Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare disease in China, and very little large-scale studies have been conducted to date. We aimed to investigate the clinical and genetic features of CGD in Chinese pediatric patients. METHODS: Pediatric patients with CGD from Beijing Children's Hospital, Capital Medical University, China, were enrolled from January 2006 to December 2016. RESULTS: A total of 159 pediatric patients with CGD were enrolled. The median age of clinical onset was 1.4 months, and 73% (116/159) had clinical onset symptoms before the 1 year of age. The most common site of invasion was the lungs. The lymph nodes, liver, and skin were more frequently invaded in X-linked (XL) CGD patients than in autosomal recessive (AR) CGD patients (P < 0.05). Approximately 64% (92/144) of the pediatric patients suffered from abnormal response to BCG vaccination. The most frequent pathogens were Aspergillus and Mycobacterium tuberculosis. Gene analysis indicated that 132 cases (89%, 132/147) harbored CYBB pathogenic variants, 7 (5%, 7/147) carried CYBA pathogenic variants, 4 (3%, 4/147) had NCF1 pathogenic variants, and 4 (3%, 4/147) had NCF2 pathogenic variants. The overall mortality rate in this study was 43%, particularly the patients were males, with CYBB mutant and did not receive HSCT treatment. CONCLUSIONS: Chronic granulomatous disease is a rare disease affecting Chinese children; however, it is often diagnosed at a later age, and thus, the mortality rate is relatively high. The prevalence and the severity of disease in XL-CGD are higher than AR-CGD.

[Clinical analysis of 20 cases with Streptococcus pneumoniae necrotizing pneumonia in China].

OBJECTIVE: Streptococcus pneumoniae necrotizing pneumonia (SPNP) was reported elsewhere but not in China yet. Inappropriate treatment due to poor recognition of this disease could influence its prognosis. This paper presents the clinical characteristics, diagnosis and treatment of SPNP hoping to elevate pediatrician's recognition level for this disease. METHOD: Clinical manifestations, radiological findings, treatment and prognosis of 20 patients (9 boys, 11 girls) who had been hospitalized with SPNP in Beijing Children's Hospital from 2004-2011 were retrospectively analyzed. RESULT: The patients included in this study aged from 9 months to 6 years [(27.9 ± 15.8) m] and were healthy before admission. They were febrile for 8 to 50 days [(27.7 ± 13.5) d] and hospital day was 24 - 55 days [(36.5 ± 8.3) d]. The general condition of all subjects was relatively poor and they all had fever and cough. One child had moderate fever and nineteen children had high fever. Dyspnea was found in sixteen children. Fine rales were found on auscultation in 18 children, among whom diffuse wheeze appeared in 4 children, and wheezy phlegm was found in two children. Signs of pleural effusion were discovered in all cases by physical examination and chest X-ray. White blood cell (WBC) count was 16.2 - 60.95×10(9)/L and neutrophil was 70.5% - 80.2% in peripheral blood routine test. Erythrocyte sedimentation rate (ESR) was 44 - 109 mm/h [(69.6 ± 16) mm/h]and C-reactive protein (CRP) was 80 - > 160 mg/L. The pleural effusion biochemistry and routine test revealed a WBC count of 6400×10(6)/L-too much to count, polykaryocyte of 51% - 90%, glucose of 0.02 - 1.8 mmol/L, protein of 32 - 51 g/L and LDH of 5475 IU/L-or higher. Pleural effusion culture in all cases and blood culture in 2 cases was positive for Streptococcus pneumoniae. Chest X-ray or CT revealed high density and well-distributed lobar consolidation in one lung or two lungs initially. Single or multiple low density lesions in the area of lobar consolidation were found a week later, accompanied by multiple cystic shadow or cavity at the same time or afterwards. Bulla of lung appeared later. Pleural effusions were found in all patients. Seven cases complicated with hydropneumothorax, two with otitis media, one with heart failure, one with cardiac insufficiency. Seventeen patients were treated with vancomycin or teicoplanin or linezolid two with amoxicillin and clavulanate potassium. Other two patients had been treated with meropenem and cephalosporin antibiotics respectively before admission, and they had been at recovery stage when they were hospitalized. Thoracic close drainage and thoracoscopy were performed respectively in 18 cases and 3 cases, respectively. After a follow up of more than 6 months, chest CT showed that almost all lesions in lungs recovered during 4-6 months. No one received pneumonectomy. CONCLUSION: SPNP has special manifestations. The incidence in infants is higher. Patients' general condition is poor and febrile course is relatively long. All patients manifested fever and cough, with a presence of dyspnea in most of them. WBC, neutrophil and CRP elevated apparently. The characteristic of pleural effusion indicates empyema. In early stage, the chest X-ray and CT showed high-density lobar lesions, followed by low-density lesions and cyst gradually. Bulla of lung and/or hydropneumothorax may appear at the late stage. But if diagnosed and treated promptly, the prognosis of SPNP was relatively good.

[Clinical manifestations and gene analysis of 2 Chinese children with cystic fibrosis].

OBJECTIVE: Cystic fibrosis (CF) is rare in Chinese mainland. We present two cases of CF patients diagnosed by gene analysis. Their clinical manifestations and genetic mutation features are analyzed in this article. It will be of special interest to pediatricians in recognition of CF. METHOD: The clinical material of two CF patients who were diagnosed by gene analysis was retrospectively analyzed. RESULT: The first patient is a 13-year-old girl. She had a complaint of recurrent fever and cough for 6 months, expectoration for 2 months and hemoptysis for 20 days. After 3 months of her birth, she was operated on for bullae of lung. She was susceptible to upper respiratory tract infection. There was no family history of recurrent wheeze and other special diseases. Aspergillus fumigatus specific IgE was at grade 3 and aspergillus fumigatus IgG was high. Pseudomonas aeruginosa was positive in sputum culture. Sweat testing was performed and Na+ was higher. Pulmonary CT indicated bronchiectasis. Nasal sinus CT showed optical density of soft tissue within maxillary sinus and chronic bilateral sinusitis. The electron microscopy of cilia suggested immobile cilia syndrome. A heterozygotic mutation (263T > G, 2909G > A) was found after CFTR genetic mutation analysis. Both her parents were carriers. She was treated with inhalation of nebulized hypertonic saline and postural drainage for a long time. And she got better during a follow up period of 1 year. The second patient was a 10-year-old girl who complained of recurrent expectoration for 3 years and shortness of breath for half a year. She had a history of sinusitis and steatorrhea. The family history was normal. Both the lipase and insulin level in blood serum was lower.Pseudomonas aerugino and Aspergillus fumigatus were both positive in sputum culture. Aspergillus fumigatus IgE was normal. Pulmonary CT indicated bronchiolitis and bronchiectasis. Nasal sinus CT showed bilateral maxillary sinusitis. CFTR genetic mutation analysis revealed a homozygous mutation (3196C > T). Her parents and relatives did not participate in this study. Unfortunately, this child died of respiratory failure 3 months after discharge. CONCLUSION: CFTR gene mutation was a main cause of CF. Common symptoms are those of bronchiectasis, pancreatitis and sinusitis. The two Chinese patients were diagnosed by gene analysis. One had a heterozygous mutation (263T > G, 2909G > A) and the other had a homozygous mutation (3196C > T), not ΔF508 which is common in western countries.

[Clinical features of 3 cases with acute interstitial pneumonia in children].

OBJECTIVE: Acute interstitial pneumonia (AIP) is a rare lung interstitial disease in children. This study was conducted to understand the clinical features of the AIP in children. METHOD: The data of the three cases with AIP admitted to our hospital from March 2008 to November 2009 were reviewed. Of the 3 cases, 2 were male, one was female. Their age ranged from 1 year and 4 months to 10 years. The clinical manifestation, pulmonary function test and the high resolution computed tomography (HRCT) and pathology of the lung were studied retrospectively. Tissue specimens of the lung were obtained by video-assisted thoracoscopic biopsy. Viral etiologic examinations for the respiratory syncytial virus, adenovirus, influenza virus, parainfluenza viruses, EB virus, cytomegalovirus, enterovirus and herpes simplex virus were performed. The IgM antibody to Mycoplasma pneumoniae in the serum was also detected. RESULT: All the 3 cases rapidly developed respiratory failure of unknown origin, none of these cases had failure of any other organs. All three cases had cough and dyspnea. No case had the rales and digital clubbing. The examinations for viruses, bacteria and Mycoplasma pneumoniae infection were all negative. No evidence for the diagnosis of connective tissue disease was obtained. The HRCT of the chest showed diffuse alveolar consolidation, air bronchogram and ground glass appearance in the bilateral lungs, and the traction-associated bronchiectasis in areas. All the three cases had the histological proof of diffuse alveolar damage by the biopsy. All the three cases were treated with CPAP and corticosteroid. Two cases were treated with corticosteroid in early stage of the disease, the condition of these cases were improved obviously. The third case was treated with high-dose steroid pulse therapy days, the condition of this case was improved slightly in a month. One year follow-up showed that case 1 and case 2 had no hypoxemia and the HRCT of the chest showed obvious improvement. The pulmonary function of case 2 had restrictive deficiency. CONCLUSION: AIP has a rapidly progressive clinical course leading to respiratory failure. The HRCT of the chest showed alveolar consolidation and ground glass-like change. The pathology of the lung includes diffuse alveolar damage. The prognosis of the AIP in children may be improved by the treatment with respiratory assistance and corticosteroids.

[Clinical features and molecular analysis of 2 Chinese children with autosomal recessive chronic granulomatous disease caused by CYBA mutations].

OBJECTIVE: To summarize clinical and molecular features of two children with autosomal recessive chronic granulomatous disease caused by CYBA mutations. METHOD: The clinical records and CYBA mutations were reviewed for analysis of infections and inflammatory complications. RESULT: The first case was a girl diagnosed with "liver and spleen abscess" in our hospital when she was 2.9 years old, with past history of neonatal impetigo and recurrent purulent lymphadenitis and positive family history. The results of DHR123 flow-cytometry showed that positive phagocytes after phorbol ester (PMA) stimulation was 84.63%. CYBA mutation analysis showed that she had heterozygous 35C > T, Q3X and IVS-2A > G. The second case was a boy diagnosed with "sepsis (salmonella D)" when he was 4 years old with a past history of impetigo, sepsis, perianal abscess, skin infection and positive family history. The results of flow cytometry showed that positive phagocytes after PMA stimulation was 96.13%. CYBA mutation analysis showed that he had homozygous 35C > T, Q3X and his parents were all carriers. All of them had BCG related axillary lymphnode calcification. CONCLUSION: A22CGD cases had recurrent purulent infections (skin, lymphnode, liver and spleen, lung, blood), DHR123 flow cytometric analysis helped the diagnosis of CGD, CYBA mutation analysis ascertained the diagnosis of A22CGD.

[Idiopathic interstitial pneumonias in 7 children].

OBJECTIVE: Idiopathic interstitial pneumonias (IIPs) have been increasing in children in recent years. The type and prognosis of IIPs in children in China has not been clear. The purpose of this study was to investigate the type and prognosis of IIPs in children. METHOD: Seven children diagnosed with IIPs from December 2003 to March 2007 were retrospectively studied. The clinical, radiologic, and pathologic features, type and prognosis of IIPs, were reviewed. RESULT: Of the seven patients with IIPs, three were diagnosed with cryptogenic organizing pneumonia (COP)/bronchiolitis obliterans organizing pneumonia (BOOP), one was diagnosed with usual interstitial pneumonia (UIP) and the remaining three were diagnosed with nonspecific interstitial pneumonia (NSIP). The chief complaints of these patients were chronic cough. Six patients had shortness of breath. Clubbed fingers were found in one patient with UIP and two patients with NSIP. The characteristic computed tomographic findings of COP/BOOP were multiple patchy peripheral consolidation, associated with centrilobular nodules and bronchiole wall thickening in 2 cases and bronchiolectasis in 1 case. In NSIP, diffuse or basal ground-glass opacities predominated over reticular opacities with traction bronchiectasis only in one case. UIP was manifested by patchy infiltrate with predominant honeycombing, traction bronchiectasis and interlobular septal thickening. Two patients with COP/BOOP had plugs of connective tissue within a bronchiole and the adjacent alveolar ducts and alveolar spaces. Lung biopsies showed predominantly interstitial chronic inflammation with infiltrate of lymphocytes and some plasma cells and alveolar septum thickening in three patients with NSIP. One case with NSIP showed a mixed fibrosing and prominent interstitial chronic inflammation. The key histological findings of the UIP was a heterogeneous appearance, with alternating areas of relatively normal lung, interstitial inflammation and fibrosis. All patients were treated with prednisone. The abnormal findings of chest radiography resolved completely after four to twelve months' therapy in three patients with COP/BOOP. The combination of prednisone and MTX or 6-MP was given to the two patients with NSIP. The symptoms and chest radiographic abnormality disappeared except the presence of a few cyst after treatment. One case with NSIP and the case with UIP had not been improved remarkably. CONCLUSION: COP/BOOP, NSIP and UIP might occur in children in China. The typing of IIPs was based on clinical-radiologic-pathologic features. Steroid was the first choice for IIPs. The prognosis of IIPs varied among different types.

[Clinical analysis of 18 children with disseminated Bacille Calmette-Guérin infection].

OBJECTIVE: To explore the clinical manifestation, immune abnormality and outcome of disseminated Bacille Calmette-Guérin (BCG) infection in children. METHOD: The clinical data of 18 children with disseminated BCG infection seen from January 2000 to December 2007 were analyzed retrospectively. RESULT: Thirteen of the children were male among 18 patients. Disseminated infection first appeared in armpit lymph nodes ipsilateral to the vaccination site, then spread to lungs in 15, lymphnodes of mediastinum or abdominal cavity in 18, skin and soft tissues in 5, skeletons in 4, liver in 4, spleen in 8, kidney, adrenal gland or meninges in 3. Twelve children were diagnosed to have primary immunodeficiency; 3 had severe combined immunodeficiency (SCID); 7 had chronic granulomatous disease (CGD), 2 had IL-12/IFN-gamma passageway deficiency. Eleven of the 18 patients died, and the remaining 7 patients were followed up from 1 to 9 years and are alive at present, but presented recurrent skin and bone tuberculosis in 4 and recurrent other infection in 3. CONCLUSION: Most Children with disseminated BCG infection had primary immunodeficiency. CGD and IL-12/IFN-gamma passageway deficiency accounted for considerable proportion, so special immune function should be detected in these patients. The prognosis was poor. The type of the immunodeficiency diseases should be identified in early stage and the specific immune treatment should be given to the patients.

[Diagnosis and treatment of invasive pulmonary aspergillosis in 21 children with non-hematologic diseases].

OBJECTIVE: To explore diagnosis and treatments of invasive pulmonary aspergillosis (IPA) in children with non-hematologic diseases. METHOD: Twenty one patients without hematological malignancy were diagnosed with proven or possible IPA from July 2002 to June 2008. The risk factors, clinical manifestations, chest radiographic findings, microbiological and histopathological evidence, diagnostic procedures, treatment and prognosis were retrospectively reviewed. RESULT: Five children had proven IPA, and 16 patients had possible IPA. Thirteen children were classified as having acute invasive pulmonary aspergillosis (AIPA), eight children as having chronic necrotizing pulmonary aspergillosis (CNPA). Definitive diagnosis of primary immunodeficiency (PID) was made in 6 children (4 with chronic granulomatous disease, 2 with cellular immunodeficiency); three children were suspected of having PID. Corticosteroids and multiple broad-spectrum antibiotics had been administered in 5 patients (3 of these 5 patients also had invasive mechanical ventilation). Two children had underlying pulmonary disease. Three patients had unknown risk factors. Among these three patients, two had history of environmental exposure. Fever and cough were present in all the children. Fine rales were found in nineteen children. Six children had hepatosplenomegaly. The common roentgenographic feature of AIPA in 13 patients was nodular or mass-like consolidation with multiple cavity. "air-crescent" was seen in 10 of patients with AIPA. Lobar consolidation with cavity and adjacent pleural thickening was found in all children with CNPA. The positive rate of sputum and/or BALF culture in AIPA and CNPA were 72.1% and 22.4%, respectively. A large number of septate hyphae on wet smear were found in all of the children whose sputum and/or BALF culture were positive. Lung biopsy was performed in 3 children with CNPA, and necrosis, granulomatous inflammation, as well as septate, branching hyphae were observed on histopathologic examination. Fifteen children were treated with anti-fungal therapy (amphotericin B, voriconazole, itraconazole and caspofungin used alone or in combination), symptoms and lung lesions resolved in 12 children. Three children died. Six children did not receive anti-fungal therapy and died. The side effects of amphotericin B include chill, fever, hypokalemia and transient increase in BUN, none of which needed discontinuation of the antifungal therapy. Children had a good tolerance to fluconazole and caspofungin, there were no apparent side effects. CONCLUSION: Most of the children without hematologic diseases who suffered from invasive pulmonary aspergillosis had risk factors or exposure history. Roentgenographic findings were relatively characteristic for invasive pulmonary aspergillosis. Risk factors and roentgenographic findings were clues to consider clinically invasive pulmonary aspergillosis. Sputum culture was the key point to clinical diagnosis. The patients in whom the antifungal therapy was initiated early had a good outcome.

[Association of NRAMP1 gene polymorphisms with the susceptibility to tuberculosis in ethnic Han Chinese children].

OBJECTIVE: Tuberculosis is still a public health problem. Host genetic factors, such as polymorphisms in NRAMP1 gene, may play a role in the development of tuberculosis. To clarify the effect of NRAMP1 gene polymorphisms on the development of childhood tuberculosis, the association of NRAMP1 gene polymorphisms with susceptibility to tuberculosis in the ethnic Han Chinese children was investigated. METHODS: From January 2005 to March 2008, 130 ethnic Han children with tuberculosis (TB group) were enrolled. Three hundred and ninety hospitalized ethnic Han children for physical examination in the surgery department were used as the control group. The controls were matched with tuberculosis children by age, sex and area. PCR-RFLP analysis was performed on DNA samples to identify allele genotypes of INT4 and D543N in NRAMP1 gene. Genotype frequency differences between tuberculosis patients and controls were analyzed using x2 test. RESULTS: No statistical difference was found in the genotype frequency of variants G/C and C/C at the INT4 locus between the TB and the control groups. At the D543N locus, the frequency of genotype variants (G/A and A/A) was significantly higher in the TB group (34/130) than that in the control group (66/390) (x2=5.349, P<0.05; OR=1.74, 95%CI=1.08-2.79). When stratified by sex, differences in the genotype distribution were observed only in females at the D543N locus, which the variant genotypes were higher in the TB group (16/52) than in the control group (21/155) (x2=7.866, P<0.05; OR=2.84, 95%CI=1.34-5.99). For males, there was no difference between the TB and the control groups. At the INT4 locus, no difference was observed between the two groups in boys and girls. CONCLUSIONS: Genotypic variation at the D543N locus in NRAMP1 gene may be associated with susceptibility to tuberculosis in ethnic Han Chinese children. Variant genotypes in NRAMP1 gene (G/A and A/A) may be susceptible genotypes to tuberculosis in ethnic Han Chinese children. Girls with variant genotypes were more susceptible to tuberculosis.

[Diffuse panbronchiolitis in a child: case report and literature review].

OBJECTIVE: Diffuse panbronchiolitis (DPB) is a chronic progressive disease of the lower respiratory tract, which is prevalent in Asian population. So far, many DPB cases have been found in adults in China. To our knowledge, no pediatric DPB case has ever been reported in China. We describe the first pediatric DPB case in Chinese literature and the second case in the English-language literature. METHOD: The clinical manifestations, characteristic imaging and histological features of this DPB case were summarized. RESULTS: The patient was a 13-year old girl complained of chronic productive cough with wheezing. Chest auscultation revealed fine moist rales and wheezing over both lung fields. The chest X-ray showed small nodules and reticular opacities in left lower lobe. High-resolution thorax computerized tomography (HRCT) demonstrated bilateral diffuse small centrilobuler nodules and bronchial wall thickening or bronchiectasis in some parts of the lungs. Histopathological examination of transbronchial biopsy specimen revealed lymphocytes and foamy histocytes infiltrated in the walls of bronchi, respiratory bronchioles and adjacent alveoli. Lymphoid follicles were present around some bronchi. Sinus radiographs revealed sinusitis. Lung function studies showed obstruction and restriction. PaO2 was 65 mm Hg. The diagnosis of DPB was made according to the current diagnostic criteria. Low-dose erythromycin [5 - 10 mg/(kg.d)] was effective. CONCLUSION: DPB could occur in children in China. The major diagnostic clues may include the following: (1) persistent cough, sputum, and dyspnea; (2) coexistent chronic sinusitis; (3) bilateral diffuse small nodular opacities on HRCT. Low-dose erythromycin was effective in treatment of the case with DPB.

[Galectin-7 is associated with bronchial epithelial cell apoptosis in asthmatic children].

OBJECTIVE: It is supposed that bronchial epithelial cells responses to the environmental stimuli are different between asthmatic and non-asthmatic individuals, which contribute to the pathogenesis of asthma. These different responses produce different mediators. If differential gene expressions are found in bronchial epithelial cells of asthmatic and non-asthmatic individuals after the same stimuli in vitro, and these genes are overexpressed in asthmatic children in vivo, then it is concluded that these genes may be associated with asthma. Therefore the authors analyzed the differential gene expressions in the bronchial epithelium cells of asthmatic and non-asthmatic children after RSV infection in vitro. Among these genes, Galectine-7 (lectin, galactoside-binding, soluble, 7, Galectin-7) was 8 times up-regulated in asthmatic children. Galectine-7 was associated with skin keratinocyte apoptosis. The authors hypothesized that Galectin-7 may also be associated with bronchial epithelial cell apoptosis in asthmatic children. The aim of this study was to understand the role of Galectine-7 in bronchial epithelial cell apoptosis in asthma. METHODS: The bronchial mucosae of one asthmatic child and one non-asthmatic child were obtained by biopsy and cultured in vitro. The bronchial epithelial cells were infected by RSV. The differential gene expressions were analyzed with micro array. Among those differentially expressed genes, Galectin-7 was 8 times up-regulated in asthmatic children. The bronchial mucosae from 10 asthmatic children and 17 non-asthma children were investigated for cell DNA break, Galectine-7 and mRNA expression, Caspase-3 expression by TUNEL, hybridization in situ and immunochemistry. Image analysis was used for quantitative assessment. RESULTS: Galectine-7 gene was 8 times up-regulated in bronchial epithelial cells from asthmatic children after RSV infection in vitro. Galectin-7 and mRNA were overexpressed in bronchial epithelial cells in asthma in vivo. Bronchial epithelial cell apoptosis increased in asthma in vivo. CONCLUSION: Galectin-7 may be associated with bronchial epithelial cell apoptosis in asthma.

[Diagnosis and treatment of chronic pulmonary aspergillosis in 4 children].

OBJECTIVE: Chronic pulmonary aspergillosis is different from acute pulmonary aspergillosis in clinical picture, radiogram, diagnostic procedures and prognosis. Four patients with chronic pulmonary aspergillosis had been misdiagnosed as having pneumonia or pulmonary tuberculosis for a long time before admission to the hospital. The purpose of this report was to summarize the clinical manifestations and laboratory findings for correct diagnosis of chronic pulmonary aspergillosis. METHODS: Four patients with chronic pulmonary aspergillosis seen between October 2002 and October 2004 were retrospectively studied. Their clinical manifestations, chest radiographic feature, immune status, diagnostic procedure, therapy and prognosis were reviewed. RESULTS: The chief complaints of these patients were chronic cough and fever for 3 to 12 months. Chest wall abscess developed in the late course in case 1 and 4. Fine moist rales were heard and hepatosplenomegaly was found in case 1 and 2. No abnormal sign was found in case 3 and 4. Chest radiographic feature: lobar consolidation with adjacent pleural thickening was present in all cases. In early phase, solitary or multiple small nodules were found in 2 cases. Case 1-3 had normal IgG, IgM, IgA, IgE, T Cell subsets and NBT test. Case 4 had chronic granulomatous disease. Etiologic evidences: culture was positive for Aspergillus (A.) fulmigatus in sputum and in chest wall abscess in case 1 and 4; for A. niger in sputum and spore existing in lung tissue in case 2; for A. fulmigatus in sputum and hypha existing in lung tissue in case 3. All patients were treated with combination of amphotericin B and itraconazole. Their symptoms were controlled 10-30 d after treatment. In case 1 the disease relapsed 6 months later and the patient died at last due to giving up treatment by his parents. Case 2 was free of symptom for 12 months and his chest radiographic lesion disappeared completely 6 months later. Treatment of case 4 was given up. Case 3 continued to receive treatment and observation. CONCLUSION: Chronic pulmonary aspergillosis should be considered in children with long period fever and cough and lobar consolidation associated with adjacent pleural thickening or with nodular infiltration. The diagnosis of chronic pulmonary aspergillosis depended on identification of aspergillus from sputum or lung tissue. Combined amphotericin B and itraconazole might control the disease.

[Clinical feature of four cases with bronchiolitis obliterans].

OBJECTIVE: To recognize the clinical features of the bronchiolitis obliterans. METHOD: Clinical manifestation, chest X-ray, computed tomography (CT) and pulmonary function of 4 cases with bronchiolitis obliterans were retrospectively analyzed. RESULT: Two cases were after Stevens-Johnson syndrome (SJS), the other 2 were after severe pneumonia, including one suffered from adenovirus pneumonia. Cough, tachypnea and wheezing persisted in all the 4 patients. The symptoms lasted for at least 6 weeks, in one case for over one year. Crackles and wheezing were present in all the 4 cases. Hyperinflation was seen in chest radiographs in all cases. On pulmonary CT/high-resolution CT (HRCT), patchy opacity and bronchial wall thickening were seen in each patient. Areas of air trapping were seen in three cases. Bronchiectasis was seen in 2 cases, atelectasis and mosaic perfusion were seen respectively in one case. PO(2) was low in all the four cases. Wheezing was not responsive to beta(2) agonist and other bronchodilating therapy. Prednisone was used at a dose of 1 mg/(kg.d) in 3 cases. Two cases were followed up for 3 months. The clinical condition of one case was improved, whose wheezing and bronchiolar constriction disappeared, cough and dyspnea were also relieved. However, the condition of one patient was not improved, although the wheezing disappeared. The HRCT of these two cases showed no improvement. CONCLUSION: Clinical symptoms of BO were cough, tachypnea, and wheezing after acute lung injury. Crackles and wheezing were the most common signs in the BO. Chest radiographs showed hyperinflation. Pulmonary CT showed bronchial wall thickening, bronchiectasis, atelectasis, and mosaic perfusion. Pulmonary function tests suggested obstruction of small airway.

[Causes and diagnostic procedure of diffuse lung disease in 28 children].

OBJECTIVE: Diffuse lung disease comprises a large, heterogeneous group of pulmonary interstitial and parenchymal disease. It is therefore difficult to some extent to make etiologic diagnosis. Little information on clinical spectrum and diagnostic evaluation of pediatric diffuse lung disease is available in our country. The purpose of this study was to explore the causes of and diagnostic approach to diffuse lung disease in children. METHODS: Twenty-eight children with diffuse lung disease aged 2 months to 14 years were studied retrospectively. Their history, physical examination, radiographic findings, final diagnosis and diagnostic processes were reviewed. RESULTS: Confirmed diagnosis was established in 25 cases and suggestive diagnosis in 3 cases. Confirmed diagnoses included: mycoplasma pneumonia in 1 case, Chlamydia trachomatis pneumonia in 2 cases, Epstein-Barr virus pneumonia in 1, CMV pneumonia in 2, hematogenous disseminated pulmonary tuberculosis in 3, pulmonary cryptococcosis in 1, invasive pulmonary aspergillosis in 2, Staphylococcus aureus sepsis in 1, diffuse bronchiectasis in 2, idiopathic pulmonary hemosiderosis in 1, idiopathic pulmonary fibrosis in 1, extrinsic allergic alveolitis in 1, HIV-related lymphocytic interstitial pneumonitis in 1, Wegner's granulomatosis in 1, Langerhan's cell histiocytosis in 2, and lymphoma in 3. Suggestive diagnoses included Nocardia pneumonia in 1, Pneumocystis carinii pneumonia in 1, and juvenile rheumatoid arthritis-associated pulmonary fibrosis in 1. The diagnostic directions of 26 patients were conducted by radiographic features. In 17 of 26 cases, the diagnostic range was confined by history. The diagnosis of 14 cases was made by noninvasive tests including antibody detection, bacterial culture, those of 8 cases by examination of biopsy material, and those of 2 cases by autopsy. CONCLUSIONS: The causes of pediatric diffuse lung disease included pulmonary infectious disease, idiopathic pulmonary disease and pulmonary lesion associated with systemic diseases. The diagnosis may be made by radiography, history, physical examination, noninvasive tests in most cases, while in some cases invasive procedures were necessary.