儿童囊性纤维化并发变应性支气管肺曲霉菌病1例报告并文献复习

目的 分析囊性纤维化(CF)并发变应性支气管肺曲霉菌病(ABPA)的临床特征.方法 回顾分析1例确诊为CF并发ABPA患儿的临床资料,分析近10年PubMed、中国知网、万方数据库中报道CF并发ABPA的资料.结果 11岁患儿,男,曾诊断哮喘,因持续咳嗽、喘息入院,初步确诊ABPA.基因检测显示患儿CFTR基因变异,汗...     

Allergic bronchopulmonary aspergillosis complicating childhood asthma

While Allergic bronchopulmonary aspergillosis (ABPA) is known to complicate asthma in adults, its association with childhood asthma is very rare. We present two patients, a four-and half year old boy who presented with severe asthma and a 12 year-old girl whose previous chest radiographs revealed fleeting opacities. Both were diagnosed to be suffering from ABPA.     

Aspergillus and the paediatric lung

Aspergillus spp produce a wide range of saprophytic and invasive syndromes in the lungs, including allergic bronchopulmonary aspergillosis (ABPA), aspergilloma and invasive pulmonary aspergillosis (IPA). ABPA results from hypersensitivity to the fungus, and mainly affects patients with asthma or cystic fibrosis (CF). The treatment of choice consists of systemic corticosteroids and itraconazole. Aspergilloma is managed by observation or surgery. IPA is predominantly seen in patients with haematological malignancies, chronic granulomatous disease or immunosuppressive treatment. With the use of aggressive therapies for end-stage CF, such as heart-lung transplantation, the potential for a patient to convert from colonization or ABPA to IPA has increased. Suggestive clinical and radiological findings, supplemented with mycological data using serology and molecular biology, have enhanced the capacity to diagnose IPA in paediatric patients. While voriconazole is considered the first-line therapy in IPA, several other antifungal agents may be appropriate alternatives.     

Pneumonia in the first 2 years of life,and asthma in preschool‐age children

Background: The relationship between viral bronchiolitis in early infancy and subsequent wheezing and asthma has been well established. The aim of the present cross‐sectional study was to test the hypothesis that pneumonia severe enough to require hospitalization during the first 2 years of life could also be associated with asthma or asthma‐like symptoms in pre‐school children. Methods: Structured interviews were conducted with parents of children who were classified as exposed (n= 36) or non‐exposed (n= 84), based on whether they were hospitalized with radiologically confirmed pneumonia during the first 2 years of life. The main outcomes were ever physician‐diagnosed asthma, asthma‐like symptoms and use of anti‐asthmatic medications during the last 2 months and during the last 12 months. Results: The prevalence of ever physician‐diagnosed asthma was higher in the exposed group compared with the non‐exposed group (41.6% vs 22.6%, P= 0.01), with an adjusted prevalence ratio of 2.03 (95% confidence interval: 1.10–3.62). The exposed group had a trend toward a higher prevalence of asthma‐like symptoms and use of anti‐asthmatic medications during the last 2 months and during the last 12 months. Conclusions: Radiologically confirmed pneumonia in the first 2 years of life may be associated with asthma or asthma‐like symptoms in pre‐school children.     

Allergic bronchopulmonary aspergillosis in paediatric cystic fibrosis patients

Allergic bronchopulmonary aspergillosis (ABPA) is a severe complication in children, adolescents and adults with cystic fibrosis (CF), the prevalence of which ranges from 6-25%. The disease is the result of the colonisation of the respiratory tract by fungi of the genus Aspergillus, commonly Aspergillus fumigatus, and subsequent host sensitisation to fungal antigens, accompanied by a Th2 CD4 type response mediated by the production of specific IgE. The consequent inflammatory and obstructive bronchopulmonary injury can progress to fibrosis. The diagnosis should be considered early in patients with CF who show wheezing, transient pulmonary infiltrates and reduced lung function. The objective diagnosis is not straightforward because of overlapping clinical and radiological signs, particularly the progression of bronchiectasis. Specific criteria are needed for the diagnosis of ABPA in patients with CF, such as those proposed by the Cystic Fibrosis Foundation. The study of specific IgE against recombinant antigens of A. fumigatus has contributed to the early diagnosis of ABPA with high sensitivity and specificity. The technique has also shown promise in the follow-up of patients after steroid therapy and the early detection of recurrences. Treatment consists of long-term systemic corticosteroid usage, the monitoring of their adverse effects, and of the measurement of total serum IgE levels. The concomitant use of oral itraconazole seems to promote a better control of the disease and to reduce the duration of systemic steroid therapy but its use continues to be controversial. Controlled studies involving larger numbers of patients are necessary if we are to better understand the management of ABPA.     

16q12 microdeletion syndrome in two Japanese boys

Microdeletion of 16q12 is a rare chromosomal abnormality. We present the cases of two Japanese patients with developmental and renal symptoms of differing clinical severity. Both patients had 16q12 interstitial microdeletions that included the entire SALL1 gene. Patient 1 was a 15‐year‐old Japanese boy clinically diagnosed with branchio‐oto‐renal syndrome with mild developmental delay, but with no imperforate anus or polydactyly. Array comparative genome hybridization (aCGH) indicated a 5.2 Mb deletion in 16q12, which included SALL1. Patient 2 was a 13‐year‐old Japanese boy diagnosed with Townes–Brocks syndrome and severe developmental delay, epilepsy, and renal insufficiency requiring renal replacement therapy. Fluorescence in situ hybridization indicated deletion of the entire SALL1 gene. Subsequent aCGH showed a 6 Mb deletion in 16q12q13, which included SALL1. Precise analysis of the present two cases will give us some clues to elucidate the pathogenic mechanisms of 16q12 microdeletion syndrome.     

Die allergisch-bronchopulmonale Aspergillose bei zystischer Fibrose

Early diagnosis of allergic bronchopulmonary aspergillosis in patients suffering from cystic fibrosis (CF) is difficult because mild ABPA and severe forms of CF share common clinical features difficult to be clearly assigned to one of the diseases. This could explain “silent” cases of ABPA already showing distinct radiological and immunological changes not sufficient for a clear cut diagnosis of the disease. Therefore, the diagnosis of ABPA is often made in late stages compromising an efficient patient’s management. However, for disease management a reliable diagnostic screening followed by a rapid therapy would be essential. Classical diagnostic criteria established in clinical practice and new studies performed during the last years which contributed to an improved diagnosis and therapy of ABPA in CF are summarized here in a position paper aimed to help the clinicians treating CF patients in diagnosing ABPA.     

Long-term respiratory symptoms following oesophageal atresia

Background: Oesophageal atresia (OA) is a congenital malformation that can lead to persistent respiratory symptoms in adulthood. Aim: To describe the prevalence of respiratory symptoms in adulthood in a population‐based study of patients with repaired OA and to compare this with the prevalence in the general population. Methods: Of 80 patients operated for OA in Gothenburg in 1968–1983, 79 were located. The patients received a questionnaire on respiratory symptoms. Controls were 4979 gender‐ and age‐matched subjects who answered the same questions. Results: The questionnaire was answered by 73 of 79 (92%) patients. Physician‐diagnosed asthma was reported by 30% in the OA group vs 10% in the control group (OR 4.1; 95% CI 2.4–6.8), and recurrent wheeze in 29% vs 5.5% (OR 6.9; 4.1–11.6). Also wheeze during the last year, asthma medication, a long‐standing cough, cough with sputum production and chronic bronchitis were significantly more common among the patients with OA. In contrast, there was no significant difference regarding risk factors for asthma. The prevalence of respiratory symptoms did not appear to decrease with age. Conclusion: A high prevalence of respiratory symptoms remains among adult patients with repaired OA. Many of the patients had an asthma diagnosis. However, asthma heredity or allergic rhinitis was not overrepresented.     

Epidemiological studies of the very high prevalence of asthma and related symptoms among school children in Costa Rica from 1989 to 1998

The aim of our study was to determine the prevalence of asthma and related respiratory symptoms in school children from Costa Rica during the last 10 years, from 1989 to 1998. Using nationally representative samples of school children from Costa Rica during the last 10 years we have performed three studies. Altogether 9931 children were investigated. The age groups: study I, 5–17 years (n = 2682), study II, 6–7 years (n = 2944), 13–14 years (n = 3200) and study III, 10 years (n = 1105). The diagnostic criteria for asthma used in these studies was as follows: study I (1989), diagnosis by a doctor in combination with the presence of four kinds of respiratory symptoms; studies II (1995) and III (1998), history of wheeze in the past 12 months. The two latter were part of the International Study of Asthma and Allergies in Childhood (ISAAC). A very high prevalence of a history of wheezing was found in the three studies (46.8%, 42.9%, and 45.1%) as well as a diagnosis of asthma (23.4%, 27.7% and 27.1%). The physician's diagnosis of asthma reported in the first study (23%) increased from 23.1 in study II to 27.7% in study III (p = 0.004). This increment could be a real increase in asthma prevalence, or be due to a better awareness about asthma. In study II the group of 6–7‐year‐olds had respiratory symptoms significantly more often than 13–14‐year‐olds (p < 0.001). Boys more often had a history of wheezing (p = 0.001), wheeze during the previous 12 months (p = 0.01) and an asthma diagnosis at the age of 6–7 years (p = 0.002) than girls, but girls had more respiratory symptoms than boys at the age of 13–14 years (p < 0.005). Wheezing in the past 12 months was more common for those living in urban areas aged 6–7 years (p = 0.04), and there was an increase of wheeze after exercise (p = 0.01). For the 13–14‐year‐olds the risk of wheezing was higher during the previous 12 months if they lived in temperate areas (<20°C) and at a high altitude (>1000 m). Living in a rural area and in a warm region (>20°C), increased the risk of dry cough during the previous 12 months in the group of 13–14‐year‐olds. In conclusion, Costa Rica is located in the tropics with a very high humidity, an enormous variety of flora and fauna and a very high prevalence of mite and cockroach allergens, which provide important risk factors that may explain the high prevalence of asthma and asthma‐related symptoms. Further possible factors, such as the change towards a more Western life style, resulting in fewer infections and parasitic diseases in the first years of life and changes in bedding material, may also be unresolved. Increased environmental pollution may add to the very high prevalence of asthma and related respiratory symptoms. The very extensive exposure to mites and cockroaches in bed material and in homes with poor ventilation may be an important factor, but many asthmatic children behave as non atopic, with a viral respiratory infection as a major precipitating factor.     

The indication and effectiveness of low‐dose erythromycin therapy in pediatric patients with bronchial asthma*

Korematsu S, Yamamoto K, Nagakura T, Miyahara H, Okazaki N, Akiyoshi K, Maeda T, Suenobu S‐i, Izumi T. The indication and effectiveness of low‐dose erythromycin therapy in pediatric patients with bronchial asthma.
Pediatr Allergy Immunol 2010: 21: 489–492.
© 2010 John Wiley & Sons A/S To elucidate the mechanisms of intractable pediatric bronchial asthma and the indication of low‐dose erythromycin (EM) therapy, the serum chemokine levels of and the angiogenic factor were evaluated in 55 pediatric patients with bronchial asthma; 7.4 ± 3.5 yr old, who had been treated with inhaled steroid, leukotriene receptor antagonist, theophylline and others for more than a year. Both the levels of interleukin (IL) 8 (p = 0.036) and vascular endothelial growth factor (VEGF) (p = 0.005) were higher in patients with severe type than those of patients with the milder type, while other chemokine levels such as serum eotaxin and MCP1 did not show the correlation with the severity of bronchial asthma. Induction of therapy with low‐dose EM induced improvement of the clinical symptoms in patients with severe type and decrease of their serum chemokine levels: IL8; from 736 ± 88 to 75 ± 85 pg/ml (p < 0.0005), and VEGF; from 352.0 ± 160.5 to 132.2 ± 59.9 pg/ml (p = 0.021) within the next 6 months. Moreover, low‐dose EM resulted in a decreased daily peak‐trough fluctuation rate of the serum theophylline concentration; (C_max ? C_min)/C_min, from 1.3 ± 0.5 to 0.5 ± 0.3, which led to the maintenance of effective serum levels. These results indicated that IL8 and VEGF affect the severity of standard therapies resistance intractable bronchial asthma. Through the suppression of these chemokines and maintenance of effective theophylline levels, low‐dose EM therapy improves the symptoms of bronchial asthma.     

Japanese familial case of myoclonus–dystonia syndrome with a splicing mutation in SGCE

Myoclonus–dystonia syndrome (MDS) is a rare autosomal‐dominant movement disorder characterized by brief, frequently alcohol‐responsive myoclonic jerks that begin in childhood or early adolescence, caused by mutations in the ε‐sarcoglycan gene (SGCE). The patient was a 6‐year‐old boy. At 2 years 8 months, he had abnormal movement when he ran due to dystonia of his left leg. At 3 years 5 months, he exhibited dystonia and myoclonic movement of his arms when eating. Myoclonus was likely to develop when he felt anxiety or exhaustion. Genomic DNA showed a heterozygous mutation in SGCE (c.109 + 1 G > T). His father and uncle with the same mutation also experienced milder dystonia or myoclonic movements. SGCE mutation can cause a broad range of clinical symptoms between and within families. We should consider MDS as a differential diagnosis for patients with paroxysmal walking abnormalities and/or myoclonic movements.     

Asthma and Fungus: Role in Allergic Bronchopulmonary Aspergillosis (ABPA) and Other Conditions

Asthma is an allergic, respiratory disorder characterized by hyper responsiveness of the airway to external stimuli. Considerable research is currently being directed towards understanding the role of environmental and genetic factors contributing to the development of asthma and its severity. Recent years have seen a substantial rise in evidence linking fungi to asthma. Few major clinical conditions associated with fungal sensitization and hypersensitive immune response are Allergic bronchopulmonary aspergillosis (ABPA), Allergic fungal rhinosinusitis (AFRS) and Severe asthma with fungal sensitization (SAFS). The most common fungi implicated in these conditions belong to genus Aspergillus, although an association with several other fungi has been described. In this review authors discuss the varying clinical characteristics of fungus induced respiratory complications in individuals with asthma. They also highlight the epidemiology of these conditions including their prevalence in children and their fungal etiological profile. Laboratory diagnostic methods and clinical case definitions have also been discussed. Future studies evaluating the role of fungal exposure and susceptibility to asthma are required. Till date there are no guidelines for the diagnosis and treatment of ABPA in pediatric population, thus it is also imperative to establish validated clinical definitions of fungal allergic manifestations in pediatric patients with asthma to fully understand this complex interaction.     

Asthma severity in childhood,untangling clinical phenotypes*

Lang A, Mowinckel P, Sachs‐Olsen C, Riiser A, Lunde J, Carlsen K‐H, Lødrup Carlsen KC. Asthma severity in childhood, untangling clinical phenotypes.
Pediatr Allergy Immunol 2010: 21: 945–953.
© 2010 John Wiley & Sons A/S Assessment of childhood asthma severity and asthma control encompasses heterogeneous clinical presentations. The relationship between patterns of asthma symptoms and objective measurements is poorly defined in paediatric asthma. This study includes 115 asthmatic schoolchildren, of which 31 were at inclusion defined as Problematic severe asthma because of inadequate asthma control in the presence of high‐dose inhaled corticosteroid (HD‐ICS) treatment and at least one other asthma controller drug. Two partially overlapping clinical outcomes were defined irrespective of severity classification (Exacerbations and Chronic persistent asthma) in patients with uncontrolled asthma. The same symptom criteria were used as for Problematic severe asthma, but disregarding current medication. Lung function, exhaled nitric oxide (FE_NO), bronchial hyperresponsiveness, allergic sensitization and Quality of life (QoL) in the symptom subgroups were compared to children with well‐controlled asthma. Multifactor analysis was performed to assess the relative explanatory power of clinical asthma presentations and of HD‐ICS treatment on objective measurements. Whereas children included in the Exacerbations subgroup had objective features similar to patients with well‐controlled asthma, the Chronic persistent asthma subgroup demonstrated significantly reduced lung function, increased immunoglobin E, allergic poly‐sensitization and impaired QoL, similar to that in patients pre‐defined as Problematic severe asthma. The presence of chronic asthma symptoms was a significant explanatory factor for reduced lung function, QoL and increased FE_NO in multifactor analysis. Differences in objective measurements suggest that children with Chronic persistent asthma and those who are symptomatic predominantly during exacerbations may represent distinct phenotypes of childhood asthma with different clinical prognoses.     

Extremely elevated cerebrospinal fluid protein levels in a child with neurologic symptoms: Beware of haemophagocytic lymphohistiocytosis

Neurologic symptoms can be the initial manifestation of haemophagocytic lymphohistiocytosis (HLH). In this case study, we present a 3-year old boy with a clinical picture of encephalitis, a cerebrospinal fluid (CSF) protein level up to 1165 mg/dl and diffuse cerebral MRI abnormalities. The diagnosis of HLH was established only 6 weeks after initial presentation. The boy recovered after HLH therapy with persisting mild cognitive defects. Genetic investigation demonstrated X-linked lymphoproliferative disease (XLP) as the underlying cause of HLH. The extremely elevated protein level in CSF in this case has not yet been reported in patients with HLH.     

Vocal cord dysfunction in three children - misdiagnosis of bronchial asthma?

Vocal cord dysfunction (VCD) is a paradoxical function of the vocal cords, leading to intermittent predominantly inspiratory dyspnea, but with no response to bronchodilator and anti-inflammatory drug therapy. We report on three children with VCD: 1) A 12-year old boy, who was treated for many years for bronchial asthma and who presented with inspiratory dyspnea and a functional reduction of the inspiratory and expiratory flow-volume curve, 2) a 13-year old girl who was also treated for bronchial asthma on a long-term basis and in whom the paradoxical vocal cord movement could be demonstrated by laryngoscopy, and 3) a 17-year old girl who, besides clinical symptoms of bronchial asthma in her anamnesis, suffered from an intermittent severe inspiratory dyspnea, refractory to bronchodilator treatment. Laryngoscopy proved the diagnosis of VCD. No patient showed a deterioration on discontinuation of their antiasthmatic therapy. VCD is best diagnosed by assessment of the vocal cords during laryngoscopy. The following therapeutic measures are helpful: 1) Demonstration of diagnosis (e.g. videodocumentation of laryngoscopy) and reassurance of patients and parents, 2) speech therapy, and 3) psychological intervention and/or psychotherapy. Our three cases point to a differential diagnosis of recurrent dyspnea in children and adolescents which may be overlooked. It is important to question earlier diagnoses, and to objectively evaluate the type of dyspnea.     

Markers of eosinophilic inflammation and tissue re-modelling in children before clinically diagnosed bronchial asthma

Chronic inflammatory changes in the bronchial mucosa have been well documented in patients with established asthma. Much less is known of the changes, which occur in the airways of children early in the evolution of their disease with most of the information based on indirect markers of inflammation only. We evaluated markers of inflammation and tissue re-modelling in bronchial biopsies from children with early respiratory symptoms before a clear clinical diagnosis of bronchial asthma could be made. We examined bronchial biopsies performed in 27 children between the ages of 1.2 and 11.7 yr who were bronchoscoped for a clinical indication because of recurrent or chronic respiratory symptoms. The patients were re-evaluated 22-80 months after the original bronchoscopy to determine whether or not they had subsequently developed bronchial asthma. There were more eosinophils in the bronchial mucosa (129.4 vs. 19.1 cells/mm2 of lamina propria, p <0.001) and the thickness of the subepithelial lamina reticularis was greater (4.65 vs. 3.72 microm, p=0.044) in children with bronchial asthma diagnosed at follow-up, compared with the children who did not progress to asthma. Eosinophilic inflammation and airway re-modelling occur early in the natural history of bronchial asthma and are present even before asthma would be diagnosed based on clinical symptoms. Recognition of these changes and their significance for clinical disease should emphasize the need for timely detection and diagnosis of asthma in children to facilitate the early introduction of anti-asthma therapy.     

Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia

Background A 4‐week course of high‐dose glucocorticoids may cause prolonged adrenal suppression even after a 9‐day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high‐dose prednisone (PDN) or dexamethasone (DXM). Procedures Sixty‐four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD‐ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1–2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period. Results All patients had normal basal cortisol values at diagnosis. Twenty‐four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD‐ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7–14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression. Conclusions High‐dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated. Pediatr Blood Cancer 2008;50:537–541. © 2007 Wiley‐Liss, Inc.     

Afebrile Kawasaki disease with coronary artery dilatation

Herein we describe the cases of two afebrile patients who were thought to have Kawasaki disease (KD). Patient 1 was a 7‐month‐old‐Japanese girl. She presented with bulbar conjunctival injection, diarrhea, skin erythema, and redness around the bacillus Calmette–Guerin (BCG) inoculation site. Thirteen days after the first symptoms, ultrasonic cardiogram (UCG) showed dilatations of the bilateral coronary arteries (CA). The dilatations had completely resolved 5 months later. Patient 2 was a 13‐month‐old Japanese boy. He first presented with bulbar conjunctival injection and redness around the BCG inoculation site. Twenty‐two days after the first symptoms, UCG indicated bilateral and peripheral CA dilatations. The mild dilatations of the proximal CA remained. Although fever is the principal symptom of KD, some incomplete KD patients may be afebrile. Although it is difficult to diagnose these patients as having KD, redness at the BCG inoculation site may be a clue to the diagnosis.     

肾脏疾病合并头孢曲松相关假性胆结石患儿的临床分析

目的 探讨肾脏疾病患儿合并头孢曲松相关假性胆结石的临床特点.方法 回顾性分析3例合并头孢曲松相关假性胆结石的肾脏疾病患儿临床资料.结果 病例1,男,11岁,诊断"肾病综合征",因"胃肠炎"予头孢曲松2g/d[50 mg/(kg·d)]抗感染,3 d后发现胆囊内泥沙样沉积,伴纳差、恶心;停药16 d后胆囊结石消失.病例2,男,10岁,诊断"急性链球菌感染后肾小球肾炎、肾功能不全",因"胃肠炎"予头孢曲松1.5 g/d[30 mg/(kg·d)],疗程6 d时发现胆囊结石,伴恶心、呕吐和腹痛,Murphy's征阳性;停药18 d后胆囊结石消失.病例3,男,12岁,诊断"肾病综合征",因"胃肠炎?"给予头孢曲松2g/d[40 mg/(kg·d)]联合甲硝唑抗感染、疗程2周,感染控制,但有中上腹压痛,停药3 d后发现胆囊结石;停药2个月后复查结石回声消失.结论 上述3例患儿出现胆囊结石时头孢曲松治疗剂量较低、结石出现早、临床表现相对重,可能与肾脏疾病患儿同时存在血液浓缩、高凝状态、肾功能不全或补充钙剂等高危因素有关.