Latent metabolic bone disease, skeletal dysplasia and other conditions related to low bone formation among 38 patients with subtrochanteric femoral fractures: a retrospective observational study.

Subtrochanteric femoral fracture is rare and intractable due to the possible association with low bone formation. Retrospective analysis of 38 patients with subtrochanteric femoral fractures revealed that four patients suffered from disorders related to low bone formation and there were specific treatments for two of them. PURPOSE: The main aim of this study was to detect latent metabolic bone diseases and skeletal dysplasia associated with low bone formation among patients with morphologic atypical femoral fracture (AFF). A second aim was to evaluate the frequency of recognized risk factors, such as antiresorptive agents, glucocorticoids, and age. METHODS: Clinical information was retrospectively analyzed among 38 Japanese patients who were admitted to the Department of Orthopedic Surgery and Spinal Surgery and the Division of Emergency and Critical Care Medicine at the University of Tokyo Hospital with diagnoses of subtrochanteric fractures between February 2012 and March 2022. RESULTS: Among 38 patients (including 30 females), 21 patients were aged 75 and over. Ten patients had past oral glucocorticoid use, and 18 had past antiresorptive agent use. Two patients were diagnosed with hypophosphatemic osteomalacia after the development of fractures. One patient was suspected to be a carrier of a loss-of-function variant of alkaline phosphatase, biomineralization associated (ALPL), and one other patient had previously been genetically diagnosed with pycnodysostosis. Among four patients with a diagnosis or suspicion of these metabolic bone diseases and skeletal dysplasia, four had past clinical fractures, two had past subtrochanteric femoral fractures, and two had subtrochanteric femoral fractures on both sides. CONCLUSION: If clinicians encounter patients with morphologic AFF, latent diseases related to low bone formation should be carefully differentiated because appropriate treatment may prevent delayed union and recurrent fractures. Additionally, it may be desirable to exclude these bone diseases in advance before initiating long-term use of antiresorptive agents in osteoporotic patients by screening with serum alkaline phosphatase levels to reduce the risk of morphologic AFF.

Hypopituitarism with secondary adrenocortical insufficiency and arginine vasopressin deficiency due to hypophysitis after COVID-19 vaccination: a case report.

BACKGROUND: Although vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported. CASE PRESENTATION: An 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 µg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 µIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient's disease course was stable with continued thyroid and adrenal corticosteroid supplementation. CONCLUSIONS: Herein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination.

The cross-sectional area of erector spinae muscle and the liver-to-spleen ratio are associated with frailty in older patients with diabetes: a cross-sectional study.

BACKGROUND: Older patients with diabetes mellitus are more susceptible to frailty. Although some imaging markers of appendicular skeletal muscle mass obtained using dual-energy X-ray absorptiometry or computed tomography (CT) imaging can reflect frailty status, the association between imaging indices obtained by abdominal CT scans and frailty in older inpatients has not been reported. METHODS: A total of 151 older inpatients with diabetes mellitus (median age, 79 years; men, 42%) who underwent abdominal CT scans close to the admission date were studied to examine the associations between abdominal CT indices and frailty. Two frailty definitions were used: the modified Cardiovascular Health Study (mCHS) criteria and Kihon Checklist (KCL) criteria. Using the imaging analysis software SYNAPSE VINCENT®, we compared the cross-sectional areas (CSA) of four truncal muscles (erector spinae, iliopsoas, rectus abdominis, and abdominal oblique muscles) and the liver-to-spleen ratio (L/S), the ratio of the CT values of the liver and spleen between frail and non-frail patients. The muscle areas that showed the strongest associations with frailty were also investigated in relation to grip strength and walking speed. Finally, multivariate binominal logistic regression analyses were performed to assess the independent associations of CSA of muscle and L/S with the prevalence of frailty. RESULTS: The prevalence of frailty defined by the mCHS and KCL criteria was 55% and 52%, respectively. The CSA of the erector spinae muscle was most significantly associated with frailty, and was significantly smaller in both sexes of mCHS-defined frail patients and in men with KCL-defined frailty. The CSA of erector spinae muscle was also positively correlated with grip strength and walking speed. In contrast, the L/S was higher in men with KCL-defined frailty. Multivariate logistic regression analyses revealed that the CSA of the erector spinae muscle was independently associated with mCHS-defined frailty in women, and the L/S was associated with KCL-defined frailty in men. CONCLUSIONS: The CSA of erector spinae muscle and low liver fat content could be indices of frailty in older patients with diabetes.

[A geriatric case of hyperosmolar hyperglycemic state with osmotic demyelination syndrome that manifested with dysphagia].

The patient was an 84-year-old man who had been on insulin therapy for type 2 diabetes mellitus for 55 years. He had undergone bile duct stenting to avoid obstruction due to adenocarcinoma of the bile duct. The patient had suffered from fever and anorexia for two weeks, and had subsequently stopped insulin therapy. Since he showed signs of impaired consciousness, he was taken to the emergency room, and was diagnosed with a hyperosmotic hyperglycemic state (HHS) based on the following laboratory findings: blood glucose, 632 mg/dL; plasma osmolality, 391 mOsm/kg·H2O; and serum Na, 163 mEq/L, with urine ketone bodies±and sepsis (Klebsiella pneumoniae). He was therefore admitted to the hospital. His blood glucose and serum Na levels slowly improved following the administration of fluids, insulin, and antibiotics. The patient's consciousness disturbance also improved. However, on the third day after admission, dysphagia was newly observed when the patient resumed eating, and swallowing endoscopy revealed a delayed gag reflex and pharyngeal retention of saliva. Cranial magnetic resonance imaging showed a high-intensity area in the central pontine, which was considered to be caused by osmotic demyelination syndrome (ODS). The patient's oral intake ability recovered with swallowing rehabilitation. ODS is a rare complication of HHS. We report a case of HHS with ODS, in which the patient's chief complaint was dysphagia, which should be distinguished from other diseases.

Multigenerational effects of whole body exposure to 2.14 GHz W-CDMA cellular phone signals on brain function in rats.

The present experimental study was carried out with rats to evaluate the effects of whole body exposure to 2.14 GHz band code division multiple access (W-CDMA) signals for 20 h a day, over three generations. The average specific absorption rate (SAR, in unit of W/kg) for dams was designed at three levels: high (<0.24 W/kg), low (<0.08 W/kg), and 0 (sham exposure). Pregnant mothers (4 rats/group) were exposed from gestational day (GD) 7 to weaning and then their offspring (F1 generation, 4 males and 4 females/dam, respectively) were continuously exposed until 6 weeks of age. The F1 females were mated with F1 males at 11 weeks old, and then starting from GD 7, they were exposed continuously to the electromagnetic field (EMF; one half of the F1 offspring was used for mating, that is, two of each sex per dam and 8 males and 8 females/group, except for all offspring for the functional development tests). This protocol was repeated in the same manner on pregnant F2 females and F3 pups; the latter were killed at 10 weeks of age. No abnormalities were observed in the mother rats (F0 , F1 , and F2 ) and in the offspring (F1 , F2 , and F3 ) in any biological parameters, including neurobehavioral function. Thus, it was concluded that under the experimental conditions applied, multigenerational whole body exposure to 2.14 GHz W-CDMA signals for 20 h/day did not cause any adverse effects on the F1 , F2 , and F3 offspring.

Categorization using the Dementia Assessment Sheet for Community-Based Integrated Care System 8-items (DASC-8) based on cognitive function and activities of daily living predicts frailty, disability and mortality in older adults.

AIM: This longitudinal study aimed to determine whether categorization by the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) is associated with risk of frailty onset, disability, and mortality. METHODS: We analyzed longitudinal data from outpatients aged 65 years and older evaluated for the DASC-8 at the Frailty Clinic. The outcomes during the 3-year follow-up period were (Study A) frailty onset (Kihon Checklist ≥8) and (Study B) disability (new certification of nursing care needs) or mortality. Multivariate Cox regression analyses were performed to examine independent associations between the DASC-8 category and outcomes, and hazard ratios and 95% confidence intervals (CIs) were calculated after adjustment for age, sex, and the presence or absence of diabetes, hypertension, and dyslipidemia. RESULTS: (Study A) Out of the 216 patients without frailty in Categories I or II at baseline, 40 (20.4%) and 11 (55.0%) developed frailty, respectively. The adjusted hazard ratio was 3.62 (95% CI: 1.69-7.76, P < 0.001). (Study B) Out of the 350 patients who did not require long-term care at baseline, disability or death occurred for 20 (7.3%) in Category I, 14 (23.0%) in Category II, and 9 (56.3%) in Category III. The adjusted hazard ratios were 2.40 (Category I vs. II; 95% CI: 1.13-5.11, P = 0.023) and 5.43 (Category I vs. III; 95% CI: 2.23-13.3, P < 0.001). CONCLUSION: Categorization according to DASC-8 is associated with the risk of frailty, disability, and mortality in older patients. Geriatr Gerontol Int 2024; 24: 150-155.

Coexistence of high visceral fat area and sarcopenia is associated with atherosclerotic markers in old-old patients with diabetes: A cross-sectional study.

AIMS/INTRODUCTION: To investigate whether sarcopenic obesity is associated with the progression of atherosclerotic lesions in older patients with diabetes and to identify the obesity components of sarcopenic obesity that best reflect atherosclerosis. MATERIALS AND METHODS: In 118 inpatients aged ≥75 years with diabetes mellitus, sarcopenia defined as a low skeletal muscle mass and low grip strength was assessed, and sarcopenia coexisting with a high body-fat percentage or visceral fat area was defined as sarcopenic obesity. Correlations between the obesity components and atherosclerotic markers, including the carotid intima-media thickness, were analyzed; the intima-media thickness was analyzed in four groups with and without obesity and sarcopenia, and a multiple linear regression analysis adjusted for covariates was conducted to investigate whether sarcopenic obesity was independently associated with the intima-media thickness. RESULTS: The visceral fat area and intima-media thickness showed positive correlations in the overall patients (P = 0.032) and the sarcopenia (P = 0.016) group but showed no associations in participants without sarcopenia. The intima-media thickness in the group showing sarcopenia with a high visceral fat area was significantly higher than that in the control group (P = 0.012). Sarcopenic obesity defined by a high body-fat percentage and high visceral fat area was independently associated with the intima-media thickness even after adjusting for age, sex, and atherogenic risk factors. However, sarcopenic obesity defined by a high visceral fat area was more strongly associated with the intima-media thickness (ß = 0.384, P = 0.002) than that defined by the high body-fat percentage (ß = 0.237, P = 0.068). CONCLUSIONS: Sarcopenic obesity, especially that defined by visceral fat accumulation, reflected the risk of atherosclerotic lesion progression in older patients with diabetes.

Effects of electromagnetic fields emitted from W-CDMA-like mobile phones on sleep in humans.

In this study, we investigated subjective and objective effects of mobile phones using a Wideband Code Division Multiple Access (W-CDMA)-like system on human sleep. Subjects were 19 volunteers. Real or sham electromagnetic field (EMF) exposures for 3 h were performed before their usual sleep time on 3 consecutive days. They were exposed to real EMF on the second or third experimental day in a double-blind design. Sleepiness and sleep insufficiency were evaluated the next morning. Polysomnograms were recorded for analyses of the sleep variables and power spectra of electroencephalograms (EEG). No significant differences were observed between the two conditions in subjective feelings. Sleep parameters including sleep stage percentages and EEG power spectra did not differ significantly between real and sham exposures. We conclude that continuous wave EMF exposure for 3 h from a W-CDMA-like system has no detectable effects on human sleep.

The Effect of Asfotase Alfa on Plasma and Urine Pyrophosphate Levels and Pseudofractures in a Patient With Adult-Onset Hypophosphatasia.

Hypophosphatasia (HPP) is an inherited disease caused by variants of the ALPL gene encoding tissue-nonspecific alkaline phosphatase. Adult-onset HPP (adult HPP), known as a mild form of HPP, develops symptoms involving osteomalacia after the age of 18 years. Asfotase alfa (AA) is a modulated recombinant human alkaline phosphatase (ALP) that has been established as a first-line therapy for severe forms of HPP, such as perinatal and infantile forms. We described a 64-year-old female who presented with pseudofractures in bilateral femur diaphyses and impaired mobility. Low serum ALP activity and a high concentration of urine phosphoethanolamine indicated the diagnosis of HPP, which was confirmed by the identification of a homozygous variant in the ALPL gene (c.319G > A; p.Val107Ile). An in vitro transfection experiment to measure the ALP activity of this novel variant protein was performed, resulting in 40% of the residual enzymatic activity compared with the wild type. AA was initiated to facilitate the union of pseudofracture and to improve mobility. After 6 months, radiographic images revealed the disappearance of fracture lines, and improvement of ambulatory ability was confirmed by the 6-minute walk test (525 to 606 m). The EQ-5D-5L index was also improved (0.757 to 0.895). Within a follow-up period, the levels of urine pyrophosphate corrected by urine creatinine (uPPi/Cre) declined in parallel with the level of plasma PPi (plasma PPi: 6.34 to 1.04 µM, uPPi/Cre: 226.8 to 75.4 nmol/mg). The beneficial effect of AA on pseudofracture healing in adult HPP was presented, although the application of AA should be restricted to patients exhibiting relatively severe manifestations. In addition, a novel pathogenic variant of the ALPL gene was identified with the supportive result of functional analysis. Furthermore, when monitoring patients with HPP treated with AA, uPPi/Cre might be a convenient substitute for plasma PPi, which requires immediate filtration after blood sampling. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Subclinical Atherosclerosis, Vascular Risk Factors, and White Matter Alterations in Diffusion Tensor Imaging Findings of Older Adults With Cardiometabolic Diseases.

White matter abnormalities may reflect cerebral microvessel disease. Diffusion tensor imaging (DTI) can help detect early changes in white matter integrity in each tract. However, studies investigating the relationship between subclinical atherosclerosis markers and white matter alterations in DTI findings are limited. This study aimed to examine associations between cardiovascular risk factors and indices of subclinical atherosclerosis-ankle brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and carotid artery intima-media thickness (IMT)-and altered white matter integrity in older patients. A total of 224 patients (aged ≥65 years) with cardiometabolic disease who underwent magnetic resonance imaging (MRI) and either plethysmography or cervical ultrasound at the start of the 3-year observational study period were included in this study. We measured fractional anisotropy (FA) and mean diffusivity (MD), which are indices of white matter integrity in seven white matter tracts. In a univariate analysis, lower ABI and higher baPWV values were associated with FA or MD abnormalities in several tracts, whereas IMT was scarcely associated with such change. In addition, high blood pressure and glycoalbumin/glycohemoglobin ratio (GA/HbA1c) and low body mass index (BMI) and triglyceride (TG) levels were associated with FA or MD abnormalities. In a multivariate analysis adjusted for age, sex, BMI, diastolic blood pressure, TG, and GA/HbA1c, the associations between ABI and FA or MD remained in all of either side of the following tracts: anterior thalamic radiation, forceps minor, inferior frontooccipital fasciculus (p < 0.001 for all) and superior longitudinal fasciculus (SLF; p < 0.05), whereas most of those between baPWV and FA or MD disappeared except for SLF (p < 0.05). These results indicate that low ABI could be an indicator of white matter abnormalities.

Effects of gestational exposure to 1.95-GHz W-CDMA signals for IMT-2000 cellular phones: Lack of embryotoxicity and teratogenicity in rats.

The present study was designed to evaluate whether gestational exposure to an EMF targeting the head region, similar to that from cellular phones, might affect embryogenesis in rats. A 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is one applied for the International Mobile Telecommunication 2000 (IMT-2000) system and used for the freedom of mobile multimedia access (FOMA), was employed for exposure to the heads of four groups of pregnant CD(SD) IGS rats (20 per group) for gestational days 7-17. The exposure was performed for 90 min/day in the morning. The spatial average specific absorption rate (SAR) for individual brains was designed to be 0.67 and 2.0 W/kg with peak brain SARs of 3.1 and 7.0 W/kg for low (group 3) and high (group 4) exposures, respectively, and a whole-body average SAR less than 0.4 W/kg so as not to cause thermal effects due to temperature elevation. Control and sham exposure groups were also included. At gestational day 20, all dams were killed and fetuses were taken out by cesarean section. There were no differences in maternal body weight gain. No adverse effects of EMF exposure were observed on any reproductive and embryotoxic parameters such as number of live (243-271 fetuses), dead or resorbed embryos, placental weights, sex ratios, weights or external, visceral or skeletal abnormalities of live fetuses.

Successful treatment of eosinophilic otitis media associated with severe bronchial asthma with an anti-IL-5 monoclonal antibody, mepolizumab.

Eosinophilic otitis media (EOM), which is characterized by the accumulation of eosinophils in middle ear effusion and the middle ear mucosa, is a refractory type of otitis media that is often associated with asthma. Although an early diagnosis and appropriate treatment are necessary to prevent the progression of hearing loss in patients with EOM, there are currently no well-established treatments for this condition. We treated a 60-year-old male patient with asthma and EOM. The patient's asthma was poorly controlled, despite the use of high-dose inhaled corticosteroids, long-acting beta-agonist treatment, and the regular use of systemic corticosteroids. Mepolizumab, an anti-IL-5 monoclonal antibody, was started to treat the patient's refractory asthma. At 4 months after the initiation of mepolizumab treatment, the patient's asthma, hearing, and middle ear effusion improved. The present case suggests that mepolizumab therapy can control EOM and asthma.

Changes of glucocorticoid receptor expression in the nasal polyps of patients with chronic sinusitis following treatment with glucocorticoid.

Glucocorticoids (GCs) bind to the cellular glucocorticoid receptors (GRs) to exert anti-inflammatory and immunosuppressive actions. We investigated the changes in the expressions of the two GR isoforms, GR-alpha and GR-beta, in nasal polyps treated with GC. Immunofluorescent staining revealed prominent expression of GR-alpha in the inflammatory cell infiltrate in the polyps obtained from patients with chronic sinusitis and bronchial asthma. Furthermore, while the expression of GR-alpha was significantly reduced following GC treatment, that of GR-beta remained unchanged. The results of real-time PCR also revealed that the prominent expression of GR-alpha mRNA in the polyps decreased following GC treatment, while the expression of GR-beta mRNA remained unchanged. The observations indicate that GR-alpha may play the major role in the inflammation associated with nasal polyps and the ratio of the expression level of GR-beta to that of GR-alpha may serve as a useful index of the clinical efficacy of GC treatment.

Modulation of eosinophil survival by epinastine hydrochloride, an H1 receptor antagonist, in vitro.

The influence of epinastine hydrochloride (EP) on eosinophil survival was examined by an in vitro cell culture technique. Nasal epithelial cells (NECs) were stimulated with 25 ng/ml TNF-alpha in the presence of EP (10 to 30 ng/ml). After 24 h, the culture supernatants were obtained and used as conditioned media of NECs (CM). Eosinophils (1 x 10(3) cells/ml) prepared from healthy human peripheral blood were incubated with 25% CM and eosinophil survival was assessed by trypan blue dye exclusion test 48 h later. CM prepared from NEC cultures pre-treated with TNF-alpha and EP caused a decrease in eosinophil survival as compared with that from NEC cells pre-treated with TNF-alpha alone. The minimum concentration of EP that caused a significant decrease in eosinophil survival was 25 ng/ml. The addition of EP into eosinophil cultures did not cause inhibition of eosinophil survival, which was prolonged by stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF), even when 40 ng/ml EP was added to cell cultures. We then examined the levels of GM-CSF in CM by ELISA. Treatment of NECs with EP at more than 25 ng/ml, reduced the ability of NECs to produce GM-CSF in response to TNF-alpha stimulation. These results may suggest that EP suppresses eosinophil survival through the suppression of GM-CSF production from NECs induced by inflammatory stimulation and that this suppressive effect contributes, in part, to the therapeutic mode of action of EP on allergic diseases.

No adverse effects detected for simultaneous whole-body exposure to multiple-frequency radiofrequency electromagnetic fields for rats in the intrauterine and pre- and post-weaning periods.

In everyday life, people are exposed to radiofrequency (RF) electromagnetic fields (EMFs) with multiple frequencies. To evaluate the possible adverse effects of multifrequency RF EMFs, we performed an experiment in which pregnant rats and their delivered offspring were simultaneously exposed to eight different communication signal EMFs (two of 800 MHz band, two of 2 GHz band, one of 2.4 GHz band, two of 2.5 GHz band and one of 5.2 GHz band). Thirty six pregnant Sprague-Dawley (SD) 10-week-old rats were divided into three groups of 12 rats: one control (sham exposure) group and two experimental (low- and high-level RF EMF exposure) groups. The whole body of the mother rats was exposed to the RF EMFs for 20 h per day from Gestational Day 7 to weaning, and F1 offspring rats (46-48 F1 pups per group) were then exposed up to 6 weeks of age also for 20 h per day. The parameters evaluated included the growth, gestational condition and organ weights of the dams; the survival rates, development, growth, physical and functional development, memory function, and reproductive ability of the F1 offspring; and the embryotoxicity and teratogenicity in the F2 rats. No abnormal findings were observed in the dams or F1 offspring exposed to the RF EMFs or to the F2 offspring for any of the parameters evaluated. Thus, under the conditions of the present experiment, simultaneous whole-body exposure to eight different communication signal EMFs at frequencies between 800 MHz and 5.2 GHz did not show any adverse effects on pregnancy or on the development of rats.

Influence of fluticasone propionate on the production of vascular endothelial growth factor and basic fibroblast growth factor from nasal fibroblasts in vitro.

The influence of fluticasone propionate (FP) on vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) production from nasal polyp fibroblasts (NPFs) was examined in vitro. NPFs, at a density of 2.5 x 10(5) cells/ml, were stimulated with 25 ng/ml TNF-alpha in the presence or absence of FP for 24 h. FP at more than 10(-6) M could suppress VEGF production from NPFs. bFGF production induced by TNF-alpha stimulation was also suppressed by FP, when the agent was added to cell cultures at more than 10(-7) M. The present results also showed the suppressive activity of FP on mRNA expression for VEGF and bFGF, which were increased by TNF-alpha stimulation.

Suppression of matrix metalloproteinase production from nasal fibroblasts by fluticasone propionate in vitro.

OBJECTIVE: To examine the influence of fluticasone propionate (FP) on matrix metalloproteinase (MMP) production from nasal polyp fibroblasts in vitro. MATERIAL AND METHODS: Fibroblasts derived from five nasal polyps were stimulated with tumor necrosis factor (TNF)-alpha in the presence of various concentrations of FP. The influence of FP on MMP production was assessed by examining the levels of MMP-2 and -9 in culture supernatants using ELISA. We also examined the influence of FP on MMP mRNA expression using reverse transcriptase polymerase chain reaction. RESULTS: The addition of FP caused significant suppression of MMP-2 and -9 production from nasal polyp fibroblasts in response to TNF-alpha stimulation. MMP mRNA expression was also suppressed by the addition of FP to cell cultures. The minimum concentration of the agent required to cause suppression was 10(-5) M. CONCLUSION: These results suggest that the inhibitory action of FP on tissue remodeling may underlie the clinical efficacy of corticosteroids in nasal polyposis.

Seasonal allergic rhinitis affects sinonasal microbiota.

BACKGROUND: Microbes and allergens can stimulate the nasal mucosa, potentially leading to the development of acute bacterial rhinosinusitis (ABRS). This study was designed to determine if allergen exposure alters the sinonasal microbiome. METHODS: We performed a parallel observational study of healthy adults with seasonal allergic rhinitis (SAR; grass or tree, n = 20) or nonallergic subjects (n = 19). Microbiota specimens were obtained by endoscopy from the middle meatus and vestibule before and during the relevant season and were analyzed by terminal restriction fragment length polymorphism analysis. Differences in bacterial microbiota were assessed by standard ecological measures of bacterial diversity. Quality of life and symptom scores were recorded, and nasal lavages for eosinophils were performed. RESULTS: SAR subjects had increased nasal symptoms in season, impaired disease-specific quality of life, and increased nasal eosinophils, compared with no changes in nonallergic subjects. During the season, SAR subjects had a significantly greater variety of organisms in the middle meatus compared with nonallergic subjects (p < 0.036) and increased bacterial diversity (Shannon index, p < 0.013). We found a significant positive correlation between bacterial diversity in the middle meatus during the season and the nasal lavage eosinophil count of SAR subjects. There were no significant changes in the nasal vestibule (p > 0.05, all comparisons). CONCLUSION: The interaction of allergy and microbiota may affect the sinonasal physiology, with broad implications for several airway diseases. Characterization of the specific organisms involved using next-generation sequencing may clarify the relationship between allergic inflammation and ABRS. This finding may help explain why allergic inflammation predisposes to ABRS.

Effect of prednisone on nasal symptoms and peripheral blood T-cell function in chronic rhinosinusitis.

BACKGROUND: Systemic corticosteroids are the most effective anti-inflammatory drugs used for controlling chronic rhinosinusitis (CRS) symptoms. The potential mechanisms for their beneficial effects include increasing the number and function of T regulatory cells (Tregs), as reported in the local tissue post-intranasal steroid treatment. We investigated the effect of systemic corticosteroids on peripheral blood (PB) Tregs in subjects with CRS. METHODS: Twenty CRS subjects and 19 controls were recruited. PB mononuclear cells (PBMCs) were isolated from CRS subjects before and after systemic corticosteroid administration in the course of clinical treatment. Control subjects received no treatment and were studied at one visit. Nasal symptoms were recorded. CD4(+) CD25(+) Foxp3(+) cells (Tregs) were analyzed by flow cytometry. Messenger RNA (mRNA) levels for interferon γ (IFN-γ), interleukin 4 (IL-4), IL-10, IL-13, IL-17A, transforming growth factor ß1 (TGF-ß1), forkhead box P3 (FoxP3), and GATA-binding factor 3 (GATA-3) were measured in PBMCs using real-time polymerase chain reaction (PCR). RESULTS: CRS subjects reported improved nasal symptoms (p = 0.005) and significantly reduced PB Tregs after treatment with corticosteroids (p = 0.042). The transcript levels of IL-4 and GATA-3 were significantly higher in the CRS subjects at their first visit when compared to controls (p = 0.019 and p = 0.05, respectively). Corticosteroid treatment lowered the transcript levels of immunoregulatory transcription factors [FoxP3 (p = 0.048) and GATA-3 (p = 0.012)] and IFN-γ (p = 0.036) in PB. CONCLUSION: In contrast to prior work in local nasal tissue, our study reports reduced PB Tregs and decreased T helper 1 (T(H)1) and T(H)2 function after treatment with systemic corticosteroids. These data indicate that corticosteroid effects on Tregs in CRS are complex involving local signals in the tissue that are distinct from those in circulating cells.

Rhinosinusitis and asthma-microbiome and new perspectives.

PURPOSE OF REVIEW: Microbiome is one of the new perspectives in human health research, including airway diseases. There are several publications about the relationship of the microbiome and allergic diseases. Although pathogenesis of chronic rhinosinusitis (CRS) as well as its relationship with asthma has been widely investigated, the relationship of the microbiome and CRS is not yet well known. RECENT FINDINGS: The relationship between the hygiene hypothesis and microorganisms inside the human body and in the environment around it has been clearly shown. Furthermore, several researchers have reported that the microorganisms in the gut play a major role in regulating the immune cells that are of relevance to asthma and allergic diseases, such as Th1, Th2, Th17, Treg and dendritic cells as well as Toll-like receptors. Reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity.Some studies have shown a close relationship between CRS and Staphylococcus aureus, anaerobes and so on in the nasal cavity or paranasal sinuses, although the relationship between CRS and microorganisms in the gut has not been demonstrated. SUMMARY: In this review, we summarized about the microbiome, mainly in asthma and allergic diseases. The relationship between asthma and CRS has been clearly shown, and in particular, CRS with nasal polyps (CRSwNP) has been considered to be Th2-dominant. Studies examining environmental microbial exposure in populations at risk for CRS are necessary to improve our understanding of the role this factor plays in disease development.