Acute ozone exposure increases bronchial blood flow in conscious sheep

This study was initiated to determine the effects of ozone (O3) on sheep airway blood flow. Twenty-three nasally intubated sheep were exposed to filtered air (n = 5), 1 ppm O3 (n = 4), 2 ppm O3 (n = 5), 3 ppm O3 (n = 5), and 4 ppm O3 (n = 4) for 3 h. Bronchial artery flow (Qbr) was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored during the period of the exposures. Exposure to 3 and 4 ppm O3 resulted in a significant increase in Qbr (103 and 204% change, respectively) without affecting any of the other cardiopulmonary parameters measured. These results indicate that O3 induces a dose dependent increase in Qbr which is the result of a vasodilation of the bronchial vasculature which is not dependent upon changes in blood gases or upstream driving pressure.     

Scoliosis and bronchial obstruction

Severe scoliosis may have a significant effect on respiratory function. The effect is most often restrictive due to severe anatomical distortion of the chest, leading to reduced lung volumes, limited diaphragmatic excursion and chest wall muscle inefficiency. Bronchial compression by the deformed spine may also occur but is more unusual. Management options include a conservative approach using bracing and physiotherapy in mild cases, as well as surgical correction of the scoliosis in more severe cases. Bronchial stenting has also been used successfully as an alternative to surgical correction, and in cases in which spinal surgery was either unsuccessful or not feasible. The authors present a case involving a 52-year-old woman who exhibited symptomatic compression of the bronchus intermedius by severe residual scoliosis despite previous corrective surgery. She was treated with an indwelling bronchial stent.     

Fully automated assessment of inflammatory cell counts and cytokine expression in bronchial tissue

Automated image analysis of bronchial tissue offers the opportunity to quantify stained area and staining intensity in a standardized way to obtain robust estimates of inflammatory cell counts and cytokine expression from multiple large areas of histopathologic sections. We compared fully automated digital image analysis with interactive digital cell counting and semiquantitative scoring of cytokine expression in terms of repeatability and agreement in bronchial biopsies in 52 patients with mild to moderate atopic asthma. Immunohistochemistry with antibodies against CD3, interleukin (IL)-4, IL-5, and interferon-gamma protein was performed on frozen tissue sections, using 3-amino-9-ethylcarbazole as chromogen and hematoxylin as counterstaining. IL-4 and IL-5 messenger RNAs were localized by in situ hybridization without hematoxylin staining. Separation of 3-amino-9-ethylcarbazole and hematoxylin-stained pixels was achieved by linear combination of red- and blue-filtered gray-scale images. Using baseline biopsy specimens, fully automated CD3+ cell counts showed perfect repeatability (r = 1.0) and a strong linear relationship with the interactive procedure (r = 0.98). Automated densitometry showed perfect repeatability (1.0) and a moderate to strong relationship with semiquantitative scoring of protein and messenger RNA expression (r = 0.43-0.89). Relationships between automated and semiquantitative assessments of changes in cytokine expression during 2 years of follow-up were moderate to strong (r = 0.40-0.84). We conclude that fully automated cell counts and automated densitometric analyses in bronchial tissue of patients with asthma are unbiased and help to reduce variability in inflammatory outcomes.     

Case report: inflammatory bronchial flap and 'check valve' bronchial obstruction.

The authors report the case of a patient in whom check valve bronchial obstruction was the result of an inflamed bronchial mucosal flap. Bronchoscopic examination showed that the mucosal flap opened with inspiration and closed with expiration. Protective brush and semiquantitative bronchoalveolar lavage cultures grew Staphylococcus aureus and Pseudomonas spp. An inflammatory mucosal flap and check valve bronchiolar obstruction has been described previously in only one patient and this was on postmortem examination.     

Airway obstruction in bronchial sarcoidosis: outcome with treatment

STUDY OBJECTIVE: Airway obstruction (AO) in sarcoidosis is reported to be associated with respiratory symptoms, increased morbidity, and an increased mortality risk. Because AO in sarcoidosis may result from several causes, the therapeutic benefit of corticosteroids is difficult to determine. The aim of this study was to evaluate the therapeutic response of AO attributable to sarcoid granulomas in the bronchial wall. PATIENTS: We selected 11 patients who had sarcoidosis with AO (defined as FEV(1)/vital capacity [VC] < 70%) associated with sarcoid granulomas on an endobronchial biopsy. Exclusion criteria were history of asthma, smoker or ex-smoker, stage 4 disease, evidence of extrinsic compression by enlarged lymph nodes, and localized endobronchial stenosis seen during fiberoptic bronchoscopy. INTERVENTIONS: We compared the results of pulmonary function tests and clinical, radiologic, and biological findings at baseline with those obtained at the time of the last pulmonary function tests available, between the sixth and 12th months of treatment. Eight patients took oral corticosteroids (20 to 60 mg/d initially), one received IV methylprednisolone pulses, another took oral hydroxychloroquine, and the last one received IM methotrexate. Measurements and results: With treatment, FEV(1) and FEV(1)/VC significantly improved in eight patients (72%), normalized in four patients, and was unchanged in the remaining three patients. The mean FEV(1) increased from 60.8 +/- 10.8% to 76 +/- 13.7% of the predicted value (p < 0.02). VC did not change significantly. FEV(1)/VC increased from 76.1 +/- 6.4% to 87.6 +/- 10.7% of the predicted value (p < 0.01). Dyspnea on exertion and other clinical findings were attenuated in 10 patients; the chest radiograph improved in 9 patients, and normalized in 5 patients. The mean serum angiotensin-converting enzyme level decreased from 112 +/- 48 to 58 +/- 40 IU/mL (p < 0.05), and normalized in four patients. CONCLUSION: The present study indicates that AO caused by sarcoid granulomas in the bronchial wall can be either partially or completely reversed by treatment with a concomitant attenuation of pulmonary symptoms.     

Underestimation of bronchial obstruction in sarcoidosis

We compared the frequency of airway obstruction in 27 patients with pulmonary sarcoidosis using both spirography (FEV1, FEF25-75) and plethysmography (Gus50). FEF25-75 was abnormal in 5 patients and Gus in 8 patients; however, only 3 of them showed abnormal values of both parameters. In the 2 patients with only a spirographic obstruction we observed an increase in static lung compliance. In 5 patients without spirographic obstruction we observed an increase of the elastic recoil of the lung, which probably balanced the decrease of Gus, leading to normal flow. In conclusion, airway obstruction is not frequent in sarcoidosis and can be masked in fibrosing forms, if spirographic measurements only are used.     

白介素17细胞因子家族与支气管哮喘

白介素17(IL-17)家族的提出,揭示了又一独特的受、配体信号系统.目前,IL-17A(IL-17)和IL-17F作为该家族的重要成员,其与哮喘的发生发展已经引起人们的关注,然而基于IL-17家族分子特性的支气管哮喘发生机制研究尚缺乏深度和系统性.本文就IL-17与IL-17F细胞因子的分子结构、受体、信号转导途径、功能及其与支气管哮喘关系的研究进展作一简要综述.     

Soot-exposed mononuclear cells increase inflammatory cytokine mRNA expression and protein secretion in cocultured bronchial epithelial cells

BACKGROUND: Soot particles are air pollutants capable of inducing airway and lung parenchymal injury. Mononuclear and bronchial epithelial cells are central to the maintenance of homeostasis and inflammation in the airways. OBJECTIVES: The aim of this study was to evaluate the contribution of mononuclear cells to the release of inflammatory mediators by bronchial epithelial cells. Methods: To model the in vivo situation, an in vitro system of cocultured blood monocytes and BEAS-2B cells was established in a transwell system. Blood monocytes were exposed to soot particles (FR 101) at concentrations of up to 100 microg/10(6) cells. Inflammatory cytokine mRNA and protein concentrations were quantified in BEAS-2B mono- and BEAS-2B-BM cocultures by RT-PCR and ELISA following exposure to soot for 1 and 8 h. RESULTS: No inflammatory cytokine mRNA expression was observed in unstimulated BEAS-2B cells. IL-6 and IL-8 mRNA and protein levels showed a dose-dependent elevation in FR 101-exposed blood monocytes. In addition, both IL-6 and IL-8 mRNA expression was upregulated in cocultured BEAS-2B cells while cytokine concentrations in the blood monocyte-BEAS-2B coculture medium were significantly increased. This upregulation was likely due to a synergism of two cell populations. CONCLUSIONS: Exposure to soot particles induces an autocrine stimulation of inflammatory cytokine release by blood monocytes and BEAS-2B cells. Since IL-6 and IL-8 play a major role in the pathogenesis and persistence of bronchial inflammation, these findings may serve as a partial explanation for the aggravation of asthmatic and bronchitic symptoms after exposure to soot.     

Airway reactivity and cotton bract-induced bronchial obstruction

Most seemingly healthy persons challenged with an aerosol of cotton bract extract develop some degree of bronchospasm. The role of nonspecific reactivity of the airways in this reaction to cotton bract extract is undefined. We examined the relationship between airway responses to cotton bract extract and to methacholine, as well as between airway responses to cotton bract extract and to a bronchodilator. Twenty-two healthy subjects were screened for sensitivity to inhaled cotton bract extract. Pulmonary function was measured using partial expiratory flow-volume curves on which flow at 60 percent of the control vital capacity below total lung capacity was measured (MEF40%[P]) following ten minutes of inhalation of cotton bract extract. In the group screened, 12 were found to be responders to the extract, with drops in MEF40%(P) of 20 percent or more, and ten were found to be nonresponders. On separate days, we measured the responses of our subjects' airways to inhaled metaproterenol and methacholine. The mean threshold dose for methacholine in the responding group was 26.8 mg/ml, as compared to 55.6 mg/ml for the nonresponders (t = 2.52; p less than 0.05). Furthermore, the mean percent increase in MEF40%(P) following inhalation of metaproterenol was 41 percent in responders and 24 percent in nonresponders (t = 2.19; p less than 0.05). We conclude that some responders to cotton bract extract exhibit greater reactivity of the airways than nonresponders.     

Hypoxia-induced bronchial responsiveness in awake sheep: role of carotid chemoreceptors

Hypoxia enhances bronchial responsiveness in sheep and dogs and we recently reported a similar effect in asthmatic subjects. Activation of a reflex arc due to stimulation of peripheral chemoreceptors has been suggested to explain this finding. We evaluated the contribution of carotid body chemoreceptors to hypoxia-induced bronchial responsiveness in conscious sheep. Incremental concentrations of aerosolized methacholine were given to each of seven sheep ventilated successively (in a random order) with a normoxic and a hypoxic gas mixture (15% O2 in N2), both before and after peripheral surgical chemodenervation. Hypoxia alone did not affect lung mechanics in intact or chemodenervated animals. Bronchial responsiveness to methacholine was significantly increased by hypoxia in intact sheep, as compared to chemodenervated sheep. We conclude that hypoxia has a stimulating effect on bronchial responsiveness in awake sheep similar to that seen in human patients with asthma. This increased responsiveness may be mediated by hypoxic stimulation of carotid body chemoreceptors, which in turn may influence the nervous control of airway calibre.     

Acute cricopharyngeal obstruction in dermatomyositis

We report a case of a 44-year-old woman with dermatomyositis complicated by acute total cricopharyngeal obstruction resistant to corticosteroid therapy. This condition was successfully resolved by cricopharyngeal myotomy.     

Inflammatory pseudotumor: a rare cause of proximal bronchial obstruction

Inflammatory pseudotumor of the lung is a rare disease with usual benign course. Relapse after incomplete resection and aggressive forms have already been described. We report the case of a 67-year-old woman with atelectasis of the left lung related to an endobronchial inflammatory pseudotumor. After laser resection, relapse occurred 3 months later, requiring surgical treatment.     

Atypical mycobacterial pulmonary disease and bronchial obstruction in HIV-negative children

Atypical mycobacterial infection in HIV-negative children usually presents with cervical lymphadenopathy. We report on 10 children who are HIV-negative and who presented with pulmonary disease, in whom either culture-proven atypical mycobacterium infection (four), positive avian Mantoux test (five), or lack of response to human tuberculosis treatment (one) had been observed. One case was subsequently diagnosed as chronic granulomatous disease and illustrates that children with atypical mycobacterial pulmonary infection should have their immune status fully investigated. Bronchial obstruction was observed in eight cases, and of these, endobronchial disease was found in six children. The diagnosis of atypical mycobacterial disease is difficult, and a negative avian Mantoux test does not exclude the diagnosis. The availability of clarithromycin and rifabutin has offered new therapeutic options in treating atypical mycobacterial pulmonary infection, but management of these cases can be prolonged and difficult. Pediatr Pulmonol. 1998; 26:380–388. © 1998 Wiley-Liss, Inc.     

Glucocorticoid regulation of proopiomelanocortin gene expression in the pituitary gland of hypothalamopituitary intact and hypothalamopituitary disconnected sheep

Proopiomelanocortin (POMC) gene expression in the anterior pituitary (AP) gland has previously been shown to be positively regulated by CRF and AVP and negatively regulated by glucocorticoids. In the neurointermediate lobe (NIL) of the pituitary, however, POMC gene expression is under tonic inhibitory dopaminergic control. In the present study we have used hypothalamopituitary intact (HPI), ovariectomized (OVX), and OVX/hypothalamopituitary disconnected (OVX/HPD) ewes to examine direct (i.e. nonhypothalamic) effects of glucocorticoids on POMC gene expression in both the AP and the NIL. There was no difference between POMC mRNA levels in intact and OVX sheep. In intact animals treated with dexamethasone, AP POMC mRNA levels were half those of controls. POMC mRNA levels were increased 3-fold in OVX/HPD sheep, compared with OVX, and lowered by dexamethasone to half OVX/HPD levels. In the NIL, hypothalamopituitary disconnection resulted in slightly higher mean POMC mRNA levels than in intact animals but the large intragroup variation did not allow a significant change. Dexamethasone administration had no effect on NIL levels of POMC mRNA in intact or OVX/HPD sheep.