asma diagnosis and management

8/3/2019 Asma Diagnosis and Management

1/44

_____________________________________________________ #3039 Asthma: Diagnosis and Management

CME Resource Sacramento, California Phone: 800 / 232-4238 FAX: 916 / 783-6067 1

Asthma:Diagnosis and Management

Mention o commercial products does not indicate endorsement.A complete Works Cited list begins on page 42.

Faculty

Sharn M. Grin, RN, PhD, specializes in HealthEducation and Chronic Disease Management especiallyas it relates to her primary areas o study and research.She has over twenty years o healthcare experiencenationwide and is an accomplished author, presenterand consultant. She requently lectures on the subjectso Attention Decit/Hyperactivity Disorder (AD/HD),Obsessive-Compulsive Disorder (OCD) and relateddisorders. Dr. Grin is the coounder o the Univer-sity Center or Assessment and Learning (UCAL) oAndrews University in Berrien Springs, Michigan.She enjoys writing and teaching and has been listedin Whos Who in American Nursing, Two ThousandNotable American Women, and the eleventh editiono the World Whos Who o Women, Cambridge,England.

Patricia Waltrs-Fischr, RN, BS, has worked in thehealthcare eld since 1992. Starting out as a nursesaide, she worked her way rom LVN to ASN whileworking in several hospital units, including ICU/CCU and adult and pediatric trauma. During hercareer, she worked at the busiest pediatric emergencycenter in the country, Childrens Medical Center o

Copyright 2009 CME Resource

CouRSe #3039 10 CoNTACT HouRS Release Date: 11/01/09 expiRationDate: 10/31/12

Dallas Emergency Room. While there, she cared orand educated asthmatic children and their caregiv-ers. Ms. Walters-Fischer is also an honors graduate oWashington University, St. Louis, with a BachelorsDegree in Communications and Journalism and hasbeen writing or the past ten years in local, national,and international publications.

Faculty Disclosure

Contributing aculty, Sharon M. Grin, RN, PhD, hasdisclosed no relevant nancial relationship with anyproduct manuacturer or service provider mentioned.

Contributing aculty, Patricia Walters-Fischer, RN, BS,has disclosed no relevant nancial relationship with anyproduct manuacturer or service provider mentioned.

Division Planner

Jane Norman, RN, MSN, CNE, PhD

Division Planner Disclosure

The division planner has disclosed no relevant nancialrelationship with any product manuacturer or serviceprovider mentioned.

Audience

This course is designed or nurses and nurse practitio-ners who may care or patients with asthma.

Accreditation

CME Resource is accredited as a provider o continu-ing nursing education by the American Nurses Cre-dentialing Centers Commission on Accreditation.

CME Resource is an approved provider o case managercontinuing education by the Commission or CaseManager Certication, sponsor code CM8406.

Designation o Credit

CME Resource designates this continuing educationactivity or 10 ANCC contact hours.

CME Resource designates this continuing educationactivity or 12 hours or Alabama nurses.

CME Resource designates this continuing educationactivity or 2 pharmacology contact hours.

HoW To ReCeIVe CReDIT

Read the enclosed course.

Complete the questions at the end o the course.

Return your completed Evaluation to CMEResource by mail or ax, or complete online atwww.NetCE.com. (I you are a Florida nurse or abehavioral health proessional, please return theincluded Answer Sheet.) Your postmark or acsimiledate will be used as your completion date.

Receive your Certicate(s) o Completion by mail,ax, or email.


2/44

#3039 Asthma: Diagnosis and Management _____________________________________________________

2 CME Resource April 11, 2011 www.NetCE.com

AACN Synergy CERP Category A.

This course is approved or 4 CEUs. Sponsor code:CM8406. Approval number CM8406-A200.

Individual State Nursing Approvals

In addition to states that accept ANCC, CME Resourceis approved as a provider o continuing education

in nursing by: Alabama, ABNP0353 (valid throughDecember 12, 2013); Caliornia, CEP9784; CaliorniaBVNPT Provider #V10662; Florida Provider #50-2405;Iowa, #295; Kentucky, 7-0054, Kentucky Board oNursing approval o an individual nursing continuingeducation provider does not constitute endorsement oprogram content; Texas, ANCC/Type I Provider.

About the Sponsor

The purpose o CME Resource is to provide challeng-ing curricula to assist healthcare proessionals to raisetheir levels o expertise while ullling their continuing

education requirements, thereby improving the qualityo healthcare.

Our contributing aculty members have taken care toensure that the inormation and recommendations areaccurate and compatible with the standards generallyaccepted at the time o publication. The publisher dis-claims any liability, loss or damage incurred as a conse-quence, directly or indirectly, o the use and applicationo any o the contents. Participants are cautioned aboutthe potential risk o using limited knowledge whenintegrating new techniques into practice.

Disclosure StatementIt is the policy o CME Resource not to accept com-mercial support.

Course Objective

Asthma is increasingly common, and most healthcareproessionals will encounter patients with the condi-tion in their practice. The purpose o the course is toprovide nurses and nurse practitioners with up-to-dateand accurate inormation on asthma, diagnosis, man-agement, and long-term outcomes or those with thecondition.

Learning Objectives

Upon completion of this course, you should be able to:

1. Summarize the history o asthma,including current denitions.

2. Describe the impact o asthma globallyand nationally.

3. Identiy risk actors that contributeto the development o asthma.

4. Dene the pathophysiology o asthma.

5. Discuss the pathogenesis o an asthmaattack in its ve phases.

6. Discuss the process o diagnosing asthma,including dierential diagnosis and availabletests.

7. Outline the appropriate treatment andmanagement o asthma, the medicationsused, and application o the various guidelines.

8. Discuss specic population considerations.

9. Explain the importance o patient educationwhen discussing prevention and managemento asthma.

10. Identiy triggers o asthma attacks.

Sections marked with this symbol includeevidence-based practice recommendations.The level o evidence and/or strength

o recommendation, as provided by theevidence-based source, are also includedso you may determine the validity or relevance o theinormation. These sections may be used in conjunc-tion with the course material or better application toyour daily practice.


3/44



INTRoDuCTIoN

Despite the act that asthma has existed or thou-sands o years, only in the past ty years has themedical community developed a better under-standing o asthma. Even with the great progressmade toward improved treatments and conceptso asthma, the disorder is requently misdiagnosedand mismanaged in many healthcare settings. Fur-thermore, the condition is increasingly commonand most healthcare proessionals will encounterpatients with asthma.

In the United States alone, more than 22 millionAmericans have asthma, a number that is steadilygrowing each year [1]. This increase in the numbero asthma cases extends globally. It is estimated

that there could be 100 million more asthmaticsworldwide by 2025 i the current trends continue[47].

In the United States in 2004, there were 14.7 mil-lion outpatient asthma visits to physician ocesand hospital outpatient departments. In the sameyear, there were 1.8 million asthma-related visits toemergency departments or asthma [2]. The costsassociated with healthcare usage related to asthmahas put a tremendous burden on healthcare systems

and proessionals as well as on patients and publicorganizations.

Direct healthcare costs or asthma in the UnitedStates total more than $10 billion annually; indi-rect costs (mainly lost productivity) add another$8 billion [48; 49]. In addition to direct and indi-rect costs, prescription drugs or the treatment oasthma represented the largest single direct medicalexpenditure, accounting or more than $5 billionannually.

Proper treatment and management can minimizethe eects o asthma. Along with pharmacologictreatment, there are many contributing agents(known as triggers or asthmagens) that, onceidentied, can be addressed with the patient andtaught to be successully managed.

Reviewing the signs and symptoms, pathophysiol-ogy, risk actors, diagnosis, treatment and manage-ment, and prevention strategies allows healthcareproessionals to be prepared to provide optimal careor the asthmatic patient.

HISToRY oF ASTHMA

The irst record o asthma-like symptoms wasdocumented in an Egyptian manuscript circa 1500B.C.E. [3]. Hippocrates rst reered to asthma as aspecic condition, using the Greek word asthma,meaning the act o panting or labored breathing[4]. Asthma-like symptoms and their treatmentswere described thousands o years ago in ancientChinese writings. The herbal medicine ma-huang,

traditionally used in Chinese medicine to treatasthma-like symptoms, comes rom the bark o treeso the genus Ephedra equisetina. The modern medi-cation ephedrine, a common ingredient in someasthma medicines, is derived rom this plant.

In the early 1700s, Bernardino Ramazzini, an Ital-ian physician, noted links between asthmatics andtheir occupations. Ramazzini documented asthmaresulting rom mill workers exposure to mill dustand armers contact with animal dander. Thiswas one o the rst attempts to identiy asthma-gens or triggers as causes o asthmatic attacks.Although most physicians in the 18th centurywere in agreement that asthma was a new disorder,it remained dicult to auscultate the lungs andexamine the patients lung tissue or secretions. By1761, Leopold Auenbrugger, an Austrian physi-cian, discovered a new technique or examiningthe lungs by percussion, or tapping on the patientschest, to elicit dierences in reverberating sounds[5]. Approximately sixty years later, French physi-

cian Ren Lannec, also an asthmatic, designedthe rst crude stethoscopea rolled piece o paperheld to the chest to listen to a patients heart andlungs. The ollowing decade would also bringimprovements in microscopic technology thatallowed physicians to examine lung tissue andsecretions.


4/44



British surgeon John Hutchinson developed therst spirometer in about 1850. It was originallyintended or his research in respiratory physiology,as a tool to measure respiratory fow rates. Soon,smaller devices were being widely used by patientswith lung disease in Europe, Australia, and the

United States [5].By the end o the 19th century, many companieswere shipping asthma medications all over thecountry and around the world. These were in theorm o powders, tablets, and liquids and otentimes labeled as secret ormulas. It was not uncom-mon to nd alcohol, cocaine, and/or morphine asactive ingredients. Until the late 20th century,inhaling medications via steam or smoke was one othe only ways o introducing medications directlyinto an asthmatics bronchial tubes and lungs [5].

DeFINITIoN

Since 1958, several attempts have been made toestablish a consensus denition o asthma. The lasto these was published in August 2007 as part othe National Asthma Education and PreventionProgram (NAEPP) Guidelines or the Diagnosisand Management o Asthma [6]. Asthma was notrecognized as a specic disease with a single cause.Instead, asthma is considered to be a conditionand an incompletely understood abnormality.

Asthma is considered a chronic, albeit reversible,respiratory disorder. Infammatory in nature, thecondition produces hyper-reactive and hyper-responsive airway and lungs, causing episodic,reversible airway obstruction through bronchos-pasms, increased mucus secretions, and mucosaledema [7; 8]. An asthmatics hyper-reactive lungsare more sensitive than most individuals and may

become infamed or edematous when exposed toirritants, such as cold air, animal dander, dust,tobacco smoke, or grass [8]. The asthmaticsimmune system overreacts to these irritants, con-

stricting the airways and lling them with mucus;constricted airways interere with the movemento air in and out o the lungs, making breathingdicult [8].

Asthma is marked by recurrent episodes o wheez-ing, breathlessness, chest tightness, and coughing.

Usually, these periods are associated with wide-spread but variable airfow obstruction ollowedby a period o relie, either spontaneously or inresponse to treatment [9]. Asthma has many puz-zling aspects, and its symptoms may wax and wane,especially seasonally [8]. Unlike other respiratorydiseases, such as congestive obstructive pulmo-nary disease (COPD) and emphysema, in whichair trapping and hyperinfation o the lungs alsooccur, asthma is reversible with the use o propermedications and therapies. Long-term lung tissuedamage can occur when asthma attacks occurrequently or the disorder is poorly controlled.Permanent damage would require many instanceso severe attacks.

ePIDeMIoLoGY

GLoBAL IMPACT

The World Health Organization (WHO) estimates

that 300 million people worldwide suer romasthma. In 2005, asthma was the cause o deatho 255,000 individuals [11]. The incidence andseverity o the condition varies globally.

Although or many years asthma was characterizedas a condition limited to industrialized countries, ithas now been identied as a health issue in devel-oping countries as well. Nearly 40 million peoplein Central and South America have asthma. InMexico, there was a sharp increase in asthma cases

in the 1990s; however, that rate has since startedto decline [50]. The countries o Brazil, Paraguay,Peru, and Uruguay all have childhood asthmaprevalence rates in the top quartile o countriesworldwide [10]. More than 80% o asthma deathsoccur in developing countries [11].


5/44



NATIoNAL STATISTICS

The global increase in asthma incidence and itsimpact on public health are also evidenced in theUnited States. In 2005, it was estimated that 7.7%o Americans (22.2 million people) had asthma.The number o reported asthmatics increased by

almost 75% between 1980 and 1996 [11]. Ratesdecrease with age; 9.3% o children have asthmacompared to 7.3% o adults [1; 51].

The cause o the prolieration o asthma within thelast ew decades is not yet known, although somehave attributed the raise to environmental actorsand expansion o the conditions diagnostic crite-ria. The National Health Survey questions, romwhich most o the statistics on asthma prevalenceare obtained, changed slightly ater 1997, causing a

shit in how the condition and associated statisticswere reported [12]. In 2001, the Centers or Dis-ease Control and Prevention (CDC) introduced amore precise measurement o asthma. Since then,the trend has remained stable at historically highlevels [12].

THe PeDIATRIC PoPuLATIoN

Asthma also remains an important infuence onpediatric health. As noted, in 2006, 9.3% o chil-dren were reported to have asthma [51]. Child-

hood asthma contributes considerably to schoolabsenteeism in the United States. In 2003 alone,children 5 to 17 years o age missed 12.8 millionschool days due to asthma [1].

It is estimated that 25% o all school days lost dueto chronic diseases or illnesses are due to asthma,making it the leading cause o school absencesdue to chronic illness [13]. Additionally, almost24% o asthmatic children have activity limita-tion as a result o their asthma [15]. With increas-

ing consequences o sedentary liestyle becomingevident in children, including overweight, obesity,and childhood-onset diabetes, asthma is seen as asignicant threat to pediatric health.

RACe AND GeNDeR

Studies ound asthma prevalence in the UnitedStates between 1980 and 1996 had increased inmales by 41%, to 5.75 million men. However, inemales in the same time period, the increase wasan incredible 105%, to more than 8.84 million

women. The higher incidence o asthma amongwomen may produce additional health conse-quences during pregnancy and/or childbirth [15].

The American Academy o Asthma, Allergy, andImmunology reports that the prevalence o asthmais 39% higher among black Americans than amongwhites [15]. Among Americans, the CDC hasound that the asthma rate among Puerto Ricansis 125% greater than that o non-Hispanic whiteindividuals and 80% greater than non-Hispanic

black individuals.

The National Asthma Education andPrevention Program Expert Panelrecommends heightened awareness ocultural barriers between the clinicianand patient that may infuence asthmamanagement as well as modication o

educational/communication strategies to addressthese barriers.

(http://www.guideline.gov/summary/summary.aspx?doc_id=11677. Last accessed September 16, 2009.)

Lvl evidnc: D (Panel Consensus Judgment)

As the incidence o asthma continues to rise, theamount o people suering rom allergies continuesto grow as well. Allergies are one o the most com-mon causes o recurrent respiratory inections, earinections, and breathing diculties, all o whichcan result in permanent damage to aected organsand body structures [13]. The most serious compli-

cation o allergic rhinitis is bronchial asthma [13].Individuals with untreated allergic rhinitis have anincreased likelihood o developing asthma [14].


6/44



RISK FACToRS

Although experts have been unable to denitivelyidentiy the cause or causes o asthma, there areseveral actors that increase the risk o developingthe condition in ones lietime. Identiying possible

risk actors specic to certain patients may allowliestyle changes or more strenuous observation osymptoms or better control o asthma symptoms.Overweight/obesity, heredity, and low birth weighthave all been linked to the development o asthma.Additional risk actors include living in an urbanarea, exposure to secondhand smoke, exposure tooccupational triggers (such as chemicals used inarming and hairdressing), respiratory inectionsin childhood, and gastroesophageal refux disease

(GERD) [16].oVeRWeIGHT AND oBeSITY

There have been many studies indicating a linkbetween obesity and asthma in adults and children.Research indicates that being overweight or obesesignicantly increases ones chances o developingasthma. Studies have shown that an overwhelmingmajority, approximately 75%, o asthma patientswho seek emergency medical care are obese [17].Patients who are excessively overweight place an

additional burden on their bodies, especially ontheir heart and lungs. Researchers in one studyound that both unctional residual capacity (theamount o air let in the lungs ater exhalation) andtidal volume were decreased in obese individuals[18]. These decreases were associated with severalactors, including changes in lung development andchronic systemic infammation, that may aect,induce, or exacerbate asthma symptoms.

Additional studies have revealed that weight loss

can increase respiratory unction. In one random-ized, controlled study, conducted by the Divisiono Pulmonary Medicine and Allergology, HelsinkiUniversity Central Hospital, subjects with a bodymass index (BMI) between 30 and 42 and a diag-nosis o asthma were studied or the eect that acontrolled diet had on their experiences o asthmasymptoms. Participants were placed on a regulated

diet or 14 weeks, during which time pulmonaryunction was regularly tested. At the end o the14 weeks, the subjects had a mean weight loss o31.2 pounds and a 7.2% improvement in theirpulmonary unction tests [19].

Unless contraindicated, moderate exercise is

encouraged or all people with asthma, as itstrengthens the lungs and improves respiratoryunction. Those patients whose asthma is triggeredby activity may be advised to take a short-actingbeta2 agonist or other bronchodilator 30 minutes to1 hour prior to exercising. Regular aerobic activityis essential or any asthmatic, taking into consider-ation contraindications or complications.

Asthma and obesity present a unique problem withpediatric patients. With the growing number o

both overweight and obese children and instanceso asthma in the United States, it has been theo-rized that the rise in obesity in children has contrib-uted to the rise o asthma. Studies have concludedthat overweight children are 1.5 to 2 times morelikely to develop asthma than other children [20;21]. The causative link between obesity and asthmaremains unclear, but the sedentary liestyle may bea risk actor or both asthma and obesity. Furtherresearch is underway to determine the impact oobesity on pediatric lung development and possible

implications in the development o asthma.

GeNeTIC PReDISPoSITIoN/FAMILY HISToRY

A genetic predisposition to develop immunoglobu-lin E (IgE) antibodies has been shown to increasethe incidence o allergy and asthma. However,since the mapping o the human genome has beencompleted, additional genetic actors contribut-ing to the development o asthma have been

recognized. The rst gene associated with asthmasusceptibility and airway hyper-responsiveness,ADAM33, was mapped in 2002. Researchers atChanning Laboratory, Brigham and WomensHospital in Boston, were able to link variants othis gene to a amilial history o asthma and asthmasymptoms. In 2003, two more genes relating toasthma, PHF11 and DPP10, were identied [22].


7/44



Results have been mixed regarding the role o Claracell secretory protein gene variants and the asthmaphenotype on the development o asthma, but as o2009, research seemed to indicate a link [43]. Thesediscoveries have opened new avenues or researchin asthma and allergy. Although causative chromo-

somal regions and candidate genes are now beingrevealed, this has not ruled out the infuence oenvironmental actors in asthma development.

Should a amily have a history o allergies andasthma, the rst two years o a childs lie arecritical; exposure to potential allergens duringthis time increases the likelihood that a child willdevelop asthma [23]. In addition, early contactsto such potential allergens may contribute to theseverity o the childs asthma. Genetic tendencytoward lung sensitivity may not ollow a directline; asthma may bypass a generation or suracein other amily branches [8]. The exact mode oinheritance is unclear.

PReMATuRe BIRTH

Premature birth and associated low birth weighthave been considered a risk actor or asthma ormany years. A 2005 U.S. study ound that school-age children who had been extremely low birthweight inants (less than 1000 grams or 2.2 pounds)

experienced several long-term health, educational,and social eects. This included asthma, which wasreported in 21% o the children o extremely lowbirth weights, compared to only 9% o those whohad been o normal weight at birth [24]. Addition-ally, investigators in another study ound that blackinants weighing less than 2,500 grams at birthwere signicantly more likely than other inantsto develop asthma later in lie [25]. The causal linkbetween low birth weight and premature deliveryand asthma development has not been completely

determined. Poor intrauterine growth and lungand immune system development have long beenbelieved to be the cause; however, additional ac-tors that are oten present in premature inants,including antibiotic use in early lie, respiratorysyncytial virus (RSV) inection in inancy, andpneumonia in early childhood, have been associ-ated with the development o asthma and requireadditional research [52; 73].

PATHoPHYSIoLoGY

ANAToMY AND PHYSIoLoGY

Asthma most prominently aects the respiratoryand immune systems, and knowledge o the struc-

tures and workings o these systems is vital to anunderstanding o the condition.

The brie review o the related anatomy andpathophysiology o asthma and allergies thatollows may be useul to some healthcare proes-sionals.

The most obviously aected structures are thebronchial tubes. As the bronchi stretch deeper intothe lungs, they subdivide into smaller bronchioles.A pale, thin membrane, known as the bronchial

mucosa, lines these bronchial tubes [8]. Mucousglands, which keep airways lubricated with waterymucus, are embedded within the many layers obronchial lining [8]. Harmul substances stick tothe mucus or sputum and are propelled out o thelungs by the movement o the cilia; this mucus pro-duction is one way the body ghts inection [8].

The outer walls o the bronchial tubes are sur-rounded by smooth muscles; movement o thesemuscles controls the size o airways openings,

permitting air in or out o the bronchioles. Whenmuscles are relaxed, airways remain open, allowingair to pass through without eort. Upon exhala-tion, the muscles contract [8]. Contraction canoccur with amazing rapidity. When the lungs and/or bronchi are irritated, the muscles contract andnarrow the diameter o the tubes [4]. As with allmuscle, continued contraction will cause growthor hypertrophy. The muscle itsel may becomechronically thickened even in its resting state,which narrows the tube urther [4]. When a

stimulus is encountered, proound narrowing othe bronchial tubes due to muscle constriction, orbronchospasm, can occur within just a ew seconds.Such narrowing in its most severe orm can resultin sudden death rom asphyxiation [4]. Usually,automatic refexes control whether muscles con-tract or relax.


8/44



Deep inside the lungs, surrounding each bronchi-ole, are millions o tiny balloon-like air sacs calledalveoli. These structures provide the environmentor the exchange o gases, allowing oxygen rominhaled air to pass into the bloodstream throughthe capillaries within the sacs [8].

Asthma is considered a disorder o exhalation, notinhalation. Patients with asthma are uncomort-able not because they cannot inhale enough air,but because obstructed airways are preventingthem rom exhaling the air that is already in theirlungs. In act, autopsies o patients who died oasthma complications have revealed lungs ull oair [8]. When bronchioles narrow during an asthmaattack, upstream obstruction causes premature clo-sure o airways with expiration, as pleural pressurebecomes greater than the pressure inside the airway(the equal pressure point, or EPP). Downstreamairways become compressed with expiration, trap-ping air in the alveolar sacs. Reduced respiratorymuscle eciency and unction can be caused bylung hyperinfation and thoracic hyperexpansion,resulting in air trapping. Respiratory muscle advan-tage is compromised, and the fattened diaphragmis orced to contract with shortened muscle bers,resulting in a eeling o chest tightness. Thiscan lead to airway rupture, maniested as pneu-

mothorax, pneumomediastinum, or subcutaneousemphysema.

INFLAMMATIoN ANDTHe IMMuNe SYSTeM

The most common eatures o asthma are infam-mation and edema (swelling) o the airways,and treatments have ocused on the connectionbetween inlammation and asthma since themid-1980s. At that time, researchers developedber-optic bronchoscopes, with which they were

able to view the lungs (and take samples o airwaytissues) o those with chronic asthma [8]. With thisadvancement, researchers concluded that airwayinfammation in asthmatics never clears, evenwith mild asthma; thereore, treatment ocusingon infammation reduction was determined to bethe most eective or long-term management [8].

When the infammatory cascade, the physiologicalprocess o an asthma attack, is not treated, reboundo acute symptoms can occur, resulting in extremedamage and potentially permanent scarring.

Infammation is a process involving the immunesystems reaction to what it identies as oreign

or harmul items. The immune system consistso three primary components: the thymus gland,lymph nodes, and bone marrow. These parts pro-duce two major types o blood cells: red bloodcells, which transport oxygen rom the lungs to thetissues o the body, and white blood cells, whichdeend the body against invasion and inection.

Lymphocytes, a type o white blood cell, are dividedinto two categories: B cells, which manuactureantibodies or immunoglobulins that identiy or-

eign contacts as harmul agents, and T cells (romthe thymus gland), which release chemicals knownas cytokines that kill the invading antigen [8].Antibodies aid the immune system in recogniz-ing organisms that have inected the body in thepast, allowing the immune system to ortiy andstrengthen the body against uture invasions bythe recognized antigen [8].

PATHoGeNeSIS oF ASTHMA

The pathogenesis o an asthma attack can be bestdescribed as an infammatory cascade composedo triggered, acute inlammation and chronicinfammatory changes. In a nonasthmatic body,the immune responses in the bronchi (swelling,excretion o mucus, recruitment o infammatorycells, etc.) are present in a lesser degree to protectthe body against any inectious agents or oreignobjects. However, an asthmatics system producesan extreme reaction to otherwise relatively harm-

less irritants, reerred to as asthmagens or triggers.Exposure to a trigger causes infammatory mastcells to release specic infammatory mediators,including histamine and interleukins, resulting inan acute response. Histamine causes local tissueedema; interleukins generally act as chemotacticactors and activate other inlammatory cells.


9/44



Studies reveal that leukotrienes, another chemicalreleased by mast cells, prolong bronchial muscleand airway constriction [8].

As a result o the infammation, bronchospasmoccurs. Bronchospasm and local tissue edema causenarrowing o the airways. Release o interleukins

and other chemotactic substances causes migrationo other infammatory cells including eosinophils,airway macrophages, and neutrophils. The physicalpresence o these cells can also cause airway nar-rowing. The migration o the infammatory cellsstarts within 30 minutes o exposure and may takehours to reach peak levels.

Several dierent types o antibodies contribute tothe infammation process. One group o antibod-ies has evolved to be particularly harmul: IgE.

Researchers believe that IgE once helped individu-als ward o common ancient parasites; althoughIgE is not needed today, the body continues tomanuacture it [8]. Most individuals are unaectedby the presence o IgE, as it only accounts or about1% o all antibodies [8]. However, millions o indi-viduals have inherited the genetic predisposition tooverproduce IgE; in some cases, B cells release up to20 times the normal amount o IgE. I an excess othe antibody is produced, the immune system mayoverreact to routine substances. Each substance to

which an individual is sensitive triggers a dierentIgE antibody; any one o these substances couldresult in allergies that can trigger asthma.

CAuSeS oF HYPeR-ReSPoNSIVeNeSS IN ASTHMATICS

The actual cause o the hyper-reaction by an asth-matics immune system is unclear. While manycases may be attributed to a reaction in responseto exposure to an asthmagen, the possibility o

nervous system involvement is also an acceptedtheory. Generally, the sympathetic nervous system(SNS) and the parasympathetic nervous system(PNS) work in harmony to balance the bodys unc-tions; the PNS stimulates the bronchial tubes toconstrict while, at the same time, the SNS stimu-lates the bronchial tubes to dilate [8]. Ideally, thesetwo systems coordinate to maintain open airways,

allowing an eortless fow o air during inhalationand exhalation.In the asthmatic lung, it is thoughtthat the balance may be tipped toward the PNS andthat this imbalance results in narrowed bronchialtubes and asthma symptoms [8]. There was oncea belie that the PNS was solely responsible or

airway sensitivity; however, studies now seem toindicate that, although the PNS is involved, it isnot the major reason or infammation in asthma[8]. Researchers continue to study the importanceo these neurotransmitters relative to bronchialmuscle tone.

Additionally, there is a proposed theory that someasthmatics have abnormal beta receptors and theproper neurotransmitters are blocked rom reachingthe appropriate receptors [8]. When the nervoussystem becomes unbalanced due to this blockage,the parasympathetic nerves overreact and constrictthe bronchial tubes. For some researchers, thebeta blockage theory oers a better explanationo the cause(s) o asthmatic symptoms present insome patients ater exposure to what are known asnonspecic triggers, such as viruses and extremeweather changes [8]. However, it is still not under-stood how and when beta receptors would becomedeective.

eLeMeNTS oF AN ASTHMA ATTACK

There are essentially ve key elements o an asthmaattack: muscle spasm, excess mucus, coughing,wheezing, and atigue. While not all ve elementsare present or all patients, they are the most com-mon physical maniestations o an episodic attacko the condition and should be evaluated andtreated urgently.

Mscl Spasm

In response to irritation and immune response,

muscles on the outer layer o the bronchi contract,causing a bronchospasm. Tightened muscles restrictthe movement o air. Depending on the degree oairway narrowing, which diers or each asthmapatient and with the severity o the attack, thecharacteristic breathing diculty, chest tightness,wheezing, and coughing will ollow [8].


10/44



ecss Mcs

Inlammation can produce excess mucus as aprotective mechanism. During an asthma attack,glands secrete excessive amounts o thick mucus tocompensate or the increased amount o irritantsor allergens. The excess mucus clumps together in

the airways, urther narrowing the bronchial tubesby partially blocking the passageway and hinderingbreathing. This increased amount o mucus canalso orm plugs that clog very small airways. Duringan asthma episode, some patients attempt to cleartheir airways by coughing up what seems to be amucous plug. However, patients may produce manyplugs; consequently, they may have a continuous,irritating hacking cough. I let untreated, mucousplugs can prolong asthma episodes and increase therisk o inection [8].

Cghing

When secretions become too thick or cilia tohandle, the system responds by coughing to removethe unwanted substance. Dry coughs in asthmaticpatients are generally the product o extra-thickmucous plugs or bronchioles so blocked that themucus cannot be removed or move through. Nasaland sinus drainage, a common symptom o aller-gies, may also irritate airways and produce a nag-ging, unproductive cough [8]. I a patient has beenmouth breathing, the airways may become dry andhave decreased elasticity, making it more dicultto clear them. I this is the case, the patient shouldbe encouraged to take requent sips o water orisotonic fuids (electrolyte replacement drinks).

Whzing

Wheezing is considered to be a trademark oasthma, but it is not a denite indicator. Thewheezing sound associated with asthma results rom

a orceul rush o air pushing through narrowed,constricted airway lumens. The surge o air causesvibrations that make the wheezing sound. In somecases, airways can be so constricted that the airfowing past a blockage is not sucient to producea wheeze. In very severe attacks, the absence owheezing is a worrisome sign.

Note with importance that a patient with severeasthma has acute airway infammation during anepisode, and as stated previously, patients withchronic asthma have continuous symptoms oairway infammation, which can eventually destroyairway tissue and alter lung unction. Prolonged

infammation may result in permanent obstruc-tion as a result o alteration o the bronchial walls.Unortunately, ater this change occurs, the airwaysmay not respond to common treatment as quicklyor at all, which is the reason medication to reduceairway inlammation, subsequently preventingpermanent obstruction, is so important [8].

Fatig

Breathing with asthma can atigue the body. Asexhalation is blocked and air is trapped in the

lungs, more orce is required to maintain adequateoxygen supply. To aid in exhalation, accessorymuscles become involved, which can deplete thebody o energy. Untreated asthma can producesevere degrees o atigue or the patient, and thiscan become a critical situation warranting immedi-ate intervention [8]. Lethargy, decreased responsetime, and weakness are all late signs o atigue.

DIAGNoSIS

PHYSICAL exAMINATIoNAND PATIeNT HISToRY

In some instances, a physical examination and athorough exploration o a patients medical his-tory oer enough inormation or an accurateasthma diagnosis. There are several main criteriathat must be present or a diagnosis o asthma tobe ascertained. It is vital that a history o episodicasthma symptoms, characterized by airfow obstruc-

tion, be established. Symptoms that increase theprobability o an asthma diagnosis include episodicwheeze, chest tightness, allergic rhinitis, atopic der-matitis, shortness o breath, and cough. It shouldalso be noted i symptoms worsen at night or inthe presence o aeroallergens, irritants, or exercise.A amily history o asthma, allergies, sinusitis, orrhinitis is also an indication o potential asthma.


11/44



According to the National Institutes o Health(NIH), most recurrent episodes o coughing and/or wheezing may be attributed to asthma [6]. Clini-cal signs o airway narrowing generally consist owheezing, increased respiratory rate, retractions,nasal faring, and grunting. Later signs can include

tripoding (using accessory muscles to breathe) andaltered mental status. In general, asthma symptomsare revealed in dierent combinations and varyingintensities. Due to the act that asthma symptomscan vary throughout a day, month, or even year,absence o the symptoms during the examinationdoes not exclude a diagnosis.

The physical examination should include an assess-ment o the upper respiratory tract, chest, andskin. One presenting sign is hyperexpansion o thethorax. Patients with severe asthma oten developa barrel-shaped chest due to the orced inhalationand exhalation, which may cause chest and ribmuscles to overdevelop. In time, the chest wallsstretch out o shape, assuming a rounded appear-ance. As the patient inhales and exhales deeply,the quality o the breath sounds can be assessed.Sounds o wheezing during normal breathing or aprolonged phase o orced exhalation may indicateasthma. Observing increased nasal secretions,mucosal swelling, sinusitis, rhinitis, nasal polyps, or

edema under the eyes are possible signs o allergicasthma. Any o these indications should be noted.Lastly, the skin should be examined or evidenceo atopic dermatitis, eczema, or other allergic skinreactions. Red, scaly skin with pruritus may indi-cate eczema and can signal other orms o allergyand possibly allergy-related asthma.

PuLMoNARY TeSTS

Most physicians order tests to conrm an asthmadiagnosis or to rule out any complications and

evaluate the severity o the condition. The objec-tivity o pulmonary tests allows or a reliableanalysis o lung unction that patient history andphysical examination may not provide; this inor-mation may be valuable to the diagnosis process.The most critical tests or evaluating asthma assesspulmonary unction, which measures lung per-

ormance. Pulmonary tests calculate the amountand rate o air expelled during a single breath,helping to discern whether constricted airwaysare responsible or blocked airfow [8]. Guidelinesor normal breathing are based on analysis o dataobtained rom large segments o the population. A

patients inormation is plotted on a continuum,allowing comparison to average breathing patternsor healthy individuals o the same sex, age, andsize. Two common methods o measuring airfowassess orced expiratory volume (FEV1) and peakexpiratory fow (PEF) [8].

Spirmtry

A spirometer is a simple machine used to determineboth the total amount o air that can be orceullyexhaled ater maximum inspiration, reerred to

as orced vital capacity (FVC), and how ully aircan be expelled rom the lungs, measured by theamount o air orced rom the lungs in one second,which is expressed as orced expiratory volumeor FEV1 [8]. The spirometer is generally used indiagnosis to establish airlow obstruction andreversibility. Obstruction may be ascertained i theFEV1 is less than 80% o the predicted value or iFEV1 divided by FVC is less than 65%. Normally,the FEV1 should account or more than 75% othe FVC; anything less than 75% should indicate

a possible obstruction and 65% or less may indicatea diagnosis o asthma [6].

The National Asthma Education andPrevention Program Expert Panelrecommends the ollowing requenciesor spirometry measurements: at the timeo initial assessment; ater treatment isinitiated and symptoms and peak expiratory

fow (PEF) have stabilized, to document attainmento (near) normal airway unction; during a period

o progressive or prolonged loss o asthma control; andat least every 1 to 2 years to assess the maintenance oairway unction.

(http://www.guideline.gov/summary/summary.aspx?doc_id=11332. Last accessed September 16, 2009.)

Lvl evidnc: B (randomized controlled trials,limited body o data) and C (nonrandomized trialsand observational studies)


12/44



Pak Flw Mtr

A peak fow meter measures the speed o exhala-tion. The highest speed or best fow is reerred toas peak expiratory fow rate (PEF) or peak fow.The peak fow meter is less sophisticated than aspirometer, which provides a more thorough assess-

ment o lung unction. However, the meter has theadvantages o being less expensive, portable, andeasy to use. The severity o a patients asthma canbe determined by careul and consistent monitor-ing o peak fow and comparing it to a patients bestpeak fow and to standard measurements. Studiesconrm that short-term peak fow measurementsassist healthcare providers in assessing asthmaseverity [8].

Nitric oid

Studies have shown that measuring exhaled nitricoxide is a helpul tool in evaluating and diagnosingasthma. Nitric oxide is a mediator or the infam-mation that occurs during an asthmatic episode;the amount o nitric oxide measured during exhala-tion will directly correlate with the infammationin the bronchial tubes [27]. Monitoring the con-centration o nitric oxide in expired breath mayallow healthcare providers to conrm the reversiblenature o the infammation and assess the eective-ness and adherence to the prescribed therapeutictreatment. In general, higher concentrations onitric oxide would be a sign o more severe ormso asthma.

ASTHMA CHALLeNGe TeSTS

When an asthma condition is dicult to conrmor treat, asthma challenge tests may be undertakento veriy the diagnosis. O course, any challengetest is potentially dangerous, as there is a risk thatthe test may induce a serious asthma emergency

or unpredicted delayed reaction. So, preerably,challenge tests should be perormed in a hospitalsetting under controlled conditions.

There are two main challenge tests that are use-ul in assessing a patient or a possible asthmadiagnosis. The rst is an inhalational or chemicalchallenge, whereby patients inhale a small amounto either a suspected asthma trigger or one o twochemicals: histamine, which occurs naturally in

the body and may induce asthma-like symptoms,or methacholine, which is known to cause airwayconstriction only in people with asthma [8]. Aterexposure, spirometry is perormed. I a reactiondoes not occur initially, the concentration o thesubstance is increased and spirometry is repeated.The procedure is repeated until it is determinedthat there is no sensitivity or until FEV1 decreasesby 20%, which would be indicative o asthma.

Second, i respiratory distress increases with exer-cise, an exercise challenge may be recommended.Spirometry is perormed beore, during, and aterthe patient engages in moderate-to-strenuousactivity, such as running on a treadmill or riding astationary bicycle, in a controlled laboratory set-ting. I peak fow or FEV1 drops more than 12% to15% during or ater the activity, the diagnosis willmost likely be exercise-induced asthma [8].

ALLeRGY TeSTING

Because the comorbidity rate associated with

asthma and allergies is so high, it is advisable toengage those patients suspected o having asthmain standard skin and blood tests to determine i heor she is atopic. The most common allergy testsinvolve introducing the suspected allergen intothe skins surace and monitoring the area or areaction. This skin testing can be expensive, timeconsuming, and i conducted improperly, resultsmay be misleading. Nonetheless, skin testing canbe useul in conrming suspected allergies. Thethree types o skin tests are prick, scratch, and

intradermal, each o which involves adding smallamounts o a given allergen to the skin, eitherpercutaneously or intradermally. The test siteshould be assessed ater approximately 15 to 20minutes to determine i a reaction has occurred.


13/44



A positive allergic reaction is characterized by awheal at least 3 mm in diameter greater than thenegative control. A ew patients may experiencedelayed anaphylactic reactions to even the small-est amounts o allergen; untreated, these reactionscan result in asthma attacks o increasing severity,

especially in sensitive individuals [8]. Thereore,many physicians and allergists avor eliminationdiets over skin tests or dierentiating ood sen-sitivity.

In addition to elimination diets and skin testing,there are various blood tests that may be used toassess allergy or allergic reactions in a patient.These tests are able to calculate the proportion othe antibody IgE in the body. In inancy, IgE levelstend to be low, rising gradually over the ollow-ing decades and decreasing beginning around 40years o age. Lowest levels are recorded when anindividual is 70 years o age. Thereore, high IgElevels can imply that allergies may be triggering theasthma. Elevated IgE levels in inants and youngchildren are one test used to help predict utureallergies. Although the analysis is airly common, itis rarely used as a sole indicator o allergy or allergicasthma [8]. A group o tests, the radioallergosor-bent test (RAST), the multiple allergosorbent test(MAST), and the fuorescent allergosorbent test

(FAST), evaluate blood levels o IgE or sensitivityto specic allergens [8].

Although the connection between asthma andallergies is compelling, it is vital to remember thatnot all people who develop asthma have allergies[8]. Whereas allergies play a part in asthma or 80%to 90% o children, the gure is thought to be loweror adults [22]. Nevertheless, it is worth investigat-ing the possible role o allergens in asthma because,quite simply, knowledge o allergic triggers associ-

ated with asthma will allow patients to avoid theharmul agents and better manage the condition.Allergen and asthmagen avoidance is one o themost eective treatments or asthma and allergypatients [28].

DIFFeReNTIAL DIAGNoSIS

Because the signs and symptoms o asthma aresimilar to several other diseases and disorders, it isimportant to rule out other conditions that mayhave a similar outward appearance o asthma. Thisis particularly imperative or patients unable to

express symptoms or history verbally.In particular, panic disorders, physical airwayobstructions, congestive heart ailure (CHF),GERD, and other pulmonary conditions, such asCOPD, pneumonia, and bronchitis, may eitherexacerbate or mimic the signs and symptoms oasthma. Shortness o breath, decreased exercisetolerance, chest tightness, and wheezing may occurwith any o these conditions.

Although not all asthmatics wheeze, it is one o

the characteristic symptoms o asthma, occurringeither during episodic attacks or quite regularly,depending on the severity o the condition. How-ever, there are several other potential causes owheezing that should be investigated as part othe diagnosis process. For example, wheezing inchildren may be attributed to acute inections,including bronchiolitis or pneumonia. I thesediseases are suspected, chest x-rays and/or bloodgas tests may be ordered.

Pdiatric Cncrns

Dierential diagnosis or children presenting withwheezing and recurrent lower respiratory inectionsshould include cystic brosis, bronchopulmonarydysplasia (prevalent in premature inants), dysmo-tile cilia syndrome, alpha-1-antitrypsin deciency,and immunodeciencies.

Cystic Fibrosis

Cystic ibrosis is the leading cause o chronic

debilitating pulmonary disease and pancreaticexocrine deciency in the rst three decades o lie[9]. It occurs most oten in white children, and itis estimated that 1 in every 29 white Americansis a carrier o the cystic brosis mutation. Amongblack individuals, the incidence is 1 in 16,300,and in Asian Americans, it is 1 in 32,100 [9].


14/44



Although cystic ibrosis can be a multisystemdisorder, the respiratory system is almost alwaysinvolved and tends to dominate the clinical pic-ture. Common respiratory complications includeair trapping and wheezing, chronic cough andsputum production, retractions, tachypnea, and

recurrent or chronic pneumonia. However, theearliest signs o cystic brosis can be gastrointesti-nal and pancreatic, not respiratory. Signs o cysticbrosis include radiograph abnormalities such asbronchiectasis, atelectasis, inltrates, and hyper-infation. Thereore, a chest x-ray or computedtomography scan may be useul in determining thecorrect diagnosis, especially in children.

GERD

Excessive mucosal secretion secondary to GERD or

gastrointestinal malormation may cause wheezingin both children and adults and should be consid-ered during evaluation. It is reported that 34% opatients with GERD experience chronic coughand/or wheezing as part o their symptomology[29]. Additionally, bronchiole irritation result-ing rom repeated exposure to gastric acid maytrigger asthma symptoms. Generally, asthma-likesymptoms that stem rom GERD can be controlledwith initiation o refux medications and liestylemodication.

Structural Issues

I respiratory diculties are suspected to be moreo a structural issue, a bronchoscopy may beperormed. This is especially important i con-genital abnormality, such as laryngomalacia ortracheobronchomalacia, or tumors or growths aresuspected. It can also rule out oreign body aspira-tion. Samples o tissue and sputum to be used inadditional testing may be taken during the proce-

dure, i necessary.Adlt and Griatric Cncrns

In adults, CHF and other cardiac conditions, suchas mitral valve disease, should be considered inthe dierential diagnosis o asthma. Establishingan asthma diagnosis is dicult or patients olderthan 55 years o age due to the increased incidenceo CHF and cardiac asthma, respiratory dicul-

ties resulting rom cardiac problems. Conversely,asthma can aggravate heart disease when oxygensupplied by the lungs is inadequate or the reducedblood supply to the heart. Any diseases or condi-tions that may cause dyspnea are considerationswhen determining a dierential diagnosis o

asthma.A particular orm o an inection-plus-allergycondition known as allergic bronchopulmonaryaspergillosis, oten shortened to aspergillosis orABPA should also be considered [28]. The condi-tion initiates with the introduction o the ungusAspergillus fumigatus, a mold that is abundant indamp straw, compost heaps, birdcages, and anydecomposing material.A. fumigatus does not usu-ally have an adverse eect on those with normalimmune systems [28]. However, in asthmaticor immunocompromised individuals, the sporesrom this mold may begin to grow in the lung tis-sue [74; 75]. An allergic reaction may then occurin response to the ungus. This is an importantconsideration or those who work in agriculturaloccupations and is one example o the useulnesso a thorough history and liestyle questionnaire inthe diagnosis and management o asthma.

ABPA may present comorbid with asthma or thesimilar symptoms may result in a alse asthma

diagnosis [28]. The signs and symptoms o ABPAinclude rubbery plugs o golden-brown or greensputum; a ever apparent only when the asthmasymptoms are severe; worsening symptoms despitetreatment; dependence on steroid medications; andvery high levels o serum IgE [28]. ABPA is nor-mally treated with steroids to control the allergicreaction and with physiotherapy to clear the mucusrom the lungs [28].

There are also certain medications that may

induce asthma-like symptoms. Specically, thereare two conditions, aspirin-sensitive triad andnonallergic rhinitis with eosinophilia syndrome(NARES), known or their similar presentationto asthma. The diagnosis o aspirin-sensitive triadis based on three distinct symptoms: perennialrhinitis, nasal polyps, and asthma. Patients with anaspirin-sensitive triad diagnosis tend to collect all


15/44



three symptoms gradually, in no particular order,over a period o years or decades [28]. Althoughit is not known how common non-steroidal anti-imfammatory drug (NSAID) sensitivity is or adultasthmatic patients, various reports site requen-cies rom 3% to approximately 40%. It is ar less

common in pediatric asthmatic patients; womenin their third decade are most commonly aected[4; 76]. Quite oten, aspirin-sensitive asthmaticpatients have other related respiratory conditions,including sinusitis, severe rhinitis, and nasal polyps[4]. Nasal polyps are benign infammatory growthsthat begin in the sinuses but protrude into the nos-tril [4]. However, the absence o sinusitis and nasalpolyps does not automatically rule out the presenceo aspirin sensitivity [4]. Aspirin sensitivity candevelop suddenly and produce a reaction similar

to anaphylaxis, but it usually builds over manyyears. Asthma patients ound to have a sensitivity,usually by an aspirin challenge test, are advised toavoid all NSAIDs even i they have not reacted tothese medications in the past [76]. Also, patientswith aspirin-sensitive triad will oten have crossintolerances with suldes, particularly wine andother alcoholic beverages containing suldes, andnaturally occurring salicylates, which are ound incitrus ruit, nuts, and grapes. Food additives mayalso be problematic [76].

NARES is caused by the invasion o eosinophilsinto the nasal passages, resulting in severe infam-mation. Nasal secretions testing positive or thepresence o eosinophils (usually greater than 20%o the cells on nasal smears) are used to conrma positive diagnosis o NARES [77]. NARES maydevelop as part o aspirin-sensitive triad or com-pletely separately rom any aspirin sensitivities.The cause o the eosinophil inltration is notclear.

In general, a diagnosis o asthma may be reached ia patient has a strong amily history, has repeatedepisodes o wheezing or other breathing dicul-ties, and responds to bronchodilators [6]. However,because a wide spectrum o diseases and disordershave strikingly similar symptomology, it is vital thatthose avenues are exhausted prior to establishingan asthma diagnosis.

MeDICAL TReATMeNT

AND MANAGeMeNT

The treatment o asthma is generally divided intoone o two categories, either short- or long-termmanagement. Short-term treatments are used onlyin the case o an asthma attack or immediate relierom the devastating symptoms. The ocus o treat-ment or stable asthma is long-term prevention,planning ahead or emergencies, and being alert toincreased symptoms [8]. Asthma may be controlledwith early, accurate diagnosis and a treatment planthat involves a patients, and perhaps an entireamilys, active participation.

Asthma exacerbations can be rightening experi-ences or both patients and their caregivers, espe-

cially the rst time an attack occurs. A thoroughexplanation o all the treatments administeredwill better educate patients or uture attacks andprepare them or uture treatment.

CReATING A TReATMeNT PLAN

The NAEPP advocates the use o a stepwiseapproach to asthma management [6]. In thisprogram, the asthma classications are treated asseparate steps, beginning with mild intermittentat step one and advancing to severe persistent atstep six.

Asthma is classied based on symptom severity andrequency (Table 1) [6]. Those patients or whomsymptoms occur more requently (more than 2times per week) and who experience intererencewith normal activity as a result o asthma symp-toms are classied as having persistent asthma.Patients who experience asthma less than 2 timesper week, have less than 2 nighttime awakeningsdue to asthma per month, use rescue inhalers less

than 2 times per week, have no intererence withnormal activity, and have normal peak FEV1 arecategorized as having intermittent asthma. Theasthma is then urther classied as mild, moder-ate, or severe based on the extent o intererencein daily lie, lung unction tests, and use o rescuemedications. Ater asthma severity has been clas-sied, the treatment step is determined and begun(Table 2).


16/44



STePWISe APPRoACH FoR MANAGING ASTHMA IN PATIeNTS 12 YeARS oF AGe AND oLDeR

Stp Prrrd Tratmnt Altrnativ Tratmnt Indicatin

1 Short-acting beta2 agonist as needed -- Intermittent asthma

2 Low-dose inhaled corticosteroid Cromolyn, leukotriene antagonist,nedocromil, or theophylline

Persistent asthma(Consider subcutaneousallergen immunotherapyor patients who have

allergic asthma)

3 Either low-dose inhaled corticosteroid

and long-acting inhaled beta2 agonistOR medium-dose inhaled corticosteroid

Low-dose inhaled corticosteroid

AND either leukotriene antagonist,theophylline, OR zileuton

4 Medium-dose inhaled corticosteroidAND long-acting inhaled beta2 agonist

Medium-dose inhaled corticosteroidAND either leukotriene antagonist,theophylline, OR zileuton

5 High-dose inhaled corticosteroidAND long-acting inhaled beta2 agonistConsider omalizumab or patients withallergies

--

6 High-dose inhaled corticosteroid,long-acting inhaled beta2 agonist,AND oral corticosteroids

Consider omalizumab or patientswith allergies

--

Quick-relie o asthma exacerbations in all patients short-acting beta2 agonist, up to 3 treatments at 20-minuteintervals as needed. Short course o oral systemic corticosteroids may be needed. Use o short-acting beta2 agonists>2 days a week or symptom relie generally indicates inadequate control and the need to step up treatment.

Source: [6] Table 2

CLASSIFICATIoN oF ASTHMA SeVeRITY IN PATIeNTS 12 YeARS oF AGe oR oLDeR

Cmpnnt Intrmittnt Prsistnt

Mild Mdrat Svr

Symptoms 2 days/week 2 days/weekbut not daily

Daily Throughout the day

Nighttime

awakenings

2 times/month 3 to 4 times/month >1 time/week

but not nightly

Oten every night

Short-acting beta2agonist use orsymptom control

2 days/week >2 days/week but notdaily and not morethan once per day

Daily Several times per day

Intererence withnormal activity

None Minor limitation Some limitation Extremely limited

Lung unction Normal FEV1between exacerbationsFEV1 >80% predicted

FEV1/FVC normal

FEV1 >80% predictedFEV1/FVC normal

FEV1 >60% predictedbut


17/44



The goal o each step o treatment is to preventasthmatic symptoms and provide the best therapyor the patient. Physicians and other healthcareproviders may dier in their step approach tomedication prescriptions. Some may treat symp-toms with the weakest medications or a specic

step and add stronger medications i symptomsare dicult or persist; others may preer to rapidlycontrol symptoms and then reduce medicationsto the smallest eective doses [8]. The NAEPPrecommends the step-down approach to managingasthma symptoms [6]. In any case, the goal o thetreatment plan should be expressed to the patientand outlined clearly, to ensure the best patientadherence possible.

Each step o the management plan requires a short-acting inhaled beta

2agonist or relie o sudden

onset and/or inrequent symptoms. Steps 2 (mildpersistent classication) and above include long-term control measures. There are separate stepplans or children 0 to 4 years o age and children 5to 12 years o age. Adolescents older than 12 yearso age ollow the plan established or adults.

Regular ollow-ups are vital to monitor the progressin the management o asthma symptoms. A reviewo current symptoms and improvements should beundertaken every 1 to 6 months, depending on the

patients condition, stage in treatment, and man-agement process. I symptoms start to subside andappear controlled ater several months, considerstepping down to less intense treatment.

The NAEPP also recommends that any patientsthat require that treatment or steps 4 or abovebe reerred to an asthma specialist. Other actorsthat may require reerral include initiation oimmunotherapy, diculty achieving or maintain-ing control o asthma symptoms, or the presence

o lie-threatening asthma episodes. Reerral to aspecialist may also be considered or those whorequire step 3 treatment [6].

PHARMACoLoGICAL INTeRVeNTIoNS

When considering pharmacological treatment oasthma, the dosage, timing, and type o medicationmust be tailored to individual needs. Optimal treat-ment should include methods to reverse airfowbarriers, stop symptoms rom occurring, prevent

serious attacks and need or emergency care andhospitalization, keep asthma rom interering withactivities o daily living, minimize side eects,and control symptoms with the least amount omedication [8]. As with the approach to manage-ment, medication therapy generally adheres to twopossible uses: to relieve symptoms quickly with theuse o bronchodilators or to reduce chronic airwayinfammation with anti-infammatory medications,preventing asthma rom recurring in the uture.

Mdicatin AdministratinAsthma medications may be inhaled, taken orallyin pill or liquid orm, or in emergency situations,injected intravenously.

Inhalers

There are several types o inhalers availableincluding aerosol, dry powder, and nebulizers.Metered-dose inhalers (MDIs) rely on a mixtureo medication, preservatives, and liquid propellantgas to deliver medicine into the lungs in aerosolorm. As o December 2008, inhalers that containchloroluorocarbon (CFC) propellants are nolonger permitted to be sold [26]. Although thenew inhalers, with non-CFC propellants, are avail-able, they are not identical to the older versions,and patients who are transitioned to new inhalersrequire education regarding the use and care othe new inhaler. Furthermore, patients should bemonitored or changes in response to treatmentand any deviations in asthma status should be

reported.


18/44



Some short-acting inhaled medications begin toreverse airway constriction within 5 minutes; how-ever, long-acting medications have been developedin inhalant orm as well [8]. Inhaled medicationshave advantages over oral administration becausethe medication is able to enter directly into the

lungs rather than through the circulatory system.Some MDIs discharge medication ater a trigger ispressed, but newer versions are breath activated.For patients with poor coordination or impairedhand unction, such as those with arthritis or witha history o stroke, breath-activated devices mayimprove medication delivery. The drawback o thebreath-activated inhalers is that, during a severeattack, a lack o air may make device triggeringdicult [8].

Some patients require the assistance o a spacerwhen using an inhaler. A spacer is a plastic tubethat attaches to an MDI; its unction is to momen-tarily trap medication as it exits the inhaler, allow-ing the medication to be inhaled more easily andpreventing it rom being lost. Spacers may benetpatients who nd it dicult to squeeze the triggerand inhale at the same moment, such as youngchildren or older adults [8]. As medicine depositedin the mouth area can produce side eects, spacerscan help limit this and ensure that more medica-

tion reaches the lungs instead o the tongue orback o the throat.

A major problem with MDIs is knowing when theyare empty. Usually, a patient cannot see, hear, ortaste when a canister is empty or delivering lessmedication than intended; in act, at times, inhal-ers may eel heavy enough to hold medication butonly contain propellant and preservatives [8]. Insome cases, empty inhalers may leave a strangetaste or heavier spray in the patients mouth [8].

Each inhaler should have a label that indicates howmany measured metered doses the canister holds.For regularly scheduled medications, it is best tocalculate the number o usable doses beore a newinhaler is needed. Patients may mark calendars or

the canister to remind themselves when to reorderanother inhaler [8]. In the past, some patients haveutilized the so-called foat test to determine theamount o medication remaining in the canister.This has been proven to be inaccurate and shouldnot be recommended [36]. Some canisters may

require cleaning to prevent the accumulation obacteria.

Breath-activated dry powder inhalers incorporatethe same benets as other breath-activated inhal-ers; patients are not required to coordinate inhal-ing with releasing medication. Some dry powderinhalers have a dierent delivery system involvingthe insertion o a capsule with medicated, nepowder into the canister. In general, each capsulecontains a single dose that equals two sprays omedication (although double doses are available)[8]. One disadvantage o the dry powder is theamount o coordination needed to load the cap-sule into some inhalers. This can be a problem orthe young or elderly or or people with arthritis,Parkinsons disease, or other neurological diseasesaecting coordination or dexterity. Furthermore,depending upon the patients ability to breathein deeply, variable amounts o medication maybe inhaled. Another concern involves the eecto humidity on dry powder, which may infuence

dose strength [8].The nebulizer is a orm o inhaler that acts as avaporizer or humidier, delivering microdropletsoasthma medication in spray orm and allowinga patient to breathe it in through a mouthpieceor ace mask. Larger doses rom nebulizers mayincrease the risk o side eects, and studies haveshown MDIs to be as eective as nebulizers indelivering medication to the lungs [53; 54]. Nebu-lizers are used requently in children as they are

easier to administer and provide more accuratedosing. In the past, hospitals requently providedmedication in nebulizers to treat emergency asthmaepisodes, but now many acilities have convertedto the use o MDIs [8].


19/44



Oral Administration

In addition to inhalers, many asthma medicationsare manuactured as pills or liquids to be ingestedorally. Oral medications benet patients by reach-ing the small bronchial tubes that most inhaledmedication cannot reach. Newer developments

in longer-acting, timed-release oral medicationsadapt to the needs and liestyles o many patients.However, the amount o medication absorbed overa given time period can vary. Some patients maytake up to 6 times longer than others to reach peakconcentrations o a medication, which means eachpatient may require a dierent dose and requencyo administration to reverse breathing problems[8].

The disadvantage associated with oral medications

is the systemic distribution. I negative or unpleas-ant side eects occur, they last the entire timethe medication is active in the body. Dependingupon the orm and dose, day-long oral medicationmay be more dicult or the system to balancethroughout a 12- or 24-hour period than inhaledormulations [8].

Brnchdilatrs

Bronchodilators are used to address the acutesymptoms o an asthma attack. They act by relax-

ing the muscles surrounding airways, therebydilating bronchial tubes. The primary categorieso bronchodilators are beta2 agonists, theophyllinederivatives, and anticholinergics [8]. Most oten,bronchodilators are prescribed in inhaler or aerosolorm. They are also available in liquid, tablet, andcapsule orms, but these are generally not used dueto gastrointestinal side eects. The bronchodila-tor inhaler is usually the rst line o deense in anasthma attack [8].

Epinephrine

The rst oral medication to become availableor the relie o an acute asthma episode was epi-nephrine, a hormone produced by the sympatheticnervous system [8]. Epinephrine was once therst choice or treating acute asthma, but it has

proved to be a weak bronchodilator with quicklydiminished action. Moreover, epinephrine has verypotent systemic eects, causing tachycardia, highblood pressure, nervousness, headache, and in somecases, panic attacks. However, this medication maystill be used intravenously or subcutaneously insevere asthma emergencies. Epinephrine can bedescribed as nonselective; that is, the medicationacts on both the lungs and the heart.

Despite its limitations, epinephrine remains the

treatment o choice or severe asthma and airwayconstriction related to allergy. There is agreementthat sel-injectable epinephrine (EpiPen or EpiPenJr.) should be prescribed or patients who have hadprevious allergic reaction involving the respiratoryor cardiovascular systems. The patient, as well ascaregivers and all members o the amily, shouldbe instructed in how to administer the injection.Parents o children who have been prescribedsel-injectable epinephrine should inorm schoolpersonnel about the allergy and the availability o

the medication.

Beta2 Agonists

Bronchodilators that selectively act on the lungshave largely replaced the routine use o epineph-rine. These drugs are called beta2 agonists [8]. Beta2agonists stimulate the sympathetic nervous system,similar to epinephrine. However, they only act onreceptors located in nerve endings inside the lungs.These medications provoke specic beta2 receptorsin the muscles encasing the bronchial tubes to

reverse; when the drug stimulates these receptors,bronchial muscles relax and bronchial tubes dilate[8]. Beta2 agonists last longer in the body thanepinephrine and result in less risk o cardiovascularside eects, making them the drugs o choice orsae, short-acting bronchodilation.


20/44



According to the National AsthmaEducation and Prevention Program ExpertPanel, long-acting beta2 agonists are used incombination with inhaled corticosteroidsor long-term control and prevention osymptoms in moderate- or severe-persistent

asthma (step 3 care or higher in adults and children

5 years o age or older).(http://www.guideline.gov/summary/summary.aspx?doc_id=11674. Last accessed September 16, 2009.)

Lvl evidnc: A (randomized controlled trials,rich body o data) and B (randomized controlled trials,limited body o data)

Beta2 agonists may cause negative side eects, espe-cially i ast-acting orms are taken too requentlyor too long. Overuse can lead to poor asthma

control and possibly desensitization. Inhaling morethan one canister a month indicates an excessivereliance on bronchodilators to improve asthma.Patients with severe asthma may preer a beta2agonist or quicker action than anti-infammatorymedications, which take days to act. However,patients may then expose themselves to potentiallyatal attacks due to decreased beta2 agonist eec-tiveness i asthma fares out o control [8].

Inhaled beta2 agonist medications are associated

with ewer major side eects than orally adminis-tered beta2 agonists. However, patients who useinhalers may report problems as well. The mostcommon complaint is shakiness; other noticeableside eects may include tachycardia, heart palpi-tations, headache, dizziness, and increased serumglucose [30]. These side eects tend to diminishover time. Patients using oral beta2 agonists havereported tremors, nervousness, tachycardia, musclecramps, and sleeplessness [8].

There are more than 10 beta2 agonists approvedby the FDA or use as bronchodilators [30]. Beta2agonists come in every administration orm, whichcan assist in individualizing treatment. Injectionsmay work quickly in case o emergency, althoughthe eect lasts only about 20 minutes. Two toour pus o an inhaled beta2 agonist taken beoreexercise or travel in cold air can block wheezingor up to 4 hours [8]. Long-acting beta2 agonists are

usually taken twice a day and last up to 12 hours.Their longer action can help prevent interruptionsrom nighttime symptoms and/or allow patients toengage in activities that they would otherwise beadvised to avoid.

However, even longer-acting beta2 agonists cannot

control unstable asthma. These medications areunable to reverse the chronic airway infammationound in asthma patients, necessitating the addi-tional use o an anti-infammatory drug to preventsymptoms in the long-term [8]. And, as discussesd,overuse o these medications can lead to poorasthma control and possibly desensitization.

Theophylline Derivatives

Beore inhalers became widely available, meth-ylxanthines were the leading asthma medications.They could be administered intravenously ororally. Theophylline was ormerly the most widelyprescribed bronchodilator in the methylxanthinecategory and a keystone o asthma treatment inthe United States. However, controversies overthe medications benets and action have cloudedits popularity [8]. Exactly how theophylline worksin the lungs remains unclear. Some believe thattheophylline inhibits mast cells in the airway lin-ing rom discharging chemicals, such as histamine,

which suppresses the cell migration that triggersallergic asthma symptoms [31]. Theophylline mayalso relax airway muscles, allowing the tubes toopen and airfow to continue [8].

Theophylline provides a short- and long-termalternative or patients who cannot tolerate beta2agonists. The drug reduces mucus buildup andblocks nighttime symptoms in mild-to-moderateasthma. Its long-term beneits or preventingsymptoms are well documented or up to 12 hours,

although theophylline is generally less eectivethan beta2 agonists [8]. It should be noted thatcaeine is considered a methylxanthine drug, sopatients must be advised to monitor coee, tea, andchocolate intake while using this medication [8].Many actors may aect the metabolism or serumconcentration o theophylline, including diet,viral inections, hypoxia, age, some antibiotics,and smoking [23].


21/44



Anticholinergics

Anticholinergics such as ipratropium bromideand atropine continue to be eective in relievingbreathing disorders, including asthma. When usedor asthma, these medications are not usually therst line o deense but rather are used to supple-

ment beta2 agonists. Anticholinergics act on di-erent nerves than beta2 agonists, although bothblock nerve pathways to the lung and alter muscletone in the bronchial wall. Anticholinergics aectspecic lung nervous system receptors, or cholin-ergics, in the vagus nerve; this nerve branches intothe smooth muscles responsible or airway open-ing and the mucous glands that discharge thicksecretions. The result is reduced infammationand relaxed bronchial muscles. Throughout therespiratory tract, the drug stimulates nerve activity

in other reactive cells to decrease mouth and lungsecretions [8].

Anti-Infammatry Mdicatins

In 1991, a panel o international experts, underthe guidance o the NAEPP, recommended a newtreatment ocus acknowledging that asthma is anongoing problem involving airway infammation[33]. On the basis o research and similar studiesrom the mid-1980s, they oered a treatment shitaway rom calming acute fare-ups to preventativemeasures [8]. The panels report agreed that bron-chodilators work best or acute asthma situationsand or preventative treatment beore exertionor exercise, but it emphasized anti-infammatorymedications as the oundation or long-termtreatment or asthma [8]. This approach relies ondaily medication to maintain healthy lungs. It wasrecommended that patients who require regularlyadministered bronchodilators switch to longer-acting drugs designed to reduce airway infam-

mation [8]. These guidelines have been updatedseveral times.

Anti-infammatory medications block productiono substances rom cells involved in infammation,such as mast cells; this action reduces or reversesthe swelling that causes asthma symptoms [8].

Equally important, these medications lessen airwaysensitivity, which prevents edema [8]. I asthmasymptoms appear more than once or twice a weekand less powerul options cannot control them,anti-infammatory medication is indicated [8].Beore newer drugs were developed, the only anti-

infammatory asthma medication available was anoral corticosteroid, such as prednisone. Long-termtreatment with oral corticosteroids is associatedwith serious side eects, including stunted growthin children, hyperlipidemia, thinning skin, andimmune system impairment, making patient com-pliance dicult. As a result, several inhaled anti-infammatory drugs were developed, which greatlyreduced negative reactions [8]. The our primarytypes o anti-infammatory drugs are corticoster-oids, mast cell stabilizers, antiallergic medications,

and antileukotriene medications [8].

Corticosteroids

The most common group o anti-infammatorymedications is oral corticosteroids. Oral corticos-teroids are powerul anti-infammatory medica-tions. They are easy to administer and oer dra-matic reversal o symptoms during lie-threateningasthma situations. Although some corticosteroidstake a ew hours to work, their protection is long-lasting. Oral corticosteroids can be used or a brie

period to gain control o asthma beore moving toother long-term treatments that have ewer sideeects. Although reports about side eects romsteroids may concern some asthma patients, oralor inhaled corticosteroids can be a promising rem-edy or severe, uncontrolled asthma [8]. Patientsand/or parents may require reassurance that theseare not the same class o steroids used illegally byathletes.

Corticosteroids used in the treatment o asthma are

adrenal hormones [8]. Oral corticosteroid medica-tions are absorbed into the circulatory system andare distributed throughout the body. In the lungs,they prevent the development o airway edema.Signicant amounts o corticosteroids or pro-longed periods can adversely aect organ systems,such as bones and skin [8].


22/44



Severe asthma may require higher doses or longerperiods and may be tapered o over a period o 1to 3 weeks. Corticosteroids are usually taken uponawakening, mimicking the bodys natural steroidproduction schedule. Nighttime symptoms maybe managed with split doses taken in the morning

and at night [8].A major disadvantage o oral corticosteroids isthe array o negative side eects associated withtaking large doses over long periods o time [8].Because these medications enter the circulatorysystem, there is potential or damage to otherorgans. I taken or severe asthma, patients shouldbe diligent about identiying and reporting anyside eects [8].

Inhaled corticosteroid therapy concentrates on

reducing airway edema and improves resultsobtained rom bronchodilators while eliminat-ing extraneous eects to other systems. A beta2agonist may be prescribed in conjunction with aninhaled corticosteroid; the beta2 agonist is usedrst to unblock airways so the corticosteroid canpenetrate deeper [8]. Common inhaled corticos-teroids include beclomethasone, dexamethasone,funisolide, triamcinolone, and budesonide (avail-able in a dry powder inhaler) [8].

Patients who take inhaled corticosteroids maycomplain about the lack o immediate symptomrelie and cite it as a reason or not taking the medi-cation [8]. It is important to stress the long-termbenets when discussing this therapy with patients.Although risks o corticosteroid side eects aregreatly reduced with inhalers, they do exist; pro-longed use o high doses can increase chances orthe same types o unpleasant symptoms attributedto the oral or injected orms.

The doses o the inhaled corticosteroid must bevery high to equal the risk o side eects associatedwith oral corticosteroids [8]. Two more commonadverse reactions to inhaled corticosteroids arethroat irritation and candidiasis. Candidiasis candevelop when a patient is taking antibiotic medica-tions in addition to the corticosteroid inhaler ori other medical problems, such as diabetes, exist

[8]. To prevent candidiasis, advise patients to rinsetheir mouths ater each inhaler treatment and togargle with warm water to remove any medicationlet in the throat. The use o a spacer may also beadvisable, as it should ensure that medicine par-ticles are delivered to the lungs rather than to the

mouth and throat [8].Mast Cell Stabilizers

Mast cell stabilizers or inhibitors are consideredmild-to-moderate anti-infammatory agents andare most eective in the treatment and preventiono exercise- or allergen-induced asthma. Mast cellstabilizers interere with the infammatory processby stabilizing mast cell membranes and inhibitingthe activation and release o mediators such ashistamine and leukotrienes [33]. They may also

restrain the development o early and late broncho-constriction responses to inhaled antigens. Mastcell stabilizers used to treat asthma are generallyadministered by inhalation, but eye and nasal dropsare also available. Common mast cell inhibitorsavailable or the management o asthma includecromolyn and nedocromil. These medications areconsidered less eective than inhaled steroids inthe treatment o moderate-to-severe persistentasthma in adults. However, they are more desirablein the treatment o children and other patients or

whom the side eects experienced as a result osteroid therapy may be debilitating.

Other Antiallergic Medications

Similar to mast cell stabilizers, the concept oantiallergic medications as a separate category isunder intense study. The idea behind antiallergicdrugs is simpleeliminate the allergic reaction soallergic asthma symptoms are greatly reduced [8].Particularly, some studies have been undertaken to

research the eectiveness o antihistamine medica-tions on the long-term control o asthma symptoms[56]. However, research generally shows that theeect o antihistamines or the control o asthmais modest, especially i the patient is receivingthe recommended treatment with corticosteroids.I the patient also has allergic rhinitis, as manyasthmatics do, antihistamine medications may


23/44



help to control the rhinitis with secondary benetsto asthma symptoms. I antihistamines are taken,the newer ormulations, such as exoenadine, willhave a more selective action [34]. There is somepreliminary data, however, that suggest that thelong-term use o immune mediators such as anti-

histamine medications may be a cancer risk or thedevelopment o adult malignant gliomas [55]. Moreresearch is necessary to support this hypothesis.

Antileukotrienes

Antileukotriene medications, introduced in 1996,were the rst new class o asthma medicationsreleased in decades [8]. Leukotrienes act as a com-munication system or the infammation process.Antileukotrienes disrupt this communication pro-cess, reducing the eects o hyper-responsiveness in

asthma patients. There are two types o antileukot-riene drugs: leukotriene synthesis inhibitors, whichprevent these chemicals rom being generated, andleukotriene receptor antagonists, which preventthe chemicals rom delivering their messages byblocking their receptors [8].

Antileukotrienes are strong and very eectivein preventing exercise-induced asthma; they canalso prevent the development o bronchospasmcaused by aspirin and may be useul in milder

orms o asthma. Their role in the managemento moderate-to-severe asthma is o interest, but soar medical research has not supported its useul-ness in this population [69]. A trial therapy maybe indicated to determine i the medications willbe eective.

Common antileukotriene medications approvedin the United States include montelukast, zarlu-kast, and zileuton [30]. Compared to other anti-infammatory drugs, antileukotrienes may produce

more serious side eects,

asma diagnosis and management

Documents