Serum Surfactant Protein D Levels Research Articles

Prescreening based on the presence of CT-scan abnormalities and biomarkers (KL-6 and SP-D) may reduce severe radiation pneumonitis after stereotactic radiotherapy

PurposeTo determine the risk factors of severe radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for primary or secondary lung tumors.Materials and methodsFrom January 2003 to March 2009, SBRT was performed on 117 patients (32 patients before 2005 and 85 patients after 2006) with lung tumors (primary = 74 patients and metastatic/recurrent = 43 patients) in our institution. In the current study, the results on cases with severe RP (grades 4-5) were evaluated. Serum Krebs von den Lungen-6 (KL-6) and serum Surfactant protein-D (SP-D) were used to predict the incidence of RP. A shadow of interstitial pneumonitis (IP) on the CT image before performing SBRT was also used as an indicator for RP. Since 2006, patients have been prescreened for biological markers (KL-6 & SP-D) as well as checking for an IP-shadow in CT.ResultsGrades 4-5 RP was observed in nine patients (7.7%) after SBRT and seven of these cases (6.0%) were grade 5 in our institution. A correlation was found between the incidence of RP and higher serum KL-6 & SP-D levels. IP-shadow in patient's CT was also found to correlate well with the severe RP. Severe RP was reduced from 18.8% before 2005 to 3.5% after 2006 (p = 0.042). There was no correlation between the dose volume histogram parameters and these severe RP patients.ConclusionPatients presenting with an IP shadow in the CT and a high value of the serum KL-6 & SP-D before SBRT treatment developed severe radiation pneumonitis at a high rate. The reduction of RP incidence in patients treated after 2006 may have been attributed to prescreening of the patients. Therefore, pre-screening before SBRT for an IP shadow in CT and serum KL-6 & SP-D is recommended in the management and treatment of patients with primary or secondary lung tumors.

Circulating Surfactant Protein D Is Decreased in Systemic Lupus Erythematosus

Deficiencies of innate immune molecules like mannan binding lectin (MBL) have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Surfactant protein D (SP-D) and MBL belong to the same family of innate immune molecules - the collectins, which share important structural and functional properties. We aimed to compare concentrations of serum SP-D in patients with SLE and in healthy controls, and to investigate if SP-D is associated with selected disease indicators. We investigated the possible association of the Met11Thr polymorphism with disease, since this polymorphism is an important determinant for serum level, oligomerization pattern, and function of SP-D. Serum SP-D was measured using a 5-layer ELISA in 70 SLE patients and 1476 healthy subjects. DNA was genotyped for the Met11Thr variant. Median SP-D level in serum was 911 ng/ml (95% CI 776-1118) in patients and 1068 ng/ml (95% CI 901-1246) in controls (p = 0.0004). Circulating SP-D did not differ significantly in patients with high, intermediate, or low SLE disease activity. Similarly, SP-D did not correlate with C-reactive protein, erythrocyte sedimentation rate, and anti-dsDNA seropositivity. Genetic analysis did not support an association of the Met11Thr genotype with SLE. These findings suggest that low SP-D, unrelated to conventional disease indicators, represents an aspect of SLE etiopathogenesis.

Serum Surfactant Protein D during Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Background: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations.Objectives: To determine whether or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease.Study design: case control study.Methods: We measured serum SP-D levels from patients with stable COPD (n= 14), patients experiencing acute exacerbations (n= 13) and in control subjects (n= 54) using a specific immunoassay and compared the levels using analysis of variance.Results: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 ± 120 ng/mL) compared to patients with stable disease (151 ± 83 ng/mL) or control subjects (128 ± 65 ng/mL;p= 0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV1/FVC% predicted.Conclusions: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations.

Serum surfactant protein D during acute exacerbations of chronic obstructive pulmonary disease.

Background: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations. Objectives: To determine whether or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease. Study design: case control study. Methods: We measured serum SP-D levels from patients with stable COPD (n = 14), patients experiencing acute exacerbations (n = 13) and in control subjects (n = 54) using a specific immunoassay and compared the levels using analysis of variance. Results: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 ± 120 ng/mL) compared to patients with stable disease (151 ± 83 ng/mL) or control subjects (128 ± 65 ng/mL; p = 0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV1/FVC% predicted. Conclusions: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations.

Elevation of Serum KL-6 Glycoprotein or Surfactant Protein-D in Adult T-cell Leukemia with Distinct Pulmonary Complications

Patients with hematological malignancies frequently suffer from lung diseases as a complication. However, it is difficult to discriminate leukemic invasion into the lung from infectious pulmonary complications. The serum level of Krebs von den Lungen-6 (KL-6), which is a mucin-like glycoprotein, is increased in more than 70% of patients with interstitial pneumonia. Surfactant protein-D (SP-D) is produced mainly in the lung by alveolar type II and bronchiolar epithelial cells and is a useful serum marker for interstitial pneumonia. We therefore measured the levels of KL-6 and SP-D in sera from 128 patients (76 males and 52 females, mean age: 59 years) with hematological malignancies, including adult T-cell leukemia (ATL). Overall, the increase in KL-6 or SP-D, above each cut-off value (500 U/ml for KL-6 and 110 ng/ml for SP-D), was detected in 11 patients (8.6%) or 10 patients (7.8%), respectively. In contrast, among 67 ATL patients, 15 patients had high serum levels of KL-6 and/or SP-D; both were elevated in 2 patients, only KL-6 was elevated in 6 patients and only SP-D was elevated in 7 patients. Thus, serum KL-6 and SP-D appear to be elevated in a mutually exclusive manner in ATL. Indeed, high serum levels of KL-6 were closely related to the stage of ATL, while the serum SP-D was elevated in ATL patients with pulmonary infection. In conclusion, the combined measurement of KL-6 and SP-D in ATL may become a useful means to discriminate leukemic pulmonary lesions from infectious pulmonary complications.

Association of polymorphisms in the human surfactant protein‐D (SFTPD) gene and postnatal pulmonary adaptation in the preterm infant

Surfactant protein-D (SP-D) is a member of the collagenous subfamily of calcium-dependent lectins (collectins). Associations between single nucleotide polymorphisms (SNPs) of the human gene coding surfactant protein-D (SFTPD) and infectious pulmonary diseases have been established by several groups. As the outcome of very preterm infants is mainly determined by pulmonary morbidity, the aim of the present study was to investigate the potential association between sequence variations within the SFTPD gene and pulmonary morbidity in preterm infants below 32 weeks of gestational age (GA). Four validated SNPs were genotyped with sequence-specific probes (TaqMan 7000) in 284 newborn infants below 32 weeks of GA. An association between the SNP rs1923537 and the development of respiratory distress syndrome (RDS) in the study population was found with a lower prevalence of RDS in infants having homozygous a minor allele genotype (odds ratio = 1.733, 95% confidence interval 1.139-2.636, adjusted p = 0.0408). Consecutively, the indicated polymorphism was found to be associated with a lower number of repetitive surfactant doses, and with a lower prevalence for the requirement of oxygen supplementation on day 28, as well as the use of diuretics. The finding of an association of a variant of the SFTPD gene, that has previously been shown to be associated with increased SP-D serum levels in adult patients with acute respiratory failure, i.e. RDS in preterm infants, may provide a basis for the initial risk assessment of RDS and modification of surfactant treatment strategies. A role for SP-D in neonatal pulmonary adaptation has to be postulated.

The Effects of Fluticasone with or without Salmeterol on Systemic Biomarkers of Inflammation in Chronic Obstructive Pulmonary Disease

Small studies have suggested that inhaled corticosteroids can suppress systemic inflammation in chronic obstructive pulmonary disease (COPD). To determine the effect of inhaled corticosteroids with or without long-acting beta(2)-adrenergic agonist on systemic biomarkers of inflammation. We conducted a double-blind randomized placebo-controlled trial across 11 centers (n = 289 patients with FEV(1) of 47.8 +/- 16.2% of predicted) to compare the effects of inhaled fluticasone alone or in combination with salmeterol against placebo on circulating biomarkers of systemic inflammation over 4 weeks. The primary endpoint was C-reactive protein (CRP) level. Secondary molecules of interest were IL-6 and surfactant protein D (SP-D). Neither fluticasone nor the combination of fluticasone/salmeterol had a significant effect on CRP or IL-6 levels. There was, however, a significant reduction in SP-D levels with fluticasone and fluticasone/salmeterol compared with placebo (P = 0.002). Health status also improved significantly in both the fluticasone and fluticasone/salmeterol groups compared with placebo, driven mostly by improvements in the symptom scores. Changes in the circulating SP-D levels were related to changes in health status scores. FEV(1) improved significantly only in the fluticasone/salmeterol group compared with placebo. ICS in conjunction with long-acting beta(2)-adrenergic agonist do not reduce CRP or IL-6 levels in serum of patients with COPD over 4 weeks. They do, however, significantly reduce serum SP-D levels. These data suggest that these drugs reduce lung-specific but not generalized biomarkers of systemic inflammation in COPD.

Circulating Surfactant Protein D is Decreased in Early Rheumatoid Arthritis: A 1‐year Prospective Study

Innate immune system abnormalities, e.g., mannan-binding lectin (MBL) genotype variants, have been demonstrated to modify the disease course of rheumatoid arthritis (RA). Surfactant protein D (SP-D) shares important structural and functional properties with MBL suggesting that SP-D may be an additional RA disease modifier. The Met11Thr polymorphism in the N-terminal part of SP-D is an important determinant for the SP-D serum level, but this polymorphism is also essential to the function and assembly into oligomers. We aimed to compare the serum levels of SP-D in a cohort of newly diagnosed untreated RA patients with healthy matched controls, and to investigate if there was an association to core measures of disease activity within the first year after disease onset. Secondly, we aimed to investigate whether the Met11Thr polymorphism was associated with RA. Serum SP-D was significantly lower in DMARD naive RA patients compared with healthy controls (P = 0.016). Median SP-D concentration at inclusion was 878 ng/ml (95% CI: 730-1033) and 1164 ng/ml (95% CI: 1093-1366) in RA patients and matched controls, respectively. SP-D increased during Methotrexate treatment (P < 0.0001), and at 1-year follow-up median SP-D was 1032 ng/ml (95% CI: 777-1255). SP-D levels did not correlate with traditional disease activity measures. The Thr11/Thr11 genotype and the Thr11 allele tended to be more frequent in RA patients. In conclusion, the low serum level of SP-D and the lack of correlation with traditional disease activity measures indicate that SP-D reflects a distinctive aspect in the RA pathogenesis.

Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study

BackgroundThere is a paucity of surrogate lung-specific biological markers that can be used to track disease progression and predict clinical outcomes in chronic obstructive pulmonary disease (COPD). The principal aim of this pilot study was to determine whether circulating surfactant protein D (SPD) or Clara Cell protein-16 (CC16) levels are associated with lung function or health status in patients with severe COPD.MethodsWe studied 23 patients with advanced COPD. Lung function measurements, Chronic Respiratory Disease Questionnaire (CRQ) scores, and serum levels of SPD, CC16, and C-reactive protein (CRP) were determined at baseline and at 3 months.ResultsAt baseline, FEV1 was inversely associated with serum SPD levels (P = 0.045) but not with CC16 (P = 0.675) or CRP levels (P = 0.549). Over a 3 month period, changes in SPD levels correlated significantly with changes in CRQ scores (adjusted P = 0.008) such that patients who had the largest declines in serum SPD levels experienced the largest gains in health status. The association was particularly notable between circulating SPD level and the dyspnea domain of the CRQ score (P = 0.018). Changes in CC16 or CRP levels did not correlate with changes in CRQ scores.ConclusionChanges in serum SPD levels tracked well with changes in health status over a 3 month period in patients with severe COPD. These data suggest that circulating SPD levels may be useful biomarkers to track health outcomes of COPD patients.

Roles of Serum Clara Cell Protein 16 and Surfactant Protein-D in the Early Diagnosis and Progression of Silicosis

To study roles of Clara cell protein 16 (CC16) and surfactant protein-D (SP-D) as serum biomarkers in the early diagnosis and the pathogenesis of silicosis. Thirty healthy volunteers, 30 silica-exposed workers, and 30 workers with suspected silicosis and phase I silicosis were included. Serum CC16 and SP-D concentrations were determined using enzyme-linked immunosorbent assay. Serum CC16 concentrations decreased in silica-exposed workers when compared with in controls, but serum SP-D levels increased, and this trend was obvious in phase 0 and I groups. Discriminant analysis showed that the accuracies of classifying group membership into control, phase 0, phase 0, and phase I were 86.7%, 46.7%, 66.7%, and 70%, respectively, and the total classification accuracy rate was 67.5%. Serum CC16 and SP-D may be useful biomarkers for early diagnosis, and serum SP-D concentration may associate with the pathogenesis of silicosis.

Plasma Surfactant Protein D Levels and the Relation to Body Mass Index in a Chinese Population

Surfactant protein D (SP-D) is a member of the collectin family and is an important component of the pulmonary innate host defence. The protein has a widespread distribution in the human body and is present in multiple epithelia, in endothelium and in blood. Various studies have looked at the relationship between serum SP-D levels and pulmonary inflammatory diseases. The SP-D distribution has been most thoroughly described in European populations and appears with a broad range of serum values highly influenced by genetic factors. In the present study, we investigated the plasma SP-D distribution in a Chinese population from the Tai An region comprising 268 individuals. We found that (i) plasma SP-D in the Chinese population was distributed with a median value of 380.2 ng/ml (324.9; 418.7) and a range from 79.4 to 3965.3 ng/ml, (ii) significantly higher plasma SP-D in men than in women, and no significant effect of age, and (iii) a significant inverse association between serum SP-D and body mass index (BMI) (P = 0.012). The data indicate that racial differences in SP-D expression exist as the median plasma SP-D in the Chinese population was approximately two times lower than the median serum SP-D previously measured in a Danish population using the same immuno-assay. The inverse association between serum SP-D and BMI found in the Chinese population indicates that serum SP-D is related to obesity in similar ways in Chinese and Danes.

Plasma surfactant D in patients following acute paraquat intoxication

Free radical-induced lung injury is a major problem that occurs because of paraquat intoxication. Serum surfactant protein D (SP-D) reflects the severity of various lung diseases. The purpose of this study is to investigate the changes in plasma SP-D concentrations and to correlate disease severity with SP-D concentrations in patients with acute paraqaut intoxication. Twelve paraquat-intoxicated patients participated in this study. Their paraquat exposure was assessed by their plasma's paraquat level. Serial plasma SP-Ds were measured by ELISA. SP-D was decreased two and three days after the initial measurement within 2 to 72 hours of ingestion. There was no difference in initial SP-D levels between survivors and non-survivors. The SP-D test revealed a significant positive correlation between the SP-D level and PaO2 (r = 0.384, p = 0.003, N = 57). SP-D did not predict the likelihood of survival, but it was positively correlated with PaO2. This finding suggests that low concentrations of plasma SP-D could reflect hypoxia due to free radical-induced injury.

Decreased Serum Levels of Surfactant Protein D (SP-D) Prior Transplant Is Associated with the Development of Bronchiolitis Obliterans (BO) and Idiopathic Pneumonia Syndrome (IPS) Following Allogeneic Hematopoietic Stem Cell Transplantation.

Non-infectious pulmonary complications which occur beyond 3 months of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have become recognized as a critical problem. Above all, bronchiolitis obliterans (BO) and idiopathic pneumonia syndrome (IPS) are difficult to be cured and cause high mortality. Therefore, early identification of patients with higher risk for BO/IPS may lead to improving outcome of allo-HSCT.Surfactant protein D (SP-D) is one of collectins mainly synthesized by alveolar type II cells. The best known function is to prevent the collapse of alveoli by decreasing surface tension at alveolar air-lipid interface, and SP-D plays an important roles as a mediator in innate immunity in the lung. In clinical practice, high serum SP-D level is used as a marker lung diseases. Recently, low production of SP-D in the alveoli has been considered as an important pathgenesis of adult respiratory distress.We analyzed serum SP-D levels before allo-HSCT of 42 patients who received allo-HSCT in our institution between November 2001 and February 2006 and survived more than 90 days after transplant. In all patients, 5 patients had BO and 3 had IPS at a median interval of 303 and 117 days of transplantation (range; 100–452 and 95–153 days). As a result of univariate analysis, BO/IPS patients had lower serum SP-D levels prior allo-HSCT and extensive type of cGVHD except lung compared with no BO/IPS patients (p=0.06 and 0.07). KL-6 had also mildly associated with BO/IPS. On the other hand, we couldn't find the association in sex, age, donor source, conditioning regimen, disease status, aGVHD, and FEV1.0/FVC and SP-A prior HSCT. We could not clarify the precise mechanism of the association between Decreased serum levels of SP-D and the development of BO and IPS following allo-HSCT. However, we speculate that low production of SP-D in the alveoli, which causes innate immune compromise, might contribute to extreme pulmonary alloreaction.

Surfactant protein D in human lung diseases

The lung is continuously exposed to inhaled pollutants, microbes and allergens. Therefore, the pulmonary immune system has to defend against harmful pathogens, while an inappropriate inflammatory response to harmless particles must be avoided. In the bronchoalveolar space this critical balance is maintained by innate immune proteins, termed surfactant proteins. Among these, surfactant protein D (SP-D) plays a central role in the pulmonary host defence and the modulation of allergic responses. Several human lung diseases are characterized by decreased levels of bronchoalveolar SP-D. Thus, recombinant SP-D has been proposed as a therapeutical option for cystic fibrosis, neonatal lung disease and smoking-induced emphysema. Furthermore, SP-D serum levels can be used as disease activity markers for interstitial lung diseases. This review illustrates the emerging role of SP-D translated from in vitro studies to human lung diseases.

Surfactant protein D in atopic dermatitis and psoriasis

The collectin surfactant protein-D (SP-D) shows antimicrobial and immuno-regulatory properties and has recently been detected in the basal layers of normal human skin. This molecule potentially plays an important role in inflammatory skin diseases and therefore SP-D content and location was examined using immunohistochemistry on skin biopsies from patients with the two major dermatologic diseases, psoriasis and atopic dermatitis. SP-D was located in the stratum basale of all biopsies with similar intense staining in both diseased and normal skin. Differences were detected in stratum spinosum where involved psoriatic skin showed intense staining through the entire region significantly different from uninvolved and normal skin. Lesional atopic skin showed moderate staining extending through the basal three-fourths of stratum spinosum. Using real time polymerase chain reaction analysis, no substantial up-regulation of SP-D mRNA was detected in lesional psoriatic skin, and a comparison of serum levels of SP-D between patients with atopic dermatitis or psoriasis and a group of age matched healthy controls did not show significant differences. In conclusion SP-D was significantly more abundant in the stratum spinosum of lesional psoriatic and atopic skin due to more cells producing the molecule rather than up-regulation of production in single cells of diseased skin. Further studies are needed to show if SP-D plays a role in the protection against skin infections or modulation of the inflammatory process in these common skin diseases.

Genetic and environmental influences of surfactant protein D serum levels

The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate immune system, but SP-D is also present on extrapulmonary epithelial surfaces and in serum, where it has been used as a biomarker for pulmonary disease states. In this study, we investigate the mechanisms defining the constitutional serum level of SP-D and determine the magnitude of the genetic contribution to serum SP-D in the adult population. Recent studies have demonstrated that serum SP-D concentrations in children are genetically determined and that a single nucleotide polymorphism (SNP) located in the NH(2)-terminal region (Met11Thr) of the mature protein is significantly associated with the serum SP-D levels. A classic twin study was performed on a twin population including 1,476 self-reported healthy adults. The serum SP-D levels increased with male sex, age, and smoking status. The intraclass correlation was significantly higher for monozygotic (MZ) twin pairs than for dizygotic (DZ) twin pairs. Serum SP-D variance was influenced by nonshared environmental effects and additive genetic effects. Multivariate analysis of MZ and DZ covariance matrixes showed significant genetic correlation among serum SP-D and metabolic variables. The Met11Thr variant explained a significant part of the heritability indicating that serum SP-D variance could be decomposed into non-shared environmental effects (e(2) = 0.19), additive genetic effects (h(2) = 0.42), and the effect of the Met11Thr variations (q(2) = 0.39).

Serum pulmonary and activation‐regulated chemokine/CCL18 levels in patients with systemic sclerosis: A sensitive indicator of active pulmonary fibrosis

To clarify the clinical significance of serum levels of pulmonary and activation-regulated chemokine (PARC) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc) and to compare PARC levels with KL-6 antigen or surfactant protein D (SP-D) levels. Serum PARC levels were determined by enzyme-linked immunosorbent assay in 123 SSc patients. In a retrospective longitudinal study, correlation of serum PARC levels with the activity of PF was assessed in 21 SSc patients with active PF. PARC levels at the first visit were higher in patients with SSc than in patients with systemic lupus erythematosus (SLE) or healthy controls. Increased serum PARC levels were associated with involvement of PF, decreased diffusing capacity for carbon monoxide, and decreased vital capacity in SSc patients. In the longitudinal study, serum PARC levels were significantly decreased in SSc patients with inactive PF compared with those with active PF. Elevated serum PARC levels correlated with PF and more sensitively reflected the PF activity than did serum KL-6 or SP-D levels in SSc. Serum PARC levels may be a useful new serum marker for active PF in SSc.

Polymorphisms in the human surfactant protein-D (SFTPD) gene: strong evidence that serum levels of surfactant protein-D (SP-D) are genetically influenced

The collectin surfactant protein-D (SP-D) plays a significant role in innate immunity. Epidemiological studies described associations between single nucleotide polymorphisms (SNPs) of the human gene coding surfactant protein-D (SFTPD) and infectious pulmonary diseases. Studies on twins indicated very strong genetic dependence for serum levels of SP-D. The aim of this study was to determine the genetic influence of sequence variations within the SFTPD gene on the constitutional serum SP-D levels. We sequenced the 5′ untranslated region (5′UTR), the coding region and the 3′ region of the SFTPD gene of 32 randomly selected blood donors. Six validated SNPs were genotyped with sequence-specific probes (TaqMan 7000) in 290 German blood donors. Serum SP-D levels were analysed by ELISA, and the association of SFTPD haplotype estimates with the quantitative phenotype serum SP-D level was determined. One single SFTPD haplotype (allele frequency 13.53%) revealed a negative association with serum SP-D levels (P<0.0001). This was confirmed in a second prospectively collected group of blood donors (n=160, P=0.0034). The discovery of a frequent negative variant of the SFTPD gene provides a basis for genetic analysis of the function of SP-D in the resistance against pulmonary infections and inflammatory disorders in humans.

Serum KL-6 and Surfactant Proteins A and D in Pediatric Interstitial Lung Disease

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. 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. 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). 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.

Circulating KL-6 level at baseline is a predictive indicator for the occurrence of interstitial pneumonia during interferon treatment for chronic hepatitis C

Interstitial pneumonia (IP) is a serious adverse event of interferon alpha (IFNα) treatment for chronic hepatitis C (CH-C). Among 558 CH-C patients who received IFNα treatment with or without ribavirin between January 1992 and June 2002, six patients (1.1%) developed IP, including one patient who developed IP in 1993 and again in 2002. Among the seven cases who contracted IP, at the onset of IP, seven (100%), five (71%), and two cases (29%) had elevated serum levels of KL-6, surfactant protein A (SP-A), and surfactant protein D (SP-D), respectively. Prior to starting IFN treatment (baseline), the serum SP-A and SP-D levels were within the normal range in all seven cases, but the serum KL-6 level was elevated in five of the seven cases, contrasting with that in three of 48 age-adjusted CH-C patients who did not develop IP during IFN treatment (71 vs. 6%; P=0.0003). Furthermore, the circulating KL-6 level at baseline was significantly higher among the seven cases than among the controls (543±105 vs. 304±98 U/ml, P=0.0001). These results indicate that measurement of the circulating KL-6 level in CH-C patients before IFN treatment may be useful for predicting the occurrence of IP during IFN treatment.