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Background: Elevated surfactant protein D (SP-D) is a relatively specific indicator of lung injury and is associated with both acute and chronic lung disease in adults and respiratory distress syndrome in premature infants. The relationship between plasma SP-D and lung injury in children with acute respiratory failure is unclear., Research Question: Is plasma SP-D associated with lung injury or outcome in children with acute respiratory failure?, Study Design and Methods: This was a prospective cohort study in children 2 weeks to 17 years of age with acute respiratory failure who participated in the BALI multi-center study. Analyses were done using SP-D levels in plasma from the first sample taken on either the day of intubation or one of the following 2 days. SP-D level was measured by enzyme-linked immunosorbent assay., Results: Plasma samples from 350 patients were used in the analysis; 233 had pediatric ARDS (PARDS). SP-D levels varied across primary diagnoses (P < .001). Elevated SP-D levels were associated with severe PARDS after adjusting for age, pediatric risk of mortality III (PRISM-III), and primary diagnosis (OR = 1.02; CI = 1.01-1.04; P = .011). Multivariable analyses also indicated that elevated SP-D levels were associated with death (OR = 1.02; CI = 1.01-1.04; P = .004), duration of mechanical ventilation (P = .012), PICU length of stay (P = .019), and highest oxygenation index (P = .040). SP-D levels also correlated with age (r s  = 0.16, P = .002)., Interpretation: Elevated plasma SP-D levels are associated with severe PARDS and poor outcomes in children with acute respiratory failure. Future studies will determine whether SP-D can be used to predict the degree of lung injury or response to treatment and whether SP-D is useful in identifying PARDS endotypes., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Serum levels of surfactant protein D (SP-D) have been suggested as reflecting epithelial damage in acute lung injury, COPD, and idiopathic pulmonary fibrosis (IPF). However, little is known about SP-D levels in the setting of lung transplantation., Methods: We examined plasma SP-D levels in 104 subjects from a prospective, multicenter cohort study of lung allograft recipients. Plasma SP-D was measured by enzyme-linked immunosorbent assay prior to transplant and daily for 3 days after transplant., Results: Subjects undergoing transplant for IPF had higher baseline SP-D levels (median, 325 ng/mL) compared with subjects with cystic fibrosis, COPD, and pulmonary hypertension (median, 100, 80, and 82 ng/mL, respectively; P = .0001). Among subjects with IPF undergoing bilateral transplant, SP-D levels declined rapidly postoperatively. In contrast, SP-D levels in subjects undergoing single lung transplant for IPF remained significantly higher than those of bilateral allograft recipients. Among subjects undergoing single lung transplant for IPF, the development of primary graft dysfunction (PGD) was associated with a subsequent rise in SP-D levels, whereas SP-D levels in IPF subjects undergoing bilateral transplant declined, even in the presence of grade 3 PGD. Importantly, single lung allograft recipients without PGD had higher postoperative SP-D levels than bilateral allograft recipients with PGD., Conclusions: Subjects undergoing lung transplant for IPF have significantly higher baseline plasma SP-D levels compared with those with other diagnoses. Plasma SP-D is likely a biomarker of the air-blood barrier integrity in the native IPF lung, but may be less useful as a biomarker of PGD after transplant.

Background: Acquired pulmonary alveolar proteinosis (PAP) has been reclassified into autoimmune or secondary PAP according to the occurrence of serum granulocyte macrophage colony-stimulating factor autoantibody. Most patients undergo high-resolution CT (HRCT) scanning in order for physicians to make a differential diagnosis of diffuse lung diseases, but no information is available to distinguish the HRCT scan features of secondary PAP from those of autoimmune PAP. The objective of this study was to characterize the HRCT scan features of autoimmune and secondary PAP., Methods: HRCT scans of 42 patients (21 patients each in the autoimmune PAP and secondary PAP groups) were centrally collected and evaluated in a blinded manner., Results: Ground-glass opacities (GGO) were a major finding in both the autoimmune PAP and secondary PAP groups. In the secondary PAP group, GGOs typically showed a diffuse pattern (62%), whereas GGOs showed a patchy geographic pattern in the autoimmune PAP group (71%; p < 0.005). The so-called "crazy-paving" appearance and subpleural sparing were frequently seen in the autoimmune PAP group (both 71%), whereas they were less frequently seen in the secondary PAP group (14% and 33%, respectively). The involved area of GGO was even in craniocaudal distribution for the secondary PAP group, whereas it was predominant in the lower lung field compared with the upper lung field in the autoimmune PAP group (p < 0.05)., Conclusions: Typical HRCT scan findings for autoimmune PAP patients were GGO with a patchy geographic pattern, subpleural sparing, crazy-paving appearance, and predominance in the lower lung field. These findings were rather infrequent for secondary PAP patients.

Background: Serum surfactant protein (SP) A and SP-D had prognostic value for mortality in patients with idiopathic pulmonary fibrosis (IPF) in prior studies before the reclassification of the idiopathic interstitial pneumonias. We hypothesized that baseline serum SP-A and SP-D concentrations would be independently associated with mortality among patients with biopsy-proven IPF and would improve a prediction model for mortality., Methods: We evaluated the association between serum SP-A and SP-D concentrations and mortality in 82 patients with surgical lung biopsy-proven IPF. Regression models with clinical predictors alone and clinical and biomarker predictors were used to predict mortality at 1 year., Results: After controlling for known clinical predictors of mortality, we found that each increase of 49 ng/mL (1 SD) in baseline SP-A level was associated with a 3.3-fold increased risk of mortality (adjusted hazard ratio, 3.27; 95% confidence interval, 1.49 to 7.17; adjusted p = 0.003) in the first year after presentation. We did not observe a statistically significant association between serum SP-D and mortality (adjusted hazard ratio, 2.04; p = 0.053). Regression models demonstrated a significant improvement in the 1-year mortality prediction model when serum SP-A and SP-D (area under the receiving operator curve [AROC], 0.89) were added to the clinical predictors alone (AROC, 0.79; p = 0.03)., Conclusions: Increased serum SP-A level is a strong and independent predictor of early mortality among patients with IPF. A prediction model containing SP-A and SP-D was substantially superior to a model with clinical predictors alone.

Background: The presentation of acute eosinophilic pneumonia (AEP) closely resembles that of acute lung injury (ALI)/ARDS, including its idiopathic form, acute interstitial pneumonia (AIP). AEP usually lacks peripheral eosinophilia at the acute phase; therefore, the establishment of serum biomarkers for AEP would be clinically useful., Methods: We measured the levels of thymus- and activation-regulated chemokine (TARC)/CCL17, eotaxin/CCL11, KL-6, and surfactant protein-D (SP-D) in serum for patients with acute parenchymal lung diseases including AEP (n = 17), AIP (n = 13), pneumonia-associated ALI/ARDS (n = 12), and alveolar hemorrhage (n = 7). To evaluate diagnostic ability, each marker was estimated by measuring the area under the receiver operating characteristic curve (AUC)., Results: Serum TARC/CCL17 levels of AEP patients were much higher than those of patients in other disease groups. More importantly, high circulating TARC/CCL17 levels were observed in AEP even at acute phase when peripheral eosinophilia was absent. TARC/CCL17 showed the largest AUC, and the TARC/CCL17 levels with cutoff points from 6,259 to 7,039 pg/mL discriminated AEP from other syndromes with sensitivity and specificity of 100%. The KL-6 level was low in most patients with AEP, and the sensitivity was 81.6% in cutoff with 100% specificity. The AUC for eotaxin/CCL11 and SP-D was small, with values of 0.73 (95% confidence interval [CI], 0.60 to 0.86) and 0.53 (95% CI, 0.31 to 0.64), respectively., Conclusions: This study indicates that the measurement of circulating TARC/CCL17 and KL-6 is useful for discriminating AEP from other causes of ALI.

Study Objectives: The aim of this study was to characterize the elemental composition of exhaled breath condensate (EBC) in order to identify new biomarkers of exposure and susceptibility in COPD patients. Serum pneumoproteins were used as lung-specific biomarkers of effect., Design: EBC was obtained from 50 healthy subjects, 30 healthy smokers, 30 asthmatics, and 50 patients with stable COPD, and was collected by cooling exhaled air. Trace elements and toxic metals in the samples were measured by means of inductively coupled plasma-mass spectrometry and electrothermal atomic absorption spectroscopy. The serum pneumoproteins were immunoassayed., Results: The EBC of COPD subjects had higher levels of such toxic elements as lead, cadmium, and aluminum, and lower levels of iron and copper, than that of the nonsmoking control subjects. There were no between-group differences in surfactant protein (SP)-A and SP-B levels. Clara-cell protein and SP-D levels were negatively and positively influenced, respectively, by tobacco smoke., Conclusions: Our results show that toxic metals and transition elements are detectable in the EBC of studied subjects. We propose new biomarkers of exposure as a means of assessing the target tissue dose of carcinogenic and pneumotoxic substances from tobacco smoke or polluted workplaces, and the use of the transition elements involved in redox systems of oxidative stress as disease biomarkers associated with effect or susceptibility. Together with biomarkers of effect, such as serum pneumoproteins, the elemental composition of EBC may be clinically useful in distinguishing similar diseases.

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.