Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inhalation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed2006

Assessment of personal direct-reading dust monitors for the measurement of airborne inhalable dust.

The performances of five portable direct-reading dust monitors were investigated in a wind tunnel for a range of industrial dusts and three sizes of aluminium oxide test dust to mainly determine their suitability for measuring the inhalable fraction of airborne dust in workplaces. The instruments tested were Split 2 (SKC Ltd), Sidepak (TSI Inc.), Dataram (Thermo Electron Ltd), PDS-2 (Sibata Scientific Technology Ltd) and the Respicon TM (Hund Ltd). The instruments' responses were compared with reference dust samplers. These were the IOM sampler for the inhalable fraction and the Casella cyclone sampler for the respirable fraction. All instruments are predominantly responsive to and are designed to measure particles in the respirable size range, although two of the instruments, the Split 2 and Respicon TM, are claimed to be capable of measuring inhalable-sized particles. For the purpose of the tests, major modifications to an existing wind tunnel dust injection system were made to facilitate the generation of uniform concentrations of large inhalable-sized dust particles at low air velocities. Each monitor greatly underestimated the measurement of inhalable concentration for all the dusts tested, although the linearity was good over a wide range of concentrations for any particular size distribution of dust. However, their calibration factors, defined as the ratio of reference inhalable concentration to monitor concentration, were especially sensitive to changes in particle size as the response of the instruments decreased rapidly with increasing particle size. The monitors generally overestimated the measurement of respirable dust concentration by up to a factor of about 2, apart from the PDS-2, which underestimated it by a factor of up to 3. There was, however, a great deal more scatter in the reference respirable concentration measurements owing to the collection of small dust samples. Therefore, monitor linearity and effects of monitor response to changes in particle size could not be accurately investigated for the respirable fraction. The sampling head of the Split 2 monitor incorporates an IOM inlet and filter to gravimetrically collect the inhalable fraction of airborne dust. This can give a concurrent reference measure of inhalable airborne dust concentration. However, poor sealing within the sampling head resulted in some of the sampled dust not reaching the backup filter. This resulted in the Split 2 underestimating the reference inhalable dust concentration, which meant that it could not be accurately used as a calibration standard. Communications with the manufacturers have since revealed that the sampling head has recently been redesigned in order to improve the seal and eliminate leakage. The Respicon sampler gravimetrically underestimated the inhalable dust concentration, and did so increasingly as the particle size increased.

Air Pollutants, Occupational↗
PubMed2004

Prescribing for osteoporosis following the use of inhaled and oral glucocorticoids in general practice.

AIMS: Systemic absorption from inhaled glucocorticoids may lead to bone loss. We determined the extent to which their use alone and in addition to short courses of oral glucocorticoids was associated with increased prescribing for osteoporosis in a large general practice population. METHODS: In a cohort study with follow-up of co-prescribing of antiosteoporotic drug therapy in the Irish national prescribing database (1.1 million people over 16 years), we identified 32 081 patients who received inhaled glucocorticoids alone during a 12-month period (following an identical lead-in period). We determined the odds ratio (OR), adjusting for age and gender for the co-prescription of bisphosphonates or other antiosteoporotic therapy with inhaled glucocorticoids by logistic regression. RESULTS: The adjusted OR (95% confidence interval) for co-prescribing of bisphosphonates and all inhaled glucocorticoids was 1.87 (1.71, 2.04); 1.58 (1.41, 1.78) for inhaled beclomethasone, 2.11 (1.75, 2.54) for inhaled budesonide and 3.29 (2.65, 4.1) for inhaled fluticasone. The ORs were significantly increased when patients who also received oral glucocorticoids were included and greater still in those under 45 years: 14.03 (10.6, 18.6). The results remained significant when the effects of comorbidity were adjusted for. The odds of receiving bisphosphonate therapy increased linearly with increasing exposure to inhaled glucocorticoids during the study period. CONCLUSIONS: Treatment with inhaled glucocorticoids in general practice is associated with an increased risk of co-prescribing for antiosteoporotic therapy in a potency- and a dose-related manner. Exposure to a course of oral glucocorticoids doubles this risk. These results suggest that the systemic effects on bone mineral density from using inhaled glucocorticoids may be clinically relevant but may also reflect prescribers' concerns for the development of osteoporosis in these patients.

Administration, Inhalation↗
PubMed1998

Effects of inhaled nitric oxide on platelet-activating factor-induced pulmonary hypertension in dogs.

BACKGROUND: Platelet-activating factor (PAF), a lipid mediator released during endotoxin shock, induces pulmonary hypertension, systemic hypotension and cardiac dysfunction. In this study, we compared the effect of inhaled nitric oxide (NO) on PAF-induced pulmonary hypertension and NO metabolism with that on pulmonary hypertension induced by a stable thromboxane A2 mimetic, U46619. Since PAF-induced hypotension might be mediated by NO, the effect of inhaled NO combined with an intravenously administered NO synthase inhibitor, NG-nitro-L-arginine (L-NNA), on PAF-induced hemodynamic change was also investigated. METHODS: In a total of 28 beagles anesthetized with pentobarbital the following substances were intravenously administered: PAF 0.56 +/- 0.30 microgram.kg-1.min-1 (group PAF), L-NNA 10 mg.kg-1 + PAF 0.04 +/- 0.03 microgram.kg-1.min-1 (group L-NNA + PAF), U46619 0.60 +/- 0.11 microgram.kg-1.min-1 (group U46619) or L-NNA 10 mg.kg-1 + U46619 0.61 +/- 0.23 microgram.kg-1.min-1 (group L-NNA + U46619) to obtain a mean pulmonary arterial pressure (MPAP) of 25 mmHg. Nitric oxide was then inhaled at 5, 10, 20 and 40 ppm for 15 min at 15-min intervals in the order of increasing concentration. An additional 7 dogs (control group) inhaled NO at normal MPAP (17 mmHg). Hemodynamic and respiratory parameters, NOHb, NO2- + NO3-, and MetHb levels in blood were measured before and during NO administration. RESULTS: In the control group, hemodynamic and respiratory values did not change significantly during NO administration. In group PAF, NO significantly reversed the PAF-induced pulmonary hypertension. PAF induced a marked systemic hypotension and cardiac output reduction, but these changes were not affected by inhalation of NO. L-NNA pretreatment markedly decreased the dose of PAF required to maintain a MPAP of 25 mmHg, and abolished the PAF-induced hypotension. In group L-NNA + PAF, the diminishing effect of inhaled NO on pulmonary vascular resistance (PVR) was significantly greater than that in group PAF. U46619 induced pulmonary hypertension and increases in blood pressure, intrapulmonary shunt and peak airway pressure. L-NNA pretreatment did not change the dose of U46619 required to maintain a MPAP of 25 mmHg. The effects of inhaled NO on PVR decrease were similar in groups U46619 and L-NNA + U46619. No NOHb was detected in any group. NO2- + NO3- concentration increased during NO administrations. There were no significant differences in NO2- + NO3- concentration among groups. CONCLUSIONS: Inhaled NO at the dose of 5-40 ppm effectively reversed PAF-induced pulmonary hypertension, especially following pretreatment with L-NNA. Inhaled NO did not affect PAF-induced hypotension or cardiac dysfunction. These findings indicate that low concentrations of inhaled NO may be useful in reversing pulmonary hypertension in the endotoxemia where PAF may be one mediator.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Relationship between solvent inhalation and antisocial behavior: special emphasis on two types of violence seen in solvent abusers.

Organic solvent inhalation is a serious problem among youths in Japan. It induces physical and mental disorders, and is related closely to crime and delinquency. The relationship between solvent inhalation and antisocial behavior was investigated in 75 youths. The subjects were divided into three groups according to the level of violent behavior and the time of appearance: a non-violent group, a late-onset group (violence occurred after the start of inhalation) and an early-onset group (violence had occurred before the start of inhalation). Various parameters were compared among the groups. The late-onset group showed the following characteristics; (i) the frequency of inhalation was high, and many subjects experienced hallucinations and mood changes caused by inhalation; (ii) the family environment was characterized by conflict; and (iii) the subjects had strong psychological conflicts and showed dissociative coping with frustration. The violence, psychological conflict and dissociation in this group were found to be related to the inhalation, with familial conflict as a background. The violence in the early-onset group was considered to be the manifestation of a violent personality as the frequency of inhalation and the incidence of mental symptoms were both low. The subjects in this group showed weak psychological conflict and tended to be demanding of others when attempting to cope with frustration. Two types of violent behaviors in the teenagers who inhaled solvents were identified. The violence of solvent inhalers should be managed according to the type.

Administration, Inhalation↗
PubMed1997

Weaning strategy with inhaled nitric oxide treatment in persistent pulmonary hypertension of the newborn.

AIM: To determine if infants who had become dependent on inhaled nitric oxide treatment could be successfully weaned off it if FIO2 was increased briefly during withdrawal. METHODS: Sixteen infants admitted for conditions associated with increased pulmonary vascular resistance responded well to inhaled nitric oxide treatment with a significant increase in PaO2 (maximum inhaled nitric oxide given 25 ppm). Weaning from inhaled nitric oxide in 5 ppm decrements was initiated once the FIO2 requirement was less than 0.5. When patients were stable on 5 ppm of inhaled nitric oxide, the gas was then discontinued. If a patient showed inhaled nitric oxide dependence-that is, oxygen saturation fell by more than 10% or below 85%-inhaled nitric oxide was reinstated at 5 ppm and the patient allowed to stabilise for 30 minutes. At this time, FIO2 was increased by 0.40 and weaning from inhaled nitric oxide was attempted again. RESULTS: Nine infants were successfully weaned on the first attempt. The seven infants who failed the initial trial were all successfully weaned following the increase in FIO2. After successful weaning, FIO2 was returned to the pre-weaning level in mean 148(SD 51) minutes and inhaled nitric oxide was never reinstated. CONCLUSION: Infants showing inhaled nitric oxide dependency can be successfully weaned by increasing FIO2 transiently.

Administration, Inhalation↗
PubMed1995

A large volume spacer significantly reduces the effect of inhaled steroids on bone formation.

Inhaled steroids are increasingly advocated as first line treatment for mild asthma. Some studies suggest that inhaled steroids suppress bone formation as reflected by a fall in plasma osteocalcin. Spacers have been shown to increase the proportion of inhaled aerosol that is deposited in the lungs and to reduce the amount swallowed. We measured plasma osteocalcin levels to determine the effect on bone formation of inhaled beclomethasone dipropionate (BDP) with and without a 750 ml spacer in a double-blind, randomised, placebo-controlled, cross-over study. Twenty-six healthy male volunteers took BDP 500 micrograms (two puffs of Becloforte) together with two puffs of placebo, inhaled twice daily for seven days. One inhaler was taken directly while the other was inhaled through a 750 ml spacer. After a two week washout period, the inhalers were exchanged so that BDP was taken by the alternate route for a further seven days. Fasting plasma osteocalcin levels were measured at 09.00 h before and at the end of each week. After a week of BDP taken directly (without a spacer), osteocalcin levels fell from 11.8 (SEM 0.6) ng/ml to 9.5 (SEM 0.5) ng/ml (p < 0.001). After a week of BDP taken through a spacer, osteocalcin levels fell from 12.1 (SEM 0.5) ng/ml to 11.1 (SEM 0.5) ng/ml (p < 0.001). The fall in osteocalcin when a spacer was used was significantly less than when BDP was taken directly (p < 0.005). This is likely to be because the systemic effects on bone are caused by swallowed rather than inhaled BDP, and this is limited by the use of a spacer. Spacers should be more widely prescribed with inhaled steroids. Further prospective studies are indicated to evaluate whether spacers protect bone mass.

Administration, Inhalation↗
PubMed1993

Improvement in sodium cromoglycate delivery from a spacer device by use of an antistatic lining, immediate inhalation, and avoiding multiple actuations of drug.

BACKGROUND: Aerosols generated from metered dose inhalers may be highly charged. The aim of this study was to determine whether lining the walls of a polycarbonate spacer device with an antistatic agent would result in an increase in drug output. The effects of multiple actuations of drug into the spacer device and increasing residence time of drug within the spacer were also determined. METHODS: The amount of sodium cromoglycate contained in particles of various size available for inhalation (per 5 mg actuation) from a 750 ml polycarbonate spacer was determined by impinger measurement and spectrophotometric assay. RESULTS: Lining the spacer with an antistatic agent increased the mean (SD) amount of sodium cromoglycate in particles < 5 microns available for inhalation (per 5 mg actuation) by 244% from (0.59 (0.03) to 1.44 (0.2) mg). When there was a 20 second interval between actuation into the spacer device and inhalation, sodium cromoglycate available for inhalation in particles < 5 micrograms decreased by 67% (from 0.59 (0.03) mg to 0.2 (0.01) mg). Use of the spacer device increased sodium cromoglycate available for inhalation in respirable particles (< 5 microns) by 18% compared with direct delivery by metered dose inhaler. Multiple actuations into the spacer decreased the amount of sodium cromoglycate available for inhalation in particles < 5 microns by 31% after two actuations and 56% after three acutations. CONCLUSIONS: Multiple actuations of sodium cromoglycate into a spacer device before inhalation should be avoided, and inhalation from spacer devices should take place immediately after actuation to ensure maximum dose. Lining of a standard spacer device with an antistatic agent significantly increased output of sodium cromoglycate. This may have implications for improved therapeutic response and drug cost.

Administration, Inhalation↗
PubMed1994

Which patients are prescribed inhaled anti-asthma drugs?

BACKGROUND: Prescribing rates for inhaled anti-asthmatic drugs in the UK vary considerably from area to area and between individual practices. The objectives of this study were to determine the prevalence of patients prescribed inhaled steroids and beta agonist bronchodilators, the indications for these prescriptions, and to relate prescribing to the recorded levels of morbidity for specific respiratory disease. METHODS: Anonymised patient-specific prescription and diagnostic data were extracted from computerised general practice records for the 41 practices in the Northern region (total population 330,749) whose data had been validated for inclusion in a research databank. Patients were included if they were either prescribed an inhaled steroid or bronchodilator during a 12 month period, or had a recorded diagnosis of asthma, bronchitis or chronic obstructive pulmonary disease. Prescribing of inhalers per 1000 population was determined within age, sex, and diagnostic groups. Respiratory diagnosis rates within different patient groups were used to measure the underlying level of morbidity in the population. RESULTS: Inhaled anti-asthma drugs were prescribed for 5% of the study population. Prescribing prevalences peaked at ages 5-14 (steroids 40 per 1000 population; bronchodilators 68 per 1000) and at ages 65-74 (steroids 53 per 1000; bronchodilators 79 per 1000). Prescribing frequency for both drugs increased from two or three items per patient annually at age 0-14 to about six in the over 65 age group. Of the 39,424 respiratory patients 38% received inhalers and 7% only non-inhaler medication. Inhaler therapy was used in only 6% of patients with bronchitis, but in 66% of those with asthma, though the proportions varied with patient age and gender. Study practices differed in their overall levels of both inhaler prescribing and respiratory diagnosis, and had lower prescribing patterns of these drugs than other practices in the Northern region. CONCLUSIONS: Inhaled steroid and bronchodilator prescribing have age-related and gender-related prevalences. Treatment for respiratory diagnoses varies with patient age and gender, and with the diagnosis. Prescribing differences between practices are attributable to variation in both diagnostic rates for respiratory disease and therapeutic intervention patterns. For asthma patients study practices show consensus in approach, perhaps illustrating the value of clear guidelines for asthma prescribing.

Administration, Inhalation↗
PubMed1994

Volumatic usage: some generic salbutamol metered dose inhalers can be used.

BACKGROUND: The 30 minute and 24 hour post-inhalation urinary excretion of salbutamol represents the relative amount of drug deposited in the lungs and total systemic absorption, respectively. Using this method two metered dose inhalers used with a Volumatic (Allen and Hanburys Ltd, UK) large volume spacer have been compared. METHOD: Eleven healthy volunteers inhaled 4 x 100 micrograms salbutamol from either a generic salbutamol (Baker Norton, UK) or Ventolin (Allen and Hanburys Ltd, UK) metered dose inhaler with a Volumatic. The order of administration was randomised with a seven day washout period. Urine samples were collected for 0-30 minutes and then pooled up to 24 hours after inhalation. RESULTS: The mean (SD) urinary salbutamol excretion 30 minutes after inhalation with the metered dose inhalers used with the Volumatic was 22.22 (4.63) and 21.30 (5.91) micrograms for the Baker Norton and Ventolin respectively, with a mean difference (95% confidence interval (CI)) of 0.92 (-0.65 to 2.49) micrograms. Similar amounts were excreted up to 24 hours after the dose with a mean (SD) urinary excretion of 116.1 (24.3) micrograms and 114.8 (22.3) micrograms, respectively, and a mean difference (95% CI) of 1.22 (-20.39 to 22.84) micrograms. CONCLUSION: Inhalations from generic salbutamol (Baker Norton) and Ventolin metered dose inhalers with a Volumatic inhalation aid deliver similar amounts of drug to the lungs and the total systemic absorption from the two products is the same.

Administration, Inhalation↗
PubMed1995

Salmeterol inhaler using a non-chlorinated propellant, HFA134a: systemic pharmacodynamic activity in healthy volunteers.

BACKGROUND: Metered dose inhalers for the treatment of asthma use chlorofluorocarbons as propellants. These face an international ban due to their effect on the ozone layer. Salmeterol has been reformulated using the non-chlorinated propellant Glaxo inhalation grade HFA134a. METHODS: The safety, tolerability and systemic pharmacodynamic activity of the salmeterol/HFA134a inhaler, the current salmeterol inhaler, and placebo (HFA134a) were compared in 12 healthy volunteers in a double blind, randomised crossover study using a cumulative dosing design. RESULTS: Safety and tolerability were similar and the response was related to the dose over the range used (50-400 micrograms) with both salmeterol inhalers. The salmeterol/HFA134a inhaler showed no differences from the current inhaler for pulse rate, blood pressure, tremor, QTc interval, and plasma glucose levels. The salmeterol/HFA134a inhaler had significantly less effect on plasma potassium levels. CONCLUSIONS: In healthy volunteers the salmeterol/HFA134a inhaler is at least as safe and well tolerated as the current salmeterol inhaler, and has similar systemic pharmacodynamic activity.

Administration, Inhalation↗
PubMed1997

Inhaled nitric oxide and arterial oxygen tension in patients with chronic obstructive pulmonary disease and severe pulmonary hypertension.

BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator which can improve gas exchange in acute lung injury. However, it is uncertain that this effect on arterial oxygenation can be generalised to all lung diseases. METHODS: The effects of inhaled NO on gas exchange were studied in nine patients with chronic obstructive pulmonary disease (COPD), 11 patients with severe pulmonary hypertension, and 14 healthy volunteers. A randomized sequence of 40 ppm of NO or air was inhaled for 20 minutes through an orofacial mask. RESULTS: Inhaled NO reduced mean (SE) transcutaneous arterial oxygen tension (TcPO2) from 9.6 (0.3) to 8.9 (0.4) kPa in healthy volunteers and from 7.4 (0.6) to 7.0 (0.5) kPa in patients with COPD. There was no change in TcPO2 in patients with severe pulmonary hypertension. During inhalation of NO and air no change occurred in transcutaneous arterial carbon dioxide tension (TcPCO2), arterial oxygen saturation (SaO2) measured by pulse oximeter, or cardiac output determined by the transthoracic impedance method. CONCLUSIONS: Inhaled NO does not improve TcPO2 nor increase cardiac output in normal subjects and patients with COPD, suggesting that inhaled NO worsens gas exchange. This could represent inhaled NO overriding hypoxic pulmonary vasoconstriction in COPD. The finding that TcPO2 also fell when normal subjects inhaled NO suggests that a similar mechanism normally contributes to optimal gas exchange. Whilst inhaled NO can improve oxygenation, this effect should not be considered to be a general response but is dependent on the type of lung disease.

Administration, Inhalation↗
PubMed1994

Effect of an inhaled corticosteroid on airway eosinophils and allergen-induced airway hyperresponsiveness in dogs.

The presence of airway eosinophils before allergen inhalation may contribute to the development of allergen-induced airway responses. We examined whether a reduction in airway eosinophil numbers before allergen inhalation as a result of inhalation of the corticosteroid budesonide would prevent allergen-induced airway hyperresponsiveness in seven dogs. Acetylcholine airway responsiveness was measured before and 24 h after inhalation of Ascaris suum allergen (10(-6)-10(-2) wt/vol) or its diluent on 4 test days separated by > or = 4 wk. Dogs were pretreated for 7 days before and on the morning of each test day with inhaled budesonide (2.69 mg/day) or a placebo (lactose). Airway eosinophil numbers were assessed by bronchoalveolar lavage. Inhaled budesonide significantly reduced the number of airway eosinophils before allergen inhalation from 3.6 +/- 2.38 x 10(4) (SE) cells/ml after inhaled lactose to 0.3 +/- 0.21 x 10(4) cells/ml after inhaled budesonide (P = 0.028). The decrease in eosinophil number was associated with a significant reduction in allergen-induced airway hyperresponsiveness (P = 0.005). These results support the hypothesis that the number of eosinophils in the airways before allergen inhalation is an important determinant in the development of allergen-induced airway hyperresponsiveness in dogs.

Administration, Inhalation↗
PubMed1995

The effect of inhalation of platelet-activating factor on the pulmonary clearance of 99mTc-DTPA aerosol.

Platelet-activating factor (PAF) is a short-acting, lipid-soluble autocoid, inhalation of which causes an immediate pulmonary vascular sequestration of granulocytes and a peripheral neutropenia. We investigated the effect of PAF inhalation on the pulmonary clearance rate of inhaled 99mTc-DTPA in order to test the hypothesis that the pulmonary sequestration of granulocytes results in acute lung injury. In nine normal nonsmoking adults, the rate of clearance of DTPA, corrected for background activity, was 1.5 (SD 0.7) %/min over the first 10 min after inhalation. Inhalation of 4.8 micrograms PAF abruptly increased the clearance rate to a mean value of 2.3 (1.4) %/min (p < 0.05). No increase in clearance was observed in four nonsmoking subjects who inhaled vehicle only. The mean overall increase after PAF was 87% of the baseline clearance, significantly different (p < 0.05) from the corresponding change in the control group, which was -17%. After PAF, the clearance rate returned to baseline values within 10 min in all subjects. In all subjects who inhaled PAF, but in none who inhaled vehicle, there was an immediate neutropenia of 51 (SD 25) % of the baseline value (p < 0.01). This neutropenia persisted longer than the corresponding accelerated DTPA clearance and was still 74 (36) % of the baseline value at 10 min. Furthermore, there was no correlation between the increase in DTPA clearance induced by PAF inhalation and the decrease in peripheral blood granulocyte count. We conclude that PAF inhalation results in an increase in pulmonary DTPA clearance, probably not mediated by pulmonary vascular granulocyte sequestration.

Administration, Inhalation↗
PubMed1996

The effect of regular inhaled albuterol on exercise-induced bronchoconstriction.

Pretreatment with inhaled beta 2-agonists is often recommended for the prevention of exercise-induced bronchoconstriction. Regular treatment with inhaled beta 2-agonists has been associated with worsened baseline airway caliber and increased airway responsiveness. In this study, we have investigated the effects of regular inhaled albuterol on the severity of exercise-induced bronchoconstriction using a double-blind, placebo-controlled, randomized, crossover design. Ten subjects inhaled either albuterol or placebo (2 x 100 micrograms, four times per day) for 7 d. On the eighth and ninth days of treatment periods, subjects performed 5-min constant work rate cycle ergometry exercise challenges after inhaling 200 micrograms of placebo (eighth day) or albuterol (ninth day). Forced expired volume in 1 s (FEV1) was measured on arrival in the laboratory as well as before and for 1 h after exercise. One week of regular inhaled albuterol compared with placebo resulted in: (1) a lower baseline FEV1 (mean difference, 230 ml) (p = 0.02); (2) a lower minimum postexercises FEV1 without inhaled albuterol pretreatment (mean difference, 390 ml; range, -50 ml to 1,250 ml) (p = 0.01); (3) a lower minimum postexercise FEV1 with inhaled albuterol pretreatment (p < 0.01). The smallest degree of exercise-induced bronchoconstriction occurred after a week of regular placebo and pretreatment with inhaled albuterol immediately before exercise. Inhalation of albuterol four times daily for 1 wk worsens exercise-induced bronchoconstriction; however, it remains extremely effective when used immediately before exercise for preventing bronchoconstriction.

Administration, Inhalation↗
PubMed1990

Acute and long-term amiloride inhalation in cystic fibrosis lung disease. A rational approach to cystic fibrosis therapy.

Cystic fibrosis (CF) is the most common inherited fatal disorder among Caucasians. Bronchial mucus in CF contains more potassium and less sodium, which may be due to increased sodium absorption, resulting in a reduced airway water content. We studied 23 patients with CF after inhalation of normal saline or amiloride (10(-3) M), a sodium transport blocker. Mucociliary clearance (MC) and cough clearance (CC) were determined with a gamma camera that traced the movement of 99mTc-labeled, hardened erythrocytes over a 1-h period after the patients inhaled these particles as an aerosol. Before and after each investigation pulmonary function tests (PFT) and blood pressure (BP) were measured. Sputum thread formation was measured by means of a filancemeter. Six of the patients also completed a 3-wk trial of amiloride inhalation therapy. MC increased significantly (p less than 0.001) after acute amiloride inhalation (bronchial deposition, 0.07 mg amiloride) compared with that in the saline control. CC also increased, but not as much as MC. After 3 wk of amiloride inhalation (2 times a day) clearance values (both MC and CC) were markedly enhanced (p less than 0.01); after a similar period of saline inhalation, clearance values were not different from baseline. Sputum filance values also decreased significantly after amiloride inhalation. There were no adverse effects of the amiloride inhalation compared with saline. We conclude that amiloride inhalation administered as a single dose or as long-term therapy is able to increase MC and CC in CF airways and that the effect of 10(-3) M amiloride inhalation on MC lasts at least 40 min. (ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Metered-dose inhaler adherence in a clinical trial.

We studied patterns of inhaler usage in a sample of participants from two centers in the Lung Health Study clinical trial. The inhaler, containing either ipratropium bromide or a placebo, was prescribed to be taken as two inhalations three times daily. For 4 months we recorded adherence by both self-report (n = 95) and canister weight change (n = 70). We compared these results with data obtained from a microprocessor monitoring device, the Nebulizer Chronolog (NC), which records the date and time of each inhaler actuation. Seventy-three percent of the participants reported using the inhaler an average of three times daily; however, NC data showed that only 15% of the participants actually used the inhaler an average of 2.5 or more times per day. Canister weight overestimated adherence because only 62% of the NC sets contained the prescribed two actuations. Fourteen percent showed a pattern of actuation of their inhalers more than 100 times in a 3-h interval. We interpret this usage pattern to reflect deliberate emptying of inhalers to appear to be in good compliance with the prescribed program. We conclude that self-report and weighing of inhaler canisters overestimate adherence to the prescribed regimens. Furthermore, a substantial number of monitored inhaler users appear to deliberately dump their medication prior to follow-up visits.

Administration, Inhalation↗
PubMedDate not supplied

Inhalation studies in laboratory animals--current concepts and alternatives.

Highly standardized and controlled inhalation studies are required for hazard identification to make test results reproducible and comparable and to fulfill general regulatory requirements for the registration of new drugs, pesticides, or chemicals. Despite significant efforts, the results of inhalation studies have to be analyzed judiciously due to the great number of variables. These variables may be related to technical issues or to the specific features of the animal model. Although inhalation exposure of animals mimics human exposure best, ie, error-prone route-to-route extrapolations are not necessary, not all results obtained under such very rigorous test conditions may necessarily also occur under real-life exposure conditions. Attempts are often made to duplicate as closely as possible these real-life exposure conditions of humans in appropriate bioassays. However, this in turn might affect established baseline data, rendering the interpretation of new findings difficult. In addition, specific use patterns, eg, of inhalation pharmaceuticals or pesticide-containing consumer products, may impose test agent-specific constraints that challenge traditional approaches. Moreover, specific modes of action of the substance under investigation, the evaluation of specific endpoints, or the clarification of equivocal findings in common rodent species may require exposure paradigms or the use of animal species not commonly used in inhalation toxicology. However, particularly in inhalation toxicology, the choice of animal models for inhalation toxicity testing is usually based on guideline requirements and practical considerations, such as exposure technology, expediency, and previous experience rather than validity for use in human beings. Larger animal species, apart from the welfare aspects, may require larger inhalation chambers to accommodate the animals, but for technical reasons and the difficulty of generating homogeneous exposure atmospheres in such inhalation chambers, this may jeopardize the outcome of the study. Some of the many variables and possible artifacts likely to occur in animal inhalation studies are addressed in this paper.

Administration, Inhalation↗
PubMed2006

Safety of incremental inhaled lipopolysaccharide challenge in humans.

BACKGROUND: Inhalation of environmental endotoxin is important in the pathogenesis of asthma and other environmental airway diseases. Inhaled airway challenge using lipopolysaccharide in humans has been performed for over 20 years to assess the airway response to endotoxin. However, there are no published data on the short-term safety of endotoxin inhalation protocols. OBJECTIVE: To characterize the safety and tolerability of incremental inhaled lipopolysaccharide challenge in humans. PATIENTS AND METHODS: We performed a retrospective analysis of data obtained from 119 subjects who underwent inhaled challenge with up to 41.5 mug of lipopolysaccharide. We measured pulmonary function, temperature, mean arterial pressure, heart rate, and systemic symptoms for 3 h after challenge. RESULTS: Fever occurred in 30% of subjects and was associated with a higher cumulative dose of lipopolysaccharide. Reduced mean arterial pressure occurred in 21% of subjects and was dose-related. There was no association between fever or decreased mean arterial pressure and airway responsiveness to inhaled lipopolysaccharide. Common symptoms reported by subjects included: chills (64%), malaise (56%), cough (56%), chest tightness (49%), headache (43%), and myalgias (27%). None of the subjects experienced delayed discharge or a serious adverse event. CONCLUSIONS: Inhaled lipopolysaccharide causes dose-related systemic responses that include fever, reduced blood pressure, and constitutional symptoms that are not associated with the airway response to inhaled lipopolysaccharide. Systemic responses to inhaled lipopolysaccharide should be expected and subjects undergoing inhaled lipopolysaccharide challenge in the research setting should be carefully monitored for non-pulmonary adverse events for several hours after challenge.

Administration, Inhalation↗