A 47-year-old man was referred to our hospital because of a 2-month history of dry cough, 2-kg weight loss, and a feeling of abdominal fullness. The PET-CT scan depicts the intense standard uptake values (SUVs) of the anterior and subphrenic lymphnodes, and intraperitoneal cavity, especially in the omentum, while, no uptake was found in the pleural cavity. Based on the pathological findings of the open lung biopsy specimens, he was diagnosed with malignant peritoneal mesothelioma of epithelioid type with thoracic metastasis. The present case demonstrated the some of the limitations of PET-CT in the diagnosis of malignant mesothelioma, which failed to detect pleural involvement despite aggressive invasion by this tumor.

We described two patients with Guillain-Barré syndrome and respiratory failure with or without mechanical ventilation. Case 1 was a 44-year-old man who treated as pneumonia under mechanical ventilation for a month and transferred to our hospital with unsuccessful weaning trials because of phrenic nerve palsy. Case 2 was a 74-year-old man who presented with aspiration pneumonia because of bulbar palsy. The present two cases with review of the Japanese literature showed that antecedent infection with initial symptoms within the most recent 5 to 46 days is a clinical clue to the diagnosis even in patients with Guillain-Barré syndrome accompanied by respiratory failure.

Background

Opportunistic pulmonary infection with Nocardia species is rare in humans, and only a few studies have radiologically analyzed patients with pulmonary nocardiosis using high-resolution computed tomography (HRCT).

Methods

We retrospectively reviewed the medical records of patients with pulmonary nocardiosis at our hospital between April 2006 and December 2011 to assess HRCT and clinical findings. We also searched the medical literature for pulmonary nocardiosis reported in Japan between 2002 and 2011 for comparison.

Results

We identified seven patients at our institution and 33 reported infections in Japan. Four of our patients were immunocompetent, whereas the other three had impaired cellular immunity due to type 2 diabetes mellitus or having been inappropriately treated with steroid. Thoracic HRCT revealed no zonal predominance, but tropism for distribution from the middle to the peripheral area, and radiological findings of nodules, cavitation, mass, consolidations, bronchial wall thickening, septal line thickening and ground glass opacity (GGO) were evident. The main HRCT finding in our study comprised nodules (n=5, 71.4%) <30 mm and four patients had multiple nodules as described in other reports. Furthermore, we discovered a crazy paving appearance (CPA) around nodules, cavities, masses or consolidations in five patients (71.4%).

Conclusions

Multiple nodules distributed from the middle to the peripheral area on HRCT might reflect pulmonary nocardiosis, and CPA seemed to be a worth paying attention to the diagnosis.

Background

The saw-tooth sign was first described by Sanders et al in patients with obstructive sleep apnea syndrome as one cause of extrathoracic central airway obstruction. The mechanism of the saw-tooth sign has not been conclusively clarified. The sign has also been described in various extrathoracic central airway diseases, such as in burn victims with thermal injury to the upper airways, Parkinson’s disease, tracheobronchomalacia, laryngeal dyskinesia, and pedunculated tumors of the upper airway.

Case presentation

A 61-year-old man was referred to our hospital with a two-month history of persistent dry cough and dyspnea. He was diagnosed with lung cancer located in an intrathoracic central airway, which was accompanied by the saw-tooth sign on flow-volume loops. This peculiar sign repeatedly improved and deteriorated, in accordance with the waxing and waning of central airway stenosis by anti-cancer treatments.

Conclusion

This report suggests that the so-called saw-tooth sign may be found even in intrathoracic central airway obstruction due to lung cancer.

Background

Substantial data have demonstrated that air pollution is associated with cardiopulmonary mortality and morbidity in the world. Among a variety of pollutants, particulate components, particularly PM2.5, are especially suggested to be harmful to our lung health. Diesel exhaust particles (DEPs) are the major component of PM2.5, and therefore the relationship between PM2.5 or PM10 and airway inflammatory responses of asthmatic and people of not-yet asthma onset is important to be investigated. Recent findings suggested that susceptibility to DEPs is dependent upon certain genetic variations of anti-oxidative stress enzymes such as GSTP1, which is largely regulated by a transcription factor Nrf2. By preliminary experiments, we found that exhaled breath condensates (EBC) are safely and repeatedly obtained from both disease and health persons, and that several biomarkers including growth factors, cytokines and oxidant stress markers could be measured.

Methods

In the present study, we attempted to study the airway inflammatory/fibrogenic responses from patients with asthma, and further, those from people who have suggestive, but not yet definite symptoms of asthma. Participants are asked to present exhaled breath condensates (EBC) by R-tubes during spontaneous breathing for 5 minutes, which are processed to measure several inflammatory/fibrogenic markers.

Results

These molecules, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), basic fibroblast growth factor (FGF), IL-1 receptor antagonist, IL-8 and epidermal growth factor (EGF) tended to be increased in asthmatic group. These markers were significantly increased in severity step 4 patients as compared to mild asthmatics. There was a significant correlation between the PM10 concentration 1 month before the sampling of EBC and EBC EGF concentration. NO2 concentration and several markers in EBC in patients with asthma correlated with each other. EBC pH showed a significant relationship with the distance from main traffic roads.

Conclusions

These results suggested that mass screening using simple methods such as EBC and appropriate biomarkers might facilitate the progress in the prophylaxis against hazardous health effects of DE exposures in subjects with high susceptibility to DEPs.

The incidence of allergic diseases in most industrialized countries has increased. Although the exact mechanisms behind this rapid increase in prevalence remain uncertain, a variety of air pollutants have been attracting attention as one causative factor. Epidemiological and toxicological research suggests a causative relationship between air pollution and the increased incidence of asthma, allergic rhinitis, and other allergic disorders. These include ozone, nitrogen dioxide and, especially particulate matter, produced by traffic-related and industrial activities. Strong epidemiological evidence supports a relationship between air pollution and the exacerbation of asthma and other respiratory diseases. Recent studies have suggested that air pollutants play a role in the development of asthma and allergies. Researchers have elucidated the mechanisms whereby these pollutants induce adverse effects; they appear to affect the balance between antioxidant pathways and airway inflammation. Gene polymorphisms involved in antioxidant pathways can modify responses to air pollution exposure. While the characterization and monitoring of pollutant components currently dictates pollution control policies, it will be necessary to identify susceptible subpopulations to target therapy/prevention of pollution-induced respiratory diseases.

Allergic airway diseases are related to exposure to atmospheric pollutants, which have been suggested to be one factor in the increasing prevalence of asthma. Little is known about the effect of ozone and diesel exhaust particulates (DEP) on the development or aggravation of asthma. We have used a mouse asthma model to determine the effect of ozone and DEP on airway hyperresponsiveness and inflammation. Methacholine enhanced pause (Penh) was measured. Levels of IL-4 and IFN-γ were quantified in bronchoalveolar lavage fluids by enzyme immunoassays. The OVA-sensitized-challenged and ozone and DEP exposure group had higher Penh than the OVA-sensitized-challenged group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone exposure group. Levels of IFN-γ were decreased in the OVA-sensitized-challenged and DEP exposure group and the OVA-sensitized-challenged and ozone and DEP exposure group compared to the OVA-sensitized-challenged and ozone exposure group. Levels of IL-4 were increased in the OVA-sensitized-challenged and ozone exposure group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone and DEP exposure group compared to OVA-sensitized-challenged group. Co-exposure of ozone and DEP has additive effect on airway hyperresponsiveness by modulation of IL-4 and IFN-γ suggesting that DEP amplify Th2 immune response.

Long-term macrolide therapy has been proven to improve survival in patients with diffuse panbronchiolitis. Although its mechanisms remain unknown, previous studies have suggested the effects of macrolide might be anti-inflammatory rather than antibacterial. To elucidate the molecular mechanisms of its action, we studied here the effects of erythromycin (EM) and its new derivative, EM703, which shows no antibacterial action, on the activation of the transcription factor nuclear factor-κB (NF-κB) in human bronchial epithelial cells. Western blotting analysis showed that EM did not inhibit the degradation of IκBα, suggesting the molecular target for EM was not the dissociation of NF-κB from IκB. An electrophoretic mobility shift assay showed that EM did not interrupt the NF-κB DNA-binding activity in the nucleus under the conditions tested. Moreover, not only EM but also EM703 suppressed the activation of NF-κB and the production of interleukin-8, demonstrating that the anti-inflammatory action of the macrolide is independent of its antibacterial activity. Taken together, these data suggest EM has an anti-inflammatory action, presumably via an interaction with the NF-κB signaling pathway in the downstream of the dissociation from IκB, resulting in the inhibition of NF-κB.

Macrolide antibiotics such as erythromycin have been reported to be effective for asthma. However, the precise mechanisms of this effect remain unclear. We studied the effect of erythromycin, clarithromycin, josamycin, and other antibiotics on the release by eosinophils of interleukin-8 (IL-8), a potent chemokine for inflammatory cells, including eosinophils themselves. Human eosinophils were isolated from atopic patients, and the effects of the drugs on IL-8 release were evaluated. Only 14-member macrolides (erythromycin and clarithromycin) showed a concentration-dependent suppressive effect on IL-8 release (control, 100%; erythromycin at 1 μg/ml, 67.82% ± 3.45% [P < 0.01]; clarithromycin at 5 μg/ml, 56.81% ± 9.61% [P < 0.01]). The effect was found at therapeutic concentrations and appeared to occur at the posttranscriprtional level. In contrast, a 16-member macrolide (josamycin) had no significant effect. We suggest that 14-member macrolides inhibit IL-8 release by eosinophils and may thereby prevent the autocrine cycle necessary for the recruitment of these cells into the airways.

We evaluated the effect of roxithromycin on cytokine production and neutrophil attachment to human airway epithelial cells. Roxithromycin suppressed production of interleukin 8 (IL-8), IL-6, and granulocyte-macrophage colony-stimulating factor. It inhibited neutrophil adhesion to epithelial cells. Roxithromycin modulates local recruitment and activation of inflammatory cells, which may have relevance to its efficacy in airway diseases.