Monitoring markers of disease activity for interstitial lung diseases with serum surfactant proteins A and D

Objectives:   Surfactant protein (SP) A and D are specific serum markers for interstitial lung diseases including idiopathic pulmonary fibrosis (IPF). The authors evaluated the critical roles of these markers on the prognoses of patients with IPF and the mechanisms of their elevation in sera.
Methodology:   The authors evaluated the relationship between prognosis and the serum markers in 82 IPF patients. The protein content and mRNA expression of the markers were evaluated using rats with interstitial pneumonia induced by bleomycin administration.
Results:   Higher levels of serum SP-D at the time of the initial visit to the Sapporo Medical University Hospital were associated with poorer prognoses, while SP-A showed no significant affect on survival. Causes of the elevation in sera were due to the acceleration of, not only production in the lungs, leakage into the circulation. The elevation was associated with alveolitis but not fibrosis.
Conclusions:   SP-D is a good predictor of the prognosis in patients with IPF.     

Increased circulating levels of soluble Fas ligand are correlated with disease activity in patients with fibrosing lung diseases

OBJECTIVE: The Fas-Fas ligand (FasL) pathway is one of the important apoptosis-signalling molecule systems. We previously determined that this pathway may be involved in the pathogenesis of fibrosing lung diseases. In the present study, we evaluated the clinical significance of the levels of soluble forms of Fas (sFas) and FasL (sFasL) in serum from patients with fibrosing lung diseases. METHODOLOGY: We measured sFas, sFasL, KL-6 (a measure of alveolar type II cell damage), surfactant protein D (SP-D), and surfactant protein A (SP-A) levels in serum from 35 patients with idiopathic pulmonary fibrosis (IPF), 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP), and 13 normal healthy controls using enzyme-linked immunosorbent assays (ELISA). RESULTS: The serum levels of sFasL were significantly increased in patients with active IPF and CVD-IP, compared with those with inactive disease and controls. There was no significant difference in sFasL levels between patients with inactive disease and controls. Serum sFasL levels were significantly correlated with lactate dehydrogenase and KL-6 levels in IPF. The decrease in sFasL levels following corticosteroid therapy was not correlated with the clinical course of IPF. There was no significant difference in serum sFas levels between IPF or CVD-IP patients and controls. CONCLUSIONS: Although further studies need to be performed on a large number of patients with histologically proven IPF or CVD-IP, it would seem that serum sFasL levels may reflect the activity of IPF and CVD-IP.     

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。     

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.     

Clinical characterization of interleukin-8 in patients with idiopathic pulmonary fibrosis]

The levels of interleukin-8 (IL-8) in the serum, bronchoalveolar fluid (BALF) and epithelial lining fluid (ELF) were measured in patients with idiopathic pulmonary fibrosis. (IPF), in order to evaluate the clinical significance of IL-8. The serum levels were significantly higher in patients with active IPF (34.4 +/- 11.9 pg/ml, n = 8) than in those with stable IPF (mean: 14.6 +/- 10.9 pg/ml, n = 18), but neither correlated with the serum level of KL-6 or of SP-D, or with the intensity of chest Ga67-scintigraphy. There were no significant differences in BALF or ELF IL-8 levels between the active and stable IPF groups. These results suggest that the serum level of IL-8 is a useful marker for evaluating the disease activity in patients with IPF.     

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.     

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.     

Prognostic value of serum surfactant protein D level prior to transplant for the development of bronchiolitis obliterans syndrome and idiopathic pneumonia syndrome following allogeneic hematopoietic stem cell transplantation

Bronchiolitis obliterans syndrome (BOS) and idiopathic pneumonia syndrome (IPS) cause high mortality and impaired survival after allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Early recognition of patients at high risk of developing BOS/IPS may lead to improving the outcome of allo-HSCT. We retrospectively analyzed serum surfactant protein A, D (SP-A, -D) and Kerbs von Lungren 6 Ag (KL-6) levels before allo-HSCT in 56 patients who survived more than 90 days after allo-HSCT and compared values of these serum markers and other transplant factors in BOS/IPS patients with those in non-BOS/IPS patients. Five patients developed BOS and two developed IPS at a median interval of 303 and 117 days (range, 100-452 and 95-153) from transplantation. As a result of univariate analysis, pretransplant serum SP-D levels but not SP-A, KL-6 in BOS/IPS patients were significantly lower than those in non-BOS/IPS patients (P=0.03). In multivariate analysis, the patients with lower pretransplant serum SP-D level had a trend toward frequent development of BOS/IPS (P=0.08). Constitutive serum SP-D level before allo-HSCT may be a useful, noninvasive predictor for the development of BOS/IPS.     

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.     

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.     

肺表面活性物质相关蛋白A与D在肺结核诊断中的研究

目的 研究肺表面活性物质相关蛋白A、D（pulmonary surfactant associated protein A、D,SP-A、SP-D）在肺结核患者中的表达，探讨2者的相关性。 方法 采用ELISA方法检测涂阳肺结核50例，涂阴肺结核51例，慢性阻塞性肺疾病（COPD）患者30例及健康人85名血清及痰液中SP-A、SP-D的表达情况。 结果 涂阳肺结核组痰液中SP-A、SP-D的表达与痰液中结核分枝杆菌的含菌量有相关性；血清SP-A、SP-D在肺结核组高表达（P<0.05），痰SP-D在肺结核组低表达（P<0.01）。 结论 SP-A、SP-D的表达与肺结核之间可能有相关性，或可成为协助肺结核诊断的辅助指标。     

Increased surfactant protein-A levels in patients with newly diagnosed idiopathic pulmonary fibrosis

STUDY OBJECTIVES: To measure surfactant protein-A (SP-A) in the BAL of patients with idiopathic pulmonary fibrosis (IPF). DESIGN: We examined SP-A in BAL and lung tissue of patients with IPF who met the stricter recommended criteria for IPF at the time of diagnosis and prior to the beginning of treatment. PATIENTS: Twenty-six patients with IPF confirmed at biopsy and 22 patients with hypersensitivity pneumonitis (HP) were compared with 9 normal volunteers. INTERVENTIONS: All patients were subjected to pulmonary function testing, BAL, and lung biopsy prior to the beginning of treatment. Measurements and results: We measured SP-A in BAL fluids and performed SP-A immunohistochemistry on lung specimens. Lung tissues of patients with IPF showed extensive type II cell hyperplasia, usually containing greatly increased levels of immunoreactive SP-A. By enzyme-linked immunosorbent assay, we found a twofold increase over normal values in BAL SP-A without changes in total phospholipids. These data were in agreement with semiquantitative assessments of SP-A by protein immunoblotting and by Western blotting of sodium dodecyl sulfate gels. Patients with HP exhibited a threefold increase of BAL SP-A. CONCLUSIONS: The reasons for the difference between our results and previously published reports describing decreased SP-A levels in IPF is not clear. It may relate to the stricter criteria for diagnosis, the absence of treatment prior to BAL, differences in the patient population, or to other methodologic differences.     

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.     

Evaluation of changes in the serum levels of Krebs von den Lungen-6 and surfactant protein-D over time as important biomarkers in idiopathic fibrotic nonspecific interstitial pneumonia

BackgroundSome cases of idiopathic fibrotic nonspecific interstitial pneumonia (f-NSIP) show a progressive course that is similar to that of idiopathic pulmonary fibrosis. However, it is difficult to predict poor patient outcomes. This study aimed to evaluate whether serial changes in serum levels of Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) can predict disease progression.MethodsWe retrospectively analyzed the medical records of 75 patients with idiopathic f-NSIP. Disease behavior was categorized into two groups depending on long-term change of pulmonary function: progressive type (≥5%/year relative decline in the slope of forced vital capacity [FVC] and/or ≥7.5%/year relative decline in the slope of %diffusing capacity of the lung for carbon monoxide [%D_LCO]) and stable type. Levels of KL-6 and SP-D and results of pulmonary function tests, which were performed parallelly, were reviewed and analyzed using a linear mixed-effects model.ResultsThe study subjects comprised 62 patients with stable type and 13 patients with progressive type disease behavior. Among these subjects, 50 patients fulfilled the diagnostic criteria of interstitial pneumonia with autoimmune features (IPAF). Serum levels of both KL-6 and SP-D at baseline showed a negative correlation with %D_LCO, but not with FVC, and these biomarkers were not related to disease progression. Persistently high levels of KL-6 and SP-D correlated with progressive type disease behavior in idiopathic (non-IPAF) f-NSIP.ConclusionsChanges in serum KL-6 and SP-D levels over time may provide useful predictive information on disease behavior during treatment in patients with idiopathic f-NSIP and especially in those with non-IPAF f-NSIP.     

Idiopathic pulmonary fibrosis. Abnormalities in the bronchoalveolar lavage content of surfactant protein A

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the lung characterized by an inflammatory infiltrate, alveolar type II cell hypertrophy and hyperplasia, and ultimate parenchymal scarring. The phospholipid composition of the surface-active material recovered by bronchoalveolar lavage (BAL) is abnormal in this disease. In the present study we have extended the analysis of surfactant components in IPF to include the major surfactant-associated protein, surfactant protein A (SP-A). SP-A has been reported to be essential for the formation of tubular myelin, to facilitate the adsorption of phospholipid to the air/liquid interface, and to stimulate uptake and inhibit secretion of surfactant in vitro. The BAL of 25 normal volunteers and 42 patients with interstitial lung disease (ILD) was analyzed for surfactant protein A content by ELISA and for phospholipids. The changes in BAL components were correlated to histopathologic markers at open-lung biopsy, clinical status, and survival. The total phospholipid (PL) recovered at lavage was reduced in patients with IPF relative to normal volunteers (p less than 0.0005). In addition, the percentage of phosphatidyl-glycerol (% PG) was decreased in patients with IPF (p less than 0.0001), whereas the percentage of phosphatidylcholine that was saturated was not altered. The content of surfactant protein A in lavage was reduced, even when normalized for the total amount of surface-active material recovered (SP-A/PL) (p less than 0.007). The reduction in SP-A was not specific to IPF but also occurred in other interstitial lung diseases.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Clinical significance of MCP-1 levels in BALF and serum in patients with interstitial lung diseases.

It has previously been reported that the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung tissues of patients with idiopathic pulmonary fibrosis (IPF) was different from that in the tissues of patients with other interstitial lung diseases (ILDs). The aim of this study was to determine whether this difference reflects the amount of MCP-1 in the bronchoalveolar lavage fluid (BALF) or serum of patients with ILD, and whether such a correlation, if it exists, is clinically useful. MCP-1 concentrations in the BALF and sera were evaluated in 86 patients with ILDs including IPF, acute interstitial pneumonia, interstitial pneumonia with collagen vascular disease (IP-CVD), chronic interstitial pneumonia (CIP), bronchiolitis obliterans-organizing pneumonia, sarcoidosis, hypersensitivity pneumonitis, and in 10 normal healthy volunteers who were controls (NC). BALF MCP-1 levels were significantly elevated in the IPF, IP-CVD, CIP and sarcoidosis groups compared with the NC group. The level in the IPF group was significantly higher than that in any other patient group. Serum MCP-1 levels in the IPF, IP-CVD, CIP and sarcoidosis groups were significantly higher than the NC group. No statistical difference was found in serum MCP-1 levels between the IPF, IP-CVD and CIP groups. BALF MCP-1 levels were significantly higher than serum MCP-1 levels in the IPF group and lower than in the IP-CVD and CIP groups. Serum MCP-1 levels correlated with the clinical course of ILD treated with corticosteroid therapy. These results show that measurement of monocyte chemoattractant protein-1 levels in both bronchoalveolar lavage fluid and serum may be helpful in discriminating idiopathic pulmonary fibrosis from other types of interstitial lung disease and that monitoring of serum monocyte chemoattractant protein-1 may be useful for predicting the clinical course of interstitial lung diseases.     

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.     

Surfactant protein D in serum from patients with allergic bronchopulmonary aspergillosis.

Surfactant protein D (SP-D) interacts with Aspergillus fumigatus and is strongly increased in the lavage from animals with acute allergic reactions to the fungus, suggesting a central role for SP-D. As the course of cystic fibrosis (CF) is often complicated by an allergic bronchopulmonary aspergillosis (ABPA), the authors hypothesised that SP-D may also be increased in serum during an ABPA, potentially assisting in its diagnosis and follow-up. In 22 patients with CF (11 with ABPA, 11 matched without ABPA) and 19 control patients without a pulmonary disease, SP-D concentrations in serum were assessed by an enzyme immunoassay. Serum SP-D in CF patients (130 +/- 16 ng x mL(-1) (mean +/- SEM)) was significantly higher than in the controls without lung disease (66 +/- 8 ng x mL(-1)). During the whole ABPA-episode, SP-D level did not change significantly, despite large changes of total serum immunoglobulin E. There was a clear negative correlation between SP-D concentration and overall lung function, i.e. forced expiratory volume in one second and forced vital capacity. Serum level of surfactant protein D may be of value to follow pulmonary function and lung injury in cystic fibrosis patients. Surfactant protein D serum levels are not helpful for the diagnosis and follow-up of an allergic bronchopulmonary aspergillosis episode, contrary to what was expected from animal experiments.     

Diagnostic Values For Club Cell Secretory Protein (CC16) in Serum of Patients of Combined Pulmonary Fibrosis and Emphysema

Combined pulmonary fibrosis and emphysema (CPFE) is an under-recognized syndrome for which the diagnostic use of serum biomarkers is an attractive possibility. We hypothesized that CC16 and/or TGF-β1 or combinations with other biomarkers are useful for diagnosing CPFE. Patients with respiratory symptoms and a smoking history, with or without chronic obstructive pulmonary disease, were divided into the following three groups according to findings of high-resolution computed tomography of the chest: controls without either emphysema or fibrosis, patients with emphysema alone, and patients compatible with the diagnosis of CPFE. Serum concentrations of CC16, TGF-β1, SP-D, and KL-6 were measured in patients whose condition was stable for at least 3 months. To investigate changes in biomarkers of lung fibrosis in patients with a life-long smoking history, additional measurements were performed on the patients with idiopathic pulmonary fibrosis (IPF) of smoking history. The mean age of the first three groups was 68.0 years, whereas that of the IPF group was 71.8 years, and the groups contained 36, 115, 27, and 10 individuals, respectively. The serum concentration of CC16 in the four groups was 5.67 ± 0.42, 5.66 ± 0.35, 9.38 ± 1.04 and 22.15 ± 4.64 ng/ml, respectively, indicating that those patients with lung fibrosis had a significantly higher concentration. The combined use of CC16, SP-D, and KL-6 provided supportive diagnosis in conjunction with radiological imaging in diagnosis of CPFE. We conclude that a combination of biomarkers including CC16 could provide useful information to screen and predict the possible diagnosis of CPFE.