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PubMedDate not supplied

Inhaled iloprost in pulmonary arterial hypertension.

OBJECTIVE: To review the pharmacology, pharmacodynamics, and clinical trials evaluating inhaled iloprost in pulmonary arterial hypertension (PAH). DATA SOURCES: A MEDLINE search (1996-February 2005) was performed using the key words pulmonary hypertension, iloprost, and epoprostenol. Information regarding Food and Drug Administration approval was obtained via the Internet. STUDY SELECTION AND DATA EXTRACTION: All clinical trials using inhaled iloprost in PAH published in English were identified. Additionally, references from the identified articles were reviewed. DATA SYNTHESIS: A stable analog of prostacyclin, inhaled iloprost is thought to promote benefit in PAH through vasodilation, antiproliferative effects, and inhibition of platelet aggregation. In a placebo-controlled trial of 203 patients, inhaled iloprost significantly improved the combined endpoint of change in New York Heart Association functional class and 10% improvement in 6-minute walk distance (p = 0.007). Small, short-term clinical trials demonstrated hemodynamic benefits for inhaled iloprost alone and in combination with other pulmonary vasodilating agents. The aerosolized delivery route and low incidence of adverse events are positive attributes for inhaled iloprost, while the frequency of administration and lack of comparative data limit its role in PAH. CONCLUSIONS: Currently, inhaled iloprost offers potential benefit for patients with contraindications to bosentan, preference for non-parenteral products, ineligibility for parenteral therapy, or as adjunctive therapy with other pulmonary vasodilators. Larger, long-term clinical trials are needed to solidify the role for inhaled iloprost in the management of PAH.

Administration, Inhalation↗
PubMed1992

A comparison of the effects of bid and qid dosing on compliance with inhaled flunisolide.

Noncompliance with inhaled steroids is a well-recognized problem in asthma therapy. We compared compliance with bid and qid regimens of inhaled flunisolide in 16 asthmatic subjects. Patients were instructed to take four inhalations bid for T1 to establish baseline compliance. During T2, half (group A) continued this dosing regimen, while the other half (group B) switched to two inhalations qid. Group A compliance did not significantly change from T1 to T2. The percentage of days with less than eight inhalations (underuse) for group B, however, increased from 20.2 +/- 40.3 in T1 (bid dosing) to 57.1 +/- 49.6 in T2 (qid dosing) (p less than 0.001). Concomitantly, the number of daily inhalations decreased from 7.9 +/- 2.5 to 6.8 +/- 3.1 (p less than 0.01). Reduced compliance with qid dosing was due in large part to an increase in frequency of six inhalations per day, resulting from tid use. Compliance with inhaled flunisolide, therefore, was worse with qid than bid dosing.

Administration, Inhalation↗
PubMed1992

An evaluation of severity-modulated compliance with q.i.d. dosing of inhaled beclomethasone.

Although the asthmatic subject's compliance with a regimen of inhaled corticosteroids is often poor, it has been suggested this may improve during periods of increased severity. To test this, we measured daily peak expiratory flow rates (PEFRs), asthma symptoms, and the use of an albuterol inhaler over nine weeks period in ten patients with moderately severe asthma. The effect of changes in these severity indices on compliance with a q.i.d. regimen of inhaled beclomethasone was evaluated. The PEFR was measured in the morning before bronchodilator administration, and symptoms were graded on a scale of 4 to 16, while albuterol and beclomethasone inhalations were electronically recorded. Three measures of compliance with the beclomethasone regimen were used: (1) mean daily compliance ([number of inhalations/number of prescribed inhalations] x 100); (2) underuse, ie, the percentage of days with less than the prescribed number of inhalations; and (3) overuse, ie, the percentage of days with greater than the prescribed number of inhalations. Mean daily compliance was 67 +/- 36 percent, while underuse was observed in 69 percent and overuse in 11 percent of the days. Despite clinical exacerbations in six of the ten patients and considerable variation in the severity indices, no significant relationship was found between the change in asthma severity and compliance with the beclomethasone regimen. These findings do not support the concept of severity-modulated compliance with inhaled corticosteroids.

Administration, Inhalation↗
PubMed1996

Inhaled corticosteroids do not prevent the development of tolerance to the bronchoprotective effect of salmeterol.

INTRODUCTION: Twice-daily inhaled salmeterol produces rapid reduction in its acute bronchoprotective effect against methacholine in patients with mild asthma. This investigation examined this effect in patients with moderate asthma who were using inhaled corticosteroids. SUBJECTS AND METHODS: Eight asthmatic volunteers who required inhaled corticosteroids for control of their symptoms and who were able to withhold treatment with beta 2-agonists for 4 weeks before and during the study participated in a double-blind, crossover, placebo-controlled study with two random-order treatment periods: inhaled salmeterol, 50 microg twice a day for seven doses, and placebo in similar fashion, with a 7-day or greater washout between these periods. Methacholine inhalation tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose of the study inhaler, 10 min post-200 microg salbutamol. RESULTS: Baseline FEV1 measurements before doses 3, 5, and 7 of salmeterol, ie, 12 h after salmeterol, were significantly higher than all other baseline values. Twenty-four hours after the last dose of salmeterol, the FEV1 was no different from that during the placebo period. The geometric mean methacholine concentration causing a 20% fall in FEV1 (PC20) following the third dose of salmeterol (6.8 mg/mL) was significantly lower than after the first dose of salmeterol (12.0 mg/mL; p=0.031), and this reduction of bronchoprotection persisted following doses 5 and 7. The methacholine PC20 10 min postsalbutamol measured after the salmeterol period was significantly lower than after placebo (5.6 vs 13.3 mg/mL; p<0.001). CONCLUSIONS: Tolerance to the acute bronchoprotective effect of salmeterol was significant after the first two doses and persisted after the seventh dose. Tolerance to the acute bronchoprotective effect of salbutamol was also significant after regular use of salmeterol for seven doses. These effects, in subjects using inhaled corticosteroids regularly, were similar to the those previously seen in patients with mild asthma using as-required beta 2-agonists only, indicating that tolerance is not prevented by use of inhaled corticosteroids.

Administration, Inhalation↗
PubMed1996

Is delayed introduction of inhaled corticosteroids harmful in patients with obstructive airways disease (asthma and COPD)? The Dutch CNSLD Study Group. The Dutch Chronic Nonspecific Lung Disease Study Groups.

BACKGROUND: The institution of inhaled corticosteroids is generally advocated for effective treatment of patients with asthma. It is yet unknown what is the best time to start inhaled corticosteroid therapy and especially whether delayed introduction is harmful. PHASE 1: In a previous study in patients with asthma and COPD, we found that 2.5 years of treatment with a beta 2-agonist plus inhaled corticosteroid (BA + CS) was more effective in improving the FEV1 and the provocative concentration of histamine causing a 20% reduction in FEV1 (PC20) than treatment with a beta 2-agonist plus anticholinergic (BA + AC) or placebo (BA + PL). PHASE 2: We extended this study with 6 months to investigate whether delayed introduction of inhaled CS therapy (800 micrograms beclomethasone dipropionate) in the groups previously not treated with inhaled CS (BA +/- AC) could also improve FEV1 and PC20 to the same degree. A distinction was made between patients with predominantly asthma (high baseline reversibility, delta FEV1 > or = 9% of predicted), and predominantly COPD (low baseline reversibility, delta FEV1 < 9% of predicted). RESULTS: Improvement of FEV1 percent predicted by inhaled CS was comparable both in the asthmatics between phase 1 (13.8% predicted) and phase 2 (8.5% predicted; p = 0.31) as well as in the patients with COPD (2.5% and 1.5% predicted, respectively). PC20, however, increased significantly more in the asthmatics in phase 1 (1.77 doubling concentration [DC]) than in phase 2 (0.79 DC; p = 0.03). Improvement of PC20 in the patients with COPD was not significantly higher in phase 1 (0.74 DC) than in phase 2 (0.00 DC; p = 0.19). CONCLUSIONS: Our study indicates that although delayed introduction of inhaled CS in asthmatics leads to similar improvements in FEV1, improvements in PC20 are significantly less. These findings in patients with longer-existing asthma concur with other findings in newly detected asthma. We suggest that institution of inhaled CS therapy should not be postponed in asthmatics with documented airways obstruction and reversibility.

Administration, Inhalation↗
PubMed1997

A randomized, controlled study of the 1-hour and 24-hour effects of inhaled nitric oxide therapy in children with acute hypoxemic respiratory failure.

STUDY OBJECTIVE: To determine whether 24 h of inhaled nitric oxide improves oxygenation greater than conventional therapy alone in children with acute hypoxemic respiratory failure. DESIGN: Prospective, randomized, controlled study. SETTING: Twenty-six-bed pediatric ICU in a tertiary children's hospital. PATIENTS: Twenty-four patients with acute bilateral lung disease requiring a positive-end expiratory pressure >6 cm H2O and a fraction of inspired oxygen >0.5 for >12 h. INTERVENTIONS: Twelve patients were treated with 10 ppm inhaled nitric oxide from the onset of randomization and 12 control patients were initially maintained on a regimen of conventional therapy alone. After a period of 24 h, control patients were also treated with 10 ppm inhaled nitric oxide. Hemodynamic and blood gas measurements were performed at baseline, at 1 h after randomization, and at 24-h intervals for 2 days. MEASUREMENTS AND RESULTS: Inhaled nitric oxide decreased the ratio of pulmonary to systemic vascular resistance and improved oxygenation indexes during the initial hour following randomization. However, 24 h after randomization, the oxygenation indexes of 11 surviving treated patients were not improved in comparison to baseline or the oxygenation indexes of 10 surviving control patients. Oxygenation indexes acutely improved in control patients when inhaled nitric oxide was started after 24 h of conventional therapy. Oxygenation indexes remained improved in the initial control patients after 24 h of inhaled nitric oxide. CONCLUSIONS: Pulmonary vascular resistance and systemic oxygenation are acutely improved by 10 ppm inhaled nitric oxide in some children with severe lung disease. However, a sustained improvement in oxygenation may not occur during prolonged therapy. Thus, inhaled nitric oxide may have a limited therapeutic role in children with acute hypoxemic respiratory failure.

Acute Disease↗
PubMed2001

Induced sputum: comparison between isotonic and hypertonic saline solution inhalation in patients with asthma.

BACKGROUND: Sputum induction by hypertonic saline solution inhalation is widely used to study airways secretions in patients with asthma. However, hypertonic saline solution is a potent indirect bronchoconstrictor. STUDY OBJECTIVES: We studied the validity of isotonic saline solution (0.9%) inhalation as a means to induce sputum by comparing it to hypertonic saline solution (4.5%) inhalation. PATIENTS: Sixteen patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion. METHODS: Subjects underwent sputum induction twice at 1-week intervals. Saline solution (hypertonic or isotonic) was inhaled for three periods of 5 min. The parameters assessed in sputum samples were cell counts, sodium, eosinophil cationic protein (ECP), and albumin concentrations, osmolality, and pro-matrix metalloproteinase (MMP)-9 activity by zymography. RESULTS: The maximal fall in peak expiratory flow during sputum induction was greater after inhalation of hypertonic saline solution than after inhalation of isotonic saline solution (p < 0.01). Each subject produced analyzable sputum on both visits. There were no statistically significant differences in total and differential sputum cell counts, and the reproducibility coefficients were high for eosinophils and neutrophils when comparing the two methods. Likewise, sputum levels of ECP and albumin as well as sputum pro-MMP-9 activity were not different between the two methods, and were highly reproducible as shown by high intraclass coefficients (Ri) of correlation (0.72, 0.74, and 0.77 for ECP, albumin, and pro-MMP-9, respectively). Sputum sodium concentrations and osmolality were higher after inhalation of hypertonic saline solution (p < 0.05). CONCLUSION: In patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion, inducing sputum by isotonic or hypertonic saline solution inhalation leads to comparable results in eosinophil and neutrophil cell counts and fluid phase mediators/proteins.

Administration, Inhalation↗
PubMed2001

Inhaled beclomethasone dipropionate improves acoustic measures of voice in patients with asthma.

BACKGROUND: Inhaled corticosteroids have the potential to produce upper-airway side effects such as hoarseness. As new compounds and delivery devices are developed and compared, it is difficult to quantify their adverse upper-airway effects. OBJECTIVE: We undertook the following study to test the ability of an acoustic analysis technique to quantify changes in vocal function in steroid-naive patients with asthma who receive inhaled beclomethasone dipropionate (BDP), 1,000 microg/d for 4 months. METHODS: Patients self-administered one of four regimens of inhaled BDP. Group 1 patients received one 250-microg puff qid via metered-dose inhaler (MDI); group 2 patients received one 250-microg puff qid via MDI with a holding chamber; group 3 patients received two 250-microg puffs bid via MDI; and group 4 patients received two 250-microg puffs bid via MDI with a holding chamber. A smaller cohort of nonsmoking asthmatic patients was managed without steroid intervention for 4 months. At baseline and again at 8 weeks and 16 weeks after the initiation of BDP treatment, patients underwent spirometry and methacholine challenge. At baseline and again at 2, 4, 8, 12, and 16 weeks, patients underwent voice recording for analysis of voice parameters. The recorded vowels were low-pass filtered (10 KHz), digitized (22 KHz), and analyzed by software to obtain two acoustic measures: (1) jitter, the cycle-to-cycle variation in the time period of the voice signal; and (2) shimmer, the cycle-to-cycle variation in voice signal amplitude. RESULTS: We recruited 77 patients for randomization to inhaled steroid therapy and 10 patients who continued to receive only occasional inhaled bronchodilator therapy. In all active treatment groups, FEV(1), FVC, and provocative concentration of methacholine causing a 20% fall in FEV(1) improved significantly after BDP treatment. Mean jitter scores, a measurement of variation in voice pitch, were not significantly influenced by BDP treatment. However, mean shimmer scores, a reflection of perturbation in vocal amplitude, fell significantly (p < 0.05) in the active treatment groups. These reductions in shimmer scores were not significantly different in the active treatment groups. Shimmer scores in the bronchodilator-treated group were unchanged during the 16 weeks of follow-up. CONCLUSIONS: Our data show that a simple and noninvasive acoustic analysis of voice is sensitive to subclinical changes associated with inhaled corticosteroid therapy. We have shown that 1,000 microg/d of inhaled BDP actually improves specific acoustic measures of voice in patients with inadequately controlled asthma. These improvements were uninfluenced by dosing schedule and whether a spacing chamber was used.

Administration, Inhalation↗
PubMed2004

The effect of lung burden on biopersistence and pulmonary effects in rats exposed to potassium octatitanate whiskers by inhalation.

The effect of lung burden on biopersistence and histopathological changes caused by potassium octatitanate whiskers (POW) which is one of the asbestos substitutes were investigated for 1-yr and 4-wk inhalation periods. In the 1-yr inhalation experiment, male Wistar rats were exposed to POW (TW) for 6 h/d, 5 d/wk under the same conditions as a previous study of POW (PT1, JFM fiber) which is made by different manufacturer. The exposure concentration was 1.9 +/- 0.7 mg/m(3) and the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) in the chamber were 1.6 microm and 2.9. Rats were sacrificed at 3 d and 1 yr after the inhalation experiment and TW deposits in the lungs were determined by ICP-AES. Lung burden at 3 d and 1 yr after the inhalation was 2.39 +/- 0.50 mg and 1.37 +/- 0.96 mg, respectively, the deposition fraction was 8.1% and biological half time (BHT) was 15 months. Aggregated dust cells and mild fibrotic changes around these dust cells were observed in the exposed rat lung. These results were almost the same as those obtained in the previous 1-yr PT1 study. In the 4-wk inhalation experiment, to investigate the effect of lung burden on biopersistence and histopathological change, male Wistar rats were exposed to PT1. The exposure concentration was 102 +/- 21 mg/m(3), MMAD (GSD), the geometiric mean length and diameter (GSD) of the PT1 in the chamber were 1.6 microm (3.0), 2.2 microm (1.8) and 0.33 microm (1.5), respectively. Rats were sacrificed at 3 d, 1 wk, and 1, 3, 6 and 12 months after the inhalation experiment. The lung burden of POW at 3 d after 4 wk inhalation was 1.49 +/- 0.19 mg, which was close to the estimated amount of overload. The BHT of the total mass (4.1 months) was not prolonged, but aggregated dust cells were observed in the subpleural region and around the bronchioles and mild fibrotic changes were observed only around the dust cells at one year after the 4-wk inhalation. It is considered that the excessive exposure which impairs the function of alveolar macrophage mediated clearance may cause the aggregation of dust cells and fibrotic changes.

Animals↗
PubMed1989

[Effects of inhalation of several organic solvents on left ventricular dp/dt].

Effects of inhalation of several organic solvents on left ventricular contractility were investigated by using left ventricular dp/dt in anesthetized dogs. The first derivative of the left ventricular pressure was obtained by an electronic differentiating circuit and recorded continuously. As organic solvents, 1,1,1-trichloroethane (1,1,1-TCE), trichloroethylene, tetrachloroethylene, toluene, m-xylene and trichloro-trifluoroethane (FC-113) were used in this study. Each solvent was separately inhaled for a period of approximately 2 min. In the acute inhalation experiments, peak dp/dt that was the maximal left ventricular dp/dt decreased following inhalation of each organic solvent. The threshold concentration of 1,1,1-TCE, trichloroethylene, tetrachloroethylene, toluene, m-xylene and FC-113 required to decrease peak dp/dt was approximately 0.2%, 0.15%, 0.2%, 0.38%, 0.35% and 0.35%, respectively. These results indicated that the decrease in peak dp/dt was induced following inhalation of each solvent, but threshold concentration of the solvents to produce decrease in peak dp/dt was different. Inhalation of organic solvents of higher concentrations markedly decrease peak dp/dt. A dose response relationship was observed between decrease in peak dp/dt and concentration of the solvent greater than the threshold level. The degree of decrease in peak dp/dt following inhalation differed by kind of solvents with the greatest decrease in peak dp/dt being induced by tetrachloroethylene inhalation.

Administration, Inhalation↗
PubMed2002

Benefits and risks of inhaled corticosteroids in chronic obstructive pulmonary disease.

Inhaled corticosteroids have a proven benefit in the management of asthma, but until recently, their efficacy in non-asthmatic, smoking-related chronic obstructive pulmonary disease (COPD) was not evidence-based. Airway inflammation in COPD differs from inflammation in asthma. Some studies have shown an effect of inhaled corticosteroids on airway inflammation in COPD but the clinical relevance of these results are unknown. Short-term studies evaluating the effect of inhaled corticosteroids in patients with COPD were associated with no or modest improvements in lung function. Data from five, long-term, large studies have provided evidence that prolonged treatment with inhaled corticosteroids does not modify the rate of decline of forced expiratory volume in one second (FEV(1)) in patients with COPD and no reversibility to short-acting beta(2)-adrenoceptor agonists. FEV(1) was slightly improved over the first 6 months of treatment in two studies and lower airway reactivity in response to methacholine challenge has been observed. Improvement of respiratory symptoms and health status was also reported in three studies. A reduction in the rate of exacerbations was observed in two studies. No survival benefit was demonstrated in any study. The advantage of using inhaled, rather than oral, corticosteroids is a reduction in adverse effects for the same therapeutic effect, because inhaled corticosteroids rely more on topical action than systemic activity. The long-term safety of inhaled corticosteroids is not known in patients with COPD. However, 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 in patients with COPD after 3 years of treatment with inhaled corticosteroids.

Administration, Inhalation↗
PubMed2006

Clinical safety of inhaled corticosteroids for asthma in children: an update of long-term trials.

Inhaled corticosteroids are established as the mainstay of maintenance therapy for chronic asthma. However, there remains some debate regarding the safety of long-term use of these agents, particularly in children. This concern mainly stems from the findings of short-term studies assessing the effects of inhaled corticosteroids on lower leg growth rate or the hypothalamic-pituitary-adrenal axis. However, the clinical relevance of these findings to long-term treatment is unknown and significant uncertainty exists regarding the predictive value of changes in cortisol levels and clinically relevant changes in growth or bone mineral density. To assess the safety of long-term use of inhaled corticosteroids in children with asthma, a systematic review of the literature was performed focusing on randomised, controlled studies of >or=12 months' duration, to obtain data with maximum relevance to clinical practice. Specific searches were conducted to identify studies examining each of the following three areas: growth, bone mineral density and cortisol levels. Fourteen studies met the inclusion criteria for statural growth, four for bone mineral density, and ten for cortisol levels. There was some evidence of a small decrease in statural growth during the initial period of inhaled corticosteroid therapy. This effect was more marked at daily doses of >200 microg and did not apply to all treatment regimens. Studies examining final attained adult height found no difference between patients treated with inhaled corticosteroids and those receiving nonsteroidal therapy. None of the studies investigating effects on bone mineral density found any adverse effects of inhaled corticosteroid therapy. Finally, recommended doses of inhaled corticosteroids generally had little or no effect on plasma- or urinary-cortisol levels versus nonsteroidal therapy. In conclusion, this literature review supports the theory that recommended doses of inhaled corticosteroids can be administered to children for the long-term management of asthma with minimal risk of clinically relevant adverse effects on growth, bone density or cortisol levels.

Administration, Inhalation↗
PubMed2003

Inhaled corticosteroids in the long-term management of patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major problem in the elderly population, with approximately 10% of the population affected. Since COPD is an inflammatory disorder of the pulmonary system, corticosteroids might be expected to improve clinical outcomes of the disease. Data from large, well designed randomised clinical trials in which approximately one third of patients were > or =65 years of age indicate that inhaled corticosteroids do not modify the natural history of COPD, as measured by the rate of decline in forced expiratory volume in 1 second (FEV1). However, these same studies also suggest that corticosteroids reduce the frequency of clinical exacerbations by nearly a third (compared with placebo). This beneficial effect is particularly pronounced among those with an FEV1 less than 50% of the predicted value. Withdrawal of inhaled corticosteroids, on the other hand, leads to increased symptoms and elevates the risk of exacerbations by 50% above baseline levels. Patients' health-related quality of life is also improved by the use of inhaled corticosteroids. It is clear that inhaled corticosteroids elevate the risk of thrush, dysphonia and skin bruising by 2-fold compared with placebo. In addition, the sum of evidence suggests a modest deleterious effect for inhaled corticosteroids on bone mineral density, especially for formulations that have an increased rate of systemic absorption. However, the clinical evidence of this observation is uncertain. The effect of inhaled corticosteroids on fracture risk is controversial with some observational studies suggesting a possible association. Whether inhaled corticosteroids increase the risk of ophthalmic complications (cataracts and glaucoma) is also uncertain. In conclusion, the current evidence indicates that inhaled corticosteroid therapy produces short- and long-term clinical benefits in COPD patients with moderate-to-severe disease and should be used as adjunctive therapy for elderly patients with COPD who experience frequent exacerbations or have moderately reduced lung function.

Administration, Inhalation↗
PubMed2004

Clinical pharmacokinetics and pharmacodynamics of inhaled insulin.

The benefits of intensive insulin therapy in the prevention of complications in patients with diabetes mellitus are now well established. However, the current methods of insulin administration fall well short of the ideal. Consequently, alternative routes of insulin administration have been investigated. The pulmonary route has received the most attention, helped by advances in inhaler devices and insulin formulation technology. As a result, several insulin inhalation systems are at varying stages of development, with one already filed for marketing approval in Europe. Knowledge of the pharmacokinetic and pharmacodynamic characteristics of the various inhaled insulin formulations will help to determine their positioning in current and evolving diabetes treatment strategies. For instance, a rapid onset and short duration of action would be desirable for use in postprandial glucose control. Pharmacokinetic studies with inhaled insulin reveal that serum insulin concentrations peak earlier and decay more rapidly following inhalation compared with subcutaneously administered regular insulin, and pharmacodynamic studies measuring glucose infusion rate under euglycaemic glucose clamp show corresponding rapid changes in glucose control. Furthermore, intrapatient variability in the pharmacokinetics and pharmacodynamics of inhaled insulin is low; variability is similar to (or perhaps less than) that seen when insulin is administered subcutaneously. Estimates of the bioavailability and bioefficacy achievable with the current inhalation systems are typically in the region of 10% of that experienced with subcutaneously administered insulin. Most of the losses are in the device, mouth and throat, with approximately 30-50% of the insulin deposited in the lungs being absorbed. Clinical experience to date indicates that inhaled insulin has the potential to be an effective treatment in patients with diabetes, and that it may have particular utility in the treatment of postprandial hyperglycaemia.

Administration, Inhalation↗
PubMed1999

Inhaled corticosteroid therapy in newly detected mild asthma.

Inhaled corticosteroids are the most effective medications currently available to treat symptomatic asthma, and are free of clinically relevant unwanted effects, when used at the doses needed to provide optimal control in most patients with asthma. Inhaled corticosteroids also improve the physiological abnormalities of variable airflow obstruction and airway hyperresponsiveness that characterise asthma. Inhaled corticosteroids are also cost-beneficial when compared with other treatments, even in patients with milder asthma who are treated in primary care. For these reasons, inhaled corticosteroids are now being considered as first-line therapy for patients with regular daily asthma symptoms. Inhaled corticosteroids are, however, often not utilised until other treatments have been demonstrated not to provide optimal asthma control. Available evidence from both children and adults with asthma suggests that the benefits achieved from inhaled corticosteroids are reduced when their introduction as therapy is delayed for several years after persistent symptoms develop. For this reason, corticosteroids should be started soon after a diagnosis is made and persistent symptoms develop. It is not yet known, however, whether inhaled corticosteroids should be used in asthmatic patients who have very mild and infrequent symptoms and who have normal airway calibre most of the time. The current consensus statements do not recommend regular treatment in such patients. Airway biopsies from these asthmatic patients do show evidence of airway inflammation and structural changes; however, we do not yet know whether they lose lung function more rapidly than individuals without asthma, or whether the morbidity associated with very mild asthma warrants the use of regular treatment. This issue is being addressed in a large, multinational, placebo-controlled trial. The results of this study (available in 3 more years) will resolve this persisting question about inhaled corticosteroid use in mild asthma.

Administration, Inhalation↗
PubMed2001

Nocturnal asthma uncontrolled by inhaled corticosteroids: theophylline or long-acting beta2 agonists?

Asthma is an inflammatory disease of the airways that is frequently characterised by marked circadian rhythm. Nocturnal and early morning symptoms are quite common among patients with asthma. Increased mortality and decreased quality of life are associated with nocturnal asthma. Although numerous mechanisms contribute to the pathophysiology of nocturnal asthma, increasing evidence suggests the most important mechanisms relate to airway inflammation. According to international guidelines, patients with persistent asthma should receive long term daily anti-inflammatory therapy. A therapeutic trial with anti-inflammatory therapy alone (without a long-acting bronchodilator) should be assessed to determine if this therapy will eliminate nocturnal and early morning symptoms. If environmental control and low to moderate doses of inhaled corticosteroids do not eliminate nocturnal symptoms, the addition of a long-acting bronchodilator is warranted. Long-acting inhaled beta2 agonists (e.g. salmeterol, formoterol) are effective in managing nocturnal asthma that is inadequately controlled by anti-inflammatory agents. In addition, sustained release theophylline and controlled release oral beta2 agonists are effective. In patients with nocturnal symptoms despite low to high doses of inhaled corticosteroids, the addition of salmeterol has been demonstrated to be superior to doubling the inhaled corticosteroid dose. In trials comparing salmeterol with theophylline, 3 studies revealed salmeterol was superior to theophylline (as measured by e.g. morning peak expiratory flow, percent decrease in awakenings, and need for rescue salbutamol), whereas 2 studies found the therapies of equal efficacy. Studies comparing salmeterol to oral long-acting beta2 agonists reveal salmeterol to be superior to terbutaline and equivalent in efficacy to other oral agents. Microarousals unrelated to asthma are consistently increased when theophylline is compared to salmeterol in laboratory sleep studies. In addition to efficacy data, clinicians must weigh benefits and risks in choosing therapy for nocturnal asthma. Long-acting inhaled beta2 agonists are generally well tolerated. If theophylline therapy is to be used safely, clinicians must be quite familiar with numerous factors that alter clearance of this drug, and they must be prepared to use appropriate doses and monitor serum concentrations. Comparative studies using validated, disease specific quality of life instruments (e.g. Asthma Quality of Life Questionnaire) have shown long-acting inhaled beta2 agonists are preferred to other long-acting bronchodilators. Examination of costs for these therapeutic options reveals that evening only doses of long-acting oral bronchodilators are less expensive than multiple inhaled doses. However, costs of monitoring serum concentrations, risks, quality of life and otheroutcome measures must also be considered. Long-acting inhaled beta2 agonists are the agents of choice for managing nocturnal asthma in patients who are symptomatic despite anti-inflammatory agents and other standard management (e.g. environmental control). These agents offer a high degree of efficacy along with a good margin of safety and improved quality of life.

Administration, Inhalation↗
PubMed2005

Willingness to pay for inhaled insulin: a contingent valuation approach.

PURPOSE: To determine the willingness to pay (WTP) of patients with diabetes mellitus for inhaled insulin. METHODS: A contingent valuation survey was administered to 96 diabetic outpatients at St. Michael's Hospital, Toronto, Canada. Standardised information about inhaled insulin and subcutaneous rapid-acting insulin was provided via video. Participants' WTP for their preferred product was elicited in Canadian dollars (Can dollars) using a 'payment-scale' method. RESULTS: The mean age of participants was 51.8 years (SD 13.4). Seventy-seven patients had type 2 and 19 had type 1 diabetes. Significantly more participants preferred inhaled insulin over subcutaneous insulin (85 vs 11; p < 0.01). Mean monthly WTP for inhaled insulin (153.70 Can dollars, SD 99.90) was significantly more than the typical 50 Can dollars per month for subcutaneous insulin (p < 0.01). Significantly more participants with type 2 diabetes using oral drugs than those with type 1 diabetes and using insulin preferred inhaled insulin (98.5% vs 69%, p < 0.001). Diabetic patients who did not use insulin were willing to pay significantly more than were insulin users (p < 0.001). Multiple regression analysis showed that income was significantly associated with WTP for inhaled insulin. CONCLUSION: Diabetic patients, particularly those who are not using insulin, indicated that they would prefer inhaled insulin over insulin injection and would be willing to pay a substantial amount per month to use it. An economic evaluation of inhaled insulin would provide important information to healthcare policy decision makers and private payers about its economic value.

Administration, Inhalation↗
PubMed2004

Inhaled corticosteroids versus leukotriene antagonists as first-line therapy for asthma: a systematic review of current evidence.

Inhaled corticosteroids are the most effective anti-inflammatory drugs for asthma. Leukotriene receptor antagonists are a new class of anti-inflammatory drugs that have the advantage of oral administration and the potential for better compliance compared with inhaled corticosteroids. This article summarizes evidence from randomized controlled trials, comparing the efficacy and tolerability of inhaled corticosteroids with those of leukotriene receptor antagonists in patients with persistent asthma. The evidence derived from a systematic review of randomized controlled trials confirms that patients treated with inhaled corticosteroids of chlorofluorocarbon-propelled beclomethasone 400 mug/day or fluticasone propionate 200 mug/day have better asthma control than those treated with oral leukotriene receptor antagonists. More specifically, treatment with inhaled corticosteroids is associated with 65% fewer exacerbations requiring systemic corticosteroids, greater improvement in spirometry and symptoms, fewer night-time awakenings and less use of rescue beta(2)-adrenoceptor agonists. This review does not identify any difference in short-term safety between inhaled corticosteroids and leukotriene receptor antagonists. Although adverse effects typically associated with inhaled corticosteroids (such as growth suppression, osteopenia, and adrenal suppression) were not measured, preventing a fair comparison of the safety profile on long-term use.In conclusion, the scientific evidence does not support the substitution of leukotriene receptor antagonists for low doses of inhaled corticosteroids, which should remain first-line therapy for asthma control.

Administration, Inhalation↗