Involvement of nitric oxide (NO) in cough reflex sensitivity between non-sensitized and OVA-sensitized guinea pigs.

BACKGROUND: Exhaled nitric oxide (ENO) is elevated in bronchial asthma patients, and inhaled corticosteroid therapy lowers the elevated ENO levels in such patients. ENO appears to be an inflammatory marker, but its role in the pathophysiology of cough remains unclear. This study aimed to elucidate the relationship between NO and increased cough reflex sensitivity induced by allergic airway reactions. METHODS: Cough reflex sensitivity to inhaled capsaicin was observed under NO depletion caused by NO synthase (NOS) inhibitors in non-sensitized and ovalbumin (OVA)-sensitized guinea pigs. The bronchoalveolar lavage fluid (BALF) was analyzed in an NO depletion setting using the inducible NOS (iNOS) inhibitor ONO1714 in OVA-sensitized guinea pigs. RESULTS: NO depletion by the non-selective NOS inhibitor L-NAME suppressed cough reflex sensitivity in non-sensitized guinea pigs and OVA-induced increase in cough reflex sensitivity in sensitized guinea pigs; however, iNOS inhibition caused by ONO1714 partially suppressed the OVA-induced increase in cough reflex sensitivity, but not the normal cough response in non-sensitized guinea pigs. ONO1714 did not change BAL cell components in OVA-sensitized guinea pigs. CONCLUSIONS: The results suggest that NO may be involved not only in the normal cough reflex circuit, but also in the OVA-induced increase in cough reflex sensitivity, possibly via a different mechanism of action. Further studies are needed to clarify the precise mechanism.

Pulmonary T-cell lymphoma with pulmonary arterial hypertension.

We report on a 73-year-old man with systemic lymphadenopathy and chest computed tomography (CT) findings of bilateral diffuse ground-glass opacities and interlobular septal thickening. He also had pulmonary arterial hypertension (PAH). Several lymph node biopsies were attempted, without a definitive diagnosis. A thoracoscopic lung biopsy was performed, and the specimen was diagnosed as peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Lymphoma cells had invaded lung vessels, resulting in PAH. We should include pulmonary lymphoma in the differential diagnosis of patients with PAH and chest CT findings of diffuse ground-glass opacities and interlobular septal thickening.

Bronchoconstriction-triggered cough is impaired in typical asthmatics.

BACKGROUND AND OBJECTIVE: Cough is an essential innate protective behavior, which is experienced by even healthy individuals. The mechanism of cough triggered by bronchoconstriction is not yet clear. The aim of this study was to investigate the relation between bronchoconstriction and cough caused by methacholine (Mch) inhalation in typical asthmatics and normal healthy subjects. METHODS: We measured bronchial responsiveness to Mch and counted the number of coughs induced by Mch inhalation in 15 typical asthmatics and 20 normal subjects. RESULTS: After inhalation of Mch at the concentration causing 20% or more decrease in forced expiratory volume in 1 second (FEV(1)) (PC(20)-FEV(1)), coughs were provoked in normal subjects (number of cough: 22.5/32 min, range: 3.3-45). Conversely, coughs were hardly provoked in typical asthmatics (median number of cough: 2/32 min, range: 0-4). CONCLUSIONS: Although typical asthmatics have increased airway responsiveness, their cough response to bronchoconstriction is impaired.

Effects of macrolides on antigen-induced increases in cough reflex sensitivity in guinea pigs.

BACKGROUND: Macrolides are antibiotics that have anti-inflammatory activities. Hence, they are used for both acute and chronic inflammatory airway diseases. However, the effects of these agents on allergic airway disorders presenting with an isolated chronic cough, such as non-asthmatic eosinophilic bronchitis and eosinophilic tracheobronchitis with cough hypersensitivity (atopic cough), still remain to be elucidated. OBJECTIVE: To determine if macrolides are effective in the management of chronic cough caused by eosinophilic airway inflammation. METHODS: The cough reflex sensitivity to inhaled capsaicin was measured at 48h after challenge with an aerosolized antigen in actively sensitized guinea pigs. The 14-, 15- or 16-membered macrolides (erythromycin, azythromycin, or josamycin, respectively) were given intraperitoneally every 12h after the antigen challenge. Bronchoalveolar lavage and the resection of the tracheal tissue were performed immediately after the measurement of the cough response to capsaicin. RESULTS: The antigen-induced increase in the number of coughs elicited by capsaicin inhalation was significantly reduced by treatments with erythromycin and azythromycin, but not with josamycin. Erythromycin dose-dependently inhibited the increases in the substance P, prostaglandin E(2) and leukotriene B(4) levels, but not the histamine levels, in the bronchoalveolar lavage fluid. However, erythromycin did not influence the antigen-induced decrease in the neutral endopeptidase (NEP) activity in the tracheal tissue. CONCLUSIONS: Both 14- and 15-membered, but not 16-membered, macrolides could reduce the antigen-induced cough reflex hypersensitivity by inhibiting the antigen-induced release of the afferent sensory nerve sensitizers. These macrolides may be therapeutically useful for the treatment of isolated chronic cough based on cough reflex hypersensitivity in allergic airway diseases such as non-asthmatic eosinophilic bronchitis and atopic cough.

Bronchodilator effect of deep inspiration and bronchoconstriction-triggered cough.

BACKGROUND: Cough in the patients with cough variant asthma is triggered by bronchoconstriction, which responds to bronchodilator therapy. Following airway narrowing induced by inhaled methacholine, deep inspiration (DI) causes dilation of the airways in both asthmatic and non-asthmatic subjects. The aim of the present study was to investigate the relationship between bronchodilator effect of DI and bronchoconstriction-triggered cough. METHODS: We measured airway responsiveness to methacholine using partial and full flow-volume curves in 28 healthy adults. The expiratory flow at 40% above residual volume from the full forced vital capacity (MEF40) was obtained and the volume was used as the reference volume to determine the isovolume flow from the partial curve (PEF40). Coughs were counted for 32 min during and following the inhalation of methacholine at the provocative concentration which produced a 20% fall or more in FEV1from the post-saline value (PC20-FEV1). The bronchodilator effect of DI on bronchoconstriction induced by methacholine at the PC20-FEV1 concentration was expressed as the ratio of (MEF40-PEF40)/PEF40 (DI index). RESULTS: The number of coughs for 32 min during and following the inhalation of PC20-FEV1 concentration of methacholine was 39.3 +/- 29.7 (mean +/- SD)/32 min. The number of coughs during and following the inhalation was correlated with DI index (r = 0.57, p = 0.0015), but not with PC20-FEV1 or change in FEV1 or PEF40 by inhalation of the PC20-FEV1 concentration of methacholine. CONCLUSION: We found that methacholine-induced cough was associated with the bronchodilator effect of DI on methacholine induced-bronchoconstriction in normal subjects.

Evaluation of airway hyperresponsiveness and exhaled nitric oxide as risk factors for airway remodeling in patients with stable asthma.

Chronic eosinophilic airway inflammation, airflow limitation, and airway hyperresponsiveness (AHR) are distinctive features of bronchial asthma. Exhaled nitric oxide (eNO) is a marker of eosinophilic airway inflammation. Airway remodeling due to chronic airway inflammation results in fixed airway obstruction. Asthmatic patients have been reported to have greater declines in forced expiratory volume in 1 second (FEV(1)) over time than nonasthmatic patients. This longitudinal observational study aimed to elucidate outcomes and risk factors for the decline in FEV(1) in patients with stable asthma. Postbronchodilator FEV(1) was measured in 30 outpatients with stable asthma every 6 months for 5 years. We calculated the rate of decline in postbronchodilator FEV(1) (deltaFEV(1)/year) in each subject and adjusted deltaFEV(1)/year with predictive FEV(1). Patients were examined while their asthma was well controlled. In the first observation period, we measured AHR to methacholine (the provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)]). In the second observation period (defined as the period over 2 years from start of observation), we measured methacholine PC(20) and eNO. The mean deltaFEV(1)/year (SEM) was -36 +/- 4 mL/year and the adjusted deltaFEV(1)/year (SEM) was -0.015 +/- 0.001/year. Adjusted deltaFEV(1)/year did not correlate with eNO measured during the second observation period or methacholine PC(20) measured during the first observation period. On the other hand, methacholine PC(20) measured during the latter period was correlated significantly with adjusted deltaFEV(1)/year. Persistent AHR may be a risk factor for longitudinal decline in FEV(1) in asthma patients even if their asthma is stable and well controlled by inhaled corticosteroid.

[Case of tuberculous bronchial stenosis followed-up by spirogram and successfully treated with a Dumon stent].

A 47-year-old man visited his family doctor because of chronic productive cough. Though there were no abnormal chest X-ray film findings, he was diagnosed as tuberculosis on the basis of a sputum examination. Therefore, he was introduced to our hospital and as tracheobronchial tuberculosis was diagnosed by the bronchofiberscopic findings, showing ulceration with a white nodules from the lower part of trachea to the left main bronchus. By treatment, the ulcer change was improved, but the left main bronchus narrowed to pinhole size. Furthermore, the flow-volume curve became worse, and stridor appeared. We inserted Dumon stent in the left main bronchus 4 months later. As a result, his symptoms and flow-volume curve were improved, and we removed the stent 4 years and 6 months later. In this valuable case, we could observe the progress of the post-tuberculosis bronchial stenosis respiratory physiologically.

[Asymptomatic pulmonary actinomycosis diagnosed by transbronchial lung biopsy (TBLB)].

A 65-year-old asymptomatic man was admitted to our hospital because a chest abnormal shadow had been pointed out on a medical examination. Our investigation resulted that the consolidation in the left lung had been initially documented in 2002, and had been expanding every year. Bronchofiberscopy showed flare, swelling and stenosis of the left B8, B9 and B10. Because the biopsy specimen from the B9 showed a mass of bacteria and surrounding granulation tissue, pulmonary actinomycosis was diagnosed. Pulmonary actinomycosis should be considered in the differential diagnosis of abnormal chest shadows regardless of the absence of symptoms.

[A case of malignant mesothelioma presenting with recurrent pneumothorax].

A 71-year-old man was found to have right hydropneumothorax by chest X-ray film on a regular checkup. Thoracic drainage and bullectomy by thoracoscopy did not improve the pneumothorax, so pleurodesis with OK-432 was done. Pneumothorax recurred twice, requiring thoracic drainage and pleurodesis. Although pneumothorax was treated successfully, increased pleural effusion, pleural thickening and subcutaneal tumor at the thoracic drainage suture site developed. The concentration of hyaluronic acid in the pleural fluid was very high. The histological examination of the biopsied subcutaneous tumor showed mixed type malignant pleural mesothelioma. Chemotherapy with gemcitabine and vinorelbine could not control the progression.

[A case showing Wallerian degeneration of the bilateral middle cerebellar peduncles on MRI followed by the right pontine infarction].

We report a 63-year-old man who presented with the left facial palsy, the left hemiparesis, the left limb ataxia, and the bilateral truncal ataxia. On admission, magnetic resonance imaging (MRI) showed an abnormal high intensity lesion at the right paramedian region of the upper to middle pons on T2-weighted images (T2WI). He was diagnosed as having a pontine lacunar infarction. The contralateral cerebellar lesions were caused by involvement of the pontocerebellar fibers. On the 29th day from the onset, MRI showed the new abnormal high intensity lesions at the bilateral middle cerebellar peduncles on T2WI. These lesions were supposed to be Wallerian degeneration caused by involvement of the pontocerebellar fibers. This case suggests that Wallerian degeneration occurs followed by a unilateral infarction involving pontocerebellar fibers.