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1.
J Arthroplasty ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31481288

RESUMO

BACKGROUND: Little is known about the long-term changes in physical activity (PA) after total hip arthroplasty (THA). The purpose of this study is to describe the changes in the number of steps and intensity of PA as measured by accelerometers, patient-reported physical function, and health-related quality of life of THA patient preoperatively and at 1 and 3 years after THA. METHODS: This study included 153 patients (mean age, 61.4 years; 86.3% women) who wore an accelerometer for 10 consecutive days and completed the Oxford Hip Score (OHS) and the Short Form 8 at the 5-year follow-up after THA. PA was evaluated based on the mean steps per day and the time spent performing moderate-to-vigorous PA (MVPA) per week. RESULTS: All 5 indicators had significantly increased at 1 year after THA, although only MVPA and OHS had further increased significantly at the 3-year follow-up. The predictor of improvement in the number of steps from baseline to 1 year post-THA was younger age, while those of improvement in MVPA from baseline to 3-year post-THA were younger age, higher OHS, and better Short Form 8 mental component scores using mixed-model analysis. Participation in the PA measurements was high (69.9%) at the 3-year follow-up. No significant changes were observed for these outcomes in the remaining cohort beyond 3 years after THA. CONCLUSION: In post-THA patients, MVPA continued to increase for 3 years postoperatively. Therefore, PA must be measured over the medium term to long term following THA.

2.
J Orthop Sci ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31378423

RESUMO

BACKGROUND: The Hospital for Special Surgery Hip Replacement Expectations Survey (HSS-THRES) is used in many countries to determine patient expectations before surgery. This study aimed to assess the reliability and validity of the Japanese version of HSS-THRES. METHODS: A total of 134 patients scheduled for total hip arthroplasty (THA) underwent a self-administered preoperative survey questionnaire. Patient's expectation and quality of life (QOL) were measured using the Japanese version of HSS-THRES, overall expectations for THA, Oxford hip score (OHS), and EuroQol-5D (EQ-5D). Some patients completed the Japanese version of HSS-THRES and the overall expectations for THA after a ten-day interval. Cross-cultural adaptation was validated by an expert committee comprising health professionals, a methodologist, language experts, and orthopedic specialists. The internal consistency was evaluated by the Cronbach α coefficient. The test-retest reliability was examined using the intraclass coefficient correlation (ICC) and the Bland and Altman analysis. To test the construct validity, nine priori hypotheses were tested by correlation analysis between the Japanese version of HSS-THRES and two QOL scales, and by examining the association with demographic variables. RESULTS: A total of 116 patients completed four scales. Patients were predominantly female (75.9%), with an average age of 62.2 ± 11.7. In the cross-cultural adaptation, all patients responded to the questionnaire without problems. The Japanese version of HSS-THRES showed good internal consistency (Cronbach α: 0.9). ICC was 0.94 and Bland-Altman analysis indicated no bias. The correlation between Japanese HSS-THRES and overall expectations for THA was high (r = 0.67). Similarly, the correlation with the OHS was higher than that with EQ-5D. A total of 77.8% of the hypotheses were confirmed. CONCLUSIONS: The Japanese version of HSS-THRES showed good cultural acceptability, high reliability, and validity to evaluate preoperative expectations for THA patients.

3.
Top Stroke Rehabil ; : 1-8, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30207894

RESUMO

BACKGROUND: Physical activity (PA) is beneficial for stroke prevention; in particular, moderate-to-vigorous physical activity (MVPA). However, few studies have investigated its relationship with recurrent ischemic stroke (RIS). OBJECTIVES: To clarify the relationship between MVPA and RIS and the burden of risk factors after a first-ever ischemic stroke. METHODS: A total of 45 outpatients (mean age 67.1 ± 10.2 years) who had previously experienced a transient ischemic attack or a minor non-cardioembolic ischemic stroke at a single hospital in Japan (mean 6.4 ± 4.2 years previously), were enrolled between March and June 2016. All patients wore an accelerometer around their hips for 10 days, and their percentage body fat (%BF) and visceral fat level (VFL) were measured by bioelectrical impedance. Retrospective information about the history of RIS and risk factors (blood pressure, lipoprotein cholesterol and estimated glomerular filtration rate) were extracted from the clinical records. Binary logistic regression models were used to estimate the relevance of the RIS history to MVPA and potential risk factors such as sociodemographic and clinical variables (obesity, smoking and hypertension). RESULTS: RIS occurred in 9 patients; they had significantly higher VFL (p = 0.007) and %BF (p = 0.007) values and lower MVPA (p = 0.011) values than patients without recurrence. A multivariate analysis of these factors indicated that age, VFL and MVPA were significant independent predictors of RIS. CONCLUSIONS: Patients with a history of mild ischemic stroke had low MVPA and high VFL values, which together may be a risk factor for RIS.

4.
Int J Orthop Trauma Nurs ; 31: 20-25, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30049583

RESUMO

BACKGROUND: The Asian lifestyle requires deep hip flexion, which increases the risk of dislocation. Hence, Asian total hip arthroplasty (THA) patients may have problems postoperatively. This study aimed to 1) document quality of life (QoL), Asian lifestyle-related items (five postures that require deep hip flexion), and perceived satisfaction in patients who underwent THA in Japan versus Korea, 2) assess the differences in QoL and Asian lifestyle-related items by patient lifestyle, and 3) identify the factors predicting QoL. METHODS: This cross-sectional study included 222 THA patients. Korean patients completed the questionnaires. Japanese patients were then matched with Korean patients by age, sex, and post-THA period. Assessed parameters included QoL measured by the EuroQoL, Oxford hip score (OHS), Asian lifestyle (measured by the Asian lifestyle-related items), and perceived satisfaction (measured by the five items of postoperative satisfaction). Multiple regression analysis was used to determine the predictors of QoL. RESULTS: Compared with Korean patients, Japanese patients had better QoL, but more difficulty performing postures requiring deep hip flexion. Greater QoL was associated with greater satisfaction. The predictors of decreased QoL after THA were lower OHS in both countries, worse squatting ability in Japan, and worse leg-crossing ability in Korea. CONCLUSIONS: In Japan and Korea, the OHS is an important predictor of QoL after THA.

5.
Artigo em Inglês | MEDLINE | ID: mdl-30024435

RESUMO

REVIEW OBJECTIVE AND REVIEW QUESTION: The objective of this proposed review is to explore the postoperative experiences of adult patients who have undergone lower limb joint replacement. Specifically, the review question is: What are the postoperative experiences during the six-week post-discharge period of adult patients who have undergone lower limb joint replacement?

6.
Clin Orthop Relat Res ; 475(12): 2992-3004, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28884273

RESUMO

BACKGROUND: With the increasing number of patients with knee osteoarthritis undergoing TKAs in China, there is a clear need for a valid, short, joint-specific patient-reported outcome measure such as the Oxford Knee Score (OKS). QUESTIONS/PURPOSES: To test the translated and cross-culturally adapted Chinese (Mandarin) version of the Oxford Knee Score (OKS-CV) and its (1) reliability, (2) construct validity, (3) dimensionality, and (4) responsiveness. METHODS: Three native Chinese bilingual translators (a professional English translator, an experienced orthopaedic surgeon, an advanced-practice nursing specialist) translated the English-language OKS into Mandarin Chinese. A consensus panel created a synthesis of those efforts, which then was back-translated by two bilingual nonmedical, professional English-language translators. The OKS-CV was developed according to the guidelines of copyright holders. Between March 2013 and March 2015, 253 patients underwent TKAs. Among them, 114 Mandarin-speaking patients with knee osteoarthritis underwent primary unilateral TKA (age, 67 ± 7 years; range, 55-84 years; female, 80%; preoperatively 54% had moderate to severe knee osteoarthritis), completed the preoperative questionnaires, and were followed up, with a mean postoperative followup of 2.7 years (SD, 0.5 years). Eligibility criteria were (1) patients with knee osteoarthritis who were scheduled to have a primary unilateral TKA, (2) patients who were fluent in Mandarin, and (3) consent to participate. The exclusion criteria were: (1) lack of understanding of Mandarin, and (2) inability to comprehend the questionnaires owing to cognitive impairment. To evaluate test-retest reliability, another group of 35 Mandarin-speaking outpatients with knee osteoarthritis (age, 61 ± 10 years; range, 44-84 years; female, 77%) was recruited to complete the OKS-CV twice at a 1-week interval. Reliability was tested using Cronbach's alpha and intraclass correlation coefficient (ICC). Construct validity was evaluated using Spearman's rank correlation coefficient to quantify the correlations between the OKS-CV and the WOMAC, Short Form-8 Health Survey (SF-8TM), and EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D). Exploratory factor analysis was performed to clarify dimensionality. The eigenvalue indicates the importance of each factor obtained from factor analysis. Responsiveness was determined by standardized response mean (SRM) and effect size (ES) from preoperative and postoperative scores of the OKS-CV. Floor and ceiling effects also were analyzed. RESULTS: The internal consistency (Cronbach's alpha = 0.89) and test-retest reliability (ICC = 0.93; 95% CI, 0.87-0.97) proved good. Convergent construct validity was supported by moderate to strong correlations between the OKS-CV and the WOMAC (r = -0.80, p < 0.001), the SF-8TM physical component summary (r = 0.65, p < 0.001), and the EQ-5D usual activities (r = -0.41, p < 0.001) and mobility (r = -0.35, p < 0.001). There also were correlations between the OKS-CV and the SF-8TM mental component summary (r = 0.58, p < 0.001) and the EQ-5D anxiety/depression (r = -0.35, p < 0.001). The factor analysis yielded three factors with eigenvalues greater than 1. Responsiveness was excellent (SRM = 1.52; ES = 1.52). No floor or ceiling effect was observed. CONCLUSIONS: The OKS-CV showed good acceptability and psychometric properties for the intended population. Future studies are needed to evaluate the mental state of patients with knee osteoarthritis. CLINICAL RELEVANCE: The OKS-CV appears to be a reliable, valid, and responsive instrument for Chinese patients with knee osteoarthritis. Based on these results we believe the OKS-CV can be used as a valuable tool for the assessment of patient-reported outcomes in Chinese patients with knee osteoarthritis before and after TKA.


Assuntos
Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/diagnóstico , Inquéritos e Questionários , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho , Grupo com Ancestrais do Continente Asiático/psicologia , Fenômenos Biomecânicos , China , Características Culturais , Avaliação da Deficiência , Feminino , Nível de Saúde , Humanos , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/psicologia , Osteoartrite do Joelho/cirurgia , Medição da Dor , Valor Preditivo dos Testes , Estudos Prospectivos , Psicometria , Reprodutibilidade dos Testes , Fatores de Tempo , Tradução , Resultado do Tratamento
7.
Int J Nurs Pract ; 23(5)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28691266

RESUMO

AIM: This concept analysis defined and described the components of empowerment of family caregivers who care for adults and the elderly. METHODS: Rodgers evolutionary method of concept analysis was used. Data sources included Pub Med, CINAHL, Scopus, and Igaku Chuo Zasshi. Thirty articles published between 1995 and 2015 focusing on the empowerment of family caregivers providing care to adults and the elderly were selected. RESULT: The analysis reveals 6 attributes, 5 antecedents, and 5 consequences. In addition, the results reveal structured aspects of family caregivers, care receivers, and other people surrounding them, and their relationships. Empowerment of adults' and elders' family caregivers may be defined as "positive control of one's mind and body, cultivating a positive attitude, proactively attempting to understand one's role as a caregiver to improve caregiving capabilities, focusing on others as well as oneself, supporting the independence of the care receiver, and creating constructive relationships with other people surrounding them." CONCLUSION: The components of empowerment clarified in this research can be used for the measurement of and interventions aimed at improving empowerment among family caregivers. Furthermore, clarifying the definition of empowerment among family caregivers enables researchers to better distinguish empowerment from similar concepts in the future.


Assuntos
Cuidadores/psicologia , Poder (Psicologia) , Adaptação Psicológica , Atitude , Humanos , Relações Interpessoais
8.
J Orthop Sci ; 21(2): 191-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26740433

RESUMO

BACKGROUND: In non-Western countries including Japan, activities requiring deep flexion of the hip joint, such as seiza (kneeling with calves tucked under the thighs and buttocks resting on the heels) and using squat toilets are commonly practiced. The purpose of this study was to assess longitudinal changes in traditional health-related quality of life measures and measures of physical functions associated with lifestyle for Japanese patients pre-surgery and after total hip arthroplasty. METHODS: Consecutive primary total hip arthroplasty patients between July 2003 and November 2006 were eligible. Patients were measured preoperatively and at 6 weeks, 1 year and 3 years postoperatively. Patients completed the EuroQol 5D, the Western Ontario and McMaster Universities Osteoarthritis Index and items related to Japanese lifestyle activities such as squatting. Changes in these scale scores across the four time points were tested, and we examined predictive factors of EuroQol 5D score at 3-year follow-up using multiple linear regression. RESULTS: Of 1103 eligible patients, 576 completed questionnaires at all four time points. By 6 weeks post-surgery, reductions in pain and improvements in physical function and stiffness became highly significant, and improvements continued to 3 years postoperative. In contrast, improvements were far more limited for items related to Japanese lifestyle functions such as seiza and use of a Japanese squat toilet, even 3 years after surgery. Predictive factors of EQ5D at 3-year post THA were WOMAC pain and physical function, seiza, age and comorbidity measured at 3-year post THA. CONCLUSION: The rate of improvement in QOL requiring deep flexion of the hip joint was much slower than that in QOL related to Western lifestyle. Our study suggests a need for lifestyle modification for THA patients in the other countries where kneeling and squatting are commonly performed.


Assuntos
Artroplastia de Quadril/métodos , Estilo de Vida , Dor Pós-Operatória/epidemiologia , Qualidade de Vida , Amplitude de Movimento Articular/fisiologia , Recuperação de Função Fisiológica , Inquéritos e Questionários , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Articulação do Quadril/fisiopatologia , Articulação do Quadril/cirurgia , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
9.
Int J Nurs Pract ; 21(6): 764-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24779591

RESUMO

We evaluated nocturnal sleep-wake rhythms and subjective sleep quality on the first postoperative night compared with the preoperative night in 34 patients who had total hip arthroplasty (mean age: 61.9 years; 82.4% female) under spinal anaesthesia. We also examined secondary factors related to sleep disturbances after surgery. Patients wore an accelerometer (actigraph) during the preoperative period and the first postoperative night to track sleep-wake rhythms. Secondary end-points were postsurgical pain and low back pain. Sleep parameters were measured objectively by actigraphy, and subjective sleep quality was measured by the Oguri-Shirakawa-Azumi Sleep Inventory, Middle-Aged and Aged Version and found to worsen significantly after surgery. Actigram data showed a reduction in actual sleep time from 353.7 ± 121.2 min preoperatively to 263.8 ± 104.4 min postoperatively. The data indicate that normalized continuous sleep time is important for patient healing and well-being and that postoperative sleep disturbance is related to low back pain more than to postsurgical pain.


Assuntos
Artroplastia de Quadril/efeitos adversos , Osteoartrite do Quadril/cirurgia , Dor Pós-Operatória/etiologia , Transtornos do Sono-Vigília/etiologia , Actigrafia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Nurs Health Sci ; 16(3): 365-72, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24845456

RESUMO

Total hip arthroplasty reduces pain and restores physical function in patients with hip joint problems. This study examined lifestyle and health-related quality of life before and after total hip arthroplasty in Japanese and Chinese patients. Two hospitals in China recruited 120 patients and 120 Japanese patients matched by age and operative status were drawn from a prospective cohort database. Oxford Hip Score, EuroQol, and characteristics of Asian lifestyle and attitudes toward the operation were assessed. There were no differences between patients from the two countries in quality-of-life-scale scores: postoperative patients had significantly better quality-of-life scores than preoperative patients in both countries. In China, patients who reported that living at home was inconvenient had significantly worse Oxford Hip Scores than those who did not. Mean scores for anxiety items concerning possible dislocation and durability of the implant were significantly higher in Japanese than in Chinese subjects. Our findings suggest that providing information about housing conditions and lifestyles would result in improved quality of life and reduced anxiety in patients with implanted joints.


Assuntos
Artroplastia de Quadril/psicologia , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Estilo de Vida/etnologia , Qualidade de Vida , Caminhada/psicologia , Atividades Cotidianas , Idoso , Ansiedade/complicações , Artroplastia de Quadril/reabilitação , China/etnologia , Estudos de Coortes , Comorbidade , Comparação Transcultural , Estudos Transversais , Feminino , Humanos , Japão/etnologia , Masculino , Pessoa de Meia-Idade , Pesquisa Metodológica em Enfermagem , Satisfação Pessoal , Estudos Prospectivos , Características de Residência , Fatores de Tempo
12.
Int Arch Allergy Immunol ; 160(3): 287-96, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23075521

RESUMO

BACKGROUND: Matrix metalloproteinase 12 gene (MMP12) has been shown to be associated with asthma in a Caucasian population. In this study, we investigate whether single-nucleotide polymorphisms (SNPs) of MMP12 are associated with a risk for asthma in a Japanese population. METHODS: We tested for an association between SNPs in MMP12 and asthma, including its severity, in a Japanese population (630 pediatric and 417 adult patients with atopic asthma and 336 children and 632 adults as controls). The rs652438 A and G variants (N357S) were generated by site-directed mutagenesis and an assay with artificial peptide substrates was used to compare two types of MMP12 activity. The effect of MMP12 inhibition with MMP12-specific small interfering RNA (siRNA) on chemokine secretion from airway epithelial cells was also tested in vitro. RESULTS: N357S showed a p value <0.05 for childhood and combined (adult plus childhood) asthma in the dominant model [odds ratio (OR) 1.60, 95% confidence interval (CI) 1.00-2.56, p = 0.047; OR 1.40, 95% CI 1.04-1.89, p = 0.028, respectively]. This risk variant is associated with asthma severity in adult patients. In the functional assay, the minor-allele enzyme showed significantly lower activity than the major-allele enzyme. MMP12-specific siRNA suppressed IP-10 secretion from airway epithelial cells upon stimulation with IFN-ß. CONCLUSIONS: Our results suggest that MMP12 confers susceptibility to asthma and is associated with asthma severity in a Japanese population. MMP12 may be associated with asthma through inappropriate attraction of leukocytes to the inflamed tissue.


Assuntos
Asma/genética , Metaloproteinase 12 da Matriz/genética , Mucosa Respiratória/imunologia , Adolescente , Adulto , Idoso , Asma/imunologia , Quimiocina CXCL10/metabolismo , Criança , Pré-Escolar , Análise Mutacional de DNA , Progressão da Doença , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Interferon beta/imunologia , Japão , Pessoa de Meia-Idade , Mutação/genética , Polimorfismo de Nucleotídeo Único , RNA Interferente Pequeno/genética , Risco , Adulto Jovem
13.
J Orthop Sci ; 18(1): 45-53, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23096948

RESUMO

BACKGROUND: Improvement in quality of life (QoL) in patients who went through total hip arthroplasty (THA) is well studied, while the number of studies on improvement in actual daily activity in THA patients is limited. The purpose of the study was (1) to describe the pre- to postoperative changes in physical activity (PA) levels, (2) compare PA levels with healthy controls, and (3) examine the association between PA levels and QoL in Japanese women undergoing THA. METHODS: PA was measured by pedometers, and QoL was assessed by the Short-Form 8 and the Oxford Hip Scale questionnaires. Consecutive patients undergoing primary THA at Saga University Hospital, Japan, in 2008 were eligible for the study. QoL and pedometers with accelerometers were mailed to THA patients 1 month pre-THA and 6 and 12 months post-THA. The control group completed a single assessment of questionnaires and pedometers. RESULTS: Thirty-eight THA patients completed the study. Preoperatively, the patient group had significantly lower QoL scores than the comparison group. However, these differences disappeared by 12 months post-THA. When improvement of PA function in THA patients was compared with healthy controls, light PA was already 78 % of the healthy controls at the pre-THA period and improved to 90 % at 12 months. In contrast, moderate PA was 27 % of the controls and rose to 77 % by 12 months, and vigorous PA remained low throughout the study period. PA was correlated with QoL scores. CONCLUSION: The study shows the relative recovery process of PA indicators in THA patients and the contribution of PA to the improvement of QoL.


Assuntos
Artroplastia de Quadril/reabilitação , Osteoartrite do Quadril/cirurgia , Qualidade de Vida , Recuperação de Função Fisiológica/fisiologia , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/psicologia , Feminino , Seguimentos , Humanos , Japão , Pessoa de Meia-Idade , Atividade Motora , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Quadril/reabilitação , Estudos Prospectivos , Amplitude de Movimento Articular , Inquéritos e Questionários , Resultado do Tratamento
14.
Nat Genet ; 43(9): 893-6, 2011 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-21804548

RESUMO

Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10(-12)), a locus on chromosome 10p14 (P = 1.79 × 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.


Assuntos
Asma/genética , Loci Gênicos , Predisposição Genética para Doença , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 4/genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único
15.
Am J Respir Cell Mol Biol ; 44(6): 787-93, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20656951

RESUMO

Thymic stromal lymphopoietin (TSLP) triggers dendritic cell--mediated T helper (Th) 2 inflammatory responses. A single-nucleotide polymorphism (SNP), rs3806933, in the promoter region of the TSLP gene creates a binding site for the transcription factor activating protein (AP)-1. The variant enhances AP-1 binding to the regulatory element, and increases the promoter--reporter activity of TSLP in response to polyinosinic-polycytidylic acid (poly[I:C]) stimulation in normal human bronchial epithelium (NHBE). We investigated whether polymorphisms including the SNP rs3806933 could affect the susceptibility to and clinical phenotypes of bronchial asthma. We selected three representative (i.e., Tag) SNPs and conducted association studies of the TSLP gene, using two independent populations (639 patients with childhood atopic asthma and 838 control subjects, and 641 patients with adult asthma and 376 control subjects, respectively). We further examined the effects of corticosteroids and a long-acting ß(2)-agonist (salmeterol) on the expression levels of the TSLP gene in response to poly(I:C) in NHBE. We found that the promoter polymorphisms rs3806933 and rs2289276 were significantly associated with disease susceptibility in both childhood atopic and adult asthma. The functional SNP rs3806933 was associated with asthma (meta-analysis, P = 0.000056; odds ratio, 1.29; 95% confidence interval, 1.14-1.47). A genotype of rs2289278 was correlated with pulmonary function. Moreover, the induction of TSLP mRNA and protein expression induced by poly(I:C) in NHBE was synergistically impaired by a corticosteroid and salmeterol. TSLP variants are significantly associated with bronchial asthma and pulmonary function. Thus, TSLP may serve as a therapeutic target molecule for combination therapy.


Assuntos
Asma/genética , Citocinas/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adolescente , Adulto , Idoso , Albuterol/análogos & derivados , Albuterol/farmacologia , Sítios de Ligação , Broncodilatadores/farmacologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Citocinas/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Xinafoato de Salmeterol
16.
J Hum Genet ; 55(6): 342-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20395963

RESUMO

In asthma genetics, the association of highly replicated susceptibility genes lacks consistency across populations. To identify genuine associations, we investigated the reproducibility of the 23 most promising asthma and asthma-related candidate genes in a moderately sized sample from the Japanese population. We compared the frequency of 33 polymorphisms in unrelated cases and controls and tested for their association with asthma, atopy and serum total IgE levels using allele frequency, codominant, dominant and recessive genotype models. On the basis of the consistency of our findings with previous meta-analyses and large replication studies, IL13, TNF, ADAM33, IL4RA and TBXA2R might represent common major asthma and asthma-related trait genes. Individual gene assessment was extended to the interactions between two polymorphisms using our original method. Interactions between TBXA2R and ADAM33, and IL4RA and C3 were suggested to increase the risk for childhood and all asthma (adult and childhood asthma combined). The confirmation of previously reported associations between gene polymorphisms and phenotypes was problematic when as few as several hundred samples per group were used. Stratification of the subjects by environmental factors or other confounding factors may be necessary to improve the sensitivity and reliability of association results.


Assuntos
Asma/genética , Asma/imunologia , Genes , Estudos de Associação Genética , Adulto , Asma/epidemiologia , Meio Ambiente , Feminino , Humanos , Hipersensibilidade/genética , Japão/epidemiologia , Masculino , Fenótipo , Polimorfismo Genético
17.
Am J Respir Crit Care Med ; 180(11): 1048-55, 2009 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-19745201

RESUMO

RATIONALE: IL-18 is a unique cytokine that enhances innate immunity and both Th1- and Th2-driven immune responses. Recent murine and human genetic studies have shown its role in the pathogenesis of asthma. OBJECTIVES: We conducted an association study in a Japanese population to discover variants of IL-18 that might have an effect on asthma susceptibility and/or progression and conducted functional analyses of the related variants. METHODS: The IL-18 gene locus was resequenced in 48 human chromosomes. Asthma severity was determined according to the 2002 Global Initiative for Asthma Guidelines. Association and haplotype analyses were performed using 1,172 subjects. MEASUREMENTS AND MAIN RESULTS: Although no polymorphisms differed significantly in frequency between the control and adult asthma groups, rs5744247 C>G was significantly associated with the severity of adult asthma (steps 1, 2 vs. steps 3, 4; P = 0.0034). We also found a positive association with a haplotype (P = 0.0026). By in vitro functional analyses, the rs5744247 variant was found to increase enhancer-reporter activity of the IL-18 gene in bronchial epithelial cells. Expression levels of IL-18 in response to LPS stimulation in monocytes were significantly greater in subjects homozygous for the susceptibility G allele at rs5744247 C>G. Furthermore, we found a significant correlation between the serum IL-18 level and the genotype of rs5744247 (P = 0.031). CONCLUSIONS: Although the association results need to be replicated by other studies, IL-18 variants are significantly associated with asthma severity, and the rs5744247 variant reflects higher transcriptional activity and higher expression of IL-18 in LPS-stimulated monocytes and a higher serum IL-18 level.


Assuntos
Asma/imunologia , Interleucina-18/imunologia , Polimorfismo Genético/imunologia , Adulto , Idoso , Asma/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-18/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença , Adulto Jovem
18.
J Allergy Clin Immunol ; 124(4): 779-85.e6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19767079

RESUMO

BACKGROUND: NLR family, pyrin domain containing 3 (NLRP3), controls the activity of inflammatory caspase-1 by forming inflammasomes, which leads to cleavage of the procytokines IL-1beta and IL-18. Recent studies have shown associations of human NLRP3 polymorphisms with susceptibility to various inflammatory diseases; however, the association with allergic diseases remains unclear. OBJECTIVE: We sought to examine whether NLRP3 polymorphisms are associated with susceptibility to food allergy, food-induced anaphylaxis, and aspirin-induced asthma (AIA). METHODS: We selected 15 tag single nucleotide polymorphisms (SNPs) of NLRP3 and conducted association analyses of NLRP3 using 574 and 1279 samples for food allergy and AIA, respectively. We further performed functional analyses of the susceptible SNPs. RESULTS: Two NLRP3 SNPs (rs4612666 and rs10754558) were significantly associated with susceptibility to food-induced anaphylaxis (P = .00086 and P = .00068, respectively). The NLRP3 haplotype of the 2 SNPs also showed a significant association (P = .000098). We could confirm the association with susceptibility to another hypersensitivity phenotype, AIA (rs4612666, P = .0096). Functional analysis revealed that the risk alleles of rs4612666 and rs10754558 increased the enhancer activity of NLRP3 expression and NLRP3 mRNA stability, respectively. CONCLUSION: Our results indicate that the NLRP3 SNPs might play an important role in the development of food-induced anaphylaxis and AIA in a gain-of-function manner. Further research on the NLRP3 inflammasome will contribute to the development of novel diagnostic and therapeutic methods for food-induced anaphylaxis and AIA.


Assuntos
Anafilaxia/genética , Aspirina/efeitos adversos , Proteínas de Transporte/genética , Hipersensibilidade a Drogas/genética , Hipersensibilidade Alimentar/genética , Frequência do Gene/genética , Predisposição Genética para Doença , Alelos , Anafilaxia/imunologia , Anafilaxia/metabolismo , Proteínas de Transporte/metabolismo , Criança , Pré-Escolar , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/metabolismo , Éxons/genética , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Genótipo , Haplótipos/genética , Humanos , Lactente , Íntrons/genética , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR , Polimorfismo de Nucleotídeo Único
19.
J Orthop Sci ; 14(1): 35-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19214685

RESUMO

BACKGROUND: With the increasing need for disease-specific health outcome measurements, the Oxford hip score was developed to measure health-related quality of life of total hip arthroplasty (THA) patients in the United Kingdom. The Oxford hip score comprises 12 items pertaining to pain and physical function, which are increasingly used to measure health outcomes of patients who have undergone THA. The purpose of this study was to establish the validity and responsiveness of the Oxford hip score in a prospective study of Japanese patients. METHODS: The study was conducted at two hospitals. The eligibility criterion for the study was consenting adult patients who underwent primary unilateral THA between April 2005 and October 2007. Three scales were self-administered at the preoperative stage and 6 months after THA. These scales were the Oxford hip score, the Short Form-36 (SF-36) version 2, and three activities requiring deep flexion of the hip (i.e., clipping one's toenails; use of a Japanese squat toilet; "seiza"--sitting on one's legs on the floor, a common posture while eating in Japan. RESULTS: A total of 224 consenting adult patients were recruited. Among them, 125 (61.9%) participated in pre- and postoperative surveys. Altogether, 108 (22 men, 86 women; mean age, 58.4 +/- 12.5 years) of the 125 patients answered all the items. A significant improvement in the mean scores was observed in all scales. Correlation coefficients between the Oxford hip score and the SF-36 version 2 (physical functioning, role physical, bodily pain) ranged from 0.60 to 0.76 preoperatively and postoperatively. Effect size was 1.7 for pain and 1.3 for physical function. The effect size for seiza was small (0.3). CONCLUSIONS: This study demonstrated the validity and responsiveness of the Oxford hip score in a prospective study. However, it does not measure activities requiring deep flexion of the hip joint, and the use of additional items is suggested.


Assuntos
Artroplastia de Quadril/reabilitação , Avaliação de Resultados (Cuidados de Saúde) , Qualidade de Vida , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Atividades Cotidianas , Idoso , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Am J Respir Cell Mol Biol ; 40(3): 368-74, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18787178

RESUMO

Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses, and is implicated in the pathogenesis of allergic diseases in humans. Two TSLP splice variants have been reported. To find functional genetic variants that might contribute to disease, we conducted analyses of single nucleotide polymorphisms (SNPs) of the TSLP gene in human bronchial epithelial cells. We surveyed SNPs on the TSLP gene by sequencing genomic DNA from 36 subjects, and characterized the linkage disequilibrium of the gene. We examined whether the SNPs have functional effects on mRNA expression or protein production using real-time PCR, reporter gene analysis, and enzyme-linked immunosorbent assay. We identified a total of 23 polymorphisms in the TSLP gene. The long form of TSLP, which is associated with allergic inflammation, was highly induced by poly(I:C) (double-stranded RNA) stimulation in normal human bronchial epithelial cells (NHBE) (P = 0.0060). The SNP rs3806933 (-847C > T) in the promoter region of long-form TSLP was found to create a binding site for the transcription factor activating protein (AP)-1, and in vitro functional analyses demonstrated that the SNP enhanced AP-1 binding to the regulatory element. The functional variant increased promoter-reporter activity of long-form TSLP in response to poly(I:C) stimulation in NHBE. Functional genetic polymorphism of the TSLP gene appears to contribute to Th2-polarized immunity through higher TSLP production by bronchial epithelial cells in response to viral respiratory infections.


Assuntos
Brônquios/anatomia & histologia , Citocinas , Células Epiteliais/metabolismo , Polimorfismo Genético , Isoformas de Proteínas/metabolismo , Processamento Alternativo , Animais , Citocinas/genética , Citocinas/metabolismo , Células Epiteliais/citologia , Frequência do Gene , Humanos , Desequilíbrio de Ligação , Camundongos , Poli I-C/genética , Poli I-C/metabolismo , Isoformas de Proteínas/genética , RNA de Cadeia Dupla , Fatores de Transcrição/metabolismo , Sítio de Iniciação de Transcrição
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