section ii asthma and pulmonary disorders and related medications

Section IIAsthma and Pulmonary Disorders

and Related Medications

Titie:

Authors:

Journal:

Purpose of the Study:Study Population:

Methods:

Statistically SignificantFindings:

Hypoxaemia in wheezy infants after bronchodilator treatment

A. Prendiville, A. Rose, D.L. Maxwell, and M. Silverman

Archives of Disease in Childhood, 62:997.

To evaluate the effect of nebulized salbutamol on wheezing infants.

Five infants, average age 10.4 months with a range of 5 to 16months were studied. All infants had a history of recurrent epi¬sodes of wheezing and all infants were wheezing at the time oftesting.Transcutaneous monitoring of P02, PC02, and oxygen saturationas well as heart rate were recorded five minutes before saline andsalbutamol challenges and every five minutes up to twenty min¬utes after each challenge.Measurements of maximum flow at functional residual capacitywere obtained by suddenly inflating a thoracoabdominal jacket atthe end of a tidal inspiration. This maneuver was performed as abaseline and then five minutes following nebulized saline. Twentyminutes after the nebulized saline, 2.5 mg. of nebulized sal¬butamol was administered and repeat flows were obtained twentyminutes after the nebulized salbutamol.All infants were sedated with chloral hydrate 100 mg/kg thirty min¬utes prior to each test. Bronchodilators were withheld during thetwenty-four hours preceeding the test.

Studies were repeated after two weeks in four infants.

None of the measured parameters were significantly altered beforeor after the administration of nebulized saline. However, after sal¬butamol was administered there was a significant increase inheart rate (p < .01), a significant decrease in oxygen saturation (p< .01), and a significant drop in P02 (p < .001).

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Other InterestingFindings:

Reviewer's Comments:

It is of interest that although there was a stastically significantdrop in P02 and oxygen saturation following the administration ofsalbutamol, there was no significant change in the maximum flowmeasured at functional residual capacity.This study focuses on the important issue of how selective beta2agonists may affect the course of the wheezing infant. The currentstudy puts into question the accepted practice of using inhaledbeta2 adrenergic agonists to treat wheezing in the infant popula¬tion. The results of this study suggest that nebulized salbutamolmay cause significant hypoxaemia in wheezing infants probablyinduced by an alteration in the ventilation/perfusion ratio. Thestudy, however, has important limitations. Most importantly, onlyfive infants were enrolled in the study and only four infants com¬

pleted both study phases. In addition all children were premedi-cated with chloral hydrate which could have affected the testresults.

Because of the critical nature of the issue being studied, it is imper¬ative that additional studies be pursued to evaluate the issue thathas been addressed in this paper.

John A. Zora, M.D.Atlanta, Georgia

Title:

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Methods:

Release of leukotriene C4 in respiratory tract during acute viralinfection

Volovitz B, Faden H, Ogra PL

J. Pediatrics 112:218-22, 1988.

To establish the role of pharmacologically active mediator LTC4 invirus induced airway bronchospasm.Groups of children, including 38 boys and 26 girls ranging in agefrom 1 month to 4 years (mean age 18 months), 33 with wheezing,19 with mild upper respiratory tract infections and 12 childrennormal follow-up to outpatient department for complaints of otherthan respiratory.

Fifty-two of children from the emergency room and 12 from theoutpatient department from the Children's hospital were examinedand two samples of nasopharyngeal secreations collected by Delitrap one for virus isolation or HEP-2, Hela and primary monkeykidney monolayers and one for measurement of LTC4 by HPLC(high pressure liquid chromatography) verified by RIA (radioim-munoassay). Statistical analysis was by Fisher exact test, unim¬paired student test and linear regression for correlation of LTC4level with age of children.



Viruses were isolated from 21 (40%) of 52 children including para-influenza type 3 from nine. RSV eight and influenza virus type Afrom four.LTC4 was detected in 28 or 54% of 52 ill children and two ( 17%) of12 control patients (P < 0.05). LTC4 was found in 15 (71%) of 21sick children with and 13 (42%) of 31 without virus (P = 0.06).The mean concentration of LTC4 was significantly higher in sickchildren than healthy children (P < 0.025) and in those with virusit was almost double those without virus (P < 0.05). Mean level ofLTC4 was not significantly different between children withoutvirus and control. LTC4 was detected in 22 (67%) of 33 patientswith wheezing, but in only five (16%) of 31 without wheezingwhereas all virus positive wheezers had detectable LTC4, but onlyhalf of virus negative wheezers had measureable levels of LTC4.Virus positive wheezers had significantly higher concentrations ofLTC4 (mean 1520 ± 228 pg/0.1 mL) than the virus negativewheezers (mean 709 ± 147 pg/0. lmL, P<0.05). As the age reversed,so did the amount of LTC4 in nasopharyngeal reactions (r = 0.47,P<0.01).

The investigators demonstrate a significant association betweenthe presence and concentration of LTC4 in nasopharyngeal secre¬tions and viral induced wheezing. Previously, other investigationshave demonstrated that viral specific IgE induced by RSV and para-influenza was associated with wheezing illness. Since leukotrienesare known bronchoconstrictor mediators released from airwaymast cells it is possible that various viruses such as parainf luenza,influenza and RSV may have direct effect on release of mediatorsfrom airway mast cell or other inflammatory cells or via inductionof IgE or by viral antibody immune complexes thus giving rise tothe coughing, mucous production and wheezing.

Christopher RandolphDanbury, Connecticut

TiÜe: Improvement in clinical asthma score and PaC02 in childrenwith severe asthma treated with continuously nebulizedterbutaline.

Authors: FW. Moler, M.D., M.E. Hurwitz, M.D., and J.R. Custer, M.D.Arbor, MI.

Ann

Journal:


Journal of Allergy and Clinical Immunology, 81:1101-1109, 1988.

To study the efficacy and safety of continuous nebulized terbuta¬line (CNT) therapy for severe asthma and impending respiratoryfailure in patients who fail to respond to a standard asthma treat¬ment protocol of methylprednisolone, aminophylline, and intermit¬tently nebulized terbutaline.

63

Study Population:

Methods:

Results:

Nineteen patients with 27 admissions for severe asthma (admittedto the pediatrie ICU of OS. Mott Children's Hospital, University ofMichigan), were given continuous face-mask nebulization of terbu¬taline at a dose equaling the most frequent previous intermittentdose per hour (4 mg/hour). In this study, no patient with frankrespiratory failure (i.e., PaCO3>60 torr, exhaustion, or coma) wasstudied. These patients ranged in age from 1 to 14 years (mean 7.5years). There were 16 males and 11 female patients. A nurse, respi¬ratory therapist, and physician were present at all times.

The study protocol was approved by the Human Use Committee ofthe University of Michigan Medical Center. Steroids andaminophylline were continued at the previous dosages. Theasthma score of Wood et al was used to follow the clinical responsesto CNT. The following parameters were assessed: oxygénation,inspiratory breath sounds, accessory muscle use, expiratorywheezing, and cerebral function. A clinical asthma score was

assigned, based on staff observation and arterial blood gases. Theterbutaline solution was administered by an intravenous pumpconnected to a nebulizer driven by 6 L/min of oxygen flow from one

flowmeter through standard 02 tubing and combined with otherequipment (described in article) to insure proper dosage, humidi¬fication, warming, and oxygénation.All 19 patients with 27 episodes of severe asthma treated with CNTresponded favorably. No patient required mechanical ventilation or

intravenous isoproterenol. At all successive times the mean clinicalasthma score improved during the first 8 hours of CNT. There wasno increase in mean heart rate observed during CNT therapy com¬

pared to baseline measurements through 24 hours. In 14 patientswhose PaC02 was greater than or equal to 39 torr (range 39-59 torr)and clinical asthma score of 6 or greater, PaC02 decreased a meanof 11.7 torr during a mean of 8.1 hours. In six patients whosePaC02 was 45 torr or greater at the start of CNT (mean 49, range45-58 torr), PaC02 decreased a mean of 15 torr in an average of 8.7hours. No adverse effects were observed in the treatment group(i.e., arrhythmias, seizures, pulmonary edema, etc.). The authorsconcluded that the results from this preliminary study suggeststhat CNT is an effective therapy for severe asthma in children.

Reviewer's Comments: With the serious problems associated with mechanical ventilationor intravenous isoproterenol, novel approaches to treatment ofsevere asthma are welcomed. This study represents an importantfirst step in describing a new treatment approach. Further studiesare required to investigate other selective beta adrenergic agents,apparatus for delivery, and careful assessment of short and long-term safety.

Thomas J. Fischer, M.D.Cincinnati, Ohio

64

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Extrapulmonary effects of maintenance corticosteroid therapywith alternate-day prednisone and inhaled beclomethasone inchildren with chronic asthma.

Nassif E., Weinberger M., Sherman B., Brown K.

J. Allergy Clin. Immunol. 80:518-29, 1987.

To study the long term extrapulmonary effects ofalternate-day pred¬nisone vs. daily beclomethasone in children.

20 patients on alternate-day prednisone (P), mean age 10 years; 31patients on inhaled beclomethasone (B), mean age 13 years; 20patients with asthma not on steroids (C), mean age 13 years; 21patients normal controls—no asthma (NC), mean age 12 years.Patients were chosen by random sampling of charts.

Follow-up periods of & were 2.3 and 2.1 years respectively.Early morning cortisol levels were measured (at 24 and 48 hoursfor group P) in and groups. Heights and weights were obtainedfrom patient charts. Slit-lamp exams were performed. Hgb, Hct andIgA were measured. Monilia cultures and antibody titers were done.

A.M. cortisol levels were significantly reduced in at 24 but not 48hours when compared to B. Increase in height percentile was sig¬nificantly greater in asthmatics who didn't take steroids as com¬

pared to those who did. Increase in height was not significantlydifferent between groups and P. and demonstrated signifi¬cantly greater weights with reference to heights. One patient in and 1 patient in had clinically insignificant subcapsular cata¬racts. Antibody titers to monilia did not differ among the groups.Nine of 20 and 3 of 18 had positive monilia cultures withnegative physical findings. Asthma group had significantly highHbg and Hct. IgG was lower in asthma groups than normal con¬trols. Group IgG was significantly lower than groups or C.

The differences in growth were felt to be a consequence of the dis¬ease and not the oral or inhaled steroid usage. Patients in , andC groups required occasional prednisone boosts of 1-2 days in theprevious 4 months, but not in the previous month. This will affectthe axis and possibly skew the results of the a.m. cortisolresults.

Robert W. Ziering, M.D., F.A.A.A.Vista, California

Title:

Authors:

Wheezing in Infants: The Response to EpinephrineLowell D.I., Lister G., Von Koss H., McCarthy P.

65

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Study Population:

Study Design:



Pediatrics #29: 939-945, 1987.

A double blind randomized study with placebo was designed toexamine the hypothesis that epinephrine can lead to objectiveclinical improvement in respiratory distress in children less thantwo years of age with acute episodes of wheezing.Patients less than two years of age were eligible if they had wheez¬ing on physical exam with no prior history of bronchodilatortherapy. Wheezing had to be heard on at least two exams five min¬utes apart. The study was conducted in emergency room and pri¬mary care centers of Yale-New Haven Hospital. Children withchronic cardiorespiratory problems or those with signs of respira¬tory failure (HR>200 or RR> 100) or lethargy were excluded.

Patients were stratified by age <12 months and 12 to 24 monthsand then randomized to receive epinephrine or placebo.Each patient had a respiratory assessment including 8-point scalefor wheezing and 9-point for retractions as well as respiratory ratewith proven interobserver agreement and were widely used by clini¬cians as representative of pathophysiology of wheezing. An overallrespiratory assessment change score was calculated as sum ofchange scores of each variable with improvement defined by > 4positive units. Two blinded assessments were done 15 minutesafter consecutive shots of epinephrine or placebo. The study codewas broken then and placebo groups could receive one or two injec¬tions of epinephrine and the treated group one additional epi¬nephrine at the discretion of the investigator.56% of patients improved with epinephrine versus 7% withplacebo. 70% of wheezing of children in the ambulatory setting hadstatistically significant improvement in clinical score. 63% of chil¬dren < 12 months and 92% of those between 12-24 monthsimproved. The difference in response rate was not due to arbitraryscoring system, since improvement was seen in raw score as well as8/14 placebo patients responded to epinephrine.The first dose of adrenalin was not an adequate test dose as 25% ofthose < 6 months of age and 47% of those 6-12 months and all over18 months responded to second epinephrine. Family or personalhistory was not helpful in differentiating responders, but 60% ofpatients with RSV documented by culture and/or fluorescent anti¬body responded. All children over 18 months responded to firstadrenalin.

This is a nicely done study demonstrating the efficacy of adrenalinin acutely wheezing infants under 2 years of age based on typicalclinical criteria. The use of an ambulatory population with acutesymptoms in conjunction with the B-adrenergic and A-adrenergicproperties of adrenalin favored a response not documented withother bronchodilator studies.

Christopher RandolfWaterbury, Connecticut

66

Title:

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Method:

Results:

The highly atopic infant and chronic asthma.

Zimmerman B, Chambers C, Forsyth S.

J. Allergy and Clinical Immunology 1988, 81:71-7

To investigate the relationship between allergy and asthma in in¬fants and preschool children.

109 children, all aged 5 yrs. or less (mean 2.5 yrs.), with a clinicalhistory which included symptoms consistent with asthma. None ofthe children had clinical evidence for other disease. Most infantshad been followed 1-2 yrs. after the initial assessment and thecategory of intermittency or chronicity was based on the nature oftheir course during at least 6 months.

Atopy was defined as a serum IgE> 1 SD from the normal for ageplus at least one positive RAST Serum IgE equal to 10 times themean + 1 SD was considered highly atopic. RAST to 13 allergenswas performed on all the patients. PBL's were set up in culture todetermine spontaneous IgE production.50.5% of the patients were considered atopic by the criteria men¬tioned. 42.2% had an eczematous rash consistent with atopic der¬matitis. 80% of the patients with atopic dermatitis were consideredatopic by the definition given. Of the 109 patients, 34% had a his¬tory of an immediate reaction to one or more foods for which an IgEantibody could be demonstrated (milk, egg wheat). All of these pa¬tients were considered atopic by the definition given. 25% of thenonallergic patients with asthma were considered atopic. Atopicdermatitis was seen in 76% of the food-allergic and in 25% of thenon-food allergic patients with asthma. Although a higher propor¬tion of patients with asthma in the food-allergic group had symp¬toms of chronic asthma compared to the non-food allergic group,this did not reach statistical significance. Although clinical foodreactions in infants and preschool children clearly define atopy,there were several highly atopic infants in the nonfood allergicgroups. 30 of the patients with asthma were classified as highlyatopic and 79 were nonhighly atopic by the authors definition. Theauthors conclude that the data in this study may indicate thatasthma in infants is inherited independent of allergy and first ex¬

pressed during a viral infection of the respiratory tract.

A.M. Herrera, M.D.Washington, D.C.

TiÜe: "Are Intravenous Corticosteroids Required in StatusAsthmaticus?"

67

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Conclusion:


Ratto D, Alfaro C, Sipsey J, et al

JAMA 260:527-529, 1988.

The purpose of this randomized, nonblind study was to comparethe use of intravenous vs. oral corticosteroids in patients present¬ing with status asthmaticus.

All patients 18-65 years old, admitted to the Pulmonary MedicineService at Los Angeles County Hospital between March 1986 andOctober 1986 diagnosed as having status asthmaticus, were eligi¬ble for entry into the study. All patients had been previously treatedin the Emergency Department with inhaled beta2 agonists and IVaminophylline and were eligible only if FEV, was less than 50% atthe time of admission to the hospital. Excluded were > 10 pack-year smokers or IV steroid use more than one hour before the initialspirogram. Patients could be on oral steroids as an outpatient up to40 mg/day of prednisone.Patients were randomly assigned to receive oral methylpredniso¬lone 80 mg b.i.d. orq.i.d. or IV methylprednisolone 125mgq.i.d. or250 mg q.i.d. for 72 hours or until discharged, whichever occurredfirst. No attempt at blinding the subjects or physicians was done.All patients were treated with IV aminophylline and inhaled meta-proterenol. Inhaled atropine sulfate and parenteral or oral terbuta¬line were allowed at the physician's discretion. Theophylline levelswere not stated but said to be maintained at approximately 55mcmol/L (SI units), though it was noted that 19% of the patientshad levels > 110 mcmol/L. Spirometrie data were obtained onehour after initial dose of steroids, q6h for the first 24 hours, thenq8h.Thirty-six patients entered the oral treatment group, and 34 en¬tered the IV group with a mean age of 40 and 38 years, respectively.There were no differences in sex, race, or spirometrie data for thetwo study groups except 5 subjects in the oral group and 3 in the IVwere taking > 10 mg of prednisone per day as outpatients. The rateof improvement of FEV,, PERFR, FEF25 75 showed no differences be¬tween the oral vs. intravenous groups at either dose. The numberof days hospitalized was also similar between the two groups. Com¬plications including hyperglycemia (30% of all patients) and ab¬dominal pain were not different in the two groups. Leukocytosis(maximum 30-38,000 WBC/107L) was the most common labora¬tory abnormality noted (29% of all patients) and was not statis¬tically significantly different between the two groups, though itwas noted to be two times more frequent in the intravenous group.The authors conclude that 80 mg p.o. b.i.d. of methylprednisoloneis at the top of the clinical dose response curve and that furtherincreases in dosage, whether oral or intravenous, are probably notbeneficial.

Previous studies have investigated conventional doses of steroidsvs. "high" doses and most have found no added efficacy of the highdoses. And studies have been done showing that the oral route can

68

be used effectively in patients able to tolerate these doses. Thisstudy demonstrates both.

Alan B. Goldsobel, M.D.

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Case Management and Quality Assurance to Improve Care ofInner-City Children with Asthma.

Lawrence S. Wissow, M.D., M.P.H., Michael Warshow M.H.S., JeanBox R.N., M.P.H., Douglas Baker, M.D.

American Journal of Disease of Children, Vol 142, July 1988.

Test the feasibility of case-management quality assurance inter¬vention in care of children with asthma in reducing number ofacute care visits.

88 Medicaid recipients less than 6 yrs. old with > 2 emergencyroom visits in 3 months with at least one of these visits at theJohns Hopkins Hospital. Patients followed by allergist or pul-monologist were excluded from study.Patients identified through medical records at Johns Hopkins Hos¬pital. History of illness, medication use and assessment of generalasthma knowledge made through phone contact. Discussion ofproper medication use and home management offered. Nurse or

back-up physician for consultation made available for 24° coverage.Aspects of patients care which could be improved including drugregime, parent education and specialty consultation reviewed bynurse and back-up physician and communicated to primary care

provider. Parents contacted for follow-up every 2 months and fol¬lowing ER visits. Utilization of services data collected from medi¬caid billing files and analyzed.1) Enrolled patients more than twice as likely to have identifiedprimary care providers as non-enrolled patients (40% vs 17%, <.005). 2) 47 patients on prn drugs only. 3) 39 patients on contin¬uous medication. 4) 2 patients on no medication. 5) 9% of patientson continuous medication placed on only long-half-life theophyl-lines. 6) 62% of patients on continuous medications given no back¬up medication for "break through" wheezing. 7) Of patients receiv¬ing theophylline; 21% given dose <16mg/kg/d; 18% given dose>24mg/kg/d. 8) 45% parents felt wheezing could not be prevented.9) 75% households contained smokers. 10) No after hours callswere made to nurse or back-up physician. 11 ) Only 16% of potentialprescribing problems were corrected. 12) There was a 50% fall ratein acute care visits of study patients with no significant change invisits of control group.

Wesley Burks, M.D.Little Rock, Arkansas

69

Title:

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"Aminophylline Treatment in Severe, Acute Asthma: A Meta-analysis."Littenberg B.

JAMA 259:1678-1684, 1988.

To investigate via meta-analysis, the improvements of pulmonaryfunction after one hour of treatment with intravenous amino¬phylline for acute, severe asthma.

Meta-analysis is a type of structured, comprehensive review of themedical literature which combines data from several studies forfurther review. In doing so, statistical power can be increasedwhere no statistical difference may have been previously seen. Twomain problems with meta-analysis are noted by the author, a gen¬eral internist and clinical epidemiologist. First is, that to truly ob¬tain a thorough evaluation, all reports on the subject must beidentified. He performed a thorough, comprehensive search of themedical literature for all reports of the use of IV aminophylline inthe treatment of acute, severe asthma. Three hundred forty-sevenreports were retrieved, and only thirteen reports met the eligibilitycriteria he proposed for the meta-analysis. The second potentialproblem is the possible comparison of apples vs. oranges. The thir¬teen eligible studies still varied widely as to protocol design, sever¬

ity of asthma, doses of medication, and end points.All eligible articles contained only original data in young, otherwisehealthy, adults with acute, severe asthma. All data were analyzed asto the effect of therapy on FEV, or PEFR one hour after initialtreatment. The data from each article was reanalyzed to calculatean effect size defined as the mean improvement in spirometrievalues in the aminophylline-treated group less the mean improve¬ment in the control or nonaminophylline-treated group, divided bythe pooled S.D. of the baseline spirometrie values. The mean effectsize and a 95% confidence interval were calculated for the thirteeneligible studies, individually and as a group, as well as for varioussubgroups.Five reports compared IV aminophylline as a single agent vs. an¬other single treatment (beta agonist either injected, inhaled, or IV).These studies strongly suggested that the beta agonist therapyalone was superior to aminophylline alone.Three other studies compared IV aminophylline vs. IV albuterol,both groups also receiving IV steroids. Again, it was found that theaddition of steroids does not diminish the superiority of beta ago¬nist alone vs. aminophylline alone.

Five final studies compared combined drug regimens with IVaminophylline plus beta agonist (injected or inhaled) vs. IV amino¬phylline alone (one study with steroids).The two studies comparing IV aminophylline and inhaled beta ago¬nist in combination showed no benefit over inhaled beta agonist

70

alone. But two other studies showed a possible synergistic effect ofaminophylline plus injected epinephrine.

Comment: Author's Conclusions:1. There are inadequate data to assess the use of aminophylline as

a first line treatment of acute, severe asthma.2. For single drug therapy, aminophylline is not as effective as beta

agonist.3. A trend was seen for a synergistic effect of aminophylline plus

injected epinephrine vs. epinephrine alone.

Despite this combining of data, the thirteen studies pooled onlyincluded a total of 213 patients receiving aminophylline. It must beremembered that this was not a study looking at the best treatmentfor acute, severe asthma (as most of these studies were designed),but rather specifically as to the benefits of IV aminophylline in thefirst hour of treatment. The author's réévaluation of the data fromindividual studies occasionally led to different statistical con¬clusions as compared to the authors of the original studies (i.e. a

study comparing epinephrine vs. aminophylline-epinephrine; theoriginal authors found no difference, but by meta-analysis, theaminophylline-epinephrine group was favored), and this may be a

misinterpretation of the original data.

Alan B. Goldsobel, M.D.

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Study Population andMethods:

Results:

A multicenter evaluation of the clinical benefits of cromolyn so¬dium aerosol by metered-dose inhaler in the treatment ofasthma.

Blumenthal MN, Selcow J, Spector S, Zeiger RS, Mellon M.

JACI81(4):681-687, 1988.

The purpose of this study was to determine if the pressurized cro¬

molyn sodium aerosol therapy with 1 mg per actuation was signifi¬cantly better than placebo therapy and if it was preferred by thepatients to the cromolyn sodium powder via the Spinhaler.The study population included 155 patients (8-58 yrs.) withasthma well controlled for a minimum of 4 weeks on cromolynsodium by Spinhaler and B2- agonist. Patients initially began witha 2-week control interval with cromolyn sodium capsules followedby a 4-week single-blind period with placebo capsules. Those pa¬tients whose asthma worsened on placebo were then randomized toa 10-week double-blind period of cromolyn sodium or placebo byMDI. No baseline differences existed between the two populations.Patients receiving active cromolyn sodium were significantly im¬proved compared to the placebo group in term of daily symptoms,

71

physician's assessment, FEV,, FVC and PEFR. Concomitant bron¬chodilator medication use was less in the cromolyn-treated group.The authors conclude that cromolyn sodium by MDI is highly effec¬tive for controlling asthma symptoms, improving lung functions,and decreasing the need for concomitant bronchodilators.

Alma M. Herrera, M.D.Washington, D.C.

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Persisting Airway Obstruction In Asymptomatic Children WithAsthma With Normal Peak Expiratory Flow Rates.

AC Ferguson, MB, ChB.

J Allergy Clin Immunol 1988:82:19-22.

To clarify whether or not symptom records and peak expiratoryflow rates (PEFR) monitoring are effective in indicating airwayobstruction in chronic asthma.

Twenty children with allergic asthma. All children were on

therapeutic levels of Theophylline and pra inhaled ß-agonists. Nonewere on steroids or cromolyn.Asthma symptoms scores and PEFR were recorded twice daily byparents. Diaries were collected every 2 weeks. Spirometry was per¬formed every 2 weeks. Regular medications were continuedthroughout the study. At the end of each 2 week period the follow¬ing data was calculated: mean 24-hour symptom score, mean 24-hour PEFR, number of days with PEFR < 75% of predicted, bestFEV, and FEF2575. The study continued for eight 2 week study peri¬ods per child.

Symptomatic periods were closely associated with low peak flowdays and decreased mean PEFR but not with low FEV, or lowFEF2575. There was a significant correlation of mean symptom score

per period with mean PEFR (r = 0.39;p<0.0005), low peak flow days(r = 0.41;p<0.0005) and FEV, (r = 0.16;p<0.05), but not withFEF25.75.

Asymptomatic periods with normal peak flows were associatedwith a decreased FEF25.75 seventy-six percent of the time.Asymptomatic days were associated with low peak flow days 54% ofthe time and decreased FEV, 36% of the time.

Asymptomatic asthmatic children often have evidence of peripheralsmall airway obstruction as measured by the FEF2575, FEV, andPEFR correlate more with symptom scores but are often decreasedeven on asymptomatic days. This confirms the poor correla¬tion between dyspnea and degree of airway obstruction in children.The accompanying editorial by GJ Canny and H Levison

72

(J Allergy Clin Immunol 1988;82:1-4) discuss the pathology foundin asymptomatic children with long standing asthma. Residual air¬way obstruction may increase the frequency and/or severity ofacute asthma exacerbation and may lead to an irreversible compo¬nent. The authors of both the article and accompanying editorialfeel that twice daily PEFR measurements at home are more likely toreveal the trend of asthma and are especially important in steroiddependent asthmatics and in patients with poorly controlled or life-threatening attacks of asthma. Regular determination of FEV, andFEF2575 in the office will lead to better appreciation of persistentobstruction in asymptomatic periods. There is still controversyover whether the goal of asthma therapy should be normalizationof lung function or control of asthma symptoms.

Gary B. Carpenter, M.D.Chief, Allergy/Immunology ServiceWalter Reed Army Medical CenterWashington, D.C.

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Frequent Administration by Inhalation of Salbutamol andIpatropium Bromide in the Initial Management of Severe AcuteAsthma in Children.

Reisman J., Galdes-Sebalt M., Kazin F, Canny G. and Levinson H.

JACI 81:16-20, 1988.

To determine whether the addition of ipatropium bromide to sal¬butamol provides greater and faster bronchodilatation than sal¬butamol alone.

Twenty-five children, aged 5-15, who arrived in ER with acuteasthma and had initial FEV, < 55% of predicted. Subjects enteredin double-blind randomized manner and received either sal¬butamol alone (control group) ( 150 mcg/kg (0.03 ml/kg of the 0.5%respiratory solution up to 1.0 ml) in 2 cc saline) followed by sixdoses of 0.01 ml/kg up to 0.34 ml at 20 minute intervals or incombination with ipatropium bromide (study group) (250 meg (1.0ml of the respiratory solution)) added initially and at 40 and 80minutes later. Measurements of FEV, and FVC as well as pulse,respiratory rate, and blood pressure were made at time 0, 20, 40,60, 80, 100, 120, 135 and 150 minutes with each test being donejust before administration of next nebulized dose. Subjects did notreceive theophylline or glucocorticoids during the study.Two groups were comparable for age, sex, height, weight, age ofonset of asthma, frequency of attacks, numbers of attacks in lastsix months, number of hospital admissions, and type of mainte¬nance therapy at home. Of those on oral theophylline, the meanserum theophylline level was statistically higher in the controlgroup ( 10.9 versus 4.0). Baseline FEV, was 40% and 33% predicted,

73


FVC was 47% and 41% predicted for control and study groupsrespectively.Significant bronchodilatation was noted as early as 20 minutes inboth groups and a consistent and gradual increase in the degree ofbronchodilatation through each administration occurred. Thechanges from baseline in percent predicted FEV, at 20 minuteswere 11 and 18% and at 150 minutes, 22 and 35% for the controland study groups respectively (p<0.025). No differences seen forwheeziness, pulse, respiratory rate, blood pressure, tremor, or needfor hospitalization.Levinson et al have previously demonstrated that 50 mcg/kg dosesof salbutamol administered every 20 minutes produce a smootherrise and earlier peak response as compared to 150 mcg/kg dosesgiven hourly. This method is becoming more widely used. Thisstudy shows that the addition of ipatropium bromide respiratorysolution (unfortunately not yet available in the United States)provides significant additional bronchodilatation and indicatesthat there is likely a substantial cholinergic element to the bron-chospasm observed in acute exacerbations of asthma in children.

David F Graft, M.D.Minneapolis, Minnesota

Title:

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Prevalence of Abnormalities Found by Sinus X-Rays in Child¬hood Asthma: Lack of Relation to Severity of Asthma

Zimmerman B., Stringer D., Feanny S., Reisman J., Hak H.,Rashed ., deBenedictis F., McLaughlin J. and Levison H.

JACI 80:268-273, 1987.

Sinusitis is recognized as an aggravating factor in asthma. Theauthors found previous studies lacking in controls with inadequatedescriptions of severity of the patient's asthma. This studyattempts to describe the prevalence of abnormal sinus x-rays inpatients with asthma and controls.

Patients were selected from their Asthma Clinic (combined Pulmo¬nary and Allergy) and were greater than six years of age and free ofan upper respiratory tract infection. Sinus films included threeviews: PA, lateral and Water's view. A questionnaire to determinethe severity of asthma and nasal smear were done. Controls werefrom a dental clinic with panorex films were examined for maxil¬lary antrum abnormalities.

X-ray abnormalities were found in 43 of 138 children for a preva¬lence of 31.2%; this, compared to 0 of 50 control patients. Thepercent of patients with abnormal sinus x-rays was the same,whether the asthma was rated from mild to severe.

74

Reviewer's Comments: This study confirms the high prevalence of abnormal sinus x-raysfound in children with asthma. However, they were not able to see acorrelation between the severity of the asthma and the degree ofx-ray abnormalities. They suggest that there is a need for ran¬domized, double-blind, placebo-controlled use of antibiotics fortreating sinusitis in children with asthma.

Richard J. Sveum, M.D.Minneapolis, Minnesota

Title:

Authors:

Journal:


Study Population:


Sputum changes associated with therapy for endobronchial exac¬erbation in cystic fibrosis

Arnold Smith et al.

Journal of Pediatrics 112:547-54, 1988.

The investigators sought to define objective parameters for im¬provement in cystic fibrosis with endobronchial involvement. Theconcentration of DNA, albumin and total protein in sputum as ameasure of inflammation before and after antibiotic treatmentwere assayed in conjunction with pulmonary function tests toestablish improvement in hospitalized patients.75 patients were chosen from 113 inpatients at 11 centers whosatisfied at least 5 of 10 criteria for pulmonary exacerbations andwere judged by CF clinic physicians to need hospitalization fortreatment of endobronchial P. aeruginosa infection. Valid patientsranged from 6.4 to 44.2 years (mean 16.32 ±7.13 years) withShwachman scores between 35 and 75 with prognostic scores

ranging between 46 and 80. Arbitrary values were assigned to theamount of activity, frequency of cough, appetite, chest examina¬tion, weight change and respiratory effort. A numerical value of 6indicated improvement, 18 no change and 30 worsening in allrespects. The same physician at each institution evaluated thepatients with endobronchial infection defined by fever andleukocytosis (total granulocytes > 10,000 or > 750 immaturegranulocytes).All 75 patients were hospitalized and were treated with anti-psueudomonal antibiotics singly or in antibiotics with chest andphysiotherapy three times a day.Sputum analysis was done for albumin by immunoephelometryand insoluble DNA and total protein. All patients were scored forillness severity, had quantitative sputum culture and had mea¬surement of FVC, FEV, FEV,FEF25-75%, FRC, RV/TLC ratio andPEFR.

Those patients with fever and leukocytosis had a significantlyworse prognostic score. However, all patients improved with bothendobronchial and systemic group, having smaller peripheral leu-

75


kocyte count at the end of treatment. aeruginosa density was

significantly decreased pre and post treatment as was H. Flu, butthere was no difference between the groups, except that patientswith systemic manifestations had higher sputum density of Fluat both times.

Though admission sputum DNA and total protein paralleled eachother closely with significant decline with treatment, albumin was

significantly higher in patients with fever and leukocytosis but didnot change with treatment. The correlation of sputum total proteinand DNA was lower at the end of the treatment (r = 0.57; P<0.001 ).Pulmonary functions i.e. FEV, FVC, PEFR significantly improved ingroups with systemic manifestations following treatment. OnlyRV/TLC ratios and FVC correlated with sputum density of P.aeruginosa, but lower DNA sputum concentration also correlatedwith better PFTs when admission values were compared with thoseat end of treatment.

The absolute value of PFTs of large and small airway disease corre¬lated significantly with the amount of DNA, albumin and protein insputum at the end of hospital treatment. These data suggest thathospitalization and parenteral antibiotic therapy are associatedwith lessening infection and inflammation in these foci. The trialsare flawed by failure to control observer bias between differentcenters and failure to define the presence of viral infection.

Christopher RandolfWaterbury, Connecticut

Title:

Authors:

Journal:


Study Population:Method:

Efficacy and safety of ketotifen in young children with asthma

Volovitz B, Varsano I, Cumella JC, Jaber L

J Allergy Clin Immunol 81:526-30, 1988.

To compare the prophylactic effect of ketotifen and placebo inyoung children with mild to moderate asthma.

Thirty children age 12 to 35 months with mild to moderate asthma.

In a double-blind placebo-controlled crossover study, patients' par¬ents kept a daily diary of symptoms and concurrent medicationsduring 4 periods: (1) a 2-week baseline; (2) a 12-week drug or

placebo period; (3) a 2-week washout period; and (4) a 12-week drugor placebo crossover period. Ketotifen or placebo was given as oralsyrup twice daily. Patients were seen before and after the baselineperiod, every 4 weeks during the crossover periods, and after thewashout period. Concurrent medications included oral bron¬chodilators (terbutaline), theophylline, and if needed, prednisoneburst. As symptoms subsided, patients were allowed to stop all butthe trial drugs.

76

Findings: No significant difference was observed between ketotifen andplacebo treatment. A decrease in concurrent medication use wasobserved during the first treatment period with ketotifen. Theprinciple side effect was weight gain. In contrast to adults, no seda¬tion was noted.

Reviewer's Comments: Although it does not have a role as a primary drug in asthma man¬

agement, the use of ketotifen in selected patients as an adjunct maybe valuable. Although not discussed in this article, ketotifenappears to have a beneficial effect against the action of plateletactivating factor (Am Rev Respir Dis, Apr 1988).

Gerald R. Werth, M.D. H03Russell J. Jopp, D.O.Omaha, Nebraska

Title:

Authors:

Double-blind evaluation of nebulized cromolyn, terbutaline andthe combination for childhood asthma

Gail G. Shapiro, M.D., Clifton T. Furukawa, M.D., William E. Pier-son, M.D., Marian J. Sharpe, RN, Roger Menendez, M.D., andC. Warren Bierman, M.D.

Journal:


Study Population:

Methods:

J. Allergy Clin. Immunol. 1988; 81:449-54.

The purpose of this study was to compare the effectiveness of threenebulized treatments for chronic asthma in children: (1) cromolyn,(2) terbutaline sulfate (long acting selective B2 agonist), and (3)cromolyn and terbutaline.

The population consisted of children aged 6 to 12 years with a

diagnosis of mild to moderate chronic asthma who required dailytherapy with bronchodilators and/or cromolyn. Subjects demon¬strated 15% or more reversibility of FEV1 after inhalation of Isuprelas well as a positive methacholine challenge.The study design was double-blind crossover. Each patient receivedthree treatment regimens via a Pulmo-aide nebulizer in ran¬domized order for a period of 8 weeks each. Patients received eithercromolyn 20mg with terbutaline placebo, terbutaline 0. lmg/kg upto 4mg with cromolyn placebo, or the combination of both drugs.Patients were allowed to use metaproternol every 4 hours to controlasthma exacerbation and/or single doses of immediate release the¬ophylline. If unresponsive to these the patients were permitted toreceive up to 1 week of oral prednisone drug each 8 weeks. Patientswho used steroids for 1 week during the final 4 weeks of treatmentwere considered treatment failures.Patients were observed:1. On two screening visits consisting of complete history and phys-

77

ical examination, ECG, methacholine challenge, pulmonary func¬tions, instructed in nebulizer use and told to keep a symptomdiary;2. One week post treatment with pre and post inhaled Isuprel pul¬monary function tests, ECG repeated, and diary cards reviewed;3. 4th week post treatment with physical exam, ECG, PFT's pre andpost Isuprel and diary cards reviewed; and

4. 8th week of each treatment phase with physical exam, ECG,PFT's and methacholine challenge and with diary cards reviewed.Each office visit for each patient was at the same time of the day,methacholine challenge tests were done 6 or more hours post medi¬ation. The first 4 weeks of each drug regimen were considered as awashout phase and not included in the statistical analysis ofresults.




Cough was significantly less with cromolyn than with terbutaline(p<0.05). Morning peak flow measurements were higher with thecombination therapy than with terbutaline (p<.05). Evening peakflow measurements were higher with the combination than withcromolyn alone or terbutaline alone (p<0.01). Methacholine chal¬lenge demonstrated less bronchial hyperreactivity with the com¬bination or cromolyn alone than with terbutaline alone (p<0.02).The highest scores on daily diaries for wheeze, chest tightness andnight awakening with asthma tended to occur with terbutalinealone, although the differences were not statistically significant.Patients' and physicians' opinions concerning symptom controlhad a poorer opinion of asthma control and more need for con¬comitant asthma medication in the terbutaline alone group.In this study based on the data obtained from patient daily diaries,pulmonary functions and bronchoprovocation challenge, the effec¬tiveness of nebulized cromolyn or cromolyn and terbutaline com¬bination is better than terbutaline alone.

Donna Lynn Schuster, M.D.Herndon, Virginia

Tide:

Authors:

Journal:


Clinical relevance of the substitution of different brands ofsustained-release theophylline.Baker J., Moessner H, Gonzalez U., Grabenstein J., Renard R.,DeNapoli , Summers R., Schuster B.

JACI 81(4): 664-673, 1988

The purpose of this study was to evaluate if products differ in theirrate and extent of bioavailability and if switching products resultsin clinically relevant changes in theophylline level.

78

Study Population andMethods:

Results:

The study population included 10 adult patients with documentedreversible airway obstruction by PFT's, maintained on oral 12-hourtheophylline preparations with serum theophylline levels 10-20ug/ml. Patients received equivalent doses of four different SR the¬ophylline for 2 week periods in a random, double-blinded,crossover manner. Theophylline concentrations, pulmonary func¬tions and heart rates were monitored before the dose and at 30, 60,90, 150, 240, 360, and 480 minutes after ingestion of the elixir.

Analysis revealed significant fluctuation in the mean peak-troughlevels between formulations. In at least one occasion, all patientsdemonstrated levels above therapeutic range and 5 patientsdeveloped signs of toxicity. Two patients developed worsening ofPFT's.

Reviewer's Comments: The authors conclude that formulation-related variability existsand these may be manifested by clinical worsening of the patient or

changes in serum theophylline levels. Physicians need to monitorpatients closely and follow theophylline levels if changes in for¬mulations with equivalent doses are made.

Alma M. Herrera, M.D.Washington, D.C.

Title: Allergy in asthma I. The dose relationship of allergy to severity ofchildhood asthma.

Authors:

Journal:

Purpose of the Study:Methods:


Zimmerman. B. et al.

Journal of Allergy and Clinical Immunology. 1988; 81:63-70

To define the role of allergy in asthma of school aged children.

271 children ages 6 to 16 years were skin tested with 16 common

allergens. Of this population, 142 children were asthmatics, 32were CF patients, 48 were patients with allergic rhinitis only, and29 were control patients.The asthmatics were divided into 4 groups with group 1 being theleast symptomatic and group 4 being the most severe. Selectioncriteria were based on the number and frequency of medicationusage. 57.7% of the asthmatics reported onset of symptoms at lessthan 3 years of age.

Only 18% of the asthmatics had no positive skin reactions com¬

pared with 97% of asymptomatic control subjects. 58% of C.F. pa¬tients and 33% of A.R. patients were completely negative. Using 3or more ( + ) skin tests as criteria for significant atopy, the authorsfound 65% of the asthmatics and 35.7% of the A.R. patients dem¬onstrated 3 or more ( + ) skin tests. By contrast only 14% of the C.F.patients and 0% of the control group had 3 or more ( + ) skin tests.

79


When the prevelence of patients with 3 or more ( + ) skin tests wereexamined according to grade of asthma severity, there was a strik¬ing increase with increasing grade (severity) of asthma. Patientswith grade I asthma in this study (least severe) were least positivefor three or more positive tests (23.5%) vs. 100% positivity in thegrade 4 (most severe) asthma group.A positive correlation was also seen in regard to symptoms of theasthmatic subjects and the severity of their asthma. The incidenceof eczema, allergic rhinitis, immediate symptoms after ingestion ofspecific foods or exposure to certain animals increased steadily asthe severity of asthma increased reflecting a link between atopyand airway reactivity.Lastly a positive family history was elicited for asthma or allergyamong first degree relatives in greater than a/a of the grade 2 and 3asthmatics.The authors conclude that there is significant relationshipbetween allergy and the symptomatology of asthma. Allergy acts toincrease asthma and airway reactivity, and the tendency to mountan IgE response. Thus the more atopic the child the more easilysensitized the child will be. Therefore they are more likely to haveallergen-induced inflammation in the airways. The authors alsoconfirm the suspicion that asthmatic children may indeed becomesymptomatic prior to three years of age and that a family history ofasthma/allergy is likely. Lastly, the authors recommend early recog¬nition of asthmatic children in hopes of modifying the severity oftheir disease.

This study confirms what experienced clinicians have always sus¬

pected: A definite link between sensitization of the immune systemand airway inflammation. This underscores the necessity of theuse of oral or inhaled corticosteroid for the effective treatment ofsevere asthma, particularly when the patient is identified with sig¬nificant atopy.We want to emphasize though that the presence of positive skintests is not a specific finding for asthma and that the link betweencirculating specific IgE and airway inflammation has yet to be ade¬quately defined.

Russell J. Hopp, DOOmaha, Nebraska

Title:

Authors:

Journal:


Cognitive and Behavioral Findings in Children TakingTheophylline.Furukawa CT et al.

Journal of Allergy and Clinical Immunology. 1988; 81:83-8

To study further the relationship of Theophylline and its potential80

Methods:


effects on learning and behavior in a group of children currentlyusing long term Theophylline.24 boys and 5 girls ages 7-12 years were initially entered into thestudy and completed the psychological evaluation. All patients hadbeen on oral Theophylline B.I.D. for at least one month prior toevaluation. All patients avoided methylxanthine containing foodsand drinks two weeks prior to and during the study.The trial was designed as a group comparative, double dummy,double blind study. After initial evaluation, inhaled cromolynsodium was added to the patients therapy. After a minimum ofthree weeks on Theophylline and cromolyn, patients were ran¬domized into two groups and received either Theophylline andPlacebo Cromolyn or Placebo Theophylline and active Cromolyn.The psychologic testing was selected to assess both cognitive abil¬ities and behavioral adjustments. The WISC-R battery was admin¬istered to each patient, including the Coding and Digit Spansubtests (visual and auditory memory and concentration), theBenton Visual Retention test (visual memory), the SelectiveReminding test (auditory memory and concentration), and theStroop I and II tests (concentration). Mothers of all children com¬

pleted the CBC (Child Behavior Checklist) at the initial evaluation.The WISC-R battery was repeated 5 weeks after the blinded phase ofthe study.Asthma symptoms did not vary appreciably during the study be¬tween the two groups.Among the individual tests, the difference between the perform¬ance of subjects who continued to receive Theophylline and thosewho received active Cromolyn was statistically significant for onlythe Stroop I, a measure of concentration. On this, and on all tests,the placebo theophylline/active cromolyn group improved its scoresmore than the scores of children in the group receiving activetheophylline/placebo, cromolyn.On analysis of the CBC, there was found a statistically significantcorrelation between duration of regular oral theophylline therapyand depressive behavior and obsessive-compulsive behavior. Thelonger the patients (males only) had been taking the medication,the higher the scores for these behaviors.The authors conclude that long term theophylline usage may causesome impairment of concentration skills. This may be noticed onroutine or repetitive tasks. It has been established in the past thathigh dietory xanthines increase symptoms of anxiety. Thus theauthors attribute the high depressive and obsessive compulsivescores to the chronicity of Theophylline usage, however they cau¬tion that a certain amount of emotional maladjustment may occurwith a chronic disease like asthma. Nevertheless the conclusionthat Theophylline may impair learning and behavior is not withoutsubstantiation as positive changes have been reported by parentsafter their children have been taken off Theophylline. The parentsreport their children to be less restless, less distractible, less irrita¬ble, more manageable, and to have slept better. Thus once the emo¬

tionally unsettling effects of Theophylline had been removed, the

81

children's concentration skills, memory, and attention spanimproved.

Reviewer's Comments: It is unclear what effect the very low proportion of females in thisstudy (only 5 of 29 subjects) if any had on the outcome of the study.The authors are quite right in their cautionary statements to care¬

fully assess each patient behaviorally in order to determine whichchildren would suffer exacerbations of anxiety related behaviors ifplaced on long term Theophylline therapy. Once the decisionbetween parents and clinician has been reached to place a child on

Theophylline, careful communication and follow-up should be ar¬

ranged to monitor for behavioral side effects.

Russell J. Hopp, DOOmaha, Nebraska

Title:

Authors:

Journal:

Study Population:

Methods:

Results:

Prevalence and characteristics of late asthmatic responses toexercise

Boulet L.P., Legris C, Turcotte H., Herbert J.

J Allergy Clin Immunol 1987 80:655-662.

24 patients with asthma, 8M & 16F, mean age 23.7. Patients had a

history of dyspnea, cough and chest tightness after physicalexercise.

Patients were evaluated by prick skin tests and histamine bron¬chial challenge. Exercise tests were performed on an ergometer todetermine V02 max. 48 hours later a 6-minute steady-state exercisetest was'done at 75% of the VO max. Temperature was controlled at227 + 2°C and humidity 40%-60%. B2 agonist were withheld 8 hrs.,theophylline for 48 hrs. and inhaled steroids the am of the test.FEV, was measured at 1, 3, 5, 7, 10, 15, 30, 45, 60, 90, and 120minutes after exercise and then hourly up to 8 hrs. 15 subjectswere evaluated for the measurement of neutrophil chemotactic fac¬tor before exercise and at 5, 15, 30, and 60 minutes and 3, 5, 7, 8,and 9 hours after exercise.

17/24 subjects demonstrated an isolated EAR, whereas 7/17 hadan EAR and LAR. The mean fall in the EAR group was FEV,22.8 + /- 13.9%. The maximal fall in FEV for the LAR was between4-9 hrs. (fall in FEV, 24 + /-16.6%). The LAR was more severe thanthe EAR in 5/7 patients. Baseline bronchial responsiveness to his¬tamine measured before exercise was not statistically significantlydifferent in patients with dual asthmatic response compared withpatients with only EAR. The only difference between the early andlate responders was that LAR's occurred mostly in patients whoseV02 max was <80% of predicted. The occurrence of LAR to exerciseis not dependent on the intensity of the initial bronchospastic

82

response. Recovery was reduced in the LAR group compared to thesubjects with isolated EAR. The appearance of neutrophil chem-otactic activity was observed with both the early and late compo¬nent of exercise-induced bronchospastic response, however, theincrease was small and not significant.

A.M. Herrera, M.D.Washington D.C.

Title:

Authors:

Journal:

Study Population:

Methods:

Findings:

Conclusion:

Continuous terbutaline nebulization for the treatment of severeexacerbation of asthma in children.

JayPortnoy, M.D. and Jag Aggarwal, M.D.

Annals of Allergy 60: 368, 1988.

In this study, 12 children ranging in age from 2 to 13 years old withsevere asthma, were treated in the ICU at the Childrens Hospital,(University of Missouri-Kansas City School of Medicine) for severestatus asthmaticus during 1985—1986, with continuouslynebulized terbutaline.

The 12 patients had severe asthma, retractions, cyanosis on 40% 02and failure to respond to IV theophylline, steroids, SQ epinephrineinjections and intermittent inhaled beta-adrenergic agonists.Eight of 12 patients had PC02 ^ 40 mm Hg. Treatment included theadministration of 0.25 to 3.0 mg. terbutaline IV solution 1 mg/ml(Ciba-Geigy), in saline to give a total volume of about3 ml every 15 minutes by face mask using an Intec nebulizer(Kansas City Biologicals). The nebulizers were driven by 5-10 L/secof oxygen so that treatments lasted 15 minutes.

Blood gas, pulse, respiratory rate and clinical change was noted.The dose of terbutaline was increased by 0.5 mg. per treatmentuntil improvement or the maximum dose 3 mg/15 min wasobtained. Patients also received IV aminophylline and steroids(Solumedrol). Doses of nebulized terbutaline were between 1.0and 12.0 mg/hr.All patients showed improvement in blood gases, pulse and respira¬tory in blood gases, pulse and respiratory rates. None developedsigns of toxicity such as tremor, increased tachycardia or

arrhythmia. The duration of therapy ranged from 1 to 24 hours(mean 8.3 hours) and all children were able to leave the ICU withinone day. Most children responded within one hour.

The use of continuously nebulized terbutaline appears to be a safeand effective treatment for severe asthma. It may be an alternativeto the use of mechanical ventiliation or IV isoproterenol for severe

83

asthma. More experience is required regarding optimal doses,tapering treatments and toxicity in larger numbers of patients.

Betty Miller, M.D.Daly City, California

Title:

Authors:

Journal:

Study Population:

Methods:

Findings:

Conclusion:

Delivery of Albuterol Aerosol by Aerochamber to Young Children

R. Michael Sly, J.M. Barberas, et al.

Annals of Allergy 60: 403, 1988.

In this study, 30 asthmatic children ranging in age from 3 to 6years (mean age = 4.8 years) with peak flow rates 40% to 90%predicted were selected for inhalation of albuterol aerosol 200 mg.(2 puffs) at an interval of 5 minutes with use of the Aerochamber(Monaghan Medical Corp. )

Pulse rate and PEFR were measured before treatment and 5 and 20minutes after administration of the second dose of albuterol aero¬sol. A similar group of 16 asthmatic children (mean age 4.6 years)was evaluated before and after inhalation of placebo to control forchanges in PEFR due to possible effects of learning.Peak expiratory flow rates improved in 29 of 30 children whoreceived albuterol. The increases from a mean of 70% predictednormal before treatment, to 84% at 5 minutes and 91% at 20 min¬utes were highly significant (p < .0005). Small increases in PEFRfrom 70% to 73% and 75% in the similar group of 16 children whoreceived placebo were not significant.There was no significant difference in pulse rate following inhala¬tion of albuterol compared to placebo inhalation.No patient was excluded because of inability to learn testing ortreatment procedures.Use of the aerochamber permits effective delivery of medicationfrom metered dose inhalers in children as young as 3 years of age.

Betty Miller, M.D.Daly City, California

Title:

Author:

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

Ferguson AC

84

Journal:


Study Population:

Method:

Statistically SignificantFindings:Reviewer's Comments:

J Allergy Clin Immunol 82:19-22, 1988.

To illustrate the importance of using peak flow measurements pen¬ding spirometry in so-called "still" or asymptomatic asthma pa¬tients. These pulmonary function tests will often revealabnormalities that probably may have been missed without thetest.

20 children with diagnosis of bronchial asthma from infancy. Meanage 8.8 years; range 6-14 years. All had positive skin tests orRASTs to 2 or more inhalant allergens.1. Parent recorded symptoms twice a day in a symptom diary.2. PEF readings were recorded twice daily by parents before medi¬cation was taken with mini-Wright Peak flow meters.

3. Spirometry was performed with the Jones Waterless spirometer(FVC, FEV1 and FEF2575) with the standards of Polgar andPromadhat.4. Regular medications were continued throughout the 16-weekstudy period with physician visits every 14 days.27% had decreased peak flows with no symptoms. 33% had de¬creased FEF2575 with no symptoms.This is another study which has demonstrated how home peak flowmeasurement and office spirometry can reveal significant airwayobstruction in children who claim to be asymptomatic. Futurestudies will have to prove the importance of treating these patientsand also how to get such asymptomatic patients to comply withtreatment regimens.

Gerald Klein, MDVista, California

85

section ii asthma and pulmonary disorders and related medications

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