THE ICS IN ASTHMA TREATMENT

January 24, 2012

Dennis L. Spangler, MD
Inr!"u#i!n
Asthma affects approximately 23 million American children and adults,
resulting in almost 15 million physician office and hospital visits, and nearly 2
million emergency department visits each year. Despite the publication of
National Asthma ducation and !revention !rogram guidelines, asthma remains
poorly controlled, "ith annual costs estimated at up to #5$ billion. %urrent
guidelines recommend long&term treatment "ith inhaled corticosteroids '(%)*
because of their superior effectiveness in managing the chronic air"ay
inflammation that characteri+es persistent asthma. (%) monotherapy should be
explored before alternatives such as leu,otriene modifiers and long&acting beta
agonists '-A.As* are attempted, especially after the /) 0ood and Drug
Administrations 2111 "arning that -A.As should never be used alone to treat
asthma due to the increased ris, of severe exacerbations leading to hospitali+ation
in both children and adults, "ith a possibility of death. (n the past, asthma
treatment focused solely on the central air"ays, rather than the small, more distant
air"ays, and most traditional (%) therapies are aerosols "hich deliver large
particles to the central air"ays. 2oday, the importance of the role of small air"ay
disease in asthma, particularly inflammation, is ,no"n. 2argeting the small
air"ays may help improve clinical outcomes and reduce healthcare utili+ation and
costs. 2he (%) beclomethasone dipropionate 30A does not re4uire a spacer and is
characteri+ed by small particle si+es that result in more of the drug being
deposited in both the large and small air"ays. )tudies have demonstrated that
beclomethasone dipropionate 30A is clinically effective and cost efficient
compared "ith other asthma monotherapies or combination therapies.
ASTHMA
Asthma affects approximately 23 million Americans, including almost 5 million
children 'as of 2116*, and it is estimated that by 2125 that number "ill gro" by
more than 111 million "orld"ide. Asthma is responsible for almost 15 million
physician office and hospital visits, and nearly 2 million visits to emergency
departments, every year. (n addition, results from the survey Asthma in America
indicate that the /nited )tates is not meeting asthma goals set forth by the
National 3eart, -ung, and .lood (nstitute, "hich consist of no sleep disruption,
no missed school or "or,, no 'or minimal* need for emergency department
visits7hospitali+ations, maintenance of normal activity levels, and normal or near&
normal lung function. 2his lac, of control has contributed to the annual economic
costs associated "ith asthma, "hich have been estimated to be as high as #5$
billion.
%urrent guidelines recommend long&term treatment "ith inhaled corticosteroids
'(%)* because of their superior effectiveness in managing the chronic air"ay
inflammation that characteri+es persistent asthma. Additionally, the /) 0ood and
Drug Administration '0DA* issued a "arning in 0ebruary 2111 that long&acting
beta agonists '-A.As* should never be used alone to treat asthma, specifying that
"hen they are used, they should be administered only for the shortest duration
possible and then discontinued. 2his "arning resulted from analyses sho"ing that
-A.A use "as associated "ith an increased ris, of severe exacerbations leading
to hospitali+ation in both children and adults, "ith a possibility of death.
2he National Asthma ducation and !revention !rogram 'NA!!* xpert !anel
8eport '!8*&3 9uidelines recommend a step"ise approach to asthma treatment.
(%) monotherapy as first&line controller treatment for persistent asthma 'mild,
moderate, and severe* for both adults and children.(f asthma remains uncontrolled
"ith lo"&dose (%) monotherapy, only then should physicians consider a medium&
dose (%) or adding a -A.A to a lo"&dose (%) regimen.(ncreasing the (%) dose
may reduce the ris, of severe exacerbations and hospitali+ations compared "ith
approaches that involve adding a -A.A.11 A study of more than $:,111
patients found treatment to be more successful among those "ho "ere given
stepped up (%) monotherapy compared "ith patients given (%)7-A.A
combination treatment 'odds ratio ;<8= 1.55 vs 1.>$*. !atients given (%) only
"ere 31? less li,ely to be hospitali+ed for respiratory issues than those receiving
(%)7-A.A treatment.112he National (nstitute for 3ealth and %linical xcellence
'N(%*, "hich is based in the /nited @ingdom, recommends (%) treatment as
step 2 '"ith a short&acting beta agonist ;)A.A= as step 1 for mild intermittent
asthma* if the patient meets the follo"ing re4uirementsA
%ontinued asthma exacerbations "ithin the past 2 years. 2he patient is using a
)A.A at least 3 times per "ee,. 2his does not include use for exercise&induced
asthma. 2he patient has symptoms at least 3 times per "ee,. 2he patient "a,es at
night due to symptoms
Despite these recommendations ho"ever, the use of (%) monotherapy has been
sho"n to be suboptimal. Although -A.A7(%) therapy is not recommended as
first&line treatment, and (%) therapy is less costly than -A.A7(%) treatment or
leu,otriene modifiers, evidence indicates physicians are still predominately
prescribing -A.A7(%) regimens or a leu,otriene modifier rather than attempting
to utili+e the full potential of (%) monotherapy.
(n the past, asthma treatment tended to focus solely on the central air"ays, rather
than the small, more distant air"ays 'air"ay diameter 2 mm*. 2oday, the
importance of the role of small air"ay disease in asthma, particularly
inflammation, is no" ,no"n. (nitially thought to be the 4uiet +one of the
lungs, contributing little to total lung resistance, more recent technology such as
fiber optic bronchoscopy has given "ay to an understanding that the small
air"ays contribute significantly to air"ay resistance. Among patients "ith mild
asthma having normal spirometry, small air"ay resistance "as increased up to 5&
fold "hen compared "ith controls. !atients "ith asthma "ho are asymptomatic
can also sho" significant increases in small air"ay resistance, in most cases
caused by poorly treated distal lung inflammation. 2he inflammatory process in
the central and distal air"ays is similar 'infiltrates contain activated 2
lymphocytes and eosinophils, increased mucus plugging, and smooth muscle
hyperplasia*, "ith one important difference. 2he small air"ays are a maBor site of
air"ay obstruction because of their small diameter, and because smaller amounts
of inflammation result in a greater degree of air"ay narro"ing and may contribute
significantly to air"ay hyperresponsiveness. 8emodeling can also occur in the
small air"ays of patients "ith asthma. A study sho"ed that among patients "ith
asthma "ho had died, most "ere ta,ing large&particle (%). Autopsy data indicated
that air"ay remodeling "as not altered by large&particle (%) therapy. 2hese
structural changes that occur amid air"ay hyperresponsiveness may result from
long&standing or undertreated air"ay inflammation. 2he use of small&particle
(%) has been sho"n to reduce small air"ay inflammation.
2argeting the small air"ays can help improve clinical outcomes, reduce healthcare
utili+ation7costs, and improve 4uality of life. Diagnosing small air"ay dysfunction
and treating the patient early may reverse air"ay remodeling, progression to
air"ay fibrosis, and irreversible air"ay damage in patients "ith mild&to&moderate
asthma. Although (%) treatment is the gold standard for treating asthma, aerosol
particle si+e is crucial, "ith only small, less dense particle si+es having the ability
to reach the small air"ays. !articles bet"een 1.$ and 1.3 mm are li,ely to be
exhaled, and therefore of less therapeutic benefit. Although delivery method and
dosage vary bet"een (%) products, most traditional (%) therapies are aerosols
that deliver large particle si+es '2.: to :.5 mm* to the central air"ays, resulting in
relatively lo" total lung deposition. -arge&particle metered&dose inhalers,
pressuri+ed inhalers, or dry&po"der inhalers have not sho"n great efficiency,
delivering drug to the smaller air"ays at no more than 31? of the administered
dose.
2he ,ey treatment for asthma are steroids and other anti&inflammatory drugs.
2hese asthma drugs both help to control asthma and prevent asthma attac,s.
)teroids and other anti&inflammatory drugs "or, by reducing inflammation,
s"elling, and mucus production in the air"ays of a person "ith asthma. As a
result, the air"ays are less inflamed and less li,ely to react toasthma triggers,
allo"ing people "ith symptoms of asthma to have better control over their
condition.
Signs !$ a %en"ing As&'a Aa#(
a. Chat Are the Dain 2ypes of )teroids and Anti&(nflammatory Drugs for
AsthmaE
2he main types of anti&inflammatory drugs for better asthma control are
steroids or corticosteroids. <ther anti&inflammatory treatments include
mast cell stabili+ers, leu,otriene modifiers, and immunomodulators.
b. Chat Are (nhaled )teroidsE
(nhaled steroids are the mainstay treatment for controlling asthma. 2he
use of inhaled steroids leads to better asthma control 0e"er symptoms
and flare&ups 8educed need for hospitali+ation
Note that "hile inhaled steroids help prevent asthma symptoms, they do not
relieve asthma symptoms during and attac,. Dosages of inhaled steroids in asthma
inhalers vary.
2he ,ey treatment for asthma are steroids and other anti&inflammatory drugs.
T&ese as&'a "rugs )!& &elp ! #!nr!l as&'a an" pre*en as&'a aa#(s.
)teroids and other anti&inflammatory drugs "or, by reducing inflammation,
s"elling, and mucus production in the air"ays of a person "ith asthma. As a
result, the air"ays are less inflamed and less li,ely to react toasthma triggers,
allo"ing people "ith symptoms of asthma to have better control over their
condition.
Note that "hile inhaled steroids help prevent asthma symptoms, they do not
relieve asthma symptoms during and attac,. Dosages of inhaled steroids in asthma
inhalers vary.
(nhaled steroids need to be ta,en daily for best results. )ome improvement in
asthma symptoms can be seen in one to three "ee,s after starting inhaled steroids,
"ith the best results seen after three months of daily use.
In&ale" ser!i" 'e"i#ai!ns $!r )eer as&'a #!nr!l in#lu"e +
a. Advair 'a combination drug that includes a steroid and a long &
acting bronchodilator drug*.
b. Aerobid Asmanex A+macort Dulera 'a combination drug that also includes
a long&acting bronchodilator drug*.
c. 0lovent !ulmicor t)ymbicort 'a combination drug that includes a steroid
and a long&acting bronchodilator drug*.
(nhaled steroids come in three forms the metered dose inhaler 'DD(*, dry po"der
inhaler 'D!(*, and nebuli+er solutions.
,&a Are &e Si"e E$$e#s !$ In&ale" Ser!i"s-
(nhaled steroids have fe" side effects, especially at lo"er doses. (f you are ta,ing
higher doses, thrush 'a yeast infection in the mouth* and hoarseness may occur,
although this is rare. 8insing the mouth, gargling after using the asthma inhaler
and using a spacer device "ith metered dose inhalers "ill help prevent these side
effects. 2hrush is easily treated "ith an antifungal mouth"ash.
(nhaled steroids 'asthma inhalers* are safe for adults and children. )ide effects
"ith these anti&inflammatory asthma inhalers are minimal. Four doctor "ill
prescribe the lo"est dose that effectively controls yours or your childGs asthma.
<n a side note, many parents are concerned about giving their children Hsteroids.H
2he inhaled steroids are not the same as anabolic steroids that some athletes ta,e
to build muscle. 2hese steroids are anti&inflammatory drugs, the cornerstone of
asthma therapy. 2here are many benefits of using anti&inflammatory asthma
inhalers to self&manage asthma.
2o learn more about using inhaled steroids in children, see CebDDGs article on
%hildhood Asthma.
,&a Are &e .ene$is !$ /sing In&ale" Ser!i"s-
2he benefits of inhaled steroids for better asthma control far exceed their
ris,s, and includeA
& 8educed fre4uency of asthma attac,sDecreased use of beta&agonist
bronchodilators '4uic, relief or rescue inhalers*(mproved lung
function8educed emergency room visits and hospitali+ations for life&
threatening asthma
H!0 D! %re"nis!ne an" Syse'i# Ser!i"s ,!r( ! In#rease As&'a
C!nr!l-
/sing systemic steroids 'steroids ta,en by mouth or by inBection that can
affect the entire body* such as prednisone, prednisolone, and methylprednisolone
help to treat severe asthma episodes, allo"ing people to gain better asthma
control.!rednisone and other steroid drugs may be used to help control sudden
and severe asthma attac,s or in rare cases to treat long&term, hard&to&control
asthma.
Dost often, prednisone or other steroid is ta,en in high doses for a fe" days
'called a steroid burst* for more a severe asthma attac,.
)ide effects of systemic steroids include A
a. Cea,ness
b. Acne
c. Ceight gain
d. Dood or behavior changes
e. /pset stomach
f. .one loss
g. ye changes
h. )lo"ing of gro"th.
2hese side effects rarely occur "ith short&term use, such as for an acute asthma
attac,. 0or in&depth information, see CebDDGs article on !rednisone and Asthma.
H!0 D! &e Leu(!riene M!"i$iers I'pr!*e As&'a C!nr!l-
Accolate, )ingulair, and Iyflo are called leu,otriene modifiers. -eu,otrienes
are inflammatory chemicals that occur naturally in our bodies and cause
tightening of air"ay muscles and production of mucus. -eu,otriene modifier
drugs help control asthma by bloc,ing the actions of leu,otrienes in the body.
)tudies sho" that these medications are helpful in improving airflo" and reducing
asthma symptoms.
2he leu,otriene modifiers are ta,en as pills and have been sho"n to decrease the
need for other asthma medications. 2hese medications have been sho"n to be
effective in people "ith allergic rhinitis'nasal allergies* and may be effective in
people "ith both allergic rhinitis and allergic asthma.
,&a Are &e Si"e E$$e#s !$ Leu(!riene M!"i$iers-
2he most common side effects of leu,otriene modifiers are headache, nausea,
vomiting, insomnia, and irritability. -eu,otriene modifiers may interfere "ith
other medications 'for example, theophylline and the blood thinner "arfarin*.
Da,e sure you inform your doctor of all the medications you are ta,ing.
,&a Are &e Mas Cell Sa)ili1ers-
Dast cell stabili+ers, such as cromolyn sodium, are inhaled asthma
medications 'asthma inhalers* that "or, by preventing the release of
inflammatory substances 'histamines* from immune cells called mast cells. 2hey
help prevent and reduce asthma symptoms, especially in children "ithallergies
and asthma and in people "ith exercise&induced asthma. 2hese asthma inhalers
need to be ta,en t"o to four times a day, and they ta,e three to four "ee,s to start
"or,ing.
2hese asthma inhalers have side effects that include dry throat, cough, "hee+ing,
throat irritation, and bad taste.
H!0 D! I''un!'!"ula!rs ,!r( ! I'pr!*e As&'a C!nr!l-
Jolair 'omali+umab*, an immunomodulator, "or,s differently than other anti&
inflammatory medications for asthma. Jolair bloc,s the activity of (g 'a protein
that is overproduced in people "ith allergies* before it can lead to asthma attac,s.
(mmunomodulator treatment has been sho"n to help reduce the number of asthma
attac,s in people "ith moderate to severe allergic asthma "hose symptoms are
not controlled "ith inhaled steroids
Jolair, a prescription medication, is given by inBection every t"o to four "ee,s.
(tGs recommended for people "ith moderate to severe allergic asthma. )ide effects
include redness, pain, s"elling, bruising or itching at the inBection site, Boint pain,
and tiredness. (t may increase ris, for certain cancers and carries a boxed "arning
about severe, potentially life&threatening allergic reaction 'anaphylaxis*.
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