Normal Lung Quantification in Usual Interstitial Pneumonia Pattern: The Impact of Threshold-based Volumetric CT Analysis for the Staging of Idiopathic Pulmonary Fibrosis

BackgroundAlthough several computer-aided computed tomography (CT) analysis methods have been reported to objectively assess the disease severity and progression of idiopathic pulmonary fibrosis (IPF), it is unclear which method is most practical. A universal severity classification system has not yet been adopted for IPF.ObjectiveThe purpose of this study was to test the correlation between quantitative-CT indices and lung physiology variables and to determine the ability of such indices to predict disease severity in IPF.MethodsA total of 27 IPF patients showing radiological UIP pattern on high-resolution (HR) CT were retrospectively enrolled. Staging of IPF was performed according to two classification systems: the Japanese and GAP (gender, age, and physiology) staging systems. CT images were assessed using a commercially available CT imaging analysis workstation, and the whole-lung mean CT value (MCT), the normally attenuated lung volume as defined from −950 HU to −701 Hounsfield unit (NL), the volume of the whole lung (WL), and the percentage of NL to WL (NL%), were calculated.ResultsCT indices (MCT, WL, and NL) closely correlated with lung physiology variables. Among them, NL strongly correlated with forced vital capacity (FVC) (r = 0.92, P <0.0001). NL% showed a large area under the receiver operating characteristic curve for detecting patients in the moderate or advanced stages of IPF. Multivariable logistic regression analyses showed that NL% is significantly more useful than the percentages of predicted FVC and predicted diffusing capacity of the lungs for carbon monoxide (Japanese stage II/III/IV [odds ratio, 0.73; 95% confidence intervals (CI), 0.48 to 0.92; P < 0.01]; III/IV [odds ratio. 0.80; 95% CI 0.59 to 0.96; P < 0.01]; GAP stage II/III [odds ratio, 0.79; 95% CI, 0.56 to 0.97; P < 0.05]).ConclusionThe measurement of NL% by threshold-based volumetric CT analysis may help improve IPF staging.     

Increased Serum LIGHT Levels Correlate with Disease Progression and Severity of Interstitial Pneumonia in Patients with Dermatomyositis: A Case Control Study

BackgroundActivated CD8+ T cells play an important role in the pathogenesis of dermatomyositis (DM) with interstitial pneumonia (IP). Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness.MethodsThe correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP).ResultsThe median serum LIGHT level was 119 (16–335.4) pg/ml, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL–6 level was 14.7 (2.4–154.5) pg/ml (n = 13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6–335.4] pg/ml) was significantly higher than that in DM-CIP patients (94.3 [16–164.2] pg/ml) (P = 0.02). The serum IL–6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/ml to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R = 0.55, P = 0.04) and total ground-glass opacity scores (R = 0.72, P = 0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4–259.3) pg/ml 4 weeks after treatment initiation (P = 0.04).ConclusionsThe serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP.     

Alterations in Adenosine Metabolism and Signaling in Patients with Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

Background

Adenosine is generated in response to cellular stress and damage and is elevated in the lungs of patients with chronic lung disease. Adenosine signaling through its cell surface receptors serves as an amplifier of chronic lung disorders, suggesting adenosine-based therapeutics may be beneficial in the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Previous studies in mouse models of chronic lung disease demonstrate that the key components of adenosine metabolism and signaling are altered. Changes include an up-regulation of CD73, the major enzyme of adenosine production and down-regulation of adenosine deaminase (ADA), the major enzyme for adenosine metabolism. In addition, adenosine receptors are elevated.

Methodology/Principal Findings

The focus of this study was to utilize tissues from patients with COPD or IPF to examine whether changes in purinergic metabolism and signaling occur in human disease. Results demonstrate that the levels of CD73 and A_2BR are elevated in surgical lung biopsies from severe COPD and IPF patients. Immunolocalization assays revealed abundant expression of CD73 and the A_2BR in alternatively activated macrophages in both COPD and IPF samples. In addition, mediators that are regulated by the A_2BR, such as IL-6, IL-8 and osteopontin were elevated in these samples and activation of the A_2BR on cells isolated from the airways of COPD and IPF patients was shown to directly induce the production of these mediators.

Conclusions/Significance

These findings suggest that components of adenosine metabolism and signaling are altered in a manner that promotes adenosine production and signaling in the lungs of patients with COPD and IPF, and provide proof of concept information that these disorders may benefit from adenosine-based therapeutics. Furthermore, this study provides the first evidence that A_2BR signaling can promote the production of inflammatory and fibrotic mediators in patients with these disorders.     

Prognostic Significance of Anti-Aminoacyl-tRNA Synthetase Antibodies in Polymyositis/Dermatomyositis-Associated Interstitial Lung Disease: A Retrospective Case Control Study

Background

In polymyositis/dermatomyositis (PM/DM), anti-aminoacyl-tRNA synthetase (ARS) antibodies are closely associated with interstitial lung disease (ILD), a frequent pulmonary complication. However, the clinical significance of anti-ARS antibodies is not well established.

Objective

We aimed to evaluate the clinical significance of anti-ARS antibodies in PM/DM-ILD patients.

Methods

Forty-eight consecutive PM/DM-ILD patients were studied retrospectively. Anti-ARS antibodies were screened by ELISA and confirmed by RNA immunoprecipitation test. Medical records, high-resolution computed tomography images, and surgical lung biopsy specimens were compared between ARS-positive (ARS group) and ARS-negative patients (non-ARS group).

Results

Anti-ARS antibodies were detected in 23 of 48 patients (48%). Radiologically, nonspecific interstitial pneumonia (NSIP) pattern was observed more frequently in the ARS group than in the non-ARS group (73.9% vs. 40%, P = 0.02). Pathologically, NSIP was the most frequent in both groups. Ten-year survival rate was also significantly higher in the ARS group than in the non-ARS group (91.6% vs. 58.7%, P = 0.02). Univariate Cox hazards analysis revealed that the presence of anti-ARS antibodies was associated with better prognosis (HR = 0.34, 95% CI 0.08–0.80; P = 0.01).

Conclusions

The presence of anti-ARS antibodies is a possible prognostic marker in patients with PM/DM-ILD.     

布地奈德雾化吸入治疗特发性肺纤维化临床研究的系统评价

目的:探讨布地奈德雾化吸入治疗特发性肺纤维化的有效性和安全性.方法:检索包括中国生物医学文献数据库,中国期刊全文数据库,中文科技期刊数据库和万方数据资源系统.收集2009年4月以前发表的布地奈德雾化吸入治疗特发性肺纤维化的随机对照研究.纳入研究的质量评价参考Cochrane干预性研究系统评价员手册,采用RevMan4.2分析数据.结果:6个关于布地奈德雾化吸入治疗特发性肺纤维化的随机对照研究纳入评价,纳入特发性肺纤维化患者260例(试验组/对照组:132/128),纳入研究质量较低.对同质性好的数据进行meta分析,结果表明布地奈德雾化吸入治疗特发性肺纤维化能改善患者的呼吸困难等症状,改善肺功能,氧分压,疗效与口服泼尼松(龙)组相当.且布地奈德雾化吸入方式不良反应较少,表现为口腔炎及血糖高,其不良反应明显低于口服泼尼松(龙)组,患者依从性较好.结论:纳入研究的方法学质量普遍较低,存在多种偏倚,影响了结果的可靠性.有必要开展设计严谨、管理规范的临床研究以进一步证实布地奈德雾化吸入治疗特发性肺纤维化的有效性和安全性,为临床决策提供高质量的疗效证据.     

Impact of Comorbidities on Mortality in Patients with Idiopathic Pulmonary Fibrosis

Introduction

Comorbidities significantly influence the clinical course of idiopathic pulmonary fibrosis (IPF). However, their prognostic impact is not fully understood. We therefore aimed to determine the impact of comorbidities, as individual and as whole, on survival in IPF.

Methods

The database of a tertiary referral centre for interstitial lung diseases was reviewed for comorbidities, their treatments, their frequency and survival in IPF patients.

Results

272 patients were identified of which 12% had no, 58% 1–3 and 30% 4–7 comorbidities, mainly cardiovascular, pulmonary and oncologic comorbidities. Median survival according to the frequency of comorbidities differed significantly with 66 months for patients without comorbidities, 48 months when 1–3 comorbidities were reported and 35 months when 4–7 comorbidities were prevalent (p = 0.004). A multivariate Cox proportional hazard analyses identified other cardiac diseases and lung cancer as significant predictors of death, gastro-oesophageal reflux disease (GERD) and diastolic dysfunction had a significant positive impact on survival. A significant impact of comorbidities associated therapies on survival was not discovered. This included the use of proton pump inhibitors at baseline, which was not associated with a survival benefit (p = 0.718). We also established a predictive tool for highly prevalent comorbidities, termed IPF comorbidome which demonstrates a new relationship of IPF and comorbidities.

Conclusion

Comorbidities are frequent in IPF patients. Some comorbidities, especially lung cancer, mainly influence survival in IPF, while others such as GERD may inherit a more favourable effect. Moreover, their cumulative incidence impacts survival.     

Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study

BackgroundIn developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children.MethodsIn this retrospective case-control study SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline.ResultsThe case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons).

Conclusion and Significance

We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case fatality in such children.     

The Association between Continuity of Care and All-Cause Mortality in Patients with Newly Diagnosed Obstructive Pulmonary Disease: A Population-Based Retrospective Cohort Study, 2005-2012

BackgroundThe disease burden is increasing for chronic obstructive pulmonary disease (COPD) due to increasing of the growth rate of prevalence and mortality. But the empirical researches are a little for COPD that studied the association between continuity of care and death and about predictors effect on mortality.ObjectiveTo investigate the association between continuity of care (COC) and chronic obstructive pulmonary disease (COPD) mortality and to identify other mortality-related factors in COPD patients.MethodsWe conducted a longitudinal, population-based retrospective cohort study in adult patients with COPD from 2002 to 2012 using a nationwide health insurance claims database. The study sample included individuals aged 40 years and over who developed COPD in 2005 and survived until 2006. We performed a Cox proportional hazard regression analysis with COC analyzed as a time-dependent covariate.ResultsOf the 3,090 participants, 60.8% died before the end of study (N = 1,879). The median years of survival for individuals with high COC (COC index≥0.75) was 3.92, and that for patients with low COC (COC index<0.75) was 2.58 in a Kaplan Meier analysis. In a multivariate, time-dependent analysis, low COC was associated with a 22% increased risk of all-cause mortality (HR, 1.22; 95% CI, 1.09–1.36). Not receiving oxygen therapy at home was associated with a 23% increased risk of all-cause mortality (HR, 1.23; 95% CI, 1.01–1.49). Moreover, the risk of all-cause mortality for individuals who admitted one time increased 38% (HR, 1.38; 95% CI, 1.21–1.59), two times was 63% (HR, 1.63; 95% CI, 1.34–1.99) and 3+ times was 96% (HR, 1.96; 95% CI, 1.63–2.36) relative to the reference group (no admission).ConclusionsHigh COC was associated with a decreased risk of all-cause mortality. In addition, home oxygen therapy and number of hospital admissions may predict mortality in patients with COPD.     

Idiopathic Orbital Inflammation Syndrome with Retro-Orbital Involvement: A Retrospective Study of Eight Patients

Background

The aim of this retrospective study was to document the clinical findings and radiological features of idiopathic orbital inflammation syndrome with retro-orbital involvement.

Methods

We searched for ophthalmological patients who received orbital imaging at Zhejiang Provincial People''s Hospital between October 2003 and April 2010. Seventy-three patients were diagnosed with idiopathic orbital inflammation syndrome based on clinicoradiological features, with pathological confirmation of nonspecific inflammatory conditions in 47 patients. Eight patients (11%) had MRI or CT evidence of retro-orbital involvement. All 8 patients were diagnosed with idiopathic orbital inflammation syndrome after biopsy of the orbital lesion. MR images were obtained for all 8 patients; 3 patients also had a contrast-enhanced CT scan.

Results

Seven out of 8 patients with retro-orbital involvement also had orbital apex lesions. Of the 65 patients without retro-orbital involvement, 19 had orbital apex lesions. The difference in the number of patients with orbital apex lesions between the two populations was significant (Fisher exact test P = .002). In all 8 patients with retro-orbital involvement, the inflammation spread through the superior orbital fissure. The retro-orbital lesions were isointense to grey matter on T1-weighted images, hypointense on T2-weighted images, and displayed uniform contrast enhancement; on contrast-enhanced CT scans, they were hyperdense relative to the contralateral mirror area and had radiological contours that were similar to those seen on MR images. The diffuse inflammation with marked sclerosis and hyalinization that we observed in the patients with retro-orbital involvement is consistent with the diagnosis of the sclerosing subtype of idiopathic orbital inflammation syndrome. All 8 patients also complained of mild to moderate periorbital pain (headache).

Conclusions

In patients with idiopathic orbital inflammation syndrome, it is important to perform MRI and CT scans to identify possible retro-orbital involvement. Retro-orbital involvement is more frequent when the lesion is present in the orbital apex.     

The MUC5B Variant Is Associated with Idiopathic Pulmonary Fibrosis but Not with Systemic Sclerosis Interstitial Lung Disease in the European Caucasian Population

A polymorphism on the MUC5B promoter (rs35705950) has been associated with idiopathic pulmonary fibrosis (IPF) but not with systemic sclerosis (SSc) with interstitial lung disease (ILD). We genotyped the MUC5B promoter in the first 142 patients of the French national prospective cohort of IPF, in 981 French patients with SSc (346 ILD), 598 Italian patients with SSc (207 ILD), 1383 French controls and 494 Italian controls. A meta-analysis was performed including all American data available. The T risk allele was present in 41.9% of the IPF patients, 10.8% of the controls (P = 2×10^–44), OR 6.3 [4.6–8.7] for heterozygous patients and OR 21.7 [10.4–45.3] for homozygous patients. Prevalence of the T allele was not modified according to age, gender, smoking in IPF patients. However, none of the black patients with IPF presented the T allele. The prevalence of the T risk allele was similar between French (10%) and Italian (12%) cohorts of SSc whatever the presence of an ILD (11.1% and 13.5%, respectively). Meta-analysis confirmed the similarity between French, Italian and American cohorts of IPF or SSc-ILD. This study confirms 1) an association between the T allele risk and IPF, 2) an absence of association with SSc-ILD, suggesting different pathophysiology.     

Long-Term Mortality in Patients Diagnosed with Meningococcal Disease: A Danish Nationwide Cohort Study

Background

In contrast to the case fatality rate of patients diagnosed with meningococcal disease (MD) the long-term mortality in these patients is poorly documented.

Methodology/Principal Findings

We performed a nationwide, population-based cohort study including all Danish patients diagnosed with MD from 1977 through 2006 and alive one year after diagnosis. Data was retrieved from the Danish National Hospital Register, the Danish Civil Registration System and the Danish Register of Causes of Death. For each patient four age- and gender-matched individuals were identified from the population cohort. The siblings of the MD patients and of the individuals from the population cohort were identified. We constructed Kaplan-Meier survival curves and used Cox regression analysis, cumulative incidence function and subdistribution hazard regression to estimate mortality rate ratios (MRR) and analyze causes of death. We identified 4,909 MD patients, 19,636 individuals from the population cohort, 8,126 siblings of MD patients and 31,140 siblings of the individuals from the population cohort. The overall MRR for MD patients was 1.27 (95% confidence interval (CI), 1.12–1.45), adjusted MRR, 1.21 (95% CI, 1.06–1.37). MD was associated with increased risk of death due to nervous system diseases (MRR 3.57 (95% CI, 1.82–7.00). No increased mortality due to infections, neoplasms or cardiovascular diseases was observed. The MRR for siblings of MD patients compared with siblings of the individuals from the population cohort was 1.17 (95% CI, 0.92–1.48).

Conclusions

Patients surviving the acute phase of MD have increased long-term mortality, but the excess risk of death is small and stems mainly from nervous system diseases.     

Assessment of Health Status in Patients with Newly Diagnosed Chronic Obstructive Pulmonary Disease

Subject

Chronic obstructive pulmonary disease (COPD) is a common disease worldwide. This study aimed to investigate the health status of patients with newly diagnosed COPD.

Methods

A total of 45 healthy controls and 218 patients with newly diagnosed COPD were recruited. Pulmonary function test (PFT) values, COPD assessment test (CAT) scores, exacerbation history, and demographics were recorded.

Results

Forced expiratory volume in 1 s percent (FEV1%) predicted was significantly decreased and the CAT score was significantly increased in patients with COPD compared with healthy controls (P <0.001). Among the COPD patients, the most commonly reported respiratory symptoms were cough (86.7%), sputum (80.3%), and dyspnea (45%). A total of 86.2% patients were in the moderate or severe stage (spirometric classification) of COPD, and 71.5% were in Group C or Group D (combined assessment). A total of 33.9% of the patients had 2 or more exacerbations in the previous year. Nearly half of the patients (45.4%) had a high CAT score of ≥10. Patients with a history of more exacerbations had a higher CAT score.

Conclusions

Most COPD patients were symptomatic and appeared to have moderate to severe airflow limitation or a high risk of exacerbation before definitely being diagnosed with COPD using the PFT.     

TGF-beta1 在不同类型特发性间质性肺炎患者肺组织中的表达及其意义

目的:探讨TGF-β1在不同类型特发性间质性肺炎患者肺组织中的表达及其意义。方法:选取2010年2月至2013年12月在我院就诊的72例经支气管镜肺活检的不同类型的特发性间质性肺炎患者的组织标本,对其转化生长因子-β1表达程度进行评定。结果:寻常型(普通型)、非特异性、脱屑性、急性等ⅡP、呼吸性细支气管炎并间质性肺疾病以及隐原性机化性肺炎患者肺组织中TGF-β1表达强度评分均显著高于对照组;脱屑性ⅡP和呼吸性细支气管炎并间质性肺疾病患者肺组织中TGF-β1表达强度评分均显著高于其他类型ⅡP患者;非特异性ⅡP、急性ⅡP、淋巴细胞性ⅡP以及隐原性机化性肺炎组患者肺组织中TGF-β1表达强度评分均显著低于寻常型(普通型)ⅡP组;隐原性机化性肺炎、淋巴细胞性ⅡP组患者肺组织中TGF-β1表达强度评分分别为(0.93±0.34)分、(0.82±0.27)分,显著低于急性ⅡP组患者的(1.64±0.05)分。差异均有统计学意义(P<0.05)。结论:TGF-β1表达过度可能是ⅡP患者的重要特征,在肺纤维化的过程中发挥着重要作用,但在不同类型ⅡP中的作用机制并不相同。     

CD28 Down-Regulation on Circulating CD4 T-Cells Is Associated with Poor Prognoses of Patients with Idiopathic Pulmonary Fibrosis

Background

Although the etiology of idiopathic pulmonary fibrosis (IPF) remains perplexing, adaptive immune activation is evident among many afflicted patients. Repeated cycles of antigen-induced proliferation cause T-cells to lose surface expression of CD28, and we hypothesized this process might also occur in IPF.

Methodology/Principal Findings

Peripheral blood CD4 T-cells from 89 IPF patients were analyzed by flow cytometry and cytokine multiplex assays, and correlated with clinical events. In comparison to autologous CD4⁺CD28⁺cells, the unusual CD4⁺CD28^null lymphocytes seen in many IPF patients had discordant expressions of activation markers, more frequently produced cytotoxic mediators perforin (2.4±0.8% vs. 60.0±7.4%, p<0.0001) and granzyme B (4.5±2.8% vs.74.9±6.5%, p<0.0001), produced greater amounts of many pro-inflammatory cytokines, and less frequently expressed the regulatory T-cell marker FoxP3 (12.9±1.1% vs. 3.3±0.6% p<0.0001). Infiltration of CD4⁺CD28^null T-cells in IPF lungs was confirmed by confocal microscopy. Interval changes of CD28 expression among subjects who had replicate studies were correlated with conterminous changes of their forced vital capacities (r_s = 0.49, p = 0.012). Most importantly, one-year freedom from major adverse clinical events (either death or lung transplantation) was 56±6% among 78 IPF patients with CD4⁺CD28⁺/CD4_total≥82%, compared to 9±9% among those with more extensive CD28 down-regulation (CD4⁺CD28⁺/CD4_total<82%) (p = 0.0004). The odds ratio for major adverse events among those with the most extensive CD28 down-regulation was 13.0, with 95% confidence intervals 1.6-111.1.

Conclusions/Significance

Marked down-regulation of CD28 on circulating CD4 T-cells, a result of repeated antigen-driven proliferations, is associated with poor outcomes in IPF patients. The CD4⁺CD28^null cells of these patients have potentially enhanced pathogenic characteristics, including increased productions of cytotoxic mediators and pro-inflammatory cytokines. These findings show proliferative T-cell responses to antigen(s) resulting in CD28 down-regulation are associated with progression and manifestations of IPF, and suggest assays of circulating CD4 T-cells may identify patients at greatest risk for clinical deterioration.     

Impact of Preexisting Interstitial Lung Disease on Acute,Extensive Radiation Pneumonitis: Retrospective Analysis of Patients with Lung Cancer

IntroductionThis study investigated the clinical characteristics and predictive factors for developing acute extended radiation pneumonitis with a focus on the presence and radiological characteristics of preexisting interstitial lung disease.MethodsOf 1429 irradiations for lung cancer from May 2006 to August 2013, we reviewed 651 irradiations involving the lung field. The presence, compatibility with usual interstitial pneumonia, and occupying area of preexisting interstitial lung disease were retrospectively evaluated by pretreatment computed tomography. Cases of non-infectious, non-cardiogenic, acute respiratory failure with an extended bilateral shadow developing within 30 days after the last irradiation were defined as acute extended radiation pneumonitis.ResultsNine (1.4%) patients developed acute extended radiation pneumonitis a mean of 6.7 days after the last irradiation. Although preexisting interstitial lung disease was found in 13% of patients (84 patients), 78% of patients (7 patients) with acute extended radiation pneumonitis cases had preexisting interstitial lung disease, which resulted in incidences of acute extended radiation pneumonitis of 0.35 and 8.3% in patients without and with preexisting interstitial lung disease, respectively. Multivariate logistic analysis indicated that the presence of preexisting interstitial lung disease (odds ratio = 22.6; 95% confidence interval = 5.29–155; p < 0.001) and performance status (≥2; odds ratio = 4.22; 95% confidence interval = 1.06–20.8; p = 0.049) were significant predictive factors. Further analysis of the 84 patients with preexisting interstitial lung disease revealed that involvement of more than 10% of the lung field was the only independent predictive factor associated with the risk of acute extended radiation pneumonitis (odds ratio = 6.14; 95% confidence interval = 1.0–37.4); p = 0.038).ConclusionsPretreatment computed tomography evaluations of the presence of and area size occupied by preexisting interstitial lung disease should be assessed for safer irradiation of areas involving the lung field.     

Right Ventricular Sex Differences in Patients with Idiopathic Pulmonary Arterial Hypertension Characterised by Magnetic Resonance Imaging: Pair-Matched Case Controlled Study

PurposeSex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI).MethodsA case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data.Results40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females.ConclusionMale patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females.     

Hyperhomocysteinemia in Patients with Polypoidal Choroidal Vasculopathy: A Case Control Study

Purpose

To determine whether elevated plasma homocysteine and serum high sensitivity C-reactive protein (hsCRP) levels, two established risk factors of vascular diseases, are associated with polypoidal choroidal vasculopathy (PCV).

Design

Retrospective case-control study.

Methods

One hundred and nineteen consecutive patients with PCV and 119 matched controls were enrolled in a tertiary hospital from September 2008 to June 2013. Plasma homocysteine and serum hsCRP levels were measured. Associations among plasma homocysteine, serum hsCRP levels and PCV were further evaluated using multivariable logistic regression analysis.

Results

The median plasma homocysteine level was significantly higher in patients with PCV than in the controls (12.20 µmol/L vs. 9.80 µmol/L, p<0.001). The median serum hsCRP level was slightly higher in the PCV group (0.16 mg/dl vs. 0.11 mg/dl in control group, p = 0.07). After multivariable logistic regression analysis, each 1 µmol/L increase of plasma homocysteine was associated with a 1.5-fold increase in likelihood of having PCV (OR, 1.54; 95% confidence interval (CI), 1.33–1.79, p<0.001).

Conclusions

Hyperhomocysteinemia was associated with PCV and might play a role in the pathogenesis of PCV.     

Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background

Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI).

Methods

Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease.

Results

39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes.

Conclusions

Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.