Current asthma is often excluded by the presence of normal bronchial hyperresponsiveness. We report two asthmatic patients with normal bronchial hyperresponsiveness and one asthmatic patient with mild bronchial hyperresponsiveness (methacholine PC20; 24 mg/ml) which was presumed to be caused by sensitization and exposure to Black GR, the most frequent sensitizer among reactive dyes. They all complained of lower respiratory symptoms after work as well as at the workstation. The bronchoprovocation test with Black GR revealed isolated immediate bronchoconstrictions in all 3 patients and all had high specific IgE antibodies to Black GR-human serum albumin conjugate. After one worker continued at work for 3 days, he experienced a marked drop of methacholine PC20, and it returned to the pre-exposure level during 1 week. The other patient whose initial methacholine challenge was negative developed bronchial hyperresponsiveness on the first day after the dye bronchoprovocation, and returned to normal bronchial hyperresponsiveness on the third day. These findings suggested that patients with occupational asthma caused by reactive dye may not always have bronchial hyperresponsiveness to methacholine, and the screening program utilizing methacholine challenges may not always identify these patients.
Adult ; Asthma/*chemically induced ; Bronchial Provocation Tests/methods ; Bronchoconstriction/*drug effects ; Dyes/*adverse effects ; Human ; Hypersensitivity, Delayed ; Immunoglobulin E/analysis ; Male ; Occupational Diseases/*chemically induced ; Skin Tests

OBJECTIVETo determine the inhibitory effects of BIO-1211, a very late antigen-4 (vla-4) antagonist, on bronchoconstriction and neutrophil adhesion in rats.

METHODSFor evaluating ovalbumin-induced bronchoconstriction in the sensitized rats, the changes in lung resistance (RL) and lung dynamic compliance (C(dyn)) were determined after antigen challenge. Neutrophils from the rats were used to determine fibronectin and serum-induced cell adhesion. The effect of BIO-1211 on wheezing was determined after inhalation of histamine and acetylcholine in guinea pigs.

RESULTBIO-1211 aerosol at 1, 3 and 10 mg/ml significantly inhibited the changes in lung resistance and lung dynamic compliance after antigen challenge in the sensitized rats in a dose-dependent manner. BIO-1211 at 25, 50, 100 and 200 microgram/ml inhibited the fibronectin-induced neutrophil adhesion by 23.5%, 24.6%, 61.4% and 58.1%, respectively, and serum-induced adhesion by 29.9%, 35.9%, 35.3% and 15.4%, respectively. Inhalation of 10 mg/ml BIO-1211 did not show any protection against histamine and acetylcholine-induced bronchoconstriction.

CONCLUSIONBIO-1211 inhibits bronchoconstriction and neutrophil adhesion, which may be associated with its effect against bronchoconstriction in rats.

Administration, Inhalation ; Animals ; Asthma ; drug therapy ; physiopathology ; Bronchoconstriction ; drug effects ; physiology ; Bronchodilator Agents ; administration & dosage ; pharmacology ; Cell Adhesion ; drug effects ; Female ; Guinea Pigs ; Male ; Neutrophils ; cytology ; drug effects ; Oligopeptides ; administration & dosage ; pharmacology ; Rats

OBJECTIVETo investigate bronchial responsiveness to acetylcholine in allergic airway inflammation of SD rats.

METHODSSD rats were immunized and challenged by chicken ovalbumin (OVA). Airway responsiveness, acetylcholine (Ach) provocation concentration needed to increase baseline airway resistance by 200% (PC(200)) were measured.

RESULTSThe value of baseline airway resistance in asthma group was significantly higher than that in control group (2.282 +/- 0.128 vs 3.193 +/- 0.239; P < 0.01). After multiple ovalbumin exposures, airway responsiveness to intravenous injection of acetylcholine decreased significantly (-LogPC(200): 4.006 +/- 0.554 vs 2.059 +/- 0.262; P < 0.01). Bronchial alveolar lavage fluid (BALF) and lung tissue specimen analysis indicated that airway allergic inflammation was present.

CONCLUSIONSThe study demonstrates a dissociation between the bronchoconstrictor response and bronchial hyper-responsiveness and indicates that multiple ovalbumin exposures induces persistent bronchoconstriction with airway hypo-responsiveness despite airway allergic inflammation.

Acetylcholine ; pharmacology ; Airway Resistance ; Allergens ; immunology ; Animals ; Bronchi ; drug effects ; physiology ; Bronchial Hyperreactivity ; etiology ; Bronchoconstriction ; Lung ; pathology ; Male ; Ovalbumin ; immunology ; Rats ; Rats, Sprague-Dawley

Current asthma is often diagnostically excluded by the presence of normal bronchial responsiveness. We report on a TDI-induced occupational asthma patient with normal bronchial responsiveness. He had suffered from shortness of breath during and after TDI exposure for several months. His initial methacholine bronchial challenge test showed a negative response. The bronchoprovacation test with TDI showed an isolated immediate bronchoconstriction. The following methacholine bronchial challenge tests revealed that the bronchial hyperresponsiveness developed seven hours after the TDI challenge (methacholine PC20:5.1 mg/ml), progressed up until 24 hours, and returned to normal on the seventh day. This case provides evidence that the response of the airway to TDI may not always be accompanied by bronchial hyperresponsiveness to methacholine. Screening programs utilizing methacholine challenges may not always identify TDI-sensitized asthmatic workers.
Adult ; Asthma/*chemically induced/diagnosis ; Bronchial Provocation Tests ; Bronchoconstriction/*drug effects ; Humans ; Male ; Methacholine Chloride/*diagnostic use ; Occupational Diseases/*chemically induced ; Skin Tests ; Time Factors ; Toluene 2,4-Diisocyanate/*adverse effects

BACKGROUND/AIMS: Ozone is an environmentally reactive oxidant, and pycnogenol is a mixture of flavonoid compounds extracted from pine tree bark that have antioxidant activity. We investigated the effects of pycnogenol on reactive nitrogen species, antioxidant responses, and airway responsiveness in BALB/c mice exposed to ozone. METHODS: Antioxidant levels were determined using high performance liquid chromatography with electrochemical detection. Nitric oxide (NO) metabolites in bronchoalveolar lavage (BAL) fluid from BALB/c mice in filtered air and 2 ppm ozone with pycnogenol pretreatment before ozone exposure (n = 6) were quantified colorimetrically using the Griess reaction. RESULTS: Uric acid and ascorbic acid concentrations were significantly higher in BAL fluid following pretreatment with pycnogenol, whereas gamma-tocopherol concentrations were higher in the ozone exposed group but were similar in the ozone and pycnogenol pretreatment groups. Retinol and gamma-tocopherol concentrations tended to increase in the ozone exposure group but were similar in the ozone and pycnogenol pretreatment groups following ozone exposure. Malonylaldehyde concentrations increased in the ozone exposure group but were similar in the ozone and pycnogenol plus ozone groups. The nitrite and total NO metabolite concentrations in BAL fluid, which parallel the in vivo generation of NO in the airways, were significantly greater in the ozone exposed group than the group exposed to filtered air, but decreased with pycnogenol pretreatment. CONCLUSIONS: Pycnogenol may increase levels of antioxidant enzymes and decrease levels of nitrogen species, suggesting that antioxidants minimize the effects of acute ozone exposure via a protective mechanism.
Animals ; Antioxidants/*pharmacology ; Ascorbic Acid/metabolism ; Bronchial Hyperreactivity/chemically induced/metabolism/*prevention & control ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoconstriction/drug effects ; Disease Models, Animal ; Female ; Flavonoids/*pharmacology ; Inhalation Exposure ; Lung/*drug effects/enzymology/physiopathology ; Malondialdehyde/metabolism ; Mice ; Mice, Inbred BALB C ; Nitric Oxide/metabolism ; Oxidative Stress/*drug effects ; *Ozone ; Uric Acid/metabolism ; Vitamin A/metabolism ; alpha-Tocopherol/metabolism