EurJ Clin Pharmacol (1991) 41:621
5>[hG sQc®rleg @ Springer-Verlag 1991
Letters to the editors
Effect of inhaled morphine on the bronchial response to isocapnic hyperventilation in patients with allergic asthma M. Mestiri 1, A . L u r i e 1' 2, N . Frossard 1, A . L o c k h a r t ~, J. M a r s a c 1, G. S t r a u c h 2, a n d J. F. D e s s a n g e s 1
J D6partement des Maladies Respiratoires and 2 Eclimed~InstitutdeRechercheTh6rapeutique~H6pita~UniversitaireC~chin~Paris~France Received: July 24,1990/Accepted in revised form: November 24, 1990
K e y words: Asthma, Morphine; hyperventilation, non-
adrenergic non-cholinergic nervous system, inhalation treatment
The cholinergic and non-cholinergic excitatory systems have a bronchoconstrictor effect in asthma through local release of acetylcholine and neuropeptides, respectively [1]. W h e t h e r release of such neuromediators is involved in isocapnic hyperventilation (IH)-induced asthma is not firmly established. Since opiates are capable of inhibiting the release of neuromediators in guinea-pig airways, prevention by opiates of such a bronchial response would favour the importance of the release of neuromediators in mediating IH-induced asthma [2-4]. Nine atopic asthmatic subjects underwent a multistep I H challenge whilst breathing dry air at r o o m t e m p e r a ture. T h e y were pretreated with inhaled saline or morphine hydrochloride 10 mg on two different days, in a double blind randomized cross-over design. Successive levels of ventilation (10, 20, 40 and 80% of maximal voluntary ventilation) were maintained for 3 min. A t each step, forced expiratory volume in 1 s (FEV1) was serially measured. Table 1. Baseline, post-inhalation and lowest post-hyperventilation
FEV1 (forced expiratory volume in i s) Subject FEV1(% predicted) Baseline Post-inhalation
1 2 3 4 5 6 7 8 9 Mean (SD)
Post-hyperventilation Saline Morphine Saline Morphine Saline Morphine 98.7 111 89.7 115 41.3 58.6 95.3 106 94.9 103 80.5 86.4 87.1 91.2 94.9 84.7 82.3 61.0 102 101 97.1 96.4 76.3 82.9 93.8 101 95.9 91.0 47.9 47.9 111 115 102 115 60.1 79.8 I05 102 103 104 79.6 66.5 78.8 82.3 72.3 80.0 61.4 71.9 124 127 120 121 80.6 87.0 99.5 104 96.7 101 67.8 71.3 (13.1) (13.0) (12.6) (14.3) (15.6) (13.8)
Inhalation of morphine was well tolerated. Inhaled morphine or normal saline did not cause a significant change in baseline FEV1 (Table 1). A f t e r the highest level of IH, a m a r k e d fall in FEV1 occured, which was not statistically different after morphine or saline (Table 1). Thus, the lack of effect of morphine on baseline FEV1 suggests that morphine does not activate mast cells in h u m a n airways in vivo as it does to h u m a n skin mast cells in vivo [5]. It is only possible to suggest possible explanations for the lack of a preventive effect of morphine on I H induced asthma: (a) release of neuromediators does not mediate the bronchial response to IH; (b) the effect of morphine might already have been waning towards the end of the I H challenge; and (c) the local morphine concentration was too low. However, the dose of morphine delivered here was similar to that inhibiting capsaicininduced bronchial obstruction [6]. References
1. Barnes PJ (1986) Neural control of human airways in health and disease. Am Rev Respir Dis 134:1289-1314 2. Frossard N, Barnes PJ (1987) g opioid receptors modulate noncholinergic constrictor nerves in guinea-pig airways. Eur J Pharmaco1141: 519-522 3. Belvisi MG, Stretton CD, Barnes PJ (1990) Modulation of cholinergic neurotransmission in guinea-pig airways by opioids. Am Rev Respir Dis 141: A 846 4. Wilson N, Dixon C, Silverman M (1984) Bronchial responsiveness to hyperventilation in children with asthma: inhibition by ipratropium bromide. Thorax 39:588-593 5. Ebertz JM, Hermens JM, McMillan JC, Uno H, Hirshman C, Hanifin JM (1986) Functional differences between human cutaneous mast cells and basophils. A comparison of morphine-induced histamine release. Agents Actions 18:455-462 6. Fuller RW, Karlsson JA, Choudry NB, Pride NB (1988) Effect of inhaled and systemic opiates on responses to inhaled capsaicin in humans. J Appl Physio165:1125-1130 Dr. A. Lurie Eclimed-Institut de Recherche Th6rapeutique H6pital Universitaire Cochin 27 rue du Faubourg Saint-Jacques F-75674 Paris Cedex 14, France
5>[hG sQc®rleg @ Springer-Verlag 1991
Letters to the editors
Effect of inhaled morphine on the bronchial response to isocapnic hyperventilation in patients with allergic asthma M. Mestiri 1, A . L u r i e 1' 2, N . Frossard 1, A . L o c k h a r t ~, J. M a r s a c 1, G. S t r a u c h 2, a n d J. F. D e s s a n g e s 1
J D6partement des Maladies Respiratoires and 2 Eclimed~InstitutdeRechercheTh6rapeutique~H6pita~UniversitaireC~chin~Paris~France Received: July 24,1990/Accepted in revised form: November 24, 1990
K e y words: Asthma, Morphine; hyperventilation, non-
adrenergic non-cholinergic nervous system, inhalation treatment
The cholinergic and non-cholinergic excitatory systems have a bronchoconstrictor effect in asthma through local release of acetylcholine and neuropeptides, respectively [1]. W h e t h e r release of such neuromediators is involved in isocapnic hyperventilation (IH)-induced asthma is not firmly established. Since opiates are capable of inhibiting the release of neuromediators in guinea-pig airways, prevention by opiates of such a bronchial response would favour the importance of the release of neuromediators in mediating IH-induced asthma [2-4]. Nine atopic asthmatic subjects underwent a multistep I H challenge whilst breathing dry air at r o o m t e m p e r a ture. T h e y were pretreated with inhaled saline or morphine hydrochloride 10 mg on two different days, in a double blind randomized cross-over design. Successive levels of ventilation (10, 20, 40 and 80% of maximal voluntary ventilation) were maintained for 3 min. A t each step, forced expiratory volume in 1 s (FEV1) was serially measured. Table 1. Baseline, post-inhalation and lowest post-hyperventilation
FEV1 (forced expiratory volume in i s) Subject FEV1(% predicted) Baseline Post-inhalation
1 2 3 4 5 6 7 8 9 Mean (SD)
Post-hyperventilation Saline Morphine Saline Morphine Saline Morphine 98.7 111 89.7 115 41.3 58.6 95.3 106 94.9 103 80.5 86.4 87.1 91.2 94.9 84.7 82.3 61.0 102 101 97.1 96.4 76.3 82.9 93.8 101 95.9 91.0 47.9 47.9 111 115 102 115 60.1 79.8 I05 102 103 104 79.6 66.5 78.8 82.3 72.3 80.0 61.4 71.9 124 127 120 121 80.6 87.0 99.5 104 96.7 101 67.8 71.3 (13.1) (13.0) (12.6) (14.3) (15.6) (13.8)
Inhalation of morphine was well tolerated. Inhaled morphine or normal saline did not cause a significant change in baseline FEV1 (Table 1). A f t e r the highest level of IH, a m a r k e d fall in FEV1 occured, which was not statistically different after morphine or saline (Table 1). Thus, the lack of effect of morphine on baseline FEV1 suggests that morphine does not activate mast cells in h u m a n airways in vivo as it does to h u m a n skin mast cells in vivo [5]. It is only possible to suggest possible explanations for the lack of a preventive effect of morphine on I H induced asthma: (a) release of neuromediators does not mediate the bronchial response to IH; (b) the effect of morphine might already have been waning towards the end of the I H challenge; and (c) the local morphine concentration was too low. However, the dose of morphine delivered here was similar to that inhibiting capsaicininduced bronchial obstruction [6]. References
1. Barnes PJ (1986) Neural control of human airways in health and disease. Am Rev Respir Dis 134:1289-1314 2. Frossard N, Barnes PJ (1987) g opioid receptors modulate noncholinergic constrictor nerves in guinea-pig airways. Eur J Pharmaco1141: 519-522 3. Belvisi MG, Stretton CD, Barnes PJ (1990) Modulation of cholinergic neurotransmission in guinea-pig airways by opioids. Am Rev Respir Dis 141: A 846 4. Wilson N, Dixon C, Silverman M (1984) Bronchial responsiveness to hyperventilation in children with asthma: inhibition by ipratropium bromide. Thorax 39:588-593 5. Ebertz JM, Hermens JM, McMillan JC, Uno H, Hirshman C, Hanifin JM (1986) Functional differences between human cutaneous mast cells and basophils. A comparison of morphine-induced histamine release. Agents Actions 18:455-462 6. Fuller RW, Karlsson JA, Choudry NB, Pride NB (1988) Effect of inhaled and systemic opiates on responses to inhaled capsaicin in humans. J Appl Physio165:1125-1130 Dr. A. Lurie Eclimed-Institut de Recherche Th6rapeutique H6pital Universitaire Cochin 27 rue du Faubourg Saint-Jacques F-75674 Paris Cedex 14, France
