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Lung histopathology in asthma
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LUNG HISTOPATHOLOGY IN ASTHMA. L. Ho t M.D.~ R. Stanford~ M.D.~ R.C. Strunk~ M.D., Denver, Colorado The known pathology of asthma is based abnost exclusively on material from autopsies after death due to status asthmaticus, mucosal biopsy of large bronchi, or lobectomy for removal of diseased tissue (e.g., right middle lobe syndrome). We report the pathologic findings in two chronic asthmatic children who had open lung biopsy at the time of fundoplication for hiatal hernia. Both had required corticosteroids for many years, but at the time of surgery pulmonary functions were normal except for mild limitation of airflows at low lung volumes. Pressure/volume curves showed no evidence of emphysema. Both biopsies were remarkably similar. Significant abnormalities included prominent bronchiolar muscle hypertrophy and an unusual, multifocal lymphocytic infiltration of peribronchiolar tissues. Unlike mononuclear cell infiltrates noted in lung tissue obtained during severe asthma, the lymphocytes were not accompanied by other inflammatory cell types. In addition, there was a striking and unexpected inequality of alveolar size within single acinar units. This could not be explained by proximal airway plugging alone. Unlike material obtained during status, there was no luminal exudate, basement membrane thickening, mucus gland enlargement, or eosinophilic infiltrate. Also, there was no evidence of aspiration. These findings suggest that significant residual abnormalities exist even in asymptomatic patients with relatively normal pulmonary function, and that chronic inflammation with lymphocytes, which can persist despite aggressive medical therapy, may play a prominent role in the pathophysiology of asthma.
127 LARGE LOCAL REACTIONS FOLLOWING HYMENOPTERA STINGS IN CHILDREN. D.F. Graft, M.D., K.C. Schuberth~ M.D.~ A. Kagey-Sobotka~ Ph.D., K.A. Kwiterovich, B.S.N., L.M. Lichtenstein~ M.D., and M.D. Valentine, M.D. Baltimore, MD. Of the 126 children evaluated for large local reactions (LLR) (induration exceeding 5 cm. in diameter and persisting for longer than 24 hrs), 105 (83%) had positive venom skin tests (ST). ST distribution was: honeybee (HB) only, 28%; any combination of three vespids (TV) only, 9%; Polistes (POL) only, 1%; HB and TV 24%, HB and POL 3%, TV and POL 10%, and HB, TV, and POL 25%. ST results of patients with LLR were compared to those of the first 200 children with positive skin tests evaluated for systemic Hymenoptera reactions (SYS). A major qualitative difference was that the rate of isolated positive HB ST in the LLR group was twice that seen in the SYS group. (29% vs 13%; p < .005). Using a numerical scoring system for ST results and the Mann-Whitney-U test, sensitivity in LLR was found to be significantly lower than SYS for HB (p <.02), TV (p < .001), and POL (p < .001). Thirty-two patients were stung 64 times resulting in 2 systemic reactions, 30 LLR and 32 nominal local reactions. Intergroup differences in ST and IgE antibody titers are being evaluated. We conclude that i) isolated HB sensitivity is more common in LLR than in SYS; 2) ST sensitivity is lower in LLR than in SYS, although the difference is slight; and 3) the risk of progression from LLR to SYS in children seems small.
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PREVALENCE OF HYMENOPTERA VENOM ALLERGY. D.B.K. Golden~ M.D.~ M.D. Valentine~ M.D., A. KageySobotka, Ph.D., and L.M. Lichtenstein, M.D., Baltimore, MD. Although a useful regimen for the treatment of insect allergy has been developed, criteria regarding whom to treat have not been defined because the prevalence and natural history of the disease are unknown. Therefore, we have begun an epidemiologic study in a large adult population previously studied for the determinants of atopic disease. The first phase was a survey of a random sample of the total group. We interviewed 187 subjects for their history of insect stings and reactions; venom skin tests (VST) were performed, Serum was obtained for total and specific IgE antibody (these data will be available). Insect stings had caused systemic reactions (SR) in 4% of the subjects and an additional 17% had experienced large local reactions (LLR). VST were positive in 19% of subjects with LLR and in 71% of those reporting SR. Surprisingly, among the 79% with no history of an adverse reaction to stings, more than 12% had positive VST. The frequency of positive VST decreased with the time since the last sting; further, the positive VST were not related to inhalant allergy or to a family history of insect allergy. These data indicate that the prevalence of sensitivity to insect stings is far greater than previously appreciated: fully 25% of the population is affected by virtue of a positive history and/or positive VST. The immunologic and clinical significance of these findings are being examined by prospective observation of VST, antibody titers and the sequelae of future stings.
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A COMPARISON OF VENOM TREATMENT AND NO TREATMENT IN INSECT ALLERGIC CHILDREN. K.C. Schuberth, M.D., A. Kagey-Sobotka~ Ph.D., K. Kwiterovlch, B.S.N., D.F. Graft, M.D., M. Szklo, M.D., L.M. Lichtenstein, M.D., and M.D. Valentine, M.D., Baltimore, MD. We evaluated 563 children (age 3-16 years) with a history of allergic reactions to Hymenoptera stings. 148 had life-threatening systemic reactions (LTR), 262 had non-life-threatening systemic reactions (NLTR) and 124 had large local reactions (LLR). Approximately 88% of each group had positive venom skin tests. To assess the risk/benefit ratio of venom therapy, NLTR patients (pts) with positive ST were either randomly assigned or self-selected to: venom therapy (T) (69 pts) or emergency precautions only (NT) (151 pts). 56 accidental field stings in the T pts produced 1 mild systemic reaction (reaction rate 1.8%); in the NT group, 132 stings produced only 9 mild systemic reactions (6.8%) (p=NS). 9/10 of the systemic reactions were milder than the original. LLR following subsequent stings occurred less frequently in the T than the NT pts (5% vs 33%, p <.001). Repeat ST after two years were done in 93 NLTR pts (32 T, 61 NT); 57% had at least a 10fold drop in sensitivity (72% T, 49% NT). Unstung pts were more likely to show decreased sensitivity than those stung (76% vs 42%). The low reaction rate to subsequent stings, the lack of serious reactions and the decreases in ST sensitivity suggest that the added protection offered by venom therapy may not justify its use for this selected group of children.
LUNG HISTOPATHOLOGY IN ASTHMA. L. Ho t M.D.~ R. Stanford~ M.D.~ R.C. Strunk~ M.D., Denver, Colorado The known pathology of asthma is based abnost exclusively on material from autopsies after death due to status asthmaticus, mucosal biopsy of large bronchi, or lobectomy for removal of diseased tissue (e.g., right middle lobe syndrome). We report the pathologic findings in two chronic asthmatic children who had open lung biopsy at the time of fundoplication for hiatal hernia. Both had required corticosteroids for many years, but at the time of surgery pulmonary functions were normal except for mild limitation of airflows at low lung volumes. Pressure/volume curves showed no evidence of emphysema. Both biopsies were remarkably similar. Significant abnormalities included prominent bronchiolar muscle hypertrophy and an unusual, multifocal lymphocytic infiltration of peribronchiolar tissues. Unlike mononuclear cell infiltrates noted in lung tissue obtained during severe asthma, the lymphocytes were not accompanied by other inflammatory cell types. In addition, there was a striking and unexpected inequality of alveolar size within single acinar units. This could not be explained by proximal airway plugging alone. Unlike material obtained during status, there was no luminal exudate, basement membrane thickening, mucus gland enlargement, or eosinophilic infiltrate. Also, there was no evidence of aspiration. These findings suggest that significant residual abnormalities exist even in asymptomatic patients with relatively normal pulmonary function, and that chronic inflammation with lymphocytes, which can persist despite aggressive medical therapy, may play a prominent role in the pathophysiology of asthma.
127 LARGE LOCAL REACTIONS FOLLOWING HYMENOPTERA STINGS IN CHILDREN. D.F. Graft, M.D., K.C. Schuberth~ M.D.~ A. Kagey-Sobotka~ Ph.D., K.A. Kwiterovich, B.S.N., L.M. Lichtenstein~ M.D., and M.D. Valentine, M.D. Baltimore, MD. Of the 126 children evaluated for large local reactions (LLR) (induration exceeding 5 cm. in diameter and persisting for longer than 24 hrs), 105 (83%) had positive venom skin tests (ST). ST distribution was: honeybee (HB) only, 28%; any combination of three vespids (TV) only, 9%; Polistes (POL) only, 1%; HB and TV 24%, HB and POL 3%, TV and POL 10%, and HB, TV, and POL 25%. ST results of patients with LLR were compared to those of the first 200 children with positive skin tests evaluated for systemic Hymenoptera reactions (SYS). A major qualitative difference was that the rate of isolated positive HB ST in the LLR group was twice that seen in the SYS group. (29% vs 13%; p < .005). Using a numerical scoring system for ST results and the Mann-Whitney-U test, sensitivity in LLR was found to be significantly lower than SYS for HB (p <.02), TV (p < .001), and POL (p < .001). Thirty-two patients were stung 64 times resulting in 2 systemic reactions, 30 LLR and 32 nominal local reactions. Intergroup differences in ST and IgE antibody titers are being evaluated. We conclude that i) isolated HB sensitivity is more common in LLR than in SYS; 2) ST sensitivity is lower in LLR than in SYS, although the difference is slight; and 3) the risk of progression from LLR to SYS in children seems small.
126
PREVALENCE OF HYMENOPTERA VENOM ALLERGY. D.B.K. Golden~ M.D.~ M.D. Valentine~ M.D., A. KageySobotka, Ph.D., and L.M. Lichtenstein, M.D., Baltimore, MD. Although a useful regimen for the treatment of insect allergy has been developed, criteria regarding whom to treat have not been defined because the prevalence and natural history of the disease are unknown. Therefore, we have begun an epidemiologic study in a large adult population previously studied for the determinants of atopic disease. The first phase was a survey of a random sample of the total group. We interviewed 187 subjects for their history of insect stings and reactions; venom skin tests (VST) were performed, Serum was obtained for total and specific IgE antibody (these data will be available). Insect stings had caused systemic reactions (SR) in 4% of the subjects and an additional 17% had experienced large local reactions (LLR). VST were positive in 19% of subjects with LLR and in 71% of those reporting SR. Surprisingly, among the 79% with no history of an adverse reaction to stings, more than 12% had positive VST. The frequency of positive VST decreased with the time since the last sting; further, the positive VST were not related to inhalant allergy or to a family history of insect allergy. These data indicate that the prevalence of sensitivity to insect stings is far greater than previously appreciated: fully 25% of the population is affected by virtue of a positive history and/or positive VST. The immunologic and clinical significance of these findings are being examined by prospective observation of VST, antibody titers and the sequelae of future stings.
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124
A COMPARISON OF VENOM TREATMENT AND NO TREATMENT IN INSECT ALLERGIC CHILDREN. K.C. Schuberth, M.D., A. Kagey-Sobotka~ Ph.D., K. Kwiterovlch, B.S.N., D.F. Graft, M.D., M. Szklo, M.D., L.M. Lichtenstein, M.D., and M.D. Valentine, M.D., Baltimore, MD. We evaluated 563 children (age 3-16 years) with a history of allergic reactions to Hymenoptera stings. 148 had life-threatening systemic reactions (LTR), 262 had non-life-threatening systemic reactions (NLTR) and 124 had large local reactions (LLR). Approximately 88% of each group had positive venom skin tests. To assess the risk/benefit ratio of venom therapy, NLTR patients (pts) with positive ST were either randomly assigned or self-selected to: venom therapy (T) (69 pts) or emergency precautions only (NT) (151 pts). 56 accidental field stings in the T pts produced 1 mild systemic reaction (reaction rate 1.8%); in the NT group, 132 stings produced only 9 mild systemic reactions (6.8%) (p=NS). 9/10 of the systemic reactions were milder than the original. LLR following subsequent stings occurred less frequently in the T than the NT pts (5% vs 33%, p <.001). Repeat ST after two years were done in 93 NLTR pts (32 T, 61 NT); 57% had at least a 10fold drop in sensitivity (72% T, 49% NT). Unstung pts were more likely to show decreased sensitivity than those stung (76% vs 42%). The low reaction rate to subsequent stings, the lack of serious reactions and the decreases in ST sensitivity suggest that the added protection offered by venom therapy may not justify its use for this selected group of children.