Management of COPD & Asthma Melissa Brittle & Jessica Macaro.
Dose of inhaled β2-agonists in asthma
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684 exerted no discernible effect on the L-arginine-induced hypotension. To examine if NO was responsible for the observed hypotension we measured plasma concentrations of L-arginine and L-citrulline’ (by high-performance liquid chromatography), cyclic guanosine monophosphate (cGMP), and several hormones (atrial natriuretic peptide, plasma renin activity, aldosterone arginine vasopressin, noradrenaline, and adrenaline) by radioimmunoassay. The mean plasma concentration of L-arginine after L-arginine infusion was lower than others predicted.3 L-citrulline, the by-product of NO synthesis from L-arginine and cGMP, the second messenger for NO,5 significantly increased: Plasma concentrations of hormones changed slightly with L-arginine infusion, but these changes were too small to affect haemodynamics. We also measured cardiac output, by the thoracic electrical bioimpedance method and mean arterial blood pressure by automated monitor, to calculate total peripheral resistance. Cardiac output increased, and total peripheral resistance fell. This result shows that L-arginine does cause vasodilatation. Finally, urinary nitrate concentrations increased significantly with L- arginine infusion. The stereospecificty of L-arginine-induced hypotension and vasodilatation in man remains to be clarified since we cannot infuse D-arginine and competitive L-arginine-antagonists such as NG- monomethyl-L-arginine. However, laboratory animal studies have shown that N-nitro-L-arginine significantly inhibited L-arginine- induced hypotension and that L-glycine, L-asparagine, and L-alanine did not affect systemic arterial pressure.** The only known source of endogenous nitrate in mammals is NO formation by the L-arginine-NO pathway.7,8 These results support our previous interpretation: that systemic cardiovascular effects of L-arginine infusion are due to NO release. Departments of Internal Medicine and Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan KEIICHI HISHIKAWA TOSHIO NAKAKI HIROMICHI SUZUKI TAKAO SARUTA RYUICHI KATO 1. Nakaki T, Hishikawa K, Suzuki H, Saruta T, Kato R. L-arginine-induced hypotension. Lancet 1990; 336: 696 2. Paton WDM. L-argmine-induced hypotension. Lancet 1990; 336: 1016. 3. Calver A, Collier J, Vallance P L-arginine-induced hypotension. Lancet 1990; 336: 1016-17. 4. Palmer RMJ, Moncada S A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun 1989; 158: 348-52. 5. Moncada S, Palmer RMJ, Hibbs A Biosynthesis of nitric oxide from L-arginine. Biochem Pharmacol 1989; 38: 1709-15. 6. Cernades MR, Riesco A, Gallego MJ, et al. L-arginine-induced hypotension. Lancet 1990; 336: 1017. 7. Wennmalm Å, Lanne B, Peterson AS. Detection of endothelial-derived relaxing factor in human plasma in the basal state and following ischemia using electron paramagnetic resonance spectrometry. Anal Biochem 1990; 187: 359-63. 8. Cynthia D, Wishnok LJ, Tannenbaum SR. L-arginine is a precursor for nitrate biosynthesis in humans. Biochem Biophys Res Commun 1989; 163: 1032-37. Dose of inhaled &bgr;2-agonists in asthma SIR,-Inflammatory changes in asthma are associated with enhanced bronchial responsiveness and obstruction. The presence of inflammation even in mild asthma suggests that anti- inflammatory treatment with inhaled steroids should be introduced as first-line therapy, which is supplemented only with inhaled bronchodilators. Regular inhalation of &bgr;2-agonists may even deteriorate asthma control’ and increase bronchial responsiveness.2 We have tested the hypothesis that low doses of salbutamol are as effective as higher doses in asthmatic patients who are in good clinical condition while regularly inhaling budesonide (mean daily dose 1 6 mg) or beclomethasone dipropionate (mean daily dose 1-2 Mean % changes in FEV, values after inhalation of 25 ([]), 50 (0), and 100 (.) ).1g doses of salbutamol or placebo (0) aerosol. Additional 200 ).19 dose of inhaled salbutamol 35 min after first inhalation mg). Nine women and six men who were non-smokers (mean age 50 years, range 20-64; mean duration of asthma 11 years, range 0 5-35) inhaled a single dose of salbutamol (25, 50, and 100 gg) and placebo from a metered dose inhaler. This randomised, double-blind, placebo controlled, crossover study was done in the morning for 4 days. Patients were without any &bgr;2-agonists for 12 h before inhalation of the test drug or placebo. The mean basal FEV1 was 70% (SD 18) of predicted values3 and did not differ by more than 20% between test days. FEV was recorded with a ’Vitalograph Compact’ spirometer before and 15 and 30 minutes after inhalation. 35 minutes after first inhalation patients inhaled 200 pg of salbutamol to establish if there was any further bronchodilatation, Data were analysed with two-way ’Anova’ and Scheffe’s test. All salbutamol doses produced a significant rise (p < 0,05) in FEVi values—8-10% after 15 minutes and 11-13% after 30 minutes. The increase with placebo was 4% (not significant). There were no significant differences between 25, 50, and 100 pg doses of salbutamol with respect to bronchodilatory effect (figure). The additional 200 Ilg salbutamol caused a 3-5% increase in FEV, values when inhaled after the active doses (not significant) and an increase of 10% was achieved when the drug was inhaled after placebo (p < 0-05). These results show that present salbutamol doses are unnecessarily high when given to complement the treatment with adequate anti-inflammatory therapy. There is no need for maximum bronchodilatation; in normal airways slight physiological bronchconstriction exists. If regular treatment at present doses of &bgr;2-agonists may even worsen asthma, the trend for &bgr;2-agonist therapy should be towards lower doses and use as needed. Department of Allergic Diseases, Helsinki University Central Hospital, 00250 Helsinki, Finland Orion Pharmaceutica, PO Box 1, Kuopio TARI HAAHTELA ARVID NYBERG KARI LAURIKAINEN MATTI SILVASTI MIKA VIDGREN 1. Sears MR, Taylor DR, Print CG, et al. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet 1990, 336: 1391-96. 2. Van Schayck CP, Graafsma SJ, Visch MB, Dompeling E, van Weel C, Herwaarden CLA. Increased bronchial hyperresponsiveness after inhaling salbutamol during 1 year is not caused by subsensitization to salbutamol. J Allergy Clin Immunol 1990; 86: 739-800. 3 Viljanen AA, Halttunen PK, Kreus K-E, Viljanen BC. Spirometric studies in non-smoking healthy adults. Scand J Clin Lab Invest 1982; 42 (suppl 159) 5-20 CORRECTION Genital carcinomas in psoriasis patients treated with photochemotherapy-In this letter by Prof K. Wolff and Prof H. Honigsmann (Feb 16, p 439), herpesvirus infection (paragraph 4, line 6 should have read human papillomavirus infection.
Transcript of Dose of inhaled β2-agonists in asthma
684
exerted no discernible effect on the L-arginine-inducedhypotension. To examine if NO was responsible for the observedhypotension we measured plasma concentrations of L-arginine andL-citrulline’ (by high-performance liquid chromatography), cyclicguanosine monophosphate (cGMP), and several hormones (atrialnatriuretic peptide, plasma renin activity, aldosterone argininevasopressin, noradrenaline, and adrenaline) by radioimmunoassay.The mean plasma concentration of L-arginine after L-arginineinfusion was lower than others predicted.3 L-citrulline, the
by-product of NO synthesis from L-arginine and cGMP, thesecond messenger for NO,5 significantly increased:
Plasma concentrations of hormones changed slightly with
L-arginine infusion, but these changes were too small to affecthaemodynamics. We also measured cardiac output, by the thoracicelectrical bioimpedance method and mean arterial blood pressureby automated monitor, to calculate total peripheral resistance.Cardiac output increased, and total peripheral resistance fell. Thisresult shows that L-arginine does cause vasodilatation. Finally,urinary nitrate concentrations increased significantly with L-arginine infusion.The stereospecificty of L-arginine-induced hypotension and
vasodilatation in man remains to be clarified since we cannot infuse
D-arginine and competitive L-arginine-antagonists such as NG-monomethyl-L-arginine. However, laboratory animal studies haveshown that N-nitro-L-arginine significantly inhibited L-arginine-induced hypotension and that L-glycine, L-asparagine, andL-alanine did not affect systemic arterial pressure.** The only knownsource of endogenous nitrate in mammals is NO formation by theL-arginine-NO pathway.7,8 These results support our previousinterpretation: that systemic cardiovascular effects of L-arginineinfusion are due to NO release.
Departments of Internal Medicineand Pharmacology,
Keio University School of Medicine,35 Shinanomachi, Shinjuku-ku,Tokyo 160, Japan
KEIICHI HISHIKAWATOSHIO NAKAKIHIROMICHI SUZUKITAKAO SARUTARYUICHI KATO
1. Nakaki T, Hishikawa K, Suzuki H, Saruta T, Kato R. L-arginine-inducedhypotension. Lancet 1990; 336: 696
2. Paton WDM. L-argmine-induced hypotension. Lancet 1990; 336: 1016.3. Calver A, Collier J, Vallance P L-arginine-induced hypotension. Lancet 1990; 336:
1016-17.
4. Palmer RMJ, Moncada S A novel citrulline-forming enzyme implicated in theformation of nitric oxide by vascular endothelial cells. Biochem Biophys ResCommun 1989; 158: 348-52.
5. Moncada S, Palmer RMJ, Hibbs A Biosynthesis of nitric oxide from L-arginine.Biochem Pharmacol 1989; 38: 1709-15.
6. Cernades MR, Riesco A, Gallego MJ, et al. L-arginine-induced hypotension. Lancet1990; 336: 1017.
7. Wennmalm Å, Lanne B, Peterson AS. Detection of endothelial-derived relaxing factorin human plasma in the basal state and following ischemia using electron
paramagnetic resonance spectrometry. Anal Biochem 1990; 187: 359-63.8. Cynthia D, Wishnok LJ, Tannenbaum SR. L-arginine is a precursor for nitrate
biosynthesis in humans. Biochem Biophys Res Commun 1989; 163: 1032-37.
Dose of inhaled &bgr;2-agonists in asthmaSIR,-Inflammatory changes in asthma are associated with
enhanced bronchial responsiveness and obstruction. The presenceof inflammation even in mild asthma suggests that anti-
inflammatory treatment with inhaled steroids should be introducedas first-line therapy, which is supplemented only with inhaledbronchodilators. Regular inhalation of &bgr;2-agonists may evendeteriorate asthma control’ and increase bronchial responsiveness.2We have tested the hypothesis that low doses of salbutamol are as
effective as higher doses in asthmatic patients who are in goodclinical condition while regularly inhaling budesonide (mean dailydose 1 6 mg) or beclomethasone dipropionate (mean daily dose 1-2
Mean % changes in FEV, values after inhalation of 25 ([]), 50(0), and 100 (.) ).1g doses of salbutamol or placebo (0)aerosol.
Additional 200 ).19 dose of inhaled salbutamol 35 min after firstinhalation
mg). Nine women and six men who were non-smokers (mean age 50years, range 20-64; mean duration of asthma 11 years, range 0 5-35)inhaled a single dose of salbutamol (25, 50, and 100 gg) and placebofrom a metered dose inhaler. This randomised, double-blind,placebo controlled, crossover study was done in the morning for4 days. Patients were without any &bgr;2-agonists for 12 h beforeinhalation of the test drug or placebo. The mean basal FEV1 was70% (SD 18) of predicted values3 and did not differ by more than20% between test days. FEV was recorded with a ’VitalographCompact’ spirometer before and 15 and 30 minutes after inhalation.35 minutes after first inhalation patients inhaled 200 pg ofsalbutamol to establish if there was any further bronchodilatation,Data were analysed with two-way ’Anova’ and Scheffe’s test.
All salbutamol doses produced a significant rise (p < 0,05) inFEVi values—8-10% after 15 minutes and 11-13% after 30minutes. The increase with placebo was 4% (not significant). Therewere no significant differences between 25, 50, and 100 pg doses ofsalbutamol with respect to bronchodilatory effect (figure). Theadditional 200 Ilg salbutamol caused a 3-5% increase in FEV,values when inhaled after the active doses (not significant) and anincrease of 10% was achieved when the drug was inhaled afterplacebo (p < 0-05).These results show that present salbutamol doses are
unnecessarily high when given to complement the treatment withadequate anti-inflammatory therapy. There is no need formaximum bronchodilatation; in normal airways slight physiologicalbronchconstriction exists. If regular treatment at present doses of&bgr;2-agonists may even worsen asthma, the trend for &bgr;2-agonisttherapy should be towards lower doses and use as needed.
Department of Allergic Diseases,Helsinki University Central Hospital,00250 Helsinki, Finland
Orion Pharmaceutica,PO Box 1, Kuopio
TARI HAAHTELAARVID NYBERG
KARI LAURIKAINENMATTI SILVASTIMIKA VIDGREN
1. Sears MR, Taylor DR, Print CG, et al. Regular inhaled beta-agonist treatment inbronchial asthma. Lancet 1990, 336: 1391-96.
2. Van Schayck CP, Graafsma SJ, Visch MB, Dompeling E, van Weel C, HerwaardenCLA. Increased bronchial hyperresponsiveness after inhaling salbutamol during1 year is not caused by subsensitization to salbutamol. J Allergy Clin Immunol1990; 86: 739-800.
3 Viljanen AA, Halttunen PK, Kreus K-E, Viljanen BC. Spirometric studies in
non-smoking healthy adults. Scand J Clin Lab Invest 1982; 42 (suppl 159) 5-20
CORRECTION
Genital carcinomas in psoriasis patients treated with
photochemotherapy-In this letter by Prof K. Wolff and Prof H.
Honigsmann (Feb 16, p 439), herpesvirus infection (paragraph 4, line 6should have read human papillomavirus infection.
![Research Paper Deguelin Attenuates Allergic Airway ...Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling, ... pathophysiology of asthma [4].](https://static.fdocument.org/doc/165x107/6021eed39e87047b88365ced/research-paper-deguelin-attenuates-allergic-airway-asthma-is-a-chronic-respiratory.jpg)
