Immediate Allergic and Nonallergic Reactivity of the Airways in &lt;i&gt;Ascaris&lt;/i&gt; Skin-Sensitive Sheep

Mensing²,

Fricke³

et al. 1998

Respiration

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Airway hyperresponsiveness (AHR) to water-soluble cooling lubricants (CL) induced by aerosol administered by tracheal tube was studied in a rabbit model of occupational lung disease. Two commercial CL were examined: the first was of the boric acid amine ester type without biozide (CL-BAE), the second was of the sulfonate type with biozide (CL-SB). 50, 5.0 or 0.5 mg/m³ CL was administered over a period of twice 2 h to six different groups of rabbits. Airway responsiveness (AR) to aerosols of 0.2% and 2.0% acetylcholine solution (ACH) was measured before and after each exposure to CL. A control group A of nine animals not exposed to CL showed no significant respiratory responses following inhalation of 0.2% ACH for 1 min. Conversely, inhalation of 2.0% ACH almost doubled the dynamic elastance (E_dyn) in the ACH challenge test in this animal group. Airway resistance (R_I), E_dyn, slope of inspiratory pressure generation (ΔP_es/t_I), arterial pressure (P_a) and arterial blood gas tensions (P_aO₂, P_aCO₂) were not significantly altered during and after exposures to CL. However, after CL-BAE inhalation of 50 and 5 mg/m³ over 4 h, the amplitude of the ACH-induced airway obstruction indicated by the changes in E_dyn rose significantly to almost five times the control response before exposure (group C, D, p < 0.005). Similar changes in R_I and ΔP_es/t_I were obtained. After inhalation of 0.5 mg/m³ CL-BAE (group D), no significant changes in AR were observed. Similar to CL-BAE inhalation of 50 mg/m³, CL-SB caused enlarged AR in the ACH challenge test (group E), whereas no significant changes were found after exposure to 5.0 and 0.5 mg/m³ in groups F and G. In summary, CL aerosols with and without biozide in the range of 50 and 5 mg/m³ applied via tracheal tubes increased AR to ACH within 4 h of exposure in a time- and concentration-dependent manner. It has to be assumed that this augmented AR indicates an increased risk of developing lubricant-induced obstructive lung diseases.

Section: Discussionmentioning

confidence: 54%

Water-Soluble Cooling Lubricants Induce Airway Hyper- responsiveness in Rabbits

Mensing²,

Fricke³

et al. 1998

Respiration

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“…The different response times may depend on the activity of cholinesterase [10] or on histamine-degrading enzymes such as histamine N-methyltransferase and diamine oxi dase in humans and experimental animals [22]. Elevated histamine levels in arterial blood disappeared within 5-10 min after histamine and ACH challenge in our sheep [4,19] and also after MCH provocation.…”

Section: Discussionmentioning

confidence: 99%

“…Local mediator release in the airway mucosa along with neuronal vagal mechanisms represent the basic pathomechanisms of airway obstruction induced by the inhalation of unspecific pharmacological substances or specific allergens [1][2][3][4]. Airway challenges with aerosol ized allergens are known to induce histamine release from mast cells, basophils and alveolar macrophages [5] and may cause inflammatory responses in the lungs of human subjects [6,7] as well as in experimental animals [4,8,9], Inhalation as well as infusion of Ascaris suum allergen extract (ASE) in sheep with negative skin test responses to the allergen only caused minor changes in breathing me chanics as well as in arterial plasma histamine concentra tions (HiPl) [4].…”

Section: Introductionmentioning

confidence: 99%

“…Airway challenges with aerosol ized allergens are known to induce histamine release from mast cells, basophils and alveolar macrophages [5] and may cause inflammatory responses in the lungs of human subjects [6,7] as well as in experimental animals [4,8,9], Inhalation as well as infusion of Ascaris suum allergen extract (ASE) in sheep with negative skin test responses to the allergen only caused minor changes in breathing me chanics as well as in arterial plasma histamine concentra tions (HiPl) [4]. Nearly 40% of the animals with a positive skin test responded to allergen inhalation with an acute airway obstruction which is associated with histamine lib eration and indicated by an increase in HiPl.…”

Section: Introductionmentioning

confidence: 99%

“…Allergen infusion caused a more severe alteration of airway resis tance and higher plasma histamine levels in animals responding to allergen inhalation than in animals re sponding to allergen infusion only. Acute airway constric tion correlated to histamine liberation in the lung [4]. The question of whether pharmacological cholinergic sub stances like acetylcholine (ACH), methacholine (MHC) or carbachol induce, in addition to their direct effect on cho linergic smooth muscle receptors, also the release of me diators such as histamine from cells in the lung is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Methacholine-lnduced Histamine Liberation during Airway Challenge Tests in Ascaris Skin-Sensitive Sheep

Ulmer²

1995

Respiration

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The interaction of vagal neuronal and pharmacological mediator mechanisms on the airway-constrictory responses obtained from challenges with aerosolized methacholine (MCH) before and after bilateral vagotomy and in combination with electrical stimulation of the peripheral ends of the cut vagal nerves was investigated in anesthetized Ascaris allergen skin-sensitive sheep. Inhalation of aerosols of 2 and 5% MCH for 2 min in a control group of 10 sheep resulted in airway muscle constriction indicated by an increase in dynamic elastance (E_dyn) (+70 and +256% of the basic value) or inspiratory airway resistance (R_I) (+45 and +155%) and was associated with a significant rise in plasma histamine concentration (HiP1) from 0.2 ± 0.2 to 0.9 ± 1.1 and 1.5 ± 1.2ng/ml, respectively. Respiratory and cardiovascular responses to MCH were reproducible after 90 min of recovery. A second group of another 6 intact sheep showed similar alterations of respiratory mechanical parameters and HiP1 after MCH challenges. After bilateral vagotomy, E_dyn and R_I increased after 2 and 5% MCH inhalation only by 15-30% of the control responses with intact vagi. The diminished airway constriction was associated with similar changes in HiPl as observed with intact vagi. Inspite of severe cardiovascular responses, the most effective electrical stimulation of the peripheral ends of the vagal nerves resulted in an increase in E_dyn or R_I by only 40-50% of the basic value. In a tracheal segment beneath the cuff of the endotracheal tube isometric pressure effectively increased by almost 500% of the basic value. Vagus nerve stimulation was found without detectable changes in HiPl. Stimulation of the central ends of the vagal nerves did not induce airway constriction or alterations in HiPl. The combination of electrical vagus nerve stimulation and MCH inhalation resulted in a more than additive increase in E_dyn and R_I, but the airway responses did not reach the same level of obstruction after challenge with 5% MCH as observed with intact vagi. Electrical stimulation of the efferent vagi failed to simulate spontaneous vagal nerve activity at higher levels of airway muscle responses. The results demonstrate that vagal neuronal mechanisms interact with local mediator liberation in acute airway obstruction. Airway challenge tests using cholinergic substances liberate histamine from inflammatory cells in the lungs of Ascaris skin-sensitive sheep.

Toluene diisocyanate induction of airway hyperresponsiveness at the threshold limit value (10 ppb) in rabbits

Potthast

Marczyński

et al. 1995

Lung

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Induction of acute lung injury and the development of airway hyperresponsiveness (AHR) by toluene diisocyanate (TDI) exposure was studied in a new rabbit model of occupational lung diseases. TDI in the range of the threshold limit value (TLV) of 10 ppb, as well as at 5 and 30 ppb, administered four times over a period of 1 h to three groups of eight rabbits, did not significantly alter airway resistance (RI), dynamic elastance (Edyn), slope of inspiratory pressure generation (delta Pes/tI), arterial pressure (Pa) or arterial blood gas tensions (PaO2, PaCO2). Airway responsiveness (AR) to aerosols of 2% acetylcholine (ACH) was measured before and after each TDI exposure. After TDI inhalation of 10 ppb over 4 h, the amplitude of the ACH-induced airway constrictor response indicated by the changes in Edyn rose significantly to almost twice the control response value (p < 0.005). Similar changes in the amplitude of RI and in the slope of delta Pes/tI were obtained. After inhalation of 5 ppb TDI, no changes in airway reactivity were observed. The responses of respiratory mechanical parameters to ACH rose to three to four times the control responses after exposure to 30 ppb TDI. In a control group of eight animals not undergoing TDI exposure, no significant changes of respiratory responses were obtained after inhalation of 0.2% ACH for 1 min. In summary, TDI atmospheres in the range of TLV increased AR to ACH within 4 h of exposure in this rabbit model. This augmented AR may indicate an increased risk for the development of isocyanate-induced obstructive lung diseases.