Kenji Umeki

Clinical features of healthcare-associated pneumonia (HCAP) in a Japanese community hospital: Comparisons among nursing home-acquired pneumonia (NHAP), HCAP other than NHAP, and community-acquired pneumonia

Background and objective:  More than 100 000 Japanese die of pneumonia every year. The number of people residing in nursing homes is increasing with the ageing of the population. In 2005, the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) published important guidelines for the management of healthcare‐associated pneumonia (HCAP). In Japan, however, the optimum strategy for management of HCAP is still unclear. The purpose of this study was to clarify the clinical features of patients with HCAP.

Inhibitory effect of statins on inflammatory cytokine production from human bronchial epithelial cells.

Statins are 3‐hydroxy‐3‐methylglutaryl‐co‐enzyme A reductase inhibitors of cholesterol biosynthesis, and have been reported to exert pleiotropic effects on cellular signalling and cellular functions involved in inflammation. Recent reports have demonstrated that previous statin therapy reduced the risk of pneumonia or increased survival in patients with community‐acquired pneumonia. However, the precise mechanisms responsible for these effects are unclear. In the present study, we examined the effects of statins on cytokine production from lipopolysaccharide (LPS)‐stimulated human bronchial epithelial cells (BEAS‐2B). Interleukin (IL)‐6 and IL‐8 mRNA expression and protein secretion in LPS‐stimulated cells were inhibited significantly by the lipophilic statin pitavastatin and the hydrophilic statin pravastatin. As these inhibitory effects of statin were negated by adding mevalonate, the anti‐inflammatory effects of statins appear to be exerted via the mevalonic cascade. In addition, the activation levels of Ras homologue gene family A (RhoA) in BEAS‐2B cells cultured with pitavastatin were significantly lower than those without the statin. These results suggest that statins have anti‐inflammatory effects by reducing cytokine production through inhibition of the mevalonic cascade followed by RhoA activation in the lung.

Inhibitory effects of pitavastatin on fibrogenic mediator production by human lung fibroblasts

AIMS Idiopathic pulmonary fibrosis continues to be a devastating clinical disorder for which there are few therapeutic options, and the pathogenesis of this disease remains largely unknown. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in cholesterol biosynthesis, and they have been reported to exert pleiotropic effects on the cellular signaling involved in tissue inflammation and in organ fibrosis/remodeling. We examined the preventive effects of statins on fibrogenic mediator expression and production in normal human lung fibroblasts (NHLF). MAIN METHODS NHLF were pretreated with 100nM pitavastatin or medium alone (control), and were then stimulated with transforming growth factor-β1 (TGF-β1). mRNA expression and protein secretion of several mediators from cells were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay or multiplex assay. KEY FINDINGS TGF-β1-induced expression or production of mediators, such as collagen-1, vascular endothelial growth factor and chemokine C-X-C motif ligand 8, in NHLF pretreated with pitavastatin was significantly suppressed with inhibition of Smad-3 phosphorylation, as compared to untreated controls. In addition, the inhibitory effects of pitavastatin were negated by addition of mevalonate. SIGNIFICANCE Pitavastatin appeared to inhibit TGF-β1-induced fibrogenic mediator production from lung fibroblasts via the mevalonic cascade. Although further evaluation of the signaling pathways for these phenomena is necessary, our results suggest the potential benefits of pitavastatin.

Interstitial Pneumonia Associated With Bullous Pemphigoid

Bullous pemphigoid, the most common autoimmune blistering disease, is characterized by an autoimmune response to a component of hemidesmosomes within the dermal-epidermal junction. Immunofluorescence examination of skin biopsies demonstrates linear deposition of IgG and C3 in the basement membrane zone. A 73-year-old woman was admitted to our institution because of interstitial lung disease with persistent dry cough, dyspnea on exertion, and bullous eruptions on the skin of her trunk and extremities. Chest CT scan, BAL fluid, and transbronchial lung biopsy findings indicated a likely nonspecific interstitial pneumonia pattern. Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membranes of the lung and skin specimens. Lung disorders associated with bullous pemphigoid are extremely rare, and, to our knowledge, this is the first report of an immunologically confirmed case of interstitial pneumonia.

Comparison of pulmonary thin section CT findings and serum KL-6 levels in patients with sarcoidosis

OBJECTIVE This study aimed to compare thin-section CT images from sarcoidosis patients who had either normal or elevated serum KL-6 levels. METHODS 101 patients with sarcoidosis who underwent thin-section CT examinations of the chest and serum KL-6 measurements between December 2003 and November 2008 were retrospectively identified. The study group comprised 75 sarcoidosis patients (23 male, 52 female; aged 19-82 years, mean 54.1 years) with normal KL-6 levels (152-499 U ml(-1), mean 305.7 U ml(-1)) and 26 sarcoidosis patients (7 male, 19 female; aged 19-75 years, mean 54.3 years) with elevated KL-6 levels (541-2940 U ml(-1), mean 802.4 U ml(-1)). Two chest radiologists, unaware of KL-6 levels, retrospectively and independently interpreted CT images for parenchymal abnormalities, enlarged lymph nodes and pleural effusion. RESULTS CT findings in sarcoidosis patients consisted mainly of lymph node enlargement (70/75 with normal KL-6 levels and 21/26 with elevated KL-6 levels), followed by nodules (50 and 25 with normal and elevated levels, respectively) and bronchial wall thickening (25 and 21 with normal and elevated levels, respectively). Ground-glass opacity, nodules, interlobular septal thickening, traction bronchiectasis, architectural distortion and bronchial wall thickening were significantly more frequent in patients with elevated KL-6 levels than those with normal levels (p<0.001, p<0.005, p<0.001, p<0.001, p<0.001 and p<0.001, respectively). By comparison, there was no significant difference in frequency of lymph node enlargement between the two groups. CONCLUSION These results suggest that serum KL-6 levels may be a useful marker for indicating the severity of parenchymal sarcoidosis.

Efficacy of β-Lactam-plus-Macrolide Combination Therapy in a Mouse Model of Lethal Pneumococcal Pneumonia

ABSTRACT Community-acquired pneumonia is a common disease with considerable morbidity and mortality, for which Streptococcus pneumoniae is accepted as a leading cause. Although β-lactam-plus-macrolide combination therapy for this disease is recommended in several guidelines, the clinical efficacy of this strategy against pneumococcal pneumonia remains controversial. In this study, we examined the effects of β-lactam-plus-macrolide combination therapy on lethal mouse pneumococcal pneumonia and explored the mechanisms of action in vitro and in vivo. We investigated survival, lung bacterial burden, and cellular host responses in bronchoalveolar lavage fluids obtained from mice infected with pneumonia and treated with ceftriaxone, azithromycin, or both in combination. Although in vitro synergy was not observed, significant survival benefits were demonstrated with combination treatment. Lung neutrophil influx was significantly lower in the ceftriaxone-plus-azithromycin-treated group than in the ceftriaxone-treated group, whereas no differences in the lung bacterial burden were observed on day 3 between the ceftriaxone-plus-azithromycin-treated group and the ceftriaxone-treated group. Notably, the analysis of cell surface markers in the ceftriaxone-plus-azithromycin combination group exhibited upregulation of presumed immune checkpoint ligand CD86 and major histocompatibility complex class II in neutrophils and CD11b-positive CD11c-positive (CD11b+ CD11c+) macrophages and dendritic cells, as well as downregulation of immune checkpoint receptors cytotoxic-T lymphocyte-associated antigen 4 and programmed death 1 in T helper and T regulatory cells. Our data demonstrate that the survival benefits of ceftriaxone-plus-azithromycin therapy occur through modulation of immune checkpoints in mouse pneumococcal pneumonia. In addition, immune checkpoint molecules may be a novel target class for future macrolide research.

A Case of Eosinophilic Pneumonia in a Tobacco Harvester

BACKGROUND Eosinophilic pneumonia comprises a group of lung diseases in which eosinophils appear in increased numbers in the lungs. The distinct etiology of eosinophilic pneumonia is unknown, although the previous case series have indicated a relationship between acute eosinophilic pneumonia and the exposure to exogenous substances including the constituents of cigarettes. CASE SUMMARY A 60-year-old nonsmoking female, who had started to harvest and sort tobacco leaves two months before presentation, was admitted because of persistent coughing, breathlessness, and general malaise. Her laboratory findings revealed eosinophilia. Chest computed tomography showed nonsegmental airspace consolidations bilaterally. A bronchoalveolar lavage fluid analysis also revealed that the numbers of total cells and eosinophils had increased. Although the urine level of cotinine was within the normal range, positive findings were found in the skin scratch-patch tests using tobacco leaf and its extracts, and a biopsy specimen obtained from the positive site demonstrated infiltration of eosinophils in the dermis. The patient was successfully treated with corticosteroids. DISCUSSION Green tobacco sickness, a type of nicotine poisoning caused by the dermal absorption of nicotine, is a well known occupational illness of tobacco harvesters. Although it is unclear whether the present case could be identified as a subtype of green tobacco sickness, this is the first report of eosinophilic pneumonia occurred in a tobacco harvester which was possibly induced by tobacco leaf exposure.BACKGROUND Eosinophilic pneumonia comprises a group of lung diseases in which eosinophils appear in increased numbers in the lungs. The distinct etiology of eosinophilic pneumonia is unknown, although the previous case series have indicated a relationship between acute eosinophilic pneumonia and the exposure to exogenous substances including the constituents of cigarettes. CASE SUMMARY A 60-year-old nonsmoking female, who had started to harvest and sort tobacco leaves two months before presentation, was admitted because of persistent coughing, breathlessness, and general malaise. Her laboratory findings revealed eosinophilia. Chest computed tomography showed nonsegmental airspace consolidations bilaterally. A bronchoalveolar lavage fluid analysis also revealed that the numbers of total cells and eosinophils had increased. Although the urine level of cotinine was within the normal range, positive findings were found in the skin scratch-patch tests using tobacco leaf and its extracts, and a biopsy specimen obtained from the positive site demonstrated infiltration of eosinophils in the dermis. The patient was successfully treated with corticosteroids. DISCUSSION Green tobacco sickness, a type of nicotine poisoning caused by the dermal absorption of nicotine, is a well known occupational illness of tobacco harvesters. Although it is unclear whether the present case could be identified as a subtype of green tobacco sickness, this is the first report of eosinophilic pneumonia occurred in a tobacco harvester which was possibly induced by tobacco leaf exposure.

The scab-like sign: A CT finding indicative of haemoptysis in patients with chronic pulmonary aspergillosis?

ObjectivesThe aim of this study was to assess the CT findings that characterise haemoptysis in patients with chronic pulmonary aspergillosis (CPA).MethodsWe retrospectively identified 120 consecutive patients with CPA (84 men and 36 women, 17–89 years of age, mean age 68.4 years) who had undergone a total of 829 CT examinations between January 2007 and February 2017. In the 11 patients who underwent surgical resection, CT images were compared with the pathological results.ResultsThe scab-like sign was seen on 142 of the 829 CT scans, specifically, in 87 of the 90 CT scans for haemoptysis and in 55 of the 739 CT scans obtained during therapy evaluation. In 48 of those 55 patients, haemoptysis occurred within 55 days (mean 12.0 days) after the CT scan. In the 687 CT scans with no scab-like sign, there were only three instances of subsequent haemoptysis in the respective patients over the following 6 months. Patients with and without scab-like sign differed significantly in the frequency of haemoptysis occurring after a CT scan (p<0.0001). Pathologically, the scab-like sign corresponded to a fibrinopurulent mass or blood crust.ConclusionsThe scab-like sign should be considered as a CT finding indicative of haemoptysis.Key Points• Haemoptysis is commonly found in patients with CPA.• A CT finding indicative of haemoptysis in CPA patients is described.• Scab-like sign may identify CPA patients at higher risk of haemoptysis.

Effects of Sulfamethoxazole-Trimethoprim on Airway Colonization with Pneumocystis jirovecii

Reactivation of latent infection is considered to be the main mechanism underlying the development of Pneumocystis pneumonia in immunosuppressed patients. We retrospectively assessed the effects of prophylactic administration of sulfamethoxazole-trimethoprim on the development of P. pneumonia and airway colonization with P. jirovecii in patients undergoing examinations to diagnose or rule out P. pneumonia. Polymerase chain reaction was performed to detect P. jirovecii in bronchoalveolar lavage fluid or sputum of 60 consecutive patients between 2004 and 2012. No patients who received the prophylactic administration of sulfamethoxazole-trimethoprim (n = 10) developed P. pneumonia or demonstrated airway colonization with P. jirovecii, and none of the patients who developed P. pneumonia (n = 11) or showed colonization (n = 9) had received prophylactic treatment. Furthermore, 20 (40%) of 50 patients without prophylactic treatment showed positive results on the P. jirovecii DNA polymerase chain reaction, but all 10 patients who had prophylactic treatment showed negative results (Fishers exact test, P = 0.02). Therefore, the prophylactic administration of sulfamethoxazole-trimethoprim has potential to be effective in preventing P. pneumonia as well as eliminating airway colonization with P. jirovecii. Further studies targeting large cohorts of patients with a variety of underlying diseases are required to develop recommendations regarding the prophylactic administration of sulfamethoxazole-trimethoprim.

The additive effect of clarithromycin on influenza A infection in the elderly patients and patients with comorbid diseases

Kazuhiro Yatera, Kenji Umeki, Kei Yamasaki, Shingo Noguchi, Chinatsu Nishida, Hiroshi Ishimoto, Noriho Sakamoto, Hiroshi Ishii, Jun-ichi Kadota, Hiroshi Mukae Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan Department of Respiratory Medicine and Infectious Diseases, Faculty of Medicine, Oita University, Japan Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan