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Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses.To explore novel severe asthma phenotypes by cluster analysis when including smoking patients with asthma.We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters.Five clinical clusters, including two characterized by low forced expiratory volume in 1 second/forced vital capacity, were identified. When characteristics of smoking subjects in these two clusters were compared, there were marked differences between the two groups: one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus score, and the other was characterized by low levels of the same parameters. Sputum analysis revealed intriguing differences of cytokine/chemokine pattern in these two groups. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 3 years later.This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.

A mass of 8 cm in diameter was revealed in the right upper lung field of a 46-year-old female patient. The chest X-ray film taken one year previously revealed only a linear shadow in the same position, which was thought to be a vacant cyst. The levels of carbohydrate antigen (CA) 19-9 in cyst fluid and serum were elevated, at 410,000 and 130 U/ml, respectively. After surgical resection, serum CA19-9 returned to normal. Pathologically, the cyst wall was lined with bronchial epithelium with no evidence of malignancy. Immunohistochemical study revealed CA19-9 positivity in the bronchial epithelium of the cyst wall.

Multiple bullae have often been observed in the lungs of patients with idiopathic interstitial pneumonia (IIP). The etiology of bullae has been considered to be distinct from that of interstitial pneumonia and honeycomb lesions seen in IIP. The incidence of bullae was evaluated in 27 IIP patients (male; 23 cases, female; 4 cases) and clinical factors which are related to the development of bulla were analyzed. Of the 27 patients, 16 (59%) had bullae. All 16 were male smokers, and had higher smoking indices (p

Toxic oxygen species and several proinflammatory cytokines are involved in the pathogenesis of silicosis. In order to understand whether factors that lead to susceptibility to ozone are also important in silicosis or not, we examined ozone-sensitive C57BL/6J mice and ozone-resistant C3H/HeJ mice as models of silicosis. We also analyzed the production of proinflammatory cytokines in both the acute and the chronic phases. On Day 2 after silica injection, the ozone-resistant C3H/HeJ mice showed significantly higher cellular responses as recognized by bronchoalveolar lavage (BAL) cell counts than did the C57BL/6J mice. In the chronic phase (Day 28 after silica injection), the ozone-sensitive C57BL/6J mice showed significantly greater responses to instilled silica judged by total protein and cell number in BAL fluid, hydroxyproline content, and histology than the ozone-resistant C3H/HeJ mice. TNF-alpha production by BAL cells after silica exposure was significantly higher in C57BL/6J mice than in C3H/HeJ mice in the chronic phase, whereas there was no significant difference in IL-1 alpha production between both strains of silica-injected mice. Also, the control C57BL/6J mice had significantly higher secretions of TNF-alpha than did the control C3H/HeJ mice in the acute phase. These results suggest that ozone-sensitive C57BL/6J mice are also more susceptible to silicosis than are ozone-resistant C3H/HeJ mice, and that the initial lower cellular responses and increase in TNF-alpha production may be related to the higher level of inflammatory and fibrotic response in the C57BL/6J mice.

Although the prevalence of serum precipitating antibodies for farmer's lung disease (FLD) is lower in smokers than in nonsmokers and FLD predominates in nonsmokers, the affects of smoking on the clinical course of the disease is not known. We compared the clinical findings and the prognosis between 12 smokers (SM-FLD) and 31 non-smokers with FLD (NS-FLD). There was no difference in age, sex, working years on farm, clinical symptoms, laboratory findings, radiographic findings, between the two groups. However, for the type of onset on the first visit for FLD, "acute single episode" type was less common, and "recurrent" and "insidious onset" types were more common in SM-FLD than in NS-FLD (8.3 vs 58.1, 91.7 vs 41.9%, respectively, p

Some advocate moving away from the farm environment for farmers affected with farmer's lung disease (FLD), but most affected farmers still live on farms. In this study, we evaluated the practicality of dust masks and their effectiveness in prevention of FLD. The dust masks we chose were practically used and no new severe episodes of FLD developed in 20 of 21 farmers with FLD using the masks during a 2-year period. When the farmers took off the dust masks in a farming environmental provocation test, statistically significant reductions in FVC (mean 3.43 to 3.351, p < 0.01), DLco (mean 19.6 to 18.2 ml/torr/min, p < 0.01), and DL/VA (mean 5.1 to 4.8 (x10(-3)) 1/torr/min, p < 0.01) were observed several hours after exposure. These findings suggest that the dust masks were used practically during routine dairy farming and were effective in protection against FLD.

Two acoustically different types of lung crackles, fine and coarse, occur in different pathophysiological conditions. To differentiate these crackles from objective characteristics of frequency information, crackles were recorded from 16 patients with pulmonary fibrosis judged clinically to have "fine" crackles and from 10 with chronic bronchitis who had mainly "coarse" crackles. Time expanded waveforms (1/4 cycle duration, initial deflection width, two cycle duration, and 9/4 cycle duration; duration of the first 1/4, 2/4, 8/4, and 9/4 cycles of crackle waveforms) were examined and fast Fourier transform analysis (peak and maximum frequencies) was performed. All waveform measurements for fine crackles were significantly smaller than those for coarse crackles. Peak and maximum frequencies for fine crackles were significantly higher than those for coarse crackles. Although there was some overlap in these values for individual crackles between the two groups when average values of these measurements were calculated for each patient, there was no overlap between fine and coarse crackles and the two groups could be clearly separated. Log peak frequency and log maximum frequency correlated better with 9/4 cycle duration (r = 0.85, 0.84) and two cycle duration (r = 0.87, 0.86) than with 1/4 cycle duration (r = 0.66, 0.77) or initial deflection width (r = 0.67, 0.79). Early and late segments of crackles have different characteristics, probably related to the origin of the sound and the resonance of the lung respectively. These results suggest that spectral and waveform characteristics may help to improve the accuracy of pulmonary auscultation and increase knowledge of how crackles are generated.