Saline Aerosol Research Articles

Comparison of inhalation toxicity studies of gentamicin in rats and dogs

Nebulized gentamicin solution was administered to rats (nose-only) and dogs (face mask) for 14 days with a 14-day recovery period. Control groups of each were exposed to saline aerosols. Mean estimated inhaled lung doses of gentamicin were 39, 123 and 245 mg/kg for rats (deposited doses 6, 17 and 34 mg/kg) over 30, 90 and 180 min, respectively. Since dogs do not tolerate exposures as long as rats, inhaled lung doses were limited to 7, 14 and 41 mg/kg (deposited doses of 1, 3 and 8 mg/kg) over 15, 30 and 60 min. Comparable doses were achieved at the low dose for rats and high dose for dogs. Serum AUCs (14 ± 2 µg/mL*h (mean ± SD) at 6 mg/kg in rats and 11 ± 7 µg/mL*h at 8 mg/kg in dogs) showed comparable exposure between the two, implying similar absorbed doses and confirming similar deposited lung doses. Rat exposures resulted in dose-related lung pathology (including low dose) manifested as upper respiratory tract irritant reactions with alveolar histiocytosis, inflammation, airway epithelial metaplasia and lymphomegaly in lung tissue. This was associated with high lung tissue gentamicin levels 24 h post-dose on Day 14 (375 ± 33 µg/g at deposited dose of 6 mg/kg). Dose-related kidney tubular necrosis (a well-known toxicity of parenteral gentamicin) was observed, but no test-article related effects on lung histopathology in dogs (even at highest deposited dose of 8 mg/kg) and low levels of lung tissue gentamicin (42 ± 11 µg/g) 24 h post-dose on Day 14.

Bronchoconstriction induced by increasing airway temperature in ovalbumin-sensitized rats: role of tachykinins

This study was carried out to determine the effect of allergic inflammation on the airway response to increasing airway temperature. Our results showed the following: 1) In Brown-Norway rats actively sensitized by ovalbumin (Ova), isocapnic hyperventilation with humidified warm air (HWA) for 2 min raised tracheal temperature (Ttr) from 33.4 ± 0.6°C to 40.6 ± 0.1°C, which induced an immediate and sustained (>10 min) increase in total pulmonary resistance (Rl) from 0.128 ± 0.004 to 0.212 ± 0.013 cmH2O·ml(-1)·s (n = 6, P < 0.01). In sharp contrast, the HWA challenge caused the same increase in Ttr but did not generate any increase in Rl in control rats. 2) The increase in Rl in sensitized rats was reproducible when the same HWA challenge was repeated 60-90 min later. 3) This bronchoconstrictive effect was temperature dependent: a slightly smaller increase in peak Ttr (39.6 ± 0.2°C) generated a significant but smaller increase in Rl in sensitized rats. 4) The HWA-induced bronchoconstriction was not generated by the humidity delivered by the HWA challenge alone, because the same water content delivered by saline aerosol at room temperature had no effect. 5) The HWA-evoked increase in Rl in sensitized rats was not blocked by atropine but was completely prevented by pretreatment either with a combination of neurokinin (NK)-1 and NK-2 antagonists or with formoterol, a β2 agonist, before the HWA challenge. This study showed that increasing airway temperature evoked a pronounced and reversible increase in airway resistance in sensitized rats and that tachykinins released from the vagal bronchopulmonary C-fiber endings were primarily responsible.

Does Topical Anesthesia Using Aerosolized Lidocaine Inhibit the Superior Laryngeal Nerve Reflex?

This study was designed to evaluate the effectiveness of topical lidocaine in attenuating the laryngeal reflex and blunting hemodynamic response by inhibition of the superior laryngeal nerve in laryngeal microsurgery, which would be helpful in preventing potential complications. A prospective, randomized, double-blind study. Tertiary medical center. Fifty-four patients requiring glottic and supraglottic laryngeal microsurgery were randomly assigned to 1 of 2 groups, with equal numbers. Before surgery, 10% lidocaine was topically applied to the laryngeal surface of the epiglottis and vocal folds under direct vision in the study group and saline aerosol was applied in the control group. Heart rates, arterial blood pressure, and SPO2 were recorded at baseline, after induction, immediately before and after intubation, during the surgery, and upon extubation. Laryngospasm, agitation, and coughing were recorded during the recovery period. Heart rates, arterial pressure, and SPO2 did not differ significantly from baseline to postintubation period among the groups. SPO2 values measured similar in the remaining study. Heart rates and blood pressures were slightly decreased in the study group after lidocaine administration, but only blood pressure at pre- and post-extubation was significantly decreased in the study group (P < .05). Also laryngospasm and coughing were not statistically different between the 2 groups. There was an obvious gap between the 2 groups for agitation. Study group agitation was noted significantly lower (P < .05). These findings indicate that preoperative topical lidocaine application may be helpful in attenuating airway-circulatory reflexes in laryngeal microscopic surgery.

Deposition modeling of hygroscopic saline aerosols in the human respiratory tract: Comparison between air and helium–oxygen as carrier gases

When hygroscopic aerosols are inspired, the size and temperature of the dispersed droplets, as well as the temperature and moisture content of the carrier gas may change due to heat and mass transfer between the dispersed phase and the gas, and also between the gas and the airway walls. This two-way coupled problem is numerically analyzed, with the focus on the effect of using helium–oxygen instead of air as the carrier gas on hygroscopic size changes and deposition of aqueous solution aerosols. Coefficients of heat and mass transfer in each generation of an idealized respiratory tract are specified based on realistic assumptions. Aerosols of initially isotonic droplets are considered. Differential equations of heat and mass transfer for both the continuous and dispersed phases are numerically solved to simulate the evaporation and condensation. Once the droplet sizes are determined in each respiratory tract generation, deposition is estimated based on existing correlations for stable particles. The results include regional deposition, in percentage of inhaled NaCl, for both helium–oxygen and air for a variety of size distributions: MMD between 2.5and8.5μm and GSD of 1.7. Moreover, the size and temperature variations of the droplets as well as the temperature and humidity variations of the carrier gas are reported. To investigate the impact on deposition caused by hygroscopic size changes, the hygroscopic effectiveness is defined, which specifies the differences in He–O2 and air deposition caused by hygroscopic size changes. The results, in general, suggest that the lowest deposition fraction in the extra-thoracic region and the highest deposition fraction in the alveolar region correspond to droplets with low mass fraction, inspired with helium–oxygen.

Effects of selective phosphodiesterase 4 inhibitor on expression of aquaporin 5 in airway mucus hypersecretion model of rats

To explore the mechanism of selective phosphodiesterase 4 (PDE4) inhibitor and observe its effects on the in vitro expression of aquaporin 5 (AQP5) in a rat model of airway mucus hypersecretion. Forty healthy male rats were randomized into 4 groups (n = 10 each). The normal control and drug control groups underwent normal saline aerosol inhalation or YM976 lavage respectively for 12 days while the model and treatment groups acrolein atomization inhalation or acrolein atomization inhalation plus YM976 lavage respectively for 12 days. The middle lobe of right lung were fixed, embedded and stained by hematoxylin and eosin to observe the histological changes of small airway. The mucin secretion by goblet cells in lung tissue was tested by alcian blue staining. And the effects of selective PDE4 inhibitor on the expression of AQP5 were detected by immunohistochemical stain. Reverse transcription-polymerase chain reaction and Western blot were used to determine the levels of AQP5 mRNA and protein. In the treatment group, mucus gland hyperplasia and airway mucus hypersecretion and positive staining area ratio of alcian blue staining decreased significantly compared with the model group (10.23% ± 0.94% vs 14.74% ± 1.06%, P < 0.05). And the expression of AQP5 mRNA (1.26 ± 0.19) and protein (0.56 ± 0.13) also declined significantly versus the model group ((0.96 ± 0.17), (0.43 ± 0.15), P < 0.05). Selective PDE4 inhibitors alleviate the pathological damage of lung tissue and enhance the expression of AQP-5 in airway mucus hypersecretion.

Acute airway effects of airborne formaldehyde in sensitized and non-sensitized mice housed in a dry or humid environment

We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice were sham sensitized by saline injections and challenged by saline aerosols. Once sensitized, the mice were housed at high (85–89%) or low (<10%) relative humidity, respectively for 48h prior to a 60-min exposure to either 0.4, 1.8 or about 5ppm FA. Before, during and after exposure, breathing parameters were monitored. These included the specific markers of nose and lung irritations as well as the expiratory flow rate, the latter being a marker of airflow limitation.The sensory irritation response in the upper airways was not affected by allergic inflammation or changes in humidity. At high relative humidity, the OVA-sensitized mice had a decreased expiratory airflow rate compared to the saline control mice after exposure to approximately 5ppm FA. This is in accordance with the observations that asthmatics are more sensitive than non-asthmatics to higher concentrations of airway irritants including FA. In the dry environment, the opposite trend was seen; here, the saline control mice had a significantly decreased expiratory airflow rate compared to OVA-sensitized mice when exposed to 1.8 and 4ppm FA. We speculate that increased mucus production in the OVA-sensitized mice has increased the “scrubber effect” in the nose, consequently protecting the conducting and lower airways.

Effects of aerosolized earthworm fibrinolytic enzyme on bleomycin induced pulmonary fibrosis in rats

To explore the effects of aerosolized earthworm fibrinolytic enzyme (EFE) on bleomycin-induced pulmonary fibrosis in rats. A total of 72 male SD rats were divided randomly into 3 groups of bleomycin (BLM) group with intratracheal BLM (5 mg/kg), control group with the same dose of normal saline, then after both receiving aerosolization of normal saline once daily instead of EFE, EFE group with EFE (2500 U/kg) by aerosolization once daily after BLM instillation. Lung histopathology, immunohistochemistry for transforming growth factor β(1) (TGF-β(1)), lung hydroxyproline contents, levels of urokinase PA (uPA), tissue plasminogen activator (tPA) and PA inhibitor 1 (PAI-1) in lung and blood were observed at Days 7, 14 and 28 of experiment, respectively. Compared with BLM group, pulmonary fibrosis improved and the TGF-β(1) expression of lung tissue decreased (P < 0.01). Hydroxyproline content of lung tissue decreased in EFE group compared with BLM group ((5.8 ± 2.5) vs (9.6 ± 1.3), (6.7 ± 1.4) vs (9.7 ± 1.5), (7.5 ± 1.2) vs (9.7 ± 1.4) mg/L, P < 0.01). Compared with BLM group, the uPA levels of lung were elevated in EFE group at Days 7 and 14 ((1.04 ± 0.36) vs (0.72 ± 0.11), (0.90 ± 0.09) vs (0.75 ± 0.08) µg/L, P < 0.05). Moreover, the plasma levels uPA of increased at Days 14 and 28 ((0.32 ± 0.04) vs (0.25 ± 0.02), (0.36 ± 0.05) vs (0.28 ± 0.04) µg/L, P < 0.05). Consistently, compared with BLM group, the tPA levels of lung increased in EFE group ((4.70 ± 0.87) vs (3.01 ± 0.62), (5.72 ± 0.37) vs (3.00 ± 0.51), (6.73 ± 1.12) vs (3.18 ± 0.38) µg/L, P < 0.01) and the plasma levels of tPA also increased ((3.40 ± 0.36) vs (1.79 ± 0.38), (3.17 ± 0.37) vs (2.18 ± 0.17), (3.85 ± 0.56) vs (2.80 ± 1.06) µg/L, P < 0.01). However, compared with BLM group, the PAI-1 levels of lung decreased in EFE group ((6.04 ± 0.81) vs (8.52 ± 1.01), (6.78 ± 0.81) vs (9.81 ± 1.73), (7.63 + 0.99) vs (11.44 ± 2.54), P < 0.05) and the plasma levels of PAI-1 also decreased in EFE group ((4.82 ± 0.42) vs (6.89 ± 0.84), (5.73 ± 0.40) vs (7.30 ± 1.09), (5.64 ± 0.87) vs (7.98 ± 1.10) µg/L, P < 0.05). Earthworm fibrinolytic enzyme may decrease bleomycin-induced pulmonary fibrosis and TGF-β(1) expression while increasing fibrinolytic activation. And fibrinolytic strategies are probably useful for the therapy of fibrotic lung diseases.

CPAP Has No Effect on Clearance, Sputum Properties, or Expectorated Volume in Cystic Fibrosis

Positive expiratory pressure (PEP) is used for airway clearance in cystic fibrosis (CF) patients. Hypertonic saline (HTS) aerosol increases sputum expectoration volume and may improve respiratory secretion properties. CPAP may also be used to maintain airway patency and mobilize secretions. To evaluate if CPAP would increase the beneficial clearance effect of HTS in subjects with CF, we investigated the effects of CPAP alone and CPAP followed by HTS on sputum physical properties and expectoration volume in CF subjects. In this crossover study, 15 CF subjects (mean age 19 y old) were randomized to interventions, 48 hours apart: directed coughs (control), CPAP at 10 cm H(2)O, HTS 7%, and both CPAP and HTS (CPAP+HTS). Sputum collection was performed at baseline and after interventions. Expectorated volume was determined and in vitro sputum properties were analyzed for contact angle and cough clearability. There were no significant differences between any treatment in arterial blood pressure, heart rate, or pulse oximetry, between the 2 time points. HTS and CPAP+HTS improved cough clearability by 50% (P = .001) and expectorated volume secretion by 530% (P = .001). However, there were no differences between control and CPAP on sputum contact angle, cough clearability, or volume of expectorated secretion. CPAP alone had no effect on mucus clearance, sputum properties, or expectorated volume, and did not potentiate the effect of HTS alone in CF subjects.

Therapeutic effects of inhaling aerosolized surfactant alone or with dexamethasone generated by a novel noninvasive apparatus on acute lung injury in rats

Pulmonary surfactant (PS) administration has been attempted for the treatment of adults with acute lung injury (ALI)/adult respiratory distress syndrome. Aerosolized surfactants inhaled by spontaneous breathing may be an effective method of surfactant-based therapies. Using a noninvasive apparatus, we evaluated the therapeutic effects of aerosolized PS alone or together with dexamethasone (Dex) on a rat model of ALI. Severe ALI was induced by intravenous injection of 20% oleic acid (0.2 mL/kg) into adult Sprague-Dawley rats. Animals were divided into eight groups: sham (n = 10); model (injury only, n = 10); normal saline (NS) aerosol driven by compressed air (air-NS, n = 13); PS aerosol driven by compressed air (air-PS, n = 13); NS aerosol driven by O2 (O2-NS, n = 13); PS aerosol driven by O2 (O2-PS, n = 13); Dex aerosol driven by O2 (O2-Dex, n = 13); and PS and Dex aerosol driven by O2 (O2-PS-Dex, n = 13). Blood gases, breathing rate, lung index, total protein, and proinflammatory cytokines (tumor necrosis factor-α, interleukin 1β, interleukin 6) in the bronchoalveolar lavage fluid (BALF), and lung histology were examined. Animals treated with air-PS for 20 minutes had significantly improved lung function, reduced pulmonary edema, decreased concentration of total protein and proinflammatory cytokines in BALF, ameliorated lung injury, and improved animal survival. In the O2-PS group, the breathing rates and lung injury scores were significantly lower than that of the air-PS group. In the O2-PS-Dex group, lung edema, total protein, and inflammatory cytokines in BALF were significantly reduced in comparison with the O2-PS group. Inhalation of aerosolized PS generated by the noninvasive apparatus could significantly reduce lung injury, while using oxygen line available in the clinical wards to generate PS aerosol is more convenient and adds further benefits. This method can also be used to deliver Dex and other therapeutic agents to ameliorate lung injury.

Effect of acrolein exposure on the percentage of CD4⁺CD25⁺ regulatory T cells and expression of transcription factor Foxp3 in asthmatic rats

This work was intended to investigate the effect of acrolein fog exposure on the ratio of CD4⁺CD25⁺ regulatory T cells (Treg) and expression of transcription factor Foxp3 in asthmatic rats. Sixty 6 - 8 weeks male Wistar rats were randomly divided into 4 groups according to random number table (15 rats for each group) which were control group (animals were treated with saline), aerosolized ovalbumin (OVA) exposure group, acrolein exposure group and combined OVA and acrolein fog exposure group, respectively. The rats were exposed to air or/and to saline or OVA aerosol for 6-8 weeks respectively.24 h after the last challenge, 4 ml of peripheral blood and lung tissue were collected from each rat. The percentage of CD4⁺CD25⁺ T cells was determined by flow cytometry analysis. The concentration of interleukin-4 (IL-4) and γ-interferon (IFN-γ) in peripheral blood and lung homogenates were measured by ELISA. The protein expression of Foxp3 in the lung was detected by Western blotting. The percentage of CD4⁺CD25⁺T cells in aerosolized OVA group ((6.23 ± 1.11)%) was significantly lower than that in the normal saline group ((9.97 ± 1.23)%) (P < 0.01). The percentage of CD4⁺CD25⁺ T cells ((3.26 ± 0.84)%) in OVA combined acrolein fog exposure group was remarkably lower than that in the aerosolized OVA exposure group and in the normal saline group (P < 0.01). IL-4 in both plasma and lung ((22.57 ± 4.34), (0.86 ± 0.12) ng/L) was significantly increased in the OVA exposed rats compared with the normal saline group ((11.57 ± 2.86), (0.31 ± 0.10) ng/L) (P < 0.01). Further remarkable increase in IL-4 of both plasma and lung tissue was observed in the group exposed to both OVA and acrolein ((34.32 ± 6.21), (1.45 ± 0.32)ng/L) compared with the aerosolized OVA exposure group and the normal saline group (P < 0.05). γ-IFN of plasma and lung tissue in OVA exposed group ((59.67 ± 20.12), (0.56 ± 0.17) ng/L) was significantly decreased compared with the normal saline group ((151.74 ± 56.68), (1.54 ± 0.21) ng/L) (P < 0.01), and a further remarkable decrease in IFN-γ of plasma and lung tissue was observed in the group exposed to both OVA and acrolein ((10.12 ± 2.57), (0.49 ± 0.10) ng/L) compared with the aerosolized OVA exposure group and the normal saline group (P < 0.05). Protein expression of Foxp3 in the aerosolized OVA group (8.07 ± 0.24) was lower than that in the normal saline group (10.25 ± 0.31) (P < 0.01), while the protein expression of Foxp3 in OVA combined acrolein fog exposure group (6.38 ± 0.32) was lower than that in the normal saline group and the aerosolized OVA exposure group (P < 0.01). The number of CD4⁺CD25⁺ Treg cells and the expression of Foxp3 were likely to be altered by acrolein fog exposure, which might play an important role in acrolein induced Th1/Th2 imbalance in asthmatic rats.

Stress amplifies lung tissue mechanics, inflammation and oxidative stress induced by chronic inflammation

ABSTRACTBackground: Mechanisms linking behavioral stress and inflammation are poorly understood, mainly in distal lung tissue. Objective: We have investigated whether the forced swim stress (FS) could modulate lung tissue mechanics, iNOS, cytokines, oxidative stress activation, eosinophilic recruitment, and remodeling in guinea pigs (GP) with chronic pulmonary inflammation. Methods: The GP were exposed to ovalbumin or saline aerosols (2×/wk/4wks, OVA, and SAL). Twenty-four hours after the 4th inhalation, the GP were submitted to the FS protocol (5×/wk/2wks, SAL-S, and OVA-S). Seventy-two hours after the 7th inhalation, lung strips were cut and tissue resistance (Rt) and elastance (Et) were obtained (at baseline and after OVA and Ach challenge). Strips were submitted to histopathological evaluation. Results: The adrenals' weight, the serum cortisol, and the catecholamines were measured. There was an increase in IL-2, IL-5, IL-13, IFN-γ, iNOS, 8-iso-PGF2α, and in %Rt and %Et after Ach challenge in the SAL-S group compared to the SAL one. The OVA-S group has had an increase in %Rt and %Et after the OVA challenge, in %Et after the Ach and in IL-4, 8-iso-PGF2α, and actin compared to the OVA. Adrenal weight and cortisol serum were increased in stressed animals compared to nonstressed ones, and the catecholamines were unaltered. Conclusion & clinical relevance: Repeated stress has increased distal lung constriction, which was associated with an increase of actin, IL-4, and 8-iso-PGF2α levels. Stress has also induced an activation of iNOS, cytokines, and oxidative stress pathways.

Imaging the Postdeposition Dispersion of an Inhaled Surfactant Aerosol

Aerodynamic forces provide the primary means of distributing aerosol medications within the lungs. Partial airway obstructions can limit both air flow and aerosol penetration into diseased zones. We hypothesize that low surface tension additives may help to disperse aerosol medications after deposition in the airways, improving dose uniformity and drug delivery to underventilated regions. To test this, we performed a pilot scintigraphy study of surfactant and saline deposition and postdeposition dispersion. Because inhaled antibiotics for cystic fibrosis provide an example of where self-dispersing medications may be useful, we administered calfactant and saline aerosols with added Technetium 99m sulfur colloid (Tc-SC; 100 nm filtered) on different days in randomized order to eight cystic fibrosis (CF) subjects (average FEV(1)%, p=85 ± 12%). Nebulized delivery was matched (similar aerosol sizes and volume delivery rates, fixed breathing patterns). Tc-SC distribution in the lungs was imaged continuously for 30 min after delivery. Both aerosols were well tolerated. Aerosol distribution was mostly peripheral (58/42%) and initially similar for saline and surfactant. Changes in whole lung counts after 30 min were also similar. Peripheral lung activity decreased more rapidly on average with calfactant though the difference versus saline was not statistically significant. Central to peripheral count ratio decreased with saline and increased with calfactant and c/p changes approached significance (-0.05 ± 0.16 vs. 0.10 ± 0.10; p=0.07 Wilcoxon). Our results lack statistical significance, but suggest that inhaled calfactant increased peripheral clearance, due to either surfactant-based dispersion or mucociliary effects. Further studies are needed to define the potential for low surface tension carriers to improve drug delivery.

Radon levels assessment in some Northern Romanian salt mines

Due to their low radioactivity background, underground salt mines spaces offer a unique possibility for speleotherapy use. The knowledge of radon concentration levels in such underground environments is essential for therapeutic purposes of different respiratory and rheumatic diseases. In order to develop speleotherapy in Romania, this paper presents the results of an indoor radon concentration levels survey in some salt mines in Romania. The survey was carried out using radon monitor Pylon AB-5 system methodology validated by a CIS-P5M system. In order to investigate whether differences in depth and microclimate parameters translate into significant differences in salt mine indoor radon concentrations, have been chosen three salts mine test sites placed in the Northern part of Romania (Turda, Cacica and Ocna Dej) in stable areas of the mining field at 32-120 m depth. Environmental microclimate conditions (mean values of air temperature 10-14.5 C, air humidity 65-80%, air velocity 0.2 m/s saline aerosols and low microbial factors) have anti-bacterial, anti-microbial, and anti-inflammatory properties and recognized therapeu- tically effects on human body's health. Air temperature is one of the most important factors which need to be con- sidered when carrying out a survey of indoor radon con- centrations in salt mines because temperature largely determines close spaces ventilation rates, and ventilation habits are known to have significant effects on indoor radon concentrations. The analyzed environmental conditions and recorded low levels of indoor mean radon concentration (6.9 ± 0.39 and 96.5 ± 4.76 Bq/m 3 ) demonstrated the best suitability of the investigated three salt mines in Romania for speleotherapeutic applications.

Lung aerosol deposition in suckling infants

IntroductionAerosol therapy in infants may be greatly compromised by face mask rejection due to squirming and crying. Lung aerosol deposition in crying infants may thereby be greatly reduced. Since ‘suckling’...

Impact Assessment of Saline Aerosols on Exercise Capacity of Athletes

The treatment in natural salt mines (speleotherapy) was known since a very long time ago; the miners and other persons involved in these activities might have known about the great effects of the microclimate within salt mines upon human health, long before they were described in a book published by a Polish doctor in 1843. The effectiveness of speleotherapy is associated with the unique cave microclimate; the sodium chloride aerosols represent the main curative factor. The saline aerosols are formed off the salt walls by convective diffusion.[1] Halotherapy is the natural therapy method which boroughs the main curative factor for speleotherapy, meaning the saline aerosol particles dispersed in the salt mine microclimate.[2]The salt room microclimate should have a constant humidity (a relative air humidity of 40-60%) and a temperature of 18-24¼ Celsius, as these parameters create favourable conditions for patients and they are a stable environment for aerosols.[3-4] The precinct should also ensure a stable environment, bacteria- and allergen-free; studies have shown that the microbial contamination during a halotherapy session is of 130-200 saprophyte microorganisms to 1m3 of air (the WHO standards regarding air sterility are of > 300 microorganisms/1m3 air). Thus, a 10-20minutes break after each session is necessary to purify the air within the chamber.[1]

Effects of Repeated Stress on Distal Airway Inflammation, Remodeling and Mechanics in an Animal Model of Chronic Airway Inflammation

Background/Aims: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. Methods: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1–5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. Results: The relative adrenal weight was greater in stressed guinea pigs compared to non-stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. Conclusions: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling.

Acute inhalation of hypertonic saline does not improve mucociliary clearance in all children with cystic fibrosis

BackgroundLittle is known of how mucociliary clearance (MCC) in children with cystic fibrosis (CF) and normal pulmonary function compares with healthy adults, or how an acute inhalation of 7% hypertonic saline (HS) aerosol affects MCC in these same children.MethodsWe compared MCC in 12 children with CF and normal pulmonary function after an acute inhalation of 0.12% saline (placebo), or HS, admixed with the radioisotope 99 mtechnetium sulfur colloid in a double-blind, randomized, cross-over study. Mucociliary clearance on the placebo day in the children was also compared to MCC in 10 healthy, non-CF adults. Mucociliary clearance was quantified over a 90 min period, using gamma scintigraphy, and is reported as MCC at 60 min (MCC60) and 90 min (MCC90).ResultsMedian [interquartile range] MCC60 and MCC90 in the children on the placebo visit were 15.4 [12.4-24.5]% and 19.3 [17.3-27.8%]%, respectively, which were similar to the adults with 17.8 [6.4-28.7]% and 29.6 [16.1-43.5]%, respectively. There was no significant improvement in MCC60 (2.2 [-6.2-11.8]%) or MCC90 (2.3 [-1.2-10.5]%) with HS, compared to placebo. In addition, 5/12 and 4/12 of the children showed a decrease in MCC60 and MCC90, respectively, after inhalation of HS. A post hoc subgroup analysis of the change in MCC90 after HS showed a significantly greater improvement in MCC in children with lower placebo MCC90 compared to those with higher placebo MCC90 (p = 0.045).ConclusionsThese data suggest that percent MCC varies significantly between children with CF lung disease and normal pulmonary functions, with some children demonstrating MCC values within the normal range and others showing MCC values that are below normal values. In addition, although MCC did not improve in all children after inhalation of HS, improvement did occur in children with relatively low MCC values after placebo. This finding suggests that acute inhalation of hypertonic saline may benefit a subset of children with low MCC values.Trial RegistrationClinicalTrials.gov: NCT01293084

Insulin-like Growth Factor-binding Protein-3 (IGFBP-3) Blocks the Effects of Asthma by Negatively Regulating NF-κB Signaling through IGFBP-3R-mediated Activation of Caspases

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein known for modulating mitogenic and metabolic actions of IGFs as well as exerting a variety of biological actions not involving IGFs. Here, we show that IGFBP-3 blocks specific physiological consequences of asthma in an IGF-independent manner in vitro and in vivo. IGFBP-3 treatment effectively reduced all physiological manifestations of asthma examined in vivo (airway hyper-responsiveness, cellular and pathological changes in bronchoalveolar lavage fluid and lung tissue, and expression of numerous proinflammatory molecules). These unique IGFBP-3 effects were further confirmed in IGFBP-3-transgenic mice, thus strengthening the notion of IGFBP-3 actions within the respiratory system. Using human epithelial cells, we demonstrated the following: 1) IGFBP-3 blocks TNF-α-induced expression of proinflammatory molecules; 2) IGFBP-3 attenuates the TNF-α-induced migratory response of eosinophils; and 3) IGFBP-3 negatively regulates TNF-α-induced expression of the key NF-κB regulatory molecules IκBα and p65-NF-κB at the post-translational level. We identified that IGFBP-3 degrades IκBα and p65-NF-κB proteins through IGFBP-3 receptor (IGFBP-3R)-mediated activation of caspases thereby inhibiting TNF-α-induced activation of NF-κB signaling cascades. This unique IGFBP-3/IGFBP-3R action was further confirmed by demonstrating complete inhibition of IGFBP-3 action in the presence of caspase inhibitors as well as IGFBP-3R siRNAs. Non-IGF-binding IGFBP-3 mutants further proved the IGF-independent action of IGFBP-3. Our findings indicate that IGFBP-3 inhibits airway inflammation and hyper-responsiveness via an IGF-independent mechanism that involves activation of IGFBP-3R signaling and cross-talk with NF-κB signaling. The IGFBP-3/IGFBP-3R system therefore plays a pivotal role in the pathogenesis of asthma and can serve as a newly identified potential therapeutic target for this debilitating disease.

Endotracheal nebulization of N-acetylcysteine increases airway resistance in cats with experimental asthma

N-acetylcysteine (NAC), a mucolytic and antioxidant, is speculated to cause bronchoconstriction in cats when delivered via aerosol. We hypothesized that in cats with experimental asthma, aerosol delivery of NAC (400mg cumulative dose) via an endotracheal tube would increase airflow limitation as measured by ventilator-acquired mechanics. After endotracheal drug delivery, airway resistance and inspiratory plateau pressure (Pplat) measurements were obtained in six mechanically ventilated asthmatic cats. Results demonstrated significantly increased airway resistance (P=0.0007) compared with aerosolized saline control; Pplats were not significantly different (P=0.059). All cats exhibited at least one adverse effect: excessive airway secretions (n=3), spontaneous cough (n=2), unilateral strabismus (n=1) and post-anesthetic death (n=1). No adverse reactions were noted with saline aerosol; cough was noted in one cat with methacholine challenge. In conclusion, airway resistance and adverse reactions were documented in all cats after NAC aerosol delivery. Further studies must be performed to evaluate if it is an effective mucolytic and/or antioxidant in cats and to determine if bronchodilator pre-treatment will negate NAC-induced bronchoconstriction.

Characteristics of airway inflammatory cells and cytokines in patients with gastroesophageal refluxinduced "asthma"

Objective To observe the feature of airway inflammation in patients troubled by gastro-oesophageal reflux (GER) with asthma-like symptoms. Methods Thirty-four cases of GER with asthma symptoms, 12 with asthma and 11 healthy subjects were enrolled in this study. Sputum was induced by hypertonic saline aerosol inhalation in all patients and healthy subjects, and the sputum differential cell counts were determined. The concentration of IL-8, -6, and -5 in the supernatant of induced sputum was measured by using enzyme linked immunosorbert assay (ELISA) respectively. Results The sputum eosinophilic percentage in GERDa patients was significantly decreased (P ＜0. 05 ) and the sputum neutrophil percentage was increased as compared with those in asthmatic patients ( P ＜ 0. 05 ). The concentrations of IL-5 (52.86 ±20.25, 55.69 ± 17.72, 70.56 ± 12.63), IL-6 (22. 14 ±9. 18, 18.62 ±9.94, 15.63 ±13.61 ) in the sputum supernatant in all patients were significantly increased as compared with healthy controls (P ＜ 0. 05), and the concentration of IL-5 in asthmatic patients were higher than in GERDa patients (P ＜0. 05). The concentration of IL-8 in GERD patients (308. 33 ± 178.60, 234. 28 ± 130. 98) was significantly increase as compared with healthy controls ( 143.26 ± 32.71, P ＜ 0. 05 ). There was no significant difference in the concentration of IL-8 between asthmatic patients and healthy controls ( P ＞ 0. 05 ).Conclusion Asthma and gastroesophageal reflux are both characterized by airway inflammation. Differed with asthma obtained by airway eosinophilic inflammation and mainly elevated IL-5, the GER-triggered airway inflammation is characterized by a neutrophilic airway inflammation and mainly enhanced levels of IL-8. GER does aggravate pre-existing airway inflammation in asthmatic patients through related cytokines which is the linkage between them. Key words: Gastroesophageal reflux; Airway inflammation; Interleukin