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PubMedDate not supplied

Mosquito coil smoke inhalation toxicity. Part I: validation of test approach and acute inhalation toxicity.

Burning mosquito coils indoors to repel mosquitoes is a common practice in many households in tropical countries. The evaluation and assessment of the inhalation toxicity of smoke emitted from mosquito coils appear to be particularly challenging due to the complex nature of this type of exposure atmosphere. The potential health implications of the gases, volatile agents and particulate matter emitted from burning coils or incense have frequently been addressed; however, state-of-the-art inhalation toxicity studies are scarce. The focus of this paper was comparatively to evaluate and assess the appropriateness and practical constraints of the whole-body versus the nose-only mode of exposure for inhalation toxicity studies with burning mosquito coils. With regard to the controlled exposure of laboratory animals to complex smoke atmospheres the nose-only mode of exposure had distinct advantages over the whole-body exposure, which included a rapid attainment of the inhalation chamber steady state, minimization of particle coagulation and uncontrolled adsorption of condensate onto the chamber surfaces. While in whole-body chambers a different kinetic behaviour of volatile and particulate constituents was found which caused inhomogeneous, i.e. artificially enriched atmospheres with volatile components at the expense of aerosols, the nose-only mode of exposure provided maximum exposure intensities without losses of the particulate phase of the exposure atmosphere. Collectively, the results obtained support the conclusion that the dynamic nose-only mode of exposure is experimentally superior to the quasistatic whole-body exposure mode which provides the least control over exposure atmospheres and the outcome highly contingent on selected experimental factors. Acute inhalation toxicity studies in rats suggest that the most critical metrics of exposure are apparently related to (semi)volatile upper respiratory tract sensory irritants, whilst the asphyxic component, carbon monoxide, plays a role only at overtly irritant exposure levels. However, this study was conducted at exposure concentrations much higher than encountered by people in residential settings and the effects observed under these conditions may not be relevant to hazards from exposures at common use levels. Neither an acute 8 h exposure of rats nor the 1 h sensory irritation study in mice and rats provided experimental evidence that irritant particle-related effects had occurred in the lower respiratory tract. In summary, the protocols devised evaluate and assess the acute inhalation toxicity of mosquito coil smoke demonstrating that the nose-only mode of exposure of rats to the smoke of mosquito coils is suitable to assess the toxic potency of different coils. The nose-only mode has clear advantages over the whole-body exposure mode. The inhalation studies conducted show unequivocally that acute toxic effects are difficult to produce with this type of product even under rigorous testing conditions.

Air Pollutants↗
PubMed2005

Inhalation method determines outcome of capsaicin inhalation in patients with chronic cough due to sensory hyperreactivity.

BACKGROUND: For patients with idiopathic chronic cough, a subgroup is recognised with respiratory symptoms induced by scents and chemicals. The diagnosis of sensory hyperreactivity (SHR) has been suggested for this group of patients and can be made using a capsaicin inhalation test. The aim of the present study was to compare the results of inhaling capsaicin by tidal breathing with those obtained by the dosimeter method regarding repeatability, agreement, and ability to distinguish patients with SHR from healthy controls. METHODS: A total of 15 patients with chronic cough due to SHR and 15 healthy control subjects underwent a randomised cross-over protocol and were provoked in a double-blind, randomised fashion with vehicle and two concentrations of inhaled capsaicin, using either the tidal breathing or dosimeter method, in a total of four challenges opportunities, two with each method. RESULTS: Patients coughed more and showed more respiratory symptoms than healthy controls with each dose of capsaicin. Compared with tidal breathing, inhalation of capsaicin with the dosimeter method caused a significantly greater number of coughs and respiratory symptoms in both patients and controls. Among the patients, the mean number of coughs after inhalation of 1 mL of capsaicin 0.4 micromol/L from the first provocation with tidal breathing was 12 (95% CI: 7; 17) and after inhalation from the first provocation with the dosimeter method 32 (95% CI: 19; 46) (P < 0.05). Both methods showed good repeatability and similar ability to distinguish patients with SHR from healthy control subjects. CONCLUSIONS: For patients with SHR, capsaicin cough sensitivity is increased and repeatable. The dosimeter method caused more coughs and other respiratory symptoms than the tidal breathing method, indicating that the methods cannot be used interchangeably. Knowledge of the type of inhalation device used, the particle size, the airflow rate and the inspiratory flow rate are essential when comparing different studies of capsaicin-induced cough.

Administration, Inhalation↗
PubMed1995

Clinical equivalence of a novel non-chlorofluorocarbon-containing salbutamol sulfate metered-dose inhaler and a conventional chlorofluorocarbon inhaler in patients with asthma.

BACKGROUND: New formulations of non-chlorofluorocarbon-containing propellants for pressurized metered-dose inhaler delivery systems must be developed in response to the forthcoming ban on chlorofluorocarbon (CFC) production. OBJECTIVE: This study compared the bronchodilator effects of 100, 200, and 300 micrograms (base equivalent) of salbutamol in a novel CFC-free propellant system (Airomir in the 3M CFC-Free System; 3M Pharmaceuticals, St. Paul, Minn.; 108 micrograms of salbutamol sulfate or 90 micrograms of salbutamol base equivalent per inhalation) with that of 100 and 200 micrograms of salbutamol base in a conventional CFC propellant system (Ventolin, CFC-11/12; Allen and Hanburys, Division of Glaxo Inc., Research Triangle Park, N.C.; 90 micrograms of salbutamol base per inhalation) and placebo. METHODS: Twenty-six patients with chronic, stable asthma, who had a forced expiratory volume in 1 second (FEV1) between 50.0% and 75.0% of predicted normal value, entered this randomized, double-blind, double-dummy, 6-period, crossover study. FEV1 was measured before and at multiple time points (ranging from 10 to 480 minutes) after administration of one, two, and three inhalations of salbutamol/CFC-free (100, 200, and 300 micrograms); one and two inhalations of salbutamol/CFC (100 and 200 micrograms); and placebo. Safety parameters included adverse events, heart rate, blood pressure, physical examinations, electrocardiograms, and clinical laboratory tests. Parametric analysis of variance models appropriate for a 6-period crossover design were used, along with multiple comparisons according to Tukey's method. RESULTS: All active treatments produced significantly (p < 0.0001) greater bronchodilation than placebo. The bronchodilator effect, as measured by FEV1 (peak percent change, peak as a percent of predicted value, duration, and area under the curve) after two inhalations of salbutamol/CFC-free was clinically comprable to two inhalations of salbutamol/CFC, with no clinically meaningful differences in safety parameters between the two delivery systems or between different dose levels. CONCLUSION: These results suggest that salbutamol/CFC-free may offer a suitable alternative for salbutamol/CFC when the need arises to change from CFC-containing salbutamol products.

Administration, Inhalation↗
PubMed1998

Establishing a therapeutic index for the inhaled corticosteroids: part II. Comparisons of systemic activity and safety among different inhaled corticosteroids.

The systemic activity and safety of inhaled corticosteroids are best studied in randomized, controlled, long-term trials with clinically relevant doses in subjects. These studies require large numbers of enrolled subjects and are difficult to conduct. Potential confounders to safety analyses must be controlled. The occurrence and magnitude of adrenal suppression has been the most extensively evaluated systemic effect of inhaled corticosteroids. The significance of these findings in relation to relevant clinical outcomes must be evaluated. At low to medium inhaled corticosteroid dosages, the hypothalamic-pituitary-adrenal axis is minimally and only partially suppressed. Statistically significant changes occur at high inhaled corticosteroid dosages; the magnitude of this effect is less than with prednisone, > or = 10 mg/day. Standards for the design of growth studies in children with asthma have been recommended and recently implemented. Four randomized, controlled, clinical trials have reported reductions in growth rates of > 1 cm/yr with beclomethasone < or = 400 microg/day. By comparison, 2 randomized controlled clinical trials with fluticasone, 50 to 100 microg twice daily via dry powder inhaler, could not detect differences in height velocity in prepubertal children treated with cromolyn sodium or placebo. Trials with low to medium doses of beclomethasone, fluticasone, and budesonide document little to no effect on bone mineral density and bone metabolism. Population-based and limited randomized controlled trials suggest that low to medium doses of inhaled corticosteroids do not cause cataracts or glaucoma. Patients requiring high-dose inhaled corticosteroids should be monitored for adverse effects, with appropriate lifestyle changes and pharmacologic strategies implemented.

Administration, Inhalation↗
PubMed1998

Inhaled fluticasone propionate delivered by means of two different multidose powder inhalers is effective and safe in a large pediatric population with persistent asthma.

BACKGROUND: Inhaled corticosteroids are increasingly being used to treat mild-to-moderate asthma in children. However, data regarding therapy with this class of compounds, especially in children under age 6 years, is limited. Fluticasone propionate is a third generation inhaled corticosteroid with an optimal therapeutic index. Few large prospective clinical trials have been conducted to evaluate the efficacy and safety of fluticasone propionate powder in children. OBJECTIVE: We sought to determine the efficacy and safety of fluticasone propionate powder administered by means of the Diskus and Diskhaler multidose powder inhalers in pediatric patients with persistent asthma. METHODS: Fluticasone propionate powder (50 microg or 100 microg twice daily) or placebo was administered by means of the Diskus or Diskhaler inhalers to 437 children (4 to 11 years old) with persistent asthma for 12 weeks in a randomized, double-blind, parallel-group, multi-center trial. Patients were stratified according to whether they were receiving prior treatment with inhaled corticosteroids or cromolyn or beta2-agonists alone. RESULTS: Fluticasone propionate powder administered by means of Diskus or Diskhaler significantly improved FEV1 (mean increase from baseline of 0.22 to 0.24 L; p < or = 0.023), clinic morning peak expiratory flow (mean increase from baseline of 48 to 55 L/min; p < or = 0.006), patient-measured morning (p < or = 0.001) and evening (p < or = 0.003) peak expiratory flow, and asthma symptom scores (in all but the 50 microg Diskus group; p < or = 0.036), as well as reduced albuterol use (p < or = 0.002) and nighttime awakenings (p < or = 0.019) at endpoint. Efficacy parameters were not significantly different between the two doses with either device. More placebo-treated patients discontinued the study because of lack of efficacy than patients in any fluticasone propionate group (p < 0.001). Fluticasone propionate did not suppress morning plasma cortisol concentrations and did not affect 24-hour urinary free-cortisol excretion. Adverse events were primarily pharmacologic effects of inhaled corticosteroids, and those related to the study drug occurred with low frequency. Patient satisfaction with both the Diskus and Diskhaler devices was high, with a majority of patients (> 80%) rating them favorably. CONCLUSION: This study demonstrated that fluticasone propionate powder, at the conventional recommended doses of up to 200 microg/day administered by means of Diskus or Diskhaler, was well tolerated and improved lung function in children even as young as 4 and 5 years old regardless of whether they were previously treated with inhaled corticosteroids or cromolyn or beta2-agonists alone.

Administration, Inhalation↗
PubMed2004

Effectiveness of budesonide administered via dry-powder inhaler versus triamcinolone acetonide administered via pressurized metered-dose inhaler for adults with persistent asthma in managed care settings.

BACKGROUND: Clinical studies have demonstrated the efficacy and relative safety of inhaled corticosteroids in the treatment of asthma. However, effectiveness and cost-effectiveness comparisons of available inhaled corticosteroids in real-life clinical settings are lacking. OBJECTIVE: This study compared the effectiveness and safety of budesonide administered via dry-powder inhaler versus that of triamcinolone acetonide administered via pressurized metered-dose inhaler in the treatment of adult patients with persistent asthma treated in a managed care setting. METHODS: This was a randomized, open-labe, 52-week study of adult patients (aged >or= 18 years) with persistent asthma enrolled in 25 US health plans. The primary study outcome was mean change from baseline to the end of treatment in symptom-free days. Secondary variables were changes from baseline in number of episode-free days, episode-free days at 52 weeks, forced expiratory volume in 1 second (FEV(1)), forced vital capacity, asthma symptom scores, breakthrough bronchdilator use, patient discontinuations, and health-related quality of life. Patients were issued diaries in which to record use of study medication and concomitant asthma medication use, as well as daytime and nighttime asthma symptom severity. Patients were assessed at weeks 4, 13, 26, 39, and 52. Safety was assessed based on adverse events and changes in laboratory tests, vital signs, and physical examinations. RESULTS: A total of 945 patients (344 men, 601 women; mean [SD] age, 46.8 [14] years) were enrolled; 631 received budesonide and 314 received triacinolane acetonide. Improvements in all effectiveness variables were observed with both treatments. The mean increase from baseline in the number of symptom-free days per month assessed at month 12 was 7.74 (95% CI, 6.81-8.66) for patients receiving budesonide and 3.78 (95% CI, 2.47-5.09) for patients receiving triamcinoline acetonide ( P<0.001). The estimated annual mean (SD) number symptom-free days for patients receiving budesonide was 141.1 (125.0) over the treatment phase, compared with 99.3 (112.1) for those receiving triamcinolone acetonide (P<0.001). Patients receiving budesonide demonstrated significant improvements (compared with those receiving triamcinolone acetonide) in overall quality of life, daytime and nighttime asthma symptom severity, breakthrough bronchodilator use, and FEV(1) (all P<0.001). Safety measures were similar between groups. CONCLUSION: In these managed care settings, budesonide inhalation powder administered via dry-powder inhaler was significantly more effective than triamcinolone acetonide administered via pressurized metered-dose inhaler in the treatment of adults with persistent asthma.

Administration, Inhalation↗
PubMed2003

A new agglomerated KSR-592 beta-form crystal system for dry powder inhalation formulation to improve inhalation performance in vitro and in vivo.

A new agglomerated KSR-592 (steroid) beta-form needle-like crystals with lactose system for dry powder inhalation (DPI) was developed to improve inhalation performance with Jethaler. The drug agglomerates were prepared by the method of spherical agglomeration in liquid so as to control the particle size and the mechanical strength of agglomerates by changing the agitation speed of the agglomeration system. The agglomerates mixed with lactose particles for the DPI formulation were effectively disintegrated into respirable fine particle in the milling chamber of the device (Jethaler) when inhaled. The DPI formulation with these agglomerates exhibited ideal fluidity and provided a larger fine particle fraction (FPF: 29.7%) than the formulation with agglomerates consisting of alpha-form (plate-like) crystals (24.5%). The air-flow rate of inhalation had no effect on the disintegration properties of these agglomerates, suggesting a reliable inhalation performance in vivo. Further, an in vivo test of the aerosolized KSR-592 (beta-form) crystals having the same particle size distribution as those in the aerosol produced by Jethaler was conducted by means of a dry powder inhalation testing system using Brown Norway rats. Inhaled KSR-592 (beta-form) crystals were found to be uniformly deposited in the lungs of Brown Norway rat sensitized by ovalbumin (OA) and suppressed the increase in eosinophil number in the lungs after OA challenge.

Administration, Inhalation↗
PubMed2002

Dry powder inhalation of antibiotics in cystic fibrosis therapy: part 2. Inhalation of a novel colistin dry powder formulation: a feasibility study in healthy volunteers and patients.

The aim of the present study was to perform a proof of principle study with a new colistin dry powder inhalation system in six healthy volunteers and five patients with cystic fibrosis. All subjects were asked to inhale 25 mg colistin sulfate dry powder. The patients were also asked to nebulize 160 mg colistin sulfomethate as a solution. Colistin serum concentrations were determined as an indirect parameter to compare both forms of administration. Pulmonary function tests were performed. Peak serum colistin concentrations ranged from 14 to 59 microg/l in volunteers after inhalation of 25 mg as dry powder. In patients, peak concentrations ranged from 18 to 64 microg/l after nebulization of 160 mg colistin sulfomethate solution and from 77 to 159 microg/l after inhalation of 25 mg colistin sulfate dry powder. Pulmonary function tests were not significantly different after inhalation of the dry powder by the volunteers nor after nebulization of the solution by the patients. In some patients a decrease in pulmonary function and moderate to severe cough was observed after inhalation of the dry powder. The new colistin inhaler provides an attractive alternative for nebulized colistin and was highly appreciated by the patients. The decrease in pulmonary function and cough in patients is a drawback, which may be overcome by dose reduction and a further improvement of the new dosage form.

Administration, Inhalation↗
PubMed2006

Treatment with 400 microg of inhaled budesonide vs 200 microg of inhaled budesonide and oral montelukast in children with moderate persistent asthma: randomized controlled trial.

BACKGROUND: Montelukast is reported to be beneficial in asthma as add-on therapy to inhaled corticosteroids and may reduce the need for the latter. OBJECTIVE: To evaluate whether a combination of oral montelukast and 200 microg of inhaled budesonide has comparable efficacy to 400 microg of inhaled budesonide alone in children with moderate persistent asthma. METHODS: In this prospective, blinded, hospital-based randomized controlled trial, 71 children with moderate persistent asthma were randomized to receive either montelukast, 5-mg chewable tablet, with 200 microg of inhaled budesonide or only 400 microg of inhaled budesonide daily for 12 weeks. Baseline and serial measurements of forced expiratory volume in 1 second, peak expiratory flow rate, and Asthma Symptom Score were performed; the frequency and severity of exacerbations were also recorded. RESULTS: Measurements of forced expiratory volume in 1 second, peak expiratory flow rate, and Asthma Symptom Score showed no significant differences between the 2 groups at baseline, during the serial follow-up visits, and at the end of the study. However, children who received montelukast had a greater frequency of exacerbations vs those who did not (33.3% vs 9.1%; P < .01). CONCLUSION: The overall control of asthma with 5 mg of oral montelukast and 200 microg of inhaled budesonide is inferior to that with 400 microg of inhaled budesonide in children with moderate persistent asthma.

Acetates↗
PubMed1997

Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group.

BACKGROUND: Persistent pulmonary hypertension of the newborn causes systemic arterial hypoxemia because of increased pulmonary vascular resistance and right-to-left shunting of deoxygenated blood. Inhaled nitric oxide decreases pulmonary vascular resistance in newborns. We studied whether inhaled nitric oxide decreases severe hypoxemia in infants with persistent pulmonary hypertension. METHODS: In a prospective, multicenter study, 58 full-term infants with severe hypoxemia and persistent pulmonary hypertension were randomly assigned to breathe either a control gas (nitrogen) or nitric oxide (80 parts per million), mixed with oxygen from a ventilator. If oxygenation increased after 20 minutes and systemic blood pressure did not decrease, the treatment was considered successful and was continued at lower concentrations. Otherwise, it was discontinued and alternative therapies, including extracorporeal membrane oxygenation, were used. RESULTS: Inhaled nitric oxide successfully doubled systemic oxygenation in 16 of 30 infants (53 percent), whereas conventional therapy without inhaled nitric oxide increased oxygenation in only 2 of 28 infants (7 percent). Long-term therapy with inhaled nitric oxide sustained systemic oxygenation in 75 percent of the infants who had initial improvement. Extracorporeal membrane oxygenation was required in 71 percent of the control group and 40 percent of the nitric oxide group (P=0.02). The number of deaths was similar in the two groups. Inhaled nitric oxide did not cause systemic hypotension or increase methemoglobin levels. CONCLUSIONS: Inhaled nitric oxide improves systemic oxygenation in infants with persistent pulmonary hypertension and may reduce the need for more invasive treatments.

Administration, Inhalation↗
PubMed1999

Human tracheobronchial deposition and effect of a cholinergic aerosol inhaled by extremely slow inhalations.

Ten subjects inhaled the same amounts of cholinergic aerosol of a mass median diameter (MMD) of 7.7 microns in a normal provocation test and in a test with extremely slow inhalations (ESI). This new technique using ESI and large droplets/particles gives a high degree of deposition in small ciliated airways which cannot be obtained by using small particles. The purpose was to compare measured effects with calculated doses of the aerosol in large and small ciliated airways. The effect on large airways was measured by airway resistance (R(aw)), and the effect on small airways was measured by the phase III slope of single breath nitrogen test (N2-delta). Mouth and throat deposition was calculated from human experimental data, and deposition of the cholinergic aerosol into large and small airways was calculated, using a computerized lung model. The study showed that the extremely slow inhalation caused a larger effect on R(aw) and tendency to a larger effect on N2-delta compared to the effect in the normal provocation. Deposited dose in the large airways, in percent of inhaled dose, was calculated to be 25-33% for normal inhalation and 20-24% for ESI. Calculated deposited dose in the small airways (bronchioles; generations 12-16) was 1.8-3.4% for normal inhalation and 18-25% for ESI. For large airways a stronger effect was induced by ESI, perhaps by the more uniform distribution of particles within each generation, compared to normal inhalations when particles deposit near the bifurcations. Concerning the small airways, N2-delta did not differ significantly between normal and ESI provocations, indicating that they did not react much on cholinergic exposure. We believe that our approach using ESI for small airway deposition of a nebulized aerosol can be of value for estimating the effects of various substances on large and small airways.

Administration, Inhalation↗
PubMed2000

Effectiveness and acceptability of a domiciliary multidrug inhalation treatment in elderly patients with chronic airflow obstruction: metered dose inhaler versus jet nebulizer.

The aim of this study was to compare the immediate and long-term bronchodilator effect as well as the patient acceptability of a 2-week, multidrug, inhalation treatment delivered by a metered dose inhaler (MDI) versus a jet nebulizer in a group of elderly patients with chronic obstructive pulmonary disease (COPD) or asthma and an at least partially reversible airflow obstruction. Twenty elderly outpatients (17 men; mean +/- SD age, 67 +/- 2 years; mean +/- SD baseline forced expiratory volume in 1 second [FEV1], 46.5 +/- 14% of predicted value) with COPD or asthma participated in the study, which was of an open, randomized, crossover design. After a 1-day baseline evaluation, including patient history, clinical examination, and spirometry, participants were randomly assigned to receive a multidrug inhalation treatment (a combination of salbutamol, ipratropium, and flunisolide) with either an MDI or a jet nebulizer. Two weeks later, they were shifted to treatment with the alternative system for a further 2 weeks. FEV1 was measured on the first and fourteenth days of each treatment period, on each occasion both before and 30 minutes after the morning inhalation. At the end of the study, patients were asked to express a personal preference for one of the two inhalation treatments with regard to effectiveness and acceptability by filling out a simple questionnaire. Both the MDI and jet nebulizer had a significant immediate bronchodilator effect on the first and fourteenth days of treatment, with no differences between treatments. No long-term bronchodilator effect was seen with either aerosol delivery system. Patient preferences were clearly in favor of the jet nebulizer with regard to effectiveness and in favor of the MDI with regard to acceptability. In conclusion, in elderly patients with COPD or asthma and partially reversible airflow obstruction, a maintenance multidrug bronchodilator/anti-inflammatory inhalation treatment produced a statistically significant and clinically relevant bronchodilator effect without substantial differences between the two delivery systems. Most patients considered the MDI to be more acceptable and the jet nebulizer to be more effective. These preferences should be taken into consideration when prescribing a maintenance aerosol inhalation treatment.

Administration, Inhalation↗
PubMed1996

Inhaled nitric oxide in neonatal and pediatric acute respiratory distress syndrome: dose response, prolonged inhalation, and weaning.

OBJECTIVE: Inhaled nitric oxide is a potent and selective pulmonary artery vasodilator. We studied the effects of nitric oxide inhalation in neonatal and pediatric acute respiratory distress syndrome (ARDS) patients with respect to dosage, prolonged inhalation, and weaning. DESIGN: Prospective, open-label study. SETTING: Neonatal and pediatric intensive care units of a level three university hospital. PATIENTS: Seventeen patients with severe ARDS (1 day to 6 yrs of age [mean 1.75]; oxygenation index of > 20 cm H2O/torr) were enrolled. INTERVENTIONS: To identify the optimal dosage for continuous nitric oxide inhalation, doses between 1 and 80 parts per million (ppm) of nitric oxide were tested after the patients had stabilized. Daily withdrawals of nitric oxide were made, according to predetermined criteria. MEASUREMENTS AND MAIN RESULTS: Nine neonatal and eight pediatric ARDS patients (mean Pediatric Risk of Mortality score 28.4 +/- 6.1; mortality risk 54 +/- 15%) were studied. The following variables changed within 24 hrs of nitric oxide inhalation: mean oxygenation index decreased by 56% (from 34 +/- 12 to 15 +/- 7 cm H2O/torr, p = .0004); alveolar-arterial O2 gradient decreased by 31% (from 579 +/- 71 to 399 +/- 102 torr (77.2 +/- 9.5 to 53.2 +/- 13.6 kPa), p = .0004); and mean systemic arterial pressure increased by 15% (from 49 +/- 10 to 57 +/- 12 mm Hg, p = .0029). The optimal dose of nitric oxide was 20 ppm in neonates (with additional persistent pulmonary hypertension of the newborn) and 10 ppm in pediatric patients. Prolonged inhalation (4 to 21 days) was associated with continuous improvement of oxygenation. An oxygenation index of < 5 cm H2O/torr predicted successful withdrawal, with a sensitivity of 75% and a specificity of 89%. None of the patients had to be rescued with extracorporeal membrane oxygenation and 16 of the 17 patients survived. CONCLUSIONS: Inhaled nitric oxide enhances pulmonary gas exchange, with concomitant hemodynamic stabilization, in neonatal and pediatric ARDS. Best effective doses were 10 ppm of nitric oxide in pediatric ARDS and 20 ppm in neonates. Treatment should be continued until an oxygenation index of < or = 5 cm H2O/torr is achieved. Effects on outcome need verification in larger controlled trials.

Administration, Inhalation↗
PubMed1991

Do diagnostic procedures other than inhalation challenge predict immediate bronchial responses to inhaled allergen?

To investigate the relationships between allergen inhalation challenge and other diagnostic procedures, inhalation challenge with house dust (HD) allergen, intradermal skin tests with HD allergen, inhalation challenge with methacholine and circulating HD allergen-specific IgE levels were examined in 104 patients with bronchial asthma. Using the single exposure method, allergen inhalation challenge was performed. Forty-three patients had positive bronchial responses to allergen and 61 patients had negative bronchial responses. With serially diluted HD allergen (10(-3) to 10(-6), w/v), skin-test sensitivity was expressed as the highest dilution required to produce a weal of more than 9 x 9 mm. With the continuous exposure method, bronchial responsiveness to methacholine was evaluated as the number of units of inhaled methacholine (PD35-Grs) from the start to the point at which Grs had decreased by 35% from its baseline value. The level of circulating HD allergen-specific IgE was measured with the Phadebas RAST system and the results were assessed as a RAST score. Using discriminant analysis, in which the independent variables were skin-test sensitivity, PD35-Grs and the RAST score, only in 30% of all patients was bronchial responsiveness to inhaled HD allergen predictable. Therefore, we suggest that inhalation challenge with allergen is an essential test for determining the role of a specific allergen in airways at present.

Administration, Inhalation↗
PubMed1993

A comparison of breath-actuated and conventional metered-dose inhaler inhalation techniques in elderly subjects.

BACKGROUND: Poor coordination of canister actuation and inspiration often prevents adequate metered-dose inhaler (MDI) usage by patients, perhaps especially so among the elderly. Breath-actuated inhalers (BAI) have been developed to prevent this problem. METHODS: We compared the adequacy of inhaler technique and patient preferences between MDI and BAI in a group of elderly subjects (mean age, 70.8 +/- 5.4 years). Half of the subjects were regular MDI users; half had never before used one. Two trained observers assessed the adequacy of MDI and BAI usage subjectively while performance was monitored objectively using a light source and infrared system to detect canister actuation and a spirometer to measure the inspiratory volume. If canister actuation was not followed by at least a 50 percent vital capacity, inhaler use was deemed unsuccessful. A brief teaching session preceded inhaler usage. RESULTS: By subjective assessment, BAI was used successfully more often than MDI (79 vs 60 percent, p < 0.05). By objective assessment, BAI was used successfully more often than MDI (64 vs 36 percent, p < 0.0005), although the percentage of inhalations scored adequate was lower than when assessment was subjective. Neither device was used correctly as often by those unfamiliar with MDIs as by those who were regular users. A significantly higher percentage of patients preferred BAI to MDI (71 vs 19 percent, p < 0.005), similar preferences being reported by MDI familiar and MDI unfamiliar groups. CONCLUSIONS: We conclude that (1) elderly subjects frequently handle inhalers poorly, (2) mishandling is better detected by objective than subjective monitoring, and (3) BAI is used correctly and preferred by patients more often than conventional MDIs.

Administration, Inhalation↗
PubMed1994

A comparison of inhaled ipratropium, oral theophylline plus inhaled beta-agonist, and the combination of all three in patients with COPD.

To evaluate the role of inhaled ipratropium bromide alone vs oral theophylline plus inhaled beta-agonist or the combination of all three in patients with stable COPD, the following double-blind, placebo-controlled study was conducted. Forty-eight patients with stable COPD (mean age, 61.8 years, with mean baseline FEV1 < 1.0 L) were randomized on four separate days to receive the following drug regimens: (1) theophylline tablets (dose previously determined to result in blood level of 12 to 18 mg/L), followed by inhaled albuterol (2 puffs via metered-dose inhaler [MDI]), followed by inhaled placebo (2 puffs via MDI); (2) oral placebo followed by ipratropium (2 puffs via MDI; 36 micrograms), followed by inhaled placebo; (3) oral theophylline, followed by albuterol, followed by ipratropium; or (4) oral placebo followed by two inhaled placebos. On study days, spirometry and heart rate were measured at time 0, 30 min, 60 min, and hourly for 6 h. The FEV1 peak change (liters) and area under the curve (liter x hours) for the treatment groups were compared. Ipratropium was more effective than placebo (p = 0.001 and p = 0.0078, respectively). The combination of albuterol and theophylline was superior to ipratropium alone (p = 0.001 and p = 0.0001, respectively), and all three drugs together were superior to the combination of albuterol and theophylline (p = 0.0373 and p = 0.0289), respectively; one-sided test of hypotheses). Peak heart rates were significantly higher for treatment groups compared with placebo groups (p = 0.0001). However, theophylline and albuterol and the combination of all three drugs resulted in greater peak heart rates than did ipratropium alone (p = 0.001). These data suggest that for patients with stable COPD, combination therapy with ipratropium (two puffs), theophylline, and albuterol (two puffs) is superior to ipratropium alone or the combination of theophylline and albuterol.

Administration, Inhalation↗
PubMed2002

Combination therapy with inhaled long-acting beta2-agonists and inhaled corticosteroids: a paradigm shift in asthma management.

Long-acting inhaled beta2-agonists and inhaled corticosteroids are classes of drugs with different mechanisms of action that are commonly used to provide effective long-term control of persistent asthma. Scientific and clinical data support the complementary mechanisms of action of the inhaled corticosteroids and the long-acting beta2-agonists in achieving a superior level of asthma control. In addition, evidence supports significant reductions in exacerbations and effective control of airway inflammation with an inhaled corticosteroid and a long-acting beta2-agonist versus higher dosages of inhaled corticosteroids or combinations of other therapeutic agents with an inhaled corticosteroid. Finally, there are distinct economic advantages to combining an inhaled corticosteroid and a long-acting beta2-agonist in the treatment of asthma relative to other treatment regimens.

Administration, Inhalation↗
PubMedDate not supplied

In-vitro characterisation of metered dose inhaler versus dry powder inhaler glucocorticoid products: influence of inspiratory flow rates.

PURPOSE: To study the influence of inspiratory flow rate on the fine particle mass and the particle size distribution for metered dose inhaler (MDI) and dry powder inhaler (DPI) glucocorticoid products, in vitro. To compare the performance of MDI and DPI inhalers containing the same drug and strength at an impaction flow rate of 60 L/min. METHODS: The Marple Miller cascade impactor model 150 and 160 were used to characterise several glucocorticoid MDI and DPI products at different simulated inspiratory flow rates (30 L/min, 60 L/min and 90 L/min). Following the actuation of one single inhaler puff the amount of drug deposited in each stage of the impactor was quantified using high performance liquid chromatography with UV detection at 242 nm. The size distribution of the primary particles of DPI products was measured by laser diffraction. RESULTS: DPIs were significantly more dependent on impaction flow rate than MDIs. Except for Pulmicort(R), the fine particle mass FPM delivered from the MDI products was significantly higher than that delivered from the DPI aerosols. CONCLUSIONS: Although the metered dose inhaler is the older technology it exhibits greater respirable dose in vitro than newer dry powder inhaler devices. Care should be taken when shifting from one inhaler dosage form to another because this may affect the actual dose delivered to the lung. Further in vivo studies may be warranted in light of these findings.

Administration, Inhalation↗