Pulmonary surfactant protein gene mutation associated with pediatric interstitial lung disease: a case study and the review of related literature / 中华儿科杂志

<p><b>OBJECTIVE</b>To report a case of pulmonary surfactant protein (SP) gene mutation associated with pediatric interstitial lung disease, and study the clinical diagnosis process and review of related literature, to understand the relationship between interstitial lung disease and SP gene mutation in infants and children.</p><p><b>METHOD</b>The clinical, radiological, histological, and genetic testing information of a case of SP gene mutation related pediatric interstitial lung disease were analyzed and related literature was reviewed.</p><p><b>RESULT</b>A 2-year-old girl without a history of serious illness was hospitalized because of the shortness of breath, cough, excessive sputum, and the progressive dyspnea. Physical examination on admission revealed tachypnea, slight cyanosis, and the retraction signs were positive, respiratory rate of 60 times/minute, fine crackles could be heard through the lower lobe of both lungs; heart rate was 132 beats/minute. No other abnormalities were noted, no clubbing was found. Laboratory test results: pathologic examination was negative, multiple blood gas analysis suggested hypoxemia. Chest CT showed ground-glass like opacity, diffused patchy infiltration. Bronchoalveolar lavage fluid had a large number of neutrophils, and a few tissue cells. Eosinophil staining: negative. Fluconazole and methylprednisolone were given after admission, pulmonary symptoms and signs did not improve, reexamination showed no change in chest CT. Then lung biopsy was carried out through thoracoscopy. Histopathology suggested chronic interstitial pneumonia with fibrosis. The heterozygous mutation of R219W in the SFPTA1 and the S186N in SFTPC were identified by SP-related gene sequencing. The review of related literature showed that polymorphisms at the 219th amino acid in SP-A1 allele were found in adults with idiopathic pulmonary fibrosis (IPF), but there is no related literature in pediatric cases. The patient in this report had a mutation at the SP-A1 allele consistent with related literature. Data of 17 young children with mutation in SP-C gene showed that all the 17 cases had dyspnea and tachypnea, chest CT revealed diffuse opacities in lungs, the pathology of lungs was NSIP and CPI. There were 17 kinds of mutation and the common mutation was I73T. The mutation of S186N in SFTPC in our case has never been shown in previously published literature.</p><p><b>CONCLUSION</b>A case of interstitial lung disease with S186N gene mutation in SFTPC was preliminarily diagnosed in an infant. The SP-C gene mutations and polymorphisms are associated with pediatric interstitial lung disease.</p>

Chest CT features and outcome of necrotizing pneumonia caused by Mycoplasma pneumoniae in children (report of 30 cases) / 中华儿科杂志

<p><b>OBJECTIVE</b>To summarize the chest CT features and outcome of necrotizing pneumonia (NP) caused by Mycoplasma pneumoniae in children and to review the changes of common inflammatory parameters in NP patients to help clinicians understand the proper timing of CT scan.</p><p><b>METHOD</b>The imaging data from 30 cases of Mycoplasma pneumoniae pneumonia in NP group and 24 cases with non-necrotizing Mycoplasma penumoniae pneumonia (control group) were analyzed retrospectively. The changes of common inflammatory parameters in NP group and control group were compared.</p><p><b>RESULT</b>(1) The chest CT findings of NP (30 cases): 28 cases showed unilateral pneumonia, and 20 cases showed single lobar consolidation, 10 cases had multiple lobes involvement; pulmonary cavities were seen in 27 cases. There were decreased enhancement areas in the consolidation (22 cases). (2) The dynamic changes of CT signs during follow-up: The CT scan performed during the 1 - 2 months after onset of disease (23 cases) showed that pulmonary consolidation in 2 cases (9%) were absorbed, 18 cases (78%)had cavities in lung, 16 cases (70%) had pleural thickening, 2 cases (9%) atelectasis and 1 case (4%) bronchopleural fistula;the CT scan performed during the 2 - 3 months after onset of disease (11 cases) showed pulmonary consolidation in 7 cases (64%) were absorbed, 10 cases (91%) pleural thickness, 7 cases (64%) with cavities in lung, 5 cases (45%) atelectasis, 2 cases (18%) pulmonary lobe cysts and 1 case bronchopleural fistula. The CT scan performed at 3.5 years of disease course (10 cases) showed that there were no pulmonary consolidation in any of the cases, 4 cases had atelectasis, 4 cases had pulmonary cysts, and 1 case had band-like scars. (3) There were significant differences between NP group and control group in the maximum peripheral blood WBC, proportion of neutrophil and C-reactive protein(CRP, mg/L) (P < 0.01, 0.01, 0.001, respectively), and there was significant difference between the 2 groups in the duration of fever, abnormal WBC(d) and CRP(d) (P < 0.001).</p><p><b>CONCLUSION</b>The chest CT features of NP caused by Mycoplasma pneumoniae in children were single lobular consolidation in most cases, NP had decreased parenchymal enhancement and cavity in the consolidation, and recovery was slow, the outcome included recovery, atelectasis or lobar cystic degeneration. The clinicians should pay more attention to the common inflammatory parameters when they suspect the Mycoplasma pneumoniae pneumonia is progressing into necrosis and make correct decision for chest CT examination.</p>

Clinical study of 25 children with idiopathic pulmonary hemosiderosis / 中华实用儿科临床杂志

Objective To analyze the clinical features,laboratory results,treatment and prognosis of children with idiopathic pulmonary hemosiderosis (IPH).Methods The documents of 25 children with IPH,who were hospitalized in Children's Hospital Affiliated to Capital Institute of Pediatrics from Apr.1992 to Nov.2008 were reviewed.Then some of the patients were followed up.Results The median age of onset was 4 years old (6.5 months to 8 years old).Those patients aged from 3 to 6 years old ranked the first as 48％ (12 cases).The median age at diagnosis was 5.17 years old.The course of desease was between 10 days and 6 years,the median course was 1 year.Cough,pallor,fever and hemoptysis were the common clinical features of IPH patients.The chest radiological patterns for IPH were diverse.The common features of high resolution CT scan in 15 patients included declined transparency and ground glass shadows in 11 cases,cloudy patchy infiltrate in 9 cases,reticular changes in 6 cases,and nodular changes in 2 children.Twentythree cases were once misdiagnosed and 60％ of them were delayed in diagnosis as IPH for more than 1 year.Glucocorticoid therapy was effective in improving symptoms.Some patients suffered from rheumatoid arthritis later in their life.Conclusions The manifestations of IPH in children are nonspecific,therefore it is easily to be misdiagnosed.Combined chest radiographic presentations with repeatedly looking for hemosiderin-laden macrophages in sputum,gastric aspirate or bronchoalveolar lavage fluid are helpful in diagnosis.Glucocorticoid therapy can control the symptoms.Some relationships may exist between IPH and rheumatoid arthritis.

Chest radiographic findings in children with 2009 influenza A (H1N1) virus infection / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate chest radiographic findings of children with 2009 influenza (H1N1) virus infection.</p><p><b>METHOD</b>Data of 235 patients who had microbiologically confirmed H1N1 infection and available chest radiograph obtained between May 1(st) 2009 and Jan. 31(st) 2010 were retrospectively analyzed. The final study group was divided on the basis of clinical course [group 1 mild, outpatients without hospitalization (n = 172); group 2 moderate, inpatients with brief hospitalization (n = 49); group 3 severe, ICU admission (n = 14)]. Four pediatric radiologists reviewed all the chest radiographs of lung parenchyma, airway, pleural abnormalities and also anatomic distribution of the disease.</p><p><b>RESULT</b>No significant sex or age differences were found among the study groups (P > 0.05). The mean interval between the onset of clinical symptom and the initial chest radiography was (5.91 ± 1.64) days (group 1), (3.60 ± 1.43) days (group 2) and (1.21 ± 0.41) days (group 3), respectively. The differences among the three groups were significant statistically (χ(2) = 13.368, P < 0.01). The ratio of abnormality presented at initial chest X-ray was 79.7% in group 1, 91.8% in group 2 and 100% in group 3. Radiographically, there were prominent peribronchial markings (group 1, 55.2%; group 2, 83.7%; and group 3, 78.6%), consolidation (group 1, 34.3%; group 2, 69.4%; and group 3, 100.0%), hyperinflation (group 1, 22.1%; group 2, 44.9%; and group 3, 50.0%) and ground glass opacity (group 1, 0.6%; group 2, 2.0%; and group 3, 14.3%) in the chest radiographs. The differences of presenting were statistically significant (P < 0.01). In the severe group, the lesions distributed diffusely and asymmetrically with multi-lobe involvements.</p><p><b>CONCLUSION</b>In children with 2009 influenza A H1N1 viral infection, the interval between the onset of clinical symptom and initial chest radiography, the ratio of abnormality presented at initial chest X-ray film and the severity of chest film are parallel to their clinical situation.</p>

Clinical study on interstitial lung disease in children of China / 中华儿科杂志

<p><b>OBJECTIVE</b>Interstitial lung disease in children represents a heterogeneous group of disorders of both known and unknown causes. This study aimed to understand better the causes of the disease in children and to provide information on the current approach to diagnosis and management of the disease.</p><p><b>METHOD</b>Through the Pediatric Diffuse Parenchymal Lung Disease/Pediatric Interstitial Lung Disease Cooperative Group of China, data of 93 cases of interstitial lung disease of children from 11 hospitals were collected with the same questionnaire in 2009. Respiratory tract secretions were obtained for bacterial culture. Respiratory virus antigen examination, mycoplasma antibody, EB virus, cytomegalovirus, and herpes simplex viruses antibody detection were performed. Cells in the sputum, gastric juice and bronchoalveolar lavage fluid (BALF) were tested for hemosiderin. The CT or high resolution CT (HRCT) of the lung and blood-gas analysis were also performed. Fourteen cases underwent lung biopsy and 25 cases underwent bronchomicrocopy. Data were then pooled and discussed through a series of meetings.</p><p><b>RESULT</b>Fifty-three cases were male, 40 were female and their age ranged from 8 months to 14 years. Thirty-nine cases were diagnosed as bronchiolitis obliterans (BO); 39 as idiopathic pulmonary hemosiderosis (IPH); 7 as idiopathic interstitial pneumonia (IIP) of unknown causes, of whom 4 cases had non specific interstitial pneumonia, 1 case as acute interstitial pneumonia and 1 case as lymphocytic interstitial pneumonia, 1 case as idiopathic pulmonary fibrosis; 2 cases as secondary interstitial lung disease, one was secondary to SLE, one to human immunodeficiency virus (HIV) infection; 2 cases had hypersensitive pneumonitis; 2 cases had pulmonary alveolar proteinosis; 1 case had bronchiolitis obliterans organizing pneumonia; 1 case had lipoid pneumonia;1 case of diffuse panbronchiolitis; 1 case of microlithiasis alveolaris pulmonum. Forty two cases had cough, 24 of them also had tachypnea, 8 cases had clubbing. HRCT showed that 56 cases had groundglass-like opacification; 30 cases had mosaic appearance; 1 case had diffuse micronodular opacities, 1 case had diffuse reticulonodular opacities and cysts.</p><p><b>CONCLUSION</b>Interstitial lung disease in children is a heterogeneous group of disorders. In this study diagnoses of 11 diseases were made, the top third diagnoses were BO, IPH and IIP, respectively.</p>

Analysis of clinical manifestations of 159 hospitalized children infected with 2009 novel influenza A (H1N1) virus / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics of hospitalized pediatric patients infected with 2009 H1N1 influenza.</p><p><b>METHODS</b>Totally 159 children (83 male and 76 female) with influenza A (H1N1) confirmed by the real-time reverse-transcriptase-polymerase-chain-reaction assay were admitted to a special ward of Capital Institute of Pediatrics from November 2009 to January 2010. Clinical manifestations, laboratory and therapy data from the hospitalized children were collected by designed case report form and analyzed.</p><p><b>RESULTS</b>Out of 159 hospitalized patients, 139 (87.4%) were under the age of 5 years and 34.0% of them had at least one underlying medical conditions. Proportions of the severe cases, pneumonia and underlying medical diseases were similar between the 78 infants and 81 older children. All of these 159 cases had influenza-like symptoms at onset and the most common presentations were fever (115 cases, 72.3%) and cough (154 cases, 96.8%). Five severe cases presented dyspnea, cyanosis and hypoxemia. The virus easily invaded into the lower respiratory tract as indicated by that 61% of the cases had findings consistent with pneumonia by X-ray and/or CT and 21.6% had bacterial co-infection. Part of them had mycoplasma pneumonia (20 cases, 27.0%) or other respiratory viruses (5 cases, 3.1%) co-infection simultaneously. The duration of fever was similar between the H1N1 virus sole infection group and the co-infection group (t = 0.975, P > 0.05), but the average course of the disease and hospitalized days of the latter group were longer than the former (t = 3.182 and 3.190, P < 0.01). The proportion of children with pneumonia in the co-infection group was significantly higher than that in the H1N1 sole-infection group (χ(2) = 4.082, P < 0.05).</p><p><b>CONCLUSIONS</b>Most of the H1N1 infected pediatric patients had mild respiratory symptoms, a few of them developed severe manifestations. Dyspnea and hypoxemia were the early signals for the developing severe cases. Rational and experienced treatment with antibiotics was important addition to the antiviral therapy for those co-infected with bacteria.</p>

Serological analysis of SARS Coronavirus in children diagnosed clinically as severe acute respiratory syndrome cases during SARS epidemic in Beijing / 中华儿科杂志

<p><b>OBJECTIVE</b>To identify the etiologic agents from children who had been clinically diagnosed as severe acute respiratory syndrome (SARS) during the epidemic in Beijing and to characterize the transmissibility of SARS from those children to others.</p><p><b>METHODS</b>One hundred and seventy-seven serum specimens were collected during the period of June to August, 2003 from children and adults who had been clinically diagnosed as SARS and who closely contacted with those diagnosed as SARS during SARS epidemic in Beijing. Serum specimens were also collected from 49 children from Anhui province which was non-epidemic region and 93 healthy kindergarten children without history of contacting with SARS patients in Beijing during SARS epidemic. Serum specimens collected from 90 healthy kindergarten children in Beijing in September 2002 were included in the study. All the 409 serum specimens were tested for specific antibodies against SARS-associated coronavirus (SARS-CoV) by different methods including ELISA for specific IgM and IgG, whole antibodies against SARS-CoV, IFA for specific IgM and IgG against SARS-CoV, and Western-blot for IgG to expressed N protein from SARS-CoV.</p><p><b>RESULTS</b>The positive rates of specific IgG and whole antibodies against SARS-CoV ranged from 39.1% to 43.5% in the children who had been clinically diagnosed as SARS, zero in children and 6.0% to 9.0% in adults who had closely contacted with the clinically diagnosed SARS children. Among those clinically diagnosed SARS adult patients, the positive rates of specific IgG and whole antibodies against SARS-CoV were 57.1% to 71.4%. In children and adults who closely contacted with these clinically diagnosed SARS adult patients, the positive rates of specific IgG and whole antibodies against SARS-CoV were 0 to 9.7% and 4.4% to 7.1%, respectively. None of the serum specimens collected from healthy children before and during epidemic in Beijing and children from non-epidemic region was positive when IFA methods and ELISA with Beier kits were used for detection, but some were positive when ELISA with the diagnostic kit from other source was applied.</p><p><b>CONCLUSION</b>The positive rates of specific IgG and whole antibodies against SARS-CoV in children who had been clinically diagnosed as SARS were around 40%, which is much lower than the positive rate in clinically diagnosed adult SARS patients, indicating that a large proportion of those "SARS" children were infected with respiratory viruses other than SARS-CoV during SARS epidemic in Beijing. Some of the children who closely contacted with children and adults SARS patients showed positive SARS-CoV antibodies, suggesting that asymptomatic infections may occur. The value of some approved diagnostic kit at least in children for SARS etiological diagnosis needs to be analyzed further.</p>

Clinical characteristics of bronchiolitis caused by human metapneumovirus in infants / 中华儿科杂志

<p><b>OBJECTIVE</b>The fact that the acute lower respiratory infections (ALRI) are associated with a newly discovered virus, human metapneumovirus (hMPV), has been shown in several studies. The authors conducted this study to understand the etiological and clinical characteristics of bronchiolitis, one of the most common ALRI in infants, caused by hMPV.</p><p><b>METHODS</b>Nasopharyngeal aspirate specimens from 54 out of 126 infants with bronchiolitis admitted to the Children's Hospital Affiliated to Capital Institute of Pediatrics, Beijing from November 2002 to February 2003 were examined for hMPV gene fragments by reverse transcription-polymerase chain reaction (RT-PCR). Prior to the detection, the specimens were confirmed as negative for the common respiratory pathogens including RSV, influenza A and B, parainfluenza I, II, III, adenovirus, Mycoplasma pneumoniae by indirect immunofluorescence test, virus isolation and ELISA test. The clinical data of the patients diagnosed etiologically as hMPV infection analyzed included the infants' age, sex, the degree of fever, the severity of wheezing and clinical Lowell score, the findings of chest examination and chest X-ray, the white blood cell count and blood gas analysis, the course of the disease, the major treatments and the outcome of the disease.</p><p><b>RESULTS</b>Twenty-one specimens showed the predicted 213 bp PCR products in agarose gel and the positive rate was 16.7% of all patients (21/126) and 39% of the patients with negative results for common respiratory pathogens detections (21/54). The range of patients' age was 2 - 15 months and the young infants with hMPV bronchiolitis (1 - 6 month of age) accounted for 62% and the male:female ratio was 3.2:1. The patients presented a low-medium grade fever (T < 39 degrees C) accounted for 86%; 81.0% of patients had a white blood cell count lower than 10.0 x 10(9)/L. The radiological findings were patchey opacity in both lungs (68%) and(or) hyperinflation (62%). Assessed by the Lowell score system, 5 out of 21 cases were considered as severe cases. The major clinical findings of hMPV bronchiolitis had no significant difference compared with that of subgroup A hRSV bronchiolitis, and showed longer course of disease than that of subgroup B hRSV bronchiolitis (P < 0.01).</p><p><b>CONCLUSIONS</b>Of the infants with bronchiolitis hospitalized in our hospital from November of 2002 through February of 2003, 16.7% were caused by hMPV infection. These data showed that the major clinical characteristics and the outcome of treatment of hMPV bronchiolitis had no statistically significant difference compared to the cases with either subgroup A or subgroup B hRSV infection.</p>

A preliminary investigation on the serological and epidemiological characteristics of severe acute respiratory syndrome in children / 中华儿科杂志

<p><b>OBJECTIVE</b>The severe acute respiratory syndrome (SARS) is a highly contagious infection caused by a newly discovered strain of coronavirus (SARS-CoV). During the outbreak of SARS in the first half of 2003, children appeared to be less susceptible to the SARS coronavirus and pediatric patients presented with a less aggressive clinical course than adult patients did, demonstrating the traits which were rarely observed in other viral contagious disease. The present study aimed to preliminarily examine the presence of serum specific antibodies against severe acute respiratory syndrome (SARS)-associated coronavirus virus (SARS-CoV) in pediatric SARS patients and explore the possibility of subclinical infection in children/adults through close association with SARS cases.</p><p><b>METHODS</b>(1) Clinicians and nurses visited families and collected general and epidemiological information about the subjects using a standard questionnaire and took serum specimens. (2) Specific antibodies against SARS-CoV were assayed with two methods, indirect immunofluorescence assay (IFA) for detecting IgG antibodies and enzyme linked immunosorbent assay (ELISA) for mixed antibodies. Serum specimens tested included those from 21 clinically confirmed pediatric SARS cases (aged from 8 months to 14 years, 11 male and 10 female) and their 23 parents who had close contact with the children, 36 adult patients in convalescence stage of SARS, 24 children (aged 1.5 to 14 years) and other 34 adults who had close contact with infected adults.</p><p><b>RESULTS</b>(1) The positive rates of specific IgG and mixed antibodies against SARS-CoV were 38% (8/21) and 33% (7/21) in pediatric cases; whereas the rates were 75% (27/36) and 69% (25/36) in adult patients. (2) The proportion of the patients who had close contact to SARS patients was 7/8 among the antibody-positive group vs. 1/13 for the antibody-negative group (P < 0.05). (3) The IgG antibody emerged in one of 24 children, whose mother, a nurse, had suffered from SARS (4%). (4) Among 23 parents of children with SARS, one was positive for IgG and the mixed antibodies, whose grandson and husband suffered from SARS; The IgG antibody and the mixed antibodies were also positive in another adult who had close contact with adult SARS cases (3%).</p><p><b>CONCLUSIONS</b>(1) SARS-CoV infection was confirmed by serological methods in 38.1% of clinically diagnosed pediatric SARS cases, which leads to the assumption that correct diagnosis of pediatric SARS requires more accurate and efficient ways, for example, screening for antigen or gene of SARS-CoV. (2) The proportion of the patients who had close contact to SARS patients among antibody-positive cases was higher than that in antibody-negative cases. (3) It is possible that subclinical SARS CoV infection exists in children and adults, although the rate of occurrence is low. The data of the present study did not confirm that SARS had subclinical infection among adults who had close contact to pediatric SARS cases.</p>