We developed a bronchial provocation test (BPT) with a dry powder preparation of mannitol. The mannitol was inhaled from gelatin capsules containing 5, 10, 20, or 40 mg to a cumulative dose of 635 mg, and was delivered via an inhalator, Halermatic, or Dinkihaler device. We studied the airway sensitivity to inhaled mannitol, the repeatability of the response, and the recovery after challenge in 43 asthmatic subjects 18 to 39 yr of age who had a 20% decrease in FEV1 in response to inhaling a 4.5% NaCl. We compared this with the airway response to methacholine in 25 subjects. The geometric mean (GM) for the dose of dry mannitol required to reduce the FEV1 by 15% of the baseline value (PD15) was 64 mg, with a 95% confidence interval (CI) of 45 to 91. Subjects responsive to mannitol had a PD20 to metacholine of < 7.8 mumol, with a GM of 0.7 mumol (CI: 0.4 to 1.2). For the first of two challenges to mannitol the PD15 was 59 mg (CI: 36 to 97) and for the second the PD15 was 58 mg (CI: 35 to 94) p = 0.91 (n = 23). Spontaneous recovery to within 5% of baseline occurred within 60 min and within 10 min after 0.5 mg terbutaline sulfate was inhaled. Arterial oxygen saturation (SaO2) remained at 93% or above during mannitol challenge. Subjects tolerated the inhalation of the mannitol well. A dry powder preparation of mannitol may be suitable to develop for bronchial provocation testing.
Summary. A randomized controlled trial of two environments for delivery was conducted at Queen Charlotte's Maternity Hospital. A total of 253 parous women expecting to have a labour ward delivery were invited to participate in the trial but only 148 agreed. These women were randomly allocated to be delivered either with standard labour ward management (n= 72) or in the birthroom—a small bedroom decorated in a homely manner, without facilities for epidural analgesia or electronic fetal monitoring (n= 76). Eleven women in the birthroom group and 10 in the labour ward group withdrew from the trial before labour and four were transferred from the birthroom to the labour ward when in labour. A questionnaire sent in the postnatal period to the women who completed the trial was returned by 80%. In the birthroom group there was significantly (i) decreased admission‐to‐delivery interval (ii) less analgesia (iii) more freedom of movement (iv) less suturing (v) increased rooming‐in. No difference was found in the assessment of difficulty of labour nor in the method of subsequent infant feeding.
Abstractthe blockade of chloride channels at several sites in the airways including mast cells, epiBackground -Inhaled frusemide inhibits airway narrowing and causes a transient thelial cells, and nerves. [2][3][4] The inhibitory effect of frusemide on hypertonic saline challenge increase in forced expiratory volume in one second (FEV 1 ) during hypertonic sa-could also be attributed in part to its potential to release prostaglandin E 2 (PGE 2 ) 5 6 which line challenge. This inhibitory effect could be secondary to prostaglandin release dur-may indirectly relax airway smooth muscle.7 A hypertonic stimulus alone also has the potential ing challenge. The involvement of prostaglandins in the inhibitory action of to release PGE 2 from epithelial cells. 8 The combination of frusemide and a hypertonic stimulus frusemide during challenge with 4.5% NaCl was investigated by premedicating may enhance the release of PGE 2 , resulting in the transient bronchodilation observed by with indomethacin, a prostaglandin synthetase inhibitor.Rodwell and colleagues 2 in six of the 11 asthmatic subjects they studied. Methods -Fourteen asthmatic subjects (eight women) aged 26.6 (range 18-56)There are several reasons why PGE 2 may be the cause of the transient bronchodilation: years participated in a double blind, placebo controlled, crossover study. The sub-(1) human airway epithelium releases PGE 2; 9 10 (2) frusemide stimulates PGE 2 production; 5 6 jects attended five times and inhaled 4.5% NaCl for 0.5, 0.75, 1, 1.5, 2, 4, 8, 8, and 8 (3) the protective effect of inhaled frusemide against airway narrowing caused by exercise in minutes, or part thereof, or until a provocative dose causing a 20% fall in FEV 1 asthmatic subjects is inhibited by indomethacin, 11 a drug which inhibits the synthesis (PD 20 FEV 1 ) was recorded. Indomethacin (100 mg/day) or placebo were taken three of PGE 2 ; and (4) when PGE 2 is inhaled by normal subjects five minutes before histamine days before all visits, except control day. The FEV 1 was measured and frusemide challenge there is a delay in airway narrowing 12 similar to the delay observed during challenge (38.0 (6.4) mg, pH=9) or vehicle (0.9% NaCl, pH=9) were inhaled 10 minutes be-with 4.5% NaCl after inhaling frusemide.
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.
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