Serum KL-6 and surfactant proteins A and D in pediatric interstitial lung disease

OBJECTIVE: To determine if serum KL-6, surfactant protein A (SP-A), and surfactant protein D (SP-D) levels are elevated in pediatric interstitial lung disease (ILD) and associated with pulmonary function and disease severity score. METHODS: Serum KL-6, SP-A, and SP-D levels were measured by enzyme-linked immunosorbent assay in 10 children with ILD and in 10 healthy volunteers. In the ILD group, FEV1 percentage of predicted, FVC percentage of predicted, and ILD disease severity score were measured and correlated with serum KL-6, SP-A, and SP-D levels. RESULTS: For the ILD and control groups, respectively, mean serum KL-6 was 4,523 U/mL and 206 U/mL (p = 0.007), mean serum SP-A was 133 ng/mL and 21 ng/mL (p = 0.003), and mean serum SP-D was 304 ng/mL and 75 ng/mL (p = 0.004). There was an inverse relationship between SP-A and FVC (p = 0.05), and between SP-D and FEV1 (p = 0.05). There was a direct relationship between SP-D and ILD score (p = 0.05). CONCLUSIONS: Serum KL-6, SP-D and SP-D levels are elevated in children with ILD. SP-A and SP-D levels appear to correlate with some measures of disease severity.     

Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases

KL-6, surfactant protein (SP)-A, SP-D, and monocyte chemoattractant protein-1 (MCP-1) are reported to be sensitive markers for interstitial lung diseases (ILD). However, each marker has been studied independently. The aim of this study was a comparative analysis of the diagnostic values of these markers. Subjects consisted of 33 patients with ILD (21 cases of idiopathic pulmonary fibrosis and 12 associated with collagen vascular diseases) and 82 control subjects (12 cases of bacterial pneumonia and 70 healthy volunteers). Receiver operating characteristic curves revealed that KL-6 was superior to the other markers. The cut-off levels for these markers that resulted in the highest diagnostic accuracy were determined to be 465 U/ml for KL-6, 48.2 ng/ml for SP-A, 116 ng/ml for SP-D, and 1080 pg/ml for MCP-1. The sensitivity, specificity, and diagnostic accuracy were 93.9%, 96.3%, and 95.7% for KL-6; 81.8%, 86.6%, and 85.2% for SP-A; 69.7%, 95.1%, and 87.8% for SP-D; and 51.5%, 92.7%, and 80.9% for MCP-1; respectively. The serum levels of SP-A and SP-D, but not of KL-6, were significantly higher in patients with bacterial pneumonia than in healthy volunteers. These results suggest that of the markers studied, KL-6 is the best serum marker for ILD.     

血清表面活性蛋白与系统性红斑狼疮合并间质性肺病的相关性研究

目的 探讨血清表面活性蛋白A(SP-A)和D(SP-D)与系统性红斑狼疮(SLE)合并间质性肺病(ILD)的相关性及其临床意义.方法 采用双抗体夹心酶联免疫吸附试验(ELISA)检测,并比较SLE组和对照组血清样本SP-A和SP-D水平的差异,分析其与SLE合并ILD的关系,判断与肺部高分辨率CT(HRCT)评分、肺功能、年龄、病情活动指标之间的相关性.结果 SLE组患者血清SP-A和SP-D水平高于健康对照组(P＜0.05).SLE组并发ILD患者血清SP-A和SP-D水平高于未合并ILD者以及对照组(P＜0.05).合并ILD的SLE患者血清SP-D水平与HRCT磨玻璃影评分(r=0.508,P=0.004)和间质病变评分(r=0.468,P=0.009)呈正相关关系,与肺活量(%VC)(r=-0.590,P=0.001)和一氧化碳弥散量(%DLCO)(r=-0.588,P＜0.01)呈负相关关系,而SP-A与上述指标无明显相关.SLE患者血清SP-D水平与年龄呈正相关关系(r=0.352,P=0.001).SLE-ILD组血清SP-D水平与血清IsG(r=0.376,P=0.040)呈正相关关系,SP-A水平与C反应蛋白(CRP)(r=0.403,P=0.027)呈正相关关系.结论 SP-D和SP-A是SLE并发ILD的血清学标志,SP-D与患者的HRCT评分、肺功能指标、年龄和病情活动度相关.     

KL-6, surfactant protein A and D in bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis.

BACKGROUND: KL-6, and surfactant protein A (SP-A) and surfactant protein D (SP-D) derived from alveolar type II cells and/or bronchiolar epithelial cells have been reported to be useful markers for interstitial lung diseases. OBJECTIVE: The aim of this study was to measure the levels of these molecules in bronchoalveolar lavage fluid (BALF) from patients with pulmonary sarcoidosis to investigate their relationship with other markers of inflammatory activity. METHODS: We measured KL-6, SP-A and SP-D levels in BALF from patients with pulmonary sarcoidosis using an ELISA. RESULTS: KL-6 and SP-D, but not SP-A levels were significantly increased in pulmonary sarcoidosis compared with controls. KL-6, SP-A and SP-D levels were significantly correlated with each other. KL-6 and SP-D levels were relatively and significantly correlated with the percentage of lymphocytes in BALF. KL-6, SP-D, but not SP-A levels were significantly correlated with the concentration of albumin in BALF. There was no significant correlation between KL-6, SP-A, or SP-D levels and chest X-ray findings, angiotensin-converting enzyme levels, or CD4/CD8 ratio in BALF. CONCLUSIONS: We conclude that KL-6 and SP-D levels in BALF were increased in pulmonary sarcoidosis. Since these markers are specifically derived from epithelial cells, it is considered that KL-6 and SP-D levels are reflecting damage or release of these markers from epithelial cells due to the inflammatory response.     

KL-6 and surfactant proteins A and D in serum and bronchoalveolar lavage fluid in patients with acute eosinophilic pneumonia

OBJECT: The serum levels of KL-6, surfactant protein A (SP-A), and SP-D are useful biomarkers and prognostic factors for the activity of interstitial pneumonias. The aim of this study was to determine the clinical roles of the levels of KL-6, SP-A, and SP-D in the serum and bronchoalveolar lavage fluid (BALF) of patients with acute eosinophilic pneumonia (AEP). MATERIALS AND METHODS: We researched 5 cases of AEP. The levels of KL-6, SP-A, and SP-D in the sera and BALF of those patients were measured by enzyme-linked immunosorbent assay. RESULTS: KL-6 levels in BALF did not differ between AEP patients and the healthy control group, while SP-A and SP-D levels in BALF were significantly higher in the AEP patients than in the healthy control group. In sera, AEP patients had significantly higher than normal levels of SP-A and SP-D, but not of KL-6. Only in sera there was a positive correlation between SP-A and SP-D, but no apparent correlations in BALF and also between KL-6 and the others. Furthermore, the BALF levels of SP-D, but not of SP-A or KL-6, statistically correlated with the concentration of albumin in BALF. After clinical improvement, the elevated levels of serum SP-A or SP-D in AEP patients decreased until normal levels were reached within 2 months. CONCLUSION: These results suggest that the serum or BALF levels of SP-D appear to be more sensitive than those of SP-A or KL-6 at reflecting the inflammatory response in AEP lungs.     

Gefitinib-induced interstitial lung disease showing improvement after cessation: disassociation of serum markers

Gefitinib (ZD1839), a small-molecule epidermal growth factor receptor tyrosine kinase inhibitor, is an anticancer agent for patients with non-small cell lung carcinoma. Recently, however, as a result of accumulating evidence, it has been recognized that gefitinib can give rise to lethal lung toxicity. The authors report a case of interstitial lung disease (ILD) induced by gefitinib, which improved promptly following cessation of the administration of the agent. Clinical signs suggesting a good prognosis were noted, namely, findings similar to acute eosinophilic pneumonia on CT and a disassociation in the elevation of specific serum markers of ILD. At the time of onset of ILD, serum concentrations of surfactant protein (SP)-A and SP-D were significantly increased, whereas that of KL-6 was not increased. A previous study of three cases of lethal lung toxicity resulting from gefitinib administration revealed a significant and almost equal increase in KL-6, SP-A and SP-D. These results suggest that SP-A and SP-D may be indicators of gefitinib-induced ILD and that KL-6 is a predictor of outcome. Using a combination of these markers may help to establish a differential prognosis in patients with gefitinib-induced ILD.     

Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis.

Radiation pneumonitis (RP) is the most common complication of radiotherapy for thoracic tumours. The aim of this study was to evaluate the significance of pulmonary surfactant proteins (SP)-A and SP-D as new serum markers for RP. Twenty-five patients with lung tumour, who had received radiotherapy, were studied. At the completion of radiotherapy, the presence of RP was judged by chest plain radiography and chest high resolution computed tomography (HRCT). RP findings detected on chest plain radiography were seen in only three of 12 patients in whom RP was detected by HRCT. Nevertheless, both SP-A and SP-D concentrations in sera from the patients with RP were significantly higher than those from the 13 patients without RP (p = 0.0065, p = 0.0011, respectively). As with SP-A, ratios of SP-D at the completion, compared to at the initiation (1 week post/pre ratio), were also significantly higher in patients with RP than in patients without RP. When a post/pre ratio > 1.6 was considered positive, the SP-A and SP-D assays showed an 83% and 85% specificity, respectively. In conclusion, serum assays of surfactant proteins A and D may be of diagnostic value for detection of radiation pneumonitis, even when the radiographic change is faint.     

Surfactant proteins A and D as biomarkers of disease activity in diffuse interstitial pneumonia]

We evaluated the clinical significance of surfactant proteins A (SP-A) and D (SP-D) as useful markers of disease activity in patients with diffuse interstitial pneumonia. Serum concentrations of SP-A and SP-D were measured by the sandwich ELISA method. The serum levels of SP-A and SP-D in patients with diffuse interstitial pneumonia (IIP, CVD-IP, HP, Ra-IP) were significantly higher than the levels in healthy controls, and showed high positive rates. IIP patients characterized by a predominantly ground-glass opacity (GGO) pattern on high-resolution computed tomograms had significantly higher concentrations of serum SP-A. Elevated SP-D levels reflected the extent not only of GGO but also of parenchymal collapse opacity (PCO). It is likely that the mechanisms behind the elevation of SP-A and SP-D do not correlate with pathologic changes in IIP. Serum SP-A and SP-D levels obtained at the time of initial evaluation from 9 patients who died after less than 3 years of follow-up were significantly higher than in patients with survival rates of more than 3 years. Serum SP-A and SP-D may be useful biomarkers of disease activity in patients with IIP.     

Characteristics and disease activity of early interstitial lung disease in subjects with true parenchymal abnormalities in the posterior subpleural aspect of the lung

STUDY OBJECTIVES: To evaluate characteristics or disease activity of early interstitial lung disease (ILD) in subjects with true parenchymal abnormalities in the posterior subpleural aspect of the lung. PATIENTS AND METHODS: This study enrolled 14 subjects with dependent densities that disappeared on helical CT obtained with the subject prone (control group) and 7 subjects with true parenchymal abnormalities that remained unchanged on prone CT image but were not detectable on chest radiographs (true abnormalities group). Pulmonary function tests and serum markers for idiopathic lung fibrosis as KL-6, surfactant protein D (SP-D), and surfactant protein A (SP-A) in the two groups were evaluated. RESULTS: In the true abnormalities group, curvilinear subpleural lines or thickened interlobular and intralobular lines were observed more frequently in the lower lung fields. Diffusing capacities of the lung for carbon monoxide (15.3 +/- 3.5 mL/min/mm Hg vs 18.8 +/- 3.7 mL/min/mm Hg, p = 0.0493) were lower, and KL-6 (607 +/- 297 U/mL vs 318 +/- 143 U/mL, p = 0.0090), SP-A (59 +/- 24 ng/mL vs 34 +/- 12 ng/mL, p = 0.0207), and SP-D (112 +/- 54 ng/mL vs 42 +/- 24 ng/mL, p = 0.0028) were higher in the true abnormalities group than in the control group (+/- SD). CONCLUSION: True parenchymal abnormalities in the posterior subpleural aspect of the lung may indicate early ILD activity.     

应用一氧化碳弥散功能检测结缔组织病患者肺间质病变的意义

目的　探讨对结缔组织病 (CTD)患者肺间质病变 (ILD)进行早期、安全、有效且可量化的诊断方法。方法　对 93例CTD患者 ,其中 4 8例系统性红斑狼疮 (SLE)、18例皮肌炎 (DM)、2 1例系统性硬皮病 (PSS)、6例干燥综合征 (SS)进行了一氧化碳弥散功能检测 ,并与X线胸片、肺部高分辨率CT(HRCT)结果相比较 ;同时测定了 5 0名正常人的X线胸片和一氧化碳弥散功能作为对照。结果　X线胸片、肺部HRCT和一氧化碳弥散功能检测 (以一氧化碳弥散吸收率 <80 %为标准 )在SLE中检测到ILD的比率分别是 15 %、36 %和 4 2 % ;在DM中的比率分别是 17%、36 %和 39% ;在PSS中的比率分别是 38%、4 2 %和 5 2 % ;SS的比率分别是 33%、6 7%和 5 0 %。而正常人的X线胸片均正常 ,一氧化碳弥散吸收率均≥ 80 %。结论　X线胸片在检测CTD患者ILD中敏感性最低 ,而HRCT和一氧化碳弥散功能是检测CTD患者ILD的敏感方法。尤其是后者 ,具有敏感性高、不受X线照射、易被患者接受和对其损害程度进行量化等优点 ,既可作为早期了解CTD患者ILD的检测方法 ,又可通过一氧化碳弥散功能的改变对治疗效果进行评价。     

特发性肺纤维化患者肺泡灌洗液和血清中Napsin A、KL-6、SP-A、SP-D表达的意义及与肺功能相关性

目的特发性肺纤维化(IPF)是一种不明原因的慢性进行性间质性肺疾病。其发病率、死亡率均较高。但IPF的发病机制至今尚未完全清楚,临床上对此病发生发展的掌握不够,检验指标的敏感性及特异性不高,从而影响诊断及临床判断的准确性。因此寻找IPF发生发展的生物标记物成为近年来较为热门的研究方向。方法挑选2017年3月-2019年3月间在我院就诊并诊断明确的30例IPF患者入组IPF观察组,20例临床症状类似的I期肺结节病患者作为阴性对照组。采用双抗体夹心酶联免疫吸附(ELISA)法检测IPF和I期肺结节病对照组BALF和血清中Napsin A/KL-6/SP-A/SP-D水平,并对患者的肺功能进行检测,评估上述生物标记物与肺纤维化病程进展的相关性。结果IPF组患者的血清/肺泡灌洗液中Napsin A/KL-6/SP-A/SP-D水平均明显高于由I期肺结节病阴性对照组(P<0.05)。灌洗液中Napsin A/KL-6/SP-D含量与肺通气功能呈负相关(P<0.05),而Napsin A/KL-6含量与弥散功能呈现负相关(P<0.05)。血清中Napsin A/KL-6/SP-A/SP-D水平均与肺通气功能呈负相关(P<0.05),Napsin A/KL-6血清含量与肺弥散功能呈明显负相关(P<0.05),与肺泡灌洗液检测结果一致。结论Napsin A/KL-6/SP-A/SP-D在IPF患者灌洗液中的含量亦显著升高。其中血清Napsin A/KL-6水平相关度最高,高水平的血清及灌洗液中Napsin A/KL-6浓度提示IPF病灶进展,且与肺通气功能及弥散指标呈负相关,可作为诊断IPF严重程度判断的指标之一。而SP-A、SP-D也可以作为IPF早期的一种早期预测指标,敏感性特异性差于Napsin A/KL-6,但SP-D对于肺功能下降、肺纤维化早期炎症反应,优于SP-A。     

Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease

OBJECTIVE: To determine the clinical significance of serum surfactant protein D (SP-D) levels in patients with polymyositis/dermatomyositis (PM/DM). METHODS: Serum SP-D levels were assayed using a sensitive enzyme-linked immunosorbent assay in 59 patients with PM/DM and in 29 healthy controls. RESULTS: The serum level of SP-D was significantly higher in patients with PM/DM than in healthy controls (mean+/-S.D. 61.7+/-122.6 vs 31.0+/-12.4 ng/ml, P < 0.01). The serum SP-D level in patients with interstitial lung disease (ILD) was significantly higher than in those without ILD (118.7+/-220.2 vs 38.7+/-21.0 ng/ml, P < 0.001). Serum level of SP-D was correlated with the presence of ILD. The incidences of decreased vital capacity (%VC) and of decreased diffusing capacity of carbon monoxidase (%DLCO) were also significantly greater in patients with an elevated SP-D level than in those with a normal level (64 vs 7%, P < 0.02; 73 vs 27%, P < 0.01). Moreover, the serum SP-D level was inversely correlated with %VC (r=-0.452, P < 0.01) and %DLCO (r=-0.349, P < 0.05). CONCLUSION: The serum SP-D level may be a useful marker for ILD in patients with PM/DM.     

Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) has a high mortality rate, and current therapies are only marginally effective. A serum biomarker that predicts clinical outcome would be useful to stage disease, indicate prognosis and the need for aggressive therapy, and help stratify patients for clinical trials. The goals of this study were to determine whether serum levels of surfactant protein-A (SP-A) or surfactant protein-D (SP-D) would distinguish between IPF and other types of interstitial lung disease and whether serum SP-A or SP-D levels predict outcome in patients with IPF. The authors found that serum SP-A and SP-D levels were significantly elevated in patients with IPF and systemic sclerosis compared to sarcoidosis, beryllium disease and normal controls, and that SP-D correlated with radiographic abnormalities in patients with IPF. In addition, the authors found that both serum SP-A and SP-D levels were highly predictive of survival in patients with IPF. This is the largest North American data set of surfactant protein measurements in idiopathic pulmonary fibrosis and the first report using multivariate analysis comparing serum surfactant proteins-A and -D to other commonly measured predictors of survival in idiopathic pulmonary fibrosis. Based on these results, the authors propose that serum surfactant proteins may prove to be useful biomarkers in patients with idiopathic pulmonary fibrosis.     

乙酰半胱氨酸辅助治疗慢性阻塞性肺疾病急性加重期的临床分析

目的探讨乙酰半胱氨酸辅助治疗慢性阻塞性肺疾病急性加重期(AECOPD)的临床效果及对患者气道重塑、氧化应激及血清肺表面活性蛋白-A(SP-A)、肺表面活性蛋白-D(SP-D)、克拉拉细胞蛋白(CC16)水平的影响。 方法选择医院收治的94例AECOPD患者随机分为对照组与观察组各47例,对照组给予AECOPD基础治疗,观察组采用乙酰半胱氨酸辅助治疗,评定两组疗效,测定治疗前后两组气道重塑指标[气道壁厚度与气道管腔外径比(T/D)、气道腔面积(AI)、气道壁面积(WA)、WA占总截面积百分比(WA%)]、氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)]及血清肺表面生化标志物(SP-A、SP-D、CC16)水平的变化,记录治疗不良反应。 结果①观察组总有效率高于对照组(87.23% vs. 70.21%)(P<0.05);②治疗前,两组气道重塑相关指标、氧化应激指标及血清生化标志物水平对比差异无统计学意义(P>0.05),治疗4周,两组T/D、WA、WA%、MDA、SP-A、SP-D、CC16降低,AI、GSH-PX、SOD上升,观察组T/D、WA、WA%、MDA、SP-A、SP-D、CC16低于对照组,AI、GSH-PX、SOD高于对照组(P<0.05);③两组治疗不良反应发生率比较差异无统计学意义(6.38% vs. 4.26%)(P>0.05)。 结论AECOPD患者辅助应用乙酰半胱氨酸治疗可提升疗效,改善气道重塑及氧化应激状态,降低血清SP-A、SP-D、CC16水平,且安全性肯定。     

Bronchoalveolar lavage fluid surfactant protein-A and surfactant protein-D are inversely related to inflammation in early cystic fibrosis

The pulmonary collectins surfactant protein (SP)-A and SP-D play important roles in innate lung defense, enhancing opsonization of microbes and limiting lung inflammatory responses. To quantify relationships among collectins, bacteria, and inflammation in early cystic fibrosis (CF) airway secretions, bronchoalveolar lavage fluids (BALFs) were collected from children undergoing clinically indicated bronchoscopy. Quantitative bacteriology, differential cell counts, and ELISA for SP-A and SP-D were assessed. Significantly increased numbers of neutrophils relative to bacteria were noted in BALF from CF compared with non-CF subjects. Although SP-A levels tended to be lower in CF compared with non-CF, this was only significant in the presence of bacterial infection. Among CF patients, SP-A concentrations in BALF were inversely related to inflammation, bacterial colony-forming units per milliliter, and age. SP-D levels were significantly decreased in CF patients, and SP-D was rarely detectable in the presence of infection. Among CF patients, SP-D correlated inversely with inflammation and bacterial colony-forming units per milliliter, and there was decreased immunostaining of BALF cells for SP-D in CF. Immunohistochemistry of CF autopsy lung sections for SP-A and SP-D confirmed their paucity at sites of infection and inflammation. We conclude that relative collectin deficiency occurs early in CF airways and is inversely related to inflammation in CF airways.     

皮肌炎多发性肌炎患者间质性肺病病理资料推断性分析

目的 分析皮肌炎(DM)、多发件肌炎(PM)合并间质性肺病(ILD)患者的胸部X线、胸部高分辨CT(HRCT)及肺功能等肺部表现临床特点及其预后.方法 回顾性分析上海长海医院风湿免疫科1999年1月至2007年1月期间收住院的33例DM/PM合并ILD除外感染患者的临床资料.结果 33例ILD患者经胸部X线及HRCT证实.根据临床-影像学特点并结合血气分析、肺功能测定,参照美国胸科学会和欧洲呼吸协会问质性肺炎的分类诊断标准,推断分析病理类型主要为非特异性间质性肺炎(NSIP)(57%)和寻常性间质性肺炎(UIP)(25%). UIP类型预后差、病死率高(70%).结论 结合患者的影像学资料、肺功能、血气分析推断病理类型主要为NSIP和UIP,其中UIP病死率高、预后差.     

A case of idiopathic pulmonary upper lobe fibrosis complicated by invasive pulmonary aspergillosis]

A 72-year-old man with idiopathic pulmonary upper lobe fibrosis who had been followed for a year developed a high fever and yellow sputum in July 2001. Chest radiography and chest computed tomography (CT) showed a rapidly enlarging cavity with an internal mass and infiltration in the left upper lung field. Pulmonary aspergillosis was diagnosed by examination of bronchoalveolar lavage fluid (BALF). Administration of itraconazole improved his condition. The concentrations of surfactant proteins A (SP-A) and D (SP-D) in serum and in BALF were decreased during the clinical course. It is known that SP-A and SP-D are critical factors for host defense against aspergillus. The lowering of SP-A and SP-D in the serum and BALF seemed to reflect destructive changes of lung structure and impaired innate lung immunity that could to lead invasive pulmonary aspergillosis.     

Surfactant proteins A and D in premature baboons with chronic lung injury (Bronchopulmonary dysplasia). Evidence for an inhibition of secretion.

Surfactant proteins A and D (SP-A and SP-D) are believed to participate in the pulmonary host defense and the response to lung injury. In order to understand the effects of prematurity and lung injury on these proteins, we measured the amounts of SP-A and SP-D and their mRNAs in three groups of animals: (1) nonventilated premature baboon fetuses; (2) neonatal baboons delivered prematurely at 140 d gestation age (ga) and ventilated with PRN O(2); (3) animals of the same age ventilated with 100% O(2) to induce chronic lung injury. In nonventilated fetuses, tissue and lavage SP-A were barely detectable in baboons of 125 and 140 d ga, but they equaled or exceeded adult SP-A concentrations (g/g lung dry wt) at 175 d (term gestation, 185 d). In contrast, SP-D was readily detectable in tissue and lavage at 125 and 140 d ga. When the baboons of 140 d ga were ventilated for 10 d with 100% oxygen to produce chronic lung injury, the tissue concentration of SP-A was five times greater than that of normal adults; SP-D 16-times greater. Despite the sizable tissue pools of SP-A and SP-D, however, lavage SP-A was only 7% of that of normal adults and lavage SP-D just equaled the amount in normal adults. Nevertheless, because SP-D is normally in much lower concentration than is SP-A, their total comprised less than 12% of the SP-A and SP-D found in the lavage of a healthy adult. The results indicate that in chronic lung injury, SP-A is significantly reduced in the alveolar space. SP-D concentration in lavage is about equal to that in normal adults, possibly because of the 16-fold excess in tissue, but the total collectin pool in lavage is still significantly reduced. Because these collectins may bind and opsonize bacteria and viruses, decrements in their amounts may present additional risk to those premature infants who require prolonged periods of ventilatory support.     

Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS

The goal of this study was to determine the changes that occur in surfactant-associated proteins in bronchoalveolar lavage fluid (BAL) and serum of patients at risk for ARDS and during the course of ARDS. We found that the concentrations of SP-A and SP-B were low in the BAL of patients at risk for ARDS before the onset of clinically defined lung injury, whereas the concentration of SP-D was normal. In patients with established ARDS, BAL SP-A and SP-B concentrations were low during the entire 14-d observation period, but the median SP-D concentrations remained in the normal range. Immunoreactive SP-A and SP-D were not increased in the serum of patients at risk for ARDS, but both increased after the onset of ARDS to a maximum on Day 3 and remained elevated for as long as 14 d. The BAL SP-A concentrations were significantly lower in at-risk patients who developed ARDS, and no patient with a BAL SP-A concentration greater than 1.2 microg/ml developed ARDS. On Days 1 and 3 of ARDS, the BAL SP-D concentration was significantly lower in patients who died, and the BAL SP-D concentration was significantly related to the PI(O(2))/FI(O(2)) ratio. Thus, surfactant protein abnormalities occur before and after the onset of ARDS, and the responses of SP-A, SP-B, and SP-D differ in important ways. The BAL SP-A and SP-D measurements can be used to classify patients as high or low risk for progression to ARDS and/or death after the onset of ARDS. Strategies to increase these surfactant proteins in the lungs of patients with ARDS could be useful to modify the onset or the course of ARDS.     

Interim <Superscript>18</Superscript>F-FGD PET/CT may not predict the outcome in primary central nervous system lymphoma patients treated with sequential treatment with methotrexate and cytarabine

¹⁸F-fluoro-2-dexoy-D-glucose-positron emission tomography (PET)/computed tomography (CT) is a useful imaging technique for monitoring the treatment response in lymphoma cases. We investigated the value of interim brain PET/CT (I-PET/CT) for monitoring the response to intensive methotrexate-based chemotherapy in primary central nervous system lymphoma (PCNSL) patients with diffuse large B cell lymphoma (DLBCL). Of the 76 PCNSL patients treated with intensive methotrexate and cytarabine chemotherapy between September 2006 and December 2012, 66 patients with DLBCL were included in this study. The patient cohort of 66 individuals comprised 43 men and 23 women with a median age of 59 years (range, 17–75 years). During chemotherapy, 36 patients (54.5%) showed a negative metabolism on I-PET/CT, and 47 (71.2%) were negative on final (F) PET/CT. The baseline characteristics were similar between I-PET/CT-negative (n = 36) and I-PET/CT-positive patients (n = 30) except ECOG performance status. After a median follow-up of 27.5 months, there was no difference in the progression-free survival (PFS; P = 0.701) or overall survival (OS; P = 0.620) between the I-PET/CT-negative and I-PET/CT-positive groups. However, PFS in the F-PET/CT-negative group was significantly longer than that in the F-PET/CT-positive group (P < 0.001) without a significant difference in OS (P = 0.892). I-PET/CT may not predict the survival outcome of PCNSL patients with DLBCL treated with intensive methotrexate and cytarabine chemotherapy. Prospective trials are required to fully evaluate the role of I-PET/CT.