Early diagnosis and treatment of invasive pulmonary aspergillosis in a patient with cystic fibrosis (original) (raw)
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Aspergillus terreus Causing Probable Invasive Aspergillosis in a Patient with Cystic Fibrosis
Mycopathologia, 2018
Aspergillus terreus may colonize the airways of patients with cystic fibrosis (CF). Whether this merits antifungal treatment is still unclear due to heterogeneous reports regarding its pathogenic potential. Although allergic manifestations are documented, invasive aspergillosis (IA) caused by A. terreus has not been described. We present here one case of probable IA caused by A. terreus, highlighting its role as an emerging agent of IA in CF patients. Voriconazole was effective, and the patient was healthy after 12 weeks of treatment. Serial determination of serum galactomannan level and periodic cultures from respiratory specimens may help in monitoring CF patients by identifying such pathogens. Further studies on the fungal species colonizing the CF airways are warranted, especially in India. This case report suggests A. terreus as a potential agent of IA which should not be ignored, particularly in this patient group.
Aspergillus Infections and Progression of Structural Lung Disease in Children with Cystic Fibrosis
American Journal of Respiratory and Critical Care Medicine
Rationale: Recent data show that Aspergillus species are prevalent respiratory infections in children with cystic fibrosis (CF). The biological significance of these infections is unknown. Objectives: We aimed to evaluate longitudinal associations between Aspergillus infections and lung disease in young children with CF. Methods: Longitudinal data on 330 children participating in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis surveillance program between 2000 and 2018 who underwent annual chest computed tomography (CT) imaging and BAL were used to determine the association between Aspergillus infections and the progression of structural lung disease. Results were adjusted for the effects of other common infections, associated variables, and repeated visits. Secondary outcomes included inflammatory markers in BAL, respiratory symptoms, and admissions for exacerbations. Measurements and Main Results: Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, and Aspergillus infections were all associated with worse CT scores in the same year (P overall , 0.05). Only P. aeruginosa and Aspergillus were associated with progression in CT scores in the year after an infection and worse CT scores at the end of the observation period. P. aeruginosa was most significantly associated with development of bronchiectasis (difference, 0.9; 95% confidence interval, 0.3-1.6; P = 0.003) and Aspergillus with trapped air (difference, 3.2; 95% confidence interval, 1.0-5.4; P = 0.004). Aspergillus infections were also associated with markers of neutrophilic inflammation (P , 0.001) and respiratory admissions risk (P = 0.008). Conclusions: Lower respiratory Aspergillus infections are associated with the progression of structural lung disease in young children with CF. This study highlights the need to further evaluate early Aspergillus species infections and the feasibility, risk, and benefit of eradication regimens.
Multi-Country Estimate of Different Manifestations of Aspergillosis in Cystic Fibrosis
PLoS ONE, 2014
Aspergillus spp. can lead to allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitisation and Aspergillus bronchitis in CF. The relative frequencies of these entities have recently been ascertained in a large UK adult CF cohort. We have used this data to estimate the burden of aspergillosis and ABPA cases in adult CF patients in 30 countries reporting CF. National and international CF registry data was accessed and assessed for completeness and age distribution. Published proportions of ABPA (17.7%), Aspergillus sensitisation (14.6%) and Aspergillus bronchitis (30%) in CF were applied to those. 18 years and compared with notified ABPA cases. Of the 76,201 estimated CF patients worldwide (not including India), 37,714 were .18 years. The proportion of adults to children varied from 63% in Norway to 20% in Brazil. ABPA caseload in adults is anticipated to be 6,675 cases of which only 2,221 cases (33%) are currently recorded, indicating substantial underdiagnosis. The ABPA diagnosis rate compared with estimated rates varies by country from 101% (France) to 14.5% (Greece), although genetic variation could account for genuine differences compared with the UK. Aspergillus bronchitis is not currently recognised or recorded in CF registries but there are an anticipated 10,988 adult cases. Aspergillus sensitisation, associated with increased bronchiectasis and reduced FEV1, affects an anticipated 5,506 patients without ABPA or Aspergillus bronchitis. Together ABPA and Aspergillus bronchitis are estimated to affect 17,989 adults, 47.7% of the adult CF population. ABPA also occurs in children and teenagers and 984 cases were documented in registries. Diagnosed ABPA rates by age were available for the ECFS registry, USA, UK, Ireland, Belgium and Netherlands. The rate was ,1% under 4 years, and increased throughout childhood and adolescence, with marked variation between countries. Newly published diagnostic criteria and methods should facilitate better recognition of aspergillosis in CF, allowing better CF disease control.
Pulmonary Aspergillosis: A Short Review
Pulmonary aspergillosis refers to a spectrum of diseases resulting from Aspergillus becoming resident in the lung. These include invasive aspergillosis from angioinvasive disease, simple aspergilloma from inert colonization of pulmonary cavities, and chronic cavitary pulmonary aspergillosis from fungal germination and immune activation. Chronic pulmonary aspergillosis includes simple aspergilloma, which is occasionally complicated by life-threatening hemoptysis, and progressive destructive cavitary disease requiring antifungal therapy. Allergic bronchopulmonary aspergillosis occurs almost exclusively in patients with asthma or cystic fibrosis. Invasive aspergillosis is now recognized to occur in patients with critical illness without neutropenia and in those with mild degrees of immunosuppression, including from corticosteroid use in the setting of COPD. Improvement in outcomes for Aspergillus pulmonary syndromes requires that physicians recognize the varied and sometimes subtle presentations, be aware of populations at risk of illness, and institute potentially life-saving therapies early in the disease course.
Infection, 2003
The incidence of fungal infections, including those due to Aspergillosis species has continued to increase in recent years. Invasive aspergillosis remains an important cause of morbidity and mortality, despite therapeutics interventions. We reported five cases of invasive pulmonary aspergillosis treated with voriconazole failing to respond to conventional treatments. The clinical and radiological resolution of pulmonary aspergillosis reported in these cases following therapy with voriconazole is remarkable, considering the infections had proved refractory to standard antifungal therapies. Long-term therapy (in two cases > or = 1 year, in one case 6 months) was very well tolerated by patients who were unable to tolerate other antifungal agents. Therapy with voriconazole offers a new therapeutic option for otherwise difficult-to-treat infections and the potential to significantly improve the management of Aspergillosis infections.
Treatment of Chronic Pulmonary Aspergillosis by Voriconazole in Nonimmunocompromised Patients*
CHEST Journal, 2007
Background: There is no recognized medical treatment for chronic pulmonary aspergillosis (CPA) apart from surgery in patients with simple aspergilloma. To evaluate the efficacy of voriconazole in this setting, we conducted a retrospective multicenter study over a 3-year period. Methods: For inclusion in the study, patients had to have received voriconazole for treatment of confirmed or probable CPA with a follow-up of at least 6 months. Clinical, radiologic, and mycologic data were collected at baseline, every 2 to 3 months, and at the end of treatment or at the date point. Results: Twenty-four patients were included in the study, among which 9 patients presented with chronic cavitary pulmonary aspergillosis and 15 presented with chronic necrotizing pulmonary aspergillosis (CNPA). Voriconazole was given as a first-line treatment to 13 patients. The median duration of treatment and follow-up were 6.5 and 10 months, respectively. Three patients had to stop treatment with voriconazole because of toxicity. Symptoms and imagery findings were improved in 16 of 24 patients and 17 of 24 patients, respectively, at the end of follow-up. Mycology, which was positive at baseline in 21 of 23 patients, was negative in 18 of 19 patients at the end of follow-up; serologic test results were also negative in 6 of 19 evaluable patients, all of whom had CNPA. Improved radioclinical findings and mycologic eradication were observed at the end of follow-up in 11 of 19 patients (58%). Patients in whom the disease was controlled had a significantly longer median duration of treatment than patients in whom it was uncontrolled (9 vs 6 months, respectively; p ؍ 0.04). Conclusion: Voriconazole provides effective treatment of CPA with an acceptable level of toxicity.
Diverse clinical characteristics of aspergillus growth in patients with cystic fibrosis
The Turkish Journal of Pediatrics
Cystic fibrosis (CF) is a systemic chronic disease and abnormalities in CFTR (Cystic fibrosis transmembrane conductance regulator) function affect interactions between the epithelial surface and microorganisms such as fungi. 1 Conidial spores are usually cleared by airway epithelium; however, in CF due to disruption of epithelial barrier and germination of the fungi induce inflammatory response. Increased mucus viscosity and lung injury result in an ongoing cycle of infection, inflammation and pulmonary damage. 1,2 Aspergillus, the most commonly detected filamentous fungi in CF induces this abnormal pulmonary inflammation. 2 The main Aspergillus-associated clinical manifestations