Asthma-Here Today, Gone Tomorrow?


Childhood asthma is a chronic health condition that often improves or resolves during adolescence or adulthood. Prospectivecohortstudieshave indicatedthatasmanyas75%ofschoolaged children with asthma “outgrow” this condition by some point in adulthood, although children with more severe symptoms, more impaired pulmonary function, and a higher degree of allergic sensitization tocommonaeroallergensare less likely toexperience resolution of asthma.1 There is less evidence, however, about the rateof remissionofasthmaamongadults,andtheavailabledata suggest a lower remission rate than among children.2 In a longitudinal cohort study of 250 Swedish adultswith recent-onset asthma, documented by both symptoms and physiological testing, remission of asthma after a follow-up interval of 4 to 8 years was observed in only 3.0% to 4.8% of participants, dependingonwhether remissionwasdefinedby the absence of symptoms alone or by the combination of absence of symptoms, normal spirometry results, and the absence of airway hyperresponsiveness.3 Among 203 Finnish patients with adult-onset asthma, documented by symptoms and reversible airflow limitation on spirometry, only 3% appeared in remission, defined as the absence of any symptoms or asthmamedication use, after amean follow-up interval of 12 years.4 Aprospective cohort studyof adults in northern Europe that defined asthma on the basis of questionnaire responses alone indicated that the asthma remission ratewas approximately 20% over 10 years of follow-up, for participants with asthma onset before or after 20 years of age.5 The lower remission rates in the studies that required confirmation of asthma by physiological testing suggest the importance of such measurements in the diagnosis of asthma. According to current guidelines, the definition of asthma isbasedonthedemonstrationofreversibleairflowlimitation.6,7 For most adult patients, this is most efficiently accomplished by spirometry before and after inhaled bronchodilator showing an increase in the forced expiratory volume in the first second of expiration (FEV1) of at least 12% and 200 mL.8 In patientswithnormalspirometryresults,abronchialchallengetest such as methacholine inhalation challenge (MIC) can be used toidentifyairwayhyperresponsiveness,whichisadefiningcharacteristicofasthma.9TheMICtest isperformedbyhavingapatient inhale increasingconcentrationsofmethacholineuntil the FEV1 decreases by at least 20%or until the final concentration oftheprotocolisreached.Aprovocativeconcentrationofmethacholine causing a 20% decline in FEV1 (PC20) greater than 8mg/mL generally excludes asthma, although approximately 3% of patients with asthma diagnosed by other means have a negativeMICresult.9,10Conversely, aPC20of8mg/mLor less is a“positive”test result, indicativeofbutnotspecific forasthma, asmethacholinehyperresponsivenesshasbeenobservedinpatientswith rhinitis, cystic fibrosis, and chronic bronchitis who do not have other features of asthma.7 Thus, the Global Initiative for Asthma guidelines suggest that a negative MIC result canhelpexcludeasthmabutapositive test result shouldbeaccompanied by symptoms andother clinical features to be considered diagnostic of asthma.7 The PC20 of an individual patient can vary over time, as airway responsiveness can change in response to viral infection, asthma medication, and avoidance of exposure to allergens and chemical sensitizers. In this issueof JAMA, Aaronandcolleagues11 used random telephonedialingto16931adults inthe10largestcities inCanada to identify individualswhowere at least 18 years old, hadbeen given a diagnosis of asthma in the previous 5 years, had not smokedcigarettes forat least 10years,werenotusing long-term prednisone,werenotpregnantorbreastfeeding,andhadnothad a recentmyocardial infarction, stroke, or eye surgery.Basedon telephoneresponses,701potentialstudyparticipantswereidentified.Of these,64withdrewearlyand24wereexcludedowing to inability to undergoMIC, leaving 613 participantswho completedaprotocoldesignedtoestablishwhetherasthmawascurrently present according to objective criteria. Participantswith reversibleairflowlimitationbasedonspirometry, asdefinedearlier,werediagnosedwithasthma; those without reversibilityunderwentMIC.ApositiveMICresultwas considered to confirm asthma,whereas a negativeMIC result was followed by a 50% reduction of asthma controller medications (inhaled glucocorticoids and long-acting bronchodilators). After 3 weeks, if no symptoms of asthma had occurred,MICwas repeated,withapositive test result confirming asthma and a negative test result leading to discontinuation of asthma controller medications. After another 3 weeks, if asthma symptomswere still absent, MICwas again repeated, with a positive test result confirming asthma and a negative test result considered to exclude asthma. Basedonthisprotocol,410patients (67%)weredetermined tohave current asthma, and203 (33%)weredeterminednot to have asthma. In this latter group, 181 patients remained free of asthmasymptomsandhadanegativeMICresultafter12months. Amongthose inwhomcurrentasthmawasexcluded,43.8%had not had prior confirmation of reversible airflow limitation by spirometry,bronchialchallengetest,orserialpeakflowmeasurements, so it is not knownwhether the initial clinical diagnosis of asthmawascorrect.Nonetheless, the results suggest thatup toone-thirdofpatientswithadult-onsetasthmamayexperience remission. An additional finding was that 12 participants (2%) withoutasthmawerediagnosedwithotherseriouscardiorespiratory problems that had not previously been recognized. Related article page 269 Opinion

DOI: 10.1001/jama.2016.19676

Cite this paper

@article{Hollingsworth2017AsthmaHereTG, title={Asthma-Here Today, Gone Tomorrow?}, author={Helen M Hollingsworth and George T. O'Connor}, journal={JAMA}, year={2017}, volume={317 3}, pages={262-263} }