19 Interaction between hyperosmolar and IgE induced histamine release from basophils and mast cells

This study assessed the effect of the leukotriene receptor antagonist montelukast on hypertonic saline-induced airway obstruction.A total of 29 patients with chronic obstructive pulmonary disease (forced expiratory volume in one second (FEV1), 42 ¡ 4% predicted) received either 10 mg montelukast and 3 h later placebo via metered-dose inhaler (MDI) (M), or placebo and 3h later 200 mg salbutamol (S), or two doses of placebo (P), in a randomised order. Patients inhaled salbutamol 1 h after MDI and the challenge was performed 15 min later (3% saline, 5 min). Data are given as per cent changes versus baseline.Compared to P, S caused significant bronchodilation in FEV1 (7.3%) and forced inspiratory volume in one second (FIV1) (4.5%), and M in FIV1 (1.5%). The salineinduced fall in FEV1 was lower after M (-5.8%), compared with S (-10.3%) and P (-13.1%). FEV1 (11.3%) and FIV1 (7.6%) was improved over baseline after recovery by M but not P and S. Recovery times regarding FEV1 (8.5 min) and FIV1 (15.2 min) were shortest after M, respective values for S being 16.8 and 20.4 min, and for P 15.9 and 21.2 min. Effects were strongest in patients with low baseline FEV1 and/or inhaled corticosteroids.Data from this study indicate beneficial effects of montelukast on hypertonic salineinduced airway responses in patients with chronic obstructive pulmonary disease, particularly those with severe disease. The major effect was an accelerated recovery leading to values above baseline. Eur Respir J 2003; 22: 926-930.

Section: Discussionmentioning

confidence: 99%

Montelukast attenuates the airway response to hypertonic saline in moderate-to-severe COPD

Zühlke

Kanniess²,

Richter³

et al. 2003

“…Inhaled mannitol is thought to cause airways to narrow in asthmatics by a similar mechanism to exercise, that is by increasing the osmolarity of the airway surface liquid [8]. It is known that mediator secretion from mast cells, basophils and human lung fragments is triggered by increased osmolarity [11,12] and this release is inhibited with nedocromil sodium [13]. As with EIB, the airway response to mannitol may be modified by specific mediator antagonists [14].…”

mentioning

confidence: 99%

Evidence of mast cell activation and leukotriene release after mannitol inhalation

Brannan

Gulliksson²,

Anderson³

et al. 2003

155

108

The aim of this study was to investigate if mannitol inhalation, as a model of exercise-induced bronchoconstriction (EIB), causes mast cell activation and release of mediators of bronchoconstriction.Urinary excretion of previously identified mediators of EIB was investigated in association with mannitol-induced bronchoconstriction. Twelve asthmatic and nine nonasthmatic subjects inhaled mannitol and urine was collected 60 min before and for 90 min after challenge. The urinary concentrations of leukotriene (LT)E 4 , the prostaglandin (PG)D 2 metabolite and the mast cell marker 9a,11b-PGF 2 were measured by enzyme immunoassay. N t -methylhistamine was measured by radioimmunoassay.In asthmatic subjects, inhalation of a mean¡SEM dose of 272¡56 mg mannitol induced a reduction in forced expiratory volume in one second (FEV1) of 34.5¡2.1%. This was associated with increases in urinary 9a,11b-PGF 2 (91.9¡8.2 versus 66.9¡ 6.6 ng?mmol creatinine -1 , peak versus baseline) and LTE 4 (51.3¡7.5 versus 32.9¡4.7). In nonasthmatic subjects, the reduction in FEV1 was 1.0¡0.5% after inhaling 635 mg of mannitol. Although smaller than in the asthmatics, significant increases of urinary 9a,11b-PGF 2 (68.4¡6.9 versus 56.0¡5.8 ng?mmol creatinine -1 ) and LTE 4 (58.5¡5.3 versus 43.0¡3.3 ng?mmol creatinine -1 ) were observed in the nonasthmatic subjects. There was also a small increase in urinary excretion of N t -methylhistamine in the nonasthmatics, but not in the asthmatics.The increased urinary levels of 9a,11b-prostaglandin F 2 support mast cell activation with release of mediators following inhalation of mannitol. Increased bronchial responsiveness to the released mediators could explain the exclusive bronchoconstriction in asthmatic subjects. Eur Respir J 2003; 22: 491-496.

“…The evidence to support this contention comes from in vitro and in vivo studies. An increase in osmolarity is a potent stimulus for human lung mast cell release of histamine [27] and in humans the airway responses to hyperosmolarity are markedly inhibited by specific antihistamines [28,29]. The only evidence in support of neuropeptide comes from work in animals.…”

Section: Discussionmentioning

confidence: 99%

The effect of inhaling a dry powder of sodium chloride on the airways of asthmatic subjects

Anderson¹,

Spring²,

Moore³

et al. 1997

Wet aerosols of 4.5% sodium chloride (NaCl) are often used to assess the bronchial responsiveness associated with asthma. We questioned whether dry NaCl could be used as an alternative.Dry powder NaCl was inhaled from capsules containing either 5, 10, 20 or 40 mg to a cumulative dose of 635 mg. The powder was delivered via an Inhalator™ or Halermatic™. The airway sensitivity to the dry and wet NaCl was compared in 24 patients with asthma aged 19-39 yrs.All subjects responded to both preparations and the geometric mean (95% confidence intervals) for the provocative dose of NaCl causing forced expiratory volume in one second (FEV1) to fall 20% from baseline (PD20,NaCl) for dry NaCl was 103 mg (68-157) versus 172 mg (102-292), p<0.03 for the wet NaCl. The response to dry NaCl was reproducible and on repeat challenge the PD20 was 108 mg (75-153). The mean maximum fall in FEV1 was approximately 25% on each of the two test days. Spontaneous recovery occurred within 60 min after challenge with dry NaCl and within 5 min after bronchodilator. There were no serious sideeffects requiring medical attention, however some patients coughed on inhalation of the 40 mg dose and three gagged. Arterial oxygen saturation remained within normal limits.We conclude that a suitably prepared dry powder of sodium chloride could potentially replace wet sodium chloride to assess bronchial responsiveness in patients with asthma, but further studies are required to establish the long-term stability of the dry powder preparation.