Allergic alveolitis due to herb dust exposure.
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We report an episode of allergic alveolitis in a female farmer due to massive exposure to organic dust contaminated with microorganisms during threshing of herbs (thyme). The patient's medical history, the results of exposure test, inhalation challenge, and bronchoalveolar lavage suggested the diagnosis of allergic alveolitis (+info)
Cidofovir protects mice against lethal aerosol or intranasal cowpox virus challenge.
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The efficacy of cidofovir for treatment of cowpox virus infection in BALB/c mice was investigated in an effort to evaluate new therapies for virulent orthopoxvirus infections of the respiratory tract in a small animal model. Exposure to 2(-5)x10(6) pfu of cowpox virus by aerosol or intranasally (inl) was lethal in 3- to 7-week-old animals. One inoculation of 100 mg/kg cidofovir on day 0, 2, or 4, with respect to aerosol infection, resulted in 90%-100% survival. Treatment on day 0 reduced peak pulmonary virus titers 10- to 100-fold, reduced the severity of viral pneumonitis, and prevented pulmonary hemorrhage. The same dose on day -6 to 2 protected 80%-100% of inl infected mice, whereas 1 inoculation on day -16 to -8 or day 3 to 6 was partially protective. Cidofovir delayed but did not prevent the death of inl infected mice with severe combined immunodeficiency. Treatment at the time of tail scarification with vaccinia virus did not block vaccination efficacy. (+info)
Work-related eye symptoms and respiratory symptoms in female cleaners.
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A prospective study was conducted in order to describe the incidence of eye symptoms, nose or throat symptoms, asthma and bronchitis among cleaners compared with former cleaners and according to the 'use of sprayers'. In 1989 and in 1991 questionnaire-based studies were conducted among female cleaners employed at Danish nursing homes, schools and offices. A cohort of 1,011 females was followed over two years. At baseline in 1989, the average age was 45 years and the average of seniority was 10 years. Overall, the cleaners tended to have the same or higher risk of developing respiratory symptoms compared to former cleaners. The 'use of sprayers' during the follow-up period was associated with an increased risk of eye and respiratory symptoms. (+info)
In vitro cytotoxicity of textile paint components linked to the "Ardystil syndrome".
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The spraying of a paint formula (Acramin F system) had led to severe pulmonary disease in textile printing sprayers in Spain and Algeria (Ardystil syndrome). In order to elucidate the underlying mechanisms of the toxicity of this paint and its main polymeric components, Acramin FWR, Acramin FWN, Acrafix FHN, and Acramoll W, we have undertaken studies using a battery of different cell-types and assessing in vitro cytotoxicity by measuring LDH leakage. This study shows that, as in in vivo studies, the three polycationic paint components, Acramin FWR (a polyurea), Acramin FWN (a polyamide-amine), and Acrafix FHN (a polyamine) exhibited considerable cytotoxicity (LC50 generally below 100 microg/ml for an incubation of 20-24 h) in vitro, while Acramoll W, which is not a polycation, was almost non-toxic (in the concentration range tested). The cytotoxicity was comparable in primary cultures of rat and human type II pneumocytes and alveolar macrophages as well as in the pulmonary cell line A549 and the hepatic cell line HepG2. In human erythrocytes, the toxicity was less pronounced. We speculate that the multiple positive charges play an important role in the toxic mechanism. It is concluded that Acramin FWR and Acramin FWN have similar intrinsic toxicity and that these polymeric compounds, which have no irritant properties or systemic toxicity when given orally, exert a high, unexpected, degree of cytotoxicity. (+info)
A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group.
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OBJECTIVE: We sought to compare the acute hemodynamic effects of inhaled nitric oxide (NO) and aerosolized iloprost in primary pulmonary hypertension (PPH). BACKGROUND: Inhalation of the stable prostacyclin analogue iloprost has recently been described as a novel therapeutic strategy for PPH and may offer an alternative to continuous intravenous infusion of prostacyclin or inhalation of NO. METHODS: During right heart catheterization, 35 patients with PPH sequentially inhaled 40 ppm of NO and 14 to 17 microg of iloprost, and the effects on hemodynamics and blood gases were monitored. RESULTS: Both NO and iloprost caused significant increases in cardiac output, mixed-venous oxygen saturation and stroke volume as well as significant decreases in pulmonary artery pressure and pulmonary vascular resistance, whereas only inhaled iloprost significantly increased the arterial PO2 (p = 0.01). Compared with inhaled NO, aerosolized iloprost was more effective in reducing pulmonary artery pressure (-8.3 +/- 7.5 mm Hg vs. -4.3 +/- 8.8 mm Hg; p = 0.0001) and the pulmonary vascular resistance (-447 +/- 340 dynes x s x cm(-5) vs. -183 +/- 305 dyne x s x cm(-5); p < 0.0001). Furthermore, aerosolized iloprost caused a significantly greater increase of the cardiac output compared with NO (+0.7 +/- 0.6 liter/min vs. +0.3 +/- 0.4 liter/min; p = 0.0002) and had a more pronounced effect on the mixed-venous oxygen saturation (p = 0.003). CONCLUSIONS: During acute drug testing, aerosolized iloprost was more potent than inhaled NO as a pulmonary vasodilator in PPH at the doses used in this study. (+info)
Subthreshold doses of specific phosphodiesterase type 3 and 4 inhibitors enhance the pulmonary vasodilatory response to nebulized prostacyclin with improvement in gas exchange.
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Aerosolized prostacyclin (PGI(2)) has been suggested for selective pulmonary vasodilation, but its effect rapidly levels off after termination of nebulization. Stabilization of the second-messenger cAMP by phosphodiesterase (PDE) inhibition may offer a new strategy for amplification of the vasodilative response to nebulized PGI(2). In perfused rabbit lungs, continuous infusion of the thromboxane mimetic U46619 was used to establish stable pulmonary hypertension [increase in pulmonary arterial pressure (pPA) from approximately 7 to approximately 32 mm Hg], which is accompanied by progressive edema formation and severe disturbances in gas exchange with a predominance of shunt flow (increase from <2 to approximately 58%, as assessed by the multiple inert gas elimination technique). In the absence of PGI(2), dose-effect curves for intravascular and aerosol administration of the specific PDE3 inhibitor motapizone, the PDE4 inhibitor rolipram, and the dual-selective PDE3/4 inhibitor tolafentrine on pulmonary hemodynamics were established (potency rank order: rolipram > tolafentrine approximately motapizone; highest efficacy on coapplication of rolipram and motapizone). Ten-minute aerosolization of PGI(2) was chosen to effect a moderate pPA decrease (approximately 4 mm Hg; rapidly returning to prenebulization values within 10-15 min) with only a slight reduction in shunt flow (approximately 49%). Prior application of subthreshold doses of i.v. or inhaled PDE3 or PDE4 inhibitors, which per se did not affect pulmonary hemodynamics, caused prolongation of the post-PGI(2) decrease in pPA. The most effective approach, rolipram plus motapizone, amplified the maximum pPA decrease in response to PGI(2) to approximately 9 to 10 mm Hg, prolonged the post-PGI(2) vasorelaxation to >60 min, reduced the extent of lung edema formation by 50%, and decreased the shunt flow to approximately 19% (i.v. rolipram/motapizone) and 28% (aerosolized rolipram/motapizone). We conclude that lung PDE3/4 inhibition, achieved by intravascular or transbronchial administration of subthreshold doses of specific PDE inhibitors, synergistically amplifies the pulmonary vasodilatory response to inhaled PGI(2), concomitant with an improvement in ventilation-perfusion matching and a reduction in lung edema formation. The combination of nebulized PGI(2) and PDE3/4 inhibition may thus offer a new concept for selective pulmonary vasodilation, with maintenance of gas exchange in respiratory failure and pulmonary hypertension. (+info)
Chemoprevention of pulmonary carcinogenesis by brief exposures to aerosolized budesonide or beclomethasone dipropionate and by the combination of aerosolized budesonide and dietary myo-inositol.
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This investigation is part of an effort to develop chemoprevention for carcinogenesis of the lung. It focuses on the efficacy of low doses of synthetic glucocorticoids administered either as single agents or in combination with a second compound, myo-inositol. Glucocorticoids are potent inhibitors of carcinogenesis. The use of low doses is important to avoid potential side-effects. The synthetic glucocorticoid budesonide, administered by aerosol for 20 s three times a week, was studied to determine its effects on benzo[a]pyrene-induced pulmonary adenoma formation in female A/J mice. Two dose levels were employed, 10 and 25 microg/kg body wt. The lower dose produced a 34% reduction in lung tumor formation and the higher dose level a 60% reduction in lung tumors. In additional groups of mice, the effects of 0.3% myo-inositol added to the diet was found to reduce pulmonary tumor formation by 53%. The two agents given in combination resulted in a greater inhibition of lung tumor formation than either by itself. Budesonide at 10 microg/kg body wt plus 0.3% myo-inositol reduced the number of tumors by 60% and budesonide at 25 microg/kg body wt plus 0.3% myo-inositol reduced lung tumor formation by 79%. To determine whether a glucocorticoid other than budesonide would have inhibitory effects in this experimental model, beclomethasone dipropionate administered by aerosol for 20 s three times a week was studied as a single agent and showed almost identical inhibitory properties to budesonide. The doses of the glucocorticoids calculated on a daily basis are within the range of those used widely for control of chronic allergic respiratory diseases in the human. The capacity of low doses of inhaled glucocorticoids to prevent pulmonary neoplasia and the enhancement of this preventive effect by myo-inositol, an essentially non-toxic compound, are findings that should encourage further work to evaluate the applicability of these agents to the prevention of neoplasia of the lung in the human. (+info)
Bronchial vasodilation evoked by increased lower airway osmolarity in dogs.
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Hyperosmotic saline solutions stimulate lower airway sensory nerves. To determine whether airway hyperosmolarity evokes neurally mediated changes in bronchial artery blood flow (Qbr), we measured the effect of injection of small volumes (1 ml) of hyperosmotic saline into a right lobar bronchus on Qbr of anesthetized, artificially ventilated dogs. In 14 dogs, hyperosmotic saline (1,200 and 2,400 mmol/l) increased Qbr by 58 +/- 12 (SE) and 118 +/- 12%, respectively, from a baseline of 8 +/- 2 ml/min. Qbr increased within 6-8 s of the injections, peaked at 20 s, and returned to control over 2-3 min. Isosmotic saline had minimal effects. In contrast, hyperosmotic saline decreased flow in an intercostal artery that did not supply the airways. The bronchial vasodilation was decreased by 72 +/- 11% after combined blockade of alpha-adrenoceptors and muscarinic cholinergic receptors and by 66 +/- 6% when the cervical vagus nerves were cooled to 0 degrees C. Blockade of H(1) and H(2) histamine receptors did not reduce the nonvagal response. We conclude that hyperosmolarity of the lower airways evokes bronchial vasodilation by both a centrally mediated reflex that includes cholinergic and adrenergic efferent pathways and by unidentified local mechanisms. (+info)