Self-supervised classification of subcellular morphometric phenotypes reveals extracellular matrix-specific morphological responses.

Cell morphology is profoundly influenced by cellular interactions with microenvironmental factors such as the extracellular matrix (ECM). Upon adhesion to specific ECM, various cell types are known to exhibit different but distinctive morphologies, suggesting that ECM-dependent cell morphological responses may harbour rich information on cellular signalling states. However, the inherent morphological complexity of cellular and subcellular structures has posed an ongoing challenge for automated quantitative analysis. Since multi-channel fluorescence microscopy provides robust molecular specificity important for the biological interpretations of observed cellular architecture, here we develop a deep learning-based analysis pipeline for the classification of cell morphometric phenotypes from multi-channel fluorescence micrographs, termed SE-RNN (residual neural network with squeeze-and-excite blocks). We demonstrate SERNN-based classification of distinct morphological signatures observed when fibroblasts or epithelial cells are presented with different ECM. Our results underscore how cell shapes are non-random and established the framework for classifying cell shapes into distinct morphological signature in a cell-type and ECM-specific manner.

The respiratory impacts of air pollution in children: Global and domestic (Taiwan) situation.

Air pollution is a global issue that threatens the health of human beings. Epidemiologic reports have shown air pollution exposures to result in millions of deaths annually. Infancy and childhood, the period of organ and lung development, is most susceptible to these environmental hazards; as a result, the risks of respiratory diseases are increased after air pollution exposure. These pollutants can originate from indoor and ambient environment, presenting as vapor or particles, and differ in chemical compositions. This review will give brief introduction to various major pollutants and their origin, as well the correlation with respiratory diseases after exposure. We will also present several current facts in domestic area (Taiwan), regarding the status of local air-pollution, and discuss its impacts on pediatric respiratory health. This report will provide useful information for clinicians and offer advice for policy makers to develop public health guidelines of pollution control and prevention.

Pulmonary function evaluation in pediatric patients with primary immunodeficiency complicated by bronchiectasis.

BACKGROUND: Primary immunodeficiency (PID) accompanying with recurrent respiratory infections is thought to have a devastating effect on lung function. However, the associations between the airway structural abnormalities on chest computed tomography (CT), severity of dyspnea, and deterioration of pulmonary function test (PFT) have not been fully addressed. METHODS: Children diagnosed with PID in a tertiary referred center in northern Taiwan were enrolled. Demographic and clinical data including age, sex, age at diagnosis of PID, and follow-up period were collected. Chest CT images (modified Reiff scores), parameters of PFT, and life quality questionnaires (mMRC dyspnea scale) were analyzed and correlated using Spearman's rank correlation test. RESULTS: A total of nineteen children with PID were enrolled and thirteen patients were diagnosed as having bronchiectasis based on chest CT scans. Modified Reiff scores of chest CT scan were negatively correlated with FEV1 (% predicted) and FEV1/FVC ratio (P < 0.05). A strongly negative correlation was found between the mMRC dyspnea scale and FEV1 (% predicted) and FVC (% predicted), but positively correlated with RV (% predicted) and RV/TLC ratio (P < 0.05). Furthermore, there was a negative correlation between FVC (% predicted) with increasing follow-up period (P < 0.05). CONCLUSIONS: In pediatric patients with PID, chest CT scan appears to be a good tool for not only the diagnosis of bronchiectasis, but also the degree of pulmonary function impairment. Further quality of life impairments could be particularly due to the airflow obstruction and air trapping related to bronchiectasis.

Diagnostic pitfalls of acute eosinophilic pneumonia in an adolescent boy following cigarette smoking: A case report.

RATIONALE: Acute eosinophilic pneumonia (AEP) is characterized by acute febrile respiratory symptoms, bilateral lung infiltrates, and pulmonary eosinophilia. AEP is closely related to cigarette smoking but is rarely suspected in pediatric cases despite the fact that there is a relatively high incidence of cigarette smoking among adolescents in Taiwan. PATIENT CONCERNS: We report a case of a previously healthy 15-year-old boy who presented with fever and acute progressive dyspnea. Due to lack of awareness of cigarette smoking history in adolescents and the nonspecific signs and symptoms of AEP at early stages, the patient was initially treated as community-acquired pneumonia (CAP) but was unresponsive to antibiotics treatment. DIAGNOSES: A combination of a recent onset smoking history and pulmonary eosinophilia on bronchoalveolar lavage confirmed the diagnosis of cigarette-induced AEP. INTERVENTIONS: Corticosteroid treatment was prescribed. OUTCOMES: The condition improved within 24 hours, with resolution of alveolar infiltrates on chest radiographs. LESSONS: With the increasing incidence of smoking amongst adolescents in Taiwan, careful history questioning regarding cigarette smoking is necessary. Due to similarities in initial clinical and radiographic features of AEP and CAP, adolescents with suspected CAP who are unresponsive to antibiotic treatment but have a subsequent rise in peripheral eosinophils should raise the clinician's suspicion of AEP related to cigarette smoking.

Metabolomics Reveals Anaerobic Bacterial Fermentation and Hypoxanthine Accumulation for Fibrinous Pleural Effusions in Children with Pneumonia.

Fibrin formation in infectious parapneumonic effusion (IPE) characterizes complicated parapneumonic effusion and is important for providing guidelines for the management of IPEs that require aggressive interventions. We aim to identify metabolic mechanisms associated with bacterial invasion, inflammatory cytokines, and biochemical markers in cases of fibrinous infectious pleural effusions in children with pneumonia. Pleural fluid metabolites were determined by 1H nuclear magnetic resonance spectroscopy. Metabolites that contributed to the separation between fibrinous and nonfibrinous IPEs were identified using supervised partial least squares discriminant analysis ( Q2/ R2 = 0.84; Ppermutation < 0.01). IL-1ß in the inflammatory cytokines and glucose in the biochemical markers were significantly correlated with 11 and 9 pleural fluid metabolites, respectively, and exhibited significant overlaps. Four metabolites, including glucose, lactic acid, 3-hydroxybutyric acid, and hypoxanthine, were significantly correlated with plasminogen activator inhibitor type 1 in the fibrinolytic system enzymes. Metabolic pathway analysis revealed that anaerobic bacterial fermentation with increased lactic acid and butyric acid via glucose consumption and adenosine triphosphate hydrolysis with increased hypoxanthine appeared to be associated with fibrinous IPE. Our results demonstrate that an increase in lactic acid anaerobic fermentation and hypoxanthine accumulation under hypoxic conditions are associated with fibrin formation in IPE, representing advanced pleural inflammatory progress in children with pneumonia.

Overexpression of matrix metalloproteinase-9 in adolescents with primary spontaneous pneumothorax for surgical intervention.

OBJECTIVE: To determine gene expression profiles associated with bullae formation in patients with primary spontaneous pneumothorax and to identify candidate genes associated with surgical intervention. METHODS: Twenty-four adolescents with primary spontaneous pneumothorax were enrolled prospectively. A global gene expression analysis of 9 paired lung biopsies (lesion and normal adjacent sites) was performed to identify differentially expressed genes associated with spontaneous pneumothorax. Pathway and network analysis was performed using the Database for Annotation, Visualization and Integrated Discovery web tool. Candidate genes and encoding proteins were assessed in blood samples and compared between patients with pneumothorax and healthy control patients. RESULTS: A total of 1519 differentially expressed transcripts corresponding to known genes were identified comparing the lesion lung with paired adjacent normal lung. The altered genes were mainly associated with focal adhesion and extracellular matrix-receptor interaction pathways. Genes involved in proteolysis and peptidase activity were up-regulated predominantly, especially matrix metalloproteinase-1 and -9 genes. Compared with the recovery stage, blood levels of matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 were increased at the acute stage in patients with pneumothorax and, when compared between patients treated operatively with those treated nonoperatively, were also significantly greater. In addition, ratios of their serum levels were significantly greater in patients with pneumothorax compared with healthy control patients. Furthermore, matrix metalloproteinase-9 was predominantly overexpressed in neutrophils, alveolar macrophages, and mesothelial cells of lung biopsies. CONCLUSIONS: An imbalance of cell-extracellular matrix interactions appears to be associated with primary spontaneous pneumothorax. Matrix metalloproteinase-9 overexpression may particularly play a role in contributing to pleural porosity for surgical intervention.

Congenital tuberculosis: case report and review of the literature.

Congenital tuberculosis is rare, even where tuberculosis (TB) is endemic. A 14-day-old girl presented with a 3-day history of fever and respiratory distress. Her mother was diagnosed with a disseminated TB infection immediately after the delivery which was confirmed by a positive TB-polymerase chain reaction (TB-PCR) and subsequent culture from ascites and sputum. The infant was separated from her mother at birth. Her chest radiograph showed bilateral miliary nodules. Congenital TB was strongly suspected because of the symptoms, signs and maternal TB history, and was confirmed by TB-PCR and culture from the gastric lavage. Timely administration of standard anti-TB therapy resulted in a good outcome. The case highlights the importance of maternal TB history and typical miliary pattern on chest radiography for early diagnosis of congenital or neonatal TB which in turn facilitates prompt treatment and the prognosis.

An Age-Stratified Longitudinal Study of Primary Spontaneous Pneumothorax.

PURPOSE: The objective of this study was to determine the age-stratified incidence, frequency, and duration of recurrence of primary spontaneous pneumothorax (PSP). METHODS: This study analyzed the epidemiology of PSP among hospitalized patients using the National Health Research Institutes of Taiwan database. The incidence of PSP was determined from a cohort of 19,562 deidentified individuals with PSP between 2001 and 2013. The insurants consisted of 99% of the Taiwan population of about 23 million people. A 5- to 12-year long-term recurrence analysis was based on data from 11,190 patients with PSP between 2001 and 2008. RESULTS: The incidence of PSP in in-patients increased from 5.05 to 7.18/100,000 in a 13-year analysis. The age group at highest risk was 15-22 years with incidence rates >11/100,000 and readmission rates of 17%-31%. About 20% of patients had more than one attack based on long-term follow-ups. About .8% of patients had more than three hospital admissions. Only 3.9% of patients had repeated or recurrent attacks after more than 4 years. All patients who had been admitted on more than four occasions were adolescents, except for four patients who were aged between 20 and 24 years old. CONCLUSIONS: Adolescents with PSP had a higher incidence of attacks and more frequent and longer periods of vulnerability to recurrence. The majority of patients experienced recurrence during the first 4 years after the first attack.

Diagnostic value of bronchoalveolar lavage in children with nonresponding community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality in hospitalized children. In CAP, causative agents are seldom identified using noninvasive diagnostic procedures. For those children not responding to empiric antibiotic therapy, it is vital to identify the causative pathogens for further management. METHODS: We aimed to determine the usefulness of identifying the causative agents by bronchoalveolar lavage (BAL) in hospitalized children with nonresponding CAP. Ninety children hospitalized for CAP and treated with empiric antibiotics but having persistent fever ≥48 hours were enrolled, and their BAL data were retrospectively reviewed. RESULTS: Aerobic bacteria were isolated from 38 (42%) of 90 cultures, and anaerobic bacteria were isolated from eight (24%) of 33 cultures. The bacteria isolated most frequently were Streptococcus viridians (26.3%), Pseudomonas aeruginosa (23.7%), and Staphylococcus aureus (15.8%). Streptococcus pneumoniae was isolated from the BALs of only two children, and Haemophilus influenzae from none. For positive aerobic culture results, BAL results guided modifications of antibiotic regimens in 21 episodes (21 of 38, 55.3%). CONCLUSION: BAL results guided a change of antimicrobials in 55% of children with positive aerobic cultures (29% of all children in the study) and contributed to a high rate of successful therapy.

Whole-Genome Sequencing of a Family with Hereditary Pulmonary Alveolar Proteinosis Identifies a Rare Structural Variant Involving CSF2RA/CRLF2/IL3RA Gene Disruption.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease in which the abnormalities in alveolar surfactant accumulation are caused by impairments of GM-CSF pathway attributing to defects in a variety of genes. However, hereditary PAP is extremely uncommon and a detailed understanding in the genetic inheritance of PAP in a family may provide timely diagnosis, treatment and proper intervention including genetic consultation. Here, we described a comprehensive analysis of genome and gene expression for a family containing one affected child with a diagnosis of PAP and two other healthy siblings. Family-based whole-genome analysis revealed a homozygous deletion that disrupts CSF2RA, CRLF2, and IL3RA gene in the pseudoautosomal region of the X chromosome in the affected child and one of asymptomatic siblings. Further functional pathway analysis of differentially expressed genes in IL-1ß-treated peripheral blood mononuclear cells highlighted the insufficiency of immune response in the child with PAP, especially the protection against bacterial infection. Collectively, our results reveal a novel allele as the genetic determinant of a family with PAP and provide insights into variable expressivity and incomplete penetrance of this rare disease, which will be helpful for proper genetic consultation and prompt treatment to avoid mortality and morbidity.

Diagnostic utility of QuantiFERON-TB Gold In-Tube test in pediatric tuberculosis disease in Taiwanese children.

PURPOSE: To compare the performance of a commercial interferon-gamma release assay, QuantiFERON TB Gold-in-Tube (QFG-IT) with the tuberculin skin test (TST) in Taiwanese children for the diagnosis of active tuberculosis (TB). METHODS: A retrospective chart analysis of pediatric patients (<18 years of age) who underwent QFG-IT tests and TST for the confirmation of active TB between January 2008 and June 2014. RESULTS: The sensitivity of QFG-IT was 100% [95% confidence interval (CI): 63.1-100], versus sensitivity of 62.5% for TST (95% CI 24.5-91.5). The positive predictive value of QFG-IT was 100 (95% CI: 89.7-100), while the negative predictive value for TST was 86.9% (95% CI: 67-96.3). Among three patients with Bacillus Calmette-Guérin (BCG) osteitis, two patients with TST were positive, but all tested samples for QFG-IT were negative. CONCLUSION: QFG-IT assay was more sensitive for the diagnosis of TB disease than TST in an intermediate burden population with universal neonatal BCG vaccination. The increased recognition of BCG induced osteitis in recent years has alerted physicians that BCG induced lesions should be suspected when TST is positive but QFG-IT is negative. Despite higher costs for QFG-IT than TST, they have additional value for the diagnosis of active TB and should be performed when a diagnosis of TB remains in doubt.

Defective innate immune responses to respiratory syncytial virus infection in ovalbumin-sensitized mice.

BACKGROUND/PURPOSE: Respiratory viral infections have frequently been reported to closely correlate with asthma exacerbations. Distinctive expression of cytokine/chemokine and anomalous responses of innate immunity induced by respiratory viral infections were suggested to play a key role. This study further evaluates the effects of airway sensitization on innate immunity in response to different viruses. METHODS: Murine sensitization was established using an ovalbumin (OVA) sensitization model. Mice were subsequently infected with either respiratory syncytial virus (RSV) or human metapneumovirus (hMPV). Type I interferon (IFN), cytokines, and chemokines were measured in bronchoalveolar lavage (BAL) fluid. Pulmonary tissue samples were collected for the analysis of viral titers and type I IFN signal transcriptors. RESULTS: Distinct expressions of cytokine/chemokine responses after viral infection were also found in mice with OVA sensitization. A significant increase of virus replication was found in lungs of RSV-infected sensitized mice. The increment of RSV titer was associated with the decreased levels of type I IFN. Although Toll-like receptor 3 (TLR3) expression was significantly increased in the lungs, the key signal transcriptor, IFN regulatory factor 3, was significantly suppressed in the RSV-infected sensitized mice. CONCLUSION: A defective antiviral innate response was observed in the murine respiratory allergy model. Suppressed expression of IFN signal transcriptor contributes to decreased production of type I IFN. The defective innate immune response might result in acute viral exacerbations of allergic airway diseases.

Metabolomic Profiling of Infectious Parapneumonic Effusions Reveals Biomarkers for Guiding Management of Children with Streptococcus pneumoniae Pneumonia.

Metabolic markers in biofluids represent an attractive tool for guiding clinical management. The aim of this study was to identify metabolic mechanisms during the progress of pleural infection in children with Streptococcus pneumoniae pneumonia. Forty children diagnosed with pneumococcal pneumonia were enrolled and analysis of pleural fluid metabolites categorized by complicated parapneumonic effusions (CPE) and non-CPE was assessed by using (1)H-NMR spectroscopy. Multivariate statistical analysis including principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were performed. Metabolites identified were studied in relation to subsequent intervention procedures by receiver operating characteristic (ROC) curve analysis. Ten metabolites significantly different between CPE and non-CPE were identified. A significantly lower level of glucose for glycolysis was found in CPE compared to non-CPE. Six metabolites involving bacterial biosynthesis and three metabolites involving bacterial fermentation were significantly higher in CPE compared to non-CPE. Glucose and 3-hydroxybutyric acid were the metabolites found to be useful in discriminating from receiving intervention procedures. Metabolic profiling of pleural fluid using (1)H-NMR spectroscopy provides direct observation of bacterial metabolism in the progress of pneumococcal pneumonia. An increase in the metabolism of butyric acid fermentation of glucose could potentially lead to the need of aggressive pleural drainage.

Chest Wall Constriction after the Nuss Procedure Identified from Chest Radiograph and Multislice Computed Tomography Shortly after Removal of the Bar.

BACKGROUND: This study radiographically examined the changes in the chest walls of patients with pectus excavatum (PE) after Nuss bar removal, to define the deformation caused by the bar and stabilizer. In the first part of the study, we compared the changes in chest radiographs of patients with PE to a preoperation PE control group. In the second part, we used multislice computed tomography (CT) scans to provide three-dimensional reconstructions with which to evaluate the changes to the thoracic wall. METHODS: Part 1 From June 2006 to August 2011, 1,125 patients with PE who had posteroanterior chest radiographs taken before undergoing the Nuss procedure at four hospitals were enrolled as a preoperative control group. At the same time, 203 patients who had the bar removed were enrolled as the study group. The maximum dimensions of the outer boundary of the first to ninth rib pairs (R1-R9, rib pair width), chest height, and chest width were measured. Part 2 Thirty-one consecutive patients with PE (20 males and 11 females) who underwent Nuss bar removal were evaluated 7 to 30 days after operation. During this period, a further 34 patients with PE who had undergone CT imaging before bar insertion were evaluated and compared with the postoperative group. RESULTS: Part 1 The width of the lower ribs (R4-R9) after bar removal was significantly less than in the age-matched controls. The ribs adjacent to the bar (R5-R7) showed the greatest restriction. The width of the upper ribs (R1-R3) 2 to 3 years after bar placement did not differ significantly from the controls. Patients who were operated on after 10 years of age had less of a restrictive effect. Three years of bar placement resulted in more restriction than a 2-year period, particularly in patients younger than 10 years old. Part 2: A significant constriction of the chest wall was observed in 13 patients after removal of the Nuss bar. Constriction at ribs 5 to 8 was found to be present adjacent to the site of bar insertion. However, constriction of the chest wall was found in only 3 of the 34 patients in the preoperative group. The severity of constriction (as graded by the spline model) also increased in the postoperative group. CONCLUSION: The growth of the chest wall was restricted after placement of the Nuss bar for PE correction. Long-term follow-up of chest wall growth is needed to clarify whether such constriction resolves with time.

Preceding human metapneumovirus infection increases adherence of Streptococcus pneumoniae and severity of murine pneumococcal pneumonia.

BACKGROUND: Coinfection with respiratory virus and Streptococcus pneumoniae has been frequently reported in several epidemiologic studies. The aim of this study was to explore the effect of preceding human metapneumovirus (hMPV) inoculation on subsequent pneumococcal infection. METHODS: Hep-2 and A549 cells were infected with hMPV then inoculated with S. pneumoniae. Bacterial adhesion was measured using colony forming unit and cytometric-fluorescence assays. In vivo bacterial adhesion was examined in hMPV-infected mice after inoculation of fluorescence-conjugated S. pneumoniae. Pulmonary inflammation (bacterial titers, cytokine levels, and histopathology) of hMPV-infected mice was investigated after inoculation with S. pneumoniae. RESULTS: In vitro results of bacterial infection with S. pneumoniae on A549 and Hep-2 monolayer cells showed that even though cellular adherence was variable among different serotypes, there was significantly enhanced bacterial adherence in A549 cells with preceding hMPV infection. In addition, in vivo study of hMPV-infected mice showed increased adhesion of S. pneumoniae on the bronchial epithelium with delayed bacterial clearance and exacerbated histopathology. Furthermore, mice with preceding hMPV infection showed repressed recruitment of airway neutrophils with decreased expression of neutrophil chemoattractants during pneumococcal infection. CONCLUSION: These results suggest that hMPV-infected airway cells, especially the lower airway epithelium, express increased adherence with S. pneumoniae. Furthermore, hMPV-infected mice showed impaired recruitment of airway neutrophils, possibly leading to delayed bacterial clearance and exacerbated pulmonary inflammation, after secondary infection with pneumococcal isolates.

Value of Lung Ultrasonography in the Diagnosis and Outcome Prediction of Pediatric Community-Acquired Pneumonia with Necrotizing Change.

BACKGROUND: Lung ultrasonography has been advocated in diagnosing pediatric community-acquired pneumonia. However, its function in identifying necrotizing pneumonia, a complication, has not been explored. This study investigated the value of lung ultrasonography in diagnosing pediatric necrotizing pneumonia and its role in predicting clinical outcomes. METHODS: We retrospectively reviewed 236 children with community-acquired pneumonia who were evaluated using lung ultrasonography within 2-3 days after admission. The ultrasonographic features assessed included lung perfusion, the presence of hypoechoic lesions, and the amount of pleural effusion. Chest computed tomography was also performed in 96 patients as clinically indicated. Detailed records of clinical information were obtained. RESULTS: Our results showed a high correlation between the degree of impaired perfusion in ultrasonography and the severity of necrosis in computed tomography (r = 0.704). The degree of impaired perfusion can favorably be used to predict massive necrosis in computed tomography (area under the receiver operating characteristic curve, 0.908). The characteristics of impaired perfusion and hypoechoic lesions in ultrasonography were associated with an increased risk of pneumatocele formation (odds ratio (OR), 10.11; 95% CI, 2.95-34.64) and the subsequent requirement for surgical lung resection (OR, 8.28; 95% CI, 1.86-36.93). Furthermore, a longer hospital stay would be expected if moderate-to-massive pleural effusion was observed in addition to impaired perfusion in ultrasonography (OR, 3.08; 95% CI, 1.15-8.29). CONCLUSION: Lung ultrasonography is favorably correlated with chest computed tomography in the diagnosis of necrotizing pneumonia, especially regarding massive necrosis of the lung. Because it is a simple and reliable imaging tool that is valuable in predicting clinical outcomes, we suggest that ultrasonography be applied as a surrogate for computed tomography for the early detection of severe necrotizing pneumonia in children.

A Cross-Sectional Study of Chest Wall Development in Patients with Pectus Excavatum.

BACKGROUND: We conducted a cross-sectional study to quantify the developmental changes of the thoracic cage in patients with pectus excavatum (PE). METHODS: The preoperative posteroanterior standing chest radiographs (chest PAs) of 1,197 consecutive patients with PE, together with 1,661 age- and sex-matched minor surgery patients, as a control group, who were seen between June 2005 and February 2013, were reviewed. The maximum width of each rib pair and chest height (H) were measured on the chest PA. RESULTS: In the PE group, the normal thoracic contour in younger patients was replaced by a characteristic can-shaped chest wall, which showed protrusion of the upper ribs, an increased H, and a straightened lateral border of the chest cage, as they grew into adulthood. The chest height difference between the PE and control groups increased progressively, from the age of 8 years and most significantly from age 13 to 17 years. No difference was observed in the middle and lower rib widths. Sex did not influence these trends. CONCLUSION: The PE chest wall shows a significant increment in chest height, and upper rib width starts during the period of rapid growth and is maintained into adulthood. The thoracic deformity in patients with PE includes more than just the sternal deformity.

Increase in fitness of Streptococcus pneumoniae is associated with the severity of necrotizing pneumonia.

BACKGROUND: The incidence of necrotizing pneumococcal pneumonia has increased during the past 2 decades. We hypothesized that increased pneumococcal load or augmented inflammatory cytokine production might lead to destructive pneumococcal lung disease. METHODS: This study enrolled prospectively 0- to 18-year-old children with a diagnosis of community-acquired pneumonia with pleural effusion admitted to 6 medical centers from March 2010 to April 2012. Children were diagnosed with pneumococcal empyema if the pleural fluid tested positive for quantitative pneumococcal (lytA) detection by real-time polymerase chain reaction. Pneumococcal empyema cases were further divided into 4 groups according to necrosis severity: (0) nonnecrosis, (1) mild necrosis, (2) cavitation and (3) bronchopleural fistula. Nasopharyngeal and pleural pneumococcal load, as well as levels of proinflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-8), Th1-(IL-2, IFN-γ), Th2-(IL-4, IL-10) and Th17-cytokines (IL-17), in the pleural fluid was measured. RESULTS: Serotypes 19A and 3 accounted for 69.4% and 12.5%, respectively, of 72 cases of pneumococcal empyema. Pleural pneumococcal load was significantly higher in serotypes 19A and 3 infection than in the other strains causing infection (P = 0.006). There was a correlation between nasopharyngeal and pleural pneumococcal load (ρ = 0.35; P = 0.05). In multivariate ordinal logistic regression analysis, pleural pneumococcal load (adjusted odds ratio: 1.79; 95% confidence interval: 1.03-3.06) and IL-8 (adjusted odds ratio: 2.64; 95% confidence interval: 1.21-5.75) were independent factors associated with the severity of lung necrosis. CONCLUSIONS: Evolution of Streptococcus pneumoniae toward increased fitness in their interaction with host and exaggerated IL-8 expression may be responsible for the increase of necrotizing pneumococcal pneumonia.

Rapid increase in the height and width of the upper chest in adolescents with primary spontaneous pneumothorax.

BACKGROUND: We determined the chest height in a cohort of patients with primary spontaneous pneumothorax (PSP) who had received chest radiographic examinations prior to the attack. The aim of this study was to determine when their chest height began to change and how this was related to the PSP. METHODS: From June 2009 to February 2012, the chest posteroanterior radiographs of 156 patients with PSP (Group 1) were reviewed. Among another 3134 patients with PSP, we identified 52 patients who had a chest posteroanterior radiograph prior to the attack (Group 2). We also recruited 196 controls for comparison (Group 3). The chest height and chest width at different levels were measured and analyzed. RESULTS: Before 14 years of age, the chest height of patients in Group 2 was no different from that of patients in Group 3. By the age of 14 years, however, the chest height and upper chest width of patients with PSP was significantly higher than that of the normal controls. The difference from normal chest height did not increase at adulthood. CONCLUSION: The rapid increase in chest height and upper chest width is a unique finding in patients with PSP. It might be attributable to the occurrence of PSP. This finding may also help to identify patients who are at risk of PSP.

The value of total protein in guiding management of infectious parapneumonic effusion by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND/PURPOSE: Infectious parapneumonic effusion (PE) contains proteins originating from circulation as well as proteins locally released by inflammatory pulmonary cells. The purpose of this study was to investigate the value of total protein analysis in guiding management of infectious PE by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. METHODS: Fifty-seven children with pneumonia followed by PE were consecutively enrolled into our study. Protein profiles generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry after fractionating samples with functionalized magnetic beads (C8) were used for differentiating complicated PE (CPE) from non-CPE. A training set was used to generate classification models and the clinical efficacy of these models in detecting CPE and the need for intervention was then evaluated in an independent set. RESULTS: The MS spectra derived from PE were analyzed, and classification models were constructed in the training set. A total of 123 mass/charge (m/z) values were identified and 23 m/z values which were significant with p < 0.05 were used as classifiers. An optimized genetic algorithm model containing enforced selection of three significant downregulated m/z values (2127, 2232, and 2427) was able to classify CPE with 100% positive predictive value and predict the need of aggressive therapeutic intervention with 77% positive predictive value. CONCLUSION: A diagnostic model construction comprising three potential biomarkers can predict CPE and need for surgical intervention rapidly and precisely. Pleural fluid proteins downregulated during the progression of pneumonia could potentially guide the management of infectious PE.