Volume 121 Number 6
of state (MediCal) regulations at the time of the study, only the !ntal Spinhaler (Fisons Corp.) preparation was available to our indigent population. These patients appear to be well controlled when the Spinhaler contents are dissolved in isotonic saline solution for nebulization. The possible adverse effects of nonisotonic aerosols are well described.2 Therefore a comparison of our isotonic preparation with the commercially available hypotonic form of cromolyn was of interest. Because Of space limitations, we were not able to show our data for each of the time intervals in which "there were no significant differences," reported previously as an abstract. 3 The lowest values in pulmonary function variables at 10, 20, or 30 minutes are shown in the Figure (p.642). Although no effect was observed for measures of large airway function, there appeared to be a subgroup in whom a 17.7% decrease in forced expiratory volume in 1 second was also observed. Although the number of subjects studied was small, we believe that further studies should be undertaken to clarify the detrimental effect that we observed. This is especially important because cromolyn is the only antiinflammatory drug currently available in the United States in home nebulization therapy for very young pediatric patients and for those in whom the metered-dose inhalers with spacer and mask devices are ineffective. There are very few studies examining nebulized solutions in young pediatric patients with reactive airway disease; studies have compared the differing solutions of nebulized cromolyn in adults. 4 O'Callaghan et al. 5 found significant decreases in specific conductance in infants after challenges with nebulized water and cromolyn. As we mentioned in our discussion, the reason that few asthmatic patients have difficulties may be the addition of bronchodilators to their aerosol solutions, which may counteract any adverse effects from cromolyn. There does not appear to be any effect of osmolarity in nebulized beta-2 bronchodilators.6,v In view of concerns with the regular use of beta-2 agonists, clinicians should be aware of the potential for aggravation of underlying reactive airway disease when using only the nebulized form of cromolyn. If patients complain of respiratory symptoms, the use of an isotonic solution should be considered. Indeed, many asthma centers suggest the addition of I to 2 ml of isotonic saline solution to minimize the hypotonicity of the nebulized form.
Terry IV. Chin, MD, PhD Director, Allergy~Immunology Assistant Director, Pediatric Pulmonary and Cystic Fibrosis Center Memorial Miller Children's Hospital Assistant Professor of Pediatrics University of California, Irvine Long Beach, CA 90801-1428
REFERENCES 1. Chin TW, Nussbaum E. Detrimental effect of hypotonic cromolyn sodium. J PEDIATR 1992;120:641-3. 2. Anderson SD. Asthma induced by nonisotonic aerosols. J Respir Dis 1987;8:S19-$24. 3. Chin TW, Nussbaum E. Effect of aerosolized hypotonic and isotonic sodium cromolyn in pediatric asthma. Chest 1990; 98:84S. 4. Rhind GB, Sudlow MF. Effect on spirometry of distilled water and cromoglycate solutions nebulized by a small portable ultrasonic nebulizer. Respiration 1987;51:86-90. 5. O'Callaghan C, Milner AD, Swarbrick A. Nebulized sodium cromoglycate in infancy: airway protection after deterioration. Arch Dis Child 1990;65:404-6. 6. Soferman R, Kivity S, Topilsky M. The effect of osmolarity of respiratory salbutamol solutions on exercise-inducedasthma in children. Pediatr Asthma Allergy Imrnunol 1990;4:193-8. 7. Simkins R, Nations L, Singer J, Mullen A, Strunk RC. Inhaled bronchodilators for asthma are equally effective when diluted with either tap water or normal saline. Pediatr Asthma Allergy Immunol 1988;2:227-30.
Neonatal herpes simplex virus infection: Mean a g e at onset To the Editor: We note erroneous information in the article by Silverman eta !. I regarding mean age at onset of neonatal herpes simplex virus (HSV) infection. The authors state in their discussion section that the first symptoms of disseminated infection and of infection localized to skin, eye, or mouth occur at a slightly later mean age than do symptoms of HSV encephalitis. Exactly the opposite is the case. In the most recent study of the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, z the mean age at onset of either disseminated HSV or disease localized to the skin, eyes, or mouth was reported to be 11.0 _+ 0.5 days. For HSV encephalitis, the mean age was reported to be 16.2 _+ 0.9 days.
Mary Ann Carmack, PhD, MD Camille Sabella, MD Department of Pediatrics Division of Infectious Diseases Stanford University School of Medicine Stanford, CA 94305
Eliezer Nussbaum, MD Director, Pediatric Pulmonary and Cystic Fibrosis Center Memorial Miller Children's Hospital Professor of Pediatrics University of California, Irvine Long Beach, CA 90801-1428 9/35/41483
1. Silverman MS, Gartner JG, Halliday WC, Kohl S, Embree J. Persistent cerebrospinal fluid neutrophilia in delayed-onset neonatal encephalitis caused by herpes simplex virus type 2. J PEOtATR 1992;120:567-9. 2. Whitley R, Arvin A, Prober C, et al. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex infection. N Engl J Med 1991;324:444-9.