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PubMed2003

Inhaled nitric oxide modifies left ventricular diastolic stress in the presence of vasoactive agents in heart failure.

Nitric oxide (NO) inhalation therapy has been widely used in several diseases with pulmonary hypertension. However, application of NO inhalation therapy remains controversial in heart failure. Cardiovascular effects of inhaled NO (iNO) were evaluated in dogs before and after induction of heart failure with and without infusion of vasoactive agents. iNO did not affect the baseline left ventricular (LV) function or the response to isoproterenol in control conditions or heart failure induced by procainamide. Pulmonary vascular resistance was significantly decreased by iNO in heart failure with infusion of vasoactive agents. Unexpectedly, LV end-diastolic pressure was significantly elevated by iNO in heart failure in the presence of infusion of vasoactive agents independent of their types; either the vasodilating agents of acetylcholine and nitroglycerin or the vasoconstricting agents of norepinephrine and angiotensin-II. The end-diastolic LV dimension and wall stress were also significantly increased by iNO, however, those at end systole were not affected. These results suggested that NO inhalation therapy reduced pulmonary vascular resistance, whereas in the presence of additional stress of vasoactive agents, it increased LV preload and end-diastolic wall stress in heart failure.

Acetylcholine↗
PubMed2004

Asthma management by general practitioners in Pakistan.

SETTING: Teaching university hospital in Karachi, Pakistan. OBJECTIVES: Asthma management guidelines have been developed to assist practising physicians in treating asthma patients. The objective of this study was to evaluate if the prescribing habits of practitioners in Karachi were consistent with the published asthma guidelines. DESIGN: A questionnaire survey was conducted among practitioners attending a pulmonary continuing medical education (CME) programme. Three case scenarios of asthma were given, and the doctors were asked to write a prescription for each case. Doctors were asked about their views on inhaler therapy and dietary restrictions in asthma. RESULTS: Of 120 doctors, 100 (83%) responded. Thirty different regimens of short acting beta2-agonist and 16 regimens of steroid therapy were prescribed by the practitioners. Only 35% of the doctors prescribed corticosteroids for persistent asthma symptoms. The great majority of doctors were not aware of treatment options for persistent symptoms despite the use of preventive therapy (8% prescribed long-acting beta2-agonists, 6% high-dose inhaled corticosteroids and 13% theophyllines). Misconceptions about inhaler therapy and diet were found in 20 and 50 doctors, respectively. CONCLUSION: General practitioners in Pakistan did not follow asthma management guidelines. There was serious lack of knowledge about asthma medications coupled with misconceptions about inhaler therapy and dietary factors.

Administration, Inhalation↗
PubMed2005

Inhaled nitric oxide therapy in children.

Inhaled nitric oxide therapy improves oxygenation and reduces the need for treatment with extracorporeal membrane oxygenation in term newborns with hypoxaemic respiratory failure and persistent pulmonary hypertension. In this review, we summarise the current status of iNO therapy in the newborn and the potential role of iNO in other paediatric populations.

Child↗
PubMed2003

Bronchodilator effect of an inhaled combination therapy with salmeterol + fluticasone and formoterol + budesonide in patients with COPD.

In the present trial, we compared the broncholytic efficacy of the combination therapy with 50 microg salmeterol + 250 microg fluticasone and 12 microg formoterol + 400 microg budesonide, both in a single inhaler device, in 16 patients with moderate-to-severe COPD. The study was performed using a single-blind crossover randomized study. Lung function, pulse oximetry (SpO2) and heart rate were monitored before and 15, 30, 60, 120, 180, 240, 300, 360, 480, 600, and 720 min after bronchodilator inhalation. Both combinations were effective in reducing airflow obstruction. FEV1 AUC(0-12 h) was 2.83 l (95% CI: 2.13-3.54) after salmeterol/fluticasone and 2.57 l (95% CI: 1.97-3.2) after formoterol/budesonide. Formoterol/budesonide elicited the mean maximum improvement in FEV1 above baseline after 120 min (0.29 l; 95% CI: 0.21-0.37) and salmeterol/fluticasone after 300 min (0.32 l; 95% CI: 0.23-0.41). At 720 min, the increase in FEV1 over baseline values was 0.10 l (95% CI: 0.07-0.12) after salmeterol/fluticasone and 0.10 l (95% CI: 0.07-0.13) after formoterol/budesonide. The mean peak increase in heart rate occurred 300 min after formoterol/budesonide (1.5 b/min; 95% CI--2.3 to 5.3) and 360 min after salmeterol/fluticasone (2.6 b/min; 95% CI--1.9 to 7.0). SpO2 did not change. All differences between salmeterol/fluticasone and formoterol/budesonide were not significant (P > 0.05) except those in FEV1 at 120 and 360 min. The results indicate that an inhaled combination therapy with a long-acting beta2-agonist and an inhaled corticosteroid appears to be effective in improving airway limitation after acute administration in patients suffering from COPD.

Adrenergic beta-Agonists↗
PubMed2002

Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate.

Work in humans and laboratory animals has identified a central role for cytokines and chemokines in development and persistence of lower airway inflammation. The objectives of this study were to determine interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha induction in bronchoalveolar lavage (BAL) of control horses and horses with heaves both during remission and exacerbation of the disease, and to determine the effect of therapy with inhaled fluticasone propionate on the cytokine profile of horses with heaves. IL-1 beta and TNF-alpha mRNA expression was significantly higher in horses with heaves after exposure to moldy hay compared to either values obtained during clinical remission or to healthy controls. IL-8 mRNA expression and protein concentrations were significantly higher in horses with heaves than in controls. Both IL-4 and IFN-gamma mRNA expression was increased at various times in heaves-susceptible horses compared to controls. IL-2, IL-5 and IL-10 mRNA expression was not detected in BAL cells of either group. Therapy with inhaled fluticasone propionate after induction of a severe heaves exacerbation resulted in complete resolution of clinical signs, normalization of pulmonary function tests, and significant decrease in BAL neutrophilia. This was associated with a significant decrease in IL-4 mRNA expression and increase in IFN-gamma/IL-4 ratio in horses with heaves. These results demonstrate the clinical efficacy of inhaled fluticasone propionate for the treatment of heaves and suggest a role for cytokines in the development of lower airway inflammation in heaves-susceptible horses.

Androstadienes↗
PubMed1996

[High dose inhaled steroid therapy--usefulness and limitation].

Our data indicate that 1800 micrograms of per day is more effective than 1400 micrograms/day at the beginning of long-term management of severe asthma in adults whose symptoms are not controlled with the combination of 800 approximately 900 micrograms/day BDP and bronchodilators. Therapy with a higher dose (at least 1600 micrograms/day) of inhaled steroid is more useful and should be promptly began to treat severe asthma. Oral steroid therapy for long-term management should be introduced to mostly severe case after high dose inhaled BDP therapy reveals to be failure.

Administration, Inhalation↗
PubMed2000

Serum eosinophil cationic protein for predicting the prognosis of a step-down in inhaled corticosteroid therapy in adult chronic asthmatics.

We investigated whether the serum concentration of eosinophil cationic protein (s-ECP) can be used to determine when a step-down in inhaled corticosteroid therapy is indicated for patients with chronic asthma. A total of 24 adult patients, whose symptoms were well controlled with inhaled beclomethasone dipropionate (iBDP), were studied. The dosage of iBDP was reduced by half once a month until the dose reached one-quarter of the original level. s-ECP and blood eosinophil counts were determined once a month before and during the 6-month period after the step-down. In 12 patients, moderate and frequent exacerbation occurred, thus requiring a return to the initial or twice the initial dose of iBDP. Thus, the step-down here was defined as unsuccessful. In the remaining 12 patients, the symptoms were stable over the course of the 6 months, and the step-down was defined as successful. s-ECP correlated with eosinophil counts in peripheral blood (EOS) in both the successful and the unsuccessful groups. Although EOS before the step-down did not differ significantly between the two groups, s-ECP was significantly higher in the unsuccessful group (mean 35.7 microg/L) than in the successful group (mean 17.0 microg/L, p < 0.03). Thus, s-ECP appears to be a useful marker for determining when a step-down in iBDP therapy is indicated, and thus may contribute to successful long-term management of chronic asthma.

Adult↗
PubMed1995

The change in the distribution of Tc-99m human serum albumin radioaerosols in asthma after a 1-week course of corticosteroid inhalation treatment.

This study evaluated the effects of corticosteroid inhalation on the deposition pattern of Tc-99m HSA radioaerosols in 24 patients with asthma. The homogeneous degree of depositing radioaerosol was quantitatively evaluated using a modified standard score system over both lungs. The baseline scores were calculated before inhalation therapy of 0.05 mg beclomethasone dipropionate four times daily for 1 week. The studies were then repeated after treatment to evaluate the effects of inhalation therapy. After treatment, the scores decreased in 16 of 24 cases (67%), which means that the degree of the bronchial obstruction decreased. The statistical results revealed significant differences in the total homogeneity score (P < 0.001) before and after therapy. Thus, a 1-week course of beclomethasone dipropionate inhalation therapy improves the bronchial obstruction in asthma patients as shown by the quantitative homogeneity score system of the Tc-99m HSA radioaerosol inhalation lung scintigraphy.

Administration, Inhalation↗
PubMed2001

The effectiveness of high-dose inhaled budesonide therapy in the treatment of acute asthma exacerbations in children.

BACKGROUND: International guidelines recommend the use of systemic steroids for the treatment of acute asthma attack if it has not been resolved within 24 to 36 hours of home management with regular beta2 mimetic inhalation. Such therapy for infrequent exacerbations is unlikely to have serious systemic effects. Unfortunately, many patients receiving frequent courses are potentially at risk for corticosteroid-induced side effects such as adrenal suppression, depression of linear growth, and osteoporosis. OBJECTIVE: To decrease the use of frequent oral corticosteroid courses in children, this study was designed to evaluate the efficacy of high-dose inhaled steroids in comparison with oral steroids, in the therapy of acute asthma exacerbations in children. METHODS: Sixty children who have experienced an acute exacerbation of asthma unresponsive to home management with regular use of inhaled beta2 mimetics, yet not severe enough to hospitalize, were randomized to be treated with either high-dose inhaled budesonide (1,600 microg daily) or oral methylprednisolone (1 mg/kg daily) plus medium-dose inhaled budesonide (800 microg daily, both in addition to inhaled terbutaline, 2,000 microg daily). Pre- and posttreatment pulmonary index scores, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow 25% to 75% (FEF25%-75%) were evaluated. RESULTS: The mean number of decrease in pulmonary index score was 2.61 +/- 1.12 in the high-dose budesonide-receiving group (group I) and 1.90 +/- 1.08 in the oral steroid-receiving group (group II). There was a statistically significant difference between the two groups, in favor of group I (P = .038). No statistically significant difference was detected between the two groups with respect to the increase in lung function test measurements (FEV1, FEV1/FVC, FEF25%-75%; P = .790, .959, .819, respectively). CONCLUSIONS: Short-term high-dose budesonide therapy can be considered an alternative for children who are experiencing an acute asthma attack that is unresponsive to home management with regular use of an inhaled beta2 mimetic, yet who are not severe enough to hospitalize.

Acute Disease↗
PubMed1992

A model for conversion from small volume nebulizer to metered dose inhaler aerosol therapy.

Rationing of medical services will be necessary if we do not develop a more rational and efficient health care system. Respiratory care services are receiving emphasis as we try to curtail spiraling health care costs. In analysis of our respiratory care services, we found that small volume nebulizer (SVN) therapy was still a major portion of our workload. We instituted a protocol to convert to metered dose inhaler (MDI) therapy. All hospitalized patients, excluding those admitted to the spinal cord unit and intensive care units, with a physician's order for aerosol delivery by SVN, were evaluated by respiratory care practitioners for conversion to MDI therapy. A simple protocol for the therapist to use in this conversion was developed. All patients converted to MDI were trained in appropriate MDI use by the therapist. A three-day follow-up of each patient's compliance with proper MDI therapy was initiated. Even with a 72-h allowance for initial SVN treatment, we realized a 9,350 procedure reduction from deleted treatments and an additional 7,650 conversions to MDI. Less than 2 percent of our patients failed to make a completely successful conversion to MDI. Those patients who successfully converted to MDI resulted in reduced hospital costs of $43,758 based on excess medication, supplies, and labor costs associated with SVN treatments. We also saved 5,000 h of technician time that was used to further instruct patients in appropriate MDI therapy. Aerosol therapy by MDI is cost-effective therapy. The institution of guidelines for MDI conversion has reduced fear of failure for both clinicians and patients and illustrates the importance of patient education by qualified respiratory therapists.

Adrenergic beta-Agonists↗
PubMed2004

Inhaled combination therapy with long-acting beta 2-agonists and corticosteroids in stable COPD.

Long-acting beta(2)-agonists (LABAs) have been shown to be effective first-line bronchodilators in the treatment of COPD patients, and inhaled corticosteroids (ICSs) have been shown to reduce the frequency and/or severity of exacerbations in COPD patients. The concomitant use of a LABA and an ICS can influence both airway obstruction (ie, smooth muscle contraction, increased cholinergic tone, and loss of elastic recoil), and airway inflammation (ie, increased numbers of neutrophils, macrophages, and CD8+ lymphocytes, elevated interleukin-8 and tumor necrosis factor-alpha levels, and protease/antiprotease imbalance). They are also able to reduce the total number of bacteria adhering to the respiratory mucosa in a concentration-dependent manner without altering the bacterial tropism for mucosa, and to preserve ciliated cells. Several clinical trials support the concept of inhaled combination therapy with LABAs and corticosteroids in stable COPD patients. This type of therapy not only improves airflow obstruction but also provides clinical benefits, as manifested by sustained reduction in overall symptoms, improvements in health-related quality of life, and reductions in exacerbations. All of these effects are very important because, despite recent advances in our understanding of COPD and its treatment, therapy remains suboptimal for a considerable number of patients.

Administration, Inhalation↗
PubMed2005

Relationship between vascular endothelial growth factor and angiopoietin-2 in asthmatics before and after inhaled beclomethasone therapy.

Vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2) play complementary roles in the process of vascular remodeling. Therefore, this study was designed to examine an interaction between VEGF and Ang-2 in asthmatic airways. VEGF, Ang-2, and hepatocyte growth factor (HGF) levels in induced sputum obtained from 17 asthmatic patients and 10 normal control subjects were examined. Eight weeks of inhaled beclomethasone dipropionate (BDP) therapy (800 microg/day) was administered to all asthmatic patients, and sputum induction was repeated. VEGF, Ang-2, and HGF levels in induced sputum were significantly higher in asthmatic patients than in control subjects. Ang-2 levels were significantly correlated with VEGF levels but not with HGF levels. We also found that there was a significant correlation between airway vascular permeability index and VEGF levels but not HGF levels. In addition, VEGF/Ang-2 ratio in asthmatic patients was significantly higher than that in control subjects, and it was significantly correlated with airway vascular permeability index. After inhaled BDP therapy, VEGF levels were significantly decreased, but Ang-2 levels did not change. Therefore, VEGF/Ang-2 ratio after BDP therapy was markedly decreased to the same level as in the control subjects. Our findings suggest that interaction between VEGF and Ang-2 in asthmatic airways may exist and that high VEGF/Ang-2 ratio may be responsible for increased airway microvascular permeability. In addition, inhaled glucocorticoids therapy may reduce airway vascular permeability and remodeling via VEGF/Ang-2-dependent mechanism.

Administration, Inhalation↗
PubMed2001

The importance of the device in asthma therapy.

Inhalation is the preferred route for drug delivery in asthma treatment. Successful management of asthma depends on achieving adequate delivery of inhaled drug to the lungs, and to this end the role of the device used for delivery is very important. Aerosolized anti-asthma medications have been available for more than 40 years as pressurized metered dose inhalers (pMDIs), but more recently dry powder inhalers (DPIs) have been developed as an alternative. Laboratory assessment of fine particle dose has been shown to correlate to pulmonary deposition if the assessments are performed with an in vivo-like set up. The DPI Turbuhaler delivers a high proportion of the dose as fine particles suggesting high pulmonary deposition. This finding has been confirmed by lung deposition studies, which indicate superior pulmonary deposition from Turbuhaler compared with a pMDI. This superior delivery to the lungs with Turbuhaler is reflected in a better clinical effect, as measured by greater improvements in lung function. The DPIs such as Turbuhaler are easy to use, and Turbuhaler has been shown to function well in a constrained situation such as an acute asthmatic exacerbation. Furthermore, the use of Turbuhaler in acute asthma will provide rapid clinical improvement. The in vivo variability in lung deposition obtained with Turbuhaler is lower than with pMDI, indicating that the performance of Turbuhaler is less dependent on patient competence. Thus, the development of Turbuhaler represents an important step forward in the effective management of asthma.

Acute Disease↗
PubMed1999

[Long-acting beta-2-adrenergic agonists in bronchospasm therapy].

Inhaled long-acting beta 2-agonists are widley used in the treatment of asthma as regular prophylaxis, but not as rescue medication for the relief of acute symptoms. Comparison of salmeterol and formoterol in the review is focused on practical applications and some adverse reactions during long-time treatment.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Peripheral airways mucus clearance in stable asthma is improved by oral corticosteroid therapy.

Inhaled 99mTc-labelled particles have been used to assess mucus clearance from peripheral, intermediate and inner lung zones of 12 patients with stable asthma. The method of analysis relies on a ventilation image with 81mKr to estimate the distribution of radioaerosol alveolar deposition so that clearance from each zone can be related just to particles deposited in the ciliated conducting airways. In calculating clearance from intermediate and inner lung zones, allowance is made for particles transported into these zones from more distal regions of the lung. Peripheral zone clearance in the asthmatic subjects improved significantly (p less than 0.01) after four weeks of corticosteroid treatment (two weeks on 15 mg prednisolone orally each day, plus two weeks on 30 mg). No significant change occurred in clearance from the inner zone when all patients were considered together. However, the six patients who prior to treatment coughed relatively infrequently did show a significant (p less than 0.05) increase in clearance from the inner zone as well as from the peripheral zone.

Administration, Oral↗
PubMed2000

An interactive algorithm for the assessment of cumulative cortisol suppression during inhaled corticosteroid therapy.

The objective of the study was to develop an algorithm based on a pharmacokinetic-pharmacodynamic (PK/PD) modeling approach to quantify and predict cumulative cortisol suppression (CCS) as a surrogate marker for the systemic activity of inhaled corticosteroid therapy. Two Excel spreadsheets, one for single dose and another for steady-state multiple doses of inhaled steroids, were developed for predicting CCS. Four of the commonly used inhaled steroids were chosen for the purposes of simulation: fluticasone propionate (FP), budesonide (BUD), flunisolide (FLU), and triamcinolone acetonide (TAA). Drug-specific PK and PD parameters were obtained from previous single- and multiple-dose studies. In cases in which multiple-dose data were not available, the single-dose data were extrapolated. The algorithm was designed to calculate CCS based on 5 input parameters: name of drug, dose, dosing interval, time(s) of dosing, and type of inhaler device. In addition, a generalized algorithm was set up to calculate CCS based on clearance, volume of distribution, absorption rate, protein binding, pulmonary deposition, oral bioavailability, and unbound EC50 of the corticosteroid of interest. The spreadsheet allowed predictions of CCS for single doses as well as steady-state conditions. A simple method has been developed that facilitates comparisons between various drugs and dosing regimens and has the potential to significantly reduce the number of comparative clinical trials to be performed for evaluating the short-term systemic activity of inhaled corticosteroids.

Administration, Inhalation↗