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Spinal muscular atrophy is one of the most common fatal autosomal recessive disorders. Children diagnosed with SMA Type 1 (SMAT1) demonstrate severe oral motor weakness and flaccid dysarthria progressing to complete anarthria. A review of literature illustrates that little has been described regarding augmentative and alternative communication (AAC) use among these children, although communication has a critical impact on quality of life and participation in daily activities. Responses to an investigator-developed parent survey were obtained to appraise communication skills and opportunities among children diagnosed with SMA1. Results illustrate parent perception of greater receptive than expressive language ability and highlight the benefits of implementing speech-generating devices (SGD). Barriers to SGD acquisition and implementation, including access and funding, are reported and described. Overall, families indicated that SGD increases quality of life and provides valued improvements through expanded functional communication.

Background MicroRNAs (miRs) control gene expression and the development of the immune system and antiviral responses. MiR-155 is an evolutionarily-conserved molecule consistently induced during viral infections in different cell systems. Notably, there is still an unresolved paradox for the role of miR-155 during viral respiratory infections. Despite being essential for host antiviral TH1 immunity, miR-155 may also contribute to respiratory disease by enhancing allergic TH2 responses and NFkB-mediated inflammation. The central goal of this study was to define how airway miR-155 production is related to TH1, TH2, and pro-inflammatory cytokine responses during naturally occurring viral respiratory infections in young children. Methods Normalized nasal airway levels of miR-155 and nasal protein levels of IFN-γ, TNF-α, IL-1β, IL-13, IL-4 were quantified in young children (≤2 years) hospitalized with viral respiratory infections and uninfected controls. These data were linked to individual characteristics and respiratory disease parameters. Results A total of 151 subjects were included. Increased miR-155 levels were observed in nasal samples from patients with rhinovirus, RSV and all respiratory viruses analyzed. High miR-155 levels were strongly associated with high IFN-γ production, increased airway TH1 cytokine polarization (IFN-γ/IL-4 ratios) and increased pro-inflammatory responses. High airway miR-155 levels were linked to decreased respiratory disease severity in individuals with high airway TH1 antiviral responses. Conclusions The airway secretion of miR-155 during viral respiratory infections in young children is associated with enhanced antiviral immunity (TH1 polarization). Further studies are needed to define additional physiological roles of miR-155 in the respiratory tract of human infants and young children during health and disease.

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This paper presents a quantitative imaging method and software technology to predict the risk and assess the severity of respiratory diseases in premature babies by fusing information from multiple sources: non-invasive low-radiation chest X-ray (CXR) imaging and clinical parameters. Prematurity is the largest single cause of death in children under five in the world. Lower respiratory tract infections (LRTI) are the top cause of hospitalization and mortality in prematurity. However, there is no objective clinical marker to predict and prevent severe LRTI in the 15 million babies born prematurely every year worldwide. Traditionally, imaging biomarkers of lung disease from computed tomography have been successfully used in adults, but they entail heightened risks for children due to cumulative radiation and the need for sedation. The proposed technology is the first approach that uses low-radiation CXR imaging to predict hospitalization due to LRTI in prematurity. The method uses deep learning to quantify heterogeneous patterns (air trapping and irregular opacities) in the chest, which are combined with clinical parameters to predict the risk of LRTI. Our preliminary results obtained using a data obtained from ten premature subjects with LRTI showed high correlation between our imaging biomarkers and the rehospitalization of these subjects R2=0.98).

OBJECTIVES To determine the frequency of subtherapeutic exposure to intravenously administered β-lactam antibiotics in a cohort of cystic fibrosis (CF) patients who were treated for a pulmonary exacerbation, and its impact on pulmonary function. METHODS Nineteen CF patients between the ages of 5 and 21 years treated at Children's National Health System for a pulmonary exacerbation were followed between March 2015 and August 2016 in a prospective, longitudinal study. Pharmacokinetic modeling and minimum inhibitory concentrations (MICs) of the involved pathogens were used to determine therapeutic or subtherapeutic β-lactam antibiotic exposure based on the time the antibiotic concentration was above the MIC. Clinical outcomes were measured by spirometry values. RESULTS The 19 participants were treated with a total of 29 courses of antibiotics. The most common β-lactam antibiotics used in a treatment course were ceftazidime (62%) and meropenem (45%). There was no difference in age, CF genotype, or creatinine clearance between the 9 participants (47%) who reached therapeutic concentrations versus the 10 (53%) who did not. Those who achieved sufficiently high antibiotic exposure had more significant improvement of their pulmonary function tests. CONCLUSIONS We found that sufficient antibiotic exposure during treatment of CF pulmonary exacerbations was associated with improved pulmonary function. Moreover, it was impossible to predict, solely from the dosing regimen used, which patients were going to reach therapeutic β-lactam antibiotic serum concentrations. This suggests that CF patients may benefit from closer monitoring of their β-lactam exposure and bacterial MIC for optimal clinical outcomes.

Background Cystic fibrosis (CF) is associated with significant morbidity and early mortality due to recurrent acute and chronic lung infections. The chronic use of multiple antibiotics increases the possibility of multidrug resistance (MDR). Antibiotic susceptibility determined by culture-based techniques may not fully represent the resistance profile. The study objective was to detect additional antibiotic resistance using molecular methods and relate the presence of MDR to airway microbiome diversity and pulmonary function. Methods Bacterial DNA was extracted from sputum samples and amplified for the V4 region of the 16S rRNA gene. An qPCR array was used to detect antibiotic resistance genes. Clinical culture results and pulmonary function were also noted for each encounter. Results Six study participants contributed samples from 19 encounters. Those samples with MDR (n = 7) had significantly lower diversity measured by inverse Simpson's index than those without (n = 12) (2.193 ± 0.427 vs 6.023 ± 1.564, p = 0.035). Differential abundance showed that samples with MDR had more Streptococcus (p = 0.002) and Alcaligenaceae_unclassified (p = 0.002). Pulmonary function was also decreased when MDR was present (FEV1, 51 ± 22.9 vs 77 ± 26.7, p = 0.054; FVC, 64.5 ± 22.7 vs 91.6 ± 27.7, p = 0.047). Conclusions The presence of MDR within the CF airway microbiome was associated with decreased microbial diversity, the presence of Alcaligenes, and decreased pulmonary function.

A 9-year-old male patient, previously healthy, presented with acute-onset chest pain. The pain was on the right lateral chest, 10/10 in severity and non-reproducible. The patient had 1-week history of cough that had been improving; no fever, weight loss, dyspnoea, palpitations or night sweats were reported. He had positive sick contacts. Examination was remarkable for slight decrease in breath sounds at the right lower lung field posteriorly. Initial chest radiograph showed a well-circumscribed opacity in the right lower lobe posteriorly with adjacent consolidation seen on the lateral view. The lesion appeared to be distinct from the cardiomediastinal silhouette (figure 1). Sonography was performed to characterise the nature of the lesion; however, it was difficult to visualise and only revealed mixed echotexture (figure 2). Contrast-enhanced CT scan of the thorax was then obtained. CT …

Background Rhinovirus (RV ) has been linked to the pathogenesis of asthma. Prematurity is a risk factor for severe RV infection in early life, but is unknown if RV elicits enhanced pro‐asthmatic airway cytokine responses in premature infants. This study investigated whether young children born severely premature (

Background Rhinitis and obstructive sleep apnea (OSA) often coexist during childhood. To delineate this clinical association, we examined OSA severity and polysomnogram (PSG) features in children with rhinitis and OSA. Given that rapid-eye-movement (REM) sleep is characterized by nasal congestion, we hypothesized that children with rhinitis have more REM-related breathing abnormalities. Methods We conducted a retrospective cross-sectional analysis of 145 children with PSG-diagnosed A. Outcomes included PSG parameters and obstructive apnea–hypopnea index (OAHI) during REM and non-REM. Linear multivariable models examined the joint effect of rhinitis and OSA parameters with control for potential confounders. Results Rhinitis was present in 43% of children with OSA (n = 63) but overall OAHI severity was unaffected by the presence of rhinitis. In contrast, OAHI during REM sleep in children with moderate-severe OSA was significantly increased subjects with rhinitis and OSA (44.1/hr; SE = 6.4) compared with those with OSA alone (28.2/hr; SE = 3.8). Conclusion Rhinitis is highly prevalent in children with OSA. Although OSA is not more severe in children with rhinitis, they do have a distinct OSA phenotype characterized by more REM-related OSA. Further research is needed to delineate the link between REM-sleep and the physiology of the nose during health and disease.

Rationale The nasopharyngeal (NP) microbiota of newborns and infants plays a key role in modulating airway inflammation and respiratory symptoms during viral infections. Premature (PM) birth modifies the early NP environment and is a major risk factor for severe viral respiratory infections. However, it is currently unknown if the NP microbiota of PM infants is altered relative to full-term (FT) individuals. Objectives To characterize the NP microbiota differences in preterm and FT infants during rhinovirus (RV) infection. Methods We determined the NP microbiota of infants 6 months to ≤2 years of age born FT (n=6) or severely PMResults We observed significant differences in the NP bacterial community of PM versus FT. NP from PM infants had higher within-group dissimilarity (heterogeneity) relative to FT infants. Bacterial composition of NP samples from PM infants showed increased Proteobacteria and decreased in Firmicutes. There were also differences in the major taxonomic groups identified, including Streptococcus, Moraxella, and Haemophilus. Longitudinal data showed that these prematurity-related microbiota features persisted during RV infection. Conclusions PM is associated with NP microbiota changes beyond the neonatal stage. PM infants have an NP microbiota with high heterogeneity relative to FT infants. These prematurity-related microbiota features persisted during RV infection, suggesting that the NP microbiota of PM may play an important role in modulating airway inflammatory and immune responses in this vulnerable group.

Background Next-generation sequencing has shown the cystic fibrosis (CF) lung microbiome to be a complex polymicrobial community. Anaerobic bacteria decrease in relative abundance with older age and disease progression, and may impact host inflammatory state. Persons with CF suffer from recurrent pulmonary exacerbations (PEs) that are treated with broad-spectrum antibiotics. Our objectives were to examine the effect of broad-spectrum (BS) vs narrow-spectrum (NS) anaerobic antibacterial treatment on bacterial diversity, and on pulmonary function recovery. Methods Pulmonary function tests (PFTs) and respiratory samples were collected as part of a prospective 18 month longitudinal study in CF patients at 4 time points, baseline (B), pulmonary exacerbation (E), end of exacerbation treatment (T), and follow-up (F). Treatment antibiotics were classified as broad or narrow based on anaerobic activity. 16S rRNA sequencing generated operational taxonomic units for analysis. Alpha diversity (relative abundance) was calculated via Shannon Index and Inverse Simpson formulas and β diversity (similarity in community composition) by Morisita-Horn (MH). Differences in diversity indices and PFTs were compared with regard to BS vs NS anaerobic activity, and statistical significance determined by GLS regression. Results Changes in alpha diversity for BS vs NS were not significantly different (P > 0.05) (Figures 1 and 2). Community composition measured by MH was consistently more similar for NS than BS (T-B: 0.66 vs. 0.45, P = 0.04; F-B: 0.75 vs. 0.47, P < 0.01) (Figure 3). Recovery of forced expiratory volume in 1 second (FEV1) from E to F was significantly higher in the NS group (25.4 vs. 21.0, P < 0.01) (Figure 4). Conclusion While antibiotic spectrum did not influence bacterial abundance, BS therapy led to higher changes in community composition from B and E onset following antibiotic administration compared with NS therapy. The differences in β diversity suggest BS therapy can have a lasting impact on community composition. As those receiving NS therapy had similar or better recovery of pulmonary function than those with BS, there is no indication that NS therapy leads to worse clinical outcomes. A limitation may be that children receiving BS therapy tended to have more severe disease. Disclosures All authors: No reported disclosures.

We report a significant complication after tracheocutaneous fistula (TCF) excision with closure by secondary intention in a 4-year-old boy who had been tracheostomy dependent since infancy. He had a persistent 3 mm TCF one year after decannulation. On postoperative day 2 the patient developed profound subcutaneous emphysema and pneumomediastinum. He was extubated after 2 days and discharged from the hospital on postoperative day 7. At follow up he had complete resolution of subcutaneous emphysema and complete closure of the TCF. The main methods of TCF closure and management of subcutaneous emphysema are discussed along with the lessons learned from this case.

Background Cystic fibrosis (CF) is an autosomal recessive disease characterized by recurrent lung infections. Studies of the lung microbiome have shown an association between decreasing diversity and progressive disease. 454 pyrosequencing has frequently been used to study the lung microbiome in CF, but will no longer be supported. We sought to identify the benefits and drawbacks of using two state-of-the-art next generation sequencing (NGS) platforms, MiSeq and PacBio RSII, to characterize the CF lung microbiome. Each has its advantages and limitations. Methods Twelve samples of extracted bacterial DNA were sequenced on both MiSeq and PacBio NGS platforms. DNA was amplified for the V4 region of the 16S rRNA gene and libraries were sequenced on the MiSeq sequencing platform, while the full 16S rRNA gene was sequenced on the PacBio RSII sequencing platform. Raw FASTQ files generated by the MiSeq and PacBio platforms were processed in mothur v1.35.1. Results There was extreme discordance in alpha-diversity of the CF lung microbiome when using the two platforms. Because of its depth of coverage, sequencing of the 16S rRNA V4 gene region using MiSeq allowed for the observation of many more operational taxonomic units (OTUs) and higher Chao1 and Shannon indices than the PacBio RSII. Interestingly, several patients in our cohort had Escherichia , an unusual pathogen in CF. Also, likely because of its coverage of the complete 16S rRNA gene, only PacBio RSII was able to identify Burkholderia , an important CF pathogen. Conclusion When comparing microbiome diversity in clinical samples from CF patients using 16S sequences, MiSeq and PacBio NGS platforms may generate different results in microbial community composition and structure. It may be necessary to use different platforms when trying to correctly identify dominant pathogens versus measuring alpha-diversity estimates, and it would be important to use the same platform for comparisons to minimize errors in interpretation.

Background Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood. Methods Nasal airway secretions were obtained from children (≤3 yrs. old) during PCR-confirmed RV infections (n = 10) and age-matched controls (n = 10). Nasal EVs were isolated with polymer-based precipitation and global miR profiles generated using NanoString microarrays. We validated our in vivo airway secretory miR data in an in vitro airway epithelium model using apical secretions from primary human bronchial epithelial cells (HBEC) differentiated at air-liquid interface (ALI). Bioinformatics tools were used to determine the unified (nasal and bronchial) signature airway secretory miRNAome and changes during RV infection in children. Results Multiscale analysis identified four signature miRs comprising the baseline airway secretory miRNAome: hsa-miR-630, hsa-miR-302d-3p, hsa- miR-320e, hsa-miR-612. We identified hsa-miR-155 as the main change in the baseline miRNAome during RV infection in young children. We investigated the potential biological relevance of the airway secretion of hsa-mir-155 using in silico models derived from gene datasets of experimental in vivo human RV infection. These analyses confirmed that hsa-miR-155 targetome is an overrepresented pathway in the upper airways of individuals infected with RV. Conclusions Comparative analysis of the airway secretory microRNAome in children indicates that RV infection is associated with airway secretion of EVs containing miR-155, which is predicted in silico to regulate antiviral immunity. Further characterization of the airway secretory microRNAome during health and disease may lead to completely new strategies to treat and monitor respiratory conditions in all ages.

Significant progress has been made in recent years for computer-aided diagnosis of abnormal pulmonary textures from computed tomography (CT) images. Similar initiatives in chest radiographs (CXR), the common modality for pulmonary diagnosis, are much less developed. CXR are fast, cost effective and low-radiation solution to diagnosis over CT. However, the subtlety of textures in CXR makes them hard to discern even by trained eye. We explore the performance of deep learning abnormal tissue characterization from CXR. Prior studies have used CT imaging to characterize air trapping in subjects with pulmonary disease; however, the use of CT in children is not recommended mainly due to concerns pertaining to radiation dosage. In this work, we present a stacked autoencoder (SAE) deep learning architecture for automated tissue characterization of air-trapping from CXR. To our best knowledge this is the first study applying deep learning framework for the specific problem on 51 CXRs, an F-score of ≈ 76.5% and a strong correlation with the expert visual scoring (R=0.93, p =; 0.01) demonstrate the potential of the proposed method to characterization of air trapping.

Accurate assessment of severity of viral respiratory illnesses (VRIs) allows early interventions to prevent morbidity and mortality in young children. This paper proposes a novel imaging biomarker framework with chest X-ray image for assessing VRI's severity in infants, developed specifically to meet the distinct challenges for pediatric population. The proposed framework integrates three novel technical contributions: a) lung segmentation using weighted partitioned active shape model, b) obtrusive object removal using graph cut segmentation with asymmetry constraint, and c) severity quantification using information-theoretic heterogeneity measures. This paper presents our pilot experimental results with a dataset of 148 images and the ground-truth severity scores given by a board-certified pediatric pulmonologist, demonstrating the effectiveness and clinical relevance of the presented framework.

Rhinovirus (RV) infections account for most asthma exacerbations among children and adults, yet the fundamental mechanism responsible for why asthmatics are more susceptible to RV than otherwise healthy individuals remains largely unknown. Nonetheless, the use of models to understand the mechanisms of RV-induced airway disease in asthma has dramatically expanded our knowledge about the cellular and molecular pathogenesis of the disease. For instance, ground-breaking studies have recently established that the susceptibility to RV in asthmatic subjects is associated with a dysfunctional airway epithelial inflammatory response generated after innate recognition of viral-related molecules, such as double-stranded RNA. This review summarizes the novel cardinal features of the asthmatic condition identified in the past few years through translational and experimental RV-based approaches. Specifically, we discuss the evidence demonstrating the presence of an abnormal innate antiviral immunity (airway epithelial secretion of types I and III interferons), exaggerated production of the master Th2 molecule thymic stromal lymphopoietin, and altered antimicrobial host defense in the airways of asthmatic individuals with acute RV infection.

Background: It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity. Methods: Nasal airway secretions were collected from 140 children ≤3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFNγ, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay. Results: Full-term children with HMPV and RSV infection had increased levels of nasal airway IFNγ, CCL5, and IL-10 along with an elevation in Th1 (IFNγ)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (< 32 wk gestation) did not exhibit increased Th1/Th2 ratios or elevated nasal airway secretion of IFNγ, CCL5, and IL-10 relative to uninfected controls. Conclusion: Our study is the first to demonstrate that premature infants have defective IFNγ, CCL5/RANTES, and IL-10 airway responses during HMPV infection and provides novel insights about the potential reason why HMPV causes severe respiratory disease in children with history of prematurity.

To the Editor: Rhinovirus wheezing illnesses during early childhood are strongly linked with development of asthma later in life [1]. Indeed, rhinovirus infection in the first 3 years of life is associated with an almost 10-fold increase in risk for asthma at age 6 years [1]. The exact mechanism by which rhinovirus elicits a pro-asthmatic propensity in young children is largely unknown, but is purportedly related to a viral-induced T-helper cell (Th)2 airway inflammatory response [2]. Interestingly, the discovery of interactions between epithelial innate immunity and adaptive allergic responses has unveiled new potential links between rhinovirus and asthma. Of particular interest is the epithelial-derived cytokine thymic stromal lymphopoietin (TSLP), which is considered a “master Th2 cytokine” because it primes the differentiation of naive T0 cells into Th2 lymphocytes via activation of antigen presenting cells [3]. TSLP is induced by rhinovirus infection or by exposure to double stranded (ds)RNA (viral surrogate) in the lungs of allergic mice [4], and in human bronchial epithelial cells (HBEC) [5]. Together, these data suggest that TSLP may be the missing link between innate antiviral epithelial immunity and the Th2 immune response characteristic of asthma. This cross-sectional preliminary study aimed to investigate whether rhinovirus infections that occur naturally during the first 3 years of life are associated with elevated airway TSLP levels and enhanced Th2 responses, which may potentially facilitate the establishment of rhinovirus-induced pro-asthmatic changes during early childhood. We measured nasal airway TSLP, Th2 cytokines and antiviral responses in nasal washes obtained from newborns, infants and toddlers (≤3 years) with PCR-confirmed acute …

Background Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. Methods Primary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC) from normal (n = 3) and asthmatic (n = 3) donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20) vs. non-asthmatic uninfected controls (n = 20). Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. Results Our data demonstrate that: 1) Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2) TSLP exposure induces unidirectional (apical) secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3) Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. Conclusions There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

Rationale. The sleep-related factors that modulate the nocturnal worsening of asthma in children are poorly understood. This study addressed the hypothesis that asthmatic children have a REM sleep-related vulnerability trait that is independent of OSA.Methods. We conducted a retrospective cross-sectional analysis of pulse-oximetry signals obtained during REM and NREM sleep in control and asthmatic children (n=134). Asthma classification was based on preestablished clinical criteria. Multivariate linear regression model was built to control for potential confounders (significance levelP≤0.05).Results. Our data demonstrated that (1) baseline nocturnal respiratory parameters were not significantly different in asthmatic versus control children, (2) the maximal % of SaO2desaturation during REM, but not during NREM, was significantly higher in asthmatic children, and (3) multivariate analysis revealed that the association between asthma and REM-related maximal % SaO2desaturation was independent of demographic variables.Conclusion. These results demonstrate that children with asthma have a REM-related vulnerability trait that impacts oxygenation independently of OSA. Further research is needed to delineate the REM sleep neurobiological mechanisms that modulate the phenotypical expression of nocturnal asthma in children.

Introduction Surfactant protein D (SP-D) is expressed in the lung and plays important roles in innate immunity including defense against inhaled pathogens. While the levels of SP-D have been shown to decrease in acutely injured lung, little is known about the mechanism(s) of its inactivation and clearance. A hall-mark of acute inflammation is the recruitment and activation of polymorphonuclear neutrophils (PMNs). Activated PMNs employ different pathways to generate toxic oxidants with deleterious effect on host tissues. In the myeloperoxidase (MPO) pathway, MPO employs hydrogen peroxide (H2O2) and chloride to generate HOC1, a highly reactive and toxic oxidant. These observations prompted us to hypothesize that MPO-derived oxidants can alter the structure and function of SP-D. Experimental design and results To test our hypothesis, we exposed purified human or rat SP-D to HOC1 or MPO System (MPO+H2O2+Chloride ions). Next, the activity of treated SP-D was examined using two well-characterized in vitro assays: bacterial agglutination and binding to solid phase yeast mannan Both HOC1 and MPO System abrogated SP-D's ability to aggregate bacteria and decreased its ability to bind to mannan. Additional studies using mutant SP-D suggest oxidative inactivation of SP-D C-type lectin region, the carbohydrate recognition domain (CRD). In contrast to HOC1, H2O2 had no effect on SP-D function at ail concentrations examined. Moreover, electrophoretic analysis of HOCl-treated SP-D demonstrated high molecular weight complexes by comparison to control SP-D. Conclusion Our data suggest that MPO-derived oxidants such as HOC1 target SP-D within its CRD region and broadly interferes with its function(s). Studies are underway to investigate the mechanism(s) of oxidative inactivation of SP-D.