Saline Aerosol Research Articles

Impaired Sensorineural Function after Allergen-induced Mediator Release

We tested the hypothesis that allergen-induced mediator release augments the magnitude of isocapnic dry gas hyperpnea-induced bronchoconstriction in sensitized guinea pigs. Male Hartley guinea pigs were sensitized by spontaneous inhalation of ovalbumin (OA) aerosol on days 0 and 7 of the study. On day 14, sensitized animals again breathed OA aerosol and were prospectively divided into a group that exhibited labored breathing (LB), presumably reflecting OA-induced inflammatory mediator release, and a group that did not exhibit LB at this time. Control guinea pigs breathed saline aerosol on days 0, 7, and 14. Bronchoalveolar lavage on day 17 disclosed relative eosinophilia in OA+LB, but not in OA-LB, animals. On day 17, the bronchoconstrictor responses to increasing intravenous (i.v.) doses of acetylcholine (ACh), substance P (SP), neurokinin A (NKA), and capsaicin, as well as dry gas hyperpnea, were measured in vivo in animals from each group. Control and OA-LB guinea pigs exhibited similar responses, but OA+LB animals demonstrated augmented bronchoconstriction induced by i.v. administration of ACh, SP, or NKA. However, despite their augmented responsiveness to these exogenous constrictor agonists, OA+LB animals displayed no greater bronchoconstriction after dry gas hyperpnea or i.v. capsaicin administration. It is known that both dry gas hyperpnea and i.v. capsaicin cause bronchoconstriction in guinea pigs by releasing endogenous tachykinins from airway sensory C-fibers. Thus, our results suggest that allergen-induced mediator release impairs endogenous tachykinin release from airway sensory C-fibers in guinea pigs.

Appropriate Use of Antitussives and Protussives

As a symptom of an underlying condition, cough is one of the most common reasons patients see physicians. To the majority, a cough means that 'something is wrong' and it causes exhaustion and/or self-consciousness. Patients find these reasons as well as effects on lifestyle, fear of cancer and/or AIDS or tuberculosis to be the most troublesome concerns for which they seek medical attention. The treatment of cough can be divided into two main categories: (a) therapy that controls, prevents or eliminates cough (i.e. antitussive); and (b) therapy that makes cough more effective (i.e. protussive). Antitussive therapy can be either specific or nonspecific. Definitive or specific antitussive therapy depends on determining the aetiology or operant pathophysiological mechanism, and then initiating specific treatment. Since the cause of chronic cough can almost always be determined, it is possible to prescribe specific therapy that can be almost uniformly successful. Non-specific antitussive therapy is directed at the symptom; it is indicated when definitive therapy cannot be given. Practically speaking, the efficacy of nonspecific therapy must be evaluated in double-blind, placebo-controlled, randomised studies of pathological cough in humans. Such studies have demonstrated the efficacy of dextromethorphan, codeine and ipratropium bromide aerosol in patients with chronic bronchitis. While the preferred treatment for patients with cough due to angiotensin converting enzyme (ACE) inhibitor therapy is withdrawal of the offending drugs, it may be possible to ameliorate the cough by adding nifedipine, sulindac or indomethacin to the treatment regimen. The efficacy of protussive therapy has not been well documented. Although hypertonic saline aerosol and erdosteine in patients with bronchitis, and amiloride aerosol in patients with cystic fibrosis have been shown to improve mucus clearance, their clinical utility has not been adequately studied.

Responsiveness of and interactions between airways and tissue in guinea pigs during induced constriction.

Mechanical interdependence between airways and tissues can modify the magnitude of induced bronchoconstriction. We questioned whether the guinea pig, an animal with abundant airway smooth muscle, would differ from other species in the relative responsiveness of and interactions between airways and tissues. Therefore we induced constriction with aerosolized methacholine (MCh) and partitioned responses into airway and tissue components. We measured tracheal and alveolar pressures using alveolar capsules in open-chest guinea pigs (n = 9) during mechanical ventilation [frequency = 1 Hz, tidal volume = 6 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) before and after administration of aerosols of MCh in progressively doubling concentrations (0.063-16 mg/ml). In separate animals (n = 10), measurements were made at 3-13 cmH2O PEEP. After aerosols of saline and MCh (0.125-32 mg/ml), measurements were repeated at 3, 7, and 11 cmH2O PEEP. At submaximal levels of constriction, the airways and lung tissues demonstrated similar responsiveness. Increasing PEEP increased RL and Rti and decreased Raw under baseline conditions. At low concentrations of MCh, increasing PEEP increased RL but decreased RL at the highest concentration. Increases in PEEP significantly increased Rti at all concentrations of MCh but decreased Raw only at 8 mg/ml of MCh. These observations demonstrate that, in guinea pigs, during submaximal constriction, airways and tissues behave similarly; moreover, airway-parenchymal interdependence is important in determining the level of bronchoconstriction.

Increased pulmonary response to inhaled endotoxin in lactating rats.

An important aspect of risk assessment is identification of subpopulations particularly susceptible to the effects of inhaled pollutants. The present study examined whether female rats were more sensitive during lactation to the acute pulmonary injury produced by inhaled endotoxin. Lactating and age-matched virgin female rats were exposed to aerosols of saline or endotoxin for 3 h and lavaged at 24 h after exposure. No significant differences in lactate dehydrogenase, beta-glucuronidase, total protein, and total cell and PMN counts were observed between virgin and lactating rats after exposure to saline. Each marker of pulmonary injury except beta-glucuronidase was 1.5- to 3-fold greater in lactating than in virgin female rats exposed to 29.6 micrograms/m3 endotoxin. PMNs (6-fold), total cell counts, and protein were also significantly increased (p < 0.05) in lactating rats exposed to 1.3 micrograms/m3 endotoxin, a concentration reported to occur in a number of agricultural settings. These results demonstrate that the physiologic state of lactation is associated with an increased sensitivity to the acute pulmonary injury produced by inhaled endotoxin and are consistent with previous work demonstrating a similar increased sensitivity to ozone exposure. The possibility of a similar pattern of enhanced response in analogous groups of humans merits examination.

Airway smooth muscle shortening in excised canine lung lobes

To estimate the importance of lung parenchymal airway interdependence in attenuating airway narrowing, airway smooth muscle shortening in response to nebulized carbachol was measured in excised canine lung lobes and compared with the calculated load applied by lung elastic recoil. Pulmonary resistance of matched right and left upper lobes of five dogs was measured in a pressure-compensated volume plethysmograph by forced oscillation (6 Hz) before and after administration of an aerosol of carbachol (250 mg/ml) or saline. Matched lobes were studied at transpulmonary pressures (PL) of 5, 7, 10, 12, and 15 cmH2O. The lungs were then fixed at that PL by pulmonary arterial perfusion with formaldehyde, and cross sections of multiple airways from each lobe (n = 275) were examined by use of morphometric techniques to measure luminal area and smooth muscle length. By use of the saline lobe as a control, percentage of muscle shortening and decrease in airway lumen area caused by carbachol could be calculated. Passive and active smooth muscle stresses in each airway were calculated from PL and the calculated change in peribronchial pressure for a given change in airway diameter. The increase in pulmonary resistance and average smooth muscle shortening after administration of carbachol was greater in lobes held at lower PL. There was marked variation in narrowing between airways within a lobe: smooth muscle shortening ranged between 0 and 65% but averaged < 45% at all levels of PL.(ABSTRACT TRUNCATED AT 250 WORDS)

Capsaicin pretreatment of guinea pigs in vivo prevents ovalbumin-induced tracheal hyperreactivity in vitro

The role of substance P-containing sensory nerves in the development of tracheal hyperreactivity to histamine and arecoline was investigated in an allergic model of asthma. Male Hartley-strain guinea pigs were sensitized to ovalbumin (20 mg/kg i.p.) and 14 days later exposed to either saline or ovalbumin (2%) aerosols for 8 consecutive days. One day after the last aerosol exposure the animals were killed and the tracheas were removed. Isotonic muscle shortening in response to increasing doses of histamine and arecoline was measured. Capsaicin (50 mg/kg s.c.) or vehicle pretreatment was performed 7 days prior to sensitization. Tracheas from vehicle-pretreated sensitized and ovalbumin-aerosol exposed animals had increased reactivity to both histamine and arecoline compared to saline-aerosol exposed animals. Capsaicin pretreatment did not alter tracheal reactivity in the saline-aerosol exposed group. Capsaicin pretreatment prevented the increase in tracheal reactivity caused by both agonists in sensitized and ovalbumin-aerosol exposed guinea pigs. These results suggest that capsaicin-sensitive sensory nerves are important for the development of increased tracheal reactivity in an allergic model of asthma.

Relation of the hypertonic saline responsiveness of the airways to exercise induced asthma symptom severity and to histamine or methacholine reactivity.

Conflicting views exist over whether responsiveness of the airways to hypertonic saline relates to non-specific bronchial hyperresponsiveness measured by histamine or methacholine challenge. The bronchoconstrictor responses to exercise and hypertonic saline are reported to be closely related, but the relationship between the symptoms of exercise induced asthma and airway responsiveness to hypertonic saline is not known. In 29 asthmatic patients with a history of exercise induced asthma, the response to an ultrasonically nebulised hypertonic saline (3.6% sodium chloride) aerosol, measured as the volume of hypertonic saline laden air required to produce a fall in forced expiratory volume in one second (FEV1) of > or = 20% (PD20), was compared with the concentration of histamine (PC20; group 1) and methacholine (PC20; group 2) producing a 20% fall in baseline FEV1 and exercise induced asthma symptom severity score (groups 1 and 2). The hypertonic responsiveness was determined in a dose-response manner to a maximum dose of 310 1 and the exercise induced asthma symptom severity was scored on a scale of 0-5. Of the 29 patients, 23 (79%) were responsive to the hypertonic saline, with PD20 values ranging from 9 to 310 1. A significant correlation was found between the PD20 hypertonic saline and the exercise induced asthma symptom score. There was no significant correlation between the PD20 response to hypertonic saline and the histamine PC20 or methacholine PC20. The exclusion of those subjects who failed to respond to hypertonic saline improved the relationship between hypertonic saline and methacholine PC20. No significant correlation was found between the exercise induced asthma symptom score and histamine PC20 or methacholine PC20. These findings suggest that hypertonic saline responsiveness bears a closer relationship to the severity of exercise induced asthma symptoms than to the non-specific bronchial hyperresponsiveness measured by histamine or methacholine reactivity.

Late phase bronchoconstriction and eosinophilia as well as methacholine hyperresponsiveness in Ascaris-sensitive rhesus monkeys were reversed by oral administration of U-83836E.

We used the Ascaris-sensitive primate model to assess the effect of oral doses of the 2-aminochroman (U-83836E) lazaroid on the antigen-induced late phase (24 h) bronchoconstriction (LPBC), eosinophilia and methacholine hyperreactivity. Following establishment of consistent lung resistance measurements and bronchoalveolar lavage eosinophilia in 4 Ascaris reactor primates, we determined the baseline aerosol mecholyl provocative challenge for 50% increase (PC50 in mg/ml) in these animals. Twenty-four hours following antigen challenge, we again determined the PC50 (mg/ml). In all 4 animals, there was a statistically significant decrease in PC50 (5.4- to 32-fold, n = 5-7; p < 0.029). Bronchoconstriction at 24 h increased in all 4 (49-86% over saline aerosol, p < 0.05). Eosinophilia increased from 21 to an average of 33% of total cells (p < 0.05 compared to saline). Repeating the antigen challenge in the presence of oral doses of 10 mg/kg U-83836E 18 and 3 h before and 6 h after challenge resulted in 53-70% inhibition of LPBC, 53-81% inhibition of eosinophilia (p < 0.05 compared to Ascaris) and return of the mecholyl PC50 (mg/ml) to before antigen levels (p = NS) thus blocking increased hyperreactivity. These results indicate U-83836E, like steroids, would be an effective drug for asthma and lung inflammation.

Real-Time Measurements of Cardiac Effects During Inhalation Exposures of Monkeys or Dogs

AbstractA relevant animal model has been developed to aid in establishing safety guidelines for workplace inhalation exposures to cardioactive agents. A telemetry system was used to monitor heart rate and electrocardiogram (ECC) waveform effects noninvasiveiy during whole-body inhalation exposures of a group of four unrestrained, conscious monkeys or dogs. This method has been evaluated by measuring responses to aerosols of a known β-agonist (isoproterenol), and representative “inert” aerosols, saline, and dust (clay). A saline aerosol had no effects on heart rate or ECC at concentrations up to 6.5 mg/m3. Heart rates decreased slightly in monkeys during exposure to clay aerosols at concentrations of 5 mg/m3 or higher. Clay aerosol had no effect on heart rates in dogs. A dose-response relationship was demonstrated for isoproterenol aerosol. Mean heart rate in monkeys increased 0, 13, 18, 27, and 54% during exposures to 0.6, 1.0, 1.4, 2.5, and 4.9 mg isoproterenol/m3. In dogs, mean heart rate increased 6, 2...

Pulmonary effects of chronic exposure to liposome aerosols in mice.

Administering liposome-encapsulated drugs by aerosols could be a feasible way of targeting drugs to the lung, specifically to pulmonary alveolar macrophages (AM). In the mouse model, we characterized uptake of carboxyfluorescein- (CF-) labeled liposomes by AM in vivo after acute inhalation of liposome aerosols, and the effects of chronic exposure to liposome aerosols on lung histology and AM function. Mice were placed in a nose-only exposure module and exposed to liposome or saline aerosols for 1 h per day, 5 days per week, for 4 weeks. Five mice of both the experimental and control groups were removed weekly and their lungs examined. Liposomes were made from hydrogenated soy phosphatidylcholine (HSPC) at 50 mg/mL. In vivo uptake of liposomes by AM was documented by fluorescence microscopy and flow cytometry of bronchoalveolar lavage (BAL). A consistent amount of 1-3 micrograms of lipid inhaled per dosing per mouse was estimated from fluorescence measurements. Addition of Triton X-100 to BAL caused a significant increase in fluorescence intensity, indicating that liposomes remained intact in the lung for a period of time. The chronic inhalation study showed no histologic changes of the lung or untoward effects on the general health or survival of animals. AM phagocytic function, intracellular killing, and fatty acid composition were not affected. Transmission electron microscopy and morphometry (computerized image analysis) of AM likewise showed no alterations as a result of the treatment. It was concluded that AM uptake of liposomes delivered by aerosol was operant in vivo. This finding validates the concept of alveolar macrophage-directed delivery of liposome-encapsulated agents to the lung via inhalation. It was also concluded that chronic liposome aerosol inhalation in mice produced no untoward effects on survival, histopathology, and macrophage function. These data confirm and extend prior findings regarding the functional and morphologic interactions of liposomes with AM in vitro (Gonzalez-Rothi et al., Exp. Lung Res. 17:687-705, 1991).

Effect of Sodium Hypochlorite on Specific Airway Resistance and Airway Reactivity in Guinea Pigs

To evaluate the effect of sodium hypochlorite (NaOCl) on specific airway resistance (SRaw) and the possibility that NaOCl is involved in causing airway hyperreactivity, we studied the effect of exposure to NaOCl aerosol on SRaw and airway reactivity to inhaled histamine aerosol in intact, unanesthetized, spontaneously breathing guinea pigs. A 1-min inhalation of 1.2–10.0% NaOCl caused an increase in SRaw in three of six animals in a concentration-dependent manner. To assess the airway reactivity, the effective concentration of histamine that produced a doubling of baseline SRaw (EC200His) was determined. A 5-min inhalation of 3.6% NaOCl aerosol caused an acute decrease in EC200His without a corresponding change in SRaw, whereas a 5-min inhalation of normal saline caused no significant changes in SRaw and EC200His. Therefore, a 5-min inhalation of 3.6% NaOCl induced airway hyperreactivity. On the contrary, a 15-min inhalation of 3.6% NaOCl did not cause significant changes in mean EC200His values at 5 min, 5 hr, and 1 week after exposure. The mean SRaw at 5 hr after a 15-min inhalation of 3.6% NaOCl was higher than that of the baseline value. A 15-min inhalation of normal saline aerosol caused an increase in EC200His i.e., reduced airway reactivity, 5 min after exposure. The increased EC200His returned to baseline level at 5 hr and 1 week after exposure. A 15-min inhalation of normal saline caused no significant change in SRaw during the study period.Our study indicates that acute NaOCl aerosol inhalation causes a temporary increase in SRaw and airway hyperreactivity to inhaled histamine in guinea pigs.

Antigen-induced hyperresponsiveness to methacholine in ventilated, anesthetized guinea pigs

Guinea pigs were actively sensitized to ovalbumin and exposed 2-3 weeks later to an aerosol of ovalbumin or saline. Changes in lung function were assessed 0.5, 1, 6, 24 and 72 h later by measuring the peak increase in pulmonary inflation pressure induced by i.v. methacholine during constant-volume ventilation. Responses to methacholine were significantly potentiated at 0.5, 1, 6 and 24 h but not at 72 h following exposure to antigen. Hyperresponsiveness to methacholine was maximal at 0.5-1 h and, in terms of magnitude, comparable to the early increase in airway reactivity found in mild asthmatics after allergen challenge. Whether the hyperresponsiveness to methacholine induced by antigen in the guinea pig can be attributed solely to an increase in airway reactivity or is due, at least in part, to decreased lung compliance requires further study.

Induction of pancreatic acinar pathology via inhalation of nicotine.

This study was conducted to determine the effects of nicotine inhalation on the onset, progression, and sequential development of pancreatic lesions. Male Sprague-Dawley rats in groups of five were exposed to saline or nicotine aerosol twice daily for 15, 30, 45, and 60 min for 21 days. After sacrifice, blood samples were analyzed for plasma levels of nicotine, glucose, gastrin, and cholecystokinin. Pancreatic tissues were examined for pathological lesions. While there were no significant differences in plasma levels of glucose, gastrin, and cholecystokinin in all groups, there was a steady increase in plasma levels of nicotine with increased exposures to nicotine. Histopathological examination of pancreatic tissue revealed definitive pancreatic injuries that also appeared to be directly correlated with increased duration of nicotine exposure. The pathological changes of the pancreas were confined only to acinar cells of the exocrine pancreas. Two main types of cellular changes were observed: cellular swelling/vacuolation and nuclear condensation/cellular pyknosis. Both of these changes indicated tissue injuries in the pancreas. Transformation of the glandular acini to solid masses of epithelial cells was also observed. The results from our present study strongly suggest that the exocrine pancreas is very sensitive and susceptible to nicotine toxicity. Our data further indicate that early morphological changes in the pancreas induced by nicotine may occur without functional or metabolic alterations; however, such changes could occur at a later stage, when tissue and cellular changes become more extensive.

Tissue viscance during induced constriction in rabbit lungs: morphological-physiological correlations

Tissue viscance (Vti), the pressure drop across the lung tissues in phase with flow, increases after induced constriction. To gain information about the possible site of response, we induced increases in Vti with methacholine (MCh) and attempted to correlate these changes with alterations in lung morphology. We measured tracheal (Ptr) and alveolar pressure (PA) in open-chest rabbits during mechanical ventilation [frequency = 1 Hz, tidal volume = 5 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] under control conditions and after administration of saline or MCh (32 or 128 mg/ml) aerosols. We calculated lung elastance (EL), lung resistance (RL), Vti, and airway resistance (Raw) by fitting the equation of motion to changes in Ptr and PA. The lungs were then frozen in situ with liquid nitrogen (PEEP = 5 cmH2O), excised, and processed using freeze substitution techniques. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed area (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), the standard deviation of Lm (SDLm), and an atelectasis index (ATI) derived by calculating the ratio of tissue to air space using computer image analysis. RL, Vti, and EL were significantly increased after MCh, and Raw was unchanged. A/Ar, Lm, SDLm, and ATI all changed significantly with MCh. Log-normalized change (% of baseline) in Vti significantly correlated with A/Ar (r = -0.693), Lm (r = 0.691), SDLm (r = 0.648), and ATI (r = 0.656). Hence, changes in lung tissue mechanics correlated with changes in morphometric indexes of parenchymal distortion and airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous sensory neuropeptide release enhances nonspecific airway responsiveness in guinea pigs.

To test whether endogenous sensory neuropeptide release results in airway hyperresponsiveness to exogenous bronchoconstrictor stimuli, male Camm-Hartley guinea pigs were exposed either to capsaicin aerosol for 10 min (CAP-AER) or to saline aerosol (SAL-AER) as a control condition. The following day, animals were anesthetized, tracheostomized, and beta-adrenergically blocked with propranolol, and their bronchoconstrictor responses to intravenously administered acetylcholine (ACh), neurokinin A (NKA), or capsaicin were measured. The bronchoconstriction induced by isocapnic dry gas hyperpnea also was assessed. Compared with the SAL-AER control group, the CAP-AER-treated animals exhibited augmented bronchoconstrictor responses to ACh and NKA. In contrast, the SAL-AER and CAP-AER groups had equivalent bronchoconstrictor responses to dry gas hyperpnea and to intravenously administered capsaicin. CAP-AER treatment caused neutrophilic airway inflammation, as reflected in increased numbers of neutrophils in bronchoalveolar lavage fluid obtained from CAP-AER-treated animals. Ablation of airway c-fiber neuron function (by chronic pretreatment with capsaicin prior to capsaicin aerosol inhalation) eliminated the ACh hyperresponsiveness observed in the CAP-AER-treated animals, demonstrating that sensory nerve products play a key role in the development of this nonspecific hyperresponsiveness. Our results demonstrate that sensory nerve stimulation with capsaicin aerosol leads to nonspecific bronchoconstrictor hyperresponsiveness and cellular airway inflammation, and thus disclose another potentially important role of sensory nerves in regulating airway function.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhaled Lidocaine for Prevention of Hemodynamic Changes in Laryngoscopy and Intubation

This study was undertaken to examine the efficacy of lidocaine aerosol pretreatment in attenuating hemodynamic (HD) responses secondary to laryngoscopy and tracheal intubation in patients undergoing surgery for intracranial space occupying lesions (ICSOL). A semiclosed breathing system was improvised to generate aerosol of consistent density. Five percent lidocaine was nebulized in two different dosages (0.2 and 0.1 ml/kg in groups A and B, respectively); group C (control) received aerosol of normal saline. The average aerosol-treatment time was 24, 12, and 16 min in groups A, B, and C, respectively. Changes in heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and rate pressure product (RPP) were analyzed by analysis of variance (ANOVA). In group A, tracheal intubation did not cause significant HD changes. In group B, a significant increase was observed in each HD parameter which, when compared with control, was less severe. Lidocaine toxicity, regurgitation, nausea, vomiting, or aspiration did not occur in any patient. Patients accepted the procedure well. This study found efficacy of the technique to be related to duration of aerosol treatment.

Prostaglandin E2 inhalation increases the sensation of dyspnea during exercise.

To clarify the role of vagal afferents from the lung in the sensation of dyspnea, we examined the effects of prostaglandin E2 (PGE2) inhalation on the sensation of dyspnea during exercise in eight normal male subjects. This intervention was chosen because inhaled PGE2 is known to stimulate vagal afferent receptors in the lung, in particular C-fiber endings, without a significant increase in airway resistance. After either physiologic saline or PGE2 aerosol (100 micrograms/ml) inhalation through a Bird nebulizer for 2 min, exercise tests were performed on a bicycle ergometer. The tests consisted of 3 min at rest followed by graded work loads (zero to 150 watts, 50-watt increments). Minute ventilation (VE) and respiratory rate were monitored from an expiratory line through a face mask. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were calculated from samples of mixed expired gas. The sensation of difficulty in breathing (dyspnea) was measured on a modified Borg scale at rest and at the end of each work load. We found that although airway resistance and lung volume did not change significantly between saline and PGE2 inhalations, inhaled PGE2 significantly increased the magnitude of the dyspneic sensation when compared with inhaled saline at the same levels of work load, ventilation, and oxygen consumption. These results suggest that in addition to probable roles of motor command and chemical drive, afferent vagal activity from the lung also contributes to the sensation of dyspnea during exercise.

Changes in the cellular profile of induced sputum after allergen-induced asthmatic responses.

Allergen inhalation causes airway inflammation and an increase in histamine airway responsiveness. We have used cell counts in sputum induced by hypertonic saline aerosol to assess airway inflammation before and 32 h after asthmatic responses to allergen. Twelve asthmatic subjects (mean age, 27.4 yr; range, 20-38 yr) had an inhalation test with D. farinae, ragweed pollen, or cat extract. All of them developed an early response with a fall in FEV1, of 24.8% (SD, 6.3%); nine of 12 had a definite late response (fall in FEV1 greater than or equal to 15%), and 10 of 12 had an increase in airway responsiveness to histamine at 32 h (PC20 reduced by greater than twofold). Sputum was induced by hypertonic saline after the histamine test, before and 32 h after the allergen challenge, at the same time of day. The quality of the sample was scored according to visual inspection and inverted microscopy and by salivary contamination. Plugs arising from the lower respiratory tract were selected for further evaluation. Differential cell counts of eosinophils (Eo) and metachromatic cells (MCC) (mast cell and basophils) were obtained from direct smears, blind to the clinical procedures. The mean fall in FEV1 after hypertonic saline was 6.4% (range, zero to 28%). The sputum samples were adequate in 79.5% of attempts. Eo and MCC increased significantly from 3.8 (4.4) to 18.2 (22.8)% (p = 0.01) and from 0.05 (0.17) to 0.25 (0.76)% (p = 0.04), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Acid Aerosols on Airway Responsiveness in Asthmatics

ABSTRACT Most investigations have shown that short-term exposure to acid aerosols did not cause airway obstruction in normal subjects at concentrations up to 1 mg/m3, whereas some studies could demonstrate adverse effects in asthmatic subjects at concentrations of 0.1 mg/m3 or higher. Inhalation of acid aerosols may produce airway hyperreactivity to carbachol in normal subjects and may enhance airway hyperreactivity in asthmatic subjects. We investigated 12 patients with bronchial asthma inhaling aerosols of either saline (S), ammonium sulfate (AS), or sulfuric acid (SA). Two inhalations of 10 min were performed 30 min apart. Thirty minutes later, a hyperventilation challenge with 0.75 ppm SO2 was performed. We determined the ventilation rate necessary to increase SRaw by 100%, PV100SRaw, by stepwise increasing ventilation. The response showed large variation after AS and SA, with no significant differences between the first and the second inhalation. SRaw was significantly increased after AS. Mean PV100S...

Inflammatory mediators and cellular infiltration of the lungs in a guinea pig model of the late asthmatic reaction

Alterations in cell numbers, vascular permeability, and concentrations of various inflammatory mediators in the lung were measured in a guinea pig model of the late asthmatic reaction. Animals sensitized by inhalation of ovalbumin were challenged with an aerosol of ovalbumin or saline, and bronchoalveolar lavage fluid (BALF) and peripheral blood were collected after periods ranging from 5 min to 72 h. Increased vascular leakage within the lungs was indicated by elevated BALF/plasma albumin ratios at all time points, and was maximal 6 h after challenge. There were increased numbers of eosinophils in BALF by 6 h after challenge and they remained elevated at least until 72 h. A corresponding increase in the proportion of blood leukocytes represented by eosinophils was observed at 6 and 17 h, which suggests that these cells may be drawn to the lung following their release into the circulation, but by 72 h the proportion in blood had returned to normal. A transitory neutrophilia was evident in BALF and blood 6 h after allergen exposure, but there were no allergen-induced changes in BALF numbers of macrophages, lymphocytes, epithelial cells, or mast cells (as assessed by concentrations of cell-associated histamine). beta-Glucuronidase activity was significantly increased in BALF of guinea pigs at 2 h and 17 h following challenge. The degree to which eicosanoids can be recovered in BALF was investigated by instilling a range of tritiated compounds into the lungs of normal guinea pigs at the time of lavage. Ratio high-performance liquid chromatography revealed that there had been little metabolism of the eicosanoids recovered in BALF. However, there was evidence for a rapid removal of these mediators from the lung, a process which will militate against their accurate quantitation in BALF. Histamine, prostaglandin D2, and thromboxane B2 were detected in BALF but did not differ between treatment groups, and levels showed no simple relationship with the other inflammatory changes measured.