The clinical presentations of pulmonary aspergillosis in children with cystic fibrosis - preliminary report

Abstract

Pulmonary aspergillosis is a very serious complication in cystic fibrosis (CF) patients due to the great variety of its clinical presentations and the fact that it worsens the prognosis. We can distinguish the following: Aspergillus colonization (AC), Aspergillus infection (AI) and allergic bronchopulmonary aspergillosis (ABPA). Aspergillus colonization (AC) is defined as isolation of Aspergillus spp. from 50% ormore sputum samples over six months to one year without observing deterioration in lung function and an increase in such respiratory symptoms as cough. Aspergillus infection (AI) is diagnosed in subjects with Aspergillus colonization and a decline in lung function, respiratory exacerbation with and without cough or with an incomplete response to a 2-4 week course of appropriate broad-spectrum antibiotics. Aspergillus can also cause allergic bronchopulmonary aspergillosis (ABPA). The classic diagnostic criteria of allergic bronchopulmonary aspergillosis in cystic fibrosis have been established during the Cystic Fibrosis Foundation Conference in 2001.

Aim: To establish the prevalence of pulmonary aspergillosis in children with cystic fibrosis under the care of our centre and to investigate the potential predisposing factors to Aspergillus infection (AI) and allergic bronchopulmonary aspergillosis (ABPA).

Material and methods: An analysis was conducted of the medical documentation of 374 children aged 0-18 years monitored regularly in the Cystic Fibrosis Centre of the Institute of Mother and Child in Warsaw from 01.01.2010 to 31.08.2014. We selected 13 patients who presented an evidently worsening clinical status and course of the bronchopulmonary disease (decline in lung function parameters, respiratory exacerbations with increased cough, new or recent abnormalities in chest imaging) despite standard treatment with a high calorie diet, supplementation of pancreatic enzymes and vitamins, dornase alpha, inhaled and/or oral antibiotics, inhaled or oral corticosteroids, bronchodilators, physiotherapy. In this group of 13 CF children Aspergillus fumigatus was isolated from sputum. They represented 3.5% of the patients treated in our centre. Pulmonary aspergillosis was analyzed in relation to the age, sex, genotype, exocrine pancreatic insufficiency, body mass index, pulmonary function, microbiological examination of sputum, pulmonary complications and therapies. The mean age was 10.7 years (range 4.5-16.3). Only one child was under the age of six years. Patients were divided into 3 groups: patients with Aspergillus infection (AI), patients with allergic bronchopulmonary aspergillosis (ABPA), and a patient with Aspergillus infection and bronchopulmonary aspergillosis.

Results: Aspergillus infection (AI) was diagnosed in 9 cases (2.4%) and allergic bronchopulmonary aspergillosis (ABPA) in 3 (0.8%). One patient was treated with corticosteroids, because of allergic bronchopulmonary aspergillosis (ABPA) and after 8 months he developed Aspergillus infection (AI).n Most of the children were homo- or heterozygous for mutation F508del. Pancreatic insufficiency was recognized in all the children with ABPA, most of those with AI (8/9) and in one boy with ABPA and AI. Most of the patients had chronic respiratory colonization of Staphylococcus aureus and Pseudomonas aeruginosa. Children with AI were older (mean age:12.4), had a worse nutritional status (three of them had aBMI 3rd percentile), poorer lung function (five had severe lung disease *FEV1 40%*, complications occurred in one of the underlying diseases *haemoptysis, CFRD - Cystic Fibrosis Related Diabetes*, two of them had vascuport inserted due to the need for frequent intravenous antibiotic therapy. All the patients received inhaled antibiotics. A long-term oral azithromycin regime was applied in all the children with allergic bronchopulmonary aspergillosis, in most of those with Aspergillus infection *6,9* and in one boy with ABPA and AI. In three patients diagnosed with Aspergillus infection, antifungal treatment did not give any clinical or radiological improvement. They underwent surgical resection in the Department of Thoracic Surgery in Rabka (Poland). One patient had pneumonectomy and two underwent lobectomies. One boy had lung transplantation in Rigshospitalet in Copenhagen nine months after being diagnosed with Aspergillus infection.

Conclusions: Since pulmonary aspergillosis is a very serious complication in CF children, it seems reasonable to include screening for early detection of Aspergillus colonization in the annual assessment of CF patients who are over 6 years old. Due to the small sample size and retrospective design of our analysis, the identification of risk factors of pulmonary aspergillosis in CF children require further prospective studies. .