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Inhaled nitric oxide in patients with pulmonary hypertension due to valvular heart disease and chronic lung disease.

The objective of this study was to investigate the effects of inhaled nitric oxide (NO) on chronic pulmonary hypertension (PH). Thirty patients with valvular heart diseases (n=8, group A), chronic lung diseases (n=16, group B), primary PH or PH due to collagen disease (n=6, group C) were studied. NO was delivered for 20 min at concentration of 5, 10, and 20 ppm in spontaneous respiration. After inhalation, percentages of systolic pulmonary artery pressure (%SPAP) levels in group A were significantly decreased compared with those for pre-inhalation by 12%, 14%, and 14% at 5, 10 and 20 ppm, respectively (p<0.05). In group B, %SPAP also significantly decreased by 7, 10, and 14% at 5, 10, and 20 ppm, respectively (p<0.05). However, inhaled NO did not significantly affect %SPAP in group C (p=0.4). There was no significant difference in gas exchange in any of the groups. However, 4 out of 8 patients in group A and 10 out of 16 patients in group B showed decreased partial pressure of arterial oxygen in response to inhaled NO. This study demonstrated that inhaled NO is a selective pulmonary vasodilator in decreasing pulmonary artery pressure (PAP); however, the reaction was different in line with the background disease cause of PH. NO inhalation was most effective on patients with moderate PAP. Furthermore, higher concentrations of NO would be risky in some patients with chronic PH.

Administration, Inhalation↗

Effects of fragrance inhalation on sympathetic activity in normal adults.

We investigated the effects of fragrance inhalation on sympathetic activity in normal adult subjects using both power spectral analysis of blood pressure fluctuations and measurement of plasma catecholamine levels. Fragrance inhalation of essential oils, such as pepper oil, estragon oil, fennel oil or grapefruit oil, resulted in 1.5- to 2.5-fold increase in relative sympathetic activity, representing low frequency amplitude of systolic blood pressure (SBP-LF amplitude), compared with inhalation of an odorless solvent, triethyl citrate (P<0.05, each). In contrast, fragrance inhalation of rose oil or patchouli oil caused a 40% decrease in relative sympathetic activity (P<0.01, each). Fragrance inhalation of pepper oil induced a 1.7-fold increase in plasma adrenaline concentration compared with the resting state (P = 0.06), while fragrance inhalation of rose oil caused a 30% decrease in adrenaline concentration (P<0.01). Our results indicate that fragrance inhalation of essential oils may modulate sympathetic activity in normal adults.

Administration, Inhalation↗

Lung proliferative and clearance responses to inhaled para-aramid RFP in exposed hamsters and rats: comparisons with chrysotile asbestos fibers.

This study compared pulmonary effects of para-aramid respirable-sized, fiber-shaped particles (RFP) (p-aramid fibrils) and chrysotile asbestos fiber exposures in rats. Additional p-aramid inhalation studies were conducted in hamsters to compare species responses. The hamster results are preliminary. The parameters studied were clearance/biopersistence of inhaled p-aramid RFP or size-separated asbestos fibers as well as pulmonary cell proliferation and inflammation indices after 2-week inhalation exposures. Rats were exposed nose only to chrysotile asbestos fibers at concentrations of 459 and 782 fibers/ml or to p-aramid RFP at 419 or 772 fibrils/ml. Hamsters were exposed whole body to p-aramid RFP at concentrations of 358 and 659 fibrils/ml. Subsequently, animals were assessed immediately (time 0) as well as 5 days (10 days for hamsters), 1, 3, 6, and 12 months postexposure. Lung burdens for the p-aramid-exposed rats were 4.8 x 10(7) and 7.6 x 10(7) fibrils/lung, with similar numbers of chrysotile fibers > 5 microns recovered from the lungs of asbestos-exposed rats. In comparison, 1.4 x 10(6) fibrils/lung were recovered in the high-dose hamster group. Biopersistence studies in p-aramid-exposed rats and hamsters demonstrated an initial increase (relative to time 0) in retained p-aramid fibrils during the first month postexposure, which indicated breakage or shortening of inhaled fibrils. This result was associated with a progressive reduction, and increased residence time in the lung, in the mean lengths of the fibrils, which signified biodegradability of inhaled p-aramid fibrils in both species. In contrast, clearance of short chrysotile asbestos fibers was rapid, but clearance of the long chrysotile fibers was slow or insignificant, as evidenced by a progressive increase over time in the mean lengths of fibers recovered from the lungs of exposed rats. Two-week, high-dose exposures to p-aramid in both rats and hamsters produced transient increases in pulmonary inflammatory and cell proliferative responses. In contrast, inhalation of size-separated chrysotile asbestos fibers in rats produced persistent increases in cell labeling indices of airway, alveolar, and subpleural cells measured through a period of 1 to 3 months postexposure. These results suggest that inhaled p-aramid RFP are biodegradable in the lungs of exposed rats and hamsters. In contrast, exposures to chrysotile asbestos fibers in rats resulted in a selective pulmonary retention of long chrysotile fibers.

Administration, Inhalation↗

Metabolic effects of inhaled fenoterol in normal subjects.

Although the hypokalemic effect of inhaled beta 2-adrenergic agonists has been well documented, little is known as to their effect on plasma magnesium. We therefore examined in ten healthy young volunteers the effect of the inhalation of 2 mg of nebulized fenoterol on plasma potassium (Kpl), plasma magnesium (Mgpl), and intraerythrocytic magnesium (MgIE) levels, as well as on plasma insulin and C peptide concentrations, measured before and serially up to 110 min after fenoterol inhalation. In all subjects, fenoterol inhalation caused a reversible reduction in Kpl (range, 0.2 to 1.1 mEq/L), which was progressive, reaching a statistically significant nadir 30 to 60 min following fenoterol inhalation (largest dip in Kpl, 0.55 +/- 0.29 mEq/L; p < 0.05). The nadir in Kpl levels was preceded by a peak in plasma insulin levels in all subjects. No significant changes in Mgpl or MgIE were observed in any of the subjects. We conclude that fenoterol inhaled at a dosage used in clinical practice significantly reduces Kpl but not Mgpl nor MgIE levels in healthy subjects, indicating a lower sensitivity of Mg++ ions to beta 2-adrenergic stimulation than K+ ions. Beta 2-adrenergic-induced insulin secretion probably contributes to the hypokalemic effect of inhaled fenoterol.

Administration, Inhalation↗

Emergency department treatment of severe asthma. Metered-dose inhaler plus holding chamber is equivalent in effectiveness to nebulizer.

STUDY OBJECTIVE: To compare the effectiveness of administration of albuterol by nebulizer or by a metered-dose inhaler having a holding chamber attachment (hereafter "inhaler") for treatment of acute asthma in an emergency department (ED). DESIGN: A randomized, double-blind, placebo-controlled intervention study conducted at two sites. SETTING: The EDs of a large municipal hospital and a university teaching hospital. PATIENTS: Thirty-five patients 10 to 45 years of age seeking treatment at an ED for acute asthma. INTERVENTIONS: Patients were randomly assigned to receive either albuterol by nebulizer plus placebo by inhaler (n = 20) or albuterol by inhaler plus placebo by nebulizer (n = 15). The dose was repeated every 30 min until the FEV1 was at least 80 percent of predicted, the patient became asymptomatic, or 6 doses had been given. MEASUREMENTS AND RESULTS: All references in this article to spirometric measurements of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR) represent percentages of the predicted normal value. No significant (p > 0.58) differences occurred in baseline mean FEV1, FVC, or PEFR for the two groups. For both groups, significant improvement occurred in mean FEV1 at 30 min (p < 0.02) and at 60 min (p < 0.02), and in maximum mean FEV1 (p < 0.001). However, no significant (p > 0.6) differences occurred between groups in mean FEV1, FVC, or PEFR at 30 and 60 min, or in maximum improvement attained. The sample size was sufficiently large to detect a 12 percent difference in improvement with a power of 90 percent. Thirty-three of 35 patients were treated successfully with the study protocol, became asymptomatic, and were discharged home. One patient from each group required further treatment. CONCLUSIONS: There was no detectable difference in effectiveness of albuterol administered by nebulizer or the inhaler system for treatment of acute asthma. There was no detectable difference in effectiveness of albuterol administered by nebulizer or the inhaler system for the treatment of acute asthma when the dose was titrated to clinical response. When compared with nebulizer, the metered-dose inhaler with holding chamber delivers a full dose of albuterol more quickly and at no higher cost.

Administration, Inhalation↗

Inhaled nitric oxide reverses hypoxic pulmonary vasoconstriction in dogs. A practical nitric oxide delivery and monitoring system.

Nitric oxide (NO) is a potent dilator of vascular smooth muscle that likely represents an important endothelium-dependent relaxing factor. Recent interest has focused on inhaled NO as a pulmonary vasodilator. The purpose of this study was to design a reliable NO delivery system with on-line monitoring of NO and nitrogen dioxide (NO2) concentrations, and to test the effects of inhaled NO in a dog model of acute hypoxic pulmonary vasoconstriction (HPV). Six canines were studied. Marked HPV was induced using a hypoxic gas mixture. Using a standard blender. NO was delivered through a volume-cycled ventilator. We were able to rapidly adjust the delivered NO concentration using this system. An on-line chemoluminescence analyzer was used to continuously measure NO and NO2 concentrations. Inhaled NO at 40 and 80 ppm for 30 min rapidly reversed HPV in all animals (PVR 502 +/- 154 dynes.s.cm-5 with hypoxia, 244 +/- 52 with 40 ppm NO, 227 +/- 47 with 80 ppm NO). No significant NO2 or methemoglobin production was noted during the study. We conclude that inhaled NO can be easily delivered through a ventilator and the dose rapidly adjusted, NO and NO2 concentrations can be monitored continuously on-line, inhaled NO rapidly reverses HPV in dogs, and with short-term NO inhalation, there is no significant NO2 or methemoglobin formation. Inhaled NO may, therefore, have a future clinical role as a new agent in the diagnosis and treatment of other forms of pulmonary hypertension.

Administration, Inhalation↗

Inhaled nitric oxide selectively decreases pulmonary artery pressure and pulmonary vascular resistance following acute massive pulmonary microembolism in piglets.

Acute massive pulmonary embolism increases pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR), which may lead to early right ventricular failure and subsequent cardiocirculatory deterioration. Inhaled nitric oxide (NO) selectively dilates pulmonary vessels in vivo. Thus, inhaled NO may be useful in preventing cardiocirculatory deterioration following pulmonary embolism. We investigated the effects of inhaled NO in the acute phase of massive pulmonary microembolism in 10 anesthetized and mechanically ventilated piglets (body weight, 18 +/- 2 kg). Microspheres of 300-microns diameter were injected i.v. in an amount sufficient to initially increase mean PAP to 45 mm Hg. Forty-five minutes after pulmonary embolization, the pretreatment control values were recorded. Thereafter, the piglets inhaled 40 ppm NO, and subsequently 80 ppm NO. When 40 ppm NO was inhaled, there was a significant decrease in systolic PAP (-10.3%; 44.5 +/- 2.2 to 39.9 +/- 2.4 mm Hg; p < 0.05) and mean PAP (-9.4%; 32.9 +/- 1.3 to 29.8 +/- 1.3 mm Hg; p < 0.05). PVR was changed by -13.6% (p = 0.07). Administration of 80 ppm NO resulted in a significant decrease in systolic PAP (-12.6%; to 38.9 +/- 1.9 mm Hg; p < 0.05), mean PAP (-11.9%; to 29.0 +/- 1.4 mm Hg; p < 0.05), and PVR (-19.4%; p < 0.05) compared with pretreatment values. Discontinuation of NO inhalation was associated with an immediate return to pretreatment values. Systemic hemodynamics and the arterial and mixed venous oxygen concentrations remained unchanged. We conclude that inhaled NO following acute massive pulmonary microembolism selectively decreases PAP and PVR without influencing systemic hemodynamics in piglets.

Administration, Inhalation↗

Analysis of inhaled corticosteroid and oral theophylline use among patients with stable COPD from 1987 to 1995.

STUDY OBJECTIVE: To document temporal usage trends for commonly used respiratory medications in patients with COPD. DESIGN: We retrospectively evaluated baseline concomitant medications of 3,720 patients with COPD enrolled in 10 bronchodilator clinical trials from 1987 to 1995. The proportion of patients in each trial using inhaled corticosteroids, inhaled beta-adrenergics, inhaled anticholinergics, oral theophylline, and oral corticosteroids was analyzed using the Cochran-Armitage trend test. PATIENTS: All patients had stable, moderate-to-severe COPD without evidence of asthma or atopy. Reversibility to beta3-agonists was not a requirement. RESULTS: The percentage of patients using inhaled corticosteroids increased significantly over time (p < 0.001) from 13.2% in 1987 to 41.4% in 1995. The percentage of patients receiving oral theophylline decreased significantly (p < 0.001) over this same time interval (63.4 to 29.0%). In addition, the percentage of patients using oral corticosteroids and the percentage using oral beta-adrenergics decreased moderately (p < 0.05) (30.1 to 16.4% and 11.7 to 4.5%, respectively); the percentage of patients using inhaled anticholinergics increased slowly (p < 0.05) (48.2 to 53.8%). The percentage of patients receiving inhaled beta-adrenergics did not significantly (p > 0.05) change. CONCLUSIONS: The observed changes in use of inhaled corticosteroids and theophylline were not likely related to differences in disease severity or other patient characteristics in the evaluated trials, but related to changing prescribing and COPD management practices.

Administration, Inhalation↗

Salmeterol powder provides significantly better benefit than montelukast in asthmatic patients receiving concomitant inhaled corticosteroid therapy.

STUDY OBJECTIVES: Comparison of inhaled salmeterol powder vs oral montelukast treatment in patients with persistent asthma who remained symptomatic while receiving inhaled corticosteroids. DESIGN: Randomized, double-blind, double-dummy, parallel-group, multicenter trials of 12-week duration. SETTING: Outpatients in private and university-affiliated clinics. PATIENTS: Male and female patients > or = 15 years of age with a diagnosis of asthma (baseline FEV(1) of 50 to 80% of predicted) and symptomatic despite receiving inhaled corticosteroids. INTERVENTIONS: Inhaled salmeterol xinafoate powder, 50 microg bid, or oral montelukast, 10 mg qd. MEASUREMENTS AND RESULTS: Treatment with salmeterol powder resulted in significantly greater improvements from baseline compared with montelukast for most efficacy measurements, including morning peak expiratory flow (35.0 L/min vs 21.7 L/min; p < 0.001), percentage of symptom-free days (24% vs 16%; p < 0.001), and the percentage of rescue-free days (27% vs 20%; p = 0.002). Total supplemental albuterol use was decreased significantly more in the salmeterol group compared with the montelukast group (- 1.90 puffs per day vs - 1.66 puffs per day; p = 0.004) and nighttime awakenings per week decreased significantly more with salmeterol than with montelukast (- 1.42 vs - 1.32; p = 0.015). Patients treated with inhaled salmeterol were significantly more satisfied with their treatment regimen and how well, how fast, and how long it worked than were patients who were treated with oral montelukast. The safety profiles for the two treatments were similar. CONCLUSION: In patients with persistent asthma who remain symptomatic while receiving inhaled corticosteroids, adding inhaled salmeterol powder provided significantly greater improvement in lung function and asthma symptoms and was preferred by patients over oral montelukast.

Acetates↗

Bronchial hyperreactivity in patients who inhale heroin mixed with cocaine vaporized on aluminum foil.

BACKGROUND: In our area, inhaling heroin mixed with cocaine vaporized on aluminum foil, known as rebujo, is becoming more and more common. AIM: To define the prevalence and the characteristics of bronchial disease (wheezing, bronchial hyperreactivity [BHR], and asthma) present in subjects inhaling heroin mixed with cocaine vaporized on aluminum foil. MATERIALS AND METHODS: Ninety-one subjects who inhaled the drug mixture were included in the study: 62 subjects were from a drug rehabilitation center (INH-I group), and 29 subjects were among patients admitted to our hospital for a variety of reasons (INH-II group). A questionnaire was completed in both groups, as well as IgE determination and lung function tests (spirometry and methacholine challenge). The control group consisted of 122 individuals who did not inhale the drug mixture, and were chosen randomly from the general population (NO-INH group). All subjects were tobacco smokers. RESULTS: In the INH-I group, there was a 41.9% prevalence of wheezing over the past 12 months, a 44.4% prevalence of BHR, and a 22.02% prevalence of asthma, defined as wheezing plus BHR. In the NO-INH group, these values were 32.78% (p = 0.22), 15.57% (p < 0.0001), and 8.19% (p < 0.01), respectively. Of the subjects who inhaled the drug mixture and denied having symptoms prior to the use of the drug mixture, 31.4% had wheezing develop after commencing use of the drug, following a mean latency of 4.09 months. Wheezing remitted in only 7.6% after discontinuation of the drug. CONCLUSIONS: (1) There is a real increase in BHR in subjects who inhale heroin mixed with cocaine vaporized on aluminum foil; and (2) this BHR is associated with wheezing that develops after a variable period of latency, once drug inhalation begins, and persists despite discontinuation of the drug.

Administration, Inhalation↗

Leukotriene modifier vs inhaled corticosteroid in mild-to-moderate asthma: clinical and anti-inflammatory effects.

STUDY OBJECTIVE: Evidence for the anti-inflammatory activity of leukotriene receptor antagonists in humans is somewhat limited. There are also no data comparing the anti-inflammatory effects of leukotriene receptor antagonists with those of inhaled corticosteroids. This study was designed to assess the clinical efficacy and anti-inflammatory effects of leukotriene receptor antagonist plus low-dose inhaled corticosteroids compared to those of a high-dose inhaled corticosteroid in patients with mild-to-moderate asthma. METHODS: Forty-nine patients with newly diagnosed asthma were recruited. They were randomly assigned to groups that received, for a 6-week period, either (1) budesonide, 600 microg bid (1,200 microg/d) or (2) budesonide, 200 microg (400 microg/d), and zafirlukast, 20 mg bid. The variables of asthma control were recorded daily. Sputum induction and methacholine provocation tests were performed. RESULTS: The results indicated that the administration of a low-dose inhaled corticosteroid plus zafirlukast was as effective as that of a high-dose inhaled corticosteroid regarding clinical improvement and anti-inflammatory effects (ie, eosinophil percentage, and eosinophilic cationic protein [ECP] and cysteinyl leukotriene C4 levels in induced sputum). Nineteen (group 1, 8 patients; group 2, 11 patients) of 49 patients (38.8%) had returned to normal airway responsiveness after treatment. Among these patients, 16 patients (84.2%) had normal ECP levels and 10 patients (52.6%) had normal percentages of eosinophils. ECP level, but not the eosinophil percentage, was significantly associated with symptom scores. The peak expiratory flow rate (PEFR) showed a significant correlation with the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) instead of with symptom scores. CONCLUSIONS: The addition of a leukotriene modifier to treatment with low-dose inhaled corticosteroids is equivalent to treatment with high-dose inhaled corticosteroids in patients with newly diagnosed mild-to-moderate asthma. In addition to symptoms and PEFR, the monitoring of ECP and PC20 may be of great value in achieving optimal control of asthma.

Administration, Inhalation↗

Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of Pseudomonas aeruginosa infection in adult bronchiectasis.

RATIONALE: Pseudomonas aeruginosa lung infection in patients with bronchiectasis, a chronic airway disease that is characterized by episodes of exacerbation, is associated with more severe disease and a higher utilization of health-care resources. Inhaled tobramycin solution reduces the number of acute exacerbations in patients with cystic fibrosis (CF)-related bronchiectasis with P aeruginosa infection but remains untested in the treatment of exacerbations in patients with non-CF bronchiectasis. OBJECTIVES: This study tested the effect of adding inhaled tobramycin solution to oral ciprofloxacin (Cip) for the treatment of acute exacerbations of non-CF bronchiectasis in patients with P aeruginosa infection. METHODS: A double-blind, randomized, active comparator, parallel-design study conducted at 17 study centers (5 in the United Kingdom, and 12 in the United States) compared 2 weeks of therapy with Cip with either an inhaled tobramycin solution or placebo in 53 adults with known P aeruginosa infection who were having acute exacerbations of bronchiectasis. MEASUREMENTS: Clinical symptoms, pulmonary function, clinical efficacy, and sputum microbiology were investigated prospectively. MAIN RESULTS: An inhaled solution of Cip with tobramycin, compared to placebo, achieved greater microbiological response but no statistically significant difference in clinical efficacy at days 14 or 21. Clinical and microbiological outcomes at the test of cure (ie, the clinical outcome assessment at day 21) were concordant when an inhaled tobramycin solution was added to therapy with Cip and compared to placebo (p = 0.01). Both subject groups had similar overall adverse event rates, but subjects receiving therapy with an inhaled tobramycin solution reported an increased frequency of wheeze (50%; placebo group, 15%). CONCLUSIONS: The addition of an inhaled tobramycin solution to therapy with oral Cip for the treatment of acute exacerbations of bronchiectasis due to P aeruginosa improved microbiological outcome and was concordant with clinical outcome; the inability to demonstrate an additional clinical benefit may have been due to emergent wheeze resulting from treatment.

Administration, Inhalation↗

Inhaled corticosteroids plus long-acting beta2-agonists as a combined therapy in asthma.

Inhaled corticosteroids (ICS) are the mainstay of asthma treatment. Since 1994, when the first trial showed an equivalent effect of doubling the ICS dose or adding salmeterol, it has repeatedly been shown that the combinations of beclomethasone dipropionate and salmeterol, budesonide and formoterol, or fluticasone propionate and salmeterol have at least the same efficacy as doubling the dose of the ICS in adults, though a conclusive trial in asthmatic children is still lacking. The addition of a long-acting beta(2)-agonist (LABA) to ICS appears more efficacious than adding a short-acting beta(2)-agonist or an antileukotriene, even though available data are sparse. Concurrent (two inhalers) and combination (same inhaler) modes of administration are equivalent from the clinical point of view, as is also true regarding administration via metered dose inhaler or dry powder inhaler. Using a single inhaler might eventually have a positive effect on treatment compliance, but there are no confirmatory data yet. Despite some clues regarding a presumed agonist effect of ICS and LABAs, there are still more doubts than certainties. Even though there are still unanswered questions, the data available strongly suggest that the fixed combination of ICS and LABAs using the same inhaler is an efficacious, safe and practical approach for those asthmatic patients who are not well controlled with low doses of ICS alone.

Administration, Inhalation↗

The risk/benefit of inhaled corticosteroids in chronic obstructive pulmonary disease.

Although inhaled corticosteroids have a well defined role in asthma therapy, their use remains controversial in nonasthmatic, smoking-related chronic obstructive pulmonary disease (COPD). Some studies have shown an effect of inhaled corticosteroids on airway inflammation in COPD, but the clinical relevance of these results is unknown. Data from five long-term, large studies, provide evidence that prolonged treatment with inhaled corticosteroids does not modify the rate of decline of forced expiratory volume in one second (FEV1) in patients with COPD and no reversibility to short-acting beta(2)-agonists. FEV1 was slightly improved over the first six months of treatment and lower reactivity in response to methacholine challenge has been observed. Improvement of respiratory symptoms and health status were also reported. A reduction of exacerbations rate was observed in two studies. No survival benefit was demonstrated. Two recent reports suggest that long term use of inhaled corticosteroids in COPD patients improves quality-adjusted life expectancy and is cost-effective. Combination therapy with inhaled corticosteroids and long-acting beta(2)-agonists have proven benefit in four long term large studies compared to placebo for FEV1, exacerbation rate, symptoms and health status. However, only two studies found that combination therapy was more effective than long-acting beta(2)-agonists alone for symptoms and health status improvement. The long term safety of inhaled corticosteroids is not known in COPD patients but topical adverse effects, and systemic effects such as a decrease of bone density of lumbar spine and femur and cutaneous adverse effects, have been reported after three years of treatment. However, three recent observational studies found a slight increase in the risk of fractures (hip, upper extremities and vertebral) in association with high doses of inhaled corticotherapy.

Administration, Inhalation↗

Patterns of inhaled antiinflammatory medication use in young underserved children with asthma.

BACKGROUND: Asthma guidelines advocate inhaled corticosteroids as the cornerstone treatment of persistent asthma, yet several studies report underuse of inhaled corticosteroids in children with persistent asthma. Moreover, few studies use objective pharmacy data as a measure of drug availability of asthma medications. We examined factors associated with the use of inhaled corticosteroids in young underserved children with persistent asthma using pharmacy records as their source of asthma medications. METHODS: This was a cross-sectional analysis of questionnaire and pharmacy record data over a 12-month period from participants enrolled in a randomized clinical trial of a nebulizer educational intervention. RESULTS: Although exposure to > or = 1 inhaled corticosteroids refill was high at 72%, 1 of 5 children with persistent asthma had either no medication or only short-acting beta agonist fills for 12 months. Only 20% of children obtained > or = 6 inhaled corticosteroids fills over 12 months. Obtaining > or = 3 inhaled corticosteroids fills over 12 months was significantly associated with an increase in short-acting beta agonist fills and receiving specialty care in the regression models while controlling for child age, asthma severity, number of emergency department visits, having an asthma action plan, and seeking preventive care for the child's asthma. CONCLUSIONS: Overreliance on short-acting beta agonist and underuse of inhaled corticosteroid medications was common in this group of young children with persistent asthma. Only one fifth of children obtained sufficient controller medication fills.

Administration, Inhalation↗

Underuse of inhaled corticosteroids in adults with asthma.

Despite strong evidence that inhaled corticosteroids are beneficial in treating asthma, a number of small studies suggest a use rate of only 34-56%. The primary objective of this study was to determine patterns of prescribing inhaled corticosteroids for high-risk patients with asthma. Secondary objectives were to assess patterns of practice with respect to other agents prescribed before and at hospital discharge, and to determine if an emergency room asthma care map at one of the study hospitals was being followed. We retrospectively reviewed charts of 1022 patients with an acute attack of asthma treated in the emergency rooms of the Royal Alexandra Hospital and University of Alberta Hospital from January 1, 1996, to March 31, 1997. A forward stepwise logistic regression analysis was performed with the dependent variable defined as whether or not the patient was using an inhaled or oral corticosteroid during the index visit, and the independent variable being all major demographic variables. Inhaled corticosteroids were prescribed for 460 patients (52.0%) at the index visit. Overall, antiinflammatory drugs were prescribed for 548 patients (62.1%). An asthma care map was followed for 107 (16.8%) patients treated at the Royal Alexandra Hospital at the index visit. Logistic regression analysis showed that women and patients with more than one emergency room visit most likely were to be using inhaled or inhaled plus oral corticosteroids at the index visit. Documentation of drug therapy at discharge was poor for 42% of patients; therefore, analysis of practice patterns in this group was not attempted. This study shows that inhaled corticosteroids were prescribed for only about one-half of patients with an acute asthma attack. Given this low use by high-risk patients, the need for programs designed to improve asthma therapy is evident.

Administration, Inhalation↗

Airway hyperresponsiveness after endotoxin inhalation depends on leukocyte infiltration.

We have investigated the relationship between acute airway hyperresponsiveness and polymorphonuclear cell (PMN) migration in airways following saline or endotoxin (ET) aerosol inhalation in 63 guinea pigs. In 20 of these animals, granulocytopenia was induced by prior treatment with hydroxyurea (HU). Airway responsiveness (AR) to inhaled methacholine, together with leukocyte counts in bronchoalveolar lavage fluid (BALF) and in tracheal epithelium, was also examined before and at 30 min, 1, 3 and 6 hr after saline or ET inhalation. In saline inhalation groups, AR and PMN counts in BALF and in tracheal epithelium did not differ from control animals at any time points. However, in ET inhalation groups AR increased significantly at 1 and 3 hr and returned to the pre-exposure level at 6 hr. This period of hyperresponsiveness was associated with an increment of PMN migration into tracheal epithelium. However, the increment of PMN counts in BALF was delayed to 3 and 6 hr after ET. In HU treated animals, AR and PMN counts in BALF and in tracheal epithelium did not change during 6 hr after ET inhalation. These results suggest that the hyperresponsiveness induced by ET inhalation either depends upon PMN migration into the tracheal epithelium.

Administration, Inhalation↗

Inhaled insulin for diabetes mellitus.

PURPOSE: Pharmacokinetic and safety data related to the use of inhaled insulin for the management of diabetes mellitus are discussed. The various pulmonary insulin delivery systems under development are also reviewed. SUMMARY: Several pharmaceutical companies are developing pulmonary insulin delivery systems. These products fall into two main groups: solution and drug powder formulations, which are delivered through different patented inhaler systems. Exubera, a rapid-acting insulin in powder form, has been studied extensively in patients with type 1 and type 2 diabetes mellitus. The AERx Insulin Diabetes Management System delivers a liquid form of human insulin. Preliminary data indicate that patients converting from insulin injections to this system showed higher compliance to therapy, demonstrated by improved glycemic control. Other pulmonary insulin delivery systems, including ProMaxx, AIR, Spiros, and Technosphere, are also under investigation. In humans, inhaled regular insulin is more rapidly absorbed than insulin from the subcutaneous injection site. The efficiency of inhaled insulin is lower than that of subcutaneous injection because pulmonary delivery of insulin involves some loss of drug within the inhaler or mouth during inhalation. A concern of many clinicians is the possibility of long-term effects from the intraalveolar deposition of insulin within the lung, since insulin is known to have growth-promoting properties. The long-term safety of these products has not been established. CONCLUSION: Several inhaled insulin products are under development. If these products receive marketing approval, the pulmonary delivery of insulin may offer patients with diabetes an alternative to repeated insulin injections.

Administration, Inhalation↗