest. Nov 2000;118(5):1460-9. [Medline].

  25. Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet. Oct 23-29 2004;364(9444):1505-12. [Medline].

  26. Hendeles L, Colice GL, Meyer RJ. Withdrawal of albuterol inhalers containing chlorofluorocarbon propellants. N Engl J Med. Mar 29 2007;356(13):1344-51. [Medline].

  27. US Food and Drug Administration. National Transition from Chlorofluorocarbon (CFC) Propelled Albuterol Inhalers to Hydrofluroalkane (HFA) Propelled Albuterol Inhalers. FDA Public Health Advisory. FDA web site. August 28, 2008. Available at: http://www.fda.gov/cder/drug/advisory/albuterol_cfc.htm. Accessed January 13, 2009.

  28. Szefler SJ, Phillips BR, Martinez FD, et al. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. Feb 2005;115(2):233-42. [Medline].

  29. Sander N, Fusco-Walkert SJ, Harder JM, Chipps BE. Dose counting and the use of pressurized metered-dose inhalers: running on empty. Ann Allergy Asthma Immunol. Jul 2006;97(1):34-8. [Medline].

  30. Levenson M. Long-acting beta-agonists and adverse asthma events meta-analysis. Statistical briefing package for Joint Meeting of the Pulmonary-Allergy Drugs Advisory Committee, Drug Safety and Risk Management Advisory Committee and Pediatric Advisory Committee. December 10-11, 2008. Available at: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4398b1-01-FDA.pdf. Accessed January 13, 2009.

  31. Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. Oct 1999;14(4):902-7. [Medline].

  32. Vollmer WM, Markson LE, O'Connor E, et al. Association of asthma control with health care utilization and quality of life. Am J Respir Crit Care Med. Nov 1999;160(5 Pt 1):1647-52. [Medline].

  33. Li J, Oppenheimer J, Bernstein IL, et al. Attaining asthma control. A practice parameter. J Allerg Clin Immunol. 2005;115:S3-11.

  34. [Best Evidence] Fisher EB, Strunk RC, Highstein GR, et al. A randomized controlled evaluation of the effect of community health workers on hospitalization for asthma: the asthma coach. Arch Pediatr Adolesc Med. Mar 2009;163(3):225-32. [Medline].

  35. Oppenheimer J, Aaronson D. Impact of recent black box warnings in the allergy world. Ann Allergy Asthma Immunol. Oct 2007;99(4):364-6. [Medline].

  36. Adkinson NF Jr, Eggleston PA, Eney D, et al. A controlled trial of immunotherapy for asthma in allergic children. N Engl J Med. Jan 30 1997;336(5):324-31. [Medline].

  37. Alberts WM, do Pico GA. Reactive airways dysfunction syndrome. Chest. Jun 1996;109(6):1618-26. [Medline].

  38. American Thoracic Society. Lung function testing: selection of reference values and interpretative strategies. American Thoracic Society. Am Rev Respir Dis. Nov 1991;144(5):1202-18. [Medline].

  39. Barnes PJ. Is immunotherapy for asthma worthwhile?. N Engl J Med. Feb 22 1996;334(8):531-2. [Medline].

  40. Barnes PJ. Is there a role for immunotherapy in the treatment of asthma? No. Am J Respir Crit Care Med. Nov 1996;154(5):1227-8. [Medline].

  41. Beasley R, Burgess C, Crane J, Pearce N, Roche W. Pathology of asthma and its clinical implications. J Allergy Clin Immunol. Jul 1993;92(1 Pt 2):148-54. [Medline].

  42. Blackhall K, Appleton S, Cates CJ. Ionisers for chronic asthma. Cochrane Database Syst Rev. 2003;CD002986. [Medline].

  43. Boulet LP, Chapman KR, Cote J, et al. Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med. Jun 1997;155(6):1835-40. [Medline].

  44. Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol. Oct 1998;102(4 Pt 1):558-62. [Medline].

  45. Bousquet J, Lockey R, Malling HJ, et al. Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization. American academy of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. Nov 1998;81(5 Pt 1):401-5. [Medline].

  46. Britton J, Lewis S. Objective measures and the diagnosis of asthma. We need a simple diagnostic test-but don't yet have one. BMJ. Jul 25 1998;317(7153):227-8. [Medline].

  47. [Best Evidence] Buist AS, Vollmer WM, Wilson SR, Frazier EA, Hayward AD. A randomized clinical trial of peak flow versus symptom monitoring in older adults with asthma. Am J Respir Crit Care Med. Nov 15 2006;174(10):1077-87. [Medline].

  48. Burney P. The changing prevalence of asthma?. Thorax. Oct 2002;57 Suppl 2:II36-II39. [Medline].

  49. Busse WW. Mechanisms and advances in allergic diseases. J Allergy Clin Immunol. Jun 2000;105(6 Pt 2):S593-8. [Medline].

  50. Busse WW, Lemanske RF Jr. Asthma. N Engl J Med. Feb 1 2001;344(5):350-62. [Medline].

  51. Christopher KL, Wood RP 2nd, Eckert RC, Blager FB, Raney RA, Souhrada JF. Vocal-cord dysfunction presenting as asthma. N Engl J Med. Jun 30 1983;308(26):1566-70. [Medline].

  52. Corren J, Casale T, Deniz Y, Ashby M. Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol. Jan 2003;111(1):87-90. [Medline].

  53. Creticos PS, Reed CE, Norman PS, et al. Ragweed immunotherapy in adult asthma. N Engl J Med. Feb 22 1996;334(8):501-6. [Medline].

  54. Cross S, Buck S, Hubbard J. Allergy in general practice. BMJ. May 23 1998;316(7144):1584-7. [Medline].

  55. Demoly P, Bousquet J. Anti-IgE therapy for asthma. Am J Respir Crit Care Med. Jun 1997;155(6):1825-7. [Medline].

  56. Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. Aug 12 1999;341(7):468-75. [Medline].

  57. Fahy JV, Fleming HE, Wong HH, et al. The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med. Jun 1997;155(6):1828-34. [Medline].

  58. Gaga M, Papageorgiou N, Zervas E, Gioulekas D, Konstantopoulos S. Control of asthma under specialist care: is it achieved?. Chest. Jul 2005;128(1):78-84. [Medline].

  59. Gardner MO, Doyle NM. Asthma in pregnancy. Obstet Gynecol Clin North Am. Jun 2004;31(2):385-413, vii. [Medline].

  60. Georgitis JW. Immunotherapy and Allergen Avoidance for Allergic Airways Disorders. Lesson 3, Vol 12. Northbrook, Ill: American College of Chest Physicians; 1997:[Full Text].

  61. Gergen PJ, Mortimer KM, Eggleston PA, et al. Results of the National Cooperative Inner-City Asthma Study (NCICAS) environmental intervention to reduce cockroach allergen exposure in inner-city homes. J Allergy Clin Immunol. Mar 1999;103(3 Pt 1):501-6. [Medline].

  62. Hamid Q, Tulic' MK, Liu MC, Moqbel R. Inflammatory cells in asthma: mechanisms and implications for therapy. J Allergy Clin Immunol. Jan 2003;111(1 Suppl):S5-S12; discussion S12-7. [Medline].

  63. Herxheimer H, Schaefer O. Letter: Asthma in Canadian Eskimos. N Engl J Med. Dec 26 1974;291(26):1419. [Medline].

  64. Holgate ST. Science, medicine, and the future. Allergic disorders. BMJ. Jan 22 2000;320(7229):231-4. [Medline].

  65. Hughes AT. Anti-IgE antibody may help treat some asthma patients. JAMA. Dec 13 2000;284(22):2859-60. [Medline].

  66. Humbert M, Beasley R, Ayres J, Slavin R, Hebert J, Bousquet J. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. Mar 2005;60(3):309-16. [Medline].

  67. Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. Oct 1999;14(4):902-7. [Medline].

  68. Kay AB. Allergy and allergic diseases. First of two parts. N Engl J Med. Jan 4 2001;344(1):30-7. [Medline].

  69. Kharitonov SA, Barnes PJ. Exhaled biomarkers. Chest. Nov 2006;130(5):1541-6. [Medline].

  70. Kuipers H, Lambrecht BN. The interplay of dendritic cells, Th2 cells and regulatory T cells in asthma. Curr Opin Immunol. Dec 2004;16(6):702-8. [Medline].

  71. Kwon HL, Belanger K, Bracken MB. Effect of pregnancy and stage of pregnancy on asthma severity: a systematic review. Am J Obstet Gynecol. May 2004;190(5):1201-10. [Medline].

  72. Lang DM, Polansky M. Patterns of asthma mortality in Philadelphia from 1969 to 1991. N Engl J Med. Dec 8 1994;331(23):1542-6. [Medline].

  73. Larche M. Regulatory T cells in allergy and asthma. Chest. Sep 2007;132(3):1007-14. [Medline].

  74. Legorreta AP, Christian-Herman J, O'Connor RD, Hasan MM, Evans R, Leung KM. Compliance with national asthma management guidelines and specialty care: a health maintenance organization experience. Arch Intern Med. Mar 9 1998;158(5):457-64. [Medline].

  75. Lewis SA, Britton JR. Measles infection, measles vaccination and the effect of birth order in the aetiology of hay fever. Clin Exp Allergy. Dec 1998;28(12):1493-500. [Medline].

  76. Leynaert B, Bousquet J, Neukirch C, Liard R, Neukirch F. Perennial rhinitis: An independent risk factor for asthma in nonatopic subjects: results from the European Community Respiratory Health Survey. J Allergy Clin Immunol. Aug 1999;104(2 Pt 1):301-4. [Medline].

  77. Li JT, Pearlman DS, Nicklas RA, et al. Algorithm for the diagnosis and management of asthma: a practice parameter update: Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. Nov 1998;81(5 Pt 1):415-20. [Medline].

  78. Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. Arch Intern Med. May 10 1999;159(9):941-55. [Medline].

  79. Littner MR, Leung FW, Ballard ED 2nd, Huang B, Samra NK,. Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptoms. Chest. Sep 2005;128(3):1128-35. [Medline].

  80. Livingston E, Thomson NC, Chalmers GW. Impact of smoking on asthma therapy: a critical review of clinical evidence. Drugs. 2005;65(11):1521-36. [Medline].

  81. Mannino DM, Homa DM, Pertowski CA, et al. Surveillance for asthma--United States, 1960-1995. MMWR CDC Surveill Summ. Apr 24 1998;47(1):1-27. [Medline].

  82. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. Jan 19 1995;332(3):133-8. [Medline].

  83. Matricardi PM, Rosmini F, Ferrigno L, et al. Cross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis A virus. BMJ. Apr 5 1997;314(7086):999-1003. [Medline].

  84. Milgrom H. Is there a role for treatment of asthma with omalizumab?. Arch Dis Child. Jan 2003;88(1):71-4. [Medline].

  85. Milgrom H, Fick RB Jr, Su JQ, et al. Treatment of allergic asthma with monoclonal anti-IgE antibody. rhuMAb-E25 Study Group. N Engl J Med. Dec 23 1999;341(26):1966-73. [Medline].

  86. Moller C, Dreborg S, Ferdousi HA, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol. Feb 2002;109(2):251-6. [Medline].

  87. National Asthma Education and Prevention Program. Guidelines for the Diagnosis and Management of Asthma: Expert Panel Report 2. NIH Publication No. 97-4051. Bethesda, Md: 1997:[Full Text].

  88. National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics--2002. J Allergy Clin Immunol. Nov 2002;110(5 Suppl):S141-219. [Medline].

  89. Nelson HS. Allergen immunotherapy: where is it now?. J Allergy Clin Immunol. Apr 2007;119(4):769-79. [Medline].

  90. Nelson HS. The Bela Schick lecture for 1985. The atopic diseases. Ann Allergy. Sep 1985;55(3):441-7. [Medline].

  91. Newman-Taylor A. Environmental determinants of asthma. Lancet. Feb 4 1995;345(8945):296-9. [Medline].

  92. Norman PS. Is there a role for immunotherapy in the treatment of asthma? Yes. Am J Respir Crit Care Med. Nov 1996;154(5):1225-6. [Medline].

  93. Oba Y, Salzman GA. Cost-effectiveness analysis of omalizumab in adults and adolescents with moderate-to-severe allergic asthma. J Allergy Clin Immunol. Aug 2004;114(2):265-9. [Medline].

  94. Osborne ML, Vollmer WM, Pedula KL, Wilkins J, Buist AS, O'Hollaren M. Lack of correlation of symptoms with specialist-assessed long-term asthma severity. Chest. Jan 1999;115(1):85-91. [Medline].

  95. Pearce N, Douwes J, Beasley R. Is allergen exposure the major primary cause of asthma?. Thorax. May 2000;55(5):424-31. [Medline].

  96. Peat JK, Li J. Reversing the trend: reducing the prevalence of asthma. J Allergy Clin Immunol. Jan 1999;103(1 Pt 1):1-10. [Medline].

  97. Pollart SM, Smith TF, Morris EC, Gelber LE, Platts-Mills TA, Chapman MD. Environmental exposure to cockroach allergens: analysis with monoclonal antibody-based enzyme immunoassays. J Allergy Clin Immunol. Feb 1991;87(2):505-10. [Medline].

  98. Rambasek TE, Lang DM, Kavuru MS. Omalizumab: where does it fit into current asthma management?. Cleve Clin J Med. Mar 2004;71(3):251-61. [Medline].

  99. Rodrigo G, Pollack C, Rodrigo C, Rowe BH. Heliox for nonintubated acute asthma patients. Cochrane Database Syst Rev. 2003;CD002884. [Medline].

  100. Rodrigo GJ, Rodrigo C. The role of anticholinergics in acute asthma treatment: an evidence-based evaluation. Chest. Jun 2002;121(6):1977-87. [Medline].

  101. Sears MR, Burrows B, Flannery EM, Herbison GP, Hewitt CJ, Holdaway MD. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med. Oct 10 1991;325(15):1067-71. [Medline].

  102. Shaheen SO, Aaby P, Hall AJ, et al. Measles and atopy in Guinea-Bissau. Lancet. Jun 29 1996;347(9018):1792-6. [Medline].

  103. Sheikh A, Alves B, Dhami S. Pneumococcal vaccine for asthma. Cochrane Database Syst Rev. 2002;CD002165. [Medline].

  104. Shirakawa T, Enomoto T, Shimazu S, Hopkin JM. The inverse association between tuberculin responses and atopic disorder. Science. Jan 3 1997;275(5296):77-9. [Medline].

  105. Sin DD, Man J, Sharpe H, Gan WQ, Man SF. Pharmacological management to reduce exacerbations in adults with asthma: a systematic review and meta-analysis. JAMA. Jul 21 2004;292(3):367-76. [Medline].

  106. Smith DH, Malone DC, Lawson KA, Okamoto LJ, Battista C, Saunders WB. A national estimate of the economic costs of asthma. Am J Respir Crit Care Med. Sep 1997;156(3 Pt 1):787-93. [Medline].

  107. Sporik R, Holgate ST, Platts-Mills TA, Cogswell JJ. Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. A prospective study. N Engl J Med. Aug 23 1990;323(8):502-7. [Medline].

  108. Sullivan TJ, Selner JC, Patterson R, et al. Expert care and immunotherapy for asthma. A review of published studies with emphasis on patient outcome and cost. American College of Allergy, Asthma, and Immunotherapy Monograph. Nov 1996;1-25.

  109. Theodoropoulos DS, Lockey RF. Allergen immunotherapy: guidelines, update, and recommendations of the World Health Organization. Allergy Asthma Proc. May-Jun 2000;21(3):159-66. [Medline].

  110. Tilles SA. Differential diagnosis of adult asthma. Med Clin North Am. Jan 2006;90(1):61-76. [Medline].

  111. Turkeltaub PC. FDA Medical Bulletin. 1994;24:7.

  112. von Hertzen L, Haahtela T. Signs of reversing trends in prevalence of asthma. Allergy. 2005/03;60(3):283-92.

  113. Weinberger M, Abu-Hasan M. Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Pediatrics. Oct 2007;120(4):855-64. [Medline].

  114. Weiss KB, Sullivan SD. The health economics of asthma and rhinitis. I. Assessing the economic impact. J Allergy Clin Immunol. Jan 2001;107(1):3-8. [Medline].

  115. Wilson DR, Torres LI, Durham SR. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev. 2003;CD002893. [Medline].

  116. [Best Evidence] Pavord ID, Jeffery PK, Qiu Y, Zhu J, Parker D, Carlsheimer A, et al. Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol. J Allergy Clin Immunol. May 2009;123(5):1083-9, 1089.e1-7. [Medline].

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Further Reading

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Keywords

reactive airways disease, RAD, occupational asthma, reversible airway obstruction, increased bronchial reactivity, airway inflammation, passive smoke inhalation, allergic disease, aeroallergen exposure, viral respiratory illness, allergen-specific immunoglobulin E, allergen-specific IgE, allergen immunotherapy, airway hyperreactivity, AHR, airway remodeling, status asthmaticus, atopy, asthma triggers, nonallergic rhinitis, early allergic response, EAR, late allergic response, LAR, mite antigens, cockroach antigens, occupation-induced airway disease, occupation-induced asthma, industry-induced airway disease, industry-induced asthma, industrial asthma, occupational asthma, seasonal pollen allergens, mold spore allergens, dust mite allergens, animal allergens, food allergens, breath-actuated inhaler, BDI, dry-powder inhaler, DPI, metered-dose inhaler, MDI, breath actuated inhaler, dry powder inhaler, metered dose inhaler

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Contributor Information and Disclosures

Author

William F Kelly III, MD, Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Staff Physician, Division of Pulmonary/Critical Care Medicine, Department of Medicine, Walter Reed Army Medical Center
William F Kelly III, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, and American College of Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

John J Oppenheimer, MD, Clinical Associate Professor, University of Medicine and Dentistry of New Jersey; Director Clinical Research, Pulmonary and Allergy Associates, PA
John J Oppenheimer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology and American College of Allergy, Asthma and Immunology
Disclosure: AZ, Glaxo, Schering, Sepracor, Novartis/Genetic, Apieron Grant/research funds Other; AZ, Glaxo, Schering, Sepracor, Novartis/Genetic Honoraria Speaking and teaching

Gregory J Argyros Col, MD, Chief, Graduate Medical and Dental Education, J7/Joint Task Force, National Capital Region Medical; Professor of Medicine, Uniformed Services University of the Health Sciences
Gregory J Argyros Col, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, and American Thoracic Society
Disclosure: Nothing to disclose.

Medical Editor

Stephen Rosenfeld, MD, Professor Emeritus, Department of Medicine, Allergy, Immunology and Rheumatology Unit, University of Rochester School of Medicine and Dentistry
Stephen Rosenfeld, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American Federation for Clinical Research, Clinical Immunology Society, and Medical Society of the State of New York
Disclosure: Elan Ownership interest None; Invitrogen Ownership interest None; Merck Ownership interest None; Pfizer Ownership interest None; Medco Health Ownership interest None; Millipore Ownership interest None

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Stephen C Dreskin, MD, PhD, Director of Allergy, Asthma, and Immunology Practice, Professor of Medicine, Departments of Internal Medicine and Immunology, University of Colorado Health Sciences Center
Stephen C Dreskin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association for the Advancement of Science, American Association of Immunologists, American Association of Neuropathologists, American Association of Ophthalmic Pathologists, American Association of Oral and Maxillofacial Surgeons, American College of Allergy, Asthma and Immunology, Clinical Immunology Society, and Joint Council of Allergy, Asthma and Immunology
Disclosure: Genentech Consulting fee Consulting

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD, Clinical Professor of Medicine, George Washington University School of Medicine; Chief, Section of Allergy and Immunology, Washington Hospital Center; Medical Director, Institute for Asthma and Allergy
Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, and Association of American Physicians
Disclosure: Abbott Consulting fee Consulting; Alcon Consulting fee Consulting; Glaxo Consulting fee Consulting; Greer Consulting fee Consulting; Sanofi Consulting fee Consulting; Schering Consulting fee Consulting; Teva  Consulting; Meda Honoraria Speaking and teaching

 
 
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