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 667 records · Page 37Linked to original sources
PubMed1999

Prescribing of beta-2 agonists and inhaled steroids in England: trends between 1992 and 1998, and association with material deprivation, chronic illness and asthma mortality rates.

BACKGROUND: British Thoracic Society guidelines published in 1990, revised in 1993 and 1997, recommended that general practitioners should make greater use of inhaled steroids in the management of asthma. British Thoracic Society guidelines have also been published on the management of chronic obstructive pulmonary disease. The objective of this study was to examine trends in the prescribing of beta-2 agonists and inhaled steroids in England between 1992 and 1998, and to investigate the variation at health authority level in the use of these drugs. METHODS: This was an observational study using prescribing analysis and cost (PACT) data, mortality data and data from the 1991 Census for all 100 health authorities in England. RESULTS: The number of defined daily doses of beta-2 agonists prescribed per quarter increased by 20 per cent, from 142 million to 170 million between June 1992 and March 1998. The number of defined daily doses of inhaled steroids prescribed per quarter increased by 78 per cent during the same period, from 69.9 million to 124.7 million. The ratio of inhaled steroids to beta-2 agonists increased from 0.49 to 0.73. The number of items per 1000 specific therapeutic group age-sex related prescribing units (STAR-PUs) in 1997 in health authorities in England varied from 41 to 115 for beta-2 agonists and from 24 to 68 for inhaled steroids. The ratio of the number of items of inhaled steroids to beta-2 agonists varied from 0.50 to 0.70. At health authority level, prescribing rates were most strongly associated with the percentage of patients reporting chronic illness (correlation coefficient 0.82 for beta-2 agonists and 0.72 for inhaled steroids). There were significant negative correlations between the ratio of inhaled steroids to beta-2 agonists and both Jarman deprivation scores (r = -0.51) and chronic illness (r = -0.38). There were no significant associations between health authority prescribing rates and death rates from asthma in people aged 5-44 years. CONCLUSIONS: Prescribing of inhaled steroids has risen more quickly than that of beta-2 agonists between 1992 and 1998, resulting in a marked increase in the ratio of inhaled steroids to beta-2 agonists. At health authority level, there remains a wide variation in the use of beta-2 agonists and inhaled steroids.

Administration, Inhalation↗
PubMed1998

The effect of prolonged inhaled nitric oxide on pulmonary vasoconstriction in rats.

UNLABELLED: Down-regulation of the endogenous nitric oxide (NO) pathway may explain rebound pulmonary hypertension after discontinuation of inhaled NO. We determined whether the prolonged administration of inhaled NO increases pulmonary vasoconstriction, which may occur from decreased endogenous NO. Rats were placed in normoxic (N; 21% O2) or hypoxic (H; 10% O2) chambers with or without inhaled NO (20 ppm) for 1 or 3 wk. Immediately after or 24 h after discontinuation of NO, vasoconstrictive responses were determined in isolated lungs to acute hypoxia (HPV; 0% O2 for 6 min), angiotensin II (0.05 microg), and the thromboxane analog U-46619 in the presence and absence of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 100 microM). Inhaled NO did not alter HPV or angiotensin II vasoconstriction in the N group immediately after or 24 h after discontinuation of NO. In the H group, inhaled NO decreased HPV but had no effect on the angiotensin II vasoconstriction compared with H alone. Inhaled NO did not alter the response to L-NAME. Inhaled NO did not alter, whereas L-NAME significantly decreased, the dose of U-46619 required to increase the pulmonary pressure by 10 mm Hg. In conclusion, prolonged inhaled NO decreased or did not alter HPV and did not alter vasoconstriction secondary to angiotensin II, U-46619, or L-NAME in N and H rats. These results suggest that prolonged inhaled NO does not increase pulmonary vasoconstriction, as would be expected from down-regulation of endogenous NO. IMPLICATIONS: High pulmonary pressure has been observed clinically after discontinuation of inhaled NO. This rat study suggests that 1-3 wk of inhaled NO does not increase pulmonary vasoconstriction, as would be expected from decreasing the endogenous vasodilator NO.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2004

Inhalant abuse and dependence among adolescents in the United States.

OBJECTIVE: To examine the patterns of inhalant use and correlates of the progression from inhalant use to abuse and dependence among adolescents aged 12 to 17. METHOD: Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Multinominal logistic regression was used to identify the characteristics associated with progression to inhalant abuse and dependence. RESULTS: Inhalant use was common among the studied adolescents. Among adolescents aged 12 to 17, 0.4% met DSM-IV inhalant abuse or dependence criteria in the past year. Inhalant abuse and dependence affected adolescents regardless of gender, age, race/ethnicity, and family income. The progression from inhalant use to abuse or dependence was related to early first use, use of multiple inhalants, and weekly inhalant use. Adolescents with inhalant use disorders reported coexisting multiple drug abuse and dependence, mental health treatment, and delinquent behaviors. CONCLUSIONS: Adolescents with an inhalant use disorder may represent a subgroup of highly troubled youths with multiple vulnerabilities. Because early use is associated with progression to abuse and dependence, prevention programs should target elementary school-age children.

Administration, Inhalation↗
PubMed1996

Comparison of three inhaled non-steroidal anti-inflammatory drugs on the airway response to sodium metabisulphite and adenosine 5'-monophosphate challenge in asthma.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are used to assess the role of prostaglandins in asthma but their effects on bronchoconstrictor challenges have been inconsistent. The effects of three nebulised nonsteroidal anti-inflammatory drugs on the airway response to inhaled sodium metabisulphite (MBS) and adenosine 5'-monophosphate (AMP) were compared in the same asthmatic subjects to see whether contractile prostaglandins were involved in MBS or AMP induced bronchoconstriction. A possible protective effect of the osmolarity or pH of the inhaled solutions was also assessed. METHODS: Two double blind placebo controlled studies were carried out. In study 1, 15 non-aspirin sensitive patients with mild asthma attended on four occasions and inhaled 5 ml of lysine aspirin (L-aspirin) 900 mg, indomethacin 50 mg, sodium salicylate 800 mg, or saline 20 minutes before an inhaled MBS challenge. On four further occasions 14 of the patients inhaled the same solutions followed by an inhaled AMP challenge. In study 2, 10 of the patients attended on four additional occasions and inhaled 5 ml of 0.9%, 3%, 10%, or 9.5% saline with indomethacin 50 mg 20 minutes before an inhaled MBS challenge. RESULTS: In study 1 inhaled lysine aspirin had a similar effect on MBS and AMP induced bronchoconstriction, increasing the provocative dose causing a 20% fall in FEV1 (PD20) by 1.29 (95% CI 0.54 to 2.03) and 1.23 (95% CI 0.53 to 1.93) doubling doses, respectively. Indomethacin increased the MBS PD20 and AMP PD20 by 0.64 (95% CI -0.1 to 1.38) and 0.99 (95% CI 0.29 to 1.69) doubling doses, respectively. Sodium salicylate had no significant effect on either challenge. The two solutions causing most inhibition were the most acidic and the most alkaline. In study 2 inhaled 9.5% saline with indomethacin (osmolarity 3005 mOsm/kg) increased the MBS PD20 by 1.1 doubling doses (95% CI 0.2 to 2.0) compared with only 0.09 (95% CI -0.83 to 1.0) and 0.04 (95% CI -0.88 to 0.95) doubling doses with 3% saline (918 mOsm/kg) and 10% saline (2994 mOsm/ kg), respectively. CONCLUSIONS: Inhaled L-aspirin and indomethacin have broadly similar protective effects against MBS and AMP induced bronchoconstriction in the doses given, although the effect of indomethacin on MBS was not quite statistically significant. The osmolarity and pH of the solutions did not appear to be important determinants of the response. The effect of L-aspirin and indomethacin is likely to be the result of cyclooxygenase inhibition reducing the production of contractile prostaglandins during MBS and AMP challenge.

Adenosine Monophosphate↗
PubMed2005

Inhaled nitric oxide induced NOS inhibition and rebound pulmonary hypertension: a role for superoxide and peroxynitrite in the intact lamb.

Previous in vivo studies indicate that inhaled nitric oxide (NO) decreases nitric oxide synthase (NOS) activity and that this decrease is associated with significant increases in pulmonary vascular resistance (PVR) upon the acute withdrawal of inhaled NO (rebound pulmonary hypertension). In vitro studies suggest that superoxide and peroxynitrite production during inhaled NO therapy may mediate these effects, but in vivo data are lacking. The objective of this study was to determine the role of superoxide in the decrease in NOS activity and rebound pulmonary hypertension associated with inhaled NO therapy in vivo. In control lambs, 24 h of inhaled NO (40 ppm) decreased NOS activity by 40% (P<0.05) and increased endothelin-1 levels by 64% (P<0.05). Withdrawal of NO resulted in an acute increase in PVR (60.7%, P<0.05). Associated with these changes, superoxide and peroxynitrite levels increased more than twofold (P<0.05) following 24 h of inhaled NO therapy. However, in lambs treated with polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) during inhaled NO therapy, there was no change in NOS activity, no increase in superoxide or peroxynitrite levels, and no increase in PVR upon the withdrawal of inhaled NO. In addition, endothelial NOS nitration was 18-fold higher (P<0.05) in control lambs than in PEG-SOD-treated lambs following 24 h of inhaled NO. These data suggest that superoxide and peroxynitrite participate in the decrease in NOS activity and rebound pulmonary hypertension associated with inhaled NO therapy. Reactive oxygen species scavenging may be a useful therapeutic strategy to ameliorate alterations in endogenous NO signaling during inhaled NO therapy.

Administration, Inhalation↗
PubMed1997

Prevalence of inhaled corticosteroid use among patients with chronic obstructive pulmonary disease: a survey.

OBJECTIVE: To determine the extent of inhaled corticosteroid use among patients with chronic obstructive pulmonary disease (COPD). DESIGN: Review of medical records. SETTING: Tertiary-care university teaching hospital. PATIENTS: Seventy-two consecutive patients prescribed an inhaled corticosteroid during hospitalization. INTERVENTION: None. MEASUREMENTS: Patient demographics, inhaled corticosteroid regimen, respiratory diagnosis, and inhaled corticosteroid use before and during hospitalization. RESULTS: The majority of patients (85%) were receiving their prescribed corticosteroid inhaler prior to admission. Beclomethasone dipropionate 250 micrograms/puff was the most commonly prescribed inhaled corticosteroid formulation accounting for 43% of the total corticosteroid inhaler orders. COPD was the most common respiratory diagnosis (43%) associated with inhaled corticosteroid use, followed by asthma (37%), COPD/asthma (13%), and no diagnosis (7%). During the study period, the proportion of all hospitalized patients with COPD who also received inhaled corticosteroid prescriptions (35%) was not significantly different from all hospitalized patients with asthma who received inhaled corticosteroid prescriptions (33%). CONCLUSIONS: The rate of inhaled corticosteroid use far exceeds the rate expected among the general population of patients with COPD. Educational intervention is needed to encourage compliance with published guidelines for the management of COPD.

Administration, Inhalation↗
PubMed2004

Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma.

OBJECTIVES: This study evaluated the efficacy and safety of a novel asthma management strategy--budesonide/formoterol for both maintenance and symptom relief (Symbicort Single Inhaler Therapy)--compared with a higher maintenance dose of budesonide in patients with moderate to severe asthma. METHODS: This was a 12-month, randomised, double-blind, parallel-group study. Symptomatic patients with asthma (n = 1890; mean age 43 years [range 11 years-80 years], mean baseline forced expiratory volume in 1 s [FEV(1)] 70% of predicted, mean inhaled corticosteroid [ICS] dose 746 microg/day) received either budesonide (160 microg, 2 inhalations twice daily) plus terbutaline 0.4 mg as needed or a daily maintenance dose of budesonide/formoterol (160/4.5 microg, 2 inhalations once daily) with additional inhalations of budesonide/formoterol 160/4.5 microg as needed. Time to first severe exacerbation (hospitalisation/emergency room [ER] treatment or systemic steroids due to asthma worsening or a fall in morning peak expiratory flow [PEF] to < or = 70% of baseline on 2 consecutive days) was the primary outcome variable. RESULTS: A total of 1890 patients were randomised, of whom 1563 (83%) had severe asthma. The time to first severe exacerbation was prolonged by budesonide/formoterol single inhaler therapy (p < 0.001) compared with a higher dose of budesonide. The risk of having a severe exacerbation was 39% lower with budesonide/formoterol single inhaler therapy compared with budesonide (p < 0.001). The number needed to treat to prevent one severe exacerbation per year with budesonide/formoterol compared with budesonide was 5. The budesonide/formoterol group had 45% fewer severe exacerbations requiring medical intervention per patient compared with the budesonide group (p < 0.001). Budesonide/formoterol patients had fewer hospitalisations/ER treatments (15 vs 25 events, respectively [descriptive statistics]) and fewer treatment days with systemic steroids (1776 days vs 3177 days, respectively [descriptive statistics]) compared with budesonide patients. Budesonide/formoterol single inhaler therapy patients used less as-needed medication compared with budesonide patients (0.90 vs 1.42 inhalations/day; p < 0.001). The mean daily ICS dose was lower in the budesonide/formoterol group than in the budesonide group (466 microg/day vs 640 microg/day). Over the 12-month study period, the budesonide/formoterol group achieved asthma control sufficient to not require any additional as-needed medication on 60% of days. Overall, budesonide/formoterol single inhaler therapy gave 31 more asthma control days (a night and day with no asthma symptoms and no as-needed medication use) per patient-year and 12 additional undisturbed nights per patient-year compared with a higher dose of budesonide. Both treatments were well tolerated. CONCLUSION: Budesonide/formoterol single inhaler therapy has the potential to provide a complete asthma management approach with one inhaler, demonstrating a high level of efficacy in patients with moderate to severe asthma.

Administration, Inhalation↗
PubMed1995

Inhaled budesonide therapy for patients with stable COPD.

A significant minority of patients with COPD have favorable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side effects. Long-term administration of inhaled steroids is a safe means of treatment. We hypothesized that treatment with high-dose inhaled budesonide would improve clinical symptoms and pulmonary function in subjects with COPD, and that the response to inhaled beta 2-agonist will serve to individualize steroid responders. We compared a 6-week course of 800 micrograms/d inhaled budesonide with placebo, separated by 4 weeks when no medication was taken, in a double-blind crossover trial, in 8 patients responding to inhaled beta 2-agonist, and in 22 nonresponders with stable COPD. In six of eight "responders to beta 2-agonist," there was a significant improvement in the FEV1 (defined as > or = 20%) following inhaled budesonide, as compared with placebo. In the 22 "nonresponders to beta 2-agonist," there was no significant improvement in the mean FEV1 (1.41 +/- 0.1 L before, and 1.61 +/- 0.1 L after treatment) with inhaled budesonide or placebo. Over the 6-week course of treatment by either budesonide or placebo, the nonresponders reported similar beta 2-agonist consumption (4.8 +/- 0.2 and 5.0 +/- 0.1 puffs per patient per day, respectively). However, there was a significant difference between the two periods of treatment in the responders as for the mean daily number of beta 2-agonist inhalations (2.4 +/- 0.1 in the budesonide period as compared with 5.3 +/- 0.1 in the placebo period; p < 0.005). We conclude that treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about 25% of patients with stable COPD, and this rate is increased to about 75% in patients who respond to beta 2-agonist inhalation.

Administration, Inhalation↗
PubMed2006

Relationship between self-reported odor intolerance and sensitivity to inhaled capsaicin: proposed definition of airway sensory hyperreactivity and estimation of its prevalence.

STUDY OBJECTIVES: The aim of this study was to investigate the relationship between the behavioral consequences of self-reported odor sensitivity with the chemical sensitivity scale for sensory hyperreactivity (CSS-SHR) and cough sensitivity to inhaled capsaicin. We also wanted to estimate the prevalence of airway sensory hyperreactivity (SHR), which was defined as a positive CSS-SHR score in combination with a positive capsaicin inhalation test result. DESIGN: A general population-based study with randomly selected individuals after stratification for age and gender. SETTING: Skövde Central Hospital, Departments of Lung Medicine and Otorhinolaryngology, Sweden. PARTICIPANTS: A total of 693 randomly selected individuals from a population-based study in which 595 persons (86%) responded to the CSS-SHR questionnaire. INTERVENTIONS: The individuals were divided into four groups with different odor sensitivity according to their CSS-SHR score. Of these, 137 individuals were randomly recruited for the capsaicin inhalation test. Capsaicin inhalation was performed with concentrations of 0.4 and 2.0 mumol/L in a randomized order. The number of coughs were registered and counted for 10 min from the start of each inhalation. MEASUREMENTS AND RESULTS: Of the 137 individuals who were recruited for the capsaicin inhalation test, 103 (75%) participated. Sixteen individuals had increased cough sensitivity and fulfilled the criteria for a positive capsaicin inhalation test result. Of the individuals with a positive capsaicin inhalation test result, > 80% also had a positive CSS-SHR score. Only 5% of the individuals with a negative CSS-SHR score had a positive capsaicin inhalation test result. The order of inhaled capsaicin concentration was found to influence the results. The prevalence of SHR with the definition given above was estimated to be 6.3% in this general population. CONCLUSIONS: A high CSS-SHR score was found to be directly related to the sensitivity for inhaled capsaicin, which made it possible to relate subjective data to objective findings.

Administration, Inhalation↗
PubMed1997

Childhood abuse and the use of inhalants: differences by degree of use.

OBJECTIVES: Using two existing ethnographic studies of drug-involved adults, this study evaluates the association between child-abuse victimization and levels of involvement in inhalant use. METHODS: Historical accounts of childhood exposure to physical or sexual abuse were compared among nonusers of inhalants (n = 197), light inhalant users (n = 64), and heavy inhalant users (n = 24). Crude and adjusted odds ratios were used to compare informants with no history of inhalant use with those having a history of light inhalant use and those having a history of heavy inhalant use. RESULTS: Heavy inhalant use was associated with history of any child abuse (adjusted odds ratio [OR] = 4.6) and physical abuse (adjusted OR = 3.8). Light inhalant use showed no association with child-abuse history. CONCLUSIONS: Child abuse may be an important correlate of extensive involvement in inhalant use. The findings invite speculation with respect to a hypothetical causal role for child abuse in the etiology of inhalant use. The lack of support for causality in this study underscores the need for replication and more carefully designed longitudinal research.

Adhesives↗
PubMed2000

Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer.

OBJECTIVE: To study the metabolic effect and the variability of the effect elicited by inhalation of 87.2 U insulin powder combined with an absorption enhancer. The metabolic effect was compared with that of 10.2 U regular insulin injected subcutaneously and of 5.5 U regular insulin given intravenously RESEARCH DESIGN AND METHODS: In this single-center open euglycemic glucose clamp study 13 healthy male volunteers received 5 insulin administrations on separate study days: once as an intravenous dose, once as a subcutaneous injection, and 3 times by inhalation, in randomized order. Glucose infusion rates (GIRs) necessary to keep blood glucose concentrations constant at 5.0 mmol/l were determined over an 8-h period after administration. RESULTS: After inhalation of the insulin powder aerosol, the onset of action was substantially more rapid than after subcutaneous insulin injection, and maximal action was reached earlier (86+/-47 vs. 182+/-53 min, P<0.0001). The maximal glucose infusion rate after inhalation of insulin was comparable to that after subcutaneous insulin injection (9.2+/-2.6 vs. 8.8+/-2.8 mg x kg(-1) x min(-1), NS). The metabolic effect in the first 2 h after inhalation was significantly greater than that after subcutaneous insulin injection (amount of glucose infused: 0.88+/-0.25 vs. 0.59+/-0.20 g x kg(-1) x 120 min(-1), P<0.0001). However, the total metabolic effect after inhalation and subcutaneous injection was comparable (2.50+/-0.76 vs. 2.56+/-0.69 g x kg(-1) x 480 min(-1), NS). The relative bioefficacy of inhaled insulin calculated in relation to the data from the subcutaneous insulin application was 12.0+/-3.5% (absolute bioefficacy 10.1+/-3.1%) but was highest in the first 2 h after application (18.5+/-3.7%; absolute bioefficacy 8.2+/-4.1%). The intraindividual variability of the metabolic response induced by insulin inhalation was 14+/-9% for the maximal glucose infusion rate, 15+/-10% for the time-to-maximal effect, and 16+/-12% for the total amount of glucose infused. CONCLUSIONS: This feasibility study shows that inhaled insulin with an absorption enhancer has a pronounced metabolic effect compared with the results of a previous study of inhaled insulin without an enhancer. The intraindividual variability of the metabolic effect was comparable with that of inhaled and subcutaneously injected insulin.

Administration, Inhalation↗
PubMedDate not supplied

Retention of particles inhaled in boli with and without induced bronchoconstriction.

Large lung retentions (up to 50%) of particles < or = 4 microns inhaled with a bolus technique at a penetration depth less than dead space have been reported to occur after 24 h. This retention may be due to retarded clearance of particles deposited in the airways of the tracheobronchial tract; an alternative explanation could be that particles are deposited in the alveolar region. The purpose of the present study was to confirm the occurrence of retained fractions and to study the influence of a cholinergic drug, which is assumed to give a more central particle deposition, on these retentions in human lungs after shallow aerosol bolus inhalation. Twelve healthy subjects inhaled, with a bolus technique, monodisperse Teflon particles (2.4 microns geometric diameter, 3.5 microns aerodynamic diameter), labeled with 111In. The volumetric lung depth of the inspired bolus was around 60 mL and flow rate was about 300 mL/s. Six subjects inhaled the test particles after a provocation with a cholinergic aerosol, which induced a threefold increase in airway resistance. The other six subjects inhaled a cholinergic aerosol after inhalation of the test particles or inhaled no cholinergic aerosol at all. Radioactivity in the body was measured after 0.5, 24, 48, and 72 h with a whole-body scanner with three 127 x 101-mm Nal detectors. The investigation confirmed results obtained earlier by a group in Frankfurt claiming that great retentions occur after 24 h. The retentions tended to be lower in the group receiving a bronchoconstricting drug before the bolus inhalations. There was a significant lung clearance of particles between 24 and 72 h, in contrast to the findings in earlier studies in healthy subjects and asthmatics who inhaled Teflon particles in large volumes. On the other hand, the clearance agreed well with the clearance in healthy subjects with extensive deposition of Teflon particles in the small ciliated airways, obtained by means of an extremely low inhalation flow rate. The results suggest that a considerable fraction of the particles in the bolus inhalation have been deposited in small ciliated airways in which the mucociliary transport is less efficient or in the alveolar region.

Administration, Inhalation↗
PubMed1996

Significance of particle parameters in the evaluation of exposure-dose-response relationships of inhaled particles.

Chronic rat inhalation studies have shown that a number of different particle types can induce significant adverse effects, including impaired lung clearance, chronic pulmonary inflammation, pulmonary fibrosis, and lung tumors. These effects occurred when highly insoluble particles of low solubility and low cytotoxicity were inhaled in long-term studies. Inhaled concentrations ranged from a few milligrams per cubic meter up to 250 mg/m3. This wide range of inhaled concentrations may indicate that the particulate compounds have differed largely in their toxicity. This view appears to be supported by the fact that cytotoxic crystalline SiO2 shows very similar effects after much lower inhaled concentrations. However, although administered doses are customarily expressed in units of mass, this may not be the appropriate dose-metric for a correlation with observed effects. For example, effects on alveolar macrophage (AM) mediated clearance of particles could best be correlated with the volumetric lung burden of different particle types, suggesting that the particle volume phagocytized by AM is an appropriate dose parameter for this endpoint. On the other hand, the inflammatory response induced by a number of different particle types could best be correlated with the surface area of the particles retained in the alveolar space. In addition, total surface area of retained particles was the best dose parameter (or a correlation when the endpoint was lung tumors. In all of these studies crystalline SiO2 did not fit into the overall exposure-response or dose-response relationship, clearly demonstrating that SiO2 is a very different (more cytotoxic) particle type. Particle size and surface area can play important roles in the response to inhaled particles, which is especially relevant for ultrafine particles. Inhalation studies with rats exposed to aggregated ultrafine TiO2 and carbon black showed that both compounds induced lung tumors in rats at considerably lower gravimetric lung burdens than larger sized TiO2. However, the different ultrafine particle types did also show differences in the strength of response that cannot be explained by differences in surface area only. Analyses of inhalation studies with ultra fine particles show that the movement of particles from alveolar spaces into interstitial sites appears to reflect the ability of inhaled ultrafine particle aggregates (TiO2; carbon black) to break down into smaller units, or even singlet particles. Further data are needed to evaluate the importance of interstitial cell-particle interactions for the long-term effects. The lung tumor response in rats after chronic high-dose particle inhalation has been suggested to be a rat-specific response that may not be relevant to humans. However, lacking an understanding about mechanistic events, the rat model should not be dismissed prematurely. What should be questioned instead is the relevance of using excessively high exposure concentrations of particles in a rat study. Exposure-response and dose-response relationships for different endpoints indicate the existence of a threshold below which no adverse effects may occur. Such a threshold could be explained by overwhelming specific defense mechanisms in the respiratory tract, such as particle loading of macrophages (prolongation of particle clearance), or limitations of pulmonary antioxidant capacities (inflammatory response). It appears, however, that duration of exposure plays a significant role that can result in a shift of exposure-dose-response relationships and a shift of a threshold when these relationships are compared at the end of a subchronic study versus the end of a chronic study. This shift will cause difficulties for defining a threshold as well as a maximum tolerated dose from results of a subchronic particle inhalation study.

Aerosols↗
PubMed1999

[The effect of inhaled nitric oxide and helium-oxygen mixture on the pulmonary function of asthmatics].

OBJECTIVE: To investigate the effect of inhaled nitric oxide (NO) combined with helium-oxygen mixture on the pulmonary function of asthmatics. METHODS: 18 asthmatic patients were included in this study. The patients were divided into two groups randomly. One group of patients inhaled 100 ppm NO combined with helium-oxygen mixture, the other group inhaled 40 ppm NO-containing helium-oxygen mixture. Pulmonary function was examined intermittently during the study process and compared with that of the patients treated with salbutamol. RESULTS: It is shown that inhalation of helium-oxygen mixture improved the forced vital capacity, forced expiratory volume during the first 1.0 second (FEV(1)), peak expiratory flow rate (PEFR) and maximal midexpiratory flow rate (MMEF) significantly as compared with inhalation of air. Although salbutamol inhalation improved FEV(1) and MMEF, the effect was weaker than helium-oxygen mixture inhalation. However the effect of helium-oxygen mixture lasted only one minute. Inhalation of 100 ppm NO with helium-oxygen mixture only slightly improved FEV(1) and PEFR as compared with inhalation of helium-oxygen mixture. 40 ppm NO with helium-oxygen mixture did not influence the pulmonary function in the asthmatic patient as compared with helium-oxygen mixture alone. CONCLUSION: It is suggested that inhalation of helium-oxygen mixture can improve the pulmonary function of asthmatic patients significantly. However, inhalation of NO exerts a weak bronchodilatory effect.

Administration, Inhalation↗
PubMed2002

[Effects of sedative odorant inhalation on patients with atopic dermatitis].

Atopic dermatitis (AD) has been clinically well-known to be frequently exacerbated by psychological and physiological stress. In this study, we examined effects of sedative odorant (modified valerian oil) inhalation on patients with AD. We investigated clinical scores, skin physiological parameters and psychological questionnaire (POMS) every 2 weeks. For first 2 weeks, we arranged non-inhalation period. Results for non-inhalation period were compared with these of 2- or 4-week inhalation. As results, sum of skin clinical scores significantly improved after odorant inhalation. Some patients improved for non-inhalation period, too. However, patients that had not improved for non-inhalation period significantly improved after odorant inhalation. Skin conductance and skin dryness/scaling score also improved after odorant inhalation without improving for non-inhalation period. Psychological parameter (POMS) also tended to improve after odorant inhalation. These results suggest that sedative odorants may be useful as a complementary therapy for AD through psychosomatic stress care.

Administration, Inhalation↗
PubMed1990

[The effect of leukotriene B4 inhalation on airway responsiveness in dogs].

We studied the effect of leukotriene B4 (LTB4) inhalation on airway responsiveness in 12 dogs. LTB4 (10 micrograms/ml) was delivered as an aerosol, generated from a Devilbiss 646 nebulizer for ten minutes. Airway responsiveness to inhaled methacholine was determined by modified Astograph (7 Hz oscillation method) 1 hr (n = 6) and 6 hr (n = 6) after LTB4 inhalation. After measurement of airway responsiveness, total cell counts, differential cell counts, thromboxane B2 (TxB2) and 6-keto-prostaglandin (PG)F1 alpha levels in bronchoalveolar lavage fluid (BALF) were measured. The total cell counts in BALF increased after LTB4 inhalation (p less than 0.05), and the neutrophil counts in BALF increased significantly 1 hr (p less than 0.05) and 6 hr after (p less than 0.01) LTB4 inhalation. Airway responsiveness to inhaled methacholine decreased significantly 1 hr (p less than 0.05) and 6 hr (p less than 0.01) after LTB4 inhalation. There were no significant changes in the levels of TxB2 or 6-keto-PGF1 alpha in BALF 1 hr and 6 hr after LTB4 inhalation. These results suggest that inhaled LTB4 causes neutrophil recruitment into the airway but does not increase airway responsiveness to inhaled methacholine, and the possibility that LTB4 reduces airway responsiveness to inhaled methacholine exists in dogs.

Administration, Inhalation↗
PubMedDate not supplied

Effects of inhaled nitric oxide in single lung transplantation in rats with monocrotaline-induced pulmonary hypertension.

BACKGROUND: The edema of grafted lungs during the early postoperative period is one of the serious complications of single lung transplantation for primary pulmonary hypertension. METHODS: The effectiveness of inhaled nitric oxide in single lung transplantation for primary pulmonary hypertension during the early postoperative period was evaluated with the use of rats with monocrotaline-induced pulmonary hypertension. In the inhaled nitric oxide group, rats were given 60 parts par million of nitric oxide for 24 hours just after left lung transplantation; in the no inhaled nitric oxide group, rats were kept without nitric oxide inhalation; in the control group, normal rats received left isografts. RESULTS: Three hours after transplantation, the mean pulmonary artery pressure of the no inhaled nitric oxide group (28.0 +/- 4.6) was significantly higher than that of the control group (23.3 +/- 0.9, p < 0.05) and the inhaled nitric oxide group (22.7 +/- 1.7, p < 0.05). On the first postoperative day, the mean left-to-right pulmonary blood flow ratio in the inhaled nitric oxide group was 0.34 +/- 0.03; it showed no significant difference to those of the other two groups, whereas that of the no inhaled nitric oxide group (0.42 +/- 0.14) was significantly elevated compared with that of the control group (0.14 +/- 0.03, p < 0.05). Histopathologically, the edema of the grafted lungs 24 hours after operation in the inhaled nitric oxide group was less severe than that in the no inhaled nitric oxide group. CONCLUSIONS: The postoperative use of inhaled nitric oxide is effective to reduce the pulmonary edema of the grafts in single lung transplantation for pulmonary hypertension by reducing acute pulmonary blood flow shift toward grafts after transplantation.

Administration, Inhalation↗
PubMed1994

Pulmonary deposition and clinical response of 99mTc-labelled salbutamol delivered from a novel multiple dose powder inhaler.

Pulmonary deposition of 99mTc-labelled sulbutamol was determined after delivery from a novel multiple dose powder inhaler (Easyhaler). The clinical efficacy of the inhalation powder, evaluated simultaneously with gamma camera detection, was compared with that obtained after drug delivery from a metered dose inhaler-spacer combination. The study was performed as an open, non-randomized cross-over trial. A single dose of radiolabelled inhalation powder was inhaled on the first and the inhalation aerosol, as control, on the second study day. Sulbutamol sulphate was labelled with 99mtechnetium, and the inhalation powder was formulated by mixing radioactive drug particles with carrier material. Aerodynamic properties of the radiolabelled inhalation powder were similar to those of the unlabelled salbutamol powder. Delivered dose from the breath-actuated powder inhaler was adjusted to be equal to two puffs from a conventional aerosol actuator with a short plastic mouthpiece. Twelve non-smoking asthmatic patients participated in the trial. The mean pulmonary deposition of 24% was obtained after drug delivery from Easyhaler powder inhaler. Clinical efficacy of the medications was similar in terms of area under the FEV1 curve, maximum FEV1 and the improvement ratio. Thus it can be suggested that powder delivery from Easyhaler powder inhaler and the aerosol delivery through the spacer are equally effective.

Adult↗