Uncovering a Severe Patient Group With Pollen-Related Extrarespiratory Allergic Symptoms: A Year-Long Diary Survey in Japan.

BACKGROUND: The most common symptoms of pollen allergy are rhinitis and conjunctivitis. However, in real-world clinical practice, we sometimes encounter patients with pollen allergy suffering from severe extrarespiratory symptoms including skin, gastrointestinal, or flu-like symptoms in relation to exposure to sensitized pollen. OBJECTIVE: To elucidate the extrarespiratory symptoms in patients with pollen allergy. METHODS: We performed a non-drug-focused prospective study of patients with pollen allergy (n = 384). During the 1-year observational period, they were asked to complete a weekly electronic diary consisting of visual analog scale (VAS) scores to assess all symptoms experienced in various organs over the past week. An association between seasonal pollen levels and seasonal increase in VAS scores was evaluated using a mixed-effects model for repeated measures. A k-means cluster analysis was performed to identify a group of patients experiencing stronger extrarespiratory symptoms. RESULTS: In patients sensitized to grass or birch pollen, higher seasonal levels of these pollen grains were associated with higher VAS scores for headache, gastrointestinal symptoms, skin symptoms, and fatigue. A cluster analysis identified a group of severe pollen-allergic patients with higher extrarespiratory symptoms (n = 42). This group was characterized by a higher frequency of comorbid food allergy/atopic dermatitis, higher rate of IgE sensitization to pollens, and higher impaired activity and work productivity. CONCLUSIONS: This 1-year survey identified a small but nonnegligible group of patients with pollen-related extrarespiratory symptoms. More attention should be paid to this patient group considering their impaired activity and work productivity.

Acute Pneumonitis Associated With the Inhalation of Pyrethroid-Based Domestic Insecticides.

We report a 72-year-old female who presented to our hospital with a worsening cough and dyspnea that had emerged a week earlier following the accidental inhalation of a significant quantity of spray-type imiprothrin (a synthetic pyrethroid)-based insecticide in her bathroom. She exhibited acute respiratory failure necessitating 4 L/minute of nasal oxygen at maximum. Chest CT images showed diffuse centrilobular ground-glass opacities with mosaic attenuation and consolidation areas in the lower lobes of both lungs. The patient was diagnosed with acute pneumonitis due to insecticide inhalation, and her symptoms improved following methylprednisolone pulse and alpha-tocopherol therapy. Generally, the accidental inhalation of aerosolized pyrethroids does not induce significant respiratory symptoms, and case reports on pulmonary toxicity related to pyrethroid inhalation are scarce. This case report underscores the need to include inhaled pyrethroid insecticides in the differential diagnosis of patients with acute pneumonitis and suggests that methylprednisolone and alpha-tocopherol therapy can be beneficial for treating this condition.

Resolvin E1 Inhibits Osteoclastogenesis and Bone Resorption by Suppressing IL-17-induced RANKL Expression in Osteoblasts and RANKL-induced Osteoclast Differentiation.

BACKGROUND: Resolvin E1 (RvE1) derived from the ω-3 polyunsaturated fatty acid eicosapentaenoic acid is known to be a potent pro-resolving lipid mediator that prevents chronic inflammation and osteoclastogenesis. We investigated the inhibitory effects of RvE1 on osteoclastogenesis and bone resorption to clarify its therapeutic potential for rheumatoid arthritis (RA). METHODS: Receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation was assessed with tartrate-resistant acid phosphatase staining. RANKL-induced bone resorption was assessed by the measurement of pit formation using calcium phosphate-labeled fluorescent polyanionic molecules in RAW264.7 cells as osteoclast precursors. The effects of RvE1 on the RANKL-induced mRNA expression of osteoclast-specific genes and transcriptional factors such as c-fos and nuclear factor of activated T cells c1 (NFATc1) in RAW264.7 cells were measured by quantitative real-time PCR. The distribution of NFATc1 induced by RANKL was evaluated by immunofluorescence staining in RAW264.7 cells. To analyze the mechanism of the inhibitory effect of RvE1 on osteoclastogenesis, we measured IL-17-induced RANKL mRNA expression in MC3T3-E1 osteoblast cells treated with RvE1 using quantitative real-time PCR and determined the level of prostaglandin E2 (PGE2) production by enzyme-linked immunosorbent assay. RESULTS: RvE1 significantly suppressed RANKL-induced osteoclast differentiation and bone resorption. RvE1 inhibited the RANKL-induced mRNA expression of osteoclast-specific genes along with the transcription factors NFATc1 and c-fos. Moreover, NFATc1 translocation from the cytoplasm to the nucleus of RAW264.7 cells was suppressed following RvE1 treatment. RvE1 also inhibited IL-17-induced RANKL mRNA expression and PGE2 production in MC3T3-E1 cells. CONCLUSION: RvE1 inhibited osteoclastogenesis and bone resorption by suppressing RANKL-induced NFATc1 and c-fos expression in osteoclasts and IL-17-induced RANKL expression through the autocrine action of PGE2 in osteoblasts. Our data suggest RvE1 as a new therapeutic target of RA.

An onion farmer with a case of hypersensitivity pneumonitis caused by Aspergillus niger.

A 62-year old man was admitted to our hospital with a 2-week complaint of a dry cough, general fatigue, and dyspnea on effort. He has been an onion farmer for several years and developed these symptoms after cleaning up onion peels with air compressors. A chest roentgenogram and computed tomography showed a ground glass shadow in the bilateral upper lung field. Cellular analysis of the bronchoalveolar lavage fluid showed elevated total cell numbers and lymphocytes. Transbronchial lung biopsies revealed a non-caseating granuloma with both epithelioid cells and Langhans giant cells. After the admission, these symptoms and radiological findings gradually improved without any treatment. Then, a returning-home provocation test was positive only when he worked cleaning up onion peels with air compressors. A. niger was cultured from his workplace and black mold from the onion peels. The precipitation antibody and the antigen were both positive for Aspergillus. Therefore, we diagnosed this case as hypersensitivity pneumonitis caused by inhalation of A. niger. Although hypersensitivity pneumonia caused by A. niger is rare, physicians should aware the possibility of this condition in farmers because A niger is ubiquitously present in several vegetables and fruits.

Relationship between Oxidative Stress, Physical Activity, and Vitamin Intake in Patients with Asthma.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of bronchial asthma. Antioxidant nutrition and supplementation have been used to reduce oxidative stress. However, a clinical trial with antioxidant supplementation showed no beneficial effects in patients with asthma. On the other hand, physical activity is related to the prognosis of chronic obstructive pulmonary disease (COPD) and is also related to oxidant status. We investigated the relationships between oxidative stress, serum levels of vitamins, dietary vitamin intake, daily activities, and pulmonary functions in patients with asthma. METHODS: Eighteen patients with bronchial asthma were enrolled in this study. Reactive oxidative stress was assessed by measuring organic hydroperoxides (diacron reactive oxygen metabolites: dROM) in sera and by measuring H2O2 levels in exhaled breath condensates. The biological antioxidant capacity in serum was evaluated by measuring antioxidant potential capacity against ferric ion. We also assessed pulmonary functions, fraction of exhaled nitric oxide, serum levels of vitamins, dietary vitamin intake, and physical activities. RESULTS: There were no relationships between the index of oxidative stress (dROM and H2O2 in exhaled breathe condensates) and pulmonary functions, serum levels of vitamins, daily vitamin intakes, and activity levels in patients with asthma. CONCLUSION: The status of transient oxidative stress may not be related to daily activities, vitamin levels, and pulmonary functions in patients with asthma in a real-life setting. However, our results were obtained in the short-term period from a small number of subjects, so a large longitudinal study is required to ascertain the relationships between oxidative stress, physical activity and vitamin intake in patients with asthma.

Leukocytapheresis for the treatment of acute exacerbation of idiopathic interstitial pneumonias: a pilot study.

OBJECTIVE: Idiopathic interstitial pneumonias (IIPs) are a group of heterogeneous diffuse parenchymal lung disorders of unknown etiology. An acute exacerbation (AE) is an acute respiratory deterioration that occurs in IIPs. The prognosis of AE of IIPs (AE-IIPs) is extremely severe; however, no established therapies exist. We aimed to evaluate the efficacy of leukocytapheresis (LCAP) to treat patients with AE-IIPs. PATIENTS AND METHODS: Six chronic IIPs patients who developed AE were enrolled in this study. We performed LCAP on days 2, 3, 9 and 10 in all six patients. All patients were also treated with high-dose corticosteroids and a continuous administration of low-molecular-weight heparin. We observed 30-day survival after the diagnosis of AE to evaluate the efficacy of LCAP. We also assessed oxygenation, high-resolution computed tomography (HRCT) findings, and certain chemical mediators in the peripheral blood. RESULTS: Five of six patients survived more than 30 days. One patient died of progressive respiratory failure. Oxygenation and HRCT findings tended to improve in all survivors. The serum levels of lactate dehydrogenase, high mobility group box-1, and interleukin-18 were significantly decreased statistically post-LCAP. No severe adverse events occurred. CONCLUSION: We suggest that LCAP is a safe and effective therapy for treating patients with AE-IIPs. J. Med. Invest. 64: 110-116, February, 2017.

γ-Tocotrienol Inhibits TGF-ß1-Induced Contractile Phenotype Expression of Human Airway Smooth Muscle Cells.

BACKGROUND: Tocotrienols, members of the vitamin E family, exist in four different isoforms (α, ß, γ and δ tocotrienol) that have can be protective against brain damage, as well as having anticancer effects in vivo and in vitro. We have shown that γ-tocotrienol inhibits human airway smooth muscle cell proliferation and migration induced by platelet-derived growth factor (PDGF)-BB by suppressing RhoA activation. In this study, we tested whether γ-tocotrienol modulates transforming growth factor (TGF) -ß-induced induction of human airway smooth muscle (ASM) into a contractile phenotype and concomitant synthesis of extracellular matrix proteins. METHODS: ASM cells were stimulated with TGF-ß1 (2 ng/mL) for 48 hours and the effect of γ-tocotrienol (50 µM) on α-smooth muscle actin, fibronectin and collagen I expression was assessed using Western blotting. The signaling pathways involved in TGF-ß1 stimulation were also investigated. RESULTS: TGF-ß1 increased α-smooth muscle actin, fibronectin and collagen Ⅰ abundance by 3- to 5-fold. This response was inhibited significantly by γ-tocotrienol. Furthermore, γ-tocotrienol suppressed RhoA activation, but did not affect Smad2 or Smad3 phosphorylation. CONCLUSION: These results indicate that γ-tocotrienol has potential for benefit in modulating on airway remodeling in asthma, likely via a mechanism involving the suppression of TGF-ß activation of RhoA.

Pulmonary Metastatic Choriocarcinoma from a Burned-out Testicular Tumor.

A 54-year-old man was referred to our hospital because of progressive dyspnea. Chest computed tomography showed multiple nodular shadows with a peripheral ground-glass halo. His clinical condition continued to deteriorate with the development of progressive respiratory failure requiring mechanical ventilation. A histological examination of a transbronchial lung biopsy revealed choriocarcinoma. The patient died within nine days of admission. A histological examination of the right testis during an autopsy revealed a burned-out testicular tumor consisting of a teratoma and a fibrous scar. We herein report a rare case of pulmonary multiple metastatic choriocarcinoma originating from a burned-out testicular tumor.

γ-Tocotrienol reduces human airway smooth muscle cell proliferation and migration.

AIMS: Vitamin E is an antioxidant that occurs in 8 different forms (α, ß, γ, and δ tocopherol and tocotrienol). Clinical trials of tocopherol supplementation to assess the impact of antioxidant activity in asthma have yielded equivocal results. Tocotrienol exhibits greater antioxidant activity than tocopherol in several biological phenomena in vivo and in vitro. We tested the effect of tocotrienol on human airway smooth muscle (ASM) cell growth and migration, both of which mediate airway remodeling in asthma. MAIN METHODS: We measured platelet-derived growth factor-BB (PDGF-BB)-induced ASM cell proliferation and migration by colorimetric and Transwell migration assays in the presence and absence of γ-tocotrienol (an isoform of tocotrienol). KEY FINDINGS: PDGF-BB-induced ASM cell proliferation and migration were inhibited by γ-tocotrienol. This effect was associated with inhibition of RhoA activation, but it had no effect on p42/p44 mitogen-activated protein kinase (MAPK) or Akt1 activation. We confirmed that pharmacological inhibition of Rho kinase activity was sufficient to inhibit PDGF-BB-induced ASM cell proliferation and migration. SIGNIFICANCE: γ-Tocotrienol could impart therapeutic benefits for airway remodeling in asthma by inhibiting human ASM cell proliferation and migration.

Causes of death in patients with asthma and asthma-chronic obstructive pulmonary disease overlap syndrome.

BACKGROUND: The administration of inhaled corticosteroids and worldwide usage of several asthma guidelines have improved asthma mortality. Elderly patients with asthma show high mortality rates, and may have several comorbidities, including overlap with chronic obstructive pulmonary disease (COPD). Among patients showing asthma overlapped with COPD (asthma-COPD overlap syndrome; ACOS), mortality is worse than for asthma alone. Therefore, we investigated comorbidities, malignancies, and causes of death in patients with asthma and ACOS. METHODS: This was a retrospective study. From January 2000 to March 2012, 650 patients were followed up at Tottori University Hospital. Medical records were reviewed to collect data regarding patient characteristics and comorbidities, and causes of death were recorded for patients who died during the study period. RESULTS: Eighty-seven patients died during the study period. The most frequent cause of death was malignancy. The proportion of malignant disease was 21.7% in all patients, 19.4% in patients with asthma alone, and 32.4% in patients with ACOS. One patient died from an asthma attack during this period. CONCLUSION: The most frequent cause of death in patients with asthma and ACOS was malignant disease. It is necessary to control not only asthma but also comorbidities in patients with asthma, especially in those with ACOS.

The relationships among sleep efficiency, pulmonary functions, and quality of life in patients with asthma.

BACKGROUND: Sleep disturbance is commonly observed in patients with asthma, especially in those with poorly controlled asthma. Evaluating sleep quality to achieve good control of asthma is important since nocturnal asthmatic symptoms such as cough, wheezing, and chest tightness may disturb sleep. Actigraphy is an objective, ambulatory monitoring method for tracking a patient's sleep and wake activities and for assessing sleep quality, as reflected by total sleep time, sleep efficiency, duration of awakening after sleep onset (WASO), and sleep onset latency. PATIENTS AND METHODS: Fifty patients with asthma were enrolled in this study. Sleep quality was assessed employing wristwatch-type actigraphy (Actiwatch 2). The level of asthma control was assessed by the Asthma Control Questionnaire (ACQ), and asthma-related quality of life was assessed by the Asthma Quality of Life Questionnaire (AQLQ). The parameters for sleep quality were compared using ACQ scores, AQLQ scores, and pulmonary function test results. RESULTS: The total sleep time was 387.2 minutes, WASO was 55.8 minutes, sleep efficiency was 87.01%, sleep onset latency was 8.17 minutes, and the average ACQ was 0.36. Neither sleep efficiency nor WASO correlated with respiratory functions, ACQ scores, or AQLQ scores. CONCLUSION: Sleep-related parameters assessed by actigraphy in well-controlled asthma do not correlate with pulmonary functions, the asthma control level, or daytime quality of life. Sleep quality should be evaluated independently when asthma is well-controlled.

Infective endocarditis caused by Achromobacter xylosoxidans: a case report and review of the literature.

An 86-year-old woman who underwent placement of a prosthetic aortic valve for regurgitation 5 years previously was admitted because of spiking fever. The blood culture results were positive for gram-negative rods, which were identified as Achromobacter xylosoxidans. Approximately 4 months after being sent to the hospital, transthoracic echocardiography revealed vegetation at the prosthetic aortic valve. Ultimately, a diagnosis of A. xylosoxidans endocarditis of the prosthetic aortic valve was made. We report an extremely rare case of bacteremia associated by prosthetic valve endocarditis with A. xylosoxidans. In addition, we review 10 previously reported cases of endocarditis caused by A. xylosoxidans.