Masanori Nishikawa

Effects of Ozone Exposure on Experimental Asthma in Guinea Pigs Sensitized with Ovalbumin through the Airway

As ozone (O3) is known to cause airway inflammation and hyperresponsiveness, we examined the effects of O3 exposure (1, 3, or 5 ppm, 2 h) on sensitization and provocation in guinea pigs sensitized with ovalbumin (OA) through the airway. In groups exposed to O3 before sensitization, 5 ppm increased the production of IgG1 antibodies and decreased the OA sensitization threshold from 0.01 to 0.002%. In those exposed before provocation, 1, 3, or 5 ppm of O3 decreased the OA provocation threshold from 0.5 to 0.02%, and this enhancement appeared to depend on airway hyperresponsiveness. We conclude that O3 exposure may play an important role in causing asthmatic attacks rather than enhancing allergic sensitization.

Dose‐response relationship of ozone‐induced airway hyperresponsiveness in unanesthetized guinea pigs

The effect of ozone dose (the product of ozone concentration and exposure time) on airway responsiveness was examined in unanesthetized, spontaneously breathing guinea pigs. Airway responsiveness was assessed by measuring specific airway resistance (sRaw) as a function of increasing concentration of inhaled methacholine (Mch) aerosol (the concentration of Mch required in order to double the baseline sRaw: PC200Mch). The airway responsiveness was measured before and at 5 min, 5 h, and 24 h after exposure. A 30-min exposure to 1 ppm ozone (dose 30 ppm.min) did not change PC200Mch at any time after exposure. Both a 90-min exposure to 1 ppm ozone and a 30-min exposure to 3 ppm ozone, which are identical in terms of ozone dose (90 ppm.min), decreased PC200Mch to a similar degree. A 120-min exposure to 3 ppm ozone (360 ppm.min) produced a much greater decrease of PC200Mch at 5 min and 5 h after exposure, compared with low-dose exposure. There was a significant correlation between ozone dose and the change in airway responsiveness. In all groups, the baseline sRaw was increased by approximately 50% at 5 min after exposure, but there was no correlation between the changes in PC200Mch and the baseline sRaw. This study suggests that ozone-induced airway hyperresponsiveness in guinea pigs is closely related to ozone dose.

Role of superoxide anions in airway hyperresponsiveness induced by cigarette smoke in conscious guinea pigs

To investigate the involvement of superoxide in airway hyperresponsiveness and bronchoconstriction induced by cigarette smoke (CS), we evaluated the effects of superoxide dismutase (SOD), a scavenger of superoxide anion, and apocynin, an inhibitor of superoxide anion-generating NADPH oxidase in phagocytes, on the airway responses induced by CS in conscious guinea pigs. Airway responsiveness was assessed by PC2OOMch, the concentration required to produce a doubling in the baseline specific airway resistance (sRaw) to an inhaled methacholine aerosol, in nonanesthetized spontaneously breathing animals. Before being exposed to ten puffs of CS, animals inhaled either SOD (5,000 units/ml or 25,000 units/ml) or vehicle. Although SOD did not affect PC2OOMch, in the air control group, this agent significantly reduced the CS-induced airway hyperresponsiveness. Repeated administration of apocynin (12 mg/kg for 4 days) did not affect PC2OOMch, after exposure to CS. These data suggest that the superoxide from CS was involved in the airway hyperresponsiveness induced by CS, whereas phagocytic reactive oxygen species were not. The data also suggest a potential therapeutic role for antioxidants in airway hyperresponsiveness.

Combined effects of ozone and cigarette smoke on airway responsiveness and vascular permeability in guinea pigs.

The effects of combined exposure to ozone and cigarette smoke on airway responsiveness and tracheal vascular permeability, compared with those of single exposure were examined in guinea pigs. Airway responsiveness was assessed by measuring the specific airway resistance (sRaw) as a function of increasing concentration of inhaled methacholine aerosol immediately, 5 hr, and 24 hr after exposure. In a parallel study, tracheal vascular permeability was quantified by measuring the tracheal extravasation of intravenously administered Evans blue dye. Neither exposure to 1 ppm ozone for 30 min nor 5 puffs of cigarette smoke increased airway responsiveness or vascular permeability at any time after exposure. Combined exposure to 1 ppm ozone for 30 min and 5 puffs of cigarette smoke caused airway hyperresponsiveness and increased vascular permeability immediately after exposure. Exposure to 1 ppm ozone for 90 min increased both airway responsiveness and vascular permeability immediately after exposure. Exposure to 10 puffs of cigarette smoke increased airway responsiveness but not vascular permeability immediately after exposure. Combined exposure to 1 ppm ozone for 90 min and 10 puffs of cigarette smoke increased both airway responsiveness and vascular permeability immediately after exposure. The combined exposure to ozone and cigarette smoke thus increased both airway responsiveness and tracheal vascular permeability to a greater extent than did exposure to a single agent, suggesting that a combination of air pollutants has a more deleterious effect both on airway responsiveness and on tracheal vascular permeability than does either agent alone in guinea pigs.

Involvement of superoxide anions in ozone-induced airway hyperresponsiveness in unanesthetized guinea pigs.

To evaluate the involvement of superoxide in ozone (O(3))-induced airway hyperresponsiveness, we studied the effects of superoxide dismutase (SOD), a scavenger of superoxide anion, and apocynin, an inhibitor of superoxide anion-generating NADPH oxidase in phagocytes, on the airway responses induced by O(3) in unanesthetized guinea pigs. Airway responsiveness was measured by PC(200)Mch, the concentration required to produce a doubling in the baseline specific airway resistance to an inhaled methacholine aerosol, in spontaneously breathing animals. Before exposure to 3 ppm O(3) for 30 min, animals inhaled either SOD (5000 U/ml) or vehicle for 5 min. Although SOD did not affect PC(200)Mch in the air control group, this agent reduced the O(3)-induced airway hyperresponsiveness. Repeated administration of apocynin (12 mg/kg for 4 days) also attenuated the O(3)-induced airway hyperresponsiveness. These data suggest that superoxide may be involved in the pathogenesis of O(3)-induced airway hyperresponsiveness, possibly through the stimulation of superoxide anions release from bronchoalveolar phagocytes. The data also suggest a potential therapeutic role for antioxidants in oxidant injury by air pollutants.

Serum Level of Eosinophil Cationic Protein in Patients with Chronic Cough: Relationship to Blood Eosinophils and Airway Hyperresponsiveness

We measured the serum level of eosinophil cationic protein (ECP), determined the blood eosinophil count, and assessed pulmonary function by spirometry and airway responsiveness to methacholine in 80 patients with a cough lasting longer than 3 weeks without an obvious cause. The serum level of ECP was above the cutoff value of 15.7 ng/mL (mean + 2 SD in 105 healthy control adults) in 30 (37.5%) of 80 patients (high-serum-ECP group). The blood eosinophil count was significantly higher in the high-serum-ECP group than in the normal-serum-ECP group (p < 0.01). The cumulative dose of methacholine causing a 35% decrease in respiratory conductance (PD35Grs) was significantly lower in the high-serum-ECP group than in the normal-serum-ECP group (p < 0.001). The serum concentration of ECP was correlated with the blood eosinophil count and the PD35Grs (r = 0.59, p < 0.001 and r = -0.48, p < 0.001, respectively). These findings suggest a possible role for serum level of ECP in management of patients with chronic cough.

Large cell carcinoma of the lung metastatic to nuchal muscle

Abstract Clinically apparent hematogenous skeletal muscle metastases from lung cancer are extremely rare. We present a 72‐year‐old man with a large cell lung carcinoma metastatic to nuchal muscle. Cervical computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a well‐defined mass in the left splenius capitis muscle. A percutaneous needle biopsy was performed to establish a diagnosis. Localized skeletal muscle swelling may rarely prove to be metastases in patients with lung cancer, but should be investigated in the case of muscle swelling.