An Assessment of Therapeutic Regimens in the Treatment of Acute Exacerbations in Chronic Obstructive Pulmonary Disease and Asthma

Acute exacerbations in chronic obstructive pulmonarydisease (COPD) and asthma are potentiallylife-threatening clinical events that may result insubstantial morbidity and mortality. Treatment ofthese episodes requires the rapid reversal of airwayobstruction by decreasing bronchoconstriction andinflammation. Consensus guidelines and recommendationsbuild on stepwise approaches to care, withthe mainstay of therapeutic interventions involvingbrochodilators and often including systemic corticosteroids,oxygen, and other treatments, dependingon severity and setting. Future therapies that targetinflammatory processes may offer improved efficacyand potential disease-modifying effects. The purposeof this article is to assess the treatment options foracute exacerbations in COPD and asthma within thescope of current consensus guidelines and recommendations(eg, Global Initiative for ChronicObstructive Lung Disease, National AsthmaEducation and Prevention Program, Global Initiativefor Asthma). Although bronchodilators and corticosteroidsare the primary therapies discussed, antibiotics,oxygen, magnesium sulfate, noninvasivepositive pressure ventilation, and helium/oxygenmixtures are also addressed. Preventive approachesfor future exacerbations are considered in the overallapproach to achieve optimal outcomes.

(Am J Manag Care. 2004;10:S139-S152)

Exacerbations in chronic obstructivepulmonary disease (COPD) and asthmaaccount for a substantial clinicaland economic burden and are often associatedwith events that ultimately result inmorbidity and mortality.¹ As such, guidelinesin the overall treatment of both COPDand asthma offer specific recommendationsfor the management of these acute episodes.The more recent guidelines for the treatmentof COPD published by the NationalHeart, Lung, and Blood Institute of theNational Institutes of Health and the WorldHealth Organization's (NHLBI/WHO) GlobalInitiative for Chronic Obstructive LungDisease (GOLD), the American College ofPhysicians-American Society of InternalMedicine, and the American College ofChest Physicians (ACCP) are based onexpert panel consensus and empirical evidence.^2,3 Although numerous other recommendationshave been developed, morerecent consensus guidelines for asthma havebeen developed by the National AsthmaEducation and Prevention Program (NAEPP)at the NHLBI and through collaborativeefforts between NHLBI/WHO's GlobalInitiative for Asthma (GINA).^4-9

Treatment regimens for acute exacerbationsgenerally follow stepwise approachesto therapy with the goals of rapidly reducingairway obstruction and restoring or maintaininglung function. Achieving optimalclinical outcomes through therapeuticapproaches requires the consideration ofpatient characteristics and risk factors, failureof initial treatment, treatment setting,and the severity of the exacerbation itself.Pharmacotherapeutic interventions emphasizethe use of bronchodilators, althoughsystemic corticosteroids, oxygen, andnumerous other agents may be considered.Prevention and risk-factor modificationremain of key importance in long-term care.Many therapies that target underlyinginflammatory processes are in developmentand may offer disease-modifying strategiesto reduce the number of substantially premature deaths and hospitalizations whileimproving quality of life in patients withCOPD or asthma.

Given the importance of managing COPDand asthma, the purpose of this article is toassess the treatment options for exacerbationswithin the scope of current consensusguidelines and recommendations. Althoughan emphasis is placed on the management ofthese acute events, preventive approachesand future treatments are also highlighted.Providing important background for thisdiscussion, the epidemiology, clinical andeconomic burden of illness, and clinicalpresentation of COPD and asthma have beendiscussed elsewhere in this supplement.¹The discussion offered herein establishesinsight into relevant material; consensusrecommendations and additional sourcesshould guide clinical decision making. Manyfacets beyond exacerbations are importantto the management of COPD and asthma,although these issues are beyond the scopeof this article.

General Considerations of AcuteExacerbations in COPD and Asthma

Guidelines for COPD. Several factorsmust be considered before treating COPDexacerbations. The first is determining theappropriate setting to establish intervention(eg, outpatient, emergency department, hospitaladmission).¹⁰ Exacerbations are managedby improving airway obstruction byreducing inflammation and bronchoconstrictionwhile promoting mucociliary clearance.¹¹ Comorbid conditions or problemsthat may precipitate respiratory worseningor failure must also be addressed; if hypoxemiahas manifested, it should be rectified.¹²The severity of the exacerbation, treatmentfailures, comorbidities, and underlying diseasecharacteristics will determine treatmentoptions and the setting in which it isadministered.¹³ Careful observation concerningunderlying and evolving pulmonaryfunction, particularly in response to therapy,is helpful in determining the need forhospital admission. Outpatient regimens mayinvolve bronchodilators, systemic corticosteroids,and antibiotics; again, a stepwiseapproach is generally recommended.^14-17Guidelines for hospital care also consideroxygen therapy and potential mechanicalventilation.² Establishing preventive measuresto decrease the likelihood of futureexacerbations is a final consideration.

Four aspects of COPD managementoffered by GOLD involve assessing andmonitoring COPD, reducing risk factors,managing stable COPD, and managing exacerbations.² The algorithm for treating acuteexacerbations of COPD in outpatient settingsappears in Figure 1; the Table outlinesthe general considerations of inpatienttreatment.

Guidelines for Asthma. GINA recommendsthat asthma management involveestablishing and maintaining control ofsymptoms, preventing exacerbations andadverse effects of medications, maintaininglung function and normal activity levels, andpreventing irreversible airflow limitationsand mortality.⁶ The restoration of lung function and the rapid improvement of both airwayobstruction and hypoxia are criticaltreatment goals for acute exacerbations.⁶Treatment approaches for these acute casesacross guidelines follow stepwise approachesthat add additional therapeutic measureswhen considering the severity of exacerbation;outpatient management emphasizesincreasing short-acting β²-agonist use andmonitoring the response to initial treatment.¹⁸ According to the NAEPP, GINA, andother experts, the primary management ofexacerbations within inpatient settingsinvolves increasing the frequency of inhaledshort-acting β₂-agonists, adding systemiccorticosteroids, and using oxygen supplementation.^4-6,19-21 In instances when exacerbationsare resistant to initial treatment orare severe in nature, hospital- or emergencydepartment—based monitoring andtreatment are recommended.⁶ NAEPPemphasizes the importance of early interventionin asthma exacerbations anddirecting special attention toward patientsat high risk for asthma-related mortality.⁴Consideration is also placed on reducingthe probability of recurrent severe exacerbationsand developing written plans toaid in guiding the early management offuture exacerbations.

Although NAEPP and GINA generally coincide,clinicians should be aware that certainnuances exist between the 2 guidelines.Recommendations for outpatient managementstipulate that the frequency of aninhaled short-acting β₂-agonist be increasedand that continued intensive treatmentshould be carried out for several days basedon severity and response.⁵ Figure 2 presentsthe most recent guidelines from GINA on thehome management of asthma exacerbations,whereas Figure 3 focuses on hospital management.More important, development of specifictreatment algorithms in acute care settingshas been shown to improve patient outcomesand decrease resource consumption.²² Acaveat of care in acute asthma involves theuse of sedatives; use of these agents is generallycontraindicated because of potentialrespiratory depression and increased mortality.^5,23,24 Clinicians treating severe casesthat require mechanical ventilation and theuse of sedatives are directed toward appropriatereferences for additional informationfor monitoring and intervention.^5,6,25

Therapeutic Considerations inManagement and Treatment

Bronchodilators. The primary therapyfor overall COPD and related exacerbationsis inhaled bronchodilator therapy.^2,14,15,26Bronchodilators recommended specificallyfor COPD exacerbations include short-actingβ₂-agonists (eg, albuterol, levalbuterol,bitolterol, pirbuterol) and anticholinergics(eg, ipratropium bromide). Outpatient managementtypically involves increasing thedose and/or frequency of agents prescribedto the patient, whereas inpatient therapyrelies on short-acting β-agonists by GOLDstandards.² A meta-analysis indicated thatno significant differences in improvedforced expiratory volume in 1 second(FEV₁) were noted in COPD exacerbationsbetween the β₂-agonists and ipratropium,although the β₂-agonists that were includedmay have worsened the arterial blood gasprofile in the hours immediately followinginitial patient presentation.²⁷ Delivery via ametered dose inhaler (MDI) and spacer hasbeen reported to produce similar effects asnebulization, although certain studies specificto asthma have noted that MDIs with aspacer may provide a more rapid onset tolessen time spent in emergency departments.^28-30 The use of long-acting β₂-agonists(eg, salmeterol, formoterol) is generallyreserved for maintenance treatment ofCOPD.^2,31,32 Taken from Bach and colleagues,³³ the following was concluded intheir review of 14 randomized trials concerningbronchodilator use in COPD:

"Short-acting β-agonist—type and anticholinergic-type inhaled bronchodilatorshave similar effects on spirometry and agreater effect than all parenterally administeredbronchodilators (ie, parenteralmethylxanthines and sympathomimetics);the toxicity profile of the methylxanthineagents makes them potentiallyharmful; and some patients may experienceadditional benefits when a secondbronchodilating agent is administered afterthe maximal dose of the initial inhaledbronchodilator is reached."³³

Tiotropium bromide, a long-acting muscarinicreceptor M₁- and M₃-selective anticholinergicagent, has demonstrated ininternational clinical trials improved efficacyrelative to ipratropium as well as salmeterolin the treatment of stable COPD.^34-37Decreases in exacerbations in COPD havebeen observed with the once-daily dosedmedication.^38,39 Given the long-acting natureof tiotropium, however, its use in the emergentcare of acute exacerbations of eitherCOPD or asthma has yet to be established.Currently, no newer short-acting anticholinergicagents are in an advanced developmentphase.⁴⁰

According to NAEPP and GINA, inpatientcare of exacerbations in asthma emphasizesthe use of inhaled short-acting β₂-agonists,whereas systemic β₂-agonists (eg, epinephrine,terbutaline) should only be considered in very severe or nonresponsivecases.^5,6,20,21 Research has found either equalor improved efficacy with aerosolized β₂-agonists versus systemic agents in acuteasthma, also noting an improved safety profileand lower potential for toxicity.⁴¹ Combinedtreatment with both intravenous andnebulized β₂-agonists is not warranted.⁴²The routine use of continuous nebulization,although commonplace, has not been empiricallyestablished as a preferred managementstrategy relative to intermittenttreatment.⁴³ The long-acting β₂-agonists (eg,salmeterol, formoterol) are generally notrecommended for emergent care of acuteasthma.^25,44

Opinion and research have indicated thatthe use of ipratropium in an adjunctive rolewith β₂-agonist regimens for acute exacerbationsin asthma may improve airflow, particularlyin more severe cases.^21,45 NAEPP andGINA consider the addition of ipratropiumto β₂-agonists for emergency departmentand hospital-based care of asthma exacerbations,and GINA guidelines state that the useof ipratropium with β₂-agonist treatmentshould be considered before methylxanthinesbecause of potentially lower hospitalizationrates and improvement in peakexpiratory flow and FEV₁.^4-6 However, uniformsupport does not yet exist concerningthe routine addition of ipratropium with β₂-agonists in acute asthma, although someexperts state that the concomitant approachmay appear to be a beneficial first-line strategyin severe adult asthma.^25,46-50 Thus, thetherapeutic placement of the agent is generallyrecommended only as an adjunctiveapproach in patients who are not responsiveto β₂-agonist therapy alone.^4,48,51,52 In children,research has noted that all individualsreceiving intensive emergency departmenttreatment did not receive benefit when ipratropiumwas added to β₂-agonist and corticosteroidtherapy; however, other literaturesuggest that ipratropium offers clinicalimprovements, particularly in more severecases.^6,21,53-57

The side-effect profile of ipratropium hasbeen purported to be milder than β-agonists,with fewer number and frequency of sideeffects being reported.^33,46,58 Within the classof short-acting β-agonists, albuterol is themost commonly used agent, and side effectsare dose-dependent.^25,44,59 Recent evidencesuggests that levalbuterol (R-albuterol) maybe associated with lower toxicity, higher efficacy,and decreased length of hospital stayswhen compared with racemic albuterol, andthe single isomer may have potential use inCOPD, asthma, and related exacerbations;its use has also been noted in children.^59-65Although evidence presented primarily frompreclinical models found that S-albuterol isassociated with pharmacologic effects andmay enhance smooth muscle contractionand airway hyperresponsiveness, clinical trialshave suggested that the S-isomer may beclinically inert.^66-68 Other clinical findingsmay be indicative of negative effects associatedwith the S-isomer; additional study iswarranted to establish more robust conclusions.^59,63,64,69 If high-dose β₂-agonist therapyis used with albuterol in acute asthma,appropriate delivery and administrationmethods should be selected to minimize sideeffects and toxicity.^22,25

The methylxanthines (eg, aminophylline,theophylline) are considered efficaciousbronchodilators, although the narrow therapeuticwindow and side-effect profile limittheir use in exacerbations of COPD andasthma.^2,4-6 Recent meta-analyses for bothCOPD and asthma exacerbations found noconsistent benefit from methylxanthines,yet an increase in adverse events wasobserved.^70,71 Of all the guidelines discussingCOPD exacerbations, only older guidelinesrecommended the use of methylxanthines inCOPD exacerbations when inhaled bronchodilatorsprovide inadequate therapy.¹⁵ Inacute asthma, GINA guidelines suggest thatthe use of these agents be considered onlyduring severe exacerbations and remain analterative therapy.^6,71 NAEPP does not recommendmethylxanthine use in emergencydepartments or hospital settings, and the useof these agents was controversial for adultswhile offering little benefit but increased riskto children.^4,5,72

Systemic Corticosteroids. Systemic corticosteroids(eg, prednisone, prednisolone,methylprednisolone) are considered effectivein both inpatient and outpatient settingsfor the treatment of COPD exacerbations byaccelerating recovery time and lung functionwhile decreasing relapse rates; meta-analyseshave found the therapies to offer short-termimprovement for exacerbations, althoughthe analyses also addressed increased risksfor adverse drug reactions associated withthe class.^73-77 GOLD suggests the addition ofsystemic corticosteroids to bronchodilatorsif moderate-to-severe COPD is present andas a general recommendation for inpatientcare.² These guidelines also state that nebulizedbudesonide may offer an alterative tooral agents in outpatient management in theabsence of respiratory acidosis.^2,78 Continuedstudy is warranted concerning the use ofcorticosteroids in outpatient venues, particularlywith optimum dosing and duration.³³For long-term treatment in COPD, a metaanalysisfound inhaled corticosteroids toslow the progression of pulmonary functiondecline dramatically, although others hadconsidered the class to offer minimal clinicalbenefit in COPD.^79,80

Although they are not recommended routinelyin acute asthma treatment, corticosteroids(eg, beclomethasone, budesonide,flunisolide, fluticasone, triamcinolone) mayeither be initiated or the frequencyincreased under certain circumstances foroutpatient management of exacerbations.⁴The GINA guidelines address the role ofinhaled corticosteroids in already-developedexacerbations, and reviews of clinical studieshave reported improved bronchodilationand decreased relapse rates with early use inmilder cases.^6,81-83 Conflicting results fromclinical trials exist concerning the use ofinhaled corticosteroids in acute asthma,however, some clinicians strongly cautionagainst routine use, particularly in children.^81,84-86 Less debatable is the use of systemicadministration of corticosteroids inmore moderate or severe exacerbationsin home management. GINA, NAEPP, andother experts place systemic corticosteroidsadministered via oral or intravenous routesas an integral component of inpatient carefor all but mild exacerbations. A metaanalysisfound the early use of systemiccorticosteroids to significantly decrease hospitaladmissions from emergency departments.^4,6,87,88 The choice of intravenousversus oral dosage forms does not appear tooffer a difference in efficacy, which is animportant consideration in their use bychildren.^89,90 Precise dosing and scheduleshave not been established, yet high dosesdo not appear to provide added clinicalbenefit.⁷⁹

Streptococcus pneumoniae, Haemophilusinfluenzae,

Moraxella catarrhalis

Antibiotics. Although approximately onethird of COPD exacerbations are either viralin nature or have no identifiable etiology,antibiotics are generally recommended ifworsening dyspnea is accompanied byincreased sputum production and/or changein sputum purulence.^91,92 Evidence has alsosuggested that more severe cases of COPDexacerbations are afforded the greatestimprovement in clinical outcomes withantibiotic therapy.⁹³ GOLD recommendsthat the spectrum of activity should echolocal patterns of sensitivity concerning and .²Concerns addressing drug resistance andrelapse rates, especially in patients withsevere COPD, have been investigated andaddressed in the literature.¹³

Mycoplasma pneumoniae

Chlamydia pneumoniae

Similar to COPD recommendations byGOLD, both NAEPP and GINA do not summarilyrecommend antibiotic use for asthmaexacerbations except in instances for whichcomorbid conditions or the presence of fever,sputum changes, or suspected pneumonia orbacterial sinusitis warrant their use.^4,6 Ameta-analysis of the role of antibiotics inacute asthma noted many challenges in interpretingresults from disparate literature andindicated that established consensus recommendationswould likely remain until morerobust empirical assessments are made.⁹⁴ Therole of bacterial infections in acute asthma isbelieved to be small, although atypical bacteriaincluding or have been found insome exacerbations.⁹⁵ Viral respiratory infections,particularly from rhinovirus, have beenreported to play a major role in precipitatingasthma exacerbations, with virus-inducedacute asthma potentially warranting specialmanagement considerations.^96-98

Oxygen. In moderate-to-severe exacerbationsof COPD, hypoxemia is considered aprimary concern in regard to morbidity.When patients present to an inpatient settingor emergency department with exacerbations,their initial therapy should be controlledoxygen as recommended by GOLD.Oximetry is helpful for determining the needand success of oxygen therapy. Oxygen therapyhas been associated with increases in survival.^2,51 Although oxygen therapy has beenfound to worsen hypercapnia and can resultin pulmonary failure, the beneficial effects ofthe therapy on respiratory and cardiovascularfunction are often considered to outweigh therisks.³³ Because of clinical concerns, however,identification of patients at highest risk forhypercapnia has been suggested.³³ In thetreatment of asthma exacerbations, especiallyin more moderate-to-severe cases, oxygentherapy is an important supportive caremeasure in emergency department or hospitalsettings and is generally recommended formost patients.^5,6,21,25

Magnesium Sulfate. Intravenous magnesiumsulfate, which relaxes smooth musclecausing bronchodilation, is consideredadjunctive therapy for acute severe asthma,with collective assessments of clinical trialsnot necessarily demonstrating a clear benefitfor routine use in emergency departmentsettings.^6,21,99,100 In certain patients withpoor response to β₂-agonists or with adultswhose FEV₁ on presentation is from 20% to30% predicted, some benefit has beendemonstrated. GINA guidelines confirm theuse of intravenous magnesium sulfate forthe hospital management of severe episodesof asthma exacerbation.^6,101

Noninvasive Positive Pressure Ventilation.Noninvasive positive pressure ventilation(NIPPV) has demonstrated efficacy inrespiratory failure among a wide range ofdiseases.¹⁰² In cases of respiratory failurerelated to COPD exacerbations, NIPPV hasbeen found to shorten hospital stays andimprove survival rates and offers an importantalternative to intubation or mechanicalventilation.¹⁰³ Overall, the treatment may beused in intensive care or hospital settingswith appropriate training of personnel.¹⁰⁴The use of NIPPV in acute exacerbations ofasthma is less clear than in COPD, althoughsome research indicates decreased hospitalizationrates and improved pulmonary function.^105,106 Expert panels have recommendedthat a more comprehensive evaluation ofNIPPV is needed from clinical trials.¹⁰⁷ It hasbeen suggested that NIPPV use be limited tocases of impending respiratory failure or asan alternative to intubating patients withacute asthma.²⁵

Mucolytics and Expectorants. The useof mucolytic agents in COPD exacerbationsis an area warranting additional research byGOLD.² Although a meta-analysis has indicatedpotential benefits based on reductionin exacerbations and in disability days instable COPD, the agents are generally notconsidered in the routine management ofacute exacerbations.¹⁰⁸ NAEPP and GINAguidelines coincide with older recommendationson the use of inhaled mucolytic agentsfor asthma exacerbations. Furthermore,they do not recommend the regimensbecause of a lack of consistently demonstratedbenefit and concerns of the risk associatedwith worsened airway obstructionand cough, particularly in more severecases.^4,6,21

Heliox. Small trials of combined heliumand oxygen (heliox) in COPD exacerbationshave shown some improvement in respiratoryfunction in inpatient settings.¹⁰⁹ Helioxis not addressed in the GOLD guidelines forCOPD exacerbations.² For asthma, clinicalstudies have generally indicated that thecombination does not necessarily improvelung function in mild or moderate asthmaexacerbations relative to standard therapy,a finding that was also offered frombroad meta-analyses concerning the therapy.^110,111 GINA guidelines for asthma statethat the mixture may be best reserved forpatients presenting with more severe disease,and that routine use in other cases isunwarranted.⁶

Leukotriene Antagonists. Leukotrieneantagonists (eg, montelukast, zafirlukast,zileuton) are used primarily for the longtermmanagement of asthma.¹¹² Initial findingsand opinions from clinical trials inacute asthma, however, may provide evidencefor a potential role in their use basedon improvements in symptoms and pulmonaryfunction; the overall cost effectivenessin acute asthma, however, has beenquestioned.^113-115 No consensus currentlyexists concerning the use of these agents inacute asthma, and additional investigation iswarranted concerning their role in the treatmentof exacerbations.¹¹⁶

Prevention

A strategy encompassing continuous,long-term, comprehensive care with appropriateclinician follow-up should be soughtto prevent or reduce future exacerbations inboth COPD and asthma. No therapy existsthat substantially modifies the long-termprogression of COPD.² As such, risk-factormodification, particularly smoking cessation,is pertinent to ease the progression ofthe disease, although patient education,influenza vaccination, and potential pulmonaryrehabilitation are also important.^2,117,118 GOLD generally recommendsthat the treatment of stable COPD follows astepwise approach based on severity andoften involves bronchodilators, exercise,and, occasionally, corticosteroids.² Methodsto both increase patient adherence to thecomplex therapies in COPD and selectingappropriate interventions have also beenemphasized.¹¹⁹ Hospital discharge recommendationsoften involve monitoring oftherapeutic interventions and lung function,increased patient education, risk modification,discussion of barriers to care or disabilities,and follow-up care.²

Overall recommendations concerning theprevention of future exacerbations in asthmainclude developing management partnershipsbetween clinicians and patients,education, appropriate assessment andmonitoring, establishing plans for medicationuse and for treating exacerbations, minimizingrisk factors, and routine follow-upcare.^5,6

Discharge from emergency department orhospital settings should involve detailedinformation concerning appropriate medicationuse, management, monitoring, and follow-up care.⁶ Discharge use of oralcorticosteroids has been shown to reducethe frequency of relapses (NAEPP). Inhaledsteroids have been specifically shown toreduce subsequent exacerbations after anacute asthmatic episode.^120-122 Long-termcontrol of asthma may also include agentssuch as long-acting inhaled β₂-agonists (eg,salmeterol, fomoterol), leukotriene receptorantagonists, cromolyn, nedocromil, or combinationproducts (eg, fluticasone/salmeterol).⁵ Management by allergy specialistshas also been shown to reduce the likelihoodof asthma exacerbations.^123-129

Future Treatment Options

Statements of future areas of research inCOPD have addressed the need for a moredetailed understanding of the specific surrogatemarkers and mechanisms involved inthe inflammatory component of the diseaseto aid in the identification of at-risk patientsand in the development of new treatments.²Ultimately, methods to potentially reverseCOPD and promote alveolar regrowthrequire advances in numerous areas. Therole of inflammatory processes in both theprevention and treatment of exacerbationsin COPD has been discussed elsewhere.^130-133Based on recent advances in the understandingof the pathogenesis of inflammationin COPD, numerous agents that may beused to treat COPD are being studied,including those that may offer disease-modifyingproperties. Specifically related toresearch with new agents for COPD, mixedfindings have been observed involvingleukotriene inhibitors, protease inhibitors(ie, α₁-antitrypsin, neutrophil elastase), andmatrix metalloproteinase inhibitors.^130-133Although cytokine inhibitors targeting mediatorsof inflammation (eg, interleukin [IL]-8,IL-10, tumor necrosis factor [TNF]-α) havegenerated considerable interest with applicationto COPD, concerns of cost and safetyhave also accompanied the agents.^130-133Additional study is warranted concerningphosphodiesterase-4 inhibitors (eg, cilomilast),retinoids, antioxidants, and mucousregulators (ie, P2Y₂ purinergic-receptor agonists,tachykinin antagonists).^131-133

In asthma, research has also been directedtoward identifying at-risk patients, inunderstanding inflammatory mechanismsof the disease, and in developing new treatmentoptions.^6,134,135 Cytokine and chemokineinhibition or modulation has beeninvestigated to target interleukins (eg, IL-4,IL-5, IL-13), TNF-α, interferons (eg, interferon[INF]-γ, INF-α), and eosinophils.^134-137Mediator antagonists (eg, mast cell tryptase,platelet activating factor, tachykinins,thromboxane) may offer treatment options,although limited potential has beenobserved in asthma for some of theagents.^6,134,138 Phosphodiesterase-4 inhibitors(eg, cilomilast, roflumilast) and α₄ integrinantagonists are also potential targets fortherapy.^{134,135,139,140} Studies with ozalizumab,an immunoglobulin E—specific monoclonalantibody for use in moderate-to-severe persistentasthma, have indicated thatdecreased asthma exacerbations and reductionsin corticosteroids accompanied thetreatment.¹⁴¹

Conclusion

Acute exacerbations in COPD and asthmarepresent potentially life-threatening clinicalevents that require appropriate diagnosis,treatment, and monitoring in bothinpatient and outpatient settings. Guidelinesfor the management of exacerbations inCOPD and asthma are built on consensusand consider therapies as a function of theresponse to initial treatment, exacerbationseverity, treatment setting, and underlyingpatient characteristics and risk factors.Although standard agents used in exacerbationsof both conditions involve bronchodilators,systemic corticosteroids, andoxygen, there are several novel agentsbeing investigated that address the inflammatorymechanisms of the conditions.Future research is required in several areasto offer improved patient care and to minimizeassociated morbidity and mortality.However, more consistent use of currentlyavailable modalities for persistent asthma,such as inhaled corticosteroids, should beconsidered.^{120-122,129,142-148}

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