Clinical Practice Guideline
for
ASTHMA
Developed for the
Aerospace Medical Association
by their constituent
organization
American Society of Aerospace Medicine Specialists
Overview: Although it’s
unlikely that asthma has ever been a rare disorder, over the past twenty years
the prevalence has increased by roughly 40%.
The mortality rate from asthma has increased by a similar
proportion. Numerous hypotheses have
been advanced to explain the rise in prevalence, such as decreased air exchange
in energy-efficient buildings, or decreased childhood infections resulting in
an upregulation of IgE-mediated immunity, but no
consensus exists. Given the concurrent
rise in mortality, and the fact that asthma as a cause of death is rarely
confused with any other etiology, the increase in prevalence is unlikely to be
an artifact of inconsistent diagnostic criteria.
That
being said, variations in diagnostic criteria do affect epidemiologic studies
of asthma, and clinical practice as well.
For such a common disease, it has been surprisingly difficult to agree
on a definition. (Asthma has also had
more than its share of aliases, such as reactive airways disease, reactive
bronchitis, and others.) For practical
purposes, it is reasonable to view asthma as inflammation of the airways in
response to trivial or enigmatic stimuli, typically manifesting with
bronchospasm and/or cough. Excluded from
this definition would be airway inflammation that accompanies other structural
lung diseases, or that results from serious insults, such as toxins (e.g.,
smoke inhalation) or significant infections (e.g., influenza). The qualification that the infection should
be significant is important, albeit hard to delimit; to give an example, several
weeks of persistent cough following a common rhinovirus infection should raise
a suspicion for asthma, and if this is a recurring pattern, the diagnosis is
probable. (Prolonged symptoms after
viral infection is considerably more common in children, as discussed below.)
Asthma
often shows an atopic association, particularly with allergic rhinitis, and on
occasion treatment of allergic rhinitis with immunotherapy leads to marked
improvement in asthmatic symptoms. Chronic
rhinitis may be accompanied by sinusitis, and treatment of sinusitis may yield
better control of asthma. There is also
an association of asthma with gastroesophageal reflux, but it is unclear which
is cause and which is effect, since pressure excursions within the thorax may
predispose to reflux. Acid suppression
with proton pump inhibitors rarely leads to clinical improvement, and most
reviews have failed to support a role for reflux in asthma pathogenesis. (Rarely, reflux with nocturnal aspiration of gastric
secretions may mimic asthma.) In the
great majority of cases, no underlying etiology for the asthma can be
implicated. Exacerbating factors are
usually easier to identify, and often tend to be idiosyncratic to the
individual. Attacks can be precipitated
or exacerbated by breathing cold, dry air, by exercise, or by exposure to pollutants
(e.g., exhaust fumes), to name a few common culprits.
Exacerbation of chronic or
intermittent asthma by exercise is an extremely common symptom, reported by
70-90% of asthmatics; since it is well documented that many individuals fail to
symptomatically differentiate asthma from normal exertional breathlessness,
even this percentage may be an underestimate.
In addition to exercise exacerbating bronchospasm in established asthma,
there is a separate phenomenon of solitary exercise-induced bronchospasm
(EIB). (Unfortunately, published reports
of EIB often fail to separate the two conditions, making interpretation of
results difficult in those studies.)
Solitary EIB appears to be due to airway hyperosmolarity induced by
hyperpnea and free water loss, and/or cooling and subsequent rewarming of the
airways. There are no published reports
of death from solitary EIB. (In
contrast, asthmatic deaths as a result of exercise in those with established
asthma are well documented.1)
Solitary EIB occurs in recreational as well as high school and
collegiate athletes; the prevalence is significant, typically affecting about
9-12% of children in athletic programs.
(This percentage is based on results of post-exercise spirometry; many
did not have significant symptoms.) The
phenomenon has been best studied in professional athletes. Endurance sports have a higher risk than
intermittent activities. Among
cross-country runners in one study, 14% of those without a history of asthma showed
objective evidence of EIB. The greatest
risk involves winter sports, which is consistent with the likely mechanism of
EIB. Screening of the 1998 Winter
Olympic Team using sport-specific challenge showed an overall rate of EIB of
23%, with cross-country skiing showing a prevalence of 50%. Another study found a 35% prevalence of
solitary EIB in figure skaters. Unlike
the case in established asthma, inflammation is generally not believed to play
a role in solitary EIB, though endurance athletes in winter sports may actually
show inflammatory changes on histopathology.
The
major symptoms of asthma include wheezing, shortness of breath, chest
tightness, and cough. Studies have shown
that subjective reporting of symptoms does not correlate well with severity of
obstruction. Patients tend to adapt to
chronic airflow obstruction, so that symptoms correlate better with the rate of
fall of FEV1 during an attack rather than with the absolute degree of
obstruction. Spirometry utilizing the
forced vital capacity maneuver is the standard method for measuring obstruction. Assuming adequate effort by the individual, a
ratio of FEV1/FVC less than 0.75 indicates airflow obstruction; an increase of
15% or more in absolute FEV1 after treatment with an inhaled bronchodilator denotes
reversible airflow obstruction. A 15% or
greater change in FEV1 over time (an interval anywhere from minutes to months) also
indicates reversible obstruction. Whether
the finding of reversible obstruction signifies asthma depends on the clinical
setting. As noted earlier, serious
respiratory infections such as influenza are often accompanied by airway
inflammation, which may persist for weeks, and the presence of reversible
airflow obstruction during this period would not equate to asthma. Reversible obstruction is often a feature of
other chronic diseases involving the airways (e.g., sarcoidosis); the
aeromedical significance of the underlying disease is likely to determine
disposition in that case.
Children
are prone to asthma; as many as a third will have symptoms compatible with
asthma at some point, most often in pre-school years. Many of these probably represent a prolonged
response to viral inflammation, in particular respiratory syncitial virus. The longer that symptoms persist, the more
likely that the problem truly represents asthma. Selection of aircrew for military aviation is
complicated by the fact that many asthmatics are free of symptoms in their late
teens and their twenties, only to have the problem recur in their twenties or
early thirties. In general, about 30-35%
of remitted childhood asthmatics will relapse.
Numerous natural history studies have attempted to correlate a variety
of factors (e.g., maternal smoking, childhood pets) to the risk of persistence
or relapse of asthma, but results have been contradictory. That has even been true of whether or not the
subject smoked, which probably reflects a bias known as the “healthy smoker
effect” in which those with more sensitive airways avoid taking up the
habit. Cofactors that have appeared to
predict the risk of relapse in a more consistent fashion have included a
history of atopy, and the frequency and severity of attacks in childhood. Although the latter has correlated reasonably
well, it is surprisingly difficult to quantify when one is looking at pediatric
records of an aviation applicant. Age
shows a clear association with asthma prevalence, with a steep decline in
prevalence in the preschool years and a progressively slower decline until age
16. Clearly, most who
remit do so at a younger age, and it seems probable that those who remit at a
later age are at greater risk of subsequent relapse. That pattern is clearly true for those who
remit at a very early age; those with wheezing confined to infancy (<2 years
old) have been shown to be at no greater risk of adult asthma than those who
never wheezed. Whether there is less
risk of adult relapse in those who stop wheezing at age 8 vice those who remit
at age 12 is not known.
A
number of studies have shown that airway inflammation and/or hyperreactivity
frequently persists in those who have clinically remitted. Whether disease activity has been measured by
bronchial eosinophils, histopathology, or methacholine challenge testing,
anywhere from a quarter to a half or more of those in apparent remission have
evidence of continued subclinical activity.
Not unreasonably, this has led to a perception that bronchoprovocation
testing of individuals in remission would identify those at greater risk of later
relapse. Reasonable or not, it has proven
to be incorrect. The prevalence of methacholine reactivity
from childhood to adulthood mirrors the prevalence of asthma; many of those who
show normal reactivity in their early twenties show a recurrence of reactivity
at a later age. A study of allergic
rhinitis patients showed no difference in the risk of developing asthma between
those with positive and negative bronchoprovocation tests. Most convincingly, in a recent publication
from the data in the Dunedin (New Zealand) cohort, of 58 subjects in their
mid-teens with remission of childhood asthma and negative methacholine
challenge testing, 33% subsequently relapsed by age 26, consistent with
historical rates of relapse. (Those with
positive bronchoprovocation testing showed a slightly greater risk of relapse,
but that group numbered only six individuals, of whom three relapsed.) Bronchoprovocation testing appears to be of
no value in predicting relapse in remitted childhood asthmatics.
A
number of modalities are available to treat asthma. Treatment of suspected etiologic factors such
as allergic rhinitis was alluded to earlier.
In the absence of significant rhinitis, the use of immunotherapy in an
attempt to treat asthma is usually disappointing. Medications
employed to treat asthma are generally classified as controller, rescue, or, in
the case of EIB, prophylactic therapy.
Rescue therapy primarily consists of a variety of short-acting
beta-agonists (SABA) delivered via inhalation; in addition to the fact that
these agents have a number of cardiac and neurologic adverse effects, the need
for a SABA generally signifies asthma that is not under control. However, prophylactic use prior to exercising
in those with solitary EIB does not indicate a similar lack of control. Use of albuterol fifteen minutes before
exertion generally confers protection for about four hours. Among controller medications, inhaled
corticosteroids (ICS) are the mainstay of asthma therapy. They have been shown to control disease and
reduce the number of exacerbations. There
exists a common misperception among patients that inhalers should give
immediate relief; as a result, patients routinely overuse
Other
medications are less satisfactory. Long-acting beta-agonists (LABA) such as salmeterol (Serevent® , also contained in Advair®) and formoterol (Foradil®, also contained in Combivent®) have been in vogue
in recent years. They are often
classified as controllers, though suppressor is a better term, since they fail
to address the underlying inflammatory process.
Administering a LABA twice a day differs little, if at all, from plying
a patient every four hours with a
Aeromedical
Concerns: Severity of
obstruction and presence/absence of symptoms are clearly important, but the principal
aeromedical concern is the risk of serious bronchospasm in response to minor
insults. Since breathing cold or dry air, or exposure to smoke, fumes or pressure breathing can
provoke asthma attacks, the danger of incapacitating bronchospasm is real. In military aviation, the combination of
exercise and cold, dry air is routinely encountered in high-performance
aviation. Additionally, military
aviation concerns include lack of available care in austere locations.
Medical
Work-up: Internal or pulmonary
medicine and, where indicated, allergy/immunology are the pertinent disciplines
to consult. The note from the treating
physician should address severity and frequency of attacks, provocative
factors, necessity for emergency room visits, and current treatment. Abnormal results on spirometry should be
followed by bronchodilator challenge. A
post-bronchodilator study may also be useful in those with low-normal airflows
who have a suspicious history; even if the FEV1/FVC is inside the normal range,
a 15% improvement or more in FEV1 indicates reversible obstruction. Though not commonly employed in clinical
practice because of issues with cost efficiency, bronchoprovocation testing to
assess sufficiency of therapy is an established use of that modality. In the
aviator, it can give valuable insight into the degree of asthma control
achieved.
Aeromedical
Disposition (military): A history of childhood asthma
may be disqualifying for entry into the military, as about a third of such
individuals will have recurrences in adulthood.
Trained aircrew who have an identifiable and
avoidable precipitating cause for their asthma may fully remit following
control of their environment; the classic example is asthma attributable to cat
exposure, which resolves after cessation of exposure. However, most triggers are difficult to
entirely avoid. Waiver can be considered
for those who are well controlled by inhaled steroids, montelukast,
immunotherapy, or any combination of those.
Deployment considerations remain a significant limitation for those
requiring ongoing therapy.
Aeromedical
Disposition (civilian): In civilian aviation, medical certification for any class
should not be issued to an individual with severe, acute or chronic asthma with
frequent exacerbations. For further consideration airmen will be required to
submit a current status report from their treating physician. In the report of evaluation, the treating
physician should describe the cause of the asthma, severity of the condition
and prognosis. This includes the type,
dosage and frequency of medication, and any adverse effects. If the symptoms are
frequent, severe, or recurrent then pulmonary function testing will be
required. All medications to include
immunotherapy are permitted, with the exception of prednisone or equivalent
steroid dose greater than 20 mg daily. If
the airman is found to be eligible for certification, follow-up should be
performed annually and results submitted in a written report. Some cases may be forwarded to a FAA
pulmonary consultant for review and recommendations.
Waiver
Experience (military): A review of recent USAF waiver records through
February 2007 showed 202 cases of asthma including history of asthma in flying
training applicants, pilots/navigators and non-pilot aircrew. The aeromedical summaries (155) for all
disqualified (67) and 88 randomly selected cases were reviewed. Of the 67 asthma cases disqualified, 14 were flying
training applicants, 16 were pilots or navigators and 37 were non-pilot aircrew. Of the 67 disqualified asthma cases, 63 were
disqualified for the asthma and the other three were disqualified for other
medical conditions [ophthalmologic (3), syncope (1)]. Of the 88 randomly selected approved waivers,
62 were for history of childhood asthma, the other 26 were for asthma controlled
on medications (17), exercise induced asthma (5), and asthma induced by
preventable triggers [cat, dog, horse] (4).
US Air Force policy was recently changed to allow non-high performance
waiver for asthma controlled with ICS, montelukast, and/or immunotherapy;
inhaled
Waiver Experience
(civilian): Civilian airmen do not receive medical certification
if they have been having frequent ER visits for asthma symptoms. In addition, they are not allowed to fly if
they are taking greater than 20 mg equivalent of prednisone. There were 2,848 First-class airmen, 2,506
Second-class and 6,272 Third-class airmen granted medical certification for
asthma by the FAA as of July 2007.
References:
Kardon EM. Acute asthma. Emergency Medicine Clinics of
Li
JT, O’Connell EJ. Clinical evaluation of asthma. Annals
of Allergy, Asthma, & Immunology, Jan 1996; 76:1-10.
Rayman
RB. Clinical Aviation Medicine, Third edition,
7/22/07