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Rationale: Subjects with preserved ratio impaired spirometry (PRISm) experience increased respiratory symptoms, although they present heterogeneous characteristics. However, the longitudinal changes in these symptoms and respiratory function are not well known. Objectives: To investigate PRISm from the viewpoint of respiratory symptoms in a longitudinal, large-scale general population study. Methods: The Nagahama study included 9,789 inhabitants, and a follow-up evaluation was conducted after 5 years. Spirometry and self-administered questionnaires regarding respiratory symptoms, including prolonged cough, sputum and dyspnea, and comorbidities were conducted. Results: In total, 9,760 subjects were analyzed, and 438 subjects had PRISm. Among the subjects with PRISm, 53% presented with respiratory symptoms; dyspnea was independently associated with PRISm. Follow-up assessment revealed that 73% of the subjects with PRISm with respiratory symptoms were consistently symptomatic, whereas 39% of the asymptomatic subjects with PRISm developed respiratory symptoms within 5 years. In addition, among subjects with respiratory symptoms without airflow limitation at baseline, PRISm was a risk factor for the development of airflow limitation independent of smoking history and comorbidities. Conclusions: This study demonstrated that 53% of the subjects with PRISm had respiratory symptoms; dyspnea was a distinct characteristic of PRISm. Approximately three-fourths of the symptomatic subjects with PRISm consistently complained of respiratory symptoms within 5 years. Together with our result that PRISm itself is an independent risk factor for the development of chronic obstructive pulmonary disease among subjects with respiratory symptoms, the clinical course of subjects with PRISm with symptoms requires careful monitoring.
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Pulmão , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Espirometria , Dispneia/diagnóstico , Dispneia/etiologia , Dispneia/epidemiologia , Fatores de Risco , Volume Expiratório ForçadoRESUMO
A woman in her 50 s with Kleine-Levin syndrome (KLS) was referred to our sleep clinic for recurrent episodes of sleep hypersomnia lasting for two to 3 days, despite attempts to remain awake. These episodes were unaccompanied by anxiety or depression, increased appetite, increased sex drive, irritability, or hallucinations, and had first appeared during chemotherapy for malignant lymphoma. Video polysomnography revealed mild obstructive sleep apnea syndrome (apnea-hypopnea index 7.9/h), but no other abnormalities. All blood tests and brain imaging investigations, including brain MRI and A 123I-ioflupane SPECT, yielded normal results. Oral L-carnitine was found to be effective for shortening the period of hypersomnolence, reducing the degree of hypersomnolence, and prolonging the inter-episode period. Since it has been reported that alkylating agents may induce carnitine deficiency, the present observations appear to support the involvement of carnitine in the onset of KLS.
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AIMS: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, and pathological PPFE is also observed in patients with secondary interstitial pneumonia. This study aimed to evaluate the pathological findings associated with radiological PPFE-like lesions and the clinical and morphological features of patients with pathological PPFE. METHODS AND RESULTS: We retrospectively reviewed the pathology of the explanted lungs from 59 lung transplant recipients with radiological PPFE-like lesions. Pathological PPFE lesions were identified in 14 patients with idiopathic disease and in 12 patients with secondary disease. Pathological PPFE was associated with previous pneumothorax, volume loss in the upper lobes, and a flattened chest. Patients with idiopathic disease and those with secondary disease with pathological PPFE had similar clinical, radiological and pathological findings, whereas fibroblastic foci were more common in patients with idiopathic disease, and patients with secondary disease more frequently showed alveolar septal thickening with elastosis or fibrosis. Post-transplantation survival did not differ between patients with idiopathic and secondary disease with pathological PPFE (log-rank; P = 0.57) and was similar between patients with idiopathic disease with pathological PPFE and those with idiopathic pulmonary fibrosis (IPF) (log-rank; P = 0.62). CONCLUSIONS: Not all patients with interstitial pneumonia with radiological PPFE-like lesions have pathological PPFE. Characteristic clinical features can suggest the presence of pathological PPFE, and idiopathic and secondary cases with pathological PPFE are similar except for fibroblastic foci in idiopathic cases and alveolar septal thickening with elastosis or fibrosis in secondary cases. Patients with pathological PPFE have a similar prognosis to those with IPF after transplantation.
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Doenças Pulmonares Intersticiais/diagnóstico , Transplante de Pulmão , Tecido Parenquimatoso/patologia , Pleura/patologia , Adulto , Feminino , Fibrose/complicações , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients. METHODS: A multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed. RESULTS: In the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01-1.07; IL-8, HR = 1.04, 95% CI 1.01-1.08; MIP-1α, HR = 1.19, 95% CI 1.00-1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02-1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01-1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls. CONCLUSIONS: CTACK is a novel prognostic biomarker of IPF. Trial registration None (because of no healthcare intervention).
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Quimiocina CCL27/sangue , Fibrose Pulmonar Idiopática/sangue , Adulto , Idoso , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: Chronic sputum production in the general population is historically associated with clinical indices including male sex and smoking history. However, its relationship with gastroesophageal reflux disease (GERD), which may prove an underlying factor in sputum production, is unclear. We aimed to clarify factors associated with sputum production in the general population in cross-sectional and longitudinal manners. METHODS: In the Nagahama study, a community-based cohort study, 9804 subjects were recruited between 2008 and 2010 (baseline assessment), 8293 of whom were followed from 2013 to 2015 (follow-up assessment). This study contained a self-completed questionnaire which included medical history, assessment of sputum production, and a frequency scale for symptoms of GERD. A Frequency Scale for Symptoms of Gastroesophageal Reflux Disease score of ≥ 8 was defined as GERD. In addition to the frequency of sputum production at each assessment, frequency of persistent sputum production defined as sputum production at both assessments was examined. RESULTS: Frequency of sputum production was 32.0% at baseline and 34.5% at follow-up. Multivariable analysis demonstrated that sputum production at baseline was significantly associated with GERD [odds ratio (OR), 1.92; 95% confidence interval (CI) 1.73-2.13] and post-nasal drip (PND) (OR, 2.40; 95% CI 2.15-2.68), independent of other known factors such as older age, male sex and smoking history. These associations between sputum production and GERD or PND were also observed at follow-up. In longitudinal analysis, 19.4% had persistent sputum production and 12.3% had transient sputum production, i.e., at baseline only. Multivariable analysis for risk of persistence of sputum production revealed that persistent sputum production was associated with GERD and PND, in addition to the known risk factors listed above. The proportion of subjects with GERD at both assessments was highest among subjects with persistent sputum production. CONCLUSIONS: Cross-sectional and longitudinal analysis demonstrated an association in the general population between sputum production and GERD, as well as PND, independent of known risk factors. The presence of GERD should be assessed in patients complaining of sputum production.
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Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/fisiopatologia , Vida Independente , Vigilância da População , Escarro/fisiologia , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Refluxo Gastroesofágico/diagnóstico , Humanos , Vida Independente/tendências , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Fumar/epidemiologia , Fumar/tendênciasRESUMO
PURPOSE: Poor quality of sleep is a common feature in patients with various lung diseases and affects their health-related quality of life (HRQL). We evaluated sleep quality and HRQL in patients on the waitlist for lung transplantation in Japan. METHODS: In this prospective study, patient-reported and physiological data were collected from patients newly registered on the waitlist for lung transplantation in Japan. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI) and HRQL using the St. George's Respiratory Questionnaire (SGRQ). The frequency of poor sleep quality, correlations between sleep quality and various clinical parameters, and predictive factors of sleep quality were examined. RESULTS: Of 193 patients, the three most-frequent indications for lung transplantation were interstitial pneumonia (n = 96), pulmonary complications of hematopoietic stem cell transplantation (n = 25), and pulmonary hypertension (n = 17). Poor sleep quality (PSQI > 5) was observed in 102 patients (53%) and was significantly associated with worse Hospital Anxiety and Depression Score (HADS), worse SGRQ score, worse modified Medical Research Council Dyspnea score, and shorter 6-min walk distance. However, it was not associated with sex, pulmonary function, interstitial pneumonia, or arterial blood gas. Stepwise multiple regression analysis indicated that poor sleep quality was explained significantly by HADS anxiety (23%) and SGRQ Symptoms (10%). CONCLUSION: Poor sleep quality was found to be common among patients on the lung transplantation waitlist in Japan. The two most significant factors responsible for impaired sleep quality were anxiety and respiratory symptoms. Additional care should be taken to ensuring a better quality of sleep for such patients.
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Ansiedade/epidemiologia , Pneumopatias/epidemiologia , Transplante de Pulmão/estatística & dados numéricos , Qualidade de Vida , Transtornos Respiratórios/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Adulto , Feminino , Humanos , Japão/epidemiologia , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Listas de EsperaRESUMO
AIMS: As the glucose tolerance of patients with diabetes worsens, autonomic nervous system (ANS) function decreases. Only a few studies, using plasma glucose, have reported on this relationship in large general populations that include people with wide range of glycemia. This study aimed to examine correlates of ANS function with special reference to HbA1c which is more stable than plasma glucose among community residents. METHODS: Spectral analysis was performed to assess heart rate variability (HRV) using 1-minute electrocardiogram RR interval data recordings from 7690 residents aged 35-79 years in Nagahama City, Japan. HRV parameters were log-transformed. Multiple regression analysis was performed using potential correlates. RESULTS: lnLF decreased with age (regression coefficient, -0.025; P < 0.001), BMI (-0.010; P = 0.035), and HbA1c (-0.068; P = 0.036). lnHF decreased with age (-0.029; P < 0.001), BMI (-0.032; P < 0.001), and HbA1c (-0.173; P < 0.001). lnLF/HF increased with age (0.003; P = 0.002), BMI (0.023; P < 0.001), and HbA1c (0.105; P < 0.001). Women showed lower lnLF and lnLF/HF than men. Sleep quality assessed by the Pittsburgh Sleep Quality Index, smoking and drinking had almost no relation. CONCLUSIONS: Although the associations were weak, age, BMI and HbA1c were inversely correlated with parasympathetic activity, while positively correlated with sympathetic activity among general residents.
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Sistema Nervoso Autônomo/fisiopatologia , Glicemia/metabolismo , Complicações do Diabetes/complicações , Hemoglobinas Glicadas/fisiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Nocturia is a risk factor for poor quality of life and increased mortality. This study was aimed to clarifying dietary habits, eating behaviors, and sleep characteristics associated with nocturia to identify modifiable lifestyle factors for nocturia. METHODS: This cross-sectional study included 5683 community residents (64.5 ± 7.7 years old). The frequency of nocturnal urination was recorded for 1 week using a sleep diary. The frequency of food intake, unfavorable eating behaviors, and sleep characteristics that may have influence on salt intake and wasting were obtained using a structured questionnaire. RESULTS: The frequency of nocturnal urination was increased with age (ß = .312, P < .001). Other basic factors associated with the frequency were the male sex (ß = .090), hypertension (ß = .038), sleep apnea (ß = .030), B-type natriuretic peptide level (ß = .089), and spot urine sodium excretion (ß = -.058). Dietary factors independently associated with nocturnal urination frequency were coffee (≥1 time/day: ß = -.059, P < .001) and green vegetable consumption (≥1 time/week: ß = -.042, P = .001), whereas habitual intake of dairy products, miso soup, and alcohol were not associated with urination frequency. Later bedtime was inversely associated with nocturnal urination frequency independent of sleep duration (before 23:00: ß = -.096; before 24:00: ß = -.225; after midnight: ß = -.240; all P < .001). CONCLUSION: Coffee and green vegetable consumption and later bedtime but not sleep duration are lifestyle factors associated with nocturnal urination frequency.
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Estilo de Vida , Noctúria/epidemiologia , Micção , Idoso , Estudos de Coortes , Estudos Transversais , Comportamento Alimentar , Feminino , Humanos , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Noctúria/fisiopatologia , Fatores Sexuais , Sono , Sódio na Dieta , Inquéritos e QuestionáriosRESUMO
RATIONALE: The Sarcoidosis Health Questionnaire (SHQ) is the first sarcoidosis-specific health status questionnaire ever developed. Worse health status, as evaluated by the SHQ, may indicate higher risk for deterioration in the following 5 years. OBJECTIVES: To evaluate the association between SHQ scores and deterioration defined clinically at 5-year follow-up. METHODS: 122 patients with biopsy-supported sarcoidosis completed the SHQ and underwent evaluation with respect to organ involvement, chest radiograph, electrocardiogram, serum biomarker measurements, pulmonary function tests, and echocardiogram. Of these 122, 88 (72.1%) were available for pulmonary, cardiac, and non-pulmonary, non-cardiac deterioration assessment during the following 5 years. MEASUREMENTS AND MAIN RESULTS: Five-year deterioration was observed in 20 patients (23%). The SHQ total score was significantly associated with 5-year deterioration, after adjusting for cardiac involvement at baseline, with adjusted odds ratio (OR) of 0.54 (95% confidence interval [95% CI], 0.29-0.99). The association of the total SHQ with 5-year outcome was not significant when adjusted for left ventricular ejection fraction (LVEF) at baseline (adjusted OR, 0.61 [0.32-1.16]), whereas LVEF was significantly associated with 5-year outcome (adjusted OR, 0.92 [0.86-0.99]). The association between total SHQ score and 5-year deterioration was marginal when adjusted for baseline usage of systemic corticosteroid (CS)/immunosuppressive (IS) agents (adjusted OR, 0.58 [0.31-1.10]), whereas systemic CS/IS usage significantly predicted 5-year deterioration (adjusted odds ratio [OR], 3.46 [1.12-10.7]). There was a marginal correlation between the total SHQ and LVEF (rhoâ¯=â¯0.19, pâ¯=â¯0.07) and a weak association between the total SHQ and systemic CS/IS usage (rhoâ¯=â¯-0.23, pâ¯=â¯0.03). The Physical Functioning domain scores of the SHQ were significantly associated with 5-year deterioration (adjusted OR, 0.45-0.51). CONCLUSIONS: Worse health status, as assessed by the SHQ score, can be a risk factor for 5-year deterioration of sarcoidosis, although usage of the CS/IS at baseline and lower LVEF at baseline are more predictive of 5-year deterioration.
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Nível de Saúde , Sarcoidose/complicações , Sarcoidose/epidemiologia , Corticosteroides/uso terapêutico , Adulto , Idoso , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Qualidade de Vida/psicologia , Testes de Função Respiratória/métodos , Sarcoidose/tratamento farmacológico , Sarcoidose/fisiopatologia , Volume Sistólico/fisiologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD). METHODS: We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed. RESULTS: Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions. CONCLUSION: Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels.
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BACKGROUND: Radiological pleuroparenchymal fibroelastosis (PPFE) lesion is characterized by pleural thickening with associated signs of subpleural fibrosis on high-resolution computed tomography (HRCT). This study evaluated the clinical significance of radiological PPFE as an isolated finding or associated with other interstitial lung diseases (ILDs) in patients having fibrotic ILDs and registered for cadaveric lung transplantation (LT). METHODS: This retrospective study included 118 fibrotic ILD patients registered for LT. Radiological PPFE on HRCT was assessed. The impact of radiological PPFE on clinical features and transplantation-censored survival were evaluated. RESULTS: Radiological PPFE was observed in 30/118 cases (25%): definite PPFE (PPFE concentrated in the upper lobes, with involvement of lower lobes being less marked) in 12 (10%) and consistent PPFE (PPFE not concentrated in the upper lobes, or PPFE with features of coexistent disease present elsewhere) in 18 (15%). Of these, 12 had late-onset non-infectious pulmonary complications after hematopoietic stem-cell transplantation and/or chemotherapy (LONIPCs), 9 idiopathic PPFE, and 9 other fibrotic ILDs (idiopathic pulmonary fibrosis, IPF; other idiopathic interstitial pneumonias, other IIPs; connective tissue disease-associated ILD, CTD-ILD, and hypersensitivity pneumonia, HP). Radiological PPFE was associated with previous history of pneumothorax, lower body mass index, lower percentage of predicted forced vital capacity (%FVC), higher percentage of predicted diffusion capacity of carbon monoxide, less desaturation on six-minute walk test, and hypercapnia. The median survival time of all study cases was 449 days. Thirty-seven (28%) received LTs: cadaveric in 31 and living-donor lobar in six. Of 93 patients who did not receive LT, 66 (71%) died. Radiological PPFE was marginally associated with better survival after adjustment for age, sex, %FVC, and six-minute walk distance < 250 m (hazard ratio 0.51 [0.25-1.05], p = 0.07). After adjustment for covariates, idiopathic PPFE and LONIPC with radiological PPFE was associated with better survival than fibrotic ILDs without radiological PPFE (hazard ratio 0.38 [0.16-0.90], p = 0.03), and marginally better survival than other fibrotic ILDs with radiological PPFE (hazard ratio, 0.20 [0.04-1.11], p = 0.07). CONCLUSIONS: idiopathic PPFE and LONIPC with radiological PPFE has better survival on the wait list for LT than fibrotic ILDs without radiological PPFE, after adjustment for age, sex, %FVC, and six-minute walk distance.
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Elasticidade/fisiologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/cirurgia , Transplante de Pulmão/tendências , Sistema de Registros , Adulto , Feminino , Humanos , Doenças Pulmonares Intersticiais/fisiopatologia , Pessoa de Meia-Idade , Tecido Parenquimatoso/diagnóstico por imagem , Cavidade Pleural/diagnóstico por imagem , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: The significance of the nutritional status in idiopathic pulmonary fibrosis (IPF) is largely unknown. Temporal body weight (BW) change, a dynamic index of nutrition status, can detect the malnutrition more accurately than the conventional single-point body mass index evaluation. OBJECTIVE: To investigate how the temporal BW change influences the clinical courses of IPF. METHODS: This multicenter study enrolled IPF patients from four referral hospitals of interstitial lung diseases in Japan (the Japanese cohort, the derivation cohort) and the Royal Brompton Hospital (the UK cohort, the validation cohort). The annual rate of BW change from the initial presentation was evaluated. A > 5% decrease of BW was defined as a significant BW loss. RESULTS: Twenty-seven out of 124 patients in the Japanese cohort and 13 out of 86 patients in the UK cohort showed significant BW loss. Patients with BW loss showed significantly worse survival in both cohorts. Multivariate analyses revealed that BW loss was an independent factor for decreased survival (Japanese cohort: p = 0.047, UK cohort: p = 0.013). A 6.1% loss of BW was chosen as the optimal cutoff value to predict the 2-year mortality from the initial presentation. The stratified analysis revealed that a 6.1% or greater BW loss could predict worse survival specifically in cases without a greater than 10% decline in forced vital capacity (FVC). CONCLUSIONS: BW loss is independently associated with the survival of IPF patients, particularly when a decline in the FVC was not observed. Further studies are needed to understand the mechanisms underlying BW loss in IPF.
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Fibrose Pulmonar Idiopática/fisiopatologia , Estado Nutricional , Redução de Peso , Idoso , Estudos de Coortes , Feminino , Humanos , Fibrose Pulmonar Idiopática/mortalidade , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Capacidade VitalRESUMO
PURPOSE: The aim of this study was to examine and compare morphological and functional outcomes after either isolated mandibular setback or bimaxillary surgery in males and females. MATERIALS AND METHODS: A retrospective study was done on 52 patients, in whom surgical correction for mandibular prognathism was performed either by isolated mandibular setback (30 cases) or by bimaxillary surgery (22 cases). Morphological changes were studied using cephalograms and functional changes studied using impulse oscillometry (IOS) taken before surgery (T0), 3 months (T1) and 1 year after surgery (T2). Also 3% oxygen desaturation index (ODI) was measured at T0 and T2. RESULT: Posterior airway space decreased significantly in both groups and both sexes but more so in males after mandibular setback surgery and in females after bimaxillary surgery. Changes in supine R20 (central airway resistance at 20 Hz) and supine R5 (total airway resistance at 5 Hz) in IOS statistically significantly increased in the period T0-T1 in males compared with females after mandibular setback surgery (p < 0.05). CONCLUSION: Gender dimorphism is present according to morphological and functional outcomes, with males at a higher risk for obstructive sleep apnea (OSA) after mandibular setback surgery and females after bimaxillary surgery; however, compensatory changes act as a barrier against this.
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Má Oclusão Classe III de Angle/cirurgia , Má Oclusão Classe III de Angle/terapia , Procedimentos Cirúrgicos Ortognáticos , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/terapia , Adolescente , Adulto , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/cirurgia , Obstrução das Vias Respiratórias/terapia , Resistência das Vias Respiratórias , Pontos de Referência Anatômicos , Cefalometria/métodos , Feminino , Humanos , Masculino , Má Oclusão Classe III de Angle/etiologia , Mandíbula/anatomia & histologia , Mandíbula/cirurgia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Bucais , Oxigênio/sangue , Estudos Retrospectivos , Fatores Sexuais , Apneia Obstrutiva do Sono/etiologia , Resultado do Tratamento , Adulto JovemRESUMO
Inhaled pathogens including Pseudomonas aeruginosa initially encounter airway epithelial cells (AECs), which are poised to evoke cell-intrinsic innate defense, affecting second tier of hematopoietic cell-mediated immune reaction. However, it is largely unknown how pulmonary immune responses mediated by a variety of immune cells are coordinated. Here we show that Regnase-1, an endoribonuclease expressed in AECs and immune cells, plays an essential role in coordinating innate responses and adaptive immunity against P. aeruginosa infection. Intratracheal treatment of mice with heat-killed P. aeruginosa resulted in prolonged disappearance of Regnase-1 consistent with sustained expression of Regnase-1 target inflammatory genes, whereas the transcription factor NF-κB was only transiently activated. AEC-specific deletion of Regnase-1 not only augmented innate defenses against P. aeruginosa but also enhanced secretion of Pseudomonas-specific IgA and Th17 accumulation in the lung, culminating in conferring significant resistance against P. aeruginosa re-infection in vivo. Although Regnase-1 directly controls distinct sets of genes in each of AECs and T cells, degradation of Regnase-1 in both cell types is beneficial for maximizing acquired immune responses. Collectively, these results demonstrate that Regnase-1 orchestrates AEC-mediated and immune cell-mediated host defense against pulmonary bacterial infection.
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Pulmão/imunologia , Pneumonia Bacteriana/imunologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/fisiologia , Mucosa Respiratória/metabolismo , Ribonucleases/metabolismo , Células Th17/imunologia , Imunidade Adaptativa , Animais , Anticorpos Antibacterianos/metabolismo , Imunidade Inata , Imunoglobulina A/metabolismo , Pulmão/microbiologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Ribonucleases/genética , Transdução de SinaisRESUMO
Sleep-disordered breathing (SDB) is characterized by repetitive episodes of decreased or arrested respiratory airflow during sleep. SDB is common and affects approximately 20% of the Japanese general population. Most traits of normal sleep and SDB show familial aggregation, suggesting significant effects of genetic factors. Obstructive sleep apnea (OSA) is the most common type of SDB and has a high heritability. Regardless of high heritability, no risk locus for OSA has reached a genome-wide level of significance (P < 5×10-8) in linkage or candidate gene analysis. However, a recent genome-wide association study identified some genetic risks for OSA with P < 5×10-8 for the first time. The identified genes are associated with inflammation, hypoxia signaling, and sleep pathways. The effects of genetic factors on the consequences of OSA has not been determined, although a correlation between OSA and cardiovascular disease may differ across races. Congenital central hypoventilation syndrome (CCHS) is a genetically inherited disorder caused by mutations in the paired-like homeobox 2B (PHOX2B) gene of polyalanine repeat mutations in the 20-alanine repeat or non-polyalanine repeat mutations. PHOX2B genotypes are also associated with clinical phenotypes of CCHS, including severity of hypoventilation. SDB, including obesity hypoventilation syndrome, is often seen in genetic obesity-associated disorders such as Prader-Willi syndrome. Although advances in genetics have resulted in identification of some genetic causes of SDB, further studies are required to elucidate the cellular and molecular mechanisms between genetic risks and clinical manifestations.
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Estudo de Associação Genômica Ampla , Hipoventilação/congênito , Apneia do Sono Tipo Central/genética , Apneia Obstrutiva do Sono/genética , Genótipo , Proteínas de Homeodomínio/genética , Humanos , Hipoventilação/genética , Mutação , Peptídeos/genética , Síndrome de Prader-Willi/genética , Risco , Índice de Gravidade de Doença , Fatores de Transcrição/genéticaRESUMO
OBJECTIVES: The aim of this study was to examine the relationship between morphologic factors of mandibular protrusion patients and clinical indices of obstructive sleep apnea (OSA). METHODS: Fifty-two Japanese patients divided into 2 groups: 1 jaw surgery group (30 patients) and 2 jaw surgery group (22 patients). Morphologic changes were studied using cephalograms taken before surgery and 1 year after surgery. Functional changes studied using impulse oscillometry and pulse oximetry during sleep, both of which are clinically useful measures in assessing OSA, taken before surgery and 1 year after surgery. RESULT: Lower face cage area significantly decreased in 1 jaw group than in 2 jaw group patients. Positive significant correlation was found between changes in 3% oxygen desaturation index (ODI) and changes of tongue area and vertical position of the hyoid bone in 1 jaw surgery group. Multiple regression analysis indicates that tongue area and airway area were independently significant predictors of 3% ODI in 1 jaw group patients. CONCLUSION: In 2 jaw surgery, maxillary surgery compensated for the effect of mandibular setback surgery. Mandibular setback surgery to mandibular protrusion patients was performed within the range of adequate movement distance, but precautions for risk of postoperative obstructive sleep apnea syndrome should be considered.
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Mandíbula/cirurgia , Oxigênio/sangue , Apneia Obstrutiva do Sono/cirurgia , Adulto , Cefalometria/métodos , Feminino , Humanos , Osso Hioide/fisiologia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Ortognáticos/métodos , Oximetria , Faringe/anatomia & histologia , Sono/fisiologia , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/fisiopatologia , Língua/fisiologia , Adulto JovemRESUMO
OBJECTIVE: Young patients with advanced interstitial lung disease (ILD) are potential candidates for cadaveric lung transplantation. This study aimed to examine clinical features, outcomes, and prognostic factors in Japanese ILD patients awaiting lung transplantation. METHODS: We investigated the clinical features and outcomes of 77 consecutive candidates with ILD who were referred to Kyoto University Hospital and subsequently actively listed for lung transplant in the Japan Organ Transplant Network between 2010 and 2014. RESULTS: Of the 77 candidates, 33 had idiopathic pulmonary fibrosis (IPF) and 15 had unclassifiable ILD. During the observational period, 23 patients (30%) received lung transplantations and 49 patients (64%) died before transplantation. Of the 33 patients with IPF, 13 (39%) had a family history of ILD and 13 (39%) had an "inconsistent with usual interstitial pneumonia pattern" on high-resolution computed tomography (HRCT). The median survival time from registration was 16.7 months, and mortality was similar among patients with IPF, unclassifiable ILD, and other ILDs. Using a multivariate stepwise Cox proportional hazards model, 6-min walking distance was shown to be an independent prognostic factor in candidates with ILD (per 10 m, hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95-0.99, p<0.01), while lower body mass index (HR: 0.83; 95% CI: 0.72-0.95, p < 0.01) independently contributed to mortality in patients with IPF. CONCLUSIONS: Japanese patients with ILD awaiting transplantation had very poor outcomes regardless of their specific diagnosis. A substantial percentage of IPF patients had an atypical HRCT pattern. 6-min walking distance in ILD patients and body mass index in IPF patients were independent predictors of mortality.
Assuntos
Fibrose Pulmonar Idiopática/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Transplante de Pulmão , Adulto , Biomarcadores/análise , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/cirurgia , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Testes de Função Respiratória , Tomografia Computadorizada por Raios X , CaminhadaRESUMO
BACKGROUND: The prevalence of chronic kidney disease (CKD) increases with age as with idiopathic pulmonary fibrosis (IPF). OBJECTIVES: We assessed the prevalence of CKD (stages 3-5) and investigated the relationship of CKD to clinical features and outcomes in patients with IPF. METHODS: This study comprised 123 patients with IPF; 61 subjects with chronic obstructive pulmonary disease (COPD), which was reportedly associated with CKD, were also enrolled as a disease control. CKD (stages 3-5) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS: Thirty-seven patients (30%) with IPF and 14 controls (23%) with COPD were diagnosed with CKD, and these frequencies were not significantly different. The patients with IPF and CKD were older (p < 0.01) and had a higher frequency of hypertension (p = 0.048) and ischemic heart disease (p = 0.02) than those with IPF but without CKD. Furthermore, the diffusing capacity of the lung for carbon monoxide (DLCO) and the 6-min walking distance in the patients with CKD were significantly lower (40.0 ± 13.2 vs. 45.9 ± 14.4%, p = 0.04, and 416 ± 129 vs. 474 ± 84 m, p = 0.01, respectively) than in the patients without CKD. The outcome of the patients with CKD showed significantly worse survival compared with the patients without CKD (p = 0.04). Moreover, eGFR remained an independent predictor of survival after adjusting for age and pulmonary function data. CONCLUSION: A substantial percentage of IPF patients have CKD. CKD with a low eGFR was associated with decreased survival in IPF.
Assuntos
Fibrose Pulmonar Idiopática/mortalidade , Insuficiência Renal Crônica/mortalidade , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Fibrose Pulmonar Idiopática/complicações , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/complicações , Estudos RetrospectivosRESUMO
RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.
Assuntos
Aminoacil-tRNA Sintetases/imunologia , Autoanticorpos/sangue , Dermatomiosite/complicações , Fibrose Pulmonar Idiopática/imunologia , Doenças Pulmonares Intersticiais/imunologia , Miosite/imunologia , Adulto , Idoso , Autoanticorpos/imunologia , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/imunologia , Doenças do Tecido Conjuntivo/mortalidade , Dermatomiosite/imunologia , Dermatomiosite/mortalidade , Feminino , Humanos , Oxigenoterapia Hiperbárica/métodos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Miosite/mortalidade , Estudos Observacionais como Assunto , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , RNA/imunologia , Estudos Retrospectivos , Análise de Sobrevida , Capacidade Vital/fisiologiaRESUMO
AIM: The present study examined the association between self-reported quality of sleep (QOS) and physical function in community-dwelling young-old adults. METHODS: This cross-sectional study included 737 community-dwelling older adults aged 60 years and older (498 women, 239 men); age 68.3 ± 5.2 years (range 60-79 years). Participants completed a self-administered questionnaire, which included the Pittsburgh Sleep Quality Index, as well as information regarding sociodemographic characteristics, physical activity, smoking and alcohol consumption. The χ2 -test was used to compare categorical variables stratified by QOS, and the unpaired t-test was used for continuous variables for men and women separately. Furthermore, logistic regression analyses were carried out to verify the association between QOS and physical function measures. RESULTS: The unpaired t-test showed a significant difference ((P < 0.05) in the Timed Up and Go test and physical strength outcomes, which included: handgrip, quadriceps setting, knee extension and hip flexion strength between the good QOS and poor QOS groups among the men. However, the t-test results for physical function outcomes did not show a significant difference among the women. In the logistic regression model, after adjusting for age, sex and potential confounding factors, handgrip strength remained significantly associated with QOS (OR 0.96, 95% CI 0.92-1.00). CONCLUSION: QOS was associated with physical function in young-old adults; those with good QOS were especially more likely to possess stronger grip strengths; however, further research is required to identify the temporal relationship. Geriatr Gerontol Int 2017; 17: 1808-1813.