Michael A. Wall

Long-term follow-up of a cohort of children with alpha-1-antitrypsin deficiency

We assessed lung function, liver function, and smoking attitudes and behavior in 22 adolescents with homozygous alpha 1-antitrypsin deficiency whose condition had been detected through neonatal screening in the early 1970s. All subjects had normal lung volumes, expiratory flow rates, and diffusing capacity except for two siblings with mild asthma whose values reverted to the normal range after administration of an inhaled bronchodilator. Liver function was normal in all subjects with the exception of one boy who had an isolated elevation of alkaline phosphatase activity. Smoking attitudes, as determined by questionnaire, did not differ from those of 130 control subjects, but smoking initiation rates were significantly lower (p = 0.02). We believe that the issue of neonatal screening for alpha 1-antitrypsin deficiency should be reexamined because augmentation therapy for adults with emphysema is now available, and screening followed by family-based smoking intervention may lead to a nonsmoking life-style. The latter is especially important because the current weight of epidemiologic evidence strongly suggests that in nonsmokers with this condition, severe emphysema may never develop or, if it does, it will do so at a much later age than in smokers.

Expression of Basic Fibroblast Growth Factor in Nasal Polyps

Basic fibroblast growth factor (bFGF) is a polypeptide that is mitogenic for a wide variety of cell types. We used Northern blot analysis and immunohistochemistry to determine if bFGF is expressed in the nasal polyp tissue; bFGF messenger RNA was detectable in the polyps examined by Northern blot analysis. Strong immunostaining for bFGF was found in blood vessels and along the basement membrane of the epithelial cell layers. Basal epithelial cells and some infiltrating mononuclear cells also stained for bFGF. Proliferating cell nuclear antigen colocalized with bFGF to basal epithelial cells, endothelial cells, and areas of focal epithelial metaplasia. The polyp tissue was double-labeled with a mouse monoclonal antitryptase, a specific mast cell marker, and anti-bFGF. A significant number (65% ± 19%) of the bFGF-positive mononuclear cells in the polyp tissues were positive for tryptase. These findings suggest that bFGF may contribute to the endothelial and epithelial proliferation in nasal polyp tissues and that mast cells are one source of this growth factor.

Bilateral tracheal bronchi

A case of bilateral tracheal bronchi, first diagnosed at 14 months, is reported in a child who is currently alive and well at more than two years of age. This is only the second such case to be described in the world literature and is the only case to survive the first year of life. A tracheal accessory lung was also present. The varieties of tracheal bronchi are described. The importance of considering this uncommon abnormality in a number of clinical situations is emphasized.

Ciprofloxacin 0.3%/dexamethasone 0.1% topical drops for the management of otic infections.

The American Academy of Otolaryngology – Head and Neck Surgery has recommended that, where possible, infections of the external auditory canal and middle ear be treated with topical preparations. The advantages of topical therapy include i) excellent efficacy; ii) decreased risk of systemic side effects; iii) less likelihood of selecting for resistant strains of microorganisms; and iv) lack of potential for ototoxicity. One advantage of topical therapy arises as a consequence of a very high concentration of antibiotic in topical preparations reaching the site of infection. Ciprofloxacin 0.3%/dexamethasone 0.1% (Ciprodex®) is the only ototopical drop approved for use in both the middle ear and external auditory canal that combines a fluoroquinolone with a steroid. At 0.3% (3000 mcg/ml), the ciprofloxacin concentration of Ciprodex exceeds the MIC of virtually all relevant organisms by a very considerable margin. The clinical efficacy of ciprofloxacin/dexamethasone suspension has been demonstrated in several large prospective clinical trials. It has been consistently equal to or superior to comparator drugs. The authors believe that the use of topical ciprofloxacin/dexamethasone will increase as the advantages of fluoroquinolone/steroid combination therapy become more widely recognized.

Changes in ventilation homogeneity from preschool through young adulthood as determined by moment analysis of nitrogen washout

ABSTRACT. This study was designed to assess potential differences in ventilation homogeneity related to growth. One hundred thirty-three healthy subjects representing four stages of growth were studied: group 1, preschool, ages 34–74 months; group 2, preadolescent, ages 8–10 yr; group 3, postpubertal, ages 15–17 yr; group 4, young adult, ages 26–40 yr. Ventilation homogeneity was assessed by moment analysis of multibreath nitrogen washout with functional residual capacity, the ratio of the 1st to 0th moment (MR 1/0), and the ratio of the 2nd to 0th moment (MR 1/0) being the outcome variables of interest. Across the four groups functional residual capacity increased as a curvilinear function of height. At all heights functional residual capacity was larger in males than females and the slope of the regression was steeper in males than females (p < 0.001). Both MRs 1/0 and 2/0 were significantly higher in group 1 than the other groups, indicating that ventilation washout was less homogeneous in the preschool subjects than in older children or adults. Males of group 1 had significantly higher values for both moment ratios (more ventilation nonuniformity) than females. In the other groups there were no significant sex based differences although there was a trend for males to have a lower MR 1/0 than females in the young adults, p = 0.08. The results indicate that both age and sex are important determinants of the growth of distribution of ventilation.

1199 SYNERGY OF COMBINED ANTIGEN INHALATION CHALLENGE IN ALLERGIC ASTHMA

To determine whether combined allergen exposure is competitive, additive or synergistic in its effect on lung function, inhalation challenges were performed in 5 asthmatic boys, 12 to 16 years old, with known sensitivity to 2 environmental antigens. Challenges were conducted according to the standards of the American Academy of Allergy on 3 occasions at least 1 week apart, first with each allergen separately then with both simultaneously. Forced Expiratory Volume in 1 sec (FEV1) before study was at least 60% of predicted value. The response to challenge was monitored by serial measurements of FEV1. Challenge ended either when a given provocative dose (PD) produced a 20-35% fall of FEV1 (PD20 - PD35) or when a concentration of 10,000 PNU/ml produced no effect. Three subjects reacted to the single antigens with a marked fall of FEV1, allowing measurement of PD35 for each antigen. In the dual challenge, these subjects reacted to a mean PD of 19% (range: 7 - 32%) of the respective PD35 of each antigen. The other 2 subjects reacted to one antigen only and the fall of FEV1 was small, only allowing measurement of PD20 for that antigen. In the dual challenge these subjects reacted with a 20% fall of FEV1 to a PD containing 32 and 47%, respectively, of their single-antigen PD20. These findings support the hypothesis that two antigens inhaled simultaneously exert synergistic effects. (Supported by NIH grant # HL-10436)