The Sapienza University of Rome network of automated external defibrillators: a prototype webMap developed to speed access to community defibrillators and increase survival from out-of-hospital cardiac arrest.

OBJECTIVE: In Italy, only around 10% of people who experience out-of-hospital cardiac arrest (OHCA) survive. A large portion of OHCA events in public settings are characterized by an initial shockable rhythm, which requires prompt defibrillation. We aimed to create a system to quickly locate nearby public access automated external defibrillators (AEDs) on the campus of Sapienza University of Rome, the largest public university in Europe. MATERIALS AND METHODS: We developed the AED webMap through a 6-step process involving the: 1) collection of information and geographical coordinates for each AED from the university management system; 2) development of a new geolocation database; 3) integration of information contained in the new database with data provided by university departments; 4) geolocation of AEDs in the Google MyMaps environment; 5) graphic representation of all AEDs on digital map templates using specific symbols, with pop-ups containing additional information for each AED; and 6) publication of the webMap on the university website. RESULTS: The AED webMap was published on the university website (https://www.uniroma1.it/it/pagina/defibrillatori-sapienza-in-rete) and facilitates prompt identification of nearby AEDs by providing: 1) detailed AED geolocalization with interactive pop-up information for each AED, including whether the AED is located internally or externally; 2) the option to use different base maps (e.g., digital street map); 3) calculation and display of the route to reach the chosen AED; and 4) the possibility to migrate towards multiple platforms. CONCLUSIONS: The webMap can help bystanders quickly identify, locate, and reach nearby AEDs present on the campus of the largest public university in Europe, a measure that could help speed defibrillation and maximize the life-saving potential of AEDs in the event of OHCA.

A one-year trial of tiotropium Respimat plus usual therapy in COPD patients.

In this randomised double-blind study, patients >or=40 years old with COPD, a smoking history of >or=10 pack-years, a pre-bronchodilator FEV(1) of

Acute local tolerability of acidic aqueous vehicles delivered via Respimat Soft Mist Inhaler in hyperreactive asthma patients.

BACKGROUND: Acidic inhalers can be associated with increased adverse reactions. OBJECTIVES: This study aimed to determine the acute local tolerability of acidic aqueous placebo formulations delivered via Respimat Soft Mist Inhaler (SMI) and placebo chlorofluorocarbon metered dose inhaler (CFC-MDI). METHODS: A single-dose (four inhalations), randomized, double-blind within Respimat SMI device, four-way crossover study in asthma patients with documented bronchial hyperresponsiveness was used. Patients received acidic placebo solutions [pH 2.7, 3.4 or 7.0 (neutral)], delivered via Respimat SMI or placebo CFC-MDI. The primary endpoint was the largest decrease in forced expiratory volume in 1 s (FEV(1)) from baseline to 0-30 min after dosing. Secondary endpoints included spirometry, paradoxical bronchoconstriction (defined as a fall in FEV(1) >or=15% below baseline within 30 min of dosing), cough episodes and adverse events. RESULTS: Thirty-two patients were included in the per-protocol population (mean age 27 years, 62.5% males). The mean percentage decrease in FEV(1) was comparable between treatment groups: -1.6% (Respimat SMI pH 2.7), -1.8% (Respimat SMI pH 7.0), -1.9% (CFC-MDI), and -2.3% (Respimat SMI pH 3.4); no patient experienced paradoxical bronchoconstriction. The mean number of cough episodes was significantly lower in the Respimat SMI pH 2.7 group versus CFC-MDI (p = 0.0165). No patient used rescue medication. Only 3 patients experienced at least one adverse event. CONCLUSIONS: The Respimat SMI pH 2.7 placebo solution does not induce adverse events in these patients. Compared with the CFC-MDI placebo suspension, Respimat SMI is a well-tolerated inhaled medication delivery system that can accommodate medication formulations with a wide range of pH solutions.

Inhaled ethanolic and aqueous solutions via Respimat Soft Mist Inhaler are well-tolerated in asthma patients.

BACKGROUND: Respimat Soft Mist Inhaler (SMI) is a new-generation inhaler offering improved lung deposition compared with other devices. Bronchodilators administered via Respimat SMI are preserved and stabilized with benzalkonium chloride (BAC) and ethylene diamine tetra-acetic acid (EDTA); both have been reported to cause paradoxical bronchoconstriction if a threshold dose is exceeded. OBJECTIVE: The aim of this randomized, double-blind, three-period, crossover study was to establish that the safety of inhaled ethanolic and aqueous placebo solutions (containing BAC and EDTA) is equivalent to that of inhaled normal saline solution when administered to asthma patients via Respimat SMI. METHODS: Thirty-seven asthma patients with airway hyper-reactivity were randomized to receive four actuations of each of the following three treatments via Respimat SMI, one on each of 3 study days: ethanolic placebo (12 microl 96% ethanol + 0.13 mug EDTA/actuation), aqueous placebo (12 microl water + 5.5 microg EDTA + 1.1 mug BAC/actuation), and normal saline (12 microl 0.9% sodium chloride/actuation). Pulmonary function tests were performed at baseline and at 5, 15, 30, 60, 120 and 180 min after inhalation; the primary endpoint was the lowest FEV(1) recorded between 0 and 30 min. RESULTS: The mean lowest FEV(1) recorded between 0 and 30 min after inhalation minus the study day baseline was -0.090 litres for ethanolic placebo, -0.121 litres for aqueous placebo and -0.094 litres for normal saline (SEM 0.034 litres for all). The mean treatment differences were: ethanolic placebo versus normal saline 0.004 litres (90% CI -0.075-0.083 litres, p = 0.002), and aqueous placebo versus normal saline -0.028 litres (90% CI -0.107-0.052 litres, p = 0.006). Since both 90% CIs fell within the pre-determined equivalence region of +/-0.15 litres, both treatments were considered equivalent to normal saline. CONCLUSION: Ethanolic and aqueous solutions administered via Respimat SMI are safe with regard to paradoxical bronchoconstriction in asthma patients with airway hyper-reactivity.

Low incidence of paradoxical bronchoconstriction with bronchodilator drugs administered by Respimat Soft Mist inhaler: results of phase II single-dose crossover studies.

BACKGROUND AND OBJECTIVES: Respimat Soft Mist Inhaler (SMI) is an innovative device that offers improved lung deposition and is an environmentally friendly alternative to conventional, chlorofluorocarbon-containing metered-dose inhalers (CFC-MDIs). The aqueous formulations of bronchodilator drugs administered from Respimat SMI contain low concentrations of ethylene diamine tetra-acetic acid (EDTA), a stabilising agent, and benzalkonium chloride (BAC), an antibacterial agent, both of which have been associated with bronchoconstriction when administered via nebulisers. The aim of this retrospective analysis was to compare the incidence of paradoxical bronchoconstriction with bronchodilator drugs administered via Respimat SMI or a CFC-MDI in patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS: Nine randomised, active- and/or placebo-controlled, double-blind, crossover studies, in which asthmatic and COPD patients (n = 444 and n = 216, respectively) received a beta(2)-agonist and/or anticholinergic or placebo via Respimat SMI or CFC-MDI, were included in the analysis. The incidence of conditions indicative of paradoxical bronchoconstriction were collated and divided into four categories: (1) 'bronchospasm'; (2) two or more of the following events: 'other respiratory adverse events', 'rescue medication use' or 'asymptomatic drop in forced expiratory volume in one second' (FEV(1)); (3) either 'rescue medication use' or 'other respiratory adverse event'; (4) 'asymptomatic drop in FEV(1)'. RESULTS: The incidence of adverse events indicative of paradoxical bronchoconstriction was low in those patients using the Respimat SMI device, and similar to that seen in the CFC-MDI group. In addition, the incidence of adverse events indicative of paradoxical bronchoconstriction observed in the Respimat SMI group was similar for BAC + EDTA and BAC-only drug formulations. CONCLUSIONS: These studies demonstrate that, due to the extremely low absolute amounts of BAC and EDTA delivered to the lungs by the device, Respimat SMI is safe with regard to paradoxical bronchoconstriction in patients with asthma or COPD.

Preliminary data from phase II studies with Respimat, a propellant-free soft mist inhaler.

Inhalation is regarded as the most effective treatment for respiratory disorders. Boehringer Ingelheim (Ingelheim am Rhein, Germany) has developed Respimat, a soft mist inhaler that delivers a metered dose of drug solution as an aerosol with a high "fine particle fraction" approximately five times slower than aerosols from chlorofluorocarbon-driven metered dose inhalers (CFC-MDIs). These characteristics have led to improved drug deposition in the lungs. In scintigraphic studies using fenoterol and flunisolide, mean drug delivery to the lungs was 31.1 to 44.6% of the dose delivered using Respimat compared with less than 20% using a CFC-MDI. Clinical studies in asthmatic patients using inhaled fenoterol alone (Berotec; Boehringer Ingelheim) or combined with ipratropium bromide (Berodual; Boehringer Ingelheim) confirmed the hypothesis that lower doses administered using Respimat should produce bronchodilator effects similar to those obtained with standard doses administered via a CFC-MDI. For Berotec, 12.5 or 25 micrograms administered by Respimat was therapeutically equivalent to either 100 or 200 micrograms administered by a CFC-MDI. For Berodual, bronchodilatory effects of 25/10- or 50/20-microgram doses using Respimat tended to be close or slightly superior to those of 100/40 micrograms using a CFC-MDI. Safety profiles did not differ between Respimat and CFC-MDI administration in either trial. Patients with airway hyperreactivity who inhaled placebo or drug solutions containing different preservatives and stabilizers had low incidences of paradoxical bronchoconstriction or asymptomatic decreases in lung function, which were similar with Respimat and a CFC-MDI. Furthermore, facial deposition data suggest a low risk of untoward effects even in potential misuse situations. Thus, Respimat promises to be a valuable alternative to conventional CFC-MDIs, with the additional benefit of improved drug targeting to the lungs.

Effect of oral antibiotics on lung mucociliary clearance during exacerbation of chronic obstructive pulmonary disease.

It has been well established that lung mucociliary clearance is depressed in patients with chronic obstructive pulmonary disease. This study examines whether oral antibiotics have a detectable effect on this clearance mechanism during exacerbation in patients with such disease. Twelve patients with a mean +/- SE age of 63 +/- 2 years participated in a randomized, double-blind, parallel group study to assess the effect of 1 week of treatment with amoxycillin (500 mg t.d.s.) or ciprofloxacin (500 mg b.d.) on lung mucociliary clearance during exacerbation. Lung mucociliary clearance rates were measured by a non-invasive radioaerosol technique. Both drugs on average resulted in small, non-significant, enhancement of mucociliary clearance. Following treatment, the numbers of coughs were reduced in both groups and significantly (P < 0.05) after treatment with ciprofloxacin. Sputum production was also significantly reduced (P < 0.01) in both groups. The magnitude of improvement in lung mucociliary clearance was relatively modest following 1 week of treatment with either antibiotic. Since the number of coughs was significantly less after ciprofloxacin treatment the measured enhancement of lung mucociliary transport is probably, however, an underestimate.

Relationship between bronchial reversibility and tracheobronchial clearance in patients with chronic bronchitis.

BACKGROUND: Patients with chronic bronchitis show a large intersubject variation in sputum rheology, tracheobronchial clearance, and reversibility of airflow obstruction to beta 2 agonists. The bronchial mediators which are known to cause bronchoconstriction, mucosal oedema, mucus hypersecretion, and cough can also affect mucociliary transport. The aim of this study was to ascertain whether changes in tracheobronchial clearance and sputum rheological properties in patients with chronic bronchitis were associated with a specific degree of airflow reversibility assessed as the bronchial response to an inhaled beta 2 agonist (fenoterol 400 micrograms). METHODS: Bronchial reversibility (percentage change in baseline forced expiratory volume in one second (FEV1)) was measured in 26 patients with chronic bronchitis on three separate occasions, at least one week apart. Tracheobronchial clearance was evaluated by a non-invasive radioaerosol technique, and an oscillatory viscometer was used for measuring sputum apparent viscosity and elasticity. The number of coughs (productive and nonproductive coughs), the wet weight of sputum, and its radioaerosol content were recorded during the six hour clearance period, as well as the 24 hour sputum production. RESULTS: The change in FEV1 after fenoterol was less than 15% in 12 patients and more than 15% in 14. Patients with airways reversibility of more than 15% had faster tracheobronchial clearance, more coughs, lower sputum viscosity and elasticity, and larger 24 hour sputum production than those with airways reversibility of less than 15%. CONCLUSIONS: In patients with chronic bronchitis a large bronchodilator response is associated with faster clearance of mucus by mucociliary transport and coughing.

Efficacy and safety of inhalation therapy in chronic obstructive pulmonary disease and asthma.

The inhaled route has a number of well-recognized advantages over other routes for administration of drugs to the lungs. As the drug is delivered directly to its required site of action, only a small quantity is required for an adequate therapeutic response. Consequently, there is a low incidence of systemic side-effects compared with oral or intravenous administration. In addition, the onset of action of inhaled drugs is generally faster than that achieved by oral administration. Factors that can affect the quantity of inhaled particles reaching the lungs and their topographical distribution are manner of inhalation, aerosol characteristics and subject characteristics. The main types of inhaler device are metered-dose inhalers (MDIs), dry powder inhalers (DPIs) and nebulizers (jet and ultrasonic). There are advantages and disadvantages associated with all types of currently available inhaler device and there is still a clear need to develop more efficient devices that are easy to use. Respimat (Boehringer Ingelheim) is a novel soft mist inhaler that operates via a mechanism utilizing mechanical power rather than gas propellants, and represents an exciting development in this field.

No effect of gender on lung mucociliary clearance in young healthy adults.

Lung mucociliary clearance (LMC) depends on age and it is adversely affected by cigarette smoking. When using the radioaerosol technique for measuring LMC the initial site of deposition of the radioaerosol within the lungs affects its rate of removal. Whether there is a difference in gender for LMC is still an open question. Forty-one (20 female, 21 male) healthy, non-smoking subjects had their lung mucociliary clearance measured using an objective, non-invasive radioaerosol technique. The male and female groups were closely matched for initial distribution of the radioaerosol. There was no statistical significant difference between males and females in the rate of clearance of inhaled radioaerosol over a 6 h observation period. When comparing the LMC of two groups although it is important to match them for age, smoking habits and initial topographical distribution of the tracer radioaerosol it does not seem essential to also match the two groups for gender.

Inhaled frusemide does not affect lung mucociliary clearance in healthy and asthmatic subjects.

Inhaled frusemide has been shown to protect against the bronchoconstrictor effect of several inhaled agents in asthmatic subjects by mechanism(s) that are unclear. Since loop diuretics can modulate Cl- transport in the airway epithelium, frusemide may alter the quality and/or the quantity of the periciliary layer, which in turn may affect lung mucociliary transport. We investigated the effect of a single inhalation of nebulized frusemide (40 mg) on lung mucociliary clearance in four healthy subjects and in seven stable, mild asthmatics using an objective radioaerosol technique. Frusemide or placebo was inhaled in a double-blind, randomized, cross-over manner half an hour after the inhalation of 5 microns polystyrene particles labelled with 99mTc, used for assessing mucociliary clearance. The pulmonary function and initial radioaerosol distribution were similar between frusemide and placebo runs within each of the two study groups. The areas under the tracheobronchial retention curves over the 6 h observation period were similar between frusemide and placebo runs for both groups. Our findings show inhaled frusemide, at a dose known to inhibit bronchoconstrictor responses, does not affect lung mucociliary clearance.

Regional lung clearance during cough and forced expiration technique (FET): effects of flow and viscoelasticity.

BACKGROUND: In vitro studies have suggested that both the viscoelastic properties of lung secretions and the peak flow attained during simulated cough influence clearance. This study examines the possible association of the viscoelastic properties of sputum and maximum expiratory flow with measured effectiveness of mucus clearance induced by instructed cough and by forced expiration technique (FET) in patients with airways obstruction. METHODS: Nineteen patients (11 men and eight women) of mean (SE) age, % predicted FEV1, and daily sputum wet weight of 64 (2) years, 52 (6)%, and 37.5 (7.9) g respectively participated in the study. Mucus movement from proximal and peripheral lung regions was measured by an objective non-invasive radioaerosol technique. Each patient underwent three assessments: control, cough, and FET. During cough and FET, maximum expiratory flow was measured at the mouth level. Apparent viscosity and elasticity of the expectorated sputum samples were measured with a viscometer. RESULTS: Compared with the control run (mean (SE) clearance: 16 (3)%) there was an increase in clearance from the whole lung during cough (44 (5)%) and FET (42 (5)%), and also an enhanced clearance of inhaled, deposited radioaerosol from the trachea, inner and intermediate regions of the lungs, but not from the outer region. There were, however, no differences in regional clearance between cough and FET. Neither regional nor total clearance correlated with maximum expiratory flow, apparent viscosity, elasticity, or daily sputum wet weight. CONCLUSIONS: These results confirm that cough and FET both promote effective clearance but suggest that, unlike in vitro studies, sputum production and viscoelasticity, as well as maximum expiratory flow, provide no guide to clearance efficacy in humans.

Regional mucus transport following unproductive cough and forced expiration technique in patients with airways obstruction.

It has previously been shown that unproductive coughing in both healthy subjects and patients with airways obstruction is not effective in clearing lung secretions. This study investigates the regional mucus transport in a group of subjects with airways obstruction who failed to expectorate following instructed cough and forced expiration technique. Fourteen patients (mean +/- SEM age: 68 +/- 2 years) with airways obstruction (mean +/- SEM percent predicted. FEV1: 54 +/- 5; daily wet weight sputum: 9.1 +/- 2.0 g) took part in the study which was a randomized, three-way crossover within-patient design. Each patient underwent three treatment maneuvers: control, cough (30 coughs over a 10-min period), and forced expiration (30 forced expirations over a 10-min period). An objective radioaerosol technique was used to monitor regional mucus movement within the lungs of the patients. The lungs were divided arbitrarily into four regions of interest: tracheal, inner, intermediate, and outer. Peak expiratory flow rate during cough and forced expiration was measured at the mouth. There was no correlation between the radioaerosol clearance from all regions and (1) mean peak flow during cough and forced expiration, and (2) mean 24-h sputum production prior to the study day. There were no differences in regional radioaerosol clearance between cough and forced expiration. However, both cough and forced expiration resulted in significant clearance compared with control for all regions with the exception of the forced expiration in the outer region. To our knowledge, this study is the first to demonstrate that unproductive cough and forced expiration result in movement of secretions proximally from all regions of the lung in patients with airways obstruction.

Effect of oral bronchodilators on lung mucociliary clearance during sleep in patients with asthma.

BACKGROUND: Lung mucociliary clearance rates are reduced during sleep in patients with asthma. Methylxanthines and beta 2 agonists have been shown to enhance rates of lung mucociliary clearance. This study examined whether oral slow release bronchodilators may also have an effect on this clearance mechanism during sleep in patients with asthma. METHODS: Nine patients with asthma with a mean(SE) age of 65(5) years and percentage predicted forced expiratory volume in one second (FEV1 of 61(9)% participated in a double blind, placebo controlled, within subject crossover study to assess the effect of two weeks of treatment with salbutamol (Volmax; 8 mg twice daily) or theophylline (Phyllocontin; 350 mg twice daily) on lung mucociliary clearance during sleep. Lung mucociliary clearance rates were measured by a radioaerosol technique. RESULTS: The observation period for radioaerosol clearance was approximately 0.3 hours before sleep, 6.0 hours during sleep and 0.6 hours after sleep. Mean mucociliary clearance rates for theophylline, placebo and salbutamol before sleep were: 39, 39, and 32%/hour respectively; during sleep: 11, 10, and 9%/hour respectively; and after sleep: 39, 32, and 35%/hour respectively. CONCLUSION: During sleep lung mucociliary clearance in stable asthma was reduced, which is in agreement with the group's previous findings. Treatment with controlled/slow release oral bronchodilators had no effect on this reduced rate of clearance associated with sleep.

Acute effect of inhaled bradykinin on tracheobronchial clearance in normal humans.

BACKGROUND: Bradykinin, a nonapeptide that contributes as a mediator to the pathogenesis of asthma, may affect lung mucociliary clearance, as it has been shown to be a potent secretagogue in canine airways and in human nasal mucosa in vivo. To evaluate this possibility the effect of inhaled bradykinin on mucociliary clearance has been studied in 10 healthy volunteers. METHODS: Subjects attended the laboratory on two occasions to take part in tracheobronchial clearance studies using a non-invasive radioisotopic technique. Inhalation of radioaerosol was followed 30 minutes later by inhalation of either bradykinin (8 mg/ml) or vehicle placebo in a randomised, double blind fashion. After each inhalation the number of coughs was recorded. Whole lung radioactivity was measured every half hour for six hours with two collimated scintillation counters, and a tracheobronchial clearance curve was plotted for each subject on each occasion. RESULTS: Mucociliary clearance, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first six hours (AUC0-6h), was greater in nine out of 10 subjects after inhalation of bradykinin than after placebo. The median values (range) for AUC0-6h were significantly reduced from 126% (78-232%)/h with placebo to 87% (51-133%)/h with bradykinin. CONCLUSION: It is concluded that acute exposure to inhaled bradykinin accelerates tracheobronchial clearance in normal human airways.

[The modulator effect of bradykinin with respect to tracheobronchial clearance in healthy subjects]. / Effetto modulatore della bradichinina nei confronti della clearance tracheobronchiale in soggetti sani.

Bradykinin (Bk), a vasoactive nonapeptide which has been proposed as mediator in the pathogenesis of bronchial asthma, is a potent secretagogue in canine airways and in human nasal mucosa in vivo. A study was carried out in order to evaluate the effect of inhaled Bk on tracheobronchial clearance (TBC), measured by a radioaerosol technique in 10 healthy volunteers. Subjects inhaled Bk (8 mg/mL) or vehicle placebo on two occasions, at least 2 weeks apart, in a double blind and randomized fashion 30 min after radioaerosol inhalation. TBC, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first 6 hours (AUC 0-6h), was enhanced in 9 of 10 subjects following inhaled Bk when compared to placebo. The mean values for AUC 0-6h were significantly reduced from 132%.h to 92%.h (p < 0.001) with placebo and Bk respectively. We conclude that Bk has a marked effect on tracheobronchial clearance in normal human airways.

Impairment of lung mucociliary clearance in pigeon fanciers.

Lung mucociliary clearance was measured in 15 pigeon fanciers. The study group was subdivided into two: a precipitin-positive group (n = 10; mean +/- SEM age 45 +/- 5 years) with circulating blood precipitins and a precipitin-negative group (n = 5; mean +/- SEM age 40 +/- 3 years) without. Clearance was measured using an objective, noninvasive radioaerosol technique. The data for both groups were compared with those of matched control groups of healthy subjects. The mean +/- SEM area under the tracheobronchial retention curves (AUC) over the 6-h observation period was 257 +/- 27 %h for the precipitin-positive group compared with 177 +/- 16 %h for its control group (p = 0.02)--a high AUC value denoting slow clearance. That for the precipitin-negative group was 282 +/- 34 %h compared with 150 +/- 15 %h for its control group (p = 0.02). Our study illustrates in pigeon fanciers involvement of the conducting airways in that a major defense mechanism of the airways--namely, mucociliary clearance--is substantially compromised. The presence or absence of precipitins appears not to be related to the degree of mucociliary clearance impairment.

Tracheobronchial clearance in patients with pulmonary sarcoidosis.

Lung mucociliary clearance was measured using an objective, noninvasive radioaerosol technique in 13 patients with pulmonary sarcoidosis and 13 matched, healthy control subjects. Four of the sarcoid patients had never received any steroid therapy, five were currently receiving oral corticosteroids, and the remaining four were using inhaled corticosteroids only. A statistically significant retardation in tracheobronchial clearance (p less than 0.02) was observed in the sarcoid patients compared to the control subjects. The sarcoid patients using inhaled corticosteroids appeared to demonstrate the greatest degree of mucociliary transport impairment. The sarcoid patients in apparent remission and those receiving oral corticosteroid therapy had clearances better than those using inhaled corticosteroids, but they were still reduced compared to the control subjects. This study demonstrates that lung mucociliary clearance is adversely affected in patients with pulmonary sarcoidosis and raises the question of the possible consequences that could follow long-term inhaled immunosuppressive therapy on the prime clearance defense mechanism within the human lungs.

Effect of temazepam on tracheobronchial mucus clearance.

BACKGROUND: Tracheobronchial clearance of mucus from the lungs is reduced during sleep and, usually, by the administration of opiates. It seemed possible therefore that temazepam, a widely used potent benzodiazepine, retarded clearance. METHODS: The effect of 10 mg temazepam on mucociliary clearance was studied in eight healthy volunteers, aged 18-50 (mean 30) years, in a randomised, placebo controlled, double blind, cross-over study. Six subjects were female and two male. Six were non-smokers and two were light current smokers. Clearance was assessed from the change in radio-activity in the lungs after inhalation of 5 microns diameter polystyrene particles, labelled with technetium-99m, under controlled conditions. RESULTS: Tracheobronchial clearance was reduced by 22% after temazepam by comparison with placebo during the first three hours after drug ingestion; this is the period when circulating drug concentrations are highest. CONCLUSION: Temazepam should be prescribed with caution in patients with impaired lung mucociliary transport.

Effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid on tracheobronchial clearance in normal human airways.

15-(s)-Hydroxyeicosatetraenoic acid (15-HETE) is the predominant metabolite of arachidonic acid in normal and asthmatic human airways and a potent mucus secretagogue in canine and human airways. A study was carried out on the effect of inhaled 15-HETE on tracheobronchial clearance, measured for six hours by a radioaerosol technique, in 10 normal subjects. Subjects inhaled 80 nmol 15-HETE or the diluent (sodium phosphate buffer) on two occasions at least two weeks apart in a double blind and randomised fashion (20 minutes after radioaerosol inhalation. Tracheobronchial clearance after inhaled 15-HETE was almost identical to that after placebo for all measurements up to six hours. It is concluded that 15-HETE has no effect on tracheobronchial clearance in normal human airways and is unlikely to account for the impaired mucociliary clearance seen in asthma.