PURPOSE: Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity-related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity. MATERIALS AND METHODS: We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) beta, and tumor necrosis factor (TNF) alpha in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid. RESULTS: Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge. CONCLUSION: Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma.
Animals ; Asthma/physiopathology ; Bronchial Hyperreactivity/*physiopathology ; Bronchoalveolar Lavage Fluid/chemistry ; Dietary Fats/adverse effects ; Mice ; Obesity/*etiology/*physiopathology ; Pneumonia/*physiopathology ; Transforming Growth Factors/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Vascular Endothelial Growth Factor A/metabolism

Airway Remodeling ; Asthma ; physiopathology ; Bronchial Hyperreactivity ; etiology ; Bronchitis ; physiopathology ; Humans

BACKGROUND/AIMS: Many patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin. METHODS: The clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus. RESULTS: Forty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders (1.46 +/- 0.02) than in the oral responders (1.36 +/- 0.03, p < 0.01) and in non-responders (n = 141, 1.37 +/- 0.01, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR. CONCLUSIONS: A considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine-AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.
Administration, Inhalation ; Adolescent ; Adult ; Aspirin/*administration & dosage/*adverse effects ; Asthma/*physiopathology ; Asthma, Aspirin-Induced/etiology/physiopathology ; Bronchial Hyperreactivity/physiopathology ; Bronchial Provocation Tests ; Drug Hypersensitivity/etiology/physiopathology ; Female ; Humans ; Male ; Methacholine Chloride/*administration & dosage ; Retrospective Studies ; Young Adult

OBJECTIVETo establish a method for measurement of airway resistance (sRaw) and reactivity in guinea pigs.

METHODSMethacholine spray at gradient concentrations was given to guinea pigs. PC100 was defined as the concentration of methacholine when the sRaw doubled in the guinea pigs using a double-chamber plethysmograph. The time for the recovery of PC100 resistance to baseline levels was measured. The sRaw and PC100 were measured twice on days 1 and 15 (4 time points) in the guinea pigs before and after OVA challenge.

RESULTSPC100 in a normal guinea pig airway was shown to recover the baseline level within 1 h. Double-chamber plethysmographical measurement of the sRaw and PC100 in normal guinea pigs did not show significant differences between the time points [sRaw: 3.25-/+0.67, 3.33-/+0.58, 3.30-/+0.56, and 3.32-/+0.75 cm H2O.s; log2PC100: 8.48-/+0.94, 8.64-/+1.04, 8.56-/+0.67, and 8.64-/+0.60, respectively, P>0.05]. The sRaw and airway reactivity were significantly increased in guinea pigs challenged with OVA [sRaw: 7.08-/+1.82 vs 2.87-/+0.53 cmH2O.s, P<0.01; log2PC100: 6.64-/+1.26 vs 8.48-/+1.17, P<0.01].

CONCLUSIONA double-chamber plethysmography for measurement of sRaw and airway reactivity in guinea pig is established successfully.

Airway Resistance ; Animals ; Asthma ; chemically induced ; physiopathology ; Bronchial Hyperreactivity ; etiology ; physiopathology ; Guinea Pigs ; Male ; Methacholine Chloride ; Plethysmography ; instrumentation ; methods ; Random Allocation

Reactive oxygen species (ROS) performs a pivotal function as a signaling mediator in receptor-mediated signaling. However, the sources of ROS in this signaling have yet to be determined, but may include lipoxygenases (LOXs) and NADPH oxidase. The stimulation of lymphoid cells with TNF-alpha, IL-1beta, and LPS resulted in significant ROS production and NF-kappaB activation. Intriguingly, these responses were markedly abolished via treatment with the LOXs inhibitor nordihydroguaiaretic acid (NDGA). We further examined in vivo anti-inflammatory effects of NDGA in allergic airway inflammation. Both intraperitoneal and intravenous NDGA administration attenuated ovalbumin (OVA)-induced influx into the lungs of total leukocytes, as well as IL-4, IL-5, IL-13, and TNF-alpha levels. NDGA also significantly reduced serum levels of OVA-specific IgE and suppressed OVA-induced airway hyperresponsiveness to inhaled methacholine. The results of our histological studies and flow cytometric analyses showed that NDGA inhibits OVA-induced lung inflammation and the infiltration of CD11b+ macrophages into the lung. Collectively, our findings indicate that LOXs performs an essential function in pro-inflammatory signaling via the regulation of ROS regulation, and also that the inhibition of LOXs activity may have therapeutic potential with regard to the treatment of allergic airway inflammation.
Animals ; Antioxidants/metabolism ; Asthma/complications/metabolism/pathology/physiopathology ; Bronchial Hyperreactivity/drug therapy/pathology ; Bronchial Provocation Tests ; Bronchoalveolar Lavage Fluid/cytology ; Cells, Cultured ; Drug Evaluation, Preclinical ; Humans ; Inflammation/*etiology/metabolism ; Jurkat Cells ; Lipoxygenase/*physiology ; Lipoxygenase Inhibitors/pharmacology/therapeutic use ; Lymphocytes/drug effects/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Nordihydroguaiaretic Acid/pharmacology/therapeutic use ; Reactive Oxygen Species/*adverse effects/*metabolism

The aim of this study was to investigate the possible adverse effects of Asian dust events on respiratory health in asthmatic children. Fifty-two children with mild asthma were studied for eight consecutive weeks in the spring of 2004 (March 8 to May 2). During the study period, five Asian dust days were identified; we included a lag period of two days following each of the events. Subjects recorded their respiratory symptom diaries and peak expiratory flow (PEF) twice daily during the study period; and they underwent methacholine bronchial challenge tests. The subjects reported a significantly higher frequency of respiratory symptoms during the Asian dust days than during the control days. They showed significantly more reduced morning and evening PEF values, and more increased PEF variability (10.1%+/-3.5% vs. 5.5%+/-2.2%) during the Asian dust days than during the control days. Methacholine PC20 was not significantly different between before and after the study period (geometric mean: 2.82 mg/mL vs. 3.16 mg/mL). These results suggest that the short-term Asian dust events might be associated with increased acute respiratory symptoms and changes in PEF outcomes. However, there might be little long-term influence on airway hyperresponsiveness in children with mild asthma.
Adolescent ; Asthma/*physiopathology ; Bronchial Hyperreactivity/physiopathology ; Child ; *Dust ; Female ; Humans ; Male ; Methacholine Chloride/diagnostic use ; *Peak Expiratory Flow Rate ; Respiration Disorders/*etiology/physiopathology

Airway Resistance ; Animals ; Bronchial Hyperreactivity ; etiology ; Histamine ; pharmacology ; Lung ; pathology ; virology ; Microscopy, Immunoelectron ; Neurofilament Proteins ; analysis ; Neuronal Plasticity ; Rats ; Rats, Sprague-Dawley ; Respiratory Syncytial Virus Infections ; physiopathology ; Respiratory Syncytial Virus, Human ; isolation & purification

Antibodies, Anti-Idiotypic ; therapeutic use ; Asthma ; etiology ; immunology ; physiopathology ; therapy ; Bronchial Hyperreactivity ; physiopathology ; Desensitization, Immunologic ; Humans ; Reflex ; Rhinitis, Allergic, Perennial ; etiology ; immunology ; physiopathology ; therapy ; Rhinitis, Allergic, Seasonal ; etiology ; immunology ; physiopathology ; therapy

Animals ; Asthma ; physiopathology ; Bronchi ; metabolism ; Bronchial Hyperreactivity ; etiology ; Humans ; Muscle, Smooth ; metabolism ; Potassium Channels ; chemistry ; physiology ; Potassium Channels, Calcium-Activated ; physiology ; Potassium Channels, Voltage-Gated ; physiology

Enhanced cough response has been frequently observed in chronic cough. Recently, extrathoracic airway constriction to inhaled histamine was demonstrated in some chronic cough patients. However, relation between extrathoracic airway hyperresponsiveness (EAHR) and cough sensitivity determined by capsaicin inhalation is unclear in each etiological entity of chronic cough. Seventy-seven patients, with dry cough persisting for 3 or more weeks, normal spirometry and chest radiography, and 15 controls, underwent methacholine bronchial provocation test and capsaicin cough provocation test. Elicited cough number and flow-volume curve was examined after inhalation of capsaicin to evaluate cough sensitivity and EAHR. Thirty-three patients, with postnasal drip, showed normal extrathoracic airway responsiveness, and 27 of them showed normal cough sensitivity to capsaicin. Cough sensitivity was enhanced in 14 patients with cough variant asthma (CVA) who showed bronchial hyperresponsiveness; EAHR to inhaled capsaicin was present in 12 of them. The remaining 30 patients were tentatively diagnosed as idiopathic chronic cough (ICC). Eleven ICC patients showed enhanced cough sensitivity and EAHR to inhaled capsaicin while 19 patients showed normal values. These results indicate that cough sensitivity is closely related with extrathoracic airway responsiveness during capsaicin provocation in some chronic cough patients. EAHR and enhanced cough sensitivity to inhaled capsaicin may be a part of mechanism developing chronic cough.
Administration, Inhalation ; Adult ; Bronchial Hyperreactivity/*etiology/physiopathology ; Bronchial Provocation Tests ; Capsaicin/*administration & dosage ; Case-Control Studies ; Chronic Disease ; Cough/*etiology/physiopathology ; Female ; Humans ; Male ; Methacholine Chloride/diagnostic use ; Middle Aged