Allergic and Environmental Asthma

Posted on Jan 5, 2009 in Health & Wellness

William Kelly, MD, Consulting Staff, Officer-in-Charge, Pulmonary Disease Clinic, Madigan Army Medical Center; Assistant Professor of Medicine, Department of Pulmonary and Critical Care Medicine, Uniformed Services University of the Health Sciences
Gregory Argyros, MD, Assistant Chief, Program Director, Department of Medicine, Department of Medicine, Walter Reed Army Medical Center; Associate Professor, Uniformed Services University of the Health Sciences; Rohit K Katial, MD, Program Director Allergy and Immunology, Associate Professor of Medicine, National Jewish Medical and Research Center, Division of Allergy and Clinical Immunology, University of Colorado Health Sciences Center
Contributor Information and DisclosuresUpdated: May 30, 2006

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Overview
Differential Diagnoses & Workup
Treatment & Medication
Follow-up
References
Keywords
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 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, 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.

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. The level of IgE is associated with the prevalence and severity of airway hyperresponsiveness (AHR) and asthma.

Although most people with asthma have aeroallergen-induced symptoms, some individuals manifest symptoms with nonallergic triggers. As many as 3-10% of people with asthma are sensitive to nonsteroidal anti-inflammatory 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 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 10 hours later, one sees the late allergic response, 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 to develop into TH 1 (ie, interferon-gamma, interleukin [IL]-2) or TH 2 (ie, IL-4, IL-5, IL-9, IL-13). Allergens drive the cytokine pattern towards 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, with subsequent exposure to the allergen, the IgE is cross-linked. This leads to degranulation of the mast cell. 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) 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 toas 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 it is likely increasing as a result of greater sensitization to common allergens and the redefinition of some nonatopic wheezing as asthma. From 1982-1992, the average age-adjusted prevalence rate increased 42% (from 34.7/1000 to 49.4/1000). Asthma may affect 31 million people, including 9.2 million children (7.2% of adults by self-report).

International
Asthma affects more than 100 million people worldwide. Some reports suggest asthma prevalence has peaked at 8-12%, perhaps because of improved management or because asthma has already been induced in the maximal number of genetically available individuals.

Mortality/Morbidity
The death rate from asthma is 17.7 deaths per million people. 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).
Annually, asthma is 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 and lost work and productivity cost an estimated $12.7 billion in 1998. Increased morbidity is multifactorial and may include 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.
Race
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 3 times greater in African Americans.

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 compared with 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 persons of any age, but children often present when younger than 6 years. Asthma is the most common chronic disease 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 develop 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. Recurrent or 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
Limits on activity, lost work or school days, and quality of life
Number of ED 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 complete a questionnaire 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
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 (seafood or 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.
Cardiac: Findings are normal. Patients with status asthmaticus may have a pulsus paradoxus greater than 10 mm Hg.
Respiratory: During an acute asthma exacerbation, lung examination findings may include wheezing, rhonchi, hyperinflation, or prolonged expiratory time. 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.

Causes
The etiology of asthma is likely multifactorial. Genetic factors may control individual predispositions to asthma and responses to medications. 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.

A hygienic hypothesis proposes that cleaner environments have led to less immunological stresses, preventing 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. 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.
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.