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PubMed1991

Clinical efficacy of two beta 2-sympathicomimetics in different inhalers in children with asthma. Comparison of pirbuterol in a breath-actuated inhaler and salbutamol in a customary metered-dose inhaler.

In a controlled clinical crossover trial, the therapeutic effect of pirbuterol (CAS 38677-81-5) in the Autohaler was compared to that of salbutamol in a customary metered-dose aerosol in 17 children with asthma. Each child was randomized to both treatments with a washout period of at least 1 day and at most 13 days. Ten children commenced with salbutamol and then switched over to pirbuterol, and the other 7 vice versa. The main criterion to evaluate efficacy was the forced expiratory volume after 1 s (FEV1). Other efficacy criteria were forced vital capacity (FVC) and peak expiratory flow (PEF). The patients were given detailed instructions on how to use the inhalers. Each treatment was applied in the morning with one shot (0.2 mg pirbuterol or 0.1 mg salbutamol). FEV1, FVC and PEF were measured in all patients 10 min before and 10 min after medication with the whole-body plethysmograph; further measurements were carried out in most patients 60 and 240 min after application. There was a mean increase of 47% in the FEV1 compared to baseline with pirbuterol in the Autohaler compared to a mean increase of only 30% with salbutamol in the customary metered-dose inhaler. The difference is statistically significant (p = 0.036). A linear crossover analysis showed a significant treatment effect 10 min after application in favour of pirbuterol with no significant period effects or interactions (p = 0.020). The increases of FVC and PEF after pirbuterol treatment were also remarkably higher than after salbutamol. No side effects were observed.

Administration, Inhalation↗

PubMed2000

Poor inhalation technique, even after inhalation instructions, in children with asthma.

The aim of this study was to evaluate the effect of instructions to children with asthma (given by general practitioners or by pharmacy assistants) on how to inhale from metered dose inhalers with spacers (MDI/s) or dry powder inhalers (DPI). We scored inhalation technique of asthmatic children according to criteria defined by the Netherlands Asthma Foundation, and related the performance to the inhalation instructions given. For each inhaler, a number of steps were considered essential for reliable drug delivery. Patients newly referred for asthma were asked to demonstrate their inhalation technique and to fill out a questionnaire on the inhalation instruction received prior to referral. Children participating in a clinical trial, who had received repeated comprehensive inhalation instructions, served as a control group. Sixty-six newly referred patients (1-14 years of age, median age 5 years; 37 boys) and 29 control patients (5-10 years of age, median age 7 years; 21 boys) completed the study. Sixty patients (91%) had received inhalation instruction prior to referral. Only 29% of these patients, using a dry powder inhaler, performed all essential steps correctly, compared to 67% of children using a metered dose inhaler/spacer combination (P < 0.01). Children who had received comprehensive inhalation instructions with repeated checks of proper inhalation technique at the pharmacy or in the clinical trial setting were more likely to perform all essential steps correctly (79% and 93%, respectively) than children who had received a single instruction by a general practitioner (39%, P < 0.01). Many asthmatic children use their inhalers devices too poorly to result in reliable drug delivery, even after inhalation instruction. Comprehensive inhalation instruction and repeated check-ups are needed to assure reliable inhalation technique.

Administration, Inhalation↗

PubMed1990

Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurised metered dose inhaler, as a dry powder, and as a nebulised solution.

The lung dose and deposition patterns of drug delivered by dry powder inhaler are not known. The effects of inhaling 400 micrograms salbutamol delivered by dry powder inhaler (two 200 micrograms salbutamol Rotacaps), by pressurised metered dose inhaler, and by Acorn nebuliser were studied in nine subjects with chronic stable asthma. Technetium-99m labelled Teflon particles were mixed with micronised salbutamol in the pressurised metered dose inhaler and in the capsules; technetium-99m labelled human serum albumin was mixed with the salbutamol solution for the nebuliser study. The pressurised metered dose inhaler deposited 11.2% (SEM 0.8%) of the dose within the lungs; this was significantly more than the dose deposited by the dry powder inhaler (9.1% (0.6%], but did not differ significantly from the dose delivered by the nebuliser (9.9% (0.7%]. Distribution within the peripheral third of the lung was significantly greater with the nebuliser than with the other two systems; FEV1 improved to a significantly greater extent after inhalation of 400 micrograms salbutamol from the pressurised metered dose inhaler (35.6% from baseline) than from the nebuliser (25.8%) or dry powder inhaler (25.2%). Thus after inhalation of similar doses of salbutamol a larger proportion of drug was deposited within the lungs when it was inhaled from a metered dose inhaler than from a dry powder system; the nebuliser achieved the greatest peripheral deposition. The bronchodilator response seems to depend on the amount of drug within the lungs rather than its pattern of distribution.

Administration, Inhalation↗

PubMed1994

Relative bioavailability of salbutamol to the lung following inhalation using metered dose inhalation methods and spacer devices.

BACKGROUND: Inhalation aids do not require coordination between actuation of a metered dose inhaler (MDI) with inspiration and reduce oropharyngeal impaction. The delivery of salbutamol to the lung and systemic availability following inhalation with three commonly used spacers and an open mouth technique have been evaluated using a simple noninvasive technique based on urinary excretion 30 minutes and 24 hours after the dose. METHODS: Ten healthy subjects inhaled, on randomised study days, 4 x 100 micrograms from a Ventolin MDI and, subsequently, with the aid of a Volumatic, Bricanyl Spacer, and Nebuhaler spacer device. In addition, an open mouth inhaler technique was evaluated. Urine samples were collected 0-30 minutes and 0.5-24 hours after inhalation. From these samples the relative bioavailability to the lung (urinary salbutamol excretion 30 minutes after dosing) and the systemic bioavailability of the dose (24 hour urinary excretion of salbutamol and its metabolite) for each inhalation method was obtained. RESULTS: The mean (SD) urinary excretion of salbutamol 30 minutes after inhalation using the MDI alone and with the Volumatic, Bricanyl Spacer, Nebuhaler, and open mouth technique was 2.83 (0.78)%, 3.37 (0.69)%, 4.09 (0.91)%, 4.34 (1.60)%, and 3.49 (0.98)%, respectively, expressed as a percentage of the nominal dose. The nebuhaler and Bricanyl Spacer spacer devices were found to increase the relative bioavailability of salbutamol to the lung compared with the MDI alone. Compared with the MDI the inhalation aid increases were much greater than the intra-individual variability of the urinary excretion method. In 11 individuals who each repeated the same inhalation procedure on four separate occasions, the mean (SD) coefficient of variation was 8.24 (2.36)%. The mean (SD) 24 hour urinary excretion of salbutamol and its metabolites was 26.6 (6.79), 27.0 (7.95), and 55.6 (9.74)% of the salbutamol dose for the Volumatic, Nebuhaler, and MDI, respectively. Similar values following the open mouth method and Bricanyl Spacer were 48.9 (10.97)% and 43.8 (11.57)%. These values, representing the systemic availability of the inhaled dose, were lower when inhaling with the aid of the Volumatic and Nebuhaler than inhalation from the MDI alone. CONCLUSIONS: Spacer devices improve pulmonary bioavailability of salbutamol and reduce the systemically available dose.

Administration, Inhalation↗

PubMed1995

Recent trends in the use of inhaled beta 2-adrenergic agonists and inhaled corticosteroids in Saskatchewan.

OBJECTIVE: To examine recent trends in the use of inhaled beta 2-adrenergic agonists and inhaled corticosteroids for the treatment of asthma among Saskatchewan residents and to determine whether these trends are in keeping with widely publicized guidelines recommending a reduction in the use of agents to treat symptoms (i.e., inhaled beta 2-adrenergic agonists) and increased use of prophylactic agents (i.e., inhaled corticosteroids). DESIGN: Descriptive pharmacoepidemiologic study conducted with the use of data from the computerized database of the Saskatchewan Prescription Drug Plan. SETTING: Saskatchewan. PATIENTS: Saskatchewan residents 5 to 54 years of age who received one or more outpatient prescriptions for drugs to treat asthma (inhaled drugs, ingested beta 2-adrenergic agonists and ingested methylxanthines) from 1989 to 1993. OUTCOME MEASURES: Epidemiologic trends, calculated for each year: number of prescriptions per 1,000 persons; number of patients who received prescriptions for inhaled corticosteroids, inhaled beta 2-adrenergic agonists and any type of drug to treat asthma; mean number of such prescriptions per patient; and weighted mean amount of salbutamol, fenoterol and beclomethasone dispensed per patient. RESULTS: There has been an increase in the proportion of the population receiving prescriptions for drugs to treat asthma. The number of patients receiving these drugs per 1,000 people rose during the study period from 33.38 to 46.59 for any drug to treat asthma, from 24.70 to 33.77 for inhaled beta 2-adrenergic agonists and from 6.1 to 19.9 for inhaled corticosteroids. The mean number of prescriptions per patient decreased steadily for all drugs to treat asthma (from 5.34 in 1989 to 3.88 in 1993), for inhaled beta 2-adrenergic agonists (from 4.35 to 3.09) and for inhaled corticosteroids (from 2.98 to 2.25). The weighted mean amount of inhaled salbutamol dispensed per patient per year decreased by 40%, from 178.08 mg in 1989 to 109.14 mg in 1993. The weighted amount of fenoterol dispensed per patient per year declined even more, by 58%, from 387.91 mg in 1989 to 164.00 mg in 1993. Conversely, the weighted amount of inhaled beclomethasone dispensed per patient per year increased by 35% from 46.95 mg in 1989 to 63.50 mg in 1992, then dropped to 56.17 mg per year in 1993. CONCLUSION: These data demonstrate a substantial change in Saskatchewan in the prescribing of drugs to treat asthma; they suggest that many physicians responded to current guidelines advocating increased attention to prevention of airway inflammation in the treatment of asthma.

Administration, Inhalation↗

PubMed2000

Inhaled corticosteroids for asthma therapy: patient compliance, devices, and inhalation technique.

BACKGROUND: Patient compliance, inhalation devices, and inhalation techniques influence the effectiveness of inhaled medications. METHODS: This article presents the results of a systematic literature review of studies measuring compliance with inhaled corticosteroids, measuring inhalation technique with different inhalation devices, and estimating the proportion of inhaled drug that is deposited in the lung. RESULTS: Overall, patients took the recommended doses of inhaled medication on 20 to 73% of days. Frequency of efficient inhalation technique ranged from 46 to 59% of patients. Education programs have been shown to improve compliance and inhalation techniques. The lung deposition achieved with different inhalers depends on particle size as well as inhaler technique. CONCLUSION: This review demonstrates that multiple factors may come between a prescription of an inhaled corticosteroid and the arrival of that medicine at its target organ, the lung.

Adrenal Cortex Hormones↗

PubMed1997

Importance of selected inhaler characteristics and acceptance of a new breath-actuated powder inhalation device.

The degree of patient comfort and satisfaction with an inhaler can have an important effect on compliance with asthma treatment and, hence, therapeutic success. The objective of this study was to assess, from the patient's perspective, the importance of various inhaler characteristics and then evaluate patient satisfaction with a new breath-actuated powder inhaler (Diskhaler) based on those characteristics. Self-administered patient satisfaction questionnaires were completed as part of a randomized, double-blind, placebo-controlled study of fluticasone propionate powder in the treatment of asthma. At baseline, patients rated the importance of five inhaler characteristics (convenient to carry, durability, easy to load, easy to hold and operate, and easy to clean). Following exposure to the Diskhaler over a period of 8 weeks, patients rated the inhaler on those same characteristics. They also rated their comfort using the inhaler and their overall satisfaction with the inhaler. Data were available from 274 patients, the majority of whom expressed a high or very high level of satisfaction with the Diskhaler on each of the five characteristics. These ratings were congruent with their ratings of the importance of those same characteristics; 80-90% rated "convenient to carry," "durability," "easy to load," and "easy to hold and operate" as important or very important characteristics for an inhaler, while "easy to clean" was considered somewhat less important, with 63% rating this characteristic as important or very important. Following the initial exposure to the Diskhaler, 67% of patients were comfortable or very comfortable with the inhaler; that percentage increased to 79% after 8 weeks of use. Following 2 and 8 weeks of use, 61 and 62%, respectively, were satisfied or very satisfied with the Diskhaler. In general, satisfaction ratings were not affected by treatment, indicating that patients were evaluating only the inhaler and not the efficacy of the study drug they received. This study helped to identify which selected inhaler characteristics are most important to patients with asthma. The Diskhaler inhaler performed well on those characteristics deemed important to the patients. From their first exposure to the Diskhaler, patients were comfortable using the device, and this overall acceptance of the inhaler was maintained throughout the study.

Adult↗

PubMed1999

[Inhaled corticosteroid therapy in mild and moderate persistent asthma. Acceptability of a new inhalation system: the jet].

The objectives of this study were to assess the acceptability and efficacy of Jet (a metered dose inhaler with a 100 ml chamber giving 250 micrograms beclomethasone dipropionate per puff) in patients with mild to moderate asthma using a dose-for-dose schedule in substitution for their standard metered dose inhaler with or without an inhalation chamber. An open trial was conducted over 5 weeks in 356 asthma patients treated with inhaled corticosteroids at a mean 914 +/- 198 micrograms/24 h dose. beta 2-agonists were used by all patients, either systematically (prescription) or as needed. Prior to the study, 27% of the patients used a standard metered dose inhaler with a large-volume inhalation chamber and 73% used a standard metered dose inhaler alone. The rate of nocturnal, early morning, and diurnal symptoms and cough decreased by 31.4, 33.4, 46.9, and 37.0% respectively and the variability of peak expiratory flow rate fell from 2 +/- 0.08% to 0.9 +/- 0.02% in the group using the metered dose inhaler with the chamber and from 1.3 +/- 0.04 to 0.5 +/- 0.01% in the group using the standard metered dose inhaler. The investigators determined that treatment efficacy was good or excellent in 94.8%. These findings should be confirmed by studies comparing Jet directly with other inhalation chamber systems or with standard metered dose inhalers. For 97.5% of the patients, it was easy to learn to use Jet and 88.2% of the patients felt no discomfort when using Jet; 64.8% of the patients stated they experienced clinical improvement. At the end of the trial, 77.9% of the patients (76.3% of those who used the inhalation chamber during the study and 78.4% of those who used the metered dose inhaler alone) stated they preferred Jet over their prior system.

Adolescent↗

PubMed1994

The effect of inhaled nitric oxide on pulmonary ventilation-perfusion matching following smoke inhalation injury.

BACKGROUND: We previously reported that inhaled nitric oxide (NO) improved pulmonary function following smoke inhalation. This study evaluates the physiologic mechanism by which inhaled NO improves pulmonary function in an ovine model. METHODS: Forty-eight hours following wood smoke exposure to produce a moderate inhalation injury, 12 animals were anesthetized and mechanically ventilated (FIO2, 0.40; tidal volume, 15 mL/kg; PEEP, 5 cm H2O) for 3 hours. For the first and third hours, each animal was ventilated without NO: for the second hour, all animals were ventilated with 40 ppm NO. Cardiopulmonary variables and blood gases were measured every 30 minutes. The multiple inert gas elimination technique (MIGET) was performed during the latter 30 minutes of each hour. The data were analyzed by ANOVA. RESULTS: Pulmonary arterial hypertension and hypoxemia following smoke inhalation were significantly attenuated by inhaled NO compared with the values without NO (p < 0.05, ANOVA). Smoke inhalation resulted in a significant increase in blood flow distribution to low VA/Q areas (VA/Q < 0.10) with increased VA/Q dispersion. These changes were only partially attenuated by the use of inhaled NO. The SF6 (sulfur hexafluoride) retention ratio was also decreased by inhaled NO. Peak inspiratory pressures and pulmonary resistance values were not affected by inhaled NO. CONCLUSIONS: Inhaled NO moderately improved VA/Q mismatching following smoke inhalation by causing selective pulmonary vasodilation of ventilated areas in the absence of bronchodilation. This modest effect appears to be limited by the severe inflammatory changes that occur as a consequence of smoke exposure.

Analysis of Variance↗

PubMedDate not supplied

Assessment of patient acceptance and inhalation technique of a pressurized aerosol inhaler and two breath-actuated devices.

OBJECTIVE: To assess inhalation technique in patients after written instruction alone, written and verbal instruction, and clinical use of two new inhalation devices. DESIGN: Randomized, crossover evaluation of the albuterol Diskhaler and the terbutaline Turbuhaler. SETTING: Canadian tertiary-care hospital. PATIENTS: Twenty hospitalized adults with asthma or chronic obstructive pulmonary disease currently using an albuterol metered-dose inhaler (MDI). Nineteen patients received Diskhaler, 16 received Turbuhaler, 15 received both inhalers, and 10 patients used both inhalers for three days each. INTERVENTIONS: Patients were randomized to receive either Diskhaler or Turbuhaler for three days. Inhaler technique was assessed after written instruction, written plus verbal instruction, at the first scheduled dose after instruction, and after three days of clinical use. Patients remaining in the hospital after three days crossed over to the other study inhaler and the same protocol was followed. MAIN OUTCOME MEASURES: Patient inhalation technique was assessed and compared for the MDI, Diskhaler, and Turbuhaler. RESULTS: Assessment of MDI technique revealed that 35 percent of patients used their MDI correctly on the first puff, and 42 percent used it correctly on the second puff. Following written instruction alone, correct technique was demonstrated by 32 percent of patients with Diskhaler and 6 percent with Turbuhaler. Technique significantly improved following verbal instruction, although 40 percent of the patients required up to three attempts to demonstrate correct technique on at least one of the study inhalers. After three days of clinical use, correct technique was demonstrated in only 54 percent of the Diskhaler and 64 percent of the Turbuhaler assessments. Performance at this assessment was, however, significantly better on the Turbuhaler than on the MDI (p = 0.01). Performance on the Diskhaler was not significantly different from the performance on the other inhalers. CONCLUSIONS: Written instruction alone is inadequate in teaching correct inhalation technique. Verbal instruction and technique assessment are essential for patients to achieve proper technique. Patients may perform better on the Turbuhaler than on other inhalation devices.

Administration, Inhalation↗

PubMed1998

Comparison of inhaled nitric oxide and inhaled aerosolized prostacyclin in the evaluation of heart transplant candidates with elevated pulmonary vascular resistance.

STUDY OBJECTIVE: Elevated pulmonary vascular resistance is a risk factor in heart transplantation and reversibility of high pulmonary vascular resistance is evaluated preoperatively in potential recipients using i.v. vasodilators or inhaled nitric oxide. Prostacyclin is a potent vasodilator, which when inhaled, has selective pulmonary vasodilatory properties. The aim of this study was to compare the central hemodynamic effects of inhaled prostacyclin with those of inhaled nitric oxide in heart transplant candidates. DESIGN: A pharmacodynamic comparative study. SETTING: Cardiothoracic ICU or laboratory for diagnostic heart catheterization at a university hospital. PATIENTS: Ten heart transplant candidates with elevated pulmonary vascular resistance (>200 dynes x s x cm(-5) and/or a transpulmonary pressure gradient > 10 mm Hg) were included in the study. INTERVENTIONS: Nitric oxide (40 ppm) and aerosolized prostacyclin (10 microg/mL) were administered by inhalation in two subsequent 10-min periods. Hemodynamic measurements preceded and followed inhalation of each agent. MEASUREMENTS AND RESULTS: Both inhaled nitric oxide and inhaled prostacyclin reduced mean pulmonary artery pressure (-7% vs -7%), pulmonary vascular resistance (-43% vs -49%), and the transpulmonary gradient (-44% vs -38%). With inhaled prostacyclin, an 11% increase in cardiac output was observed. Other hemodynamic variables, including the systemic BP, remained unaffected by each of the agents. CONCLUSIONS: Inhaled prostacyclin induces a selective pulmonary vasodilation that is comparable to the effect of inhaled nitric oxide. Major advantages with inhaled prostacyclin are its lack of toxic reactions and easy administration as compared with the potentially toxic nitric oxide requiring more complicated delivery systems.

Administration, Inhalation↗

PubMedDate not supplied

Treatment patterns among adult patients with asthma: factors associated with overuse of inhaled beta-agonists and underuse of inhaled corticosteroids.

BACKGROUND: Overuse of inhaled beta-agonists and underuse of inhaled corticosteroids by patients with asthma may have adverse consequences. This study was performed to identify factors associated with misuse of these types of asthma medication. METHODS: We examined baseline data from a longitudinal survey of adult patients with asthma. The setting was a consortium of 15 national managed care organizations serving 11 large employers. Baseline surveys were completed by 6612 health plan enrollees at least 18 years old who had had at least 2 visits with a diagnostic code for asthma in the preceding 2 years. The main outcome measures were the overuse of inhaled beta-agonists and the underuse of inhaled corticosteroids. Independent variables were patient and process of care factors. RESULTS: Among patients with moderate or severe asthma, 16% of users of inhaled beta-agonists reported overuse (>8 puffs per day on days of use), and 64% of users of inhaled corticosteroids reported underuse (use on < or =4 days/wk or < or =4 puffs per day). Overuse of inhaled beta-agonists was most strongly associated with concomitant treatment with inhaled corticosteroids or anticholinergic agents, increased asthma symptom severity, problems in obtaining asthma medication, and male sex. Underuse of inhaled corticosteroids was associated with nonwhite race, younger age (18 to 34 years), lower use of inhaled beta-agonist, lower symptom severity, and not possessing a peak flow meter. Rates of misuse of medication also varied by speciality of the patient's provider (generalist, allergist, or pulmonologist). CONCLUSIONS: Overuse of inhaled beta-agonists may be caused by symptom severity, while underusers of corticosteroids may interrupt use as symptoms abate. This study demonstrated an important opportunity to improve medication use among patients with asthma.

Administration, Inhalation↗

PubMed1986

Augmentation of antibody responses of mice to inhaled protein antigens by simultaneously inhaled bacterial lipopolysaccharides.

Serum antibody responses of mice to repeatedly inhaled protein antigens such as bovine serum albumin and ovalbumin, plus or minus bacterial lipopolysaccharide (LPS) in the form of an aerosol were studied. Results showed that the levels of responses to inhaled protein antigens varied, depending on the mouse strain-antigen combination and that LPS inhaled simultaneously with the antigens definitely augmented the responses which were not otherwise very high. LPS extracted from Klebsiella O3 (LPS-K) but not LPS from Escherichia coli O55 (LPS-E), which was inhaled at the time of initial inhalation of antigen, significantly intensified the priming for the secondary antibody response to the antigen subsequently inhaled. Both LPS-K and LPS-E, however, definitely acted to augment the response when they were inhaled repeatedly together with the antigen. Oral administration of antigen or antigen plus LPS-K did not induce any detectable antibody response in our experiment, ruling out the possibility that the antigen and LPS stimulated the immune system via alimentary canal rather than via lung. Tissue distribution of the radioactivity soon after inhalation of 131I-labeled antigen and decay speed of the radioactivity were not significantly changed by LPS-K inhaled simultaneously. This suggested that the augmentation of responses was not mediated by the action of LPS to modulate the air-blood barrier against the entry of antigen via lung. All the results prove for the first time that inhaled LPS displays a definite adjuvant action on antibody responses to inhaled antigens.

Adjuvants, Immunologic↗

PubMed1998

Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group.

OBJECTIVES: To evaluate the safety and physiologic response of inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). In addition, the effect of various doses of inhaled NO on clinical outcome parameters was assessed. DESIGN: Prospective, multicenter, randomized, double-blind, placebo-controlled study. SETTING: Intensive care units of 30 academic, teaching, and community hospitals in the United States. PATIENTS: Patients with ARDS, as defined by the American-European Consensus Conference, were enrolled into the study if the onset of disease was within 72 hrs of randomization. INTERVENTIONS: Patients were randomized to receive placebo (nitrogen gas) or inhaled NO at concentrations of 1.25, 5, 20, 40, or 80 ppm. MEASUREMENTS AND MAIN RESULTS: Acute increases in PaO2, decreases in mean pulmonary arterial pressure, intensity of mechanical ventilation, and oxygenation index were examined. Clinical outcomes examined were the dose effects of inhaled NO on mortality, the number of days alive and off mechanical ventilation, and the number of days alive after meeting oxygenation criteria for extubation. A total of 177 patients were enrolled over a 14-month period. An acute response to treatment gas, defined as a PaO2 increase > or =20%, was seen in 60% of the patients receiving inhaled NO with no significant differences between dose groups. Twenty-four percent of placebo patients also had an acute response to treatment gas during the first 4 hrs. The initial increase in oxygenation translated into a reduction in the FIO2 over the first day and in the intensity of mechanical ventilation over the first 4 days of treatment, as measured by the oxygenation index. There were no differences among the pooled inhaled NO groups and placebo with respect to mortality rate, the number of days alive and off mechanical ventilation, or the number of days alive after meeting oxygenation criteria for extubation. However, patients receiving 5 ppm inhaled NO showed an improvement in these parameters. In this dose group, the percentage of patients alive and off mechanical ventilation at day 28 (a post hoc analysis) was higher (62% vs. 44%) than the placebo group. There was no apparent difference in the number or type of adverse events reported among those patients receiving inhaled NO compared with placebo. Four patients had methemoglobin concentrations >5%. The mean inspired nitrogen dioxide concentration in inhaled NO patients was 1.5 ppm. CONCLUSIONS: From this placebo-controlled study, inhaled NO appears to be well tolerated in the population of ARDS patients studied. With mechanical ventilation held constant, inhaled NO is associated with a significant improvement in oxygenation compared with placebo over the first 4 hrs of treatment. An improvement in oxygenation index was observed over the first 4 days. Larger phase III studies are needed to ascertain if these acute physiologic improvements can lead to altered clinical outcome.

Acute Disease↗

PubMed2000

Inappropriate inhaler use: assessment of use and patient preference of seven inhalation devices. EDICI.

Inefficient inhaler technique is a common problem resulting in poor drug delivery, decreased disease control and increased inhaler use. The aim of this study was to assess patients' use of different inhaler devices and to ascertain whether patient preference is indicative of ease of use and whether current inhaler use has any influence on either technique or preference. We also wished to define the most appropriate method of selecting an inhaler for a patient, taking into account observed technique and device cost. One hundred patients received instruction, in randomized order, in the use of seven different inhaler devices. After instruction they were graded (using predetermined criteria) in their inhaler technique. After assessment patients were asked which three inhalers they most preferred and which, if any, they currently used. Technique was best using the breath-actuated inhalers; the Easi-Breathe and Autohaler, with 91% seen to have good technique. The pressurized metered dose inhaler (pMDI) fared poorly, in last position with only 79% of patients showing good technique, despite being the most commonly prescribed. The Easi-Breathe was by far the most popular device with the patients. The Autohaler came in second position closely followed by the Clickhaler and Accuhaler. The majority of patients (55%) currently used the pMDI but the pMDI did not score highly for preference or achieve better grades than the other devices. Only 79% of patients tested could use the pMDI effectively even after expert instruction yet it continues to be commonly prescribed. This has important repercussions for drug delivery and hence disease control. Prescribing a patient's preferred device increases cost but can improve efficiency and therefore be cost effective in the long term. Using an inexpensive device (pMDI) when technique is good and the patient's preferred inhaler device when not is one way to optimize delivery and may even reduce cost.

Adult↗

PubMedDate not supplied

Patient perception of the diskus inhaler: a comparison with the turbuhaler inhaler.

Asthmatic patients who were regular and experienced users of the metered-dose inhaler (MDI) but with no history of powder inhaler use were interviewed by questionnaire. Most (71%) of the 159 adults recruited had suffered from asthma for more than five years; 89% had used an MDI for more than one year. In all, 153 (97%) found their current MDI easy or very easy to handle. Effectiveness in delivering the drug and ease of operation were the two features of the device they were most satisfied with. The two features 'of an ideal inhaler' rated most highly were the presence of a dose counter and ease of use during an attack (58% and 72% of respondents, respectively). Other important features included hygiene, sensation that a dose had been taken, and small size. When attitudes towards the Diskus inhaler and the Turbuhaler inhaler were compared, 108 (68%) would have been quite or very happy to have a Diskus inhaler prescribed for them, and 79 (50%) a Turbuhaler inhaler. The Diskus inhaler scored significantly better than the Turbuhaler inhaler for knowing how many doses were left, the presence of an attached cover, attractiveness (p < 0.001), hygiene, shape, weight (p = 0.001), and perceived ease of use (p = 0.002). The Turbuhaler inhaler scored significantly better in terms of size (p < 0.001). Overall, the Diskus inhaler was preferred by 104 of 159 patients (p < 0.001), with perceived ease of use, the dose counter, and shape cited as the main reasons for preference.

Adolescent↗

PubMed1997

[An experiment study of reversed pulmonary hypertension with inhaled nitric oxide on smoke inhalation injury].

We evaluated the effect and mechanisms of reversed pulmonary hypertension with inhaled nitric oxide (NO) on smoke inhalation injury in the dog model, 21 dogs were divided into 3 groups randomly. Following smoke inhalation, the control group (n = 8) inhaled O2 (FiO2, 0.45) and the treated group (n = 9) inhaled O2 and 0.0045% (45 ppm) NO. Hemodynamics was serially measured for 12 hours. In addition, 4 dogs without smoke inhalation were used to study the normal lung histomophologic findings. The data were analyzed by ANOVA. After inhalation of NO, the mean pulmonary artery pressure (mPAP), pulmonary minute vessels pressure (Pmv), and pulmonary vascular resistance (PVR) were decreased significantly (P < 0.05), while the mean aortic pressure (mAP) and total peripheral resistance (TRP) were not remarkably changed (P > 0.05). The levels of cyclic guanosine monophosphate (cGMP) were increased significantly (P < 0.01). Inhaled NO may reverse pulmonary hypertension with smoke inhalation injury in dogs. The mechanism of selective pulmonary circulation was increased cGMP level in smooth cells. Inhaled NO may be recommended for clinical application.

Administration, Inhalation↗

PubMed1998

Adrenal insufficiency in an adult on inhaled corticosteroids; recovery of adrenal function with inhaled nedocromil sodium.

BACKGROUND: Whereas oral corticosteroids and high-dose inhaled corticosteroids may be associated with suppression of the hypothalamic-pituitary-adrenal axis, medium-dose inhaled corticosteroids have not been reported to be associated with clinically significant adrenal insufficiency in the adult. OBJECTIVE: A case study of adrenal responsiveness after prolonged medium-dose inhaled corticosteroids and after replacement of steroid therapy by inhaled nedocromil sodium is described. METHODS: Standard 250-microg dose ACTH (cosyntropin) stimulation tests were followed after replacement of inhaled triamcinolone acetonide therapy by nedocromil sodium. RESULTS: A 55-year-old woman who had been on inhaled triamcinolone acetonide, 1600 microg/day for 12 years, presented with symptoms of adrenal hypofunction upon inhaled corticosteroid taper. An ACTH stimulation test confirmed adrenal insufficiency. She was switched to inhaled nedocromil sodium with improvement in her clinical syndrome and normalization of her ACTH stimulation test. CONCLUSION: Withdrawal from prolonged use of inhaled medium-dose corticosteroids may be associated with clinically significant adrenal insufficiency in adults. Steroid sparing agents may be considered for those on long-term inhaled corticosteroid therapy.

Administration, Inhalation↗