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34. Kemenp DM, Harries MG. Youlten LJF. Antibodies to puritied

bee venom proteins and peptides. 1. ilewiopmi:nr of hrghl> specitic RAST for bee venom antigen> and :t< .&ication f~, bee sting allergy. J AI.I.ERC;Y CI.IN 1nch1t.w~ iW!:71:‘;(!5

35. Jefferis R! Reimer CB. Skvaril F, de Lang,: #Y, Ling ?4R,

et al. Evaluation o! monoc ona ant1 o( ie\ a\iiip swecifrc& 1 I ‘h 1’ h ‘I for human IgG subclasses: results of all II:IS ‘.I HO coil&o- rativc study. Immunol Let1 1985:10:2? i

36. Clark BR. Engvall E. Enryme-linked inununo~urbc”n: asay (ELISA): theoretical and practical aspects In: .M:.igg~~ ET. cd. Enzyme immunoassay. Boca Raton. 1 la <.‘K<’ Prrr.5. i%O. 167-80.

Persisting airway obstruction in asymptomatic children with asthma with normal peak expiratory flow rates

Alexander C. Ferguson, MB, ChB, FRCPC Vancouver, British Columbia, Canada

Twice-daily symptom scores and peak expiratory jaw readings were compared with spirometric values (FEV, and forced expiratoly jow rate between 25% and 75% of FVC [FEF,, ,J) measured at 2-week intervuls in assessing airway obstruction in 20 children with asthmu studied during 16 weeks. Of 56 2-week periods during which symptoms were absent, peuk Jlaw MWS decreased in 30 (54%), FEV, in 20 (36%). and FEF,, ,? in 37 periods (66%). Peakjow readings were normal in 13 of 70 periods (16%) in which FEV, was decreased, and in 33 of I I.+ periods (29%), in which FEFJ,.,5 was decreased. Of2S periods in which nmptoms were absent and peak flow was normal, 19 (76%) were associated with decreased FEFz,.,.Y. The results conjirm previous studies that indicate peak flow readings are a useful addition to symptctm diuries. More importantly, they demonstrate that airway obstruction may be present in a lurge proportion of asymptomatic children with asthma who have normal peak.jow rates and sugge.xt that frequent assessment of FEF. ,Y ,( is required, as well as daily monitoring of symptoms and peak$ow both in trials of drug therapy and for more optimal assessment of the effectiveness 0J therapy in clinical practice. (J ALLERGY CMV IMMLWOL. I988;82 tl9-22. )

Asthma is the most common chronic disorder of childhood, affecting 7% of children in North America, and its prevalence is increasing.’ It is a disease char- acterized by wide variations over short periods of time in resistance to flow in intrapulmonary airways with a spectrum of symptoms ranging from chronic dry

From the Department of Paediatrics, University of British Colum- bia, Vancouver, Canada.

Supported by a grant from Sandoz (Canada) Inc. Received for publication July 6, 1987. Accepted for publication Dec. 26, 1987. Reprint requests: A. C. Ferguson, MB, B. C. Children’s Hospital.

4480 Oak St., Vancouver, British Columbia, Canada VhH 3V4.

Forced expiratory flow between 25% and

Peak expiratary flow rate

coughing to life-threatening respiratory failure. Be- cause symptoms are, by nature, subjective, it is often difficult to relate them to a given degree of airway obstruction, and after an episode of severe acute asthma, airway obstruction may persist for several

19

20 Ferguson

TABLE I. Twice daily asthma symptom score

Score

Severity (day/night) No asthma/not wakened by asthma 0 Slight effect on normal activity/wak- 1

ened once by asthma Interfered with normal activity/wakened 2

2 to 3 times by asthma Home, severely limited activity/awake 3

most of the night Hospital admission/hospital admission 4

No. of attacks O-n Duration

None 0 <30 min 1 30 min-2 hr 2 2 hr-6 hr 4 6 hr-12 hr 8

The score for each period was the total of the score for severity, plus duration, plus the number of separate attacks. No symp- toms = 0. Maximum score = two attacks each lasting 2 to 6 hours ending in hospital admission (2 + 8 + 4 = 14).

weeks in apparently asymptomatic patients. 2, 3 These observations have led to concerns that airway obstruc- tion might frequently go undetected in apparently healthy children who have a history of chronic asthma and have prompted the use of home monitoring of PEFRs as an important way of documenting the diur- nal changes in airflow associated with asthma4s5 and of assessing response to therapy.6-‘2 Measurements of peak expiratory flow are a less sensitive indicator of airway obstruction than measurements of the FJW, and the FEF,,.,, .2, I33 I4 Normal PEFR readings could therefore result in the false impression that airway obstruction was absent. To clarify whether or not symptom records and PEFR monitoring are effective in indicating airway obstruction in chronic asthma, we studied a group of children with asthma to compare daily symptom scores recorded by parents, daily PEF readings recorded at home, and biweekly spirometry recorded in our clinic during a 4-month period.

METHODS

Twenty children, aged 6 to 14 years (mean, 8.8 years), were studied. All had a history dating from infancy of re- curring wheeze, cough, and shortness of breath with inter- mittent acute episodes several times per year, as well as periods lasting for days to weeks when they appeared to be symptom free. All had positive skin prick tests (mean di- ameter of induration >2 mm of the negative control)15 or RASTs (binding greater than mean plus 2 SD of background binding)16 to two or more inhalant allergens. Symptoms were assessed and recorded twice daily by parents on morning

J. ALLERGY CUN. IMMUNOL JULY 1988

rising and at bed time as to severity, frequency, and duration. Diaries were collected every 2 weeks, the importance of accurate recording was reemphasized, and symptom scores were computed. Severity was scored from 0 (no symptoms) to 4 (cough, wheeze, and dyspnea requiring hospitalization). Frequency was recorded as the number of separate episodes of symptoms, and duration was scored from 0 (no attacks) to 8 (episodes lasting for longer than 6 hours) (Table I). The total symptom score was added for each 24-hour period.

PEF readings were recorded twice daily by parents with mini-Wright peak flow meters (Armstrong Medical Indus- tries of Canada, Inc., Scarborough, Ontario) before medi- cations were administered. The best result of at least three blows was noted by the parent each time. The child and parents were carefully instructed in the correct technique, and this was reinforced at subsequent visits. Each child was provided with a new meter standardized by the manufac- turer, and results were expressed as percent of predicted value or percent of highest value obtained during the study period, whichever was greater. The children were reviewed in the clinic every 14 days and provided with new diaries. Spirometry was performed with a Jones waterless spirometer (Jones Medical Instrument Co., Oak Brook, Ill.) attached to a Datamatic printer (Jones Medical Instrument Co.). This provided a timed expiratory volume curve and immediate results of FVC, FEV,, and FEF,,~,, corrected for body temperature saturation. The values from the best of three to four forced expirations were recorded as percent of predicted values with the standards of Polgar and Promadhat . ”

Regular medications were continued throughout the study period, and all children initially were receiving twice daily, sustained-action oral theophylline with peak serum theoph- ylline levels within the range of IO to 20 pg/ml, measured at the first study visit. Inhaled P-adrenergic medications were used in addition, as required. None received sodium cromoglycate or steroid therapy. At the end of each 2-week period, the mean 24-hour symptom scores, mean 24-hour PEFR readings, the number of days per period on which the morning or evening PEFR was <75% of predicted value (low peak flow days), and the best attainable FEV, and FEF,,,, were recorded for analysis. From the coefficients of variation in healthy children,” PEFR was taken as de- creased if it was <75% of the predicted value for height and gender, FEV,, if it was <80%, and the FEF,,,,, if it was <70%. The study continued for a period of 16 weeks for a total of eight 2-week study periods per child, and an overall total of 159 study periods, since one child required in-hospital treatment because of severe acute asthma. Data were analyzed with chi-square analysis (2 x 2 tables) to compare the proportion of periods in which symptoms were present with the proportion in which there were decreased PEFR readings, decreased FEV,, and decreased FEF,,.,,. The relationships of symptom score to decrease in PEFR, FEV,, and FEF,,,, were assessed by computation of coef- ficients of correlation.

RESULTS

There were 103 periods in which symptoms were present and 56 in which symptoms were absent.

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Persisting airway obstruction 21

TABLE II. Comparison of the number of symptomatic and asymptomatic periods

Periods

Symptoms (103) No symptoms (56) % % X2 P

Mean PEFR decreased 31 (30) 4 (7) 9.83 0.005 Low peak flow days 83 (80) 30 (54) 11.59 L 0.005 FEV , decreased 50 (49) 20 (36) 1.93 ns FEF., .< decreased 76 (74) 37 (66) 0.72 KS

--- ---- NS = not significant. Comparison of the number (and percentage) of symptomatic (103) and asymptomatic (56) periods during which airway obstruction was

present as assessed by PEFR readings and spirornetry demonstrating the chi-square values (X’) and level of significance.

Symptomatic periods were closely associated with low peak flow days and decreased FEF,,.,, and, to a lesser extent, with FEV, and mean PEFR (Table II). Most periods in which there were no symptoms were also associated with decreased FEF,,.,, and low peak flow days and, to a lesser extent, with FEV, but not with mean PEFR. The presence of symptoms was signif- icantly associated with decreased mean PEFR and low peak flow days but not with decreased FEV, or FEhs.,, .

There was a significant correlation of mean symp- tom score per period with mean PEFR (r = 0.39; p < O.OOOS), low peak flow days (r = 0.41; p < O.OOOS), and FEV, (r = 0.16; p < 0.05), but not with FEF25-75 (r = 0.12).

Of 35 periods in which the mean PEFR was de- creased, four periods (11%) were without symptoms, the IZF,,.,, was normal in six periods (17%), and the FEV, was normal in 12 periods (34%). In contrast, there were 113 periods in which low peak flow days were present. Of these days, 30 (27%) were associated with no symptoms, 33 (29%) with normal FEF25-75, and 54 days (48%) with normal FEV,. In 70 periods, FEV, was decreased, and FEF,,.,, was decreased in 113. A substantial number of these periods was as- sociated with no symptoms and with normal PEFR readings (Table III). To assess the number of periods in which airway obstruction would have been missed if spirometry had not been done, periods in which there were no symptoms and no low peak flow days were analyzed. Of 24 such periods, 19 (76%) were associated with decreased FEF,,.,,.

DISCUSSION

These results confirm that no single test is by itself completely adequate for assessing the variable airway obstruction associated with chronic asthma. Symp- toms, even if they are objectively quantitated, are clearly unreliable. PEFR readings may provide useful information if they are recorded twice daily to confirm

TABLE III. Comparison of the number (and percentage) of periods in which decreased FEV, (70) and decreased FEF,,.,, (113) were associated with absent symptoms and normal peak flow readings

..-_ ______ Periods

FEV, decreased FEF,% deweasad (70) (%I (113) (9/c)

No symptoms 21 (28) 35 (33) Normal peak flow 13 (16) x-4 (29)

days Normal mean 47 (67) 84 174)

PEFR --.-.- -._.---

airway obstruction associated with symptoms or if symptoms are absent, but reliable results depend on excellent cooperation from the child, which is not always possible at home. Because symptoms and PEFR readings are recorded daily, they would be ex- pected to provide a more accurate record of airway obstruction than periodic spirometry. The FEF2s.7s was nevertheless decreased in a large proportion (75%) of the periods during which symptoms were absent and daily peak flow rates were normal. This is consistent with the view that FEFZS-75 is a more sensitive indica- tor of airflow obstruction than PEFR or FEV, .3. ” ” FEF,,.,, is effort independent and measures flow pre- dominantly in the peripheral airways,“. ” whereas both the FEV, and PEFR measure airflow predomi- nantly in the central airway,“, *O consistent with rhe demonstrated correlation with symptom scores.

The long-term effect of chronic airway obstruction in children is incompletely understood but may be associated with irreversible changes in the growing lung. In a study of 208 children with chronic asthma, prolonged airway obstruction was associated with loss of elastic recoil in more than two thirds. resulting in

22 Ferguson J. ALLERGY CLIN. IMMUNOL.

JULY 1988

chronic hyperinflation.” Chronic airway obstruction is also known to result in increased total lung capacity and increased lung distensibility in adults who have suffered asthma from childhood (onset before 8 years of age) in contrast to those who developed asthma after the age of 18 years.” Since the essence of pe- diatric medicine is prevention, a rational approach to treating asthma in children requires that airway ob- struction be identified with a high index of suspicion, followed by effective therapeutic intervention.

In assessing chronic asthma, our findings confirm that the absence of symptoms is an unreliable indicator of normal airway function and that twice daily PEFR readings are a useful adjunct in detecting airway ob- struction, consistent with the experience of other in- vestigators . 23, 24 They must, however, be used to in- dicate the number of days on which peak flow rates are decreased, rather than the mean peak flow rate during a length of time. FEF,,,, recorded at two weekly intervals is a much more reliable indicator of persisting airway obstruction than symptom scores, peak flow rates, or FEV,, and since there is a high probability of persisting airway obstruction in child- ren with asthma despite the absence of symptoms and normal peak flow rates, serial measurements of FEF25.,5 are required for accurate results in clinial trials of drugs used in relieving airway obstruction and for more accurate assessment of the response to therapy of children with asthma in clinical practice.

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