Don’t forget other causes of wheeze. ABPA in a boy with asthma. A case report and review of the literature

Allergic bronchopulmonary aspergillosis (ABPA) is a rare pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. The prevalence is estimated to be about 1–2% in adult patients with asthma and 2–15% in patients with cystic fibrosis. In paediatric patients with asthma, only single case reports on ABPA exist. We report on a 13‐year‐old boy with allergic asthma complicated by ABPA. Despite the presentation of typical clinical symptoms, it took 6 years before he was diagnosed. The clinical course improved rapidly after ABPA therapy was started, and 12 months after diagnosis, the boy is still free of symptoms. Clinical symptoms of ABPA may be unspecific making a rapid diagnosis difficult in some cases. Conclusion: A delay in diagnosis and treatment increases the risk for irreversible lung damage. Once bronchiectasis has developed, the outcome is unfavourable. Thus, ABPA has to be considered in patients whose asthma remains uncontrolled despite adequate therapy.     

Risk factors for allergic bronchopulmonary aspergillosis and sensitisation to <Emphasis Type="Italic"> Aspergillus fumigatus </Emphasis>in patients with cystic fibrosis

An increasing incidence of allergic bronchopulmonary aspergillosis (ABPA) as a complication in patients with cystic fibrosis (CF) is reported. The objective of this retrospective case-control study was to assess potential risk factors for ABPA and for Aspergillus fumigatus sensitisation (AFS). In a group of 160 CF patients, 11 (7%) fulfilled the diagnostic criteria for ABPA and 20 (13%) had evidence of AFS. They were compared to 62 control CF patients (25 for ABPA and 37 for AFS group) without evidence of ABPA or AFS using extended matching for sex, age and weight. AFS patients had received significantly higher cumulative doses of inhaled corticosteroids than their respective controls (OR 8.0; 95% CI 1.74–63). Bronchial colonisation with Stenotrophomonas maltophilia was strongly and independently associated with ABPA (OR 20; 95% CI 2.8– infinity). A longer duration of Pseudomonas aeruginosa colonisation was independently associated with AFS (OR per year 1.50; 95% CI 1.12– infinity). Conclusion: Cystic fibrosis patients with allergic bronchopulmonary aspergillosis have a more frequent isolation of S. maltophilia in their sputum than their controls. Longer duration of colonisation with P. aeruginosa is a risk factor for Aspergillus fumigatus sensitisation. Higher cumulative doses of inhaled corticosteroids are associated with Aspergillus fumigatus sensitisation and their role as a risk factor needs to be clarified.     

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.     

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,汗液氯离子浓度93 mmol/L。最终确诊CF并发ABPA。以“ABPA、CF、儿童”为关键词检索PubMed、中国知网、万方数据库近10年文献,病例报道7例,国内2例,国外5例。患儿基因变异不同,临床表现亦不同。中国报道CF并发ABPA病例与欧美国家不同,均为先发现ABPA,经过基因检查、汗液氯离子试验确诊CF。结论CF患儿应监测是否存在ABPA,及早发现、治疗。     

Combined heterotopic liver–pancreas transplantation as a curative treatment for liver cirrhosis and diabetes mellitus in cystic fibrosis

Cystic fibrosis (CF) is an inherited disease with a defect in epithelial chloride transport that results in a multisystem disease. Although pulmonary disease remains the primary cause of morbidity and mortality, focal biliary cirrhosis and portal hypertension may develop in up to 8% of these patients. Liver transplantation (TX) is an accepted therapy and shows good results. We report on a patient with cystic fibrosis homozygous for the most common CFTR mutation delta F 508 who received a combined heterotopic liver and pancreas transplantation at the age of 18 yr. He suffered from CFRD, which untypically required high doses of insulin. In addition, the patient had pulmonary complications, was chronically colonized with multiresistant Pseudomonas aeruginosa (MBL) and had an allergic bronchopulmonary aspergillosis (ABPA). The patient remained in stable health for 54 months post‐TX and was able to live a nearly normal life. With a follow‐up of five yr, the function of the liver and pancreas allografts was excellent. However, and sadly, his pulmonary function continued to deteriorate from progression of his CF, and he died of respiratory failure due to a severe pneumonia and septicemia at the age of 23 yr and five months.     

High-attenuation mucus plugs on MDCT in a child with cystic fibrosis: potential cause and differential diagnosis

High-attenuation mucus plugging is a rare finding in both adults and children. When it occurs, the field of differential diagnoses is typically quite small and includes acute hemorrhage, aspiration of radiodense material, and allergic bronchopulmonary aspergillosis (ABPA). The last of these three diagnoses is the most difficult to make, although ABPA is more commonly seen in children with cystic fibrosis (CF) or asthma. ABPA is radiographically characterized by recurrent mucus plugging, atelectasis, and central bronchiectasis. Thus far, high-attenuation mucus plugs have only been reported in adults. We report a rare case of a child with CF who had high-attenuation mucus plugs and atelectasis that raised the possibility of ABPA. We discuss the differential diagnoses of this finding and the role of multidetector CT in these children.     

Time course of antibody response to recombinant Aspergillus fumigatus antigens in cystic fibrosis with and without ABPA

We determined follow-up levels of specific serum IgE to the recombinant Aspergillus fumigatus (A. fumigatus) allergens rAsp f 1, 3, 4 and 6 in patients suffering from cystic fibrosis (CF) with and without allergic bronchopulmonary aspergillosis (ABPA). Over a 32-month period follow-up data of 74 patients were collected. According to serology, 11 CF patients were not sensitized (CF controls), 40 were sensitized to A. fumigatus (Asp. f-sens.) and 23 patients fulfilled the serologic criteria for ABPA. Of these 23 ABPA patients 11 expressed the full clinical ABPA picture (classicABPA) and 12 failed to show sufficient relevant clinical signs (seroABPA), despite positive serology. The 23 ABPA patients had 16-18 times higher serum levels of specific IgE to rAsp f 4 and/or rAsp f 6 than those of Asp. f-sens. patients (rAsp f 4: 31.3 +/- 45 EU/ml vs. 1.9 +/- 2.2 EU/ml and rAsp f 6: 39.0 +/- 44.3 EU/ml vs 2.1 +/- 1.7 EU/ml). The combination of increased total serum IgE (>1000 IU/l) and increased specific IgE to rAsp f 4 and/or rAsp f 6 allowed to diagnose classicABPA with 100% specificity and 64% sensitivity and with a high predicted positive (100%) and a high predicted negative (94%) value. During a combined treatment (seven patients) with oral corticosteroid and itraconazole, itraconazole alone (two patients) or neither oral corticosteroid nor itraconazole therapy (two patients) total serum IgE and specific IgE to rAsp f 4 and/or rAsp f 6 did decrease but did not normalize. Over the observation period, lung function remained unchanged, independent of whether oral steroids and/or concomitant itraconazole were either given or not given. In the follow-up of CF patients with ABPA under therapy the determination of total or specific IgE serum levels were of limited value to guide therapy.     

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.     

Prevalence and risk factors for allergic bronchopulmonary aspergillosis in Indian children with cystic fibrosis

Objectives

Allergic bronchopulmonary aspergillosis (ABPA) is a common complication in patients with cystic fibrosis. This crosssectional study was planned to determine the prevalence and risk factors for ABPA in Indian children with cystic fibrosis.

Methods

Clinical evaluation, spirometry, chest radiograph, sputum, total IgE, specific IgE for Aspergillus fumigatus, IgG precipitins and skin prick tests were done in 33 CF patients.

Results

Prevalence of allergic bronchopulmonary aspergillosis was 18.2% (95% CI 6.9%–35.4%): allergic bronchopulmonary aspergillosis was higher in patients with low cystic fibrosis score, age >12 years, atopy, and eosinophilia.

Conclusion

Prevalence of ABPA is higher in Indian children with cystic fibrosis.     

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.     

Allergic bronchopulmonary aspergillosis in two patients with cystic fibrosis

Allergic bronchopulmonary aspergillosis (ABPA) is hypersensitivity to Aspergillus fumigatus which manifests as episodic wheezing, usually refractory to bronchodilator therapy, with fixed and transient pulmonary infiltrates, central bronchiectasis, blood eosinophilia, elevated serum IgE level, immediate skin reactivity to an A. fumigatus antigen and precipitating antibodies to A. fumigatus. It is an unusual complication of asthma and cystic fibrosis (CF). We present two cystic fibrosis patients with ABPA treated successfully with prednisone and, in Case 1 also with itraconazole. The physician should be alert to the possibility of ABPA whenever CF patients present with the new infiltrates, high serum total IgE and other positive parameters of A. fumigatus sensitization. Treatment with systemic steroids should be started in order to prevent irreversible lung damage.     

Mucoviscidosis and allergic bronchopulmonary aspergillosis]

Allergic bronchopulmonary aspergillosis (ABPA) is a severe disease inducing bronchopulmonary anatomic lesions which complicate those already present in patients with cystic fibrosis. The frequency of this association is estimated between 0.6 and 10% according to American studies. Diagnosis of ABPA is difficult, as findings such as sibilant rales, pulmonary infiltrates, bronchiectasies, anti-aspergillus precipitins may be present as single features in patients with cystic fibrosis. Thus it is important to ascertain the diagnosis as oral corticosteroid treatment is the only one able to prevent evolution towards bronchiectasies and pulmonary fibrosis.     

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.     

Allergic bronchopulmonary aspergillosis in cystic fibrosis

ABSTRACT. We determined prospectively over a 12-month period the importance of the fungus Aspergillus in patients with cystic fibrosis.
Aspergillus species was cultured from 10 out of 116 children and adolescents (8.6%), and from 25 of the 1073 sputa (2.3%) collected from these patients. Eighteen of these subjects (15.5%) had positive allergen skin prick tests to Aspergillus species or Aspergillus fumigatus . Fifty-three patients (13%) had blood collected for precipitins and 7 (13%) exhibited type III hypersensitivity to Aspergillus fumigatus . Although 26% had an IgE greater than 200 I.U./ml, only one patient had an IgE greater than 1,000 I.U./ml. We found no evidence of an association between severity of lung disease and either colonisation by or sensitisation to Aspergillus .
No patient fulfilled all our criteria for the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). One teenager (with wheezing, pulmonary infiltrate, positive skin tests, positive sputum culture and markedly elevated IgE) may have had an episode of ABPA. We studied three other children with co-existent asthma in whom it was difficult to establish whether the asthma was related to sensitivity to Aspergillus .
We conclude that ABPA is an uncommon complication of cystic fibrosis in our clinic.     

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.     

Associations of plasma total phospholipid fatty acid patterns with feeding practices,growth, and psychomotor development in 6‐month‐old South African infants

The objective of this study was to assess plasma fatty acid (FA) patterns of 6‐month‐old South African infants and to determine their association with feeding practices, growth, and psychomotor development. Plasma total phospholipid FA composition (% of total FAs) of 6‐month‐old infants (n = 353) from a peri‐urban township was analysed, and principal component and factor analysis were performed to identify plasma FA patterns. Feeding practices, anthropometric measurements, and psychomotor development scores were determined. Four major plasma phospholipid FA patterns were identified: A plant‐based C18 FA, a high n‐6 long‐chain polyunsaturated fatty acids (LCPUFA), a C16:1 and long‐chain saturated fatty acid (SFA), and a high n‐3 and low n‐6 LCPUFA pattern. Formula feeding was associated with higher, whereas breastfeeding was associated with lower scores for the plant‐based C18 FA and C16:1 and long‐chain SFA patterns. On the other hand, breastfeeding, the consumption of cow's milk, and the consumption of semisolid foods were associated with higher scores, whereas formula feeding was associated with lower scores for the high n‐6 LCPUFA pattern. Breastfeeding and the consumption of semisolids were also associated with higher high n‐3 and low n‐6 LCPUFA pattern scores. The C16:1 and long‐chain SFA and high n‐3 and low n‐6 LCPUFA patterns were positively associated with psychomotor development scores. In 6‐month‐old South African infants, we identified distinct plasma FA patterns that presumably represent the FA quality of their diet and that are associated with psychomotor development. Our results suggest that breast milk is an important source of n‐6 LCPUFAs and formula‐fed infants may be at risk of inadequate LCPUFA intake.     

Prognostic significance of tissue Doppler imaging–derived myocardial performance index in pediatric patients with dilated cardiomyopathy

TDI–MPI has been shown to predict cardiovascular mortality in adults; there are a paucity of data on its use in children. We sought to determine the prognostic significance of TDI‐MPI at time of DCM diagnosis in children. Patients aged ≤18 years diagnosed with DCM were included along with age‐ and sex‐matched controls. Echo at diagnosis was analyzed to obtain standard measures of LV function, PW‐MPI, and septal and LV free wall TDI‐MPI. Survival analysis was used to assess the time to composite outcome of death, VAD, or transplant, stratified by TDI‐MPI z‐score. The study included 79 patients with DCM and 79 controls. During a median follow‐up of 182 days (IQR 41‐815 days), 16 underwent VAD placement, 21 underwent cardiac transplant, 6 died, and 36 had event‐free survival. The median septal TDI‐MPI for cases was 0.70 for patients with DCM vs 0.45 for controls (P < .001). Those with septal TDI‐MPI z‐scores ≥2 develop events significantly earlier than those with z‐score <2 (P = .014). In multivariable analysis, TDI‐MPI z‐score ≥2 was significantly associated with poor outcomes (HR 2.12, 95% CI 1.06‐4.23). TDI‐MPI can be reliably performed in pediatric patients with DCM. A TDI‐MPI z‐score ≥2 at diagnosis may be associated with earlier poor outcome. Further studies evaluating the use of TDI‐MPI in longitudinal follow‐up of patients with DCM may be helpful in refining its clinical use.     

Relapsed childhood acute myeloid leukemia patient with inversion of chromosome 16 harboring a low FLT3 internal tandem duplication allelic burden and KIT mutations

Inversion of chromosome 16 [inv(16)] has a good prognosis in acute myeloid leukemia (AML), but additional genetic aberrations influence the outcome. We herein describe the case of a 15‐year‐old Japanese boy with inv(16) harboring a low‐allelic burden internal tandem duplication of FLT3 (FLT3‐ITD) and KIT mutations. Conventional chemotherapy eradicated a clone with a low‐allelic burden FLT3‐ITD mutation, although another clone with a KIT mutation occurred 17 months later. Further investigation is necessary to identify AML with inv(16) conferring poor prognosis, to facilitate appropriate treatment with additional drugs, such as dasatinib or gemtuzumab ozogamicin.     

Nutritional status and cognitive performance of mother–child pairs in Sidama,Southern Ethiopia

The purpose of this study was to assess the nutritional status and cognitive performance of women and their 5‐year‐old children using a cross‐sectional design. Cognitive performance of mothers and children was assessed with Raven's Colored Progressive Matrices (CPM) and Kaufman Assessment Battery for Children‐II (KABC‐II). Demographic characteristics, food consumption patterns and anthropometry were also measured. Four rural districts in Sidama, southern Ethiopia served as the setting for this study. Subjects were one hundred women and their 5‐year‐old children. Mean ± standard deviation age of the mothers was 29 ± 6 years and family size was 7.0 ± 2.6. Maternal body mass index (BMI) ranged from 15.3 to 29.0 with 14% of the mothers having BMI < 18.5. Anthropometric assessment of children revealed 29% to be stunted (height‐for‐age z‐score < ?2) and 12% to be underweight (weight‐for‐age z‐score < ?2). Mothers' education significantly contributed to prediction of both mothers' and children's cognitive test scores. There were significant differences in mean cognitive test scores between stunted and non‐stunted, and between underweight and normal‐weight children. Height‐for‐age z‐scores were correlated with scores for short‐term memory (r = 0.42, P < 0.001), and visual processing (r = 0.42, P < 0.001) indices and weight‐for‐age z‐scores were also correlated with scores of short‐term memory (r = 0.41, P < 0.001) and visual processing (r = 0.43, P < 0.001) indices. Malnutrition in the community likely contributed to the cognitive performance of the subjects. Performance on memory and visual processing tasks was significantly lower in children with growth deficits suggesting that efficient and cost effective methods to alleviate malnutrition and food insecurity would impact not only child health but also cognitive function.