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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. [ABSTRACT FROM AUTHOR]

Background: Polymyositis and dermatomyositis-associated interstitial lung disease (PM/DM-ILD) can have variable courses. We evaluated the prognostic value of high-resolution computed tomography (HRCT) in PM/DM-ILD. Methods: The cases of 51 patients newly diagnosed with PM/DM-ILD were retrospectively reviewed. HRCT images at diagnosis were categorized into four radiological patterns based on the major findings and distributions of these abnormalities, and the disease extent on HRCT was scored. The impact of HRCT findings and other clinical parameters on day 90 and overall mortality were analyzed. Results: Of the 51 patients (11 with polymyositis and 40 with dermatomyositis), the lower consolidation/ground-glass attenuation (GGA) pattern was observed in 21 patients (41%), lower reticulation was observed in 23 patients (45%), random GGA was observed in four patients (8%), and other patterns were observed in three patients (6%). Twenty-one patients (42%) were positive for anti-CADM-140. The lower consolidation/GGA pattern, clinically amyopathic dermatomyositis, fever (≥38.0 °C), ferritin levels >500 ng/mL, and the presence of anti-CADM-140 were significantly associated with 90-day mortality in univariate analysis. Multivariate analysis revealed that the lower consolidation/GGA pattern (odds ratio, 23.1; P = 0.02) and the presence of anti-CADM-140 (odds ratio, 14.1; P = 0.03) were independent predictors of 90-day mortality. This HRCT pattern was also associated with a higher 90-day morality rate among anti-CADM-140-positive patients. The lower consolidation/GGA pattern was also associated with overall mortality in univariate analysis, whereas only the presence of anti-CADM-140 was an independent determinant of overall mortality in multivariate analysis. Conclusion: HRCT patterns at diagnosis can help predict the prognosis of patients with PM/DM-ILD as well as the presence of anti-CADM-140. [ABSTRACT FROM AUTHOR]

Background: Recent epidemiological evidence indicates an association between cardiovascular diseases and pulmonary fibrosis. The vascular endothelium acts to maintain vascular homeostasis through multiple mechanisms and impaired endothelial function can contribute to the development, progression and clinical expression of atherosclerosis. Methods: We consecutively recruited 39 newly-diagnosed chronic interstitial pneumonitis/fibrosis patients without any specific etiology. We assessed endothelium-dependent vasodilator response of patients using digital pulse amplitude tonometry and compared the reactive hyperemia index (RHI) with age-, sex- and body mass index-matched control subjects (n = 30). We further investigated the relationships between RHI and clinical characteristics, laboratory cardiovascular risk factors, disease-related factors and circulating levels of inflammatory biomarkers. Results: RHI was significantly lower in patients with chronic interstitial pneumonitis/fibrosis than in control subjects (p = 0.02). While circulating levels of total cholesterol, triglycerides, HbA1c and fasting glucose did not differ significantly between groups, patients with chronic interstitial pneumonitis/fibrosis had significantly lower high density lipoprotein levels and higher low density lipoprotein levels as compared with control subjects. Regarding disease-related factors, RHI was significantly associated with the diffusing capacity for carbon monoxide, alveolar-arterial oxygen pressure difference, 6-min walk distance and end-exercise oxygen saturation. Additionally, circulating levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were inversely correlated with RHI. Conclusions: We confirmed a possible link between pulmonary fibrosis and cardiovascular disease by demonstrating an impairment of endothelium-dependent vasodilator response, which was significantly associated with the severity of pulmonary fibrosis and circulating levels of adhesion molecules. [ABSTRACT FROM AUTHOR]

Summary: Background: Anti-CADM-140 antibody (anti-CADM-140), also referred to as anti-melanoma differentiation-associated gene 5 (MDA5) antibody, is a myositis-specific antibody identified in the sera of patients with clinically amyopathic dermatomyositis (C-ADM) and is associated with a worse prognosis in dermatomyositis-associated interstitial lung disease (DM-ILD). We sought to determine high-resolution computed tomography (HRCT) features of DM-ILD with anti-CADM-140. Methods: Twenty-five patients newly diagnosed with DM-ILD at Kyoto University Hospital between 2005 and 2009 were retrospectively reviewed. Serum anti-CADM-140 was measured in all patients at their first visit. Chest HRCT images taken prior to treatment were classified based on the dominant findings and their distribution, and compared between patients with and without the antibody. Results: Of 25 DM-ILD patients, 12 were positive and 13 were negative for anti-CADM-140. HRCT patterns differed significantly between anti-CADM-140-positive and negative patients (P = 0.002). Lower consolidation or ground-glass attenuation (GGA) pattern (50.0%) and random GGA pattern (33.3%) were the predominant patterns in anti-CADM-140-positive cases, while lower reticulation pattern (69.2%) was frequently seen in anti-CADM-140-negative cases. Anti-CADM-140-positive cases were also significantly characterized by the absence of intralobular reticular opacities (0% in anti-CADM-140 (+) vs. 84.6% in anti-CADM-140 (−), P < 0.0001). Conclusions: Anti-CADM-140-positive DM-ILD was characterized by lower consolidation or GGA pattern, random GGA pattern, and the absence of intralobular reticular opacities. [Copyright &y& Elsevier]

Summary: Objectives: Antisynthetase syndrome (ASS) is characterized by autoantibodies to aminoacyl-tRNA synthetases (anti-synthetase) and it is frequently associated with interstitial lung disease. The purpose of this study was to elucidate the prevalence and characteristics of the anti-synthetase positive subpopulation among idiopathic interstitial pneumonias (IIPs) and to clarify the importance of screening for these antibodies. Methods: A retrospective study was performed in 198 consecutive cases with IIPs. Screening for six anti-synthetase antibodies was performed in all cases. Clinical profiles of all cases were compared with reference to the presence of anti-synthetase. High-resolution computed tomography (HRCT) findings of anti-synthetase positive cases were also analyzed. Results: 13 cases (6.6%) were positive for anti-synthetase. Anti-EJ was most prevalent, followed by anti-PL-12. Onset ages of anti-synthetase positive cases were younger than those of anti-synthetase negative cases. Extrapulmonary features of ASS were absent in 6 anti-synthetase positive cases (46.2%). Histologically, among 5 UIP with lymphoid follicles and 11 NSIP cases, the prevalence of anti-synthetase positive cases was 8/16 (50%). On HRCT, ground glass opacity and traction bronchiectasis were the major findings in anti-synthetase positive cases, while honeycombing was absent. Conclusions: Anti-synthetase positive cases were not rare among IIPs. Anti-synthetase should be screened for in IIPs, especially in pathological NSIP or UIP with lymphoid follicles. These patients should be screened for anti-synthetase even if no suggestive extrapulmonary manifestation exists. [ABSTRACT FROM AUTHOR]

Summary: Background: Obstructive sleep apnea (OSA) has both systemic and local effects partly through the increased oxidative stress caused by intermittent hypoxia and reoxygenation. However, lung-specific biomarkers in OSA have not been fully assessed in comparison with systemic biomarkers such as C-reactive protein (CRP), although results of a recent study having a small sample size indicated KL-6 as one candidate. Methods: Subjects of the present study were 197 patients suspected to have OSA. In addition to polysomnography, we also measured serum levels of KL-6, surfactant protein-D (SP-D) and CRP and pulmonary function. We examined the relationships of different biomarkers with OSA severity and pulmonary function. Results: The apnea/hypopnea index (AHI) was significantly positively correlated with serum KL-6 levels even after adjustment for body mass index (BMI) and smoking (p = 0.03), but not with SP-D and CRP. Also, a significant trend for an increase in serum KL-6 was noted in accordance with the severity of OSA even after adjustment for BMI and smoking (β coefficient = 0.18, p = 0.02). Additionally, elevated KL-6 levels were significantly associated with restrictive lung function disturbance and gas exchange derangement after adjustment for obesity and smoking, which contrasted with CRP whose elevations were significantly associated with worsened airflow limitation and increased lung volume. Conclusions: Serum KL-6 levels may reflect the degree of subclinical lung injury associated with OSA independently of obesity or smoking, unlike CRP. We consider that KL-6 can be a potential candidate as a lung-specific biomarker of OSA and might provide complementary information on systemic biomarkers in assessing OSA. [Copyright &y& Elsevier]

Summary: Background: The level at which arterial carbon dioxide tension (PaCO2) a few months after introduction of long-term non-invasive positive pressure ventilation (NPPV) is associated with a favorable prognosis remains uncertain. Methods: Data on 184 post-tuberculosis patients with chronic restrictive ventilatory failure who were receiving long-term domiciliary NPPV were examined retrospectively. Average PaCO2 3–6 months after NPPV (3- to 6-mo PaCO2) and potential confounders were analyzed with discontinuation of long-term NPPV as the primary outcome. The effects of 3- to 6-mo PaCO2 on annual hospitalization rates due to respiratory deterioration from 1 year before to 3 years after the initiation of NPPV were examined. The effect of the difference between the PaCO2 value at the start of NPPV (0-mo PaCO2) and the PaCO2 value 3- to 6-mo later (d-PaCO2) on continuation rates for NPPV was also assessed in patients who initiated NPPV while in a chronic state. Results: Patients with relatively low 3- to 6-mo PaCO2 values maintained a relatively low PaCO2 6–36 months after NPPV (p < 0.0001) and had significantly better continuation rates (p < 0.03) and lower hospitalization rates from the 1st to 3rd year of NPPV (p = 0.008, 0.049, 0.009, respectively) than those with higher levels. The 0-mo PaCO2 (p = 0.26) or d-PaCO2 (p = 0.86) had no predictive value. Conclusion: A relatively low 3- to 6-mo PaCO2 value was predictive of long-term use of NPPV. The target values for 3- to 6-mo PaCO2 may, therefore, be less than 60 mmHg in post-tuberculosis patients, although more studies are needed. [Copyright &y& Elsevier]

Summary: Background: Long-term noninvasive positive pressure ventilation (NPPV) is associated with an excellent survival rate, especially in post-tuberculosis patients. Nothing is currently known on which method of ventilatory support is associated with a better continuation of long-term NPPV, which itself might lead to longer survival. Methods: One hundred and eighty four post-tuberculosis patients, who started NPPV at the Kyoto University Hospital group and the National Tokyo Hospital from June 1990 to August 2007, were examined retrospectively. Ventilator mode (an assisted mode or a pure controlled mode) and potential confounders were examined with the discontinuation of NPPV as the primary outcome. Results: Patients treated with a pure controlled mode had significantly better continuation rates (hazard ratio, 3.09; 95% confidential interval, 1.75–5.47; p =0.0001) and better survival rates (Log-rank test; p =0.0031) than those treated with an assisted mode. Female gender and no pulmonary lesions were also associated with a significantly better probability of continuing NPPV. The five- and ten-year probabilities of continuing NPPV for 106 patients with a pure controlled mode were 68.3% and 41.4%, respectively, while those for 76 patients with an assisted mode were 46.7% and 12.7%, respectively. Conclusions: Patients treated with pure controlled ventilation had significantly better continuation rates and survival rates than those treated with assisted ventilation. Prospective randomized controlled trials are needed to verify the effectiveness of a pure controlled mode in patients with not only restrictive thoracic disease but also other diseases including chronic obstructive pulmonary disease. [Copyright &y& Elsevier]

Background: TGF-β1 can modulate airway inflammation and exaggerate airway remodeling. A polymorphism of a promoter region of TGFB1, C-509T, might be associated with the development of asthma, but its pathophysiologic relevance remains poorly understood. Objective: We investigated relations of the C-509T polymorphism to airflow obstruction, sputum eosinophilia, and airway wall thickening, as assessed by means of computed tomography, in 85 patients with stable asthma. Methods: The CC, CT, and TT genotypes were examined by means of PCR and restriction enzyme fragment length polymorphism. At a selected bronchus, 3 indices of airway wall thickness were measured with an automatic method. Results: The CC, CT, and TT genotypes were found in 22, 46, and 17 patients, respectively. Serum TGF-β1 levels were significantly associated with the polymorphism and were increased in the CT/TT genotypes. FEV1 and sputum eosinophil percentages were also significantly associated with the polymorphism and were both decreased in the CT/TT genotypes. The polymorphism was unrelated to airway wall thickness. Conclusion: In addition to increased serum TGF-β1 levels, the T allele of the C-509T polymorphism is related to increased airflow obstruction but attenuated eosinophilic inflammation. The former relation is not attributed to thickening of the central airway walls. The latter relation might reflect the anti-inflammatory effect of TGF-β1. The C-509T polymorphism has a complex role in asthma pathophysiology, presumably because of the diverse functions of TGF-β1 and its various interactions with cells and humoral factors in vivo. [Copyright &y& Elsevier]

Background: Small airways may have an important role in asthma but are more difficult to assess pathologically than central airways. Computed tomographic indices of lung density are assumed to reflect air trapping and may be a useful noninvasive measure of small airways disease, but their pathophysiological relevance remains undetermined. Objective: To evaluate lung density on high-resolution computed tomography and examine its correlations with clinical and physiologic variables in 29 patients with stable asthma. Methods: Both lungs were scanned at full-inspiratory and full-expiratory phases to quantify percentage of lung field occupied by low attenuation area (LAA%; < −960 Hounsfield units) and mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were evaluated. Results: The mean lung density increased and LAA% decreased in all patients at expiratory phase compared with inspiratory phase. The inspiratory density indices and expiratory mean lung density correlated only with FEV1/forced vital capacity (FVC). Expiratory LAA% correlated more strongly than other variables with FEV1/FVC and with indices of peripheral airflow obstruction. Expiratory/inspiratory ratios of LAA% and mean lung density correlated, the former more strongly, with disease severity, residual volume/total lung capacity, and airway sensitivity, as well as with indices of global (FEV1 and FEV1/FVC) and peripheral airflow obstruction. Conclusion: Expiratory/inspiratory high-resolution computed tomography is useful for assessing small airways disease in asthma. Small airways involvement is associated with airflow obstruction, airway hypersensitivity, and more severe disease. Clinical implications: Small airways are an important therapeutic target in asthma. [Copyright &y& Elsevier]

Background No studies have addressed the relationship between obstructive sleep apnea (OSA) and abdominal aortic calcification (AAC), a marker for subclinical atherosclerosis and future cardiovascular events. Objectives To investigate 1) the association between OSA severity and AAC, and 2) whether OSA can impact the extent of AAC independent of comorbid atherogenic risk factors. Methods 390 participants aged 40–70 years underwent polysomnography and abdominal computed tomography. AAC was separately quantified in the upper and lower abdominal aorta using the modified Agatston scoring method, and the total AAC score was calculated as a sum of the two scores. OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 87), moderate (AHI 15–30, n = 129), and severe (AHI ≥30, n = 174). Results Log-transformed total AAC score adjusted for age and body mass index (BMI) was greater in participants with an elevated AHI (3.4 for none/mild OSA, 3.7 for moderate OSA, and 4.2 for severe OSA, p = 0.04). Multivariate linear regression analysis including age and BMI as covariates showed that severe OSA was associated with higher scores for the lower and total AAC (β = 0.15 and 0.14, p = 0.01 and 0.01, respectively). The association did not persist after additionally adjusting for traditional atherogenic risk factors including visceral fat, smoking, hypertension, dyslipidemia, and diabetes. Conclusions Severe OSA was associated with a greater extent of AAC, which was dependent on coexisting atherogenic risk factors. Comorbid cardiometabolic disorders may largely mediate the association of OSA with subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]