Vol. 13 •Issue 4 • Page 41
Asthma Across the Lifespan
Clinical Patterns Key to Making Therapeutic Decisions
The first rule of solving a mystery is to go back to the scene of the crime. Similarly, asthma specialists must investigate how and when asthma began for a patient. Determining this clinical pattern is essential for making therapeutic decisions beyond providing acute care for current symptoms.
While asthma can begin at almost any age, it most commonly begins in infancy with a viral respiratory infection that causes the lower airway inflammatory disease with consequent wheezing and coughing that’s known as bronchiolitis.
The most common cause of this initial wheezing episode is respiratory syncytial virus (RSV). The virus occurs in annual epidemics, infecting virtually all children within the first two years of life, most within the first year. When healthy babies become infected with RSV, most get only the symptoms of a common cold with coryza. However, a substantial minority suffer from bronchiolitis. As many as 3 percent of infants in the United States are hospitalized because of lower respiratory illness from this infection.1
While it’s premature to call the first episode of such symptoms asthma, this initial viral respiratory infection-induced lower airway obstruction in infancy is often the harbinger of more to come, consistent with a diagnosis of asthma.
Of those infants who experience bronchiolitis, 25 percent to 50 percent subsequently have symptoms of an intermittent pattern of asthma manifested by recurrent wheezing only in association with subsequent viral respiratory infections. While clinical experience and natural history studies suggest that the majority of such children remit later in childhood, some continue to have recurrent or chronic lower airway disease from asthma throughout childhood, and some also continue into adult life.2 (See Figure 1.)
VIRAL RESPIRATORY INFECTIONS
Viral respiratory infections (VRI), the common cold viruses, are a major cause of asthma exacerbations at all ages and appear to be the main risk factor for the large increase in hospital admissions for asthma that occurs every autumn.3 Preschool age children have a particularly high frequency of VRI, with most getting three to eight infections per year and 10 percent to 15 percent getting 12 or more per year.4 This is the likely explanation for a frequency of asthma hospitalization in the preschool age group that far exceeds that of older children and adults who get far fewer colds.5 (See Figure 2.)
The long-term clinical course of asthma in young children has been examined in a prospective study with repeated evaluations for up to 35 years.6 More than half of those with symptoms of asthma limited to an association with VRI prior to age 7 were asymptomatic at age 42. (See Figure 3.) However, a substantial number was still having episodic asthma, and a few had developed persistent asthma.
Nevertheless, the frequency of all patterns of active asthma at age 42 was greater among those in whom wheezing without VRI had been reported in childhood. About half of those with chronic asthma as children continued to have persistent symptoms at age 42, with only 11 percent reporting no recent asthma.
FEV1 wasn’t significantly different from controls at all ages among those who had only wheezing with VRI (measured during well periods), while those with chronic asthma generally had decrements in the FEV1 at age 10 that persisted but weren’t progressive.
EPIDEMIOLOGY AND ASTHMA
Asthma is very common in childhood, affecting at least 20 percent of children to some degree. An intermittent pattern of episodic symptoms is most common. Symptoms with this pattern may occur exclusively with VRI in many children and with varying frequency not limited to VRI in others. Chronic asthma with persistent symptoms is yet another pattern of asthma.
There is a spectrum of severity within the various clinical patterns. The most recent National Heart, Lung, and Blood Institute guidelines refer only to “mild” disease within the intermittent pattern of asthma.
However, asthma requiring hospitalization occurs most frequently among infants and preschool age children who suffer predominantly from VRI-induced asthma; these children are commonly asymptomatic between acute episodes. Despite the troublesome symptoms during the early years associated with this pattern of asthma, when the consequences can hardly be called mild, these children have a high rate of spontaneous improvement and are at little risk from long-term sequelae in the form of “remodeling” as manifested by persistent fixed airway obstruction.
Thus, in developing treatment strategies, clinicians must carefully consider the frequent need for urgent medical care and hospitalization associated with VRI-induced asthma. This is particularly important in young children because of the frequency with which they get VRI, but these same common cold viruses are also the major precipitants of asthmatic symptoms that result in hospitalization among adults.
ASTHMA IN ADULTS
Asthma in adults is commonly a continuation or a recurrence of childhood asthma. A substantial number of children with asthma don’t remit and continue to be symptomatic as adults. (See Figure 3.) Even among those who have remission of their childhood asthma, many have their asthma return in later years after an extended quiescent period for the disease.
This recurrence may be as persistent asthma or just may be a continuation of a previous pattern of intermittent VRI-induced asthma, perhaps also associated with the individual discovering they have exercise-induced bronchospasm when they take up jogging, particularly on cold mornings.
But there’s another pattern of asthma that begins de novo at various times in the life of adults. The ratio of males to females for asthma in childhood is 2-to-1. This becomes about 1-to-1 after adolescence as more boys go into remission, and more women develop adult onset asthma.
Another pattern of adult onset asthma occurs in midlife. Typically, following what appears to be a viral respiratory illness, asthmatic symptoms begin for the first time in a previously asymptomatic adult and then persist with varying severity. Unlike most persistent asthma beginning in .childhood, where inhalant allergy is a common precipitant of symptoms, adult-onset asthma is most commonly nonallergic.
STATE-OF-THE-ART PHARMACOTHERAPY
Currently available therapeutic options have the potential to minimize morbidity and provide normal functioning for most patients. Acute symptoms generally can be relieved by an inhaled beta2-agonist administered with a metered dose inhaler.
Even infants, toddlers and preschool age children can receive a bronchodilator effectively from an MDI when combined with a valved holding chamber. These devices also can be useful for older adults who lack the coordination to optimally use a MDI. The progression of acute exacerbations, most of which are triggered by VRI, generally can be stopped by the use of a short course of an oral corticosteroid.7
A low dose inhaled corticosteroid is the most effective safe monotherapeutic measure for maintenance therapy of persistent symptoms of asthma. The use of a combination of low dose inhaled corticosteroid with salmeterol is generally more effective than a higher dose of an inhaled steroid and is consequently the primary regimen of choice when a low dose inhaled corticosteroid doesn’t provide control of disease.
However, a limitation of inhaled corticosteroids is their failure to prevent, shorten the course of, or decrease the severity of acute exacerbations of asthma that are triggered by VRI.2,8,9 (See Figure 4.)
Theophylline is an alternative additive agent for a subgroup where salmeterol use results in decreased benefit from rescue or bronchoprotective use of albuterol or pirbuterol. Montelukast (Singulair®, Merck and Co.) may be useful for very mild daily symptoms in young children or the elderly where delivery of an inhaled medication is problematic.
The most common form of asthma at all ages is an intermittent pattern characterized by exacerbations from VRI. This is most problematic in young children because of the high frequency with which they get these common cold viruses.2
Highly successful outcomes for this pattern are attained with intervention measures including an oral corticosteroid on hand with instructions for usage, ideally at least the day prior to the need for urgent care.10 The addition of maintenance medication, including inhaled corticosteroids, doesn’t prevent VRI-induced exacerbations and is therefore not indicated for this pattern of asthma.11
Although all physicians have access to the same medication, outcome varies greatly among different practitioners. The major component of morbidity from asthma, hospitalization, hasn’t shown signs of decreasing over the past 20 years despite widely distributed national guidelines since 1991.12 (See Figure 2.) This continuing high hospitalization rate reflects the .practices in much of the general medical community.
In contrast, specialty programs have demonstrated better outcomes with fewer emergency care visits and hospitalizations.10,13,14 This reflects more skilled decision making, closer follow-up with regularly scheduled visits, use of physiological measurements of lung function, and more time and effort spent on patient education.
WHAT ELSE?
Most people with persistent asthma that began in childhood have an allergic component that contributes to symptoms. Allergy skin testing, a bioassay for immunoglobulin E (IgE) specific to various inhalant allergens, can be done at any age. About 10 percent of infants with asthma already have positive skin tests, and the presence of positive allergy skin tests in infants and toddlers, even if only appearing to be episodic with VRI at the time, is a predictive factor in identifying those at greatest risk for having or developing persistent asthma.
The newest therapeutic modality with a unique mechanism of action for the allergic component of asthma is the use of a monoclonal antibody directed against IgE. This agent, known as omalizumab (Xolair®, Genentech) profoundly decreases the amount of the free IgE that contains specific antibody to inhalant allergens. It does this by binding to the high affinity binding sites on the IgE molecule. It’s the cross-linking of IgE .antibody bound to the high-affinity receptors (FceRI) on mast cells by interaction with allergen that causes release of mediators resulting in allergic respiratory symptoms.
The anti-IgE minimizes the potential for allergen to cause mediator release by tying up the binding sites on the IgE molecule; this is associated over time with down regulation of the high-affinity receptors.
The availability of alternatives, the cost of this new agent, and it’s limitation to affecting the allergic component of asthma make this a choice for highly selected patients with poorly controlled asthma where a major allergic component can be identified.
While we await further advancements in care, including a cure for the common cold, the morbidity from asthma is already effectively minimized in specialized care programs utilizing the effective and safe medications currently available accompanied by patient education in the appropriate use of those agents.
Dr. Weinberger is professor of pediatrics and director of the pediatric allergy and pulmonary division at the University of Iowa Hospital, Iowa City, Iowa.
For a list of references, please call Mike Bederka at (610) 278-1400, ext. 1128, or visit www.Respiratory-care-sleep-medicine.advanceweb.com.
ASTHMA FROM ANCIENT TIMES
Quotations from ancient medical literature demonstrate the duration of our awareness for the clinical entity known as asthma:
“If from running, gymnastic exercises, or any other work the breathing becomes difficult, it is called asthma. The symptoms are heaviness of the chest, sluggishness to one’s accustomed work; they are hoarse and troubled with cough; and if these symptoms increase they sometimes produce suffocation.” [Aretaeus (c.A.D.120-180): On the causes and symptoms of chronic diseases]
“This disorder starts with a common cold, and the patient is forced to gasp for breath day and night, until the phlegm is expelled, the flow completed and the lung well cleared.” [Moses Maimonides (A.D. 1135-1204): Treatise on Asthma]
The above descriptions are consistent with a pragmatic definition of asthma arrived at by a committee of the American Thoracic Society in 1962:1
“Asthma is a disease characterized by an increased responsiveness of the trachea and bronchi to various stimuli and manifested by a widespread narrowing of the airways that changes in severity either spontaneously or as a result of therapy.” The narrowing of the airways occurs as a result of varying combinations of bronchial smooth muscle spasm and inflammation that causes mucosal swelling and mucous secretion.
REFERENCE
1. American Thoracic Society. Definitions and classification of chronic bronchitis, asthma, and pulmonary emphysema. Am Rev Respir Dis. 1962;85:763-8.
–Miles Weinberger, MD
