Nasopharyngeal aspirates in children with severe community-acquired pneumonia collected within 3 days before bronchoscopy can partially reflect the pathogens in bronchoalveolar lavage fluids.

BACKGROUND: There is little evidence about consistency between nasopharyngeal and pulmonary pathogens in children with severe pneumonia. This study aims to compare the difference of pathogens between nasopharyngeal aspirates (NPAs) collected before bronchoscopy and bronchoalveolar lavage fluids (BALFs) in children with severe community-acquired pneumonia (SCAP). METHODS: NPAs and BALFs were collected form pediatric SCAP cases hospitalized from January 2018 to March 2019. NPAs were colleced within 3 days before bronchoscopy. Samples were detected by direct immunofluorescence assay (DFA) for seven respiratory viruses and by routine bacterial culture in the clinical microbiology laboratory. Respiratory syncytial virus (RSV), Adenovirus (ADV), Influenza virus types A, B (IV-A and IV-B), Parainfluenza virus 1-3 (PIV1-3) were detected with a commercial assay. The virological and bacteriological detention results of NPAs were compared with the results of BALFs. RESULTS: In total 204 cases with mean age of 3.4 ± 2.8 years (IQR, 1 month-14 years) were included in the study. Both NPA and BALF were collected from those cases. The positive rates of pathogen in NPAs and BALFs were 25.0% (51/204) and 36.7% (75/204), respectively (x2 = 6.614, P = 0.010). Respiratory viruses were found in 16.1% (33/204) from NPAs and 32.3% (66/204) from BALFs (x2 = 14.524, P < 0.001). RSV and ADV were the two most frequent detected viruses in NPAs and BALFs. High consistentcy of pathogens between NPAs and BALFs was observed, and 96.9% (32/33) viruses detected in NPAs were also found in BALFs. While bacteria were isolated from 12.7% (26/204) and 10.7% (22/204) of the two kinds of samples, respectively (x2 = 0.378, P = 0.539). In addition, Haemophilus influenzae (HI) was the dominant germ in both samples. CONCLUSION: The DFA method used to detect seven respiratory viruses from NPAs collected within 3 days before bronchoscopy can partially reflect the pathogens in the lungs in children with SCAP.

Efficacy of Low-Dose rhGM-CSF Treatment in a Patient With Severe Congenital Neutropenia Due to CSF3R Deficiency: Case Report of a Novel Biallelic CSF3R Mutation and Literature Review.

This study reports the clinical manifestations, genetics, and efficacy of treatment with the efficacy of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-GSF) of a 2-year-old female patient with severe congenital neutropenia (SCN) type 7 (SCN7) caused by novel biallelic mutations in the colony-stimulating factor 3 receptor (CSF3R) gene. Genetic diagnosis of the patient was performed by whole-exome and Sanger sequencing. Expression of the CSF3R gene in the peripheral neutrophils of the patient was detected by real-time PCR and Western blotting. The patient presented with recurrent suppurative tonsillitis and decreased absolute neutrophil count <0.5 × 109/L. Novel heterozygous mutations were found to be inherited from each parent (maternal c.690delC [p.met231Cysfs*32] and paternal c.64+5G>A). The patient's neutrophils had lower CSF3R mRNA and protein levels than those of the parents. Low-dose rhGM-CSF (3 µg/kg/day once a week) prevented recurrent infection in the patient. These results demonstrate that the clinical manifestations of SCN7 with biallelic CSF3R mutations and downregulated CSF3R can be effectively treated with rhGM-CSF.

Etiology of Severe Pneumonia in Children in Alveolar Lavage Fluid Using a High-Throughput Gene Targeted Amplicon Sequencing Assay.

Objective: To evaluate the diagnostic value of a high-throughput gene targeted amplicon sequencing (TAS) assay for detecting pathogenic microorganisms in alveolar lavage fluid (ALF) from children with severe community-acquired pneumonia (SCAP). Methods: A retrospective study was performed on 48 frozen ALF samples from 47 severe pneumonia cases admitted to Children's Hospital of Fudan University from January 1, 2019, to March 31, 2019. All samples were tested by a multiplex PCR (Multi-PCR) assay and a TAS assay. The results of the TAS panels were parallel compared with Multi-PCR and Conventional Tests (CT) including culture, direct fluorescent antibody method (DFA), and singleplex polymerase chain reaction (PCR). Results: The proportion of pathogens detection by CT was 81.2% (39/48). The 8 common respiratory viruses including respiratory syncytial virus (RSV), adenovirus (ADV), influenza A virus (FLUA), influenza B virus (FLUB), parainfluenza virus 1-3 (PIV1-3), and human Metapneumovirus (hMPV) were found in 31.2% (15/48) of the 48 samples by DFA. With the criteria of CT results used as "Golden Standard" for determing of TAS results, the proportion of pathogens detection by TAS was 70.8% (34/48). The difference of proportion of pathogens detection between TAS and CT was not statistically significant (p = 0.232). The sensitivity and specificity of TAS for pathogens detection based on CT were 87.1% (95% CI, 71.77-95.18%) and 100.0% (95% CI, 62.88-100%), the positive predictive value (PPV) and negative predictive value (NPV) were 100.0% (95% CI, 87.35-100%) and 64.2% (95% CI, 35.62-86.02%), respectively. While Multi-PCR results were used as "Golden Standard," the total pathogens detection rate of TAS was 83.3% (40/48), which had a significant difference with that of Multi-PCR (p = 0.003). The sensitivity and PPV of TAS compared with Multi-PCR were 83.3% (95% CI, 69.23-92.03%) and 100.0% (95% CI, 89.08-100%), respectively. High rates of co-infection were proved by CT, Multi-PCR, and TAS. Mycoplasma pneumoniae (MP) and ADV were the two most frequently detected pathogens in all three assays. Conclusion: Compared with the CT and Multi-PCR methods, this TAS assay had a good performance in detecting bacteriological and viral pathogens from ALF. More research is needed to establish interpretation criteria based on TAS reads or analysis platforms.

Differences of inflammatory and non-inflammatory indicators in Coronavirus disease-19 (COVID-19) with different severity.

Background A variety of inflammatory and non-inflammatory indicators were increased in severe and critical Coronavirus disease-19 (COVID-19) and some of them were used to evaluate the severity and predict prognosis of community-acquired pneumonia. The aim of this study was to investigate the association of these indicators in COVID-19 with different severity. Methods Clinical data of 46 patients with severe COVID-19 and 31 patients with critical COVID-19 were collected. The general characteristics and comorbidities of the patients were retrospectively analyzed. The initial and peak concentrations of serum troponin I (cTnI), D-dimer (D-D), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), initial and peak neutrophil counts and initial and trough lymphocyte counts were compared between two groups. The correlation between the variation of cTnI, D-D, CRP, IL-6, PCT, neutrophils, lymphocytes and the severity of the disease was analyzed. The efficacy of the initial concentrations of cTnI, D-D, CRP, IL-6, PCT, the initial neutrophil and lymphocyte counts in predicting critical COVID-19 were evaluated by receiver operating characteristic (ROC) curve. Results The initial and peak concentrations of cTnI, D-D, CRP, IL-6, PCT, initial and peak neutrophil counts in critical group were higher than those in severe group, the initial and trough counts of lymphocyte were lower than those in the severe group. Except for the initial level of PCT, the other differences were statistically significant (p < 0.05). The increase of cTnI, D-D, CRP, IL-6, PCT, neutrophils and the decrease of lymphocytes were related to the severity of the disease, OR values were 28.80, 2.20, 18.47, 10.80, 52.00, 9.60 and 21.08, respectively. Except for D-D, the other differences were statistically significant. The areas under ROC curves for predicting critical COVID-19 by initial concentrations of cTnI, D-D, CRP, IL-6, PCT, initial lymphocyte and neutrophil counts were 0.76, 0.78, 0.83, 0.95, 0.56, 0.68 and 0.62, respectively. Conclusions The severe and critical COVID-19 patients had significant differences in concentrations of serum cTnI, D-D, CRP, IL-6, PCT, neutrophil and lymphocyte counts. The increase of cTnI, CRP, IL-6, PCT, neutrophils and decrease of lymphocytes indicated severe condition. The initial IL-6 might be a good indicator of COVID-19 severity.

Plastic bronchitis associated with adenovirus serotype 7 in children.

BACKGROUND: Plastic bronchitis is an uncommon but severe respiratory disease characterized by formation of casts in tracheobronchial tree. It can lead to airway obstruction and even respiratory failure. CASE PRESENTATION: Plastic bronchitis is mostly seen in both post-cardiac surgery patients, especially Fontan procedure, and infections including those caused by influenza viruses, Mycoplasma pneumoniae or tuberculosis. But it has rarely been reported to be associated with adenovirus infection. We report 2 cases of plastic bronchitis arising from adenovirus serotype 7 infection, manifested in repeated high fever, cough, and progressive dyspnea, and were diagnosed and eventually cured by bronchoscopy. CONCLUSIONS: Plastic bronchitis is a rare, variable and potentially fatal disease. In the cases we described, the cause was associated with adenovirus serotype 7 and its treatment required intervention with bronchoscopy and adequate control of the underlying disease.