Increased nitric oxide in expired air in patients with Sjogren's syndrome. BHR study group. Bronchial hyperresponsiveness.
(25/1734)
Nitric oxide has an important role in the regulation of airway function and can have pro-inflammatory effects. Bronchial hyperresponsiveness (BHR) and respiratory symptoms are common in patients with Sjogren's syndrome (SS). The aim of this study was to determine whether patients with SS have an increased amount of exhaled NO and whether this NO correlates with respiratory symptoms and BHR. Exhaled NO was measured in 18 patients with SS and 13 normal subjects on three different occasions with intervals of at least 3 days using a chemiluminescence method. Airway responsiveness was assessed with methacholine provocation. Serum levels of myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) were measured. Exhaled NO was significantly higher in patients with SS than in controls (147+/-82 versus 88+/-52 nL x min(-1); mean+/-SD; p=0.041). Exhaled NO was correlated with age (partial r=0.52, p=0.006) and serum HNL (partial r=0.46, p=0.014). There were no significant correlations between exhaled NO and respiratory symptoms, BHR or serum MPO, ECP or EPO. Disease duration was negatively associated with serum MPO (r=-0.47, p=0.043). In patients with SS, a positive correlation was found between symptom score and serum ECP (partial r=0.65, p=0.003) and EPO (partial r=0.62, p=0.004) and a negative correlation with age (partial r=-0.60, p=0.005). In conclusion, elevated levels of exhaled nitric oxide in patients with Sjogren's syndrome were demonstrated. The mechanism underlying this increase in exhaled nitric oxide in Sjogren's syndrome is not known. (+info)
Assessment of bronchial reactivity by forced oscillation admittance avoids the upper airway artefact.
(26/1734)
The forced oscillation technique (FOT) allows easy assessment of bronchial reactivity. The use of a standard FOT generator (SG) results in changes in respiratory system resistance (delta Rrs,SG) which are affected by an artefact caused by the extrathoracic upper airway (EUA). The aim was to improve the FOT assessment of bronchial reactivity with the SG by computing the change in FOT admittance (delta Ars,SG), which is theoretically unaffected by this artefact. Delta Rrs,SG and delta Ars,SG after bronchial challenge in 17 children were compared with the values measured with a head generator (HG) FOT setup (delta Rrs,HG and delta Ars,HG, respectively), which were taken as a reference, since HG provides data virtually freed from the EUA artefact. At 10 Hz, the SG significantly underestimated the resistance change: delta Rrs,SG=1.77+/-0.62 versus delta Rrs,HG=6.09+/-1.23 hPa x L(-1) x s. Delta Rrs,SG and delta Rrs,HG did not show a significant correlation. By contrast, the amplitude of the change in admittance measured by SG was close to the one obtained with the reference HG: /delta Ars,SG/=29.5+/-4.6 versus /delta Ars,HG/=32.7+/-3.9 mL x hPa(-1) x s(-1). /Delta Ars,SG/ and /delta Ars,HG/ showed a significant correlation (r=0.65, p>0.01). Similar results were found up to 20 Hz. The extrathoracic upper airway artefact was minimized when computing the change in admittance with the standard generator. This forced oscillation technique index may improve the sensitivity in assessing bronchial reactivity with the standard generator setup, which is the most common and easiest to use method for routine lung function testing. (+info)
Role of nitric oxide released from iNANC neurons in airway responsiveness in cats.
(27/1734)
The precise role of inhibitory nonadrenergic noncholinergic (iNANC) neurons and nitric oxide in airway hyperresponsiveness remains uncertain. The role of NO in the regulation of airway responsiveness was studied in anaesthetized and mechanically ventilated cats. To assess airway responsiveness, the changes in total pulmonary resistance (RL) produced by delivering serotonin aerosol to the airways were measured before and after N(omega)-nitro-L-arginine methyl ester (L-NAME), or a ganglionic blocker, hexamethonium, which has been reported to block iNANC. Serotonin was chosen because it causes bronchoconstriction in part by neural reflex. To further clarify the mechanism(s) involved, the effect of inhaled capsaicin was also determined in animals with sustained bronchoconstriction induced by serotonin after treatment with atropine and propranolol. Inhibition of NO synthase by L-NAME or blockade of iNANC neurons by hexamethonium significantly increased airway responsiveness. However, addition of L-NAME did not further increase airway responsiveness in animals treated with hexamethonium. In the presence of atropine and propranolol, inhaled capsaicin caused a marked bronchodilation during serotonin-induced sustained bronchoconstriction. The bronchodilation induced by capsaicin was significantly suppressed by hexamethonium and by L-NAME. These results suggest that the nitric oxide released from inhibitory nonadrenergic noncholinergic neurons is important in modulating the airway responsiveness of cats in vivo. (+info)
Airway remodeling in asthma amplifies heterogeneities in smooth muscle shortening causing hyperresponsiveness.
(28/1734)
Although airway remodeling and inflammation in asthma can amplify the constriction response of a single airway, their influence on the structural changes in the whole airway network is unknown. We present a morphometric model of the human lung that incorporates cross-sectional wall areas corresponding to the adventitia, airway smooth muscle (ASM), and mucosa for healthy and mildly and severely asthmatic airways and the influence of parenchymal tethering. A heterogeneous ASM percent shortening stimulus is imposed, causing distinct constriction patterns for healthy and asthmatic airways. We calculate lung resistance and elastance from 0.1 to 5 Hz. We show that, for a given ASM stimulus, the distribution of wall area in asthmatic subjects will amplify not only the mean but the heterogeneity of constriction in the lung periphery. Moreover, heterogeneous ASM shortening that would produce only mild changes in the healthy lung can cause hyperresponsive changes in lung resistance and elastance at typical breathing rates in the asthmatic lung, even with relatively small increases in airway resistance. This condition arises when airway closures occur randomly in the lung periphery. We suggest that heterogeneity is a crucial determinant of hyperresponsiveness in asthma and that acute asthma is more a consequence of extensive airway wall inflammation and remodeling, predisposing the lung to produce an acute pattern of heterogeneous constriction. (+info)
Short ragweed allergen induces eosinophilic lung disease in HLA-DQ transgenic mice.
(29/1734)
The human leukocyte antigen (HLA) restriction of the IgE response to different allergens in humans has been a subject of numerous published studies. However, the role and contribution of specific HLA class II molecules in the pathogenesis of allergic airway inflammation are unknown and difficult to assess. HLA-DQ6 and HLA-DQ8 transgenic mice lacking endogenous mouse class II gene expression were actively immunized and later challenged intranasally with short ragweed (SRW) allergenic extract. The HLA-DQ transgenic mice developed pulmonary eosinophilia and lung tissue damage. We also found an increase in total protein (TP) level and IL-5 production in bronchoalveolar lavage (BAL) fluid and an increase in SRW-specific Th2-type immunoglobulins (IgG1, IgG2b) and total serum IgE levels. Under similar treatment, DQ-negative full-sib control mice were normal. The allergic response could be significantly inhibited or abrogated in HLA-DQ mice by systemic treatment with anti-DQ mAb. The in vivo responses of HLA-DQ6 and HLA-DQ8 mice showed differences in terms of levels of eosinophilia, BAL protein, IL-5 concentration, and lung hyperreactivity to inhaled methacholine. These findings demonstrate the crucial role for specific HLA-DQ molecules in SRW-specific CD4(+) T-cell activation and resulting recruitment of eosinophils into the airways. (+info)
Asymptomatic bronchial hyperresponsiveness to exercise in childhood and the development of asthma related symptoms in young adulthood: the Odense Schoolchild Study.
(30/1734)
BACKGROUND: Exercise testing may be of value in identifying a group of children at high risk of subsequently developing respiratory symptoms. As few longitudinal studies have investigated this issue, the bronchial hyperresponsiveness to exercise in asymptomatic children was evaluated as a risk factor for developing asthma related symptoms in young adulthood. METHODS: A community based sample of 1369 schoolchildren, first investigated in 1985 at a mean age of 9.7 years, was followed up after a mean of 10.5 years. Nine hundred and twenty children (67%) were asymptomatic in childhood and 777 (84.9%) of these were re-investigated at follow up. At the first examination a maximum progressive exercise test on a bicycle ergometer was used to induce airway narrowing. The forced expiratory volume in one second (FEV1) after exercise was considered abnormal if the percentage fall in FEV1 was more than 5% of the highest fall in the reference subjects characterised by having no previous history of asthma or asthma related symptoms. The threshold for a positive test was 8.6% of pre-exercise FEV1. RESULTS: One hundred and three subjects (13%) had wheeze within the last year at follow up and, of these, nine (9%) had been hyperresponsive to exercise in 1985. One hundred and seventy subjects (22%) had non-infectious cough within the previous year, 11 of whom (6%) had been hyperresponsive to exercise in 1985. Multiple regression analysis showed that subjects with hyperresponsiveness to exercise had an increased risk of developing wheeze compared with subjects with a normal response to exercise when the fall in FEV1 after exercise was included as a variable (threshold odds ratio (OR) 2.3 (95% CI 1.1 to 5.5)). The trend was not significant when exercise induced bronchospasm was included as a continuous variable (OR 1.02 (95% CI 0.97 to 1.06)). CONCLUSIONS: Asymptomatic children who are hyperresponsive to exercise are at increased risk of developing new symptoms related to wheezing but the predictive value of exercise testing for individuals is low. (+info)
Mouse monocyte-derived chemokine is involved in airway hyperreactivity and lung inflammation.
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The cloning, expression, and function of the murine (m) homologue of human (h) monocyte-derived chemokine (MDC) is reported here. Like hMDC, mMDC is able to elicit the chemotactic migration in vitro of activated lymphocytes and monocytes. Among activated lymphocytes, Th2 cells were induced to migrate most efficiently. mMDC mRNA and protein expression is modulated during the course of an allergic reaction in the lung. Neutralization of mMDC with specific Abs in a model of lung inflammation resulted in prevention of airway hyperreactivity and significant reduction of eosinophils in the lung interstitium but not in the airway lumen. These data suggest that mMDC is essential in the transit/retention of leukocytes in the lung tissue rather than in their extravasation from the blood vessel or during their transepithelial migration into the airways. These results also highlight the relevance of factors, such as mMDC, that regulate the migration and accumulation of leukocytes within the tissue during the development of the key physiological endpoint of asthma, airway hyperreactivity. (+info)
Augmented acetylcholine-induced, Rho-mediated Ca2+ sensitization of bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats.
(32/1734)
Treatment with acetylcholine (ACh) of a beta-escin-permeabilized intrapulmonary bronchial smooth muscle of the rat induced force when the Ca2+ concentration was clamped at 1 microM. The ACh-induced Ca2+ sensitization of myofilaments was significantly greater in antigen-induced airway hyperresponsive rats than in control rats. The ACh-induced Ca2+ sensitization was completely blocked by treatment with Clostridium botulinum C3 exoenzyme, an inactivator of Rho family of proteins. Moreover, the protein level of RhoA in the intrapulmonary bronchi was significantly increased in the airway hyperresponsive rats. Thus, increased airway smooth muscle contractility observed in asthmatics may be related to augmented agonist-induced, Rho-mediated Ca2+ sensitization of myofilaments. (+info)