Airway wall structure assessed by endobronchial ultrasonography and bronchial hyperresponsiveness in patients with asthma.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the relationship between the wall structure assessed by using endobronchial ultrasonography (EBUS) and bronchial hyperresponsiveness in patients with asthma. METHODS: Twenty-four patients with stable asthma and 11 individuals without asthma were studied. EBUS was performed with a radial 20-MHz ultrasonic probe inserted into the intermediate bronchus undergoing flexible bronchoscopy to assess the airway wall structure. The percentage of airway wall thickness {WT%; defined as [(ideal outer diameter-ideal luminal diameter)/ideal outer diameter]×100} was determined by EBUS. We measured bronchial hyperresponsiveness to methacholine [the provocative concentration of methacholine causing a decrease of 20% or more in forced expiratory volume in 1 s (PC20)]. RESULTS: Percentage wall thickness measured by EBUS was significantly greater in patients with asthma than that in subjects without asthma (P<0.01). The evaluation of the laminar structure using EBUS indicated that the thickness of the second layer in patients with asthma was greater than that in subjects without asthma (P<0.05). PC20 was negatively correlated with the thickness of the second layer (r=0.52, P<0.01) but was not significantly correlated with other layers in patients with asthma. CONCLUSIONS: The evaluation of the bronchial mural structure using EBUS might be advantageous for assessing the relationship between airway wall remodeling and bronchial hyperresponsiveness.

Randomized phase II trial of OK-432 in patients with malignant pleural effusion due to non-small cell lung cancer.

To determine the optimum dose of OK-432 for intrathoracic administration, a multicenter randomized phase II trial was conducted in patients with malignant pleural effusion due to non-small cell lung cancer. Patients with histologically- or cytologically-proven malignant pleural effusions were randomized to arm A (10 Klinische Einheit (KE) of OK-432) or arm B (1 KE of OK-432). OK-432 was injected intrapleurally over 30 min on days 1 and 3 and the chest tube was clamped for 6 h. If control was inadequate on day 8, 10 KE was administered on days 8 and 10 in each treatment arm. Forty patients were enrolled and 38 patients were eligible (19 in arm A and 19 in arm B). The effusion control rate on day 8 was 79% in arm A and 53% in arm B, while control rates on day 28 were 74% and 84%, respectively. The median drainage time after administration was significantly shorter in arm A (4.0 +/- 1.2 days) than in arm B (7.0 +/- 1.7 days). The total drainage volume was also significantly less in arm A than in arm B. No grade 4 toxicities or treatment-related deaths were observed in either treatment arm. Intrathoracic injection of OK-432 is a feasible treatment for malignant pleural effusion. Although the malignant pleural effusion control rate was equivalent in each treatment arm, faster control and less drainage were achieved in arm A. A dose of OK-432 10 KE/body is, therefore, recommended for further trial.

Importance of atopic cough, cough variant asthma and sinobronchial syndrome as causes of chronic cough in the Hokuriku area of Japan.

OBJECTIVE: A prospective multicentre study was conducted to elucidate the causes of chronic cough in Japan. METHODOLOGY: All consecutive and unselected patients complaining of cough lasting 8 weeks or more, who visited our clinics from 1 June to 31 December 2001, were registered. The causes of chronic cough were diagnosed based on the criteria for definite and probable causes of cough as recommended by the Japanese Cough Research Society. RESULTS: Of the 248 patients enrolled, 72 patients (29.0%) were unavailable for follow up before their diagnostic assessment had been finalized. Among the 176 patients who were adequately assessed, a diagnosis was made in 165 patients (93.7%) either as single cause or as one of two causes: atopic cough in 48 (29.1%) and 11 patients (6.7%); cough variant asthma in 46 (27.9%) and nine patients (5.5%); cough predominant asthma in 14 (8.5%) and three patients (1.8%); and sinobronchial syndrome (SBS) in 28 (17.7%) and 14 patients (8.5%), respectively. A diagnosis of gastro-oesophageal reflux-associated cough was made in a total of four patients (2.4%). CONCLUSION: Atopic cough, asthmatic cough consisting of cough variant asthma and cough predominant asthma, and SBS are major causes of chronic cough in Japan.

Bronchodilator effects of intravenous olprinone, a phosphodiesterase 3 inhibitor, with and without aminophylline in asthmatic patients.

AIMS: There is no evidence demonstrating the clinical usefulness of phosphodiesterase (PDE) inhibitors in the treatment of asthma, although PDE3 and 4 inhibitors have received much attention for the treatment of bronchial asthma. We compared the bronchodilator effects of intravenously administered olprinone, a selective PDE3 inhibitor, and aminophylline, a nonselective PDE inhibitor, both alone and concomitantly. METHODS: In 12 patients with mild stable asthma, we compared the acute bronchodilator effects of the following two drugs, alone and together using a double-blind crossover design: intravenous administration of olprinone, 30 micro g min-1; aminophylline, 2.25 mg min-1; and olprinone plus aminophylline over a total period of 150 min. RESULTS: Mean maximal increase (95% confidence interval) in the FEV1 was 7.8% (2.4, 13.2), 17.1% (10.0, 24.2), 16.6% (11.2, 22.0), and 1.0% (-1.1, 3.1) during infusion of aminophylline, olprinone, aminophylline and olprinone, and saline, respectively. The magnitude of bronchodilatation produced by olprinone was greater than that by aminophylline. The combination of aminophylline and olprinone did not produce any greater bronchodilatation than olprinone alone. Olprinone alone or in combination with aminophylline lowered diastolic blood pressure, and increased heart rate. CONCLUSIONS: These results suggest that the intravenous administration of PDE3 inhibitors exhibits a bronchodilatory effect. There are no additive or synergistic effects of administration of olprinone and aminophylline at the same time.

Effect of intranasal administration of CV-11974, a type 1 angiotensin II receptor antagonist, on airway hyperresponsiveness and airway inflammation induced by antigen inhalation in guinea pigs.

BACKGROUND: Angiotensin II is a putative mediator in asthma, but the effect of topical administration of type 1 angiotensin II (AT1) receptor antagonists on allergic airway reactions is not known. OBJECTIVE: To investigate the effect of intranasal administration of CV-11974, an AT1 receptor antagonist, and of PD123319, a type 2 angiotensin II (AT2) receptor antagonist, on antigen-induced airway reactions in guinea pigs. METHODS: Thirty minutes after intranasal topical administration of CV-11974 (0.1 or 1.0 mg/ml) or PD123319 (10 mg/ml) into the airways, the animals were given an antigen challenge. Airway hyperresponsiveness and bronchoalveolar lavage fluid were analyzed 24 h after the antigen challenge. RESULTS: Although these compounds did not inhibit antigen-induced early-phase bronchoconstriction or late-phase airway eosinophilia, intranasal administration of CV-11974 (but not PD123319) inhibited antigen-induced airway hyperresponsiveness in a dose-dependent manner 24 h after the antigen challenge. CONCLUSION: Intranasal administration of an AT1 receptor antagonist reduces antigen-induced airway hyperresponsiveness.

Alpha(1L)-, but not alpha(1H)-, adrenoceptor antagonist prevents allergic bronchoconstriction in guinea pigs in vivo.

alpha-Adrenoceptors have been classified into alpha(1)- and alpha(2)-adrenoceptors. Recently, the alpha(1)-adrenoceptors were divided into two subtypes: alpha(1L) with low affinity and alpha(1H) with high affinity for prazosin. Little is known concerning the role of each subtype of alpha(1)-adrenoceptor in asthma. We investigated the effects of specific antagonists of alpha(1)- and alpha(2)-, alpha(1H)-, alpha(1L)-, and alpha(2)-adrenoceptors, namely moxisylyte, prazosin, 3-[N-[2-(4-hydroxy-2-isopropyl-5-methylphenoxy) ethyl]-N-methylaminomethyl]-4-methoxy-2, 5, 6-trimethylphenol hemifumarate (JTH-601), and yohimbine, respectively, on antigen-induced airway reactions in guinea pigs. Fifteen minutes after intravenous administration of moxisylyte (0.01, 0.1 or 1 mg/kg), prazosin (0.01, 0.1, 1 or 10 mg/kg), JTH-601 (1, 3, 6 or 10 mg/kg) or yohimbine (0.1 or 1 mg/kg), passively sensitized and artificially ventilated animals received an aerosolized antigen challenge. Bronchial responsiveness to inhaled methacholine was assessed as the dose of methacholine required to produce a 200% increase in the pressure at the airway opening (PC(200)) in non-sensitized animals. JTH-601 and moxisylyte, but not prazosin or yohimbine, dose dependently inhibited antigen-induced bronchoconstriction. None of the tested drugs altered PC(200). JTH-601 significantly reduced leukotriene C(4) levels in bronchoalveolar lavage fluid obtained 5 min after antigen challenge, but prazosin did not. These results indicate that prevention of antigen-induced bronchoconstriction by blockade of alpha-adrenoceptors is due to the inhibition of mediator release via alpha(1L)-adrenoceptor antagonism.