J. ALLERGY CLIN. IMMUNOL. NOVEMBER 1978

20 Abstracts

Pediatrics

Recurrent wheezing in the preschool child

Lenney, W., and Milner, A. D.: Arch. Dis. Child. 53,468, 1978.

In the preschool child, it is difficult to distinguish asthma from wheezing induced only by infection. Since prior studies have indicated that the asthmatic and healthy child can be distinguished by the degree of bronchoconstriction induced by standardized exercise tests, this study was un- dertaken to measure airflow resistance in children (3 to 5 yr) with recurrent wheezing attacks.

The study group was comprised of 23 children (3.1 to 5.2 yr) with recurrent episodes of wheezing; 8 patients had eczema, 5 had required hospitalization, and 15 had required at least one course of antibiotics. In the control group were 29 children (2.8 to 4.9 yr), none of whom had a previous episode of wheezing or a family history of asthma in first- degree relatives. All therapy was discontinued at least 12 hr before exercise testing and physical examination im- mediately prior to testing revealed no clinical evidence of airway obstruction.

Peak expiratory flow rate (PEFR), using a Wright peak flow meter, and total respiratory resistance (Rr), measured by a forced oscillation technique, were determined prior to exercise testing and 2, 5, 10, 20, and 25 min after running that induced a heart rate greater than 170/min. In addition, the patients with recurrent wheezing inhaled nebulized sal- butamol and their Rr and PEFR were measured 2 and 5 min later.

In the control group, the initial PEFR ranged from 85 to 165 L/min (mean 123 L/min) and the RT from 0.7 to 1.35 kPa/L per set (mean 1.1 kPa/L per set), and exercise had no significant effect on either measurement; in all children the Rr rose <15% and in 28 of 29 children the PEFR decreased <17% from the baseline values.

In the patients with recurrent wheezing the initial PEFR ranged from 60 to 150 L/min (mean 117 L/min) and the Rr from 0.8 to 1.6 kPa/L per set (mean 1.28). Seventeen of 20 children who could use the peak flow meter showed a mean decrease of 39.2% in PEFR after exercise and in 16 of these the decrease was 20%; after the nebulization of salbutamol the mean increase in PEFR was 29%. All children were able to use the oscillator. Twenty of these showed a mean peak rise of 65.6% in Rr postexercise and all exceeded 31%; the mean decrease in RT after salbutamol was 33%. Three pa- tients did not demonstrate apparent bronchoconstriction after exercise, but after salbutamol inhalation showed a mean rise of 12% in PEFR and a mean fall of 29% in RT.

The authors conclude that the large majority of children (3 to 5 yr of age) with recurrent wheezing have abnormal bronchial lability comparable to that seen in the older asth- matic child and that exercise testing can be used to identify these patients. They suggest that the forced oscillation technique is valuable to assess changes in airflow obstruc- tion in young children.

S. B.

Interferon production in children with respiratory syncytial, influenza, and parainfluenza virus infections

Hall, C. B., Douglas, R. G., Jr., Simmons, R. L., and Geiman, J. M.: J. Pediatr. 93:28, 1978.

Although respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory tract disease in infants and young children, recovery from infection is not well understood and does not appear to correlate with antibody response nor with the cessation of viral shedding. To further elucidate the mechanisms of recovery from RSV infection, this study was undertaken to measure interferon production in the nasal secretions of children infected with RSV.

The study group was comprised of 186 children, 129 of whom (aged 10 days to 24 months) had RSV infection, 20 (aged 4 weeks to 36 months) had influenza A infection, and 37 (aged 4 to 66 months) had parainfluenza type 1 infection. All of the children with RSV and influenza A infection were hospitalized, while most of the patients with parainfluenza infection were outpatients. Nasal washings were collected for viral isolation and interferon determination at the time of the initial evaluation and every other day throughout the study period. Isolation of RSV was accomplished by the inoculation of nasal washings onto HEp-2 cells and influenza A and parainfluenza viruses by the inoculation of Rhesus monkey kidney cells. Interferon was measured by a plaque reduction assay utilizing human foreskin fibroblast cultures and the sensitivity of the assay was determined by repeated comparison with an international standard.

Only 5 of the 129 children (4%) with RSV infection had interferon detected in their nasal washings; the quantities measured were usually low and the geometric mean titer (GMT) was 2.0 (l-10 U/ml). Interferon was initially pres- ent on days 1 to 3 of hospitalization and was not detectable beyond the tenth hospital day. Since 4 (4%) of the 100 children <6 months of age and 1 (3%) of the 29 >6 months had detectable interferon, age did not appear to influence the ability to produce interferon.

Eleven of the 20 patients with influenza A infection (55%) and 11 of the 37 with parainfluenza viral infection (37%) had detectable interferon in their nasal washings; their GMT was 26.8 (5-86 U/ml) and 23.5 (5-90 U/ml), respectively. The frequency of interferon detection in chil- dren with RSV infection was significantly less than in those with influenza A (p < 0.001) or parainfluenza virus (p < O.OOl), and the quantities measured were also significantly less (p < 0.0025 for influenza A and p < 0.005 for parain- fluenza virus).

Although interferon in the nasal washings of children with RSV infection was not associated with diminishing quantities of RSV nor a decrease in the duration of shed- ding, the appearance of interferon in the patients with influenza virus infection did correlate with diminished quantities of virus shed in the nasal secretions.

Although the explanation for the poor interferon induc- tion by RSV is not known, the authors suggest that mater- nally derived specific serum antibodies could depress or

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elicit factors I.hat inhibit interferon and may contribute to the severity of the disease and the abundant and prolonged shedding of virus.

S. B.

Pharmacology, physiology, and pathology

Massive theophylline overdose: Rapid elimination by charcoal hemoperfusion

Ehlers, S., Zaske, D., and Sawchuk, R.: J. A. M. A.

240:474, lI178.

Charcoal hemoperfusion is an efficient means for remov- ing many drugs and endogenous substances from the circu- lation. This method of treatment was successfully employed to treat a 4%year-old woman who had ingested about f i f ty 200-mg aminophylline tablets (8.5 gm of theophylline) and whose serum theophylline level was 190 pg/ml on admis- sion. Various methods employed to treat her progressively worsening condition were of no avail. When persistent car- diac arrhythmias and atrioventricular dissociation and car- diac arrest occurred requiring external cardiac massage for 20 min, charcoal hemoperfusion was instituted. Within one hour her condition began to improve and the laboratory findings showed a drop in the platelet count from 269,000 to l7O,OOO/cu mm, the serum calcium from 9.0 to 6.5 mg/ml, and a drop in the serum theophylline level to 20 pgiml.

The patient unfortunately suffered irreversible anoxic central nervous system damage probably secondary to the prolonged hypotension and cardiac arrest, a complication that perhaps could have been avoided by earlier institution of the charcoal hemoperfusion.

H.

Delay in the development of the allergic response to metals following intratracheal instillation

F.

Parker, D., and Turk, J. L.: Int. Arch. Allergy Appl.

Immunol. 57:289, 1978.

The present experiments were performed to observe the effect of the lntratracheal instillation of water-soluble metal sensitizers on the immune response in guinea pigs. lntra- tracheal intubation with the soluble metal salts potassium dichromate (K,Cr,07) and nickel sulfate (NiSOJ has been demonstrated to cause a marked delay in the development of delayed hypersensitivity to the specific agent. Two tenths ml of a 1% solution of KZCr20, or NiS04 in saline was instilled into the trachea of guinea pigs. These instillations were repeated three times, at a-day intervals for the first week. This was followed by a 9-day interval, after which the guinea pigs received another three doses at ‘-day inter- vals. Animals were sensitized to KzCr,07 and NiSO, 9 days after the final intubation. Control animals received intuba-

Abstracts 21

tions of saline without the metal. A delay in the develop- ment of sensitivity to K2Cr20, compared with that develop- ing in animals receiving saline intubation was demonstrated in two experiments. In the first experiment all the controls were sensitive 2 wk after immunization. However. only 1 of 9 of the animals intubated with the specific metal salt was reactive at this time. Fifty percent of the animals were reac- tive 1 wk later. The maximum reactivity was not present until 7 wk after immunization. A similar but more intense delay in the development of sensitivity was demonstrated in the second experiment, in which 80% of the animals re- mained unresponsive up to 8 wk after immunization. Intu- bation with K2Cr20, produced no change in the develop-

ment of sensitivity to NiSO, when compared with the saline control. This indicates that the phenomenon described is immunologically specific. As a result of these experiments it is suggested that absorption of water-soluble metal sen- sitizers via respiratory route may, under certain circum- stances. induce a temporary state of unresponsiveness even to a powerful immunologic stimulus and may not necessar- ily act directly to produce a state of sensitivity. Moreover, this phenomenon is immunologically specific. More exper- iments therefore are needed to define the role of the respi- ratory tract as a portal of entry for sensitizers, especially in an industrial situation.

V. Ilea

Miscellaneous allergies

Sulfisoxazole-induced thrombocytopenic purpura: Immunologic mechanism as cause

Hamilton, H., and Sheets, R.: J. A. M. A.

239:2586. 1978.

There is presumptive evidence implicating a large num- ber of drugs which can induce thrombocytopenic purpura on an immunologic basis, but of this number only quinidine, quinine, digitoxin, rifampin, apronalide, novobiocin, and stibophen have been shown by both in vivo and in vitro testing to have such an immunologic effect. The present study demonstrated that sulfisoxazole also can induce thrombocytic purpura on an immunologic basis.

A young farmer who had been under treatment for brucel- losis with sulfisoxazole, tetracycline, and streptomycin de- veloped severe thrombocytopenic purpura. One hour fol- lowing the first dose of sulfisoxazole and tetracycline, he felt weak and developed back and leg pain along with headache. Shortly thereafter he developed purpuric spots on his tongue and cheeks followed by epistaxis, humaturia, and bloody stools. On admission to the hospital there was ex- tensive purpura with large ecchymosis into the skin and mucous membranes. The urine and stools were strongly

positive for occult blood. The platelet count was l.OOO/cu mm, hemoglobin was 11.6 gm/dl, reticulocyte count was 4.7%. and the bone marrow showed hypercellularity with plentiful megakaryocytes. The brucella titer was I : 20,480. After a rapid recovery the patient was challenged separately