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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

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

A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma.

BACKGROUND: Inhaled glucosteroids and oral theophylline are widely used to treat asthma. We compared the benefits of adding theophylline to inhaled glucosteroid with those of doubling the dose of inhaled glucosteroid in patients with persistent symptoms despite the use of inhaled glucosteroid. METHODS: In a double-blind, placebo-controlled trial, we randomly assigned 62 patients to receive either 400 microg of inhaled budesonide (low-dose budesonide) with 250 or 375 mg of theophylline (depending on body weight) or 800 microg of inhaled budesonide (high-dose budesonide). All doses were given twice daily for three months. Lung function was measured serially, and patients kept records of peak expiratory flow, symptoms, and albuterol use. The effects of treatment on endogenous cortisol levels were also assessed. RESULTS: Both treatments resulted in improvements in lung function that were sustained throughout the study. As compared with treatment with high-dose budesonide, treatment with low-dose budesonide plus theophylline resulted in greater improvements in forced vital capacity (P=0.03) and forced expiratory volume in one second (P= 0.03). There were significant and similar reductions in beta2-agonist use and the variability of peak expiratory flow, a correlate of bronchial hyperresponsiveness and the severity of asthma. Serum cortisol concentrations were significantly reduced in the group given high-dose budesonide (from a mean [+/-SE] of 18.4+/-2.4 microg per deciliter to 15.9+/-2.1 microg per deciliter, P=0.02) but were unchanged in the other group. The median serum theophylline concentration was 8.7 microg per milliliter (therapeutic range, 10 to 20) among those who received theophylline. Both treatments were well tolerated. CONCLUSIONS: For patients with moderate asthma and persistent symptoms, low-dose inhaled budesonide with theophylline and high-dose inhaled budesonide produced similar benefits. Effects were achieved at theophylline concentrations below the recommended therapeutic range. The addition of low-dose theophylline to inhaled glucosteroid may be preferable to and cheaper than increasing the dose of inhaled glucosteroid.

Administration, Inhalation

Evaluation of inhalation aids of metered dose inhalers in asthmatic children.

Many patients have incorrect aerosol inhalation technique with metered dose inhalers (MDI). Several inhalation aids have been developed and marketed for these patients. Even those who have correct inhalation technique may benefit from these devices. We compared bronchodilator efficacy of two puffs of albuterol aerosol administered either directly from a MDI mouthpiece, or from an inhalation aid (InspirEase, Aerochamber, Aerosol Bag) in 20 children who had previously demonstrated proper inhalation technique. The children received two puffs of aerosol from a MDI in each of two modalities tested each day on four different days (double blind). One modality contained albuterol aerosol and the other placebo. Pulmonary function was tested before and at 15, 30, 60, 120, and 180 minutes after treatment. Forced expiratory volume in 1 second (FEV1) increased similarly after all four modes of administration. Six patients who had incorrect inhalation technique benefited from the three inhalation aids. The aerosol bag and InspirEase produced slightly greater bronchodilator response than the Aerochamber. The inhalation aids are useful devices for those who have incorrect inhalation technique, but those who have correct technique do not derive any benefit from these devices.

Adolescent

Effect of inhaled furosemide on the bronchial response to lysine-aspirin inhalation in asthmatic subjects.

It has been demonstrated recently that inhaled furosemide inhibits bronchoconstriction induced by cold air, physical exercise, various antigens, and metabisulfite. The goal of the present study was to determine if the inhalation of furosemide would inhibit the bronchoconstriction resulting from the inhalation of lysine-aspirin in aspirin-sensitive asthmatics. Six female subjects with known hypersensitivity to aspirin participated in this crossover study comparing 20 mg of inhaled furosemide and placebo. The volunteers inhaled increasing concentrations of lysine-aspirin after the inhalation of furosemide or placebo. The geometric mean provocative dose causing a 20 percent decrease in the FEV1 (PD20) after the inhalation of placebo was 30.4 mg/ml and the PD20 was equal or below 90 mg/ml in all patients. In contrast, the FEV1 did not decrease by 20 percent in any of the patients pretreated with furosemide when the inhaled concentration was increased to 360 mg/ml. From this study, we conclude that the administration of furosemide blocks the bronchospasm induced by the inhalation of lysine-aspirin in aspirin-sensitive asthmatics.

Administration, Inhalation

Increased inhaled bronchodilator vs increased inhaled corticosteroid in the control of moderate asthma.

Undertreatment of chronic asthma may reflect uncertainty as to how it may be best controlled. We compared the effects of increased inhaled corticosteroid vs regular inhaled bronchodilator in 32 adult asthmatics. During three 16-week treatment periods, comprising baseline inhaled corticosteroid (mean 505 micrograms daily) and on-demand beta-agonist, baseline inhaled corticosteroid and increased (regularly scheduled four times daily) beta-agonist, and increased inhaled corticosteroid (mean 1478 micrograms daily) and on-demand beta-agonist, subjects recorded symptoms, morning and evening peak flow, and additional medication. Of 25 subjects whose control differed significantly between treatments with baseline vs increased corticosteroid, 22 (88 percent) favored the increased dosage (p < 0.001). Of 28 subjects whose control differed between treatments with regular beta-agonist vs increased corticosteroid, 24 (86 percent) were better controlled with increased inhaled corticosteroid and were worse with regular beta-agonist (p < 0.001). Only one quarter the number of exacerbations were experienced during treatment with increased inhaled corticosteroid. Upper airway adverse effects were minor and easily controlled. Hence, asthma with persistent symptoms was better controlled by increased inhaled corticosteroid therapy than by increased use of inhaled beta-agonist.

Administration, Inhalation

Dose potency relationship of terbutaline inhaled via Turbuhaler or via a pressurized metered dose inhaler.

OBJECTIVE: The relative dose potency of cumulative doses of terbutaline sulfate inhaled via Turbuhaler and via a pressurized metered dose inhaler was estimated with respect to lung efficacy and systemic effect. METHODS: The study was an open, crossover, randomized, multicenter study including 31 adult patients with asthma [forced expiratory volume in one second (FEV1), 65% of predicted]. The patients inhaled terbutaline doses of 0.125, 0.125, 0.25, 0.5, 1.0, and 2.0 mg (a total of 4 mg) at 30-minute intervals. Lung function [FEV1, forced vital capacity (FVC), forced expiratory flow at 75% of FVC (FEF75%), and peak expiratory flow (PEF)], and systemic effect variables (serum potassium, tremor, pulse, blood pressure) were monitored prior to the first inhalation and 15 to 25 minutes after each inhaled dose. RESULTS: The mean relative dose potency of terbutaline inhaled via Turbuhaler compared with pressurized metered dose inhaler was 1.5 (95% confidence interval: 1.2 to 1.8) with respect to FEV1 and serum potassium, respectively. The corresponding relative dose potencies for PEF, FVC, and FEF75% were 1.0, 1.2, and 1.6, respectively, with no statistically significant difference between the two devices. No differences between the devices were evident with regard to blood pressure and pulse. CONCLUSION: The results suggest that Turbuhaler is more efficient in the delivery of inhaled terbutaline to the lungs compared with the conventional pressurized metered dose inhaler.

Administration, Inhalation

Ease of handling and clinical efficacy of fluticasone propionate Accuhaler/Diskus inhaler compared with the Turbohaler inhaler in paediatric patients. UK Study Group.

A total of 323 children aged 4-11 years who were receiving, or had symptoms indicating a clinical requirement for, inhaled corticosteroid at a daily dose of 400 micrograms budesonide (BUD) or beclomethasone dipropionate (BDP), or 200 micrograms fluticasone propionate (FP), were randomised into this multicentre, open-label, parallel group study. Patients received either FP 100 micrograms b.d. administered via the Accuhaler/Diskus inhaler (n = 159) or BUD 200 micrograms b.d. administered via a Turbohaler inhaler (n = 164) for four weeks and recorded daily their morning and evening peak expiratory flow (PEF), asthma symptoms and use of relief medication. Device handling was assessed by a questionnaire, with responses recorded on three- or five-point ordinal scales. The primary efficacy parameter was mean percent predicted morning PEF. The device handling results showed the Accuhaler/Diskus inhaler was rated more favourably than the Turbohaler inhaler in terms of ease of correct inhaler use, ease of telling how many doses were left, ease of knowing whether a dose had been inhaled and overall liking of the device. More patients in the Accuhaler/Diskus group (85%) than in the Turbohaler group (58%) said they would be happy to receive the same device again, while 8% and 25% respectively said they would not be happy to be given it again. In addition, the change from baseline to week 4 of treatment in mean percent predicted morning PEF was greater in the FP Accuhaler/Diskus group, indicating that FP 200 micrograms daily via Accuhaler/Diskus inhaler is at least as clinically effective as BUD 400 micrograms daily via the Turbohaler inhaler.

Administration, Inhalation

Comparison of terbutaline and placebo from a pressurised metered dose inhaler and a dry powder inhaler in a subgroup of patients with asthma.

BACKGROUND: Reversibility after administration of an inhaled bronchodilator is not always demonstrable in patients with asthma. Bronchodilator aerosol-induced bronchoconstriction has also been reported to occur in some patients. METHODS: Fifteen selected patients showing < 10% improvement in forced expiratory volume in one second (FEV1) when tested with four doses of salbutamol (0.1 mg/dose) or terbutaline (0.25 mg/dose) from a pressurised metered dose inhaler (MDI) participated in two randomised, double blind studies. They received 2.0 mg terbutaline (4 x 2 doses of 0.25 mg) or a corresponding placebo from an MDI connected to a 750 ml spacer, and 1.0 mg (2 x 0.5 mg) terbutaline or placebo from a multidose dry powder inhaler free of additives (Turbohaler). RESULTS: Inhalation of placebo MDI resulted in a mean (SD) decrease in FEV1 of 20.5 (14.1)% (range -42.9% to +2.6%). In 14 patients inhalation of 2.0 mg terbutaline MDI with spacer resulted in < 10% improvement (mean increase 3.1 (6.0)%). One mg of terbutaline via a Turbohaler resulted in improvements in FEV1 of > 15% in eight patients (mean increase 16.0 (9.7)%). The improvement was < 10% in four patients. Use of placebo Turbohaler did not affect airway calibre (mean change 0.2 (2.9)%). CONCLUSIONS: Additives of MDIs may cause bronchoconstriction in some patients with asthma. In these patients inhalation from a pressurised metered dose inhaler is more likely to decrease the bronchodilator response than inhalation from an additive-free inhaler. The frequency of this phenomenon is unknown.

Albuterol

Therapeutic equivalence of a novel HFA134a-containing metered-dose inhaler and the conventional CFC inhaler (Berodual) for the delivery of a fixed combination of fenoterol/ipratropium bromide. A randomized double-blind placebo-controlled crossover study in patients with asthma.

The efficacy and safety of a novel fenoterol/ipratropium bromide metered-dose inhaler (MDI) formulated with a non-chlorinated propellant, HFA134a, has been compared with placebo and the conventional chlorofluorocarbon (CFC)-containing fenoterol/ipratropium bromide inhaler (Berodual) in asthmatic patients. Fifty-two patients were enrolled in two centres. The fenoterol/ ipratropium bromide treatment produced significantly (P < 0.0001) greater bronchodilatation than placebo. There were no significant differences between the mean peak and average forced expiratory volume in the first second (FEV1) for patients receiving 2 puffs of the fenoterol/ipratropium bromide HFA134a inhaler and the conventional CFC inhaler. In addition, time to onset and duration of efficacy were comparable for these two treatments. None of the patients showed a fall of > or = 15% in baseline FEV1 or needed rescue medication within 30 min after inhalation of the test drug. No paradoxical bronchoconstriction was observed as measured by sGaw. The two inhaler formulations were well tolerated. A taste-related complaint, lasting for a few minutes after inhalation, was reported by a higher proportion of patients who inhaled the HFA134a formulation, mainly by patients selected in one of the two centres. In conclusion, a dose of 100 micrograms fenoterol/40 micrograms ipratropium bromide inhaled from a MDI containing HFA134a propellant is safe and provides effective bronchodilatation of equivalent degree, onset and duration of action to the same dose from the conventional CFC formulation.

Adult

Is the combination inhaler of salbutamol and beclomethasone dipropionate as effective as the same agents from separate inhalers in the management of childhood asthma?

A double-blind crossover study lasting 16 weeks was carried out in children with chronic extrinsic asthma to compare the clinical effects of regular inhalations of salbutamol and beclomethasone dipropionate from a combination inhaler and regular inhalations of the same two drugs used sequentially from separate inhalers. Eighteen patients entered the study and 16 completed both 8-week treatment periods. However, there was a large amount of missing data, with only 9 complete sets of paired data; efficacy analyses were performed on data from 10 patients on separate inhaler therapy and from 14 patients on combination inhaler therapy. There were no significant differences between daily peak flow rate measurements, symptom scores, additional symptomatic bronchodilator therapy, acute exacerbations of asthma or incidence of adverse events, demonstrating that both treatments were similarly effective in controlling the patient's asthmatic symptoms. There was, however, a trend for higher peak flow values and lower symptom scores on separate inhaler therapy in this small group of asthmatic children. Although the results suggest that regular therapy using a combination inhaler is as effective as sequential administration of salbutamol and beclomethasone dipropionate from separate inhalers, it is concluded that the study should be extended to a larger group of patients to determine whether there might be any statistically significant differences between the two regimens.

Adolescent

Detection of acute inhalation injury in fire victims by means of technetium-99m DTPA radioaerosol inhalation lung scintigraphy.

Mortality and morbidity in fire victims are largely a function of injury due to heat and smoke. While the degree and area of burn together constitute a reliable numerical measure of cutaneous injury due to heat, as yet no satisfactory measure of inhalation injury has been developed. In this study, we employed technetium-99m diethylene triamine penta-acetic acid (DTPA) radioaerosol lung scintigraphy (inhalation scan) to evaluate acute inhalation injury in fire victims. Ten normal controls and 17 survivors from a fire accident were enrolled in the study. All patients suffered from respiratory symptoms (dyspnoea and/or cough with sputum). 99mTc-DTPA aerosol inhalation lung scintigraphy was performed in all subjects, using a commercial lung aerosol delivery unit. The degree of lung damage was presented as the clearance rate (k; %/min) calculated from the time-activity curve over the right lungs. In addition, the distribution pattern of the radioactivity in the lungs was evaluated and classified into two groups: homogeneous distribution and inhomogeneous distribution. A plain chest radiograph (CxR) and pulmonary function test (PFT) were performed in the same group of patients. The results showed that 6/17 (35.3%) patients had inhomogeneous distribution of radioactivity in their inhalation scans, and 11/17 (64.7%) had homogeneous scans. Five of the six patients with inhomogeneous scans were admitted for further management, and all patients with homogeneous scans were discharged from the emergency department and needed no further intensive care. The clearance rates of the right lung were 0.73%+/-0.13%/min for normal controls and 1.54%+/-0.58%/min for fire victims. The difference was significant, with a P value of less than 0.01. Using a cut-off value of 0.9%/min (all normal subjects were below 0. 9%/min), 14 (82.4%) patients had abnormal clearance rates of 99mTc-DTPA from the lung. In contrast, only three (17.6%) patients had abnormal CxR and three (17.6%) had abnormal PFTs. We conclude that (1) conventional CxR and PFT are not good modalities for evaluating inhalation injury in fire victims because of their low sensitivity, and (2) 99mTc-DTPA radioaerosol inhalation scintigraphy can provide an objective evaluation of inhalation injury during a fire accident and may be useful in therapeutic decision-making and disease monitoring.

Administration, Inhalation

Inhaled nitric oxide selectively reduces pulmonary hypertension after ovine smoke inhalation but does not improve oxygenation.

Inhaled nitric oxide (NO) is known to selectively reduce pulmonary hypertension and improve the ventilation-perfusion relationship in subjects with lung injury of various origin. However, some forms of lung injury do not react to inhaled NO at all, or show only a reduction in pulmonary arterial pressure. Very little is known about the effects of inhaled NO after smoke inhalation injury. We investigated the effects of inhaled NO in an established model of ovine smoke inhalation injury. Chronically instrumented sheep (n = 8) had tracheostomies and were insufflated with smoke generated from burning cotton cloth (4 times at 12 breaths each). They were then connected to a ventilator with oxygen-enriched air to achieve arterial oxygen tensions within the normal range. After 48 hours, NO was added to the inspired gas in ascending concentrations of up to 100 ppm. Systemic and pulmonary hemodynamics as well as oxygen transport were analyzed. Inhaled NO dose dependently lowered the pulmonary hypertension. Concentrations higher than 20 ppm did not further reduce the pulmonary artery pressure. Right ventricular stroke work index was significantly improved owing to the reduction in pulmonary vascular resistance. Arterial oxygenation, however, was not optimized by inhaled NO, probably because of interstitial edema formation.

Administration, Inhalation

Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler.

The aim of this open, randomized cross-over study was to compare the efficacy and safety of inhaled budesonide administered either via a pressurized metered dose inhaler with a 750 ml spacer attached, or via a new dry powder inhaler, Turbuhaler, in 28 patients with stable bronchial asthma. During the 2-week run-in period, the patients received their ordinary inhaled steroid treatment. This was followed by two 4-week periods of active treatment with inhaled budesonide given via Turbuhaler or pressurized MDI. The patients were divided into two groups according to their previous, inhaled steroid doses. Group A received 400 micrograms of budesonide b.i.d, and Group B 800 micrograms of budesonide b.i.d. Diary cards were used by the patients at home to report asthma symptoms, beta 2-agonist consumption, and PEF twice daily, as well as the number of coughs experienced in a 5-min period after steroid inhalation. Budesonide Turbuhaler produced a significantly better effect on morning peak flow than budesonide MDI. The number of coughs in the 5 min after steroid inhalation was significantly lower with the Turbuhaler than with the MDI. In all other parameters recorded (e.g. FEV1, evening PEF, histamine PC20 and other diary measurements) there were no statistically significant differences between the two devices. Turbuhaler was significantly more appreciated than MDI in all questions of preference. The study showed that budesonide via Turbuhaler was at least as effective and safe as budesonide via a pressurized MDI at daily doses of 800 and 1,600 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

Modification of the thermogenic effect of acutely inhaled salbutamol by chronic inhalation in normal subjects.

BACKGROUND: Acute inhalation of clinical doses of salbutamol in normal volunteers increases resting metabolic rate by up to 20% above control values. This study was designed to see if chronic treatment with salbutamol causes a sustained increase in metabolic rate and whether it modifies the acute thermogenic response to the drug. METHODS: The effects of chronic inhaled salbutamol on resting oxygen consumption (VO2) and carbon dioxide output (VCO2) were studied in seven normal subjects (age 20-47 years, weight 52-105 kg, five men). An open canopy method of indirect calorimetry was used to measure VO2, VCO2, and respiratory quotient (RQ). Subjects inhaled two puffs of salbutamol or placebo four times a day in a double blind manner. Measurements of resting VO2 and VCO2 after 10 days of salbutamol were compared with the values after 10 days of placebo and with those taken at the start of the study. At the end of each treatment period subjects inhaled eight puffs (800 micrograms) of salbutamol and the acute effects on VO2, VCO2 and RQ were monitored for one hour. RESULTS: Resting VO2, VCO2, and RQ were not significantly different at the end of the salbutamol and placebo periods but the acute response to eight puffs of salbutamol was abolished by regular inhalation. The mean VO2 integrated over one hour after 800 micrograms salbutamol given acutely was different (241.3 and 210.7 ml/kg/h in the placebo and salbutamol groups respectively). Differences were not significant between placebo and salbutamol groups for changes in VCO2, heart rate, blood pressure, and RQ after acute inhalation. CONCLUSION: Regular treatment with inhaled salbutamol (800 micrograms/day) does not cause a sustained increase in resting metabolic rate but prevents the increase in VO2 that occurs after acute inhalations in normal subjects.

Administration, Inhalation

Effect of inhaled and systemic opiates on responses to inhaled capsaicin in humans.

To determine the site of action of opiates in humans, we have studied the effect of systemic and inhaled opiates on cough and increase in respiratory resistance (Rrs) caused by inhaled capsaicin. In 13 subjects, a range of doses of capsaicin inhaled in single breaths given in random order produced a reproducible dose-cough response. Inhalation of a dose of capsaicin that caused fewer than two coughs increased Rrs by 28% (21-35, mean 95% confidence interval). Inhaled codeine (50 mg) and morphine (10 mg) did not alter the cough response. In contrast, both drugs increased base-line Rrs by 24% (16-44) and 13% (3-23), respectively, and significantly reduced the increase in Rrs after inhaled capsaicin (P less than 0.05). Oral codeine (60 mg) significantly (P less than 0.05) reduced the number of coughs at 1 and 2 h but did not alter base-line Rrs or its increase after capsaicin. Intravenous morphine (0.15 mg/kg) significantly reduced the sensitivity of the cough response (P less than 0.05), which was reversed by naloxone. However, there was no significant drug effect on either the base-line Rrs or its increase after capsaicin. Systemic dosing of opiates is therefore required to reduce the cough reflex, whereas inhaled opiates may reduce the increase in Rrs after inhaled capsaicin.

Administration, Inhalation

[Inhalation chambers: an alternative to the conventional inhalator?].

BACKGROUND: Aerosol inhalers constitute the most commonly used form of administration of medication by most of the patients with respiratory disease although incorrect usage is a demonstrated fact in many studies. A previous study demonstrated that, despite correct instruction by health care staff and the patients, 30% of the same use these inhalers incorrectly. In the present study, the efficacy of inhalation chambers (750 ml) and spacers (50 ml) versus the conventional inhaler was evaluated by quantification of bronchodilator response. METHODS: Fifty-six stable patients with chronic obstruction to air flow in habitual treatment with aerosol inhalers (AI) were studied. For this study 27 patients used the chamber and 29 the spacer. The patients using the maneuvers correctly (n = 42) and those that did not (n = 14) were studied together and separately. RESULTS: Patients using the inhaler incorrectly were found to benefit significantly from either of the procedures. Upon comparison of the chambers (750 ml) with the spacers (50 ml) a significant improvement was observed with the former. CONCLUSIONS: The response to bronchodilator treatment in patients not using aerosol inhalers correctly improves significantly upon use of either inhalation chambers or spacers with the former demonstrating the best results.

Adult

The effect of inhaled nitric oxide on smoke inhalation injury in an ovine model.

Smoke inhalation is a significant comorbid factor in thermal trauma. The effect of inhaled nitric oxide (NO) on smoke inhalation injury was evaluated in an ovine model. Following smoke exposure, group 1 animals (n = 9) spontaneously breathed room air, and group 2 animals (n = 8) breathed 20 parts per million of NO in air for 48 hours. Cardiopulmonary variables and blood gases were serially measured; bronchoalveolar lavage (BAL) was performed and wet-to-dry lung weight ratios (W/D) determined at 48 hours. Pulmonary vasoconstriction following smoke inhalation was significantly attenuated by inhaled NO (p < 0.05), which exerted no apparent effect on the systemic circulation. In group 2, the serial decline in pulmonary oxygenation was less than in group 1, consistent with a smaller physiologic shunt (p < 0.05). There were no significant differences in W/D, lung compliance, BAL fluid analysis results, or histologic evaluation findings between the two groups. These results suggest that inhaled NO exerted beneficial effects on pulmonary arterial hypertension and oxygenation following smoke inhalation without apparent amelioration of airway inflammation.

Administration, Inhalation