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PubMed1998

Inhaled nitric oxide is not a myocardial depressant in a porcine model of heart failure.

BACKGROUND: Inhaled nitric oxide has been shown to be a potent and selective pulmonary vasodilator. Reports of increases in left ventricular end-diastolic pressure and episodes of pulmonary edema during the clinical use of inhaled nitric oxide in patients with preexisting left ventricular dysfunction have raised concerns that this agent may have myocardial depressant effects. We therefore undertook a study of the effects of inhaled nitric oxide on myocardial contractility in a porcine model of ventricular failure and pulmonary hypertension. METHODS: After inducing heart failure in 10 pigs by rapid ventricular pacing, hemodynamic measurements and pressure-volume diagrams (by the conductance method) were obtained in six animals at baseline and during administration of inhaled nitric oxide at concentrations of 20 and 40 ppm. Myocardial contractile state was assessed by the end-systolic pressure-volume relationship and preload-recruitable stroke work, whereas diastolic function was measured in terms of the end-diastolic pressure-volume relationship and the pressure decay time constant T. RESULTS: Baseline hemodynamics reflected heart failure and pulmonary hypertension, and inhaled nitric oxide induced significant reductions in mean pulmonary artery pressure and pulmonary vascular resistance. Although left ventricular end-diastolic pressure increased during administration of inhaled nitric oxide, no changes were observed in measures of systolic or diastolic function. CONCLUSIONS: Inhaled nitric oxide reduced pulmonary vascular resistance but did not alter myocardial contractility or diastolic function. Increases in left ventricular end-diastolic pressure during inhaled nitric oxide therapy are therefore not due to myocardial depression and may be related to increases in volume delivery to the left side of the heart resulting from reduced pulmonary vascular resistance.

Animals↗

PubMed1997

[Health workers' knowledge and skills regarding the use of the Turbuhaler inhaler].

The aim of this study was to evaluate health care workers' theoretical knowledge and skill in managing the dry powder Turbuhaler. We studied 118 individuals in three groups: 50 nurses, 34 medical residents and 34 staff physicians. Theoretical knowledge was evaluated by a questionnaire specifically designed for the purpose. Skill in managing the device was analyzed by evaluating a practical demonstration of the inhaling technique generally recommended, using a placebo inhaler. Six percent of staff physicians, 3% of the residents and 2% of the nurses answered the theoretical questionnaire correctly. Twenty-one percent of the staff physicians, 15% of the residents and 6% of the nurses inhaled correctly. However, when skill in managing the inhaler was evaluated against the maneuvers recommended by the manufacturer (which do not oblige exhaling before inhaling through the device and then holding the breath), there was significant improvement: 41% of the staff physicians, 23% of the residents, and 20% of the nurses inhaled correctly. We can conclude by saying that: a) our health care workers' general knowledge about how to handle the Turbuhaler device is deficient; b) the proportion of correct inhalation maneuvers observed doubles when these are assessed according to the manufacturer's recommendations, and c) health care workers should receive specific training in the inhalation techniques required for using the various devices usually prescribed.

Clinical Competence↗

PubMed2000

Pharmacokinetics of flunisolide administered via metered dose inhaler with and without a spacer device and following oral administration.

BACKGROUND: After inhalation of a glucocorticoid from a meter dose inhaler (MDI), a certain portion of the delivered dose is deposited in the lungs, and the remainder is deposited in the oropharynx. OBJECTIVE: To examine the absolute bioavailability of flunisolide given orally via metered dose inhaler, and metered dose inhaler with a commercially available spacer device as well as to determine the fraction of drug deposited in the lungs following inhalation. METHODS: Twenty-four healthy volunteers were enrolled in the study; twenty-two completed the study. The IRB approved the study protocol, and informed consent was obtained. Volunteers received four treatments: treatment A (MDI), 1.0 mg inhaled flunisolide; treatment B (MDI-S), 1.0 mg inhaled flunisolide with a spacer device; treatment C, 1.0 mg of orally administered flunisolide with 240 mL of water; and treatment D, 1.0 mg intravenous flunisolide by IV push in the antecubital vein over 60 seconds. Plasma and urine flunisolide were quantified by HPLC/mass spectrometry/mass spectrometry. RESULTS: Flunisolide is a corticosteroid with low oral bioavailability (6.7%), which was found to be lower than previously reported. Similar AUCs were observed between the MDI and MDI-S groups, but by using mass balance equations, it appears that more flunisolide was delivered to the lungs in the MDI-S group (410 microg versus 280 microg). Oropharyngeal deposition was an important difference between the two inhaler groups. Approximately an 11-fold reduction in the oropharyngeal deposition of flunisolide through use of the spacer device was observed. CONCLUSIONS: Use of a spacer device improved pulmonary delivery of flunisolide by almost 50% and significantly decreased the oropharyngeal exposure to drug.

Administration, Oral↗

PubMed1999

Evaluating the outcome of two teaching methods of breath actuated inhaler in an inner city asthma clinic.

OBJECTIVES: Our objective was to compare two different teaching methods used to educate patients in the use of a breath actuated inhaler (BAI) and to assess the impact of its continued use on their metered-dose inhaler (MDI) technique. DESIGN: Prospective, randomized, controlled trial. SETTING: Adult Pulmonary/Asthma clinic of Cook County Hospital, Chicago, IL. PATIENTS: Diagnosed, stable asthmatics. INTERVENTION: The patients were randomized into two groups. The experimental group received verbal instructions and demonstration on breath actuated inhaler technique while the control group received written instructions only on BAI use. The metered dose inhaler technique of both groups of patients was also evaluated. MEASURES: A checklist evaluating the key aspects of proper BAI and MDI inhalation techniques was used to assess the use of both types of inhalers at entry into the study and upon postintervention follow-up at 8 to 20 weeks. RESULTS: At baseline, 97% of patients in the experimental group and 83% of patients in the control group were initially able to demonstrate BAI inhalation technique correctly. Upon follow-up, 82% of the control group and 68% of the experimental group were able to use the BAI correctly, which was a statistically significant deterioration in the experimental group. In both of these groups, there was a statistically significant improvement in MDI technique. CONCLUSIONS: Written instructions alone may be an adequate teaching tool for proper inhalation technique of BAI. Continued BAI use appears not to impact adversely on proper MDI technique.

Adult↗

PubMed1999

The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial.

AIMS: Nicotine replacement therapy (NRT) is an established aid in stopping smoking, while the role of antidepressants remains uncertain. Antidepressants added to NRT might improve abstinence rates. Our aim was to determine the efficacy of nicotine inhaler and fluoxetine vs. nicotine inhaler and placebo in attempts to quit smoking. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: A smoker's cessation clinic. PARTICIPANTS: One hundred volunteers smoking 10 cigarettes/day or more. INTERVENTIONS: Subjects were instructed to start taking a daily dose of 10 mg of fluoxetine or placebo 16 days before stopping smoking, then 20 mg 10 days before quitting, continuing for up to at least 3 months. Subjects were instructed to use 6-12 units per day of nicotine inhalers after stopping smoking for up to 6 months. MEASUREMENTS: Continuous abstinence rates recorded at various time points up to 12 months from the quit date. FINDINGS: The sustained abstinence rate for the inhaler-fluoxetine group was 54%, 40%, 29% and 21% after 1.5, 3, 6 and 12 months, respectively, compared to 48%, 40%, 32% and 23% for the inhaler-placebo group. The differences were not significant at any time point. Abstinence up to 3 months was more likely in older smokers, those with a lower Beck Depression Inventory Score (BDI), lower Fagerström Test of Nicotine Dependence (FTND) score and no history of alcoholism. Fluoxetine appeared to increase abstinence rates among high BDI smokers compared to high BDI smokers assigned placebo. Serum levels of nicotine during treatment in the inhaler-fluoxetine group were lower than in the inhaler-placebo group so that fluoxetine may have reduced inhaler use through a common site of action. CONCLUSIONS: We found no evidence that fluoxetine treatment when used as an adjunct to NRT in unselected smokers is effective, but there may be an advantage to using it in depressed smokers.

Adult↗

PubMed1999

Sputum cellular and cytokine responses to inhaled endothelin-1 in asthma.

BACKGROUND: Endothelin (ET)-1 is a 21-amino acid peptide which has potent bronchoconstrictor activity. Animal studies show elevation of ET-1 during experimental airway inflammation, and inhibition of inflammation by endothelin-antagonists, suggesting pro-inflammatory activity for ET-1. OBJECTIVE: We wanted to assess any acute influence that bronchoconstrictor doses of inhaled ET-1 might have on cells, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, nitrite (NO2) and albumin in induced sputum in asthma. METHODS: Bronchial challenge was performed using nebulized ET-1 (nebulized dose range 0.96-15.36 nmol) and placebo in 10 adult asthmatic subjects in a randomized double-blind placebo-controlled cross-over study. Sputum induction was performed 30 min and 4 h after placebo or ET-1 bronchial challenge. RESULTS: All subjects experienced dose-dependent bronchoconstriction to inhaled ET-1 with a mean (range) PC15 forced expiratory volume in 1 s (FEV1) to ET-1 of 9.45 (1.2-21.7) nmol. Comparing ET-1 with placebo inhalation, there was no change in sputum differential cell counts, TNFalpha, IL-1beta, NO2 or albumin at 30 min or 4 h after inhalation, nor was there a difference in these parameters at 4 h compared with 30 min after ET-1 inhalation. There was no fall in FEV1 at 4 h after ET-1 inhalation, suggesting that ET-1 inhalation is not associated with a late bronchoconstrictor response. CONCLUSIONS: We conclude that inhaled ET-1 does not appear to stimulate an acute inflammatory response in asthma as assessed by differential cell count, TNFalpha, IL-1beta, NO2 and albumin concentrations in induced sputum.

Adult↗

PubMed1993

Inhaled nitric oxide for the adult respiratory distress syndrome.

BACKGROUND: The adult respiratory distress syndrome is characterized by pulmonary hypertension and right-to-left shunting of venous blood. We investigated whether inhaling nitric oxide gas would cause selective vasodilation of ventilated lung regions, thereby reducing pulmonary hypertension and improving gas exchange. METHODS: Nine of 10 consecutive patients with severe adult respiratory distress syndrome inhaled nitric oxide in two concentrations for 40 minutes each. Hemodynamic variables, gas exchange, and ventilation-perfusion distributions were measured by means of multiple inert-gas-elimination techniques during nitric oxide inhalation; the results were compared with those obtained during intravenous infusion of prostacyclin. Seven patients were treated with continuous inhalation of nitric oxide in a concentration of 5 to 20 parts per million (ppm) for 3 to 53 days. RESULTS: Inhalation of nitric oxide in a concentration of 18 ppm reduced the mean (+/- SE) pulmonary-artery pressure from 37 +/- 3 mm Hg to 30 +/- 2 mm Hg (P = 0.008) and decreased intrapulmonary shunting from 36 +/- 5 percent to 31 +/- 5 percent (P = 0.028). The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2), an index of the efficiency of arterial oxygenation, increased during nitric oxide administration from 152 +/- 15 mm Hg to 199 +/- 23 mm Hg (P = 0.008), although the mean arterial pressure and cardiac output were unchanged. Infusion of prostacyclin reduced pulmonary-artery pressure but increased intrapulmonary shunting and reduced the PaO2/FiO2 and systemic arterial pressure. Continuous nitric oxide inhalation consistently lowered the pulmonary-artery pressure and augmented the PaO2/FiO2 for 3 to 53 days. CONCLUSIONS: Inhalation of nitric oxide by patients with severe adult respiratory distress syndrome reduces the pulmonary-artery pressure and increases arterial oxygenation by improving the matching of ventilation with perfusion, without producing systemic vasodilation. Randomized, blinded trials will be required to determine whether inhaled nitric oxide will improve outcome.

Adolescent↗

PubMed1998

Awareness of environmental issues and the acceptance of CFC-free inhalers.

With the recent availability of a chlorofluorocarbon (CFC)-free metered dose inhaler (MDI) (Airomir), a patient survey was carried out to evaluate awareness of the role of CFCs in our environment and acceptance of this new inhaler. A questionnaire survey was conducted on parents and guardians of 201 children. Depending on respondents' preference, the interview was conducted in English (71%), Chinese (23%), Malay (5%) or Tamil (1%). A 'taste' test was also conducted on 103 of these children. Only 13% (26/201) of parents/guardians were aware that MDIs contained CFCs. Although 70% of children were in favour of the new taste of the CFC-free inhaler, the cost of the new inhaler was an important consideration for parents and guardians in their decision to switch to the new inhaler. The majority (93%) were willing to switch if its cost were equivalent to their current inhaler. This study has provided pertinent information with regard to acceptance of CFC-free inhalers which should be considered when making the inevitable switch to environmentally friendly inhalers.

Adult↗

PubMed2006

Inhaled nitric oxide in very preterm infants with severe respiratory distress syndrome.

AIM: To test the hypothesis that inhaled nitric oxide therapy can decrease the incidence of bronchopulmonary dysplasia and death in preterm infants with severe respiratory distress syndrome; to evaluate the possible predictive factors for the response to inhaled nitric oxide therapy. METHODS: Preterm infants (less than 30 weeks' gestation) were randomized to receive during the first week of life inhaled nitric oxide, or nothing, if they presented severe respiratory distress syndrome. Then, the treated infants were classified as non responders and responders. RESULTS: Twenty infants were enrolled in the inhaled nitric oxide therapy group and 20 in the control group. Bronchopulmonary dysplasia and death were less frequent in the inhaled nitric oxide group than in the control group (50 vs. 90%, p=0.016). Moreover, nitric oxide treatment was found to decrease as independent factor the combined incidence of death and BPD (OR=0.111; 95% C.I. 0.02-0.610). A birth weight lower than 750 grams had a significant predictive value for the failure of responding to inhaled nitric oxide therapy (OR 12; 95% C.I. 1.3-13.3). CONCLUSION: Inhaled nitric oxide decreases the incidence of bronchopulmonary dysplasia and death in preterm infants with severe respiratory distress syndrome. Birth weight may influence the effectiveness of inhaled nitric oxide therapy in promoting oxygenation improvement in preterm infants.

Birth Weight↗

PubMed2006

Performance when breathing through different respirator inhalation and exhalation resistances during hard work.

Respirator inspiratory and expiratory breathing resistances impact ventilation and performance when studied independently. However, it is less clear as to how various combinations of inhalation and exhalation resistance affect user performance. The present study investigated the performance of 11 individuals during constant load, demanding work to exhaustion while wearing respirators with eight different combinations of inhalation and exhalation resistance. Exercise performance time, performance rating, minute volume, and peak inspiratory and expiratory airflow were recorded at the end of each test trial, and independent correlations with inhalation resistance and exhalation resistance were assessed. The combined impacts of respirator inhalation and exhalation resistances were quantified as the total external work of breathing (WOB(tot)) and correlations between the test variables and WOB(tot) were also examined. Significantly linear decreases in performance were found with increased inhalation resistances independent of exhalation resistance (R(2) = 0.99; p < 0.001) and with increased WOB(tot) (R(2) = 0.92; p < 0.001). Performance also decreased with increased exhalation resistance but no significant relationships were found. Minute volume decreased linearly with increased inhalation resistance independent of exhalation resistance (R(2) = 0.99; p < 0.001), but the linear decrease observed between minute volume and WOB(tot) was weak (R(2) = 0.36; p < 0.05). These findings suggest that WOB(tot) serves as a reliable estimate of the combined impacts of respirator inhalation and exhalation resistances on user performance during hard work, but that inhalation resistance alone serves as a better predictor of ventilation during respirator wear.

Adolescent↗

PubMed2001

In vitro monodisperse aerosol deposition in a mouth and throat with six different inhalation devices.

Experiments were performed to determine the effect of different pharmaceutical aerosol inhalation devices on the deposition of monodisperse aerosols in an idealized mouth and throat geometry. The devices included two dry powder inhalers (Diskus and Turbuhaler), two nebulizers (Pari LC STAR and Hudson T-Updraft), and a metered dose inhaler with attached holding chamber (Aerochamber), in addition to a straight tube (1.7 cm inner diameter). Aerosol particles (DL-alpha tocopheryl acetate) of diameters of 2.5, 5, and 7 microm generated by a vibrating orifice generator were inhaled at steady air flow rates of Q = 5-90 L/min through the devices and into the mouth-throat. Deposition in the mouth-throat and after-filter were determined by ultraviolet (UV) spectrophotometric assay. The amount of deposition in the mouth and throat region was found to depend on the type of device that the aerosol entered through. Deposition in the extrathoracic region with the two types of jet nebulizers did not differ significantly (p > 0.1) from that of a straight tube or each other over their entire tested range of 590 > or = pd2Q > or = 11,375, where p is particle density (in g/cm3), d is particle diameter (in microm), and Q is flow rate (in cm3/s). The metered dose inhaler with attached holding chamber was found to differ from the straight tube only at two intermediate values of pd2Q = 5,145 and 16,033. The deposition occurring for the dry powder inhalers was found to be significantly greater than for the straight tube for all values of pd2Q > or = 10,954 for the Diskus and pd2Q > or = 9,435 for the Turbuhaler. Deposition with the dry powder inhalers was found to be up to 14 times greater than that with the straight tube. Thus, the inhaler geometry that the aerosol passes through prior to entering the mouth and throat region can greatly affect the deposition in the mouth-throat.

Aerosols↗

PubMed1997

Scintigraphic assessment of drug delivery from the Ultrahaler dry powder inhaler.

A new dry powder inhaler, the Ultrahaler, has been developed to deliver nedocromil sodium for the prophylaxis of asthma. This study was performed to compare the lung deposition of nedocromil sodium inhaled from the Ultrahaler at two different inhaled flow rates with that from a pressurised metered dose inhaler (MDI). A scintigraphic study was conducted in 12 healthy volunteers. On each study day, volunteers received a single 4.2 mg dose of nedocromil sodium from the Ultrahaler, using either an optimal (fast) inhaled flow rate or a suboptimal (slow) inhaled flow rate, or two doses of 2 mg nedocromil sodium from an MDI using an optimal (slow) inhaled flow rate. Used optimally, the Ultrahaler deposited significantly more (p < 0.05) of the metered dose in the lungs than either the Ultrahaler used suboptimally or the MDI used optimally [mean (SD) lung deposition values of 13.3 (4.8)%, 9.8 (3.5)%, and 7.5 (2.9)%, respectively]. Oropharyngeal deposition averaged over 80% of the dose for all three treatment regimens. This scintigraphic study demonstrated in vivo proof of concept for the Ultrahaler dry powder inhaler, and provided quantitative data on the relationship in lung deposition between the Ultrahaler and MDI which differed from that predicted by the in vitro fine particle fraction.

Anti-Asthmatic Agents↗

PubMed1991

Effectiveness of inhaled bronchodilator delivery systems for elderly patients.

A prospective study of inhaler technique using aerosol metered dose inhalers (MDIs), Rotahalers and a breath-activated device (Aerolin Autohaler) was undertaken to assess how effectively elderly patients use their inhalers. Fifty-one patients aged 67-89 years (mean 77.4 years) were enrolled. Peak flow, FEV1 and FVC were recorded, before and after inhalation of 2.5 mg of salbutamol via a nebulizer, to assess the extent of reversible airways obstruction. Inhaler technique was assessed using a scoring system, based on performance in five aspects of inhaler use. Those with poor technique were randomly allocated to an alternative inhaler and reassessed. Twenty-nine of 51 patients demonstrated reversibility in their airways disease. Twenty-one of 47 had poor technique using an MDI and were given Rotahaler or Aerolin devices to use. Ten of 11 given Aerolin Autohalers improved but seven of ten using Rotahaler showed no improvement (p = 0.006). Subsequently, five of these seven were able to improve their technique with the breath-activated autohaler. The breath-activated Aerolin Autohaler is a better delivery system than Rotahalers for inhaled bronchodilators for elderly patients.

Age Factors↗

PubMed1996

Effects of instruction by practice assistants on inhaler technique and respiratory symptoms of patients. A controlled randomized videotaped intervention study.

BACKGROUND: Many patients with asthma or chronic obstructive pulmonary disease use their medication inhalers incorrectly. General practitioners, pharmacists and other health care providers do not always have the opportunity to instruct patients in correct inhaler technique. OBJECTIVE: To find out whether the inhaler technique and respiratory symptoms of patients can be improved after instruction by practice assistants. METHODS: Single blind, randomized intervention study in which 48 patients who had been using a dry powder inhaler for at least one month took part. Their inhaler technique was videotaped on two visits with a two-week interval between visits. The inhaler technique on the videos was subsequently scored by two experts on nine criteria. At both visits the patients completed a questionnaire about their respiratory symptoms. After the first video, 25 patients were randomly chosen to receive instruction from one of six practice assistants who had followed a one evening course about inhaler instruction, and who had been issued an instruction-set. RESULTS: The patients who received instruction had a significantly greater reduction in number of mistakes at the second visit than the patients who did not (P = 0.01). The instructed patients also reported less dyspnoea at the second visit (P = 0.03). No effect of instruction was found on wheezing, cough and sputum production. CONCLUSION: The inhaler technique of patients can be improved significantly by the instruction of patients by trained practice assistants, possibly resulting in less dyspnoea.

Adolescent↗

PubMed2002

Direct comparison of the effects of nebulized nitroprusside versus inhaled nitric oxide on pulmonary and systemic hemodynamics during hypoxia-induced pulmonary hypertension in piglets.

OBJECTIVE: To test the hypothesis that nebulized nitroprusside and inhaled nitric oxide would not differ in producing selective pulmonary vasodilation during hypoxia-induced pulmonary hypertension in piglets. SETTING: University laboratory. SUBJECTS: Five piglets. INTERVENTIONS: Piglets (n = 5) were anesthetized and instrumented to monitor systemic arterial pressure, pulmonary artery pressure, and cardiac output continuously. Hypoxia was induced (DeltaFio2 from 0.5 to 0.08), and either nebulized nitroprusside (5 mg/mL at 4 L/min flow; total dose 25 mg) or inhaled nitric oxide (20 ppm) was introduced into the ventilator circuit for 15 mins. Normoxia was then restored, and a repeat cycle of hypoxia followed by the alternate vasodilator treatment was initiated. MEASUREMENTS AND MAIN RESULTS: Hypoxia significantly reduced Pao2 (from 206 to 30 torr) and elevated pulmonary artery pressure (from 18 to 33 torr) while not significantly affecting systemic arterial pressure or cardiac output. During hypoxia, inhaled nitric oxide reduced pulmonary artery pressure from 33 to 21 torr (p <.01), whereas systemic arterial pressure and cardiac output were unchanged. During hypoxia, nebulized nitroprusside also reduced pulmonary artery pressure from 33 to 23 mm Hg (p <.01; p = nonsignificant vs. inhaled nitric oxide), whereas systemic arterial pressure and cardiac output again remained constant. The time course of the reduction in pulmonary artery pressure during inhaled nitric oxide was roughly ten-fold more rapid (<5 secs) than during nebulized nitroprusside ( approximately 1 min). Neither inhaled nitric oxide nor nebulized nitroprusside altered pH, Pao2, or Paco2. CONCLUSION: Both inhaled nitric oxide and nebulized nitroprusside produced prompt, significant, selective reduction of pulmonary artery pressure and pulmonary vascular resistance in piglets with hypoxia-induced pulmonary hypertension, without apparent effects on systemic hemodynamics or pulmonary gas exchange. The equivalence of the two effects in this animal model suggests that cautious extrapolation of the use of nebulized nitroprusside as a convenient bridge to inhaled nitric oxide in selected clinical contexts for human infants may be warranted.

Analysis of Variance↗

PubMed1989

Retention patterns for inhaled particles in the lung: comparisons between laboratory animals and humans for chronic exposures.

In the absence of adequate data exclusively from studies of inhaled particles in people, the results of inhalation studies using laboratory animals are necessary to estimate particle retention in exposed people. To make accurate projections from animal studies and the limited human data, it is necessary to consider species similarities and differences in lung retention and accumulation patterns for inhaled materials. This paper reviews species similarities and differences in pulmonary retention and clearance for inhaled particles, with emphasis on animal species most commonly used in inhalation toxicology research (rats, guinea pigs, dogs, and nonhuman primates). Simulation models for these four species and for humans were used to compare projected lung burdens which would be accumulated during chronic inhalation exposures. These simulation models project an eightfold difference among these species in the lung concentration of particles per gram of lung after a 2-y chronic inhalation exposure to the same aerosol for 8 h d-1, 5 d wk-1. The largest lung accumulation would occur in guinea pigs, the smallest in rats. To reach the same target lung concentration of particles in the lungs of both animals would therefore require about an eightfold difference in air concentration of the exposure material. These comparisons are useful for selecting appropriate laboratory animal species to study as surrogates for humans, for setting aerosol concentrations to use in inhalation studies, and for making approximations of lung burdens that would result from defined exposure scenarios.

Aerosols↗

PubMed1996

Evaluation of an Auditory Feedback Equipped Metered Dose Inhaler.

BACKGROUND: Although metered dose inhalers are one of the most frequently prescribed drug delivery systems for pulmonary disease, patients usually do not employ ideal technique when using these systems. We studied the effect of a new teaching device, the MDI Tutor (MDI Tutor Inc., Palatine, IL), on patients with unsatisfactory inhalation technique. METHODS: Twelve patients with an average of 10 years' experience with metered dose inhalers (mean age, 41 years) were evaluated by two observers. All patients had deficits in their inspiratory technique such as actuation of inhaler coordinating with the beginning of inhalation cycle, uninterrupted inhalation, and incorrect length of inspiration. Following evaluation, the patients were given metered dose inhalers equipped with a MDI Tutor prototype as well as written instructions on how to use the device most effectively. RESULTS: All patients corrected their inspiratory technique deficits. CONCLUSIONS: Equipping a metered dose inhaler with a MDI Tutor allows patients to rapidly recognize correct the errors in their inspiratory technique.

Journal Article↗

PubMed2000

Meter-dosed, inhaled beclomethasone initiated at birth to prevent bronchopulmonary dysplasia.

OBJECTIVE: To examine the hypothesis that meter-dosed, inhaled beclomethasone administered to premature infants, beginning at birth and continuing in a tapering dosage schedule over the first 12 days of life, decreases the occurrence of bronchopulmonary dysplasia (BPD), at 36 wks corrected gestational age. DESIGN: Prospective, randomized, double-blind, placebo-controlled, small pilot clinical trial. SETTING: Tertiary care, neonatal intensive care unit. PATIENTS: Premature low birth weight neonates (<or=1300 g) followed from birth until 36 wks corrected gestational age. INTERVENTIONS: Aerosolized beclomethasone dipropionate was administered in a tapering dosage schedule beginning at birth and extended for the first 12 days of life, utilizing an aerosol spacer chamber and manual hand ventilation. In a subset of the subjects, a cosyntropin stimulation test was conducted on day 13 to ascertain potential hypothalamic-pituitary-adrenal axis suppression. Need for mechanical ventilation/continuous positive airway pressure (CPAP) and/or oxygen was assessed at 30 days of life and 36 wks corrected gestational age in addition to a number of other variables clinically relevant to the development of BPD. MEASUREMENTS AND MAIN RESULTS: In total, 19 placebo-treated and 20 beclomethasone-treated infants completed the study. Inhaled beclomethasone significantly reduced the need for supplemental oxygen at 30 days (p =.005) of life but not at 36 wks corrected gestational age (p =.243). A significantly greater proportion of infants receiving beclomethasone were extubated before 2 wks of age (p =.035), and infants receiving beclomethasone required significantly fewer days of mechanical ventilation (p =.004), but increased days of nasal CPAP as compared with the control group. Although fewer beclomethasone-treated than placebo-treated infants were administered intravenous steroids after 2 wks of age, this difference was not significant. No differences between groups were noted for the diagnoses of retinopathy of prematurity, nosocomial infection, or intraventricular hemorrhage. Similarly, no differences in the cosyntropin stimulation test were ascertained between treated and nontreated infants. No adverse effects were attributable to inhaled beclomethasone. CONCLUSIONS: In this small series, inhaled beclomethasone initiated at birth did not reduce the occurrence of BPD as defined by the continued requirement for supplemental oxygen at 36 wks corrected gestational age. However, inhaled beclomethasone did reduce the need for supplemental oxygen at 30 days of life and appeared to facilitate the transition from intubation/mechanical ventilation to less invasive nasal CPAP, as demonstrated by more frequent extubation before 2 wks of age and decreased total duration of mechanical ventilation in the beclomethasone-treated group. No adverse effects, including adrenal suppression, were noted in infants treated with inhaled beclomethasone. On the basis of the safety and apparent effectiveness of early inhaled beclomethasone in reducing the need for invasive mechanical ventilation and supplemental oxygen during the first month of life in premature infants, a larger clinical trial with greater power is warranted to ascertain if early inhaled beclomethasone can attenuate the occurrence of BPD.

Clinical Trial↗