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A facile method of delivery of liposomes by nebulization.

In this study, we have demonstrated a facile approach to the aerosol delivery of liposomes by nebulization. The approach involves mere dispersion of the physical mixture of phospholipid(s) and drug in saline, which results in spontaneous formation of liposomes thereby creating reservoirs for the encapsulation of drugs. Various phospholipids exhibiting different physico-chemical properties were investigated here. Two antimicrobial agents (ciprofloxacin and CM3, a novel peptide) and a bronchodilator, salbutamol sulfate, were used as model drugs to examine the nebulization properties. Nebulization properties were found to be dependent upon the nature of the phospholipids and drug. Among various phospholipids investigated, dimyristoyl phosphatidyl glycerol (DMPG), a combination of egg phosphatidylcholine (EPC) plus DMPG (i.e., EPC+DMPG) and dimyristoyl phosphatidylcholine (DMPC) plus DMPG (DMPC+DMPG) (molar ratios 1:1) showed encouraging results in terms of higher nebulization efficiency and lower leakage of drug after nebulization. The generated aerosols were characterized by an Andersen cascade impactor operated at 28.3 l/min. The mass median aerodynamic diameter (MMAD) values of the aerosol droplets obtained by nebulization of all the preparations containing DMPG reveal that these preparations are suitable for aerosol delivery by nebulization. This facile approach is expected to overcome problems associated with stability upon storage and high production costs.

1,2-Dipalmitoylphosphatidylcholine↗

[Comparative efficiency of nebulized adrenaline and salbutamol in severe acute asthma. A randomized, controlled prospective study].

OBJECTIVE: To compare nebulized salbutamol and nebulized adrenaline in acute severe asthma (ASA). STUDY DESIGN: Prospective controlled study. PATIENTS AND METHODS: October 1998 at May 99, 44 patients (31 women and 13 men, 35 +/- 11 yrs) with ASA (defined as peak expiratory flow rate (PEF) < 150 l min-1 and normo- or hypercapnia) were randomized to receive either nebulized salbutamol (n = 22), 10 mg/h-1 during 2 h then 5 mg every 4 h or nebulized adrenaline (n = 22), 6 mg/h-1 during 2 h then 3 mg every 4 h. The efficacy was assessed by PEF, forced expiratory volume in one second (FEV1) and Fischl's score during eight hours and by arterial blood gases during the first hour. Side-effects were evaluated by heart rate, systolic blood pressure, serum potassium and blood glucose. Statistical tests: Wilcoxon, Fischer exact, ANOVA and Scheffe's test. RESULTS: Both groups were similar with respect to age, sex, severity, duration of asthma and length of crisis. With the two treatments, PEF increased significantly but no statistical difference were observed between the two groups during the eight hours: 117.7 +/- 41.6 l min-1 to 203.3 +/- 56.9 l min-1 in the salbutamol group; 116.4 +/- 36.8 l min-1 to 217.3 +/- 188.8 l min-1 in the adrenaline group; p = 0.77. FEV1, Fischl's score and arterial blood gases did not differ significantly between treatments at every time interval. There were no significant difference between the two groups in terms of side-effects. The intravenous way was necessary at 3 cases of the salbutamol group and 4 cases of adrenaline group (NS). CONCLUSION: The results suggest that nebulized adrenaline is as effective as nebulized salbutamol in the ASA without significant side-effects. The nebulization could reduce systemic effects of adrenaline.

Acute Disease↗

Comparison of the efficacy and safety of high doses of beclometasone dipropionate suspension for nebulization and beclometasone dipropionate via a metered-dose inhaler in steroid-dependent adults with moderate to severe asthma.

Nebulization for the administration of high doses of inhaled corticosteroids can benefit steroid-dependent asthmatics. The objective of this double-blind, double-dummy, multicentre, randomized, parallel-group study was to compare the efficacy and safety of high-dose corticosteroids given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 2-week run-in period, 124 patients, aged 18-70 years, with moderate to severe asthma treated with high-dose inhaled steroids were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 3,000-4,000 microgday(-1) b.i.d. given via a nebulizer (n = 63), or BDP spray 1,500-2000 microgday(-1) b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) (n = 61). Comparable improvements over baseline, which were statistically significant in most cases, were reported at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, clinical symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was morning pulmonary expiratory flow rate (PEFR). For the intent-to-treat population, in the BDP nebulization group mean morning PEFR increased statistically significantly from 308.7 +/- 107.81 min(-1) to 3 19.2 +/- 104.01 min(-1) while in the BDP MDI group the increase was from 301.5 +/- 94.71 min(-1) to 309.3 +/- 86.71 min(-1). The two treatments were equally well tolerated.A total of 19 patients in each group reported adverse events during the treatment period, and these were generally mild-moderate in severity. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 3,000-4,000 microg day(-1) given via a nebulizer and BDP spray 1,500-2,000 microg day(-1) given via an MDI plus spacer are equally effective, with an acceptable safety and tolerability profile, when used in steroid-dependent adult patients with moderate to severe asthma.

Administration, Inhalation↗

Prevention of bradycardic responses to endotracheal suctioning by prior administration of nebulized atropine.

Endotracheal suctioning can elicit bradycardia and hypotension. We compared the effectiveness of nebulized atropine with that of parenterally administered atropine in preventing these responses. Six mechanically ventilated patients who reproducibly experienced a 20% or greater fall in resting heart rate exclusively with endotracheal suctioning were given three trials: a) inhaled atropine sulfate (0.05 mg/kg); b) inhaled saline aerosol (0.05 ml/kg); and c) atropine sulfate (1 mg, given im or iv). Mean heart rate fell from 114 +/- 10 to 45 +/- 5 beat/min with suctioning after the saline aerosol (p less than .001). Both nebulized and parenteral atropine sulfate prevented the bradycardic response in all six subjects (p less than .001). After nebulized saline, three patients also experienced a greater than or equal to 10 mm Hg fall in systolic BP. Both nebulized and parenteral atropine prevented the hypotensive response. Tachycardia occurred after parenteral atropine in all six patients, while only one episode of tachycardia was seen after nebulized atropine. Both parenteral and nebulized atropine can prevent bradycardia and hypotension elicited by endotracheal suctioning, but nebulized atropine may have a wider margin of safety at the doses used in this study.

Administration, Inhalation↗

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↗

Properties of aerosols produced with three nebulizers.

Investigations on the physical factors influencing the efficiency of 3 kinds of nebulizers (Wiesbadener Doppelinhalator, Heyer jet nebulizer, and Monaghan ultrasonic nebulizer) used to administer pharmaceutical agents are described. The airflow, the waterflow, and the concentration of the nebulized pharmaceutical agents in the air were determined. It was found that, for the jet nebulizers, the concentration of nebulized pharmaceuticals decreased considerably during the vaporization. The particle size distribution was measured with spiral centrifuge. The mass median diameter of the unevaporated aerosols was 3.4 mum for the Wiesbadener, 7.4 mum for the Heyer, and 5.2 mum for the Monaghan. The deposition of an aerosol produced with the Wiesbadener was measured in a glass model of the upper airways (mouth, trachea, and bifurcation). An estimate of the fraction of the aerosol that can pass the bifurcation was made. A correction for the change in the aerosol particle diameter due to the high humidity in the human lung was introduced. It was found that 35 per cent of the mass of the aerosol produced with this nebulizer can pass the human bifurcation (tidal volume, 500 ml; inhalation frequency, 12 per min).

Aerosols↗

Oxygen therapy: appropriate use of nebulizers.

Control of the inspired O2 concentration requires both an appropriate O2 fraction from the nebulizer and an adequate flow of gas to the patient. We evaluated the O2 fraction and total flow of commercially available nebulizers operated under conditions commonly encountered in clinical use. Total gas flow O2 fraction, and back pressure were measured in 8 commercially available nebulizers. Measurements were made with no outlet tubing ,with 72 inches of dry corrugated plastic tubing, and with 72 inches of corrugated plastic tubing partially occluded with water. Nebulizers were studied individually ,and in parallel sets of 2 and 3, at both 40% and 70% O2 settings. Total flow was always lower and O2 fraction higher than that predicted by the manufacture under all experimental circumstances. As the outlet resistance of the nebulizers increased, the O2 fraction increased and the total flow decreased. The O2 fraction was, in addition, increased with the addition of each nebulizer in parallel. Currently available nebulizers have operating characteristics that do not permit the easy administration of accurate O2 therapy.

Aerosols↗

Nebulization of four commercially available amphotericin B formulations in persistently granulocytopenic rats with invasive pulmonary aspergillosis: evidence for long-term biological activity.

The nebulization of amphotericin B desoxycholate (AMB-DOC), liposomal amphotericin B (L-AMB), amphotericin B lipid complex (ABLC) and amphotericin B colloidal dispersion (ABCD) has been investigated. Particle sizes of generated aerosol droplets were measured. Pulmonary amphotericin B deposition and amphotericin B concentration in blood directly after nebulization and at six weeks after nebulization was measured in healthy rats. The efficacy of nebulized amphotericin B formulations was evaluated in persistently granulocytopenic rats with invasive pulmonary aspergillosis. Treatment was given either after or before fungal inoculation. The endpoint was survival of animals. Aerosol particle sizes, expressed as the values for the mass median diameter were 1.38, 2.43, 0.90 and 2.29 microm for AMB-DOC, L-AMB, ABLC and ABCD, respectively. Amphotericin B concentrations in the lungs directly after nebulization exceeded the minimum inhibitory concentration of Aspergillus fumigatus and amphotericin B was still detected in lungs of rats at six weeks after nebulization. Treatment, started at 16 h after fungal inoculation, resulted in a significantly prolonged survival as compared with sham-treated rats for all four formulations. Prophylactic treatment at one week before fungal inoculation resulted in a significantly prolonged survival for all four formulations. Aerosol treatment given at two weeks before inoculation was effective only for AMB-DOC and L-AMB, whereas treatment given at six weeks resulted in a significantly prolonged survival for L-AMB only. All commercially available amphotericin B preparations could be nebulized efficiently and may be of value in the prophylactic treatment of invasive pulmonary aspergillosis.

Administration, Inhalation↗

The effect of nebulized albuterol on the activity of the renin-angiotensin system in asthma.

STUDY OBJECTIVE: We have previously described activation of the renin-angiotensin system (RAS) in acute severe asthma and have also reported activation of the RAS in normal subjects by single doses of nebulized beta 2-agonists. In the present study, we have examined the effect of single and multiple doses of nebulized albuterol on the activity of the RAS in mild asthma. DESIGN: Eight patients with mild asthma were studied. The effect of single and multiple doses of nebulized albuterol (5 mg) on the activity of the RAS was compared with that of placebo using a randomized, double-blind crossover study design. Nebulized drugs were administered at time 0 and 30 min. MEASUREMENTS: Plasma renin, angiotensin II (Ang II), and serum potassium levels were measured at baseline following a short rest, and thereafter at intervals up to 150 min. RESULTS: Renin levels increased after both the single (S) and double (D) nebulized doses of albuterol and were significantly greater than placebo at 30 min after S, and at 45 and 120 min after D. Plasma Ang II level also increased after S and D and was significantly greater than placebo at 30 and 45 min after S, and at 30 min and all timepoints thereafter following D. In addition, the effect of D was significantly greater than S at 45 min. CONCLUSIONS: These results confirm that there is activation of the RAS in asthmatic subjects by single doses of nebulized beta 2-agonists and that repeated dosing with nebulized albuterol has further, additive effects on plasma Ang II levels. It therefore seems likely that these agents are contributing to activation of the RAS in acute asthma, although the exact clinical significance of these transient changes in plasma Ang II levels in asthma is at present unclear.

Adrenergic beta-Agonists↗

[Is it possible to predict the number of nebulizations and the use of intravenous corticosteroid in children with asthma attacks in the emergency room?]

OBJECTIVE: To identify the number of nebulizations needed and the demand for intravenous corticosteroids in children with asthmatic attack, considering clinical and functional characteristics presented at the moment children were admitted to the emergency room. METHODS: We prospectively evaluated 130 children with asthmatic attack and from 1 to 13 years of age. At the moment children were admitted, they were evaluated according to clinical score, arterial oxygen saturation (pulse oximetry), and peak expiratory flow. Next, children received a standard treatment and were observed for the number of consecutive nebulizations required and the use of corticosteroid. Using regression analysis, we assessed the parameters evaluated for a correlation with the number of nebulizations and the use of intravenous corticosteroid. RESULTS: Eighty-eight children (67.7%) received from 1 to 3 nebulizations and 42 children (32.3%), 6 nebulizations. Sixty-eight children (52.3%) received corticosteroid. The initial values for clinical scores, arterial oxygen saturation, and peak expiratory flow showed a significant correlation with the number of nebulizations required and the need for corticosteroids. CONCLUSIONS: According to our results, it is possible to predict and anticipate, at the time chidren are admitted with asthmatic attack, the need for corticosteroid and more nebulizations, which can change the prognosis and the time of evolution of the attack.

Journal Article↗

Dose-response characteristics of nebulized albuterol in the treatment of acutely ill, hospitalized asthmatics.

We investigated the bronchodilator dose-response to nebulized albuterol and the dose of albuterol which produces maximal bronchodilation in the acutely ill, hospitalized asthmatic. Consecutively admitted patients from the emergency room in status asthmaticus who fulfilled the inclusion criteria (age <41 years old and <12 pack-years of smoking) were studied. Albuterol was administered by nebulizer (Puritan-Bennett Raindrop) in repeated 2.5-mg treatments up to a total dose of 10 mg and the bronchodilator response was measured by a computerized spirometer. Twenty-two patients were studied. Baseline spirometry showed a (mean +/- SE) forced expiratory volume in 1 sec (FEV1) of 1.26 +/- 0.14 L (42 +/- 4.0% predicted), which increased significantly (p < 0.05) during albuterol titration to a maximum FEV1 of 1.70 +/- 0.19 L (57 +/- 5% of predicted). After cumulative doses of 2.5, 5.0, 7.5, and 10.0 mg of nebulized albuterol, 27%, 45%, 72%, and 77% of patients, respectively, attained maximum bronchodilation. The remaining 23% of patients did not respond to doses up to 10 mg of albuterol. The maximum FEV1 response to albuterol did not correlate with the initial severity of airflow obstruction (r = 0.36, p > 0.05). Pulse rate and arterial oxygen saturation were not significantly affected by nebulized albuterol up to a total dose of 10 mg. No arrhythmias were noted. In summary, most hospitalized asthmatics (72%) required a cumulative dose of 7.5 mg of nebulized albuterol to achieve maximum bronchodilation and a large fraction (50%) required higher albuterol doses than the standard 2.5 mg. The bronchodilatory response to nebulized albuterol varied widely among patients in status asthmaticus and could not be predicted from the initial severity of airflow obstruction. Because side effects were minimal, it would be reasonable to use 7.5 mg of nebulized albuterol as initial therapy. Alternatively, dose-response titration with albuterol would be advantageous.

Acute Disease↗

The infection hazard of contaminated nebulizers.

Ineffectual disinfection of inhalation equipment between therapy sessions of different patients has been reported to produce serious outbreaks of infection. The role of properly disinfected equipment that becomes colonized during use was assessed. In the Vancouver General Hospital gram-negative bacilli in the nebulizer water were demonstrated in 10.5% of nebulizers being used for periods of 24 to 72 hours. In at least 15% of patients exposed to contaminated nebulizers the organism was recovered from the respiratory tract 48 hours after removal of the equipment. Only one out of 85 patients exposed to contaminated nebulizers developed pneumonia, and in this instance a clear history of aspiration of vomitus was present. The low incidence of pneumonia may be related to the high percentage of nebulizers contaminated by organisms of low virulence and might be much greater in hospitals where more highly pathogenic organisms are commonly found as nebulizer contaminants. Fifteen patients with pneumonia prior to exposure to a contaminated nebulizer failed to show any evidence of superinfection.

Bacteria↗

Airborne contamination of fine-particle nebulizers.

To determine whether bacteria present in ambient air play a role in the contamination of fine-particle reservoir nebulizers, nebulizers were placed in operation in separate hospital locations having qualitatively and quantitatively different bacterial flora in background air. Nebulizers placed in a surgical intensive care unit that had higher numbers of bacteria and a predominance of Gram-negative organisms in background air had a significantly higher incidence of nebulizer contamination (33.0%) than did nebulizers placed in a non-patient-care area that had lower bacterial counts and a predominance of Gram-positive organisms (0%) (P less than .05). The present study indicates that airborne contamination of fine-particle reservoir nebulizers occurs when bacteria present in ambient air enter the nebulizer during its operation.

Aerosols↗

Physical properties of aerosols produced by several jet- and ultrasonic nebulizers.

In order to estimate the administered dose of inhaled drugs from aqueous aerosols, we have examined the output characteristics of eleven jet- and nine ultrasonic nebulizers. Under various operating conditions we measured driving pressure, airflow, solution- and solute output of the nebulizers, particle concentration and size distribution in the aerosol. The particle size distributions were determined of the dry particles from evaporated droplets of aerosolized 9 mg X ml-1 NaCl solutions by using a mobility aerosols spectrometer. These physical properties of the aerosols were found to vary considerably between nebulizers (even among specimens of the same type). Solution output per litre of air from the ultrasonic devices was 2 to 10 times larger than that from the jets, being dependent on electric power and driving pressure respectively. The jet nebulizers showed the largest particle concentration per litre of air. The volume median aerodynamic diameter of the droplets generated by the jet nebulizers was about 1.5-4 microns. With the exception of the Siemens TV 6000 and the Bosch Halomed, this diameter ranged between 3 and 7 microns among the ultrasonic nebulizers, being dependent on the frequency of the ultrasonic vibrations. The output characteristics appeared also to be affected by extension tubes, air vents, solute concentration and airflow. Solute output varied nonproportionally with solution output, which confirms the comparative merit of output measurements by weighing. The results of the present study can be used to estimate the administered dose of therapeutic or provocative agents by nebulizer equipment. Actual drug output can only be quantified by careful calibration of each separate set-up.

Aerosols↗

The physical properties of a jet-nebulizer and their relevance for the histamine provocation test.

We have examined the physical properties of eight specimens of a frequently used jet-nebulizer (Wiesbadener Doppelinhalator). For each nebulizer, under various conditions we measured driving pressure, solution output, solute output, particle concentration and size distribution in the aerosol, and the change of solute concentration in the storage vessel. Using histamine acid phosphate solutions in distilled water, there was considerable variability between the nebulizers in solute output (range about a factor 3). Solute output was strongly related to driving pressure (r2 = 0.89), to solution output (r2 = 0.96) and to particle concentration (r2 = 0.87). The particle size distributions of the eight nebulizers were very similar. The volume median aerodynamic diameter (VMAD) of the stable evaporated particles was on average 0.33 micrograms (geometric standard deviation of 1.78), which implies a VMAD of the primary droplets of about 3.2 micrograms. In fifteen subjects with bronchial hyperreactivity, a twofold increase of histamine output of the nebulizer without a change in particle size resulted on average in a twofold decrease of the histamine concentration that caused a 20 per cent fall (PC20) in FEV1. At constant histamine output the administration of dry particles instead of direct nebulization of (partly) saturated droplets into the mouth increased PC20 by a factor 2. This difference could not be explained by a changed deposition in the hypopharynx. There were large interindividual differences in the response to the altered aerosol characteristics. We conclude that the physical properties of the administered aerosols should be carefully controlled since they influence the biological response to inhaled histamine. The solute output of the investigated jet-nebulizer can satisfactorily be validated by weighing, for which an equation is given. In bronchial provocation testing, administration of dry particles is recommended.

Adolescent↗

Effect of tidal volume on the output and particle size distribution of hypertonic saline from an ultrasonic nebulizer.

The purpose of the present study was to measure the output and particle size distribution of hypertonic saline from an ultrasonic nebulizer over the range of tidal volumes (VT) used in an epidemiological survey of asthma in children. A Starling pump was used to generate different VTs from 250 to 500 ml, at different respiratory rates of 12 and 20 breaths.min-1, to cover the normal range of respiratory pattern of children aged 7-14 yrs. The Starling pump was connected to a Timeter Compuneb Ultrasonic Nebulizer Model MP 500 with 24 cm of corrugated aerosol tubing, ID 2.2 cm, and a two-way non-rebreathing valve. Nebulizer output was measured by weighing the nebulizer chamber plus tubing and valve before and after each nebulization. To measure particle size distribution, a Malvern Particle Sizer M 3.0 (laser diffraction) was used, with a special adapter attached between valve and Starling pump. Nebulizer output increased linearly from 1.6 to 2.5 ml.min-1 for VT 250 to 500 ml, with little influence by the respiratory frequency. Furthermore, we found that in the range of VT = 300-500 ml the mass median aerodynamic diameter (MMAD) was 2.61 microns, with 100% of the particles less than 5 microns, whereas at VT = 150-250 ml the MMAD was 8.89 microns, with 90% larger than 5 microns. As output from this ultrasonic nebulizer correlates linearly with tidal volumes, size correction may not be necessary in hypertonic saline challenge tests in children. Above a VT of 300 ml, the MMAD is in the respirable range, with 100% of particles less than 5 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Nebulized but not parenteral IFN-gamma decreases IgE production and normalizes airways function in a murine model of allergen sensitization.

An animal model of local allergen (airways) sensitization was employed to study the effects of rIFN-gamma administered by ultrasonic nebulization through the airways on IgE production and airways responsiveness. BALB/c mice exposed to aerosolized OVA daily for 10 days developed a predominant anti-OVA IgE response, immediate cutaneous reactivity to OVA, and increased airways responsiveness (AR). Mice were treated with rIFN-gamma, either systemically or locally via the airways, following different protocols; i.p. rIFN-gamma failed to modulate the course of OVA sensitization, although total IgE levels in the serum were decreased by 50%. Anti-OVA IgE levels remained elevated, immediate skin test responses to OVA persisted, and AR was increased. However, local treatment of the airways with nebulized rIFN-gamma caused a 66% decrease in serum anti-OVA IgE and a twofold rise in IgG2a levels. Cutaneous reactivity to OVA was reduced and AR was also normalized after nebulized rIFN-gamma. In contrast to the i.p. route, treatment with nebulized rIFN-gamma resulted in a reduction in the in vitro IgE production by lymphocytes in response to OVA and IL-4. The timing of treatment with nebulized rIFN-gamma was important in determining the immunomodulatory response. Treatment after day 7 of OVA exposure failed to modulate sensitization. Treatment regimens with nebulized rIFN-gamma that began before day 7 of OVA exposure were able to decrease anti-OVA IgE. Only treatment regimens that included 3 days of nebulized IFN-gamma before OVA sensitization caused a decrease in cutaneous reactivity and normalization of AR. The data demonstrate that both the route and timing of rIFN-gamma administration are critical factors in the immunomodulation of the immediate allergic response to allergen sensitization via the airways.

Aerosols↗

[Nebulization for basic treatment of asthma in adults].

Many different forms of nebulizer treatment for asthma have been developed over the last few years, including several which have reached international concensus. Nevertheless, there are no widely recognized recommendations concerning the role of nebulization in the treatment of asthma in adults. We present here the main elements on the pathophysiological basis of nebulization treatment of asthma, the physical and chemical parameters of nebulization, the different nebulizers and the substances which can be administered and their costs. The indications for home nebulizer treatment of asthma in adults include asthma with chronic sinusitis or nasosinus polyposis, asthma with hypersecretion with or without bronchial dilatation, severe poorly controlled asthma, corticodependent asthma. The aim of this discussion on nebulizer administration is to reduce the amount of systemic corticosteroid delivery and underline the need for quality research in this area.

Administration, Inhalation↗