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803 Monozygotic twins as a model for study in asthma
J ALLERGY CLIN IMMUNOL VOLUME 97, NUMBER 1, PART3
801
In-Vitro Assessment of A New Efficient N e b u l i z e r
Abstracts
803
T - C e l l R e c e p t o r VII G e n e U s a g e in B A L T - C e l l s in H e a R h a n d in A s t h m a . J Dasmahavatra. E A Hedges, A E R e d i n e t o n . T Krishna. A W Bovlston. ST Holeate. JL Smith & AJ F r e w S o u t h a m p t o n & L e e d s U K T-cell receptor (TcR) Vfi repertoires o f peripheral blood and B A L C D 4 + and C D 8 + T-cells w e r e studied by 3-colour flow c y t o m e t r y using a panel o f monoclonal antibodies to 16 TcR-VI~ families. All 16 VI~ families were present in varying p r o p o r t i o n s in the 3 normal and 3 asthmatic subjects studied. In all 6 subjects, TcR usage in B A L C D 8 + T-cells was similar to that in peripheral blood. In B A L C D 4 + T-cells, there was overrepresentation o f VB7.1 in all normal and asthmatic subjects. In the normal subjects the other T c R VB families w e r e expressed in proportion to the peripheral blood usage. In the asthmatic subjects a n u m b e r o f additional T c R VI~ families w e r e also expanded. B A L T-cells bearing VI~20 and VIH2.1 were expanded in all 3 asthmatics; Vf~5.2/5.3, Vfil4 were e x p a n d e d in 2/3 asthmatics while Vf;22 w a s e x p a n d e d in 1/3. P C R analysis and s e q u e n c i n g o f T c R m R N A f r o m two o f the asthmatic B A L s revealed that the overrepresentation o f VB7.1 was due to polyclonal expansion but B A L T-cells expressing V134 w e r e oligoclonal. T h e s e data indicate that VB7.1 may b e a m a r k e r o f an airways-specific T-cell subset while the other e x p a n d e d T c R families are consistent with either a superantigenie stimulus o r a u t o i m m u n e process.
Monozygotic Twins as a M o d e l f o r Study in A s t h m a ME Miller ME) G Leikauf PhD JA Bernstein MD Cincinnati, Ohio While it is postulated that asthma results from allergic and nonallergic environmental exposure in persons with a genetic susceptibility, the exact role of these variables is unclear. Monozygotic twins are an ideal study population because of their identical genetic background, similar childhood environmental exposures and their expected high concordance rate for asthma. Using a newly developed and validated questionnaire (p < 0.0001), we have collected data on 36 pairs of monozygotic twins over a two year period. Although 20 pairs of twins were concordant (C) for asthma, 16 pairs were discordant (D) for the disease. Demographic analysis of the groups revealed a striking difference in the median age ( 19.5 y for D v. 34 y for C twins). Kendall's analysis revealed strong correlations between self-reported allergies and a history of asthma (p=0.01) and between allergies and chronic cat exposure (p=0.03) but not between allergies and positive skin test results. Not surprisingly, a family history of asthma strongly correlated with a diminished FEV~ (p=0.003) and positive skin test results (p=0.01). Interestingly, a higher incidence of childhood tobacco exposure was noted among C twins. Using logistic regression analysis it was determined that this early environmental exposure is an independent risk factor for the development of asthma (p=0.02). Early tobacco exposure also correlated with a higher disease severity score (DSS) in adulthood (p=0.04). Prospective evaluation of monozygotie twins C and D for asthma promises to be a useful epidemiologio model for identifying the impact of environmental determinants in the development of clinical asthma.
S y s t e m F o r C o n t i n u o u s O p e r a t i o n . w Gutmann. M Knoch Ph D. E Wunderlich. Stamberg, Germany The output characteristics and the delivery efficiency of a new open-vent nebulizer (PARI LC PLUS) have been investigated in vitro. Droplet size distributions as well as output rates were measured under steady state conditions. Furthermore, the nebulizer was tested by using a breath simulator both during continuous and intermittent operation. Inspiratory and expiratory valves were fired to the system in order to direct air flow. The aerosol released from the nebulizer was collected on filters, representing the amounts of aerosol delivered and wasted. The results are compared to two continuously operated conventional nebulizers. The amount of aerosol delivered is twice as high for the two PAR/CL PLUS configurations (31% continuous versus 34% intermittent) compared to the conventional systems (15% and 17%, respectively). The results reflect the economic effect of an interrupter for on-command therapy and indicate that efficient drug delivery can also be achieved by continuously operated open-vent nebulizers equipped with a valve system.
802
383
804
P r o s p e c t i v e T w i n S t u d y o f I g E I m m u n e R e s p o n s e s in A c u t e O t i t i s M e d i a ( A O M ) . L Fireman BA, M Casselbrant MD PhD, B Ancelini BSN. P Fireman MD, Pittsburgh, PA A 5 year prospective study has provided data since birth on 132 healthy, same-sex twin pairs and 2 same-sex triplets who thus far had 1,356episodes of middle ear effusions diagnosed during 7,331 monthly ENT exams. The investigators were blinded as to twins zygosity and the patients' clinical course. Recurrent AOM (otitls prone) was defined as > 3AOM episodes during 6 months or >4AOM episodes in 12 months for infants followed for >24 months. Of 164 infants followed >24months, 16 (10%, including 5 twin pairs) were classified otitis prone. To ascertain if allergy was associated with expression of ear disease, 32 families (31 twin pairs and 1 triplet) volunteered for studies of total serum IgE and prick allergy skin tests to 20 aeroallergans at 3 years of age and was repeated in U of these twin pairs at 5 years. Of these 65 infants 12 (18%) including 2 twin pairs and 1 triplet had increased serum IgE and 25 (38%) including 7 twin pairs had positive allergy skin tests to one or at most 7 of the 20 inhalant allergens tested. Of the 12 with elevated IgE 9 (75%) had positive allergy skin tests. Only 3 (5%) of these 65 infants were categorized as otitis prone and these 3 infants all had normal serum IgE and were skin test negative. These preliminary data indicate the presence of IgE immune responses in 18 to 38% of the twins allergy tested; however, there does not appear to be an association with increased IgE immune responses thus far in the several otitis prone infants studied during the first 3 years of life. Studies of infants with chronic otitis and persistent middle ear effusion are in progress. (Supported by NIH grants DC01260 and AI19262.)
801
In-Vitro Assessment of A New Efficient N e b u l i z e r
Abstracts
803
T - C e l l R e c e p t o r VII G e n e U s a g e in B A L T - C e l l s in H e a R h a n d in A s t h m a . J Dasmahavatra. E A Hedges, A E R e d i n e t o n . T Krishna. A W Bovlston. ST Holeate. JL Smith & AJ F r e w S o u t h a m p t o n & L e e d s U K T-cell receptor (TcR) Vfi repertoires o f peripheral blood and B A L C D 4 + and C D 8 + T-cells w e r e studied by 3-colour flow c y t o m e t r y using a panel o f monoclonal antibodies to 16 TcR-VI~ families. All 16 VI~ families were present in varying p r o p o r t i o n s in the 3 normal and 3 asthmatic subjects studied. In all 6 subjects, TcR usage in B A L C D 8 + T-cells was similar to that in peripheral blood. In B A L C D 4 + T-cells, there was overrepresentation o f VB7.1 in all normal and asthmatic subjects. In the normal subjects the other T c R VB families w e r e expressed in proportion to the peripheral blood usage. In the asthmatic subjects a n u m b e r o f additional T c R VI~ families w e r e also expanded. B A L T-cells bearing VI~20 and VIH2.1 were expanded in all 3 asthmatics; Vf~5.2/5.3, Vfil4 were e x p a n d e d in 2/3 asthmatics while Vf;22 w a s e x p a n d e d in 1/3. P C R analysis and s e q u e n c i n g o f T c R m R N A f r o m two o f the asthmatic B A L s revealed that the overrepresentation o f VB7.1 was due to polyclonal expansion but B A L T-cells expressing V134 w e r e oligoclonal. T h e s e data indicate that VB7.1 may b e a m a r k e r o f an airways-specific T-cell subset while the other e x p a n d e d T c R families are consistent with either a superantigenie stimulus o r a u t o i m m u n e process.
Monozygotic Twins as a M o d e l f o r Study in A s t h m a ME Miller ME) G Leikauf PhD JA Bernstein MD Cincinnati, Ohio While it is postulated that asthma results from allergic and nonallergic environmental exposure in persons with a genetic susceptibility, the exact role of these variables is unclear. Monozygotic twins are an ideal study population because of their identical genetic background, similar childhood environmental exposures and their expected high concordance rate for asthma. Using a newly developed and validated questionnaire (p < 0.0001), we have collected data on 36 pairs of monozygotic twins over a two year period. Although 20 pairs of twins were concordant (C) for asthma, 16 pairs were discordant (D) for the disease. Demographic analysis of the groups revealed a striking difference in the median age ( 19.5 y for D v. 34 y for C twins). Kendall's analysis revealed strong correlations between self-reported allergies and a history of asthma (p=0.01) and between allergies and chronic cat exposure (p=0.03) but not between allergies and positive skin test results. Not surprisingly, a family history of asthma strongly correlated with a diminished FEV~ (p=0.003) and positive skin test results (p=0.01). Interestingly, a higher incidence of childhood tobacco exposure was noted among C twins. Using logistic regression analysis it was determined that this early environmental exposure is an independent risk factor for the development of asthma (p=0.02). Early tobacco exposure also correlated with a higher disease severity score (DSS) in adulthood (p=0.04). Prospective evaluation of monozygotie twins C and D for asthma promises to be a useful epidemiologio model for identifying the impact of environmental determinants in the development of clinical asthma.
S y s t e m F o r C o n t i n u o u s O p e r a t i o n . w Gutmann. M Knoch Ph D. E Wunderlich. Stamberg, Germany The output characteristics and the delivery efficiency of a new open-vent nebulizer (PARI LC PLUS) have been investigated in vitro. Droplet size distributions as well as output rates were measured under steady state conditions. Furthermore, the nebulizer was tested by using a breath simulator both during continuous and intermittent operation. Inspiratory and expiratory valves were fired to the system in order to direct air flow. The aerosol released from the nebulizer was collected on filters, representing the amounts of aerosol delivered and wasted. The results are compared to two continuously operated conventional nebulizers. The amount of aerosol delivered is twice as high for the two PAR/CL PLUS configurations (31% continuous versus 34% intermittent) compared to the conventional systems (15% and 17%, respectively). The results reflect the economic effect of an interrupter for on-command therapy and indicate that efficient drug delivery can also be achieved by continuously operated open-vent nebulizers equipped with a valve system.
802
383
804
P r o s p e c t i v e T w i n S t u d y o f I g E I m m u n e R e s p o n s e s in A c u t e O t i t i s M e d i a ( A O M ) . L Fireman BA, M Casselbrant MD PhD, B Ancelini BSN. P Fireman MD, Pittsburgh, PA A 5 year prospective study has provided data since birth on 132 healthy, same-sex twin pairs and 2 same-sex triplets who thus far had 1,356episodes of middle ear effusions diagnosed during 7,331 monthly ENT exams. The investigators were blinded as to twins zygosity and the patients' clinical course. Recurrent AOM (otitls prone) was defined as > 3AOM episodes during 6 months or >4AOM episodes in 12 months for infants followed for >24 months. Of 164 infants followed >24months, 16 (10%, including 5 twin pairs) were classified otitis prone. To ascertain if allergy was associated with expression of ear disease, 32 families (31 twin pairs and 1 triplet) volunteered for studies of total serum IgE and prick allergy skin tests to 20 aeroallergans at 3 years of age and was repeated in U of these twin pairs at 5 years. Of these 65 infants 12 (18%) including 2 twin pairs and 1 triplet had increased serum IgE and 25 (38%) including 7 twin pairs had positive allergy skin tests to one or at most 7 of the 20 inhalant allergens tested. Of the 12 with elevated IgE 9 (75%) had positive allergy skin tests. Only 3 (5%) of these 65 infants were categorized as otitis prone and these 3 infants all had normal serum IgE and were skin test negative. These preliminary data indicate the presence of IgE immune responses in 18 to 38% of the twins allergy tested; however, there does not appear to be an association with increased IgE immune responses thus far in the several otitis prone infants studied during the first 3 years of life. Studies of infants with chronic otitis and persistent middle ear effusion are in progress. (Supported by NIH grants DC01260 and AI19262.)