Asthma:
A Modern
Perspective
Fred Leffert, M.D.
I-roi,i f/ic l)epartnu-nl of Pediatrics, “sUtjOflU! J(’WiSll Ih)S1)it(1l and Re-scare/i Center, (10(1lli(’Unirersity of
Colo)r(1(Io S(!io)o)l 01/ .I(-(!i(ioI(-, 1)en tor
Asthma occupies a rather unique position in
modern pediatrics. Although it is one of the most
commonly encountered serious chronic condition
of childhood, it is a disease whose management is
too often an unhappy and frustrating task for the pediatrician. The treatment of asthma represents an unfortunate gap in the training of many
otherwise well-educated pediatricians. Physicians
who feel comfortable with their approaches to a
wide range of common pediatric problems often
view asthma as a mysterious affliction about which little is known, a disease best left to the ministrations of the allergist-a specialist who possesses arcane knowledge about skin testing, hyposensitization, and other immunologic ap-proaches to the disease.
This is an unfortunate situation for several
reasons. It deprives the pediatrician of the
satis-faction of successfully managing one of the most fascinating and varied diseases of childhood. It often results in unnecessary referrals and extra expense for families already stressed by a chronic
disease. An.d perhaps most importantly, it
deprives the child and his family of the education and support they need from a physician who has confidence in his understanding of and ability to manage asthma. Asthma stands almost alone among the chronic diseases of childhood with regard to its high degree of reversibility and its excellent response to proper therapy in the
major-ity of children. Much of the uncertainty and
unhappiness the pediatrician feels about asthma
may be due to the influence of obsolete concepts
about the etiology of the disease. The purpose of
this review is to consider the manner in which our
present understanding of the etiology of asthma
has evolved, and to examine the impact of
modern concepts of the disease on pediatric practice.
EARLY CONCEPTS OF ASTHMA
Asthma has been recognized as a clinical entity
since antiquity. Several excellent treatises
describe its clinical manifestations with
consider-able charni and accuracy.’ However, during the
19th century, a period in which the scientific
foundations of modern medicine were being laid,
asthma was in a medical limbo. Holt gave less
than four pages to asthma of 129 pages devoted to
respiratory disease in his first textbook of
pediat-rics, dismissing it as “ vaso-motor neurosis
of the respiratory tract. “‘ Osler, in the four pages
he allowed to asthma in the first edition of his
textbook of medicine, stated that “ . . . bronchial
asthma is a neurotic affection. . . . The affection
sometinies runs in faniilies, l)articularlv those
with irritable and unstable nervous systems.” The reason for this relative neglect of such a
comnion problem is not entirely clear. An
impor-taut factor appears to have been a feeling that
asthma was not an organic disease but rather a
psychoneurotic disorder. There were reasons for
this belief. Since the asthmatic rarely died of his
affliction, an anatomic basis for asthma was not
estal)lished by examination of postmortem
mate-rial. This made asthma a suspicious entity in an
age when many classic diseases were being
iden-tified and classified in terms of anatomic
patholo-gy.
It also seemed strange, at a time when littlespecific therapy was available for most diseases,
to observe the capricious and seemingly
unpre-dictable course of the asthmatic, who might
appear perfectly healthy one day and on the
verge of asphyxia the next-a baffling situation
that might be repeated hundreds of times over
many years. In addition, there was the
well-known role of emotional stress in triggering and
exacerbating symptoms.
Received January 9: revision d(.’Cel)te(l for pi 11)1ication \4)ri 1
12. 1978.
sites of postulated
basic defect
(
Antigen
:T:”;,__
- gE
Macrophages and
T&8 Lymphocytes
attachment
to mast cell
antigen-tgE interaction
on mast cell surface
A. SENSITIZATION
respiratory or
gastrointestinal
muc osa
B. SYMPTOMS
(c
mediator effect on lung:
brochoconstriction
mucosat edema
mucus secretion
F1;. 1. The allergic theory of asthma. The pathophvsiologv may be seen as a two-stage process.
The I)asic defect, an abuorlnal response to environmental alitigens, is I)Ostulated to occur in the first stage. leading to mast cell sensitization. The mediators generated b subsequent
antigen- lgE interaction i liclude h istainine, sloss’-reacting sul)stance, eosinoph il and neutro1)hil chelnotactic factors, prostaglandins. and kinin-activating factors.
THE ALLERGIC THEORY OF ASTHMA
One of the first major steps toward a better
understanding of the etiology of asthma came
through the work of Samuel Meltzer. Meltzer
worked in the departments of physiology and
pharmacology at the Rockefeller Institute in the
early ‘ears of the 20th century, when the science
of immunology was just beginning to develop. Richet and Portier had discovered the
phenome-non of anaph1axis in 1902, and Meltzer became
greatly interested in this dramatic clinical
expres-sion of immunologic hypersensitivity. He noted
the fate of the guinea pig which, having been
sensitized by injection of a foreign protein, was
then given a second dose of the same antigen.
Death usually occurred within minutes and could
be shown to be caused by bronchial obstruction
leading to asphyxia. Meltzer was struck by the
similarity between the acute respiratory
embar-rassment of the anaphylacticall shocked guinea
pig and the patient experiencing an acute attack
of asthma. In 1910 he presented a strong
argu-ment for anaph1axis as the mechanism
responsi-ble for human asthma.
During the next decade Prausnitz and K#{252}stner
demonstrated the presence of what was later to
be called “reagin,” a substance found in the serum
and skin of individuals with immediate
hypersen-sitivity which appeared to be responsible for the
phenomenon of anaphylaxis in man.8 In 1923
Coca and Cooke proposed the concept of ‘
‘ato-p”-an inherited state predisposing to the
production of reagin and to a group of diseases
that includes asthma. Meltzer’s original
sugges-tion of anaphlaxis as a mechanism for asthma
was to lead to what may be called the allergic
theory of asthma (Fig. 1). Most pediatricians have
been taught this theory in medical school or
residency training. Its major premises are:
1. An asthmatic child is born with a genetically determined constitutional defect-atopy.
The basic defect in atopy may be abnormal
mucosal permeability to antigen” and/or
dysfunction of lymphoid cells responsible
for reaginic antibody responses.”
2. Because of his atopic constitution, he
produces large amounts of reaginic antibody to a variety of antigenic sul)stances in his environment; i.e., he becomes “sensitized.”
3. When a sensitized child comes in contact
with one of these antigens, an immunologic reaction is triggered which results in the secretion of a variety of chemical media-tors.
4. The action of these mediators on the lung
produces the clinical syndrome known as
This theory of asthma became widely accepted
and has had profound and lasting effects on the
care of the asthmatic child. An immediate
posi-tive effect was the growing acceptance of asthma
as an organic disease. After Meltzer, asthma could
command a place in textbooks with respectable
pulmonary diseases such as pneumonia and
tuber-culosis. The allergic theory also created a new
medical specialist-the allergist. It seemed
reasollat)le that a disease caused by immediate
hypersensitivity required treatment by a
phsi-cian skilled ill the detection of reaginic antibodies
and manipulation of the disease by imlnunologic
means. Pediatricians found that the problems of
niany of their patients could be explained by the
allergic theory: the child who only wheezed after
contact with a dog or when sleeping on a feather
pillow.
This is not to say that the theory won coniplete
acceptance. Eppinger and Fless presented a
concept of asthma as an inibalance in autonomic
nervous function, a “vegetative
Rackeman pointed out that in ‘many cases of
asthnia no evidence of reaginic antibody could be
found, which introduced the concept of
“intrin-sic” asthma.’ But the allergic theory became the
predominant explanation for the etiology of
asth-ma and remains so among niost practitioners
today.
In time however, thoughtful critics began to
question the allergic theory; criticisms arose on
two levels. On a basic level, the original
immunol-ogic assumptions of NIeltzer were challenged.
The clinical nianifestations of anaphvlaxis were
noted to l)e species specific. While the guinea pig
might exhibit bronchial obstruction as a manifes-tation of anaphylaxis, the dog suffered acute portal hypertension caused by spasm of hepatic venous sphincters and the rabbit died of acute cor pulmonale as a result of spasm of the pulmonary
arterial tree.’4 In man, the major “shock organ” in
anaphylaxis appeared to be the peripheral
micro-circulation, so that generalized angioedema and peripheral vascular collapse were the major
din-ical features. The respiratory symptoms seen in
human anaphylaxis were due to respiratory
muco-sal involvement in this angioedema and were usually more pronounced in the upper than in the lower respiratory tract.’ The
appropriate-ness of guinea pig anaphylaxis as a model for
human asthma became a matter of
contro-versy.
Q
tiestions were also raisedby
the pulmonaryphysiologist. Asthma could be demonstrated in
the 1)ml11ln1rY physiology laboratory to involve
1)0th large and sniall airways. But in the patient
whose asthma appeared to be related to inhaled
antigens, how did a relatively large pollen grain
or particle of animal dander reach the mucosal
surface of a siiiall bronchiole? Moreover if it could
reach small airway mucosa,’ how did this antigen
cross a mitcosal surface characterized by “tight”
intercellular junctions and reach the sensitized
niast cell s i n sul)niucosal tissue?’
Problems also arose at the clinical level.
Although mans’ children had all of their
symp-tonis explained iy allergen contact, niost did not.
Observant clinicians noted the association of
asthmatic symptoms with weather changes,
infec-tions, exercise, emotional stress, and a variety of
other stimuli, and were at a loss to relate these
factors to immediate hypersensitivity. Moreover,
the pediatrician who had to struggle with the
day-to-day management of the child with chronic
asthlna was often less impressed with the results
of the immunologic approach than his allergist colleague.
In the face of these problems, pediatricians and
allergists adopted several attitudes toward asthma
which are still evident in contemporary practice.
One group supported the allergic theory. In their
view, allergens could account for the clinical
picture of asthma if only better means were
available for their detection. For SOffiC the Holy
Grail of clinical allergy was the immunologic test
that would be sensitive and specific enough to
identify the offending antigen in every asthmatic
child. Each new laboratory procedure for the
detection of reaginic antibody-passive transfer,
leukocyte histamine release, and more recently
the Radioallergosorbent Test (RAST)-was hailed
as the long awaited test. \Vhen the patient’s
history gave no indication of any clear association
between inhaled or ingested antigens and
symp-tomns, hypothetical mechanisms such as an allergy
to upper respiratory bacteria might be invoked.
At its worst, this search for allergens led some
practitioners into expensive and scientifically
unsound approaches to diagnosis, particularly
with regard to food allergy.’’
Others, dissatisfied with the allergic theory, fell
back on the older concept of asthma as a
psycho-somatic disease. This theory reached its zenith in
the 1930s with the characterization of asthma as a
“pschophysiologic” disorder, possibly involving
a repressed cry for one’s mu This theory is
still prevalent in the late 20th century,
particular-lv among the laity. The survival of the rather
nebulous concept of “parentectomy” for
asthma is one of the theory’s less salutary
re-suIts.
FI . 2. (;-1 iL IltIcleOtide control of cell function, l’his is an ovcrsitnpl ified Pr’s’1ttti of (0 (‘01 nl)lex ssteiu
,
\lthoitgh(-onsideral)Ie evidence exists for the Inechanisln of
/3-adren-Cti1i( r(’Sl)OIiS(’ as l)i’ttIrL(l above. toan aspects of the
(-holinergic ax1 oi-adrenergic 1)ath\vavs are still hypothetical.
For (‘XaIIlI)lC, goiatl ovclase ttov he (Vtoplaslllic ill location
ratlu.’r than nlelul)rane associated. and it has not vet been ckarlv estal)lislle(l that a-adrenergic effects are Inediate(l solt’l l)\ a ec1i ,ction I n (A \ I P conceiit ration.
faced with what seemed to be an either/or choice
l)etWeemi t\vo unsatisfactory explanations of
asth-nia, decided that little was known about asthma.
It appeared to l)e a niysteriotis disease with
unknown etiology, un1)redictable cotirse, and
erratic resioiise to therapy, whose one saving
grace was the possiI)ilit that the child might
“outgrow it” with time.
THE fl.ADRENERGIC THEORY
Clearly there was a need for a fresh approach
to the p11)1)1cm. During the early 1960s
Szentiva-mlvi, Fishel, amid Talmage began a series of studies
vhich eventually led to the formulation of what is
now referred to as the /3-adrenergic theory of
asthma. Szentivanvi considered the features that
a)peared to l)e coninion to all asthmatics-the
features that would have to be explained by a
coniprehensive theory:
1. Pathophsiolog: sniooth muscle spasni,
edellia, amid hpersecretion of mucus.
2.
Pharniacologic abnormality: Asthmaticpa-tients were known to have an abnornially high
degree of bronchial reactivity to cholinergic
stini-nh, to the extent that inhalation of acetyicholine
01’ mnethacholine had l)eemi proposed as a
diagnos-tic test for the disease. There was also
consider-al)le evidence of a blunted nietabolic response to
I
-adrenergic agonists. This decreasedresponsive-ness to cirtigs such as epinephrine or isoproterenol
(‘0(11(1 l)e demonstrated in termiis of a less than
eXl)ected rise in 1)lOOd glucose, free fatty acids,
and lactate. cardio-acceleration, eosinophil and
platelet functions, and generation of cyclic
adeno-sine mnonophosphate (cAMP).
:3. Iniiiitinologic abnormality: The niajorit of
asthmatic children were “atopic” in the sense
that the’ tended to produce excessive amounts of
reaginic antibody in response to common
envi-ronniental antigemis. Although in many of these
,,o,eps,eph,ne children it was diffictilt to denionstrate a causal phenyIeph’ne relationship between this antibody and their
sniptonis, a truly comprehensive theory of
asth-nia would have to explain this unbalanced
immti-nologic m.esponse.
4. Eosinophilia: The eosinophilia comnionly
observed in the sputum, peripheral blood, and
bronchial tissue of the asthmiiatic might l)e
accotinted for iy the generation of eosinophil
cheniotactic factors in the course of immediate
hpersensitivit reactions2 in the child whose
asthmna was triggered by antigen. A more
compre-hensive theory would be reqtiired however, to
explain the eosinophilia seen in the “intrinsic”
asthmatic in whom no reaginic antibody could be
identified
5. Diversity of precipitating factors: The
theo-ry would have to provide a common pathway
through which ap)arentl tmnrelated stinitili such
as allergic reactions, infection, exercise, irritants,
emiiotional stress, and weather changes could act
on the lung to produce the same clinical
syndronie.
One approach to the problem was suggested by
the growing interest in cyclic nucleotides as
regulators of cell function. First identified as a
factor involved in the activation of liver
phos-phorvlase l)y epinephrine, cAMP was eventually
recognized as a molecule involved in the regula-tion of a wide variety of cellular functions.26 Cellular responses to many stimuli appeared to be mediated by stimulation or inhibition of adenyl
cyclase, a membrane-associated enzyme system
involved in the conversion of adenosine triphos-phate (ATP) to cAMP. The cAMP then served as
a “second messenger” that interacted with other
cellular constituents to produce changes in cell
function in response to the original stimulus.
Cyclic adenosine monophosphate was inactivated
by hydrolysis to 5’AMP by cyclic nucleotide
phosphodiesterase, an enzyme whose action could
be inhibited by theophylline. Later it was realized
that other cyclic nucleotides such as cyclic guano-sine monophosphate (cGMP) might have similar roles, and that some aspects of cell function might depend on the balance between the intracellular concentration of cAMP and cGMP.2
basic defect
Stimuli Mediators.
allergens mediators of
infections allergic reaction
emotions autonomicneurotransmitters
C Xerci cc
hormones other
other
mediator release
-adren.rgic stimuli
cholinergic’ stimuli
gE response
-bronchoconstriction
mucosal edema
mucus secretion
F,;. :3, The /3-adrenergic theory of asthtna, The immunologically triggered astlitna (Iepic-te(1 in
Figure 1 lecoties one aspect of a more general proess. The atitonoinic inbalance ptolttced liv re(htce(1 /3-adrenergic Iesl)OI1SIVCI1CS5 is reflecte(I in a livperresponsiveness of cells involved in
1)0th illlnullulogic aIl(1 l)ronchial functions.
interest with regard to responses evoked by the
neurotransmitters of the automonic nervotis
system and the ir pharm acologic analogs.
$-Adrenergic agents (epinephrine, isoproterenol)
were seen as producing their effects
(bronchodila-tion, vasodilation, etc.) through stimulation of
adenyl cyclase activity to increase cAMP
concen-tration, whereas -adrenergic agonists
(norepi-nephrine, phenlephrine) acted by reducing
cAMP concentration to elicit their effects
(bron-choconstriction), vasoconstriction, etc.).
Cholin-ergic stimuli (acetylcholine, methacholine) raised
cGMP concentration via increased guanl cyclase
activity to elicit their characteristic effects
(bron-choconstriction, exocrine gland secretion, etc.)
(Fig. 2).
Szentivanyi postulated a basic abnormality at
the level of the cellular receptor for /3-adrenergic
stimuli (Fig. 3). If the asthmatic had a
quantita-tive deficiency or qualitative dysfunction of
adenyl cyclase, the resulting impairment in his
ability to generate cAMP in response to
f3-adrenergic stimulation might leave him with a
lung in a state of autonomic imbalance-a lung that might be relatively overresponsive to
ct-adrenergic or cholinergic stinitili and
imderre-sponsive to /9-adrenergic stimuli. A variety of
apparently unrelated stimuli might produce the
pathophysiologic changes of asthma by triggering
cholinergic reflexes, which would produce
exag-gerated bronchial responses because of lack of
counterbalancing $-adrenergic tone. Some
pulmonary physiologists suggested that the vagus
nerve might represent a final comnmon pathway for both the allergic and nonallergic triggers of
asthma.2
The theory also suggested a possible
explana-tion for the imniunologic abnormalities. Cyclic
adenosine monophosphate could be shown to
have an inhibitory role in a variety of immune and
inflammatory processes,’ so that a state of
adren-ergic hporesponsiveness might result in an
imbalance in the inflammatory response,
parallel-ing the abnormal bronchial responses. The
attrac-tiveness of the theory was enhanced because it
provided a rationale for the beneficial actions of
the drugs that had been used empirically for
asthma: the catecholamines acted by raising
cAMP concentration by stimtilation of adenyl
sante result through inhibition of
phosphodiester-ase. The corticosteroids might act, at least in part,
by restoring adrenergic nn”
Other investigators approached this concept of
altered autonomic responsiveness from somewhat
different viewpoints. Evidence was produced
which stiggested that priniar hperreactivity of
the a-adrenergic’ ‘ or cholinergic’ systems might
play a role. \Vith the /3-blockade theory, these
theories might be seen as variations on a common
them e : asth iii a resulting froni autonom ic
dysfunc-tiomi at the cellular level. This modern concept is
in one sense a more sophisticated version of the
old “vagotonia” theory of Eppinger and Hess, and
even of Osler’s “ . . . irritable and unstable
nervotis system.”
The f3-adrenergic theory of asthma was well
received and at first appeared to be a truly
unitarian concept which explained many features
of asthnia that were not encompassed by older
theories. However, it has also been subjected to criticism. A detailed consideration of all the evidence bearing on this theory is beyond the scope of this review, although much of it has been reviewed in an excellent analysis of the subject.23 Briefly, critics of the /3-adrenergic theory have raised several general questions.
Does a state of /3-adrenergic
hyporesponsive-ness truly exist in the asthmatic lung? The
evidence for this state has been derived from
extrapulnionary tissue and has yet to be
demon-strated directly in the asthmatic lung. Also, the
possibility exists that decreased adrenergic
responsiveness is due to previous treatment with
adrenergic drugs and therefore is a
pharmaco-logic artifact resulting from treatment and not a basic feature of the disease itself.ll
Is f-adrenergic blockade sufficient to cause
asthma? The availability of fl-blocking drugs has
shed some light on this question. Although
propranolol is known to worsen asthma in the
asthniatic patient, it has not been possible to
prodtice asth mat ic I)ronch ial responses in normal
sul)jects 1w the administration of propranolol.
At the present timne the f3-adrenergic theory
remains an attractive but as yet unproved
expla-nation of the etiology of asthma.
PROSTAGLANDINS AND ASTHMA
A more recent theory of the etiology of asthma
has developed fromii the current interest in
prosta-glandins as niediators in htimiian disease. These
highly bioactive substances have several features
that make theni attractive candidates for a role in
causation of asthnia:
1. The lung appears to be involved in
prosta-glandin metabolism.
2. Prostaglandins can affect bronchial smooth
muscle in asthmatic subjects. Prostaglandin
F20 (PgF20) appears to be a more potent
bronchoconstrictor than histamine,#{176}5 and prostaglandin E (PgE) is a potent
broncho-dilator.36
3. Prostaglandins may be released as a result of
antigen-antibody reactions37 and may play a role in control of release of other
media-38
4. Prostaglandins interact with autonomic neu-rotransmitters#{176}1 and cyclic nucleotides.18
5. In a significant minority of asthmatic
patients, the disease is exacerbated after ingestion of aspirin,40 a drug whose antiin-flammatory action is produced by inhibition of prostaglandin synthesis.41
Evidence that supports a role for the
involve-ment of prostaglandins in asthma has been
summarized in a recent review.42 However, it has
not been possible to date to demonstrate that a
primary derangement in prostaglandin
metabo-lism is the basic etiologic factor in asthma.
CURRENT DEFINITIONS
At the present time there is no solidly estab-lished and widely agreed upon etiology for
asth-ma.41 Indeed, there may not be a single cause; we
may be dealing with a number of diseases that have in common the physiologic finding of revers-ible obstructive airway changes. In that case, we
might speak of “the asthmas” in the same fashion
as the hematologist speaks of the anemias. The
current status of the problem is illustrated by the attempt of the American Thoracic Society to define asthma: “Asthma is a disease character-ized by an increased responsiveness of the trachea and bronchi to various stimuli, and made manifest
by difficult breathing due to generalized
narrow-ing of the airways. This narrowing is dynamic and
changes in degree, either spontaneously or
because of therapy. The basic defect appears to
be an altered state of the host.”
This is a useftil operational definition of asth-ma, and it is the basis for the diagnosis of the
disease when applied in a quantitative manner in
the pulmonary phsioIogy laboratory. But its
avoidance of the issue of the nature of the “altered state” illustrates our present ignorance.
However, even in the absence of a definitive ex-planation, the decline of the allergic theory of
the approach of the modern pediatrician to the asthmatic child. This has become evident in several areas:
1. Diagnosis of asthma: It has become clear
that the diagnosis of asthma rests on physiologic,
not immunologic, criteria. \Vhen the diagnosis
cannot be made from history and physical
exami-nation, the next step is evaltiation in the
pulmo-nary phsiologv laboratory, where proper
provo-cation testing (e.g., methacholine or excercise)
will often provide a definitive answer.
Immuno-logic procedures such as skin testing become
relevant after the diagnosis is made as an aid in
determining whether immediate hypersensitivity
is playing a role in triggering symptoms in
chil-dren in whoni the clinical history indicates such a
possibility. The fact that a child has asthma is not
necessarily in itself an indication for allergy skin
testing. Indeed, even in cases where immunologic
factors are important, recent awareness that
immune mechanisms other than immediate
hypersensitivity may play a role in asthma2 may
indicate a more comprehensive immunologic
approach.
2. Communication with parents: One of the
most common misconceptions that the family of
the asthmatic child either brings to or carries
away from the pediatrician’s office is the belief
that through discovery of offending allergens and
subsequent avoidance or hyposensitization, the
asthma will be “cured.” For the child in whom
allergy plays little or no role, this can lead to
disillusionment and frustration, as ever more
vigorous efforts to find an allergen to explain each
exacerbation of the disease fail. Persistence in this
search, or in the administration of allergen
injec-tions based only on the results of skin tests, may
eventually produce a feeling of cynicism and
distrust in the family which makes further
management of the disease difficult. The modern
concept of asthma as a state of excessive bronchial
lability of as yet unknown etiology, probably
requiring a genetically determin’ed predisposition
but brought into clinical expression by
environ-niental stimtili, is often better accepted by
intel-ligent parents than the allergic explanation.
Although this theory does not furnish a final
answer to the qtiestion of nature of the basic
abnormality, it does provide a framework into
which the various triggers of asthmatic symptoms
may be fitted and furnishes a basis for a rational
discussion of therapy. This is particularly
impor-tant in helping to clarify the relationship of
psychological stress to exacerbations of asthma
observed in some children. Parents can be taught
that asthma is not a psychogenic or
psychosomat-ic disease that is caused by emotional stress, but
that psychic stress is but one of many factors that
can act through complex pathways on the
unbal-anced bronchial tree, which is the true basic cause
of asthma.
3. Treatment of asthma: The old concept of
asthma as an allergic disease implied that immu-nologic manipulation was the only primary approach to therapy. Pharmacologic therapy was often regarded as a second-line approach to be
used when the more basic immunologic approach was not sufficient to completely control symp-toms. In the more modern view, the physician who attempts to raise intracellular cAMP levels with adrenergic drugs or methyixanthines can be considered to be taking at least as “basic” an approach to asthma therapy as he does when he attempts to
modify
reagin-mediatedhypersensi-tivity with allergen injections. Indeed, recent
advances in the clinical pharmacology of asthma have put this therapeutic approach on a far more scientific basis than immunotherapy, which, despite considerable recent study, remains a rela-tively crude and empirical process at best. The increased interest in pharmacologic approaches to asthma, resulting in the introduction of several new agents4547 and the more effective use of older ones,48’49 has greatly increased the pediatrician’s ability to provide a normal lifestyle for the chronically asthmatic child.
4. Prevention of asthma: The allergic theory of
asthma implied a rather fatalistic outlook on the
possibility of preventing asthma. The basic
defect-atopy-was inherited, and it was
inevita-ble that contact with environmental antigens
would lead to sensitization. Szentivanyi, in the
studies leading to formulation of the f3-adrenergic
theory, found that many of the abnormalities
associated with asthma could be produced in
animals by extracts of Bordetella pertussis.2’ Thtis,
asthma might be, at least in part, an acquired
defect iii individuals with a genetic
predisposi-tion. If environniental events that induce the
asthniatic state can be identified and avoided,
asthnia might be a preventable disease in some
children. Preliminary evidence linking viral
respi-ratory infections in infancy with subsequent
asth-ma suggests one direction that ftiture
investiga-tion may
5. Role of the pediatric allergist:
Reexamina-tion of our concepts of the etiology of asthma has
led to a reappraisal of the role of the allergist in
the care of the asthmatic child. The older image
hvpersensitivi tv whose con tribution centers
around skin testing and hposensitization is
I)ecolliing OI)SOlete. The allergist today, while
remaining well grounded in the clinical
imniunol-og relevant to niany asthmatic children, mtist
have an equal degree of expertise in clinical
pharmacology, pulmonary physiology, and
psy-chology. In this regard it is important for the
pediatrician to realize that althotigh many of his
asthmatic patients may not have allergy as a
major part of their problem, and the efficacy of
immunotherapy for asthma reniains
controver-sial,” the niodern allergist remains the best source
of help for his more difficult problems. The pediatrician can and should manage most of the
asthmatic children in his practice. However, the
needs of the severely involved child-aggressive
pharmacotherap with potentially toxic
medica-tions, frequent assessnient of ptmlmonary
physio-logic status, delineation of the complex role of psychosocial factors in frustrating therapeutic
strategy-are often l)est met by the allergist. In
the referral process, the pediatrician must
exer-cise jimdgnient in two areas: in the selection of
children whose problems are too complex to be accommodated within his own practice, and in
the selection of an allergist with a modern
comiiprehensive approach to asthma. The
pediatri-cian Who refers a particularly difficult asthmatic
child to a modern allergist should expect a
thorough consideration of every facet of the
probleni and not simply ritualistic skin testing
followed by immunotherapy.
CONCLUSION
\\Themi viewed in the broad modern
perspec-tive, there is nothing about asthma that should
mystify or depress the pediatrician. Although
sometimes a difficult clinical problem, it is one for which rational approaches are available. The pediatrician who is willing to acquire the basic
knowledge necessary for a modern understanding of asthma will find management of the asthmatic
child to be one of the most intellectually appeal-ing and emotionally gratifying aspects of his practice. Pediatricians who demand more from the allergist than the traditional rituals can be a major force in raising the standards of the prac-tice of allergy.
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CHANGE OF ADDRESS FOR REPRINTS
The address for reprints of “Intramuscular Penicillin Administration at Birth: Prevention of Early-Onset Group B Streptococcal Disease” by Steigman
et al. (Pediatrics 62:842, November 1978) has been changed because of the
death on Oct. 4 of Dr. Alex
J.
Steigman. Reprints may be obtained by writingDr. Edward
