Cigarette smoke increases mucosal permeability in guinea pig trachea via tachykinin NK2 receptor activation.

We investigated whether exposure to cigarette smoke increases the mucosal permeability in guinea pig trachea and if this effect could be mediated by tachykinin NK2 receptor activation. Guinea pigs were exposed to either three different doses of cigarette smoke or room air. Mucosal permeability was measured by monitoring the rate of appearance in the circulation of horseradish peroxidase (HRP) that had been instilled into the isolated tracheal segment. Exposure to 20 and 30 puffs but not 10 puffs of cigarette smoke increased the tracheal mucosal permeability. Pretreatment with the tachykinin NK2 receptor antagonist SR48,968 [(S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide] completely inhibited the increase in the permeability of the tracheal mucosa induced by exposure to cigarette smoke, whereas the tachykinin NK1 receptor antagonist SSR240,600 [(R)-2-(1-{2-[4-{2-[3,5-bis(trifluoromethyl)phenyl]acetyl}-2-(3,4-dichlorophenyl)-2-morpholinyl]ethyl}-4-piperidinyl)-2-methylpropanamide] and the tachykinin NK3 receptor antagonist SR142,801 [(S)-(N)-(1-[3-(1-benzoyl-3(3,4-dichlorophenyl)piperidine-3-yl)propyl]-4-phenylpiperidin-4-yl)-N-methyl-acetamide] had no effect. It is concluded that endogenous tachykinins via NK2 receptor activation mediate the increase in the permeability of the tracheal mucosa induced by exposure to cigarette smoke in guinea pigs.

[A case of cT0N2M0 small cell lung cancer with Lambert-Eaton myasthenic syndrome].

We encountered a very rare case of cT0N2M0 small cell lung cancer (SCLC) with Lambert-Eaton myasthenic syndrome (LEMS). A 69-year-old man with a complaint of muscle weakness was admitted to our hospital. Although his chest radiograph on admission showed no abnormal findings, CT scanning detected a mediastinal lymphadenopathy. Also, 2-[18F]-2-fluorodeoxy-D-glucose position emission tomography (FDG-PET) revealed increased accumulation in the same portion in the mediastinum. A diagnosis of LEMS was made from the distinctive electromyogram (EMG) findings (waning and waxing phenomenon in response to low-and high-frequency repetitive stimulation, respectively) in combination with the increased serum level of a P/Q-type anti-voltage-gated calcium channel (VGCC) antibody. Subsequent histopathological diagnosis by mediastinoscopic resection of a paraaortic lymph node was small cell carcinoma. No distant metastasis was detected by MRI of the brain, abdominal CT scan or an FDG-PET. Eight courses of chemotherapy (carboplatin + etoposide) with radiotherapy of the mediastinum (for a total dose of 45 Gy) was performed. A decreased serum level of P/Q-type anti-VGCC antibody titers followed by marked improvement of neurological dysfunction (muscle weakness, gait disturbance and scanning speech) and of an EMG finding (a loss of waning phenomenon) was observed. A close relationship between reduction of the antibody titers and improvement of neurological symptoms after the therapy was noticed. It was suggested that monitoring the level of a P/Q-type anti-VGCC antibody titer in the serum is important for evaluating the efficacy of chemotherapy for LEMS associated with SCLC.

Pulmonary hyalinizing granuloma with laryngeal and subcutaneous involvement: report of a case successfully treated with glucocorticoids.

We report a case of pulmonary hyalinizing granuloma (PHG) with laryngeal and subcutaneous involvement. A 43-year-old man was admitted to our hospital for assessment of hoarseness. Cervical and chest computed tomography, respectively, revealed a laryngeal tumor and two pulmonary masses. Specimens obtained from the pulmonary masses were compatible with PHG. The histopathology of biopsy specimens from both the laryngeal tumor and a subcutaneous tumor resembled that of the resected lung masses. Although there is no established treatment for PHG, the laryngeal tumor was diminished and all other lesions disappeared with glucocorticoid treatment.

[A case of lung infection due to Mycobacterium abscessus].

We report a case of lung infection due to Mycobacterium abscessus (M. abscessus). A 60 year-old woman was admitted to our hospital because of an abnormal shadow found on chest radiography and a bloody sputum. Chest radiography revealed infiltrative and linear shadows in the middle and lower fields of both lungs. The sputum smears were negative for acid-fast bacilli, but sputum culture was positive. Rapidly growing mycobacteria were detected. The patient was treated with clarithromycin. Since M. abscessus was identified from repeated cultures of the sputa, the patient was treated with Imipenem/Cilastatin and Amikacin for four weeks, during which the chest radiography improved. After discharge, the treatment with clarithromycin and minocycline was continued for ten months, and the chest radiography improved further. Our treatment for M. abscessus may be a useful choice for drug treatment of such cases.

[Hypogammaglobulinemia associated with thymoma (Good syndrome) similar to diffuse panbronchiolitis].

A 65-year-old woman complained of dyspnea and a productive cough after surgical treatment and irradiation therapy for thymoma. Chest radiography and high-resolution computed tomography showed small nodules in centrilobular lesions in all of both lung fields, but predominantly in the lower fields. In addition, blood tests showed hypogammaglobulinemia. Chronic sinusitis, mild hypoxemia, severe obstructive impairment and the pathological findings of bronchiolitis led to a diagnosis of sinobronchial syndrome caused by Good syndrome. Treatment with oral erythromycin 600 mg/day was started. After 6 months, the patient improved both clinically and radiologically. Low-dose, long-term treatment with erythromycin was effective against sinobronchial syndrome caused by Good syndrome.

[Acute lung injury caused by inhalation of waterproofing spray].

A 55-year-old man was admitted to our hospital because of severe dyspnea 30 minutes after inhalation of waterproofing spray. He had used the spray outdoors and had then smoked a cigarette with spray-contaminated fingers. Chest radiography and computed tomography (CT) revealed diffuse ground glass opacities in both lungs. In pulmonary function tests, the lungs showed a moderately decreased diffusing capacity and there was slight hypoxemia. Transbronchial lung biopsy specimens demonstrated extensive alveolitis and marked eosinophil migration. Without any specific treatment, the patient recovered clinically in 4 days. We speculated that acute lung injury in this patient may have been induced by not only direct inhalation of the waterproofing spray itself, but also by inhalation of spray by-products resulting from decomposition due to heat. When waterproofing spray is used, precautions should be taken to avoid both inhalation and heating of the fumes.

Tachykinins via Tachykinin NK(2) receptor activation mediate ozone-induced increase in the permeability of the tracheal mucosa in guinea-pigs.

1. Acute exposure to ozone is known to cause airway hyperresponsiveness, which, at least in part, seems to result from an increase in the permeability of the airway mucosa. Recently, we demonstrated that depletion of sensory neuropeptides inhibits the ozone-induced increase in the permeability of the tracheal mucosa in guinea-pigs. The aim of this study was to determine whether tachykinins mediate ozone-induced increase in the permeability of the tracheal mucosa in guinea-pigs. 2. Anaesthetized guinea-pigs were exposed to either 3 p.p.m. ozone or filtered air for 30 min. Immediately after exposure, a tracheal segment was isolated in vivo and administered with horseradish peroxidase (HRP). The permeability was assessed by monitoring the appearance of HRP in the blood. 3. A low dose of NKA increased the permeability of the tracheal mucosa, whereas a low dose of SP was without effect. Low and high doses of the selective NK(3) receptor agonist, senktide, were also without effect. The effect of a low dose of NKA was abolished by the NK(2) receptor antagonist, SR-48,968. A high dose of SP increased the permeability in a manner reversible by the NK(1) receptor antagonist, CP-96,345. 4. Pretreatment with SR-48,968 completely inhibited the ozone-induced increase in the permeability, whereas CP-96,345 had no effect. 5. It is thus concluded that endogenous tachykinins mediate the ozone-induced increase in the permeability of the tracheal mucosa in guinea-pigs mainly via NK(2) receptor activation.