Characteristics of tobacco-related lung diseases in Fukuoka Prefecture, Japan: A prospective, multi-institutional, observational study.

BACKGROUND: Tobacco smoking causes a variety of smoking-related diseases, death, and economic damage. Despite targeted anti-smoking campaigns, tobacco-related deaths are expected to increase in Japan. We investigated the current state of non-cancerous lung diseases such as idiopathic interstitial pneumonias (IIPs), chronic obstructive pulmonary disease (COPD), and combined pulmonary fibrosis and emphysema (CPFE), which are known to be highly related to tobacco smoking. METHODS: This prospective multi-institutional observational study involved 29 major hospitals within the Fukuoka Prefecture area (Fukuoka tobacco-related lung disease registry study group). Patients diagnosed with IIPs, including CPFE and COPD, registered from September 1, 2013 to April 30, 2016 were included. Clinical background information, laboratory and pulmonary function test results, findings of imaging tests, including chest radiography and chest computed tomography, and DNA isolated from peripheral blood were collected from each patient. Follow-up surveillance involved collection of data regarding the exacerbation of disease and death until 5 years of registration. In the present study, we report the baseline characteristics of the patients registered in this surveillance study. RESULTS: Overall, 1016 patients (524 with IIPs, including 145 CPFE and 492 with COPD) were enrolled. Among the patients with COPD, 96.8% were current or former smokers. Among the patients with IIPs, 69.9% were current or former smokers. CONCLUSION: This study revealed the current status of lung diseases potentially related to tobacco smoking in Fukuoka Prefecture. Both COPD and CPFE were highly related to tobacco smoking, whereas 30% of patients with IIPs had never smoked.

Utility of the Quick Sequential Organ Failure Assessment in Japanese patients with nursing- and healthcare-associated pneumonia.

AIM: To clarify the utility of sepsis evaluation using the Quick Sequential Organ Failure Assessment (qSOFA) tool in addition to the Pneumonia Severity Index (PSI); age, dehydration, respiration, orientation and blood pressure (A-DROP) index; and immunodeficiency, respiration, orientation, age and dehydration (I-ROAD) scoring systems, and risk factor evaluation of potentially drug-resistant (PDR) pathogens are suggested in the 2017 guidelines for pneumonia of the Japanese Respiratory Society in nursing- and healthcare-associated pneumonia patients. METHODS: We included 289 hospitalized nursing- and healthcare-associated pneumonia patients between April 2016 and March 2017, and investigated the ability of PSI, A-DROP, I-ROAD and qSOFA to predict pneumonia-related mortality. We also evaluated the associations among the risk factors for PDR pathogens, the detection ratio of PDR pathogens and pneumonia-related mortality. RESULTS: The mortality rate of pneumonia during hospitalization was 6.9% (20/289). The area under the curve for pneumonia-related mortality predicted using PSI, A-DROP, I-ROAD and qSOFA was 0.697 (95% confidence interval [CI] 0.59-0.80), 0.63 (95% CI 0.51-0.76), 0.61 (95% CI 0.52-0.70) and 0.701 (95% CI 0.59-0.81), respectively. In addition, higher areas under the curve were observed for pneumonia-related mortality predicted according to a combination of PSI and hypoalbuminemia (<2.5 g/dL) (0.75, 95% CI 0.64-0.86), and qSOFA and hypoalbuminemia (0.74, 95% CI 0.62-0.86) than for PSI and qSOFA alone. No significant associations were observed among the risk factors for PDR pathogens, the detection ratios of PDR pathogens and pneumonia-related mortality. CONCLUSIONS: qSOFA and the combination of qSOFA and hypoalbuminemia might be simple and useful evaluation tools for predicting pneumonia-related mortality in nursing- and healthcare-associated pneumonia patients. Geriatr Gerontol Int 2019; 19: 177-183.

Bone-targeting poly(ethylene sodium phosphate).

Poly(ethylene sodium phosphate) (PEP·Na) showed excellent cytocompatibility and in vivo bone affinity. Moreover, PEP·Na did not interact with thrombin, which is a coagulation-related protein. Because immobilization of therapeutic agents and imaging probes on PEP·Na is easily performed, PEP·Na is a promising polymer for bone-targeted therapies.

Evaluation of a rapid immunochromatographic ODK0501 assay for detecting Streptococcus pneumoniae antigens in the sputum of pneumonia patients with positive S. pneumoniae urinary antigens.

BACKGROUND: A novel, rapid and noninvasive test (ODK0501, RAPIRUN(®)Streptococcus pneumoniae) uses polyclonal antibodies to detect C polysaccharide of S. pneumoniae derived from sputum samples using an immunochromatographic assay. We evaluated its usefulness in Japanese patients with pneumonia who exhibited positive urinary antigen tests for S. pneumoniae (BinaxNOW(®)S. pneumoniae). PATIENTS AND METHODS: Forty adult patients with pneumonia treated between May 2011 and August 2013 were enrolled. Bacterial cultures, Gram staining and ODK0501 assays of sputum as well as urinary antigen tests for S. pneumoniae using urine samples obtained from the same patients were performed upon admission, the fourth day after starting antimicrobial treatment and at the end of the antimicrobial treatment. RESULTS: Twenty-seven of the 40 patients were positive for ODK0501, while a negative result for ODK0501 was associated with low-quality sputum samples according to the Geckler classification of sputum. The sensitivity and specificity of the ODK0501 assay in the 40 patients were 90.9% and 61.1%, respectively, based on the culture results. The results obtained with this kit were more favorable than those observed on Gram staining. The ODK0501 assay also showed a rapid reaction to the disappearance of S. pneumoniae in the sputum samples, while approximately 80% of the patients exhibited persistent positive results on the urinary antigen detection tests at the end of treatment. CONCLUSIONS: The ODK0501 test is a noninvasive, rapid and accurate tool for diagnosing respiratory infections caused by S. pneumoniae, although good quality sputum must be obtained prior to adequate treatment with antibiotics.

[Efficacy and safety of azithromycin infusion in patients with mild or moderate community-acquired pneumonia].

Azithromycin (AZM) is one of 15-membered rings macrolide antibiotics with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria. So far, there had been no reports of the prospective studies evaluating efficacy and safety of AZM infusion in patients with mild or moderate community-acquired pneumonia (CAP). This study was conducted to evaluate prospectively the efficacy and safety of AZM in patients with mild or moderate CAP. AZM 500 mg was intravenously administered once daily, and the clinical efficacy were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-four patients were firstly registered, and eventually 61 and 62 patients were enrolled for the evaluation of clinical efficacy and safety of AZM, respectively. The efficacy of AZM in 61 patients evaluated was 88.5%. In addition, the efficacies of AZM in each pneumonia severity index by A-DROP system by the Japanese Respiratory Society (JRS) guideline in CAP were 85.2% in mild and 91.2% in moderate. Furthermore, the efficacy of AZM in each differentiation between suspicion of bacterial pneumonia and that of atypical pneumonia by JRS guideline in CAP were 91.7% in suspicion of atypical pneumonia, and its efficacy was high than that of bacterial pneumonia. Nineteen patients (20 cases; 15 with liver dysfunction, 4 with diarrhea, 1 with vascular pain) out of 62 patients were reported to have possible adverse effects of AZM. All of the patients with these adverse effects demonstrated mild dysfunction and continued AZM treatment, and these dysfunctions normalized soon after cessation of AZM. In conclusion, AZM is effective drug for patients with mild or moderate CAP, and we believe that it may be one of effective choice in the treatment of CAP patients who need hospitalization.

[Efficacy and safety of levofloxacin in patients with nursing and healthcare-associated pneumonia].

Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.

Analysis of genes for succinoyl trehalose lipid production and increasing production in Rhodococcus sp. strain SD-74.

Succinoyl trehalose lipids (STLs) are promising glycolipid biosurfactants produced from n-alkanes that are secreted by Rhodococcus species bacteria. These compounds not only exhibit unique interfacial properties but also demonstrate versatile biochemical actions. In this study, three novel types of genes involved in the biosynthesis of STLs, including a putative acyl coenzyme A (acyl-CoA) transferase (tlsA), fructose-bisphosphate aldolase (fda), and alkane monooxygenase (alkB), were identified. The predicted functions of these genes indicate that alkane metabolism, sugar synthesis, and the addition of acyl groups are important for the biosynthesis of STLs. Based on these results, we propose a biosynthesis pathway for STLs from alkanes in Rhodococcus sp. strain SD-74. By overexpressing tlsA, we achieved a 2-fold increase in the production of STLs. This study advances our understanding of bacterial glycolipid production in Rhodococcus species.

Clinical evaluation of pediatric anaphylaxis and the necessity for multiple doses of epinephrine.

BACKGROUND: Epinephrine administered intramuscularly is the treatment of choice for anaphylaxis, and more than 1 dose is occasionally required. OBJECTIVE: To determine clinical background of anaphylaxis for improving the treatment, management, and prognosis of anaphylaxis. METHODS: Children who had satisfied the diagnostic criteria for anaphylaxis according to the National Institute of Allergy and Infectious Disease Food Allergy and Anaphylaxis Network were selected from our hospital from April 1, 2009 to March 31, 2012. RESULTS: We analyzed 61 patients from the ages of 2 months to 14 years who satisfied the diagnostic criteria for anaphylaxis. Parents of 32 children (52.5%) reported that they had been administered single dose of epinephrine, and 3 children (4.9%) reported receiving multiple doses of epinephrine. The latter group experienced syncope more often (p = 0.049) than the former and suffered more often from comorbid allergic diseases (p = 0.043) that included either bronchial asthma, allergic rhinitis, or atopic dermatitis. Two (3.3%) children experienced biphasic reactions. Patients who experienced a biphasic reaction were more likely to have experienced syncope (p = 0.033), vomiting (p = 0.02), and administration of multiple doses of epinephrine (p = 0.0016). CONCLUSION: Our findings lead us to recommend that children receiving more than 1 injection of epinephrine should be observed for 24 hours, because it seems that children with requiring more than 1 injection of epinephrine might be have biphasic reactions.

Intrathoracic Rosai-Dorfman disease with spontaneous remission: a clinical report and a review of the literature.

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare non-neoplastic disease that is characterized by a proliferation of histiocytes mostly in lymph nodes. However, the etiological mechanism of RDD still remains unclear. Intrathoracic manifestations of RDD are only observed in 2% of patients with RDD. Spontaneous remission was reported in about 20% of patients with RDD; however, there are no reports of an intrathoracic manifestation of RDD that showed a spontaneous remission within a short period of time. A 64-year-old Japanese female with dry cough and left chest pain was introduced to our hospital, and computed tomography revealed a pulmonary nodular lesion and enlarged mediastinal lymph nodes. The bronchial specimen obtained from the abnormal mucosal lesion showed massive infiltration of histiocytes underneath the bronchial epithelium and emperipolesis, a typical pathological finding in RDD, which is characterized by the presence of histiocyte-like cells engulfing intact lymphocytes. These histiocytes were positive for S-100 (one of the known positive markers of RDD) and for CD68 (a marker for various cells of the macrophage lineage). All these findings are consistent with the diagnosis of RDD. These radiological and endoscopic findings spontaneously resolved within four months without any treatment. In conclusion, clinicians should be aware of this disease as one of differential diagnoses of pulmonary nodules in combination with mediastinal lymph node enlargements, especially in order to differentiate it from primary lung cancer.

[Food-dependent exercise-induced anaphylaxis that was difficult to evoke by a provocation test].

As a result of ingesting wheat- and soybean-based food products in school meals, an 8-year-old boy repeatedly experienced dyspnea and urticaria while exercising. Based on the symptoms, he was assumed to have been experiencing a food-dependent exercise-induced anaphylactic reaction. Based on the Japanese pediatric guideline for oral food challenge in food allergy 2009, examination using various combinations of food products (wheat and soybeans), medicine (aspirin), and exercise was performed. However, the examination failed to elicit any symptoms. Although we eliminated the food products from the examination, dyspnea caused by exercising after ingesting only wheat products was observed again. Thereafter, we performed a provocation test using wheat products, but symptoms were observed only on increasing the amount of ingested food and the momentum of exercise, without administering aspirin. The possibility that wheat is a more potent inducing factor than aspirin in increasing the momentum of exercise and amount of ingestion in food-dependent exercise-induced anaphylaxis was suggested.