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PubMed1988

Acidity potentiates bronchoconstriction induced by hypoosmolar aerosols.

Naturally occurring fogs are usually hypoosmolar with respect to body fluids and can be quite acidic. Because both hypoosmolarity and acidity can cause bronchoconstriction, we studied whether there was a positive interaction between these stimuli in 12 subjects with asthma. We administered the following aerosols: hypoosmolar saline (30 mOsm) at pH 5.5, 3 hypoosmolar acids (0.005 M H2SO4, 0.01 M HNO3 and a 1:1 mixture of 0.005 M H2SO4 and 0.01 M HNO3, all 30 mOsm) at pH 2, and isoosmolar 0.005 M H2SO4 (300 mOsm) at pH 2. Each aerosol was administered on a separate day and was inhaled through a mouthpiece during tidal breathing. Specific airway resistance (SRaw) was measured before and after the subjects inhaled aerosols delivered at as much as 5 doubling nebulizer outputs. For each aerosol challenge, an output-response curve was generated, and the nebulizer output required to increase SRaw by 100% above baseline (PO100) was calculated. Mean values of PO100 were significantly lower for each of the hypoosmolar acids than for hypoosmolar saline (1.65 + 0.43 g/min [mean + SEM] for saline compared with 0.95 + 0.11, 1.05 + 0.20, and 0.90 + 0.14 for H2SO4, HNO3, and a 1:1 mixture of the two; all p values less than 0.025). Mean values of PO100 did not differ among the 3 acids studied. For 7 of 12 subjects, all 3 acids caused a leftward shift in the output-response curve from the curve generated for hypoosmolar saline aerosol. Isoosmolar H2SO4 did not increase SRaw by 100% in any subjects, even at the maximal nebulizer output that delivered a concentration of H2SO4 in excess of 40 mg/m3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Enhanced aerosol deposition in the lung with mild airways obstruction.

We investigated the sensitivity of aerosol deposition to airways obstruction by measuring total deposition fraction of inert aerosol in normal conscious sheep (n = 6) after challenging cholinergic agent, pilocarpine (PL) (0.5 mg/kg intravenously) with and without a prior challenge of beta 2-adrenergic agonist, terbutaline sulfate (TS) (0.025 mg/kg subcutaneously). Aerosol deposition was measured by a light-scattering aerosol photometer in situ while sheep rebreathed 1.0-micron-diameter inert oil droplets from a 0.2-L collapsible bag at a rate of 30 breaths/min. Total accumulated deposition at the fifth breath (AD5) as a percentage of initial aerosol concentration was determined and compared with mean pulmonary airflow resistance (RL). After PL, both AD5 and RL increased significantly from baseline values by 51 +/- 9% and 597 +/- 118% (mean +/- SE), respectively, whereas AD5 and RL decreased significantly by 16 +/- 4% and 34 +/- 6%, respectively after TS (p less than 0.05). After PL subsequent to TS (TS-PL), AD5 increased in all six sheep by 33 +/- 7% from post-TS values (p less than 0.05). However, RL did not change from post-TS values. Greater changes in RL than in AD5 after PL (bronchoconstriction) or TS (bronchodilation) suggest a greater sensitivity of RL than AD5 to airway patency in the large airways. Lack of increase of RL after TS-PL indicates that bronchoconstrictive effect of PL was blocked by prior challenge with TS. Therefore, the increase in AD5 after TS-PL may be related to the peripheral airway obstructions which might have been caused by increased secretions induced by a potent secretagogue PL.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1991

Factors determining pulmonary deposition of aerosolized pentamidine in patients with human immunodeficiency virus infection.

Although aerosolized pentamidine (AP) has recently been approved for prophylaxis and is undergoing clinical trials for treatment of pneumocystis, pneumonia (PCP), factors important in the deposition of AP have not been described. Using radioaerosol techniques, deposition was measured in 22 patients receiving AP for prophylaxis or treatment of PCP. In all patients total and regional deposition of pentamidine, breathing pattern, pulmonary function (PFT), regional ventilation, and type of nebulizer were analyzed. Bronchoalveolar lavage (BAL) was performed 24 h after inhalation to assess the relationship between pentamidine levels in BAL fluid and measured aerosol deposition. The nebulizers tested were the Marquest Respirgard II and the Cadema AeroTech II, both previously characterized in our laboratory. The aerosol particles consist of water droplets containing dissolved pentamidine and technetium 99m bound to albumin. Analysis of particles sampled during inhalation via cascade impaction confirmed a close relationship between radioactivity in the droplets and the concentration of pentamidine as measured by HPLC (r = 0.971, p less than 0.0001; n = 18). Deposition was measured by capturing inhaled and exhaled particles on absolute filters and measuring radioactivity. This technique allows the determination of the deposition fraction (DF, the fraction of the amount inhaled that is deposited), which provides information on factors strictly related to the patient. To confirm the filter measurements, pentamidine deposition was also measured by gamma camera. The camera measurement was possible because each patient's thoracic attenuation of radioactivity was determined by a quantitative perfusion scan (mg pentamidine deposited via both techniques, r = 0.949, p less than 0.0001; n = 26). Regional lung volume and ventilation were determined by xenon 133 equilibrium scan and washout. Pentamidine deposition varied markedly between patients, but BAL levels of pentamidine significantly correlated with measured deposition (r = 0.819, p less than 0.01; n = 9). DF averaged 0.621 +/- 0.027 (SEM) and did not correlate with any measured lung parameter, including breathing pattern and PFT. Regional deposition did not correlate with regional ventilation. The major factor influencing pentamidine deposition was aerosol delivery (mg deposited versus mg inhaled; r = 0.963, p less than 0.0001; n = 26). The nebulizer was an important determinant of aerosol delivery, with the AeroTech delivering between 2.5 and 5 times more drug than the Respirgard. These observations are important in assessing treatment failure and cost of therapy.

Aerosols↗
PubMed1991

The effect of ozone exposure on the dispersion of inhaled aerosol boluses in healthy human subjects.

Acute exposure of humans to low levels of ozone are known to cause decreases in FVC and increases in SRaw. These alterations in lung function do not, however, elucidate the potential for acute small airway responses. In this study we employed a test of aerosol dispersion to examine the potential effects of ozone on small airways in humans. Twenty-two healthy nonsmoking male volunteers were exposed to 0.4 ppm ozone for 1 h while exercising at 20 L/min/m2 body surface area. Before and immediately after exposure, tests of spirometry (FVC, FEV1, and FEF25-75) and plethysmography (Raw and SRaw) were performed. Subjects also performed an aerosol dispersion test before and after exposure. Each test involved a subject inhaling five to seven breaths of a 300-ml bolus of a 0.5 micron triphenyl phosphate aerosol injected into a 2-L tidal volume. The bolus was injected into the tidal breath at three different depths: at Depth A the bolus was injected after 1.6 L of clean air were inhaled from FRC, at Depth B after 1.2 L, and at Depth C after 1.2 L but with inhalation beginning from RV. The primary measure of bolus dispersion was the expired half-width (HW). Secondary measures were the ratio (expressed as percent) of peak exhaled aerosol concentration to peak inhaled concentration (PR), shift in the median bolus volume between inspiration and expiration (VS), and percent of total aerosol recovered (RC). Changes in pulmonary function after ozone exposure were consistent with previous findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Effect of aerosolized pentamidine prophylaxis on the diagnosis of Pneumocystis carinii pneumonia by induced sputum examination in patients infected with the human immunodeficiency virus.

This study assessed the effect of aerosolized pentamidine prophylaxis on the clinical presentation and diagnostic sensitivity of induced sputum examination for Pneumocystis carinii pneumonia. Between January 1, 1988 and October 27, 1990, 348 induced sputum examinations were performed as the initial diagnostic procedure for P. carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). Medical records were reviewed for all induced sputum examinations, and the study group consisted of patients who either had not received prophylactic therapy (n = 193) or had received aerosolized pentamidine prophylaxis (n = 126). A total of 29 induced sputum examinations in patients receiving either other prophylactic regimens or ongoing therapy for previously documented P. carinii pneumonia were excluded from the study group. A total of 72 consecutive episodes of P. carinii pneumonia were subsequently documented by induced sputum examination (n = 54), bronchoalveolar lavage (n = 16), thoracocentesis (n = 1), or autopsy (n = 1). A total of 44 episodes occurred in patients who had not received antipneumocystis prophylaxis, and 28 episodes occurred in patients who had received aerosolized pentamidine. Of patients capable of producing a sputum specimen for analysis, induced sputum examination had a significantly lower diagnostic yield of 64.3% in patients who had received aerosolized pentamidine prophylaxis compared with 92.3% in patients who did not receive prophylaxis (p less than 0.02, Fisher's exact test). When the data were analyzed on an intention to treat basis, although there was a trend suggesting a lower overall yield in the aerosolized pentamidine patients, the difference was not statistically significant (64.3 versus 81.8%, p = 0.17, Fisher's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1992

Delivery of a nebulized aerosol to a lung model during mechanical ventilation. Effect of ventilator settings and nebulizer type, position, and volume of fill.

Several factors may affect the delivery of a nebulized aerosol to the lung through an endotracheal tube during mechanical ventilation. To study these factors in vitro, a model representing ventilation of an adult patient was constructed by linking a Servo 900C ventilator to a standard humidified circuit and an endotracheal (ET) tube positioned within a pipe representing the trachea. This was connected via a filter to a lung simulator. Nebulizers filled with 99mTc human serum albumin were positioned in the circuit, and the delivery of nebulized aerosol through the ET tube into the filter was measured using a gamma camera. With the use of an inspiratory phase-activated System 22 Acorn jet nebulizer, typical adult ventilator settings, and a 3-ml nebulizer solution volume, 5.4% of the nebulizer dose reached beyond the end of the ET tube. This was increased by increasing the inspiratory time, reducing the respiratory rate or respiratory minute volume, and by repositioning the nebulizer on the inspiratory limb of the Y-piece and was reduced by slowing the driving gas flow to the nebulizer. Under the same conditions, delivery was 3.1 and 4.4% using the Samsonic and Fisoneb ultrasonic nebulizers, respectively. Increasing the fill volume and the addition of an aerosol storage chamber increased delivery with all three nebulizers. These experiments suggest some simple ways of improving aerosol delivery during mechanical ventilation, including increasing the volume of nebulizer fill, repositioning the nebulizer in the ventilator circuit, adding an aerosol storage chamber, and adjusting ventilator settings to maximize delivery.

Adult↗
PubMed1993

Aerosolized versus instilled exogenous surfactant in a nonuniform pattern of lung injury.

Previous studies have shown that the underlying patterns of lung injury influence subsequent responses to aerosolized exogenous surfactant. The purpose of this study was to compare aerosolized versus tracheally instilled surfactant in a nonuniform lung injury. Adult sheep underwent whole lung lavage with subsequent HCl instillation into the right middle lobe (RML) and lingula (LING) to create a nonuniform injury. Animals were treated with either nebulized surfactant (Neb.Surf.), tracheally instilled surfactant (Inst.Surf.), or nebulized saline (Neb. Saline). PaO2, alveolar-arterial O2 gradient (PAO2-PaO2), PaCO2, and peak inspiratory pressure (PIP) values all significantly improved during 180 min of continuous aerosolization for Neb.Surf. animals compared with pretreatment values (p < 0.01) and with the other two treatment groups (p < 0.01). Although PaO2 and (PAO2-PaO2) values improved for the Inst.Surf. group by 180 min after treatment (p < 0.05), PaCO2 and PIP values were significantly increased 30 min after surfactant instillation (p < 0.05). Neb. Saline animals had no significant changes in physiologic parameters over 180 min. Approximately 8% of the total aerosolized surfactant deposited in lung tissue was recovered from the more severely damaged RML and LING, compared with approximately 50% of the total instilled surfactant recovered from these lobes. This resulted in significantly greater percentages of the total aerosolized surfactant deposited in each of the remaining lobes compared with the percent deposition of instilled surfactant (p < 0.05). Both the underlying pattern of lung injury and the exogenous surfactant delivery technique may influence clinical responses to surfactant therapy in patients with the adult respiratory distress syndrome (ARDS).

Aerosols↗
PubMed1976

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↗
PubMed1977

Pulmonary aerosol deposition in chronic bronchitis: intermittent positive pressure breathing versus quiet breathing.

Quiet breathing by mouth of a 3-mum aerosol was compared with intermittent positive pressure delivery of the same aerosol to the lung in a group of bronchitics. The pattern of lung deposition and the total dose delivered to the lung were measured. The differences between quiet breathing and intermittent positive pressure breathing were found not to be significant (P greater than 0.5). In addition, during similar or greater total ventilation, intermittent positive pressure breathing delivered a mean of 32% less aerosol to the lung than did quiet breathing. These findings suggest that intermittent positive pressure breathing as currently used for aerosol delivery cannot be expected to enhance peripheral deposition of inhaled aerosols in patients with airway obstruction.

Aerosols↗
PubMed1986

Airway responses to aerosolized methacholine and citric acid in ponies with recurrent airway obstruction (heaves).

We measured lung function and airway reactivity in response to methacholine and citric acid administered by aerosol in 2 groups of ponies (principal and control). Principal ponies had a history of heaves, a disease characterized by recurrent airway obstruction. Control ponies had no history of respiratory disease. Both principal and control ponies were paired (principal and control), and measurements were made when principal ponies were in clinical remission (Period A), following barn exposure when principal ponies had acute airway obstruction (Period B), and 1 and 2 wk after they were returned to pasture (Periods C and D). Differences between groups were primarily found at Period B. Barn housing (Period B) decreased dynamic compliance (Cdyn) and increased pulmonary resistance (RL) of principal but not of control ponies. When compared with control ponies at Period B, principal ponies demonstrated airway hyperreactivity. The dose of methacholine required to reduce Cdyn to 65% of baseline (ED65Cdyn) was lower, the change in RL induced by an aerosol of 0.1 mg/ml methacholine (delta RL 0.1) was higher, and the percent change in Cdyn in response to an aerosol of 0.1 mg/ml methacholine (delta %Cdyn 0.1) was larger in principal than in control ponies. A 10-min inhalation of 10% citric acid aerosol did not cause changes in Cdyn in either group of ponies. Control ponies did not increase RL in response to citric acid, whereas at Period B, RL of principal ponies increased following citric acid. We conclude that ponies in clinical remission from heaves are not hyperreactive to aerosols of methacholine or citric acid. Hyperreactivity only exists during acute exacerbations of airway obstruction.

Aerosols↗
PubMed1987

The role of titratable acidity in acid aerosol-induced bronchoconstriction.

We evaluated the importance of pH, titratable acidity, and specific chemical composition in acid aerosol-induced bronchoconstriction in 8 asthmatic subjects. We administered aerosols of HCl and H2SO4 at pH 2.0 in an unbuffered state and buffered with glycine. The buffered acids were given in order of increasing titratable acidity (defined as the number of ml of 1 N NaOH required to neutralize 100 ml of acid solution to pH 7.0). Each set of buffered or unbuffered acid aerosols was given on a separate day and each aerosol was inhaled through a mouthpiece during 3 min of tidal breathing. Bronchoconstriction was assessed by measurement of specific airway resistance (SRaw) before and after inhalation of each aerosol. SRaw increased by more than 50% above baseline in 1 of 8 subjects after inhalation of unbuffered HCl and in no subjects after inhalation of unbuffered H2SO4, even at pH 2.0. In contrast, SRaw increased by greater than 50% in all 8 subjects after inhalation of HCl and glycine at pH 2.0 and 7 of 8 subjects after inhalation of H2SO4 and glycine at pH 2.0. The mean titratable acidity required to increase SRaw by 50% above baseline was calculated for each challenge by linear interpolation; these values for H2SO4 and glycine (5.1 ml of 1 N NaOH) and HCl and glycine (2.2 ml of 1 N NaOH) were slightly, but significantly, different (p = 0.01) and were considerably higher than the titratable acidity of the unbuffered acids at pH 2 (1.0 ml of 1 N NaOH).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Proper aerosol inhalation technique for delivery of asthma medications.

Forty-two (42) children with asthma, 7 to 15 years old, who had been taking aerosol medications from canister nebulizers for longer than 6 months were evaluated for adequacy of aerosol inhalation technique. The mouthpiece of a canister nebulizer was modified so that actuation of the canister and inhalation through the mouthpiece could be recorded. Of 42 patients, 24 had correct inhalation technique (they synchronized the actuation of canister and inhalation); 18 (43%) did not. The most frequent mistake (11 patients) was releasing the aerosol into the mouth without inhaling. Those who inhaled incorrectly were taught the correct technique by repeated instructions and demonstrations; 11 learned it within 5 minutes, but 7 required a longer instruction period. Most had retained the technique when retested later. The physician should teach each patient the correct technique when aerosol therapy is started and should check again on follow-up examinations to assure that the patient obtains maximum benefit from aerosol therapy.

Adolescent↗
PubMed2001

Aerosolized PGE1, PGI2 and nitroprusside protect against vascular leakage in lung ischaemia-reperfusion.

High permeability oedema is an important feature in lung injury secondary to ischaemia-reperfusion. This study investigated the influence of aerosolized prostaglandin E1 (PGE1), prostaglandin I2 (PCI2) and the nitric oxide (NO)-donor, sodium nitroprusside (SNP) on microvascular barrier function in pulmonary ischaemia-reperfusion. Buffer-perfused rabbit lungs were exposed to 180 or 210 min of warm ischaemia while maintaining anoxic ventilation and a positive intravascular pressure. Reperfusion provoked a transient, mostly precapillary elevation of vascular resistance, followed by a severe increase of the capillary filtration coefficient (Kfc) versus nonischaemic controls (3.17+/-0.34 versus 0.85+/-0.05 cm3 x s(-1) cmH2O(-1) x g(-1) x 10(-4) after 30 min of reperfusion), and progressive oedema formation. Short-term aerosolization of SNP, PGE1 or PGI2 at the beginning of ischaemia largely suppressed the Kfc increase (1.36+/-0.22, 1.32+/-0.23 and 1.32+/-0.22 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4), respectively) and oedema formation. In contrast, application prior to reperfusion was much less effective, with some reduction of Kfc increase by PGI2 and SNP and no effect of PGE, (1.79+/-0.31, 2.2+/-0.53 and 3.2+/-0.05 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4), respectively). Haemodynamics, including microvascular pressure, were only marginally affected by the chosen doses of aerosolized vasodilators. It is concluded that short-term aerosolization of prostaglandin E1, prostaglandin I2 and sodium nitroprusside at the onset of ischaemia is highly effective in maintaining endothelial barrier properties in pulmonary ischaemia-reperfusion. This effect is apparently attributable to nonvasodilatory mechanisms exerted by these agents. Alveolar deposition of prostaglandins and/or nitric oxide donors by the aerosol technique may offer pulmonary protection in ischaemia-reperfusion injury.

Aerosols↗
PubMed1994

Detection of early lung impairment with aerosol bolus dispersion.

The broadening of inhaled aerosol boluses (aerosol bolus dispersion) during respiration provides a noninvasive measure of convective gas mixing in the lungs. In this study, the sensitivity and specificity of this technique for the diagnosis of early lung impairment due to cigarette smoking was evaluated. Two hundred and sixteen randomly selected subjects (126 smokers and 90 nonsmokers) were investigated with aerosol dispersion in comparison to conventional lung function tests. The cumulative cigarette consumption of the subjects was quantified by "pack-years" (PY). Smokers were classified into the following groups: 0 < PY < or = 10; 10 < PY < or = 20; 20 < PY < or = 30; and PY > 30. Forced expiratory volume in one second (FEV1), maximal expiratory flow at 25, 50 and 75% vital capacity (MEF25, MEF50 and MEF75) decreased significantly with increasing cigarette consumption. In comparison to nonsmokers, FEV1 was significantly reduced in smokers of 10 < PY < or = 30, and MEF75 was significantly reduced in smokers of PY > 20. Aerosol bolus dispersion increased with increasing PY. For all groups of smokers, even those with PY < 10, bolus dispersion was significantly increased in comparison to lifelong nonsmokers, indicating alterations in convective gas mixing in the lungs. Calculation of receiver operating characteristics for the lung function parameters under consideration showed that bolus dispersion has a higher sensitivity and specificity than conventional lung function parameters. Hence, the aerosol bolus dispersion test could be a promising epidemiological tool to study early abnormalities in intrapulmonary gas mixing due to environmental factors.

Adult↗
PubMed1997

An evaluation of two aerosol delivery systems for rhDNase.

Increasingly, proteins are delivered to the respiratory tract as an aerosol, and clinical efficacy is dependent on optimal delivery of the protein in an intact form. The object of this study was to compare the in vivo and in vitro results of two aerosol delivery systems for the aerosolization of recombinant human deoxyribonuclease I (rhDNase) in patients with cystic fibrosis (CF). Patients with CF who were to be initiated on rhDNase were randomized either to the Hudson nebulizer and Pulmo-Aide compressor or to the Sidestream nebulizer driven by the CR50 air compressor. An in vitro study was performed in six sets of the two aerosol delivery systems. One hundred and seventy three patients were randomized in this open study, where rhDNase was administered for 7 days. Improvements in pulmonary function were observed in both groups following 1 week of therapy with rhDNase. Changes in the Sidestream/CR50 and Hudson/Pulmo-Aide groups, respectively, were: 16 and 11% for forced expiratory volume in one second (p=0.14); 12 and 10% for forced vital capacity (p=0.70); and 14 and 7% for forced expiratory flow at 25-75% of expiration (FEF(25-75)) (p=0.18). A greater proportion of patients in the Sidestream/CR50 group (58%) had a >10% response in FEF(25-75) compared to the Hudson/Pulmo-Aide group (42%; p=0.03). The Sidestream nebulizer had a faster nebulization rate (p<0.05), lower mass median diameter for the aerosol mass produced (p<0.001), higher percentage of particles in the respirable range (p<0.001) and greater respirable output (p<0.005), compared to the Hudson nebulizer. The Sidestream/CR50 combination is a quicker, more efficient system in vitro than the Hudson/Pulmo-Aide combination, whereas the in vivo study only suggested a difference. Clinically, the two systems have similar efficacy.

Adult↗
PubMed1983

Ultrasonic and jet aerosolization of phospholipids and the effects on surface activity.

Surface active aerosols were produced from aqueous dispersions of mixed lipids (CLL), extracted from bovine lung lavage. Particle size distributions were measured as a function of humidity for two types of aerosol generators: ultrasonic and jet. Lipid dispersions before aerosolization were prepared by sonication in an ice bath and by mechanical vortexing. Over a range of high humidity greater than 60-70%, ultrasonic nebulization gave CLL aerosols with mass median aerodynamic diameters (MMAD) of 1.4 +/- 0.1 micron, compatible with predicted alveolar deposition fractions of 0.2-0.3 according to current deposition models. For humidities of 30-95%, jet nebulization gave MMAD values of 0.4-0.5 micron, which have lower predicted alveolar deposition. The surface pressure-time (pi - t) adsorption characteristics at 35 +/- 2 degrees C of CLL dispersions prepared initially by vortexing or sonication were not significantly affected by ultrasonic nebulization over a 1-2 h time period. In addition, the dynamic surface tension lowering of both kinds of CLL dispersion was not affected by ultrasonic nebulization (minimum surface tension less than 1 dyne/cm at 37 degrees C and 100% humidity). Current interest in the treatment of the respiratory distress syndrome (RDS) with exogenous surfactant replacement has focused largely on the delivery of surfactant replacement has focused largely on h delivery of surfactants to infants by tracheal instillation at birth. However, the ability to form multi-component surfactant aerosols with appreciable alveolar deposition fractions and high surface activity may help to expand the utility of replacement therapy to patients with aerated lungs.

Adsorption↗
PubMed2002

Aerosolized perfluorocarbon suppresses early pulmonary inflammatory response in a surfactant-depleted piglet model.

The effect of new ventilation strategies on initial pulmonary inflammatory reaction was studied in a surfactant-depleted piglet model. Sixty minutes after induction of lung injury by bronchoalveolar lavage, piglets received either aerosolized FC77 (aerosol-PFC, 10 mL/kg/h, n = 5) or partial liquid ventilation (PLV) with FC77 at functional residual capacity volume (FRC-PLV, 30 mL/kg, n = 5), or at low volume (LV-PLV, 10 mL/kg per hour, n = 5), or intermittent mandatory ventilation (control, n = 5). After 2 h, perfluorocarbon application was stopped and intermittent mandatory ventilation continued for 6 h. After a total experimental period of 8 h, animals were killed and lung tissue obtained. mRNA expression of IL-1beta, IL-6, IL-8, and TGF-beta in porcine lung tissue was quantified using TaqMan real-time PCR and normalized to beta-actin (A) and hypoxanthine-guanine-phosphoribosyl-transferase (H). In the aerosol-PFC group, IL-1beta, IL-6, IL-8, and transforming growth factor (TGF)-beta mRNA expression in lung tissue was significantly lower than in the control group. Reduction was 95% for IL-1beta/H (p < 0.001), 73% for IL-6/H (p < 0.05), 87% for IL-8/H (p < 0.001), and 38% for TGF-beta/H (p < 0.01). A lower mRNA gene expression was also determined for IL-1beta and IL-8 when the aerosol-PFC group was compared with the LV-PLV group [91% for IL-1beta/H (p < 0.001), 75% for IL-8/H (p < 0.001)]. In the FRC-PLV group, mRNA expression of IL-1beta was significantly lower than in the control (p < 0.05) and LV-PLV (p < 0.01) group. In a surfactant-depleted piglet model, aerosol therapy with perfluorocarbon but not LV-PLV reduces the initial pulmonary inflammatory reaction at least as potently as PLV at FRC volume.

Aerosols↗
PubMed2000

Aerosol delivery of muramyl dipeptide to rodent lungs.

Tuberculosis is the single most serious infectious disease worldwide. The respiratory tract is the primary site of infection by Mycobacterium tuberculosis(MTB). A number of immunogenic components of the cell wall of MTB, if delivered to the lungs as aerosols, can be used to study the local immune response. The site of deposition of these aerosols can be employed to control their residence time in the lungs. Muramyl dipeptide (MDP) aerosols were delivered to alveolar macrophages in the lungs of rodents. Guinea pig macrophages harvested by bronchoalveolar lavage were examined by differential interference contrast microscopy for morphological changes indicative of activation. Bronchoalveolar lavage fluid was analyzed for the presence of alkaline phosphatase, lactate dehydrogenase, N-acetyl-glucosaminidase (NAG), and total protein content. Rat alveolar macrophages were studied for the production of nitric oxide, by induction of nitric oxide synthase. Twenty-four hours following exposure to an aerosol of MDP, alveolar macrophages exhibited morphological characteristics (spreading and pseudopodia), enzyme activity (NAG 50% above control), and production of the reactive intermediate nitric oxide. Rat macrophages subjected to aerosol exposure to MDP when challenged with a second dose of MDP or lipopolysaccharide exhibited a linear dose response as measured by nitric oxide production. These studies indicate that the topical delivery of an MTB bacterial cell wall component, muramyl dipeptide, results in activation of alveolar macrophages. This approach may be useful in elucidating elements of the immune response to MTB.

Acetylmuramyl-Alanyl-Isoglutamine↗