Comparative efficacy of salbutamol via metered dose inhaler with spacer and dry powder inhaler, easyhaler, in the treatment of mechacholine induced bronchoconstriction

Comparative efficacy of salbutamol via metered dose inhaler with spacer and dry powder inhaler, easyhaler, in the treatment of mechacholine induced bronchoconstriction

J ALLERGY CLIN IMMUNOL VOLUME 109, NUMBER 1 Mercedes Ferrero§, Carlos CuretS, Dante Beltramo~ *Misericordia Hospital, Crrdoba, Argentina §Misericordi...

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Mercedes Ferrero§, Carlos CuretS, Dante Beltramo~ *Misericordia Hospital, Crrdoba, Argentina §Misericordia Hospital, Cordoba, Argentina ¥Coat, C6rdoba, Argentina CCeprocor, C6rdoba, Argentina Autoimmune inner ear diseases are of unknown etiology. Recent evidences indicate that autoimmune inner ear diseases could be an immunologic disorder, but clinical trials have failed to show increased prevalence of atopy in these patients. The purpose of this work was to investigate the presence of specific IgG and IgE antibodies in sera of autoimmune inner disease patients against 2 antigens by ELISA. The antigens used were bovine type II collagen, and alternaria. We have also studied the immediate skin test reaction to 8 common aero-allergens of C6rdoba city, Argentina such as: C Tala, grasses, ragweed, cat, Der pt, alternaria, cladosporium, aspergillus. The measurement of intradermal skin test was performed following Norman's scale. We have assayed 54 autoimmune inner ear disease and 30 control sera. The inner ear autoimmune group presented specific IgG to collagen II (+) in 44 of 54 cases, overlapping specific IgE and IgG to collagen 1I in 4 of 54 cases, and 6 of 54 were negative to both antibodies to collagen II. The specific IgG to alternaria was positive in 20 of 54 cases, and specific lgE to alternaria was positive in 10 of 54 cases. The intradermal skin test to alternaria was positive in 35 of 54 cases. The other antigens were negative in 46 of 54 cases of autoimmune inner ear disease as well as in 27 of 30 in the control group. These findings suggest that specific IgE and IgG for allergen of Alternaria could induce, drive or facilitate the process in inner ear autoimmune disease.

Estrogen and Progesterone Differentially Modulate Cell U I , WCycling, Apoptosis, and Response to Lipopolysaccharide in Monocyte Cell Lines


Torpong Thongngarm*, John K Jenkins§, Robert W McMurray§ *National Jewish Medical and Research Center, Denver, CO §University of Mississippi Medical Center, Jackson, MS BACKGROUND: Corticosteroids are known to regulate endotoxininduced cytokine production, alter cell cycle progression, and induce apoptosis in monocytes. Little is known regarding the effects on gonadal steroids on myelomonocytic cell cycle progression or apoptosis. OBJECTIVE: We used five myelomonocytic cell lines in various stages of differentiation to examine the effects of lipopolysaccharide, estrogen and progesterone and combinations of them on cell cycling, apoptosis and bcl-2 expression. METHODS: Proliferation was measured non radioactively. Cell cycle phase distribution and apoptosis was studied by flow cytometry of propidium iodide stained cells. Bcl-2 was examined by Western blot analysis. Estrogen and progesterone receptors were measured by enzyme immunoassay. RESULTS: Lipopolysaccharide inhibited cell cycle progression in U937, THP-1 and K-562 cells. Estrogen induced accumulation of all cells in S/G2/M except HL-60 cells. Progesterone had no effect on KG- la, THP- 1, or U-937, but significantly reduced the percentage of HL-60 and K-562 in S/G2/M phases. Progesterone induced apoptosis in HL-60. Differential effects of estrogen and progesterone did not correlate with hormone receptor expression. Estrogen and progesterone decreased levels of bcl-2 in THP- 1, KG- 1a and HL-60 cells. Both sex hormones increased bcl-2 protein in U-937 cells. Lipopolysaccharide antagonized both estrogen-induced THP-1 apoptosis and reduction of bcl-2 protein. CONCLUSION: Sex hormones have a role in mediating monocyte proliferation or apoptosis and Bcl-2 may be a mediator of these effects in monocytes. Further investigation should provide a better understanding of sex-based differences in monocyte function and immunologic responses.

707 Impact of Decreasing Doses of Racemic Albuterol and Levalbuterol on Efficacy: A Pooled Analysis Louis Vaickus, Kendyl Schaefer, Raymond Claus Sepracor Incorporated, Marlborough, MA Doses of ~-agonists are routinely decreased in an effort to reduce ~mediated side effects, especially in the young and old. However, the impact of dose-reduction on efficacy has not been thoroughly evaluated. Racemic



albuterol (Rac) is a 50:50 mix of (R)-albuterol (Levalbuterol, Lev) and (S)albuterol. Lev 0.63rag is clinically comparable to Rac 2.5rag with fewer side effects. To determine whether decreasing the dose of Rac or Lev effects efficacy, data from 4 asthma studies were pooled (2 pediatric and 2 adult studies, age 4-80 yrs, n=1538). Immediately post-treatment with Lev 0.63 or 1.25mg, Rac 1.25 or 2.5mg, or placebo, serial pulmonary function tests were performed. Lev 1.25 consistently produced changes that were significantly greater than Rac 2.5 (FEV 1 mean % change and % change 15 min post-dose, p<0.02), and significantly greater than Rac 1.25 and Lev 0.63. Lev 0.63 was not significantly different than Rac 2.5 for any FEV 1 parameters or in the % of patients responding 15 min post-dose. However, decreasing the Rac dose to 1.25 significantly decreased efficacy compared to all other active treatments (p<0.001). There were significantly fewer responders in the Rac 1.25 group compared with Lev 0.63 and Rac 2.5, and a trend for more responders was noted in favor of Lev 1.25 compared with Rac 1.25 (p=0.076). The rank order of efficacy was Lev 1.25 > Lev 0.63 = Rac 2.5 > Rac 1.25. Decreasing the dose of Lev from 1.25 to 0.63 resulted in efficacy that was significantly less than Lev 1.25, but not significantly different than Rac 2.5. Decreasing the dose of Rac to 1.25 produced a significant reduction in efficacy compared with all other active treatments, and was effective in significantly fewer patients. These data demonstrated that decreasing the dose of Rac resulted in suboptimal therapy. Pulmonary Functional Parameters

Placebo (n--361) FEVt: Mean % Chg FEVI: Peak % Chg FEVt: % Chg, Time 15 % Responders, Time 15

10.6 (0.96) 22.6 (1.15) 8.8 (1.07) 25.8

Lev 0.63 Lev 1.25 Rac 1.25 Rac 2.5 (n=373) (n=292) (n=151) (n--367) 26.9*+# (0.95) 40.5*+# (1.13) 32.5*+# (1.05) 82.2*@

32.7*&~ (1.07) 46.0*&# (1.28) 38.4*&#~ (1.18) 85.9*

20.4*&~" (1.49) 32.2*&+^ (1.78) 24.1*&+~ (1.64) 64.9*~;

29.3*+# (0.96) 42.9*+# (1.14) 33.6*+# (1.05) 81.7"$

LSMeans (SEM) presented; Responder: FEV l (change from baseline) >15%; Time 15=15 rain post-dose; *0.001 vs placebo; &0.001 vs Lev 0.63; +0.003 vs Lev 1.25; #0.001 vs Rac 1.25; ^0.02 vs Rac 2.5; $p=0.036 vs Rac 2.5 and 0.017 vs Lev 0.63; @p=0.017 vs Rac 1.25; $p=0.017 vs Rac 1.25.


Comparative Efficacy of Salbutamol via Metered Dose Inhaler

Spacer and Dry Powder Inhaler, Easyhaler, in the Treat7~llJeU With ment of Methacholine Induced Bronchoconstriction Charerat Direkwattanachai, Narida Tarvornpanich, Suwat Benjaponpitak Pediatric Allergy Division, Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand OBJECTIVE: To compare the clinical efficacy of salbutamol inhaled via dry powder inhaler, easyhaler, and pressurized metered - dose inhaler with spacer in the treatment of methacholine induced bronchoconstriction. M E T H O D S : Thirty - two pediatric asthmatic patients were included in the study. Methacholine bronchial challenge test was performed by the tidal breathing method, using increasing concentrations until a fall in forced expiratory volume in 1 second [FEV1] greater than or equal to 20% was achieved. The patients then inhaled 2 dose of 100 microgram of salbutamol via either easyhaler or pMDI with spacer randomly. The bronchodilating effect was determined by measuring FEV1 before and after methacholine challenge test and 5, 10, 15, 30,45, 60 min after salbutamol inhalation. RESULTS: No statistically significant differences were noted in efficacy variables between the inhalers. The mean maximum percentage of improvement in FEV1 from the post challenge value were 87.15 [SD 40.85] and 85.02 [SD 51.68] with easyhaler and pMDI with spacer respectively. However, the onset of bronchodilation [FEVI ] was faster with pMDI with spacer. CONCLUSION: We conclude that easyhaler and pMDI with spacer produce equal bronchodilation in the treatment of methacholine induced brouchoconstriction in asthmatic children.