Clinical and Serological Survey of Pulmonary Aspergillosis in Patients with Cystic Fibrosis

Schønheyder, Henrik Carl; Jensen, Trine Hammer; Høiby, Niels; Koch, Christian

doi:10.1159/000234554

Cited by 30 publications

(16 citation statements)

References 16 publications

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“…Specifically, this organism causes allergic bronchopulmonary aspergillosis (ABA). Invasive aspergillosis and aspergilloma are unusual in this population (30,165,196). The prevalence of ABA is estimated to be between 0.5 and 11% in CF patients and is believed to occur primarily in older children and young adults (30, 121).…”

Section: Pseudomonas Cepaciamentioning

confidence: 99%

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Microbiology of airway disease in patients with cystic fibrosis

1991

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Individuals with cystic fibrosis have abbreviated life spans primarily due to chronic airway infection. A limited number of types of organisms are responsible for these infections, with Staphylococcus aureus and Pseudomonas aeruginosa being of primary importance. In the pre-antibiotic era, greater than 90% of deaths due to infection were caused by S. aureus and death usually occurred in the first 2 years of life. With the advent of effective antistaphylococcal therapy, life spans increased and P. aeruginosa became the pathogen of primary importance. P. aeruginosa isolates recovered from patients with cystic fibrosis have a unique phenotypic characteristic referred to as "mucoid." The mucoid phenotype is due to the production of a mucoid exopolysaccharide. A mucoid exopolysaccharide is believed to play a central role in the establishment of chronic pseudomonal lung infection in these patients. A third organism, Pseudomonas cepacia, has recently been detected in the airways of older patients with cystic fibrosis and is associated with increased mortality. The virulence of P. cepacia is not understood, but the organism is extremely refractory to antimicrobial therapy. Other bacteria, including Haemophilus influenzae and members of the family Enterobacteriaceae, appear to play a secondary role in airway infection. Aspergillus fumigatus is the most important fungal agent causing allergic bronchopulmonary disease. The role of viruses has only recently been examined. At least in some patients with cystic fibrosis, respiratory syncytial virus may be important in predisposing to subsequent bacterial infections.

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Section: Pseudomonas Cepaciamentioning

confidence: 99%

“…Antibodies to A. fumigatus are also common. Surveys of Aspergillus precipitins (154,165,166) have shown that these antibodies are present in 31 to 37% of CF patients, suggesting that a positive serologic test supports but does not confirm diagnosis of ABA. Corticosteroids are the treatment of choice for ABA (30,196).…”

Section: Pseudomonas Cepaciamentioning

confidence: 99%

Microbiology of airway disease in patients with cystic fibrosis

1991

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“…A llergic responses to Asperigillus species are a major cause of human morbidity and have been implicated in the pathogenesis of asthma (1) and cystic fibrosis (2). Allergic responses to Aspergillus involve a number of immunologic abnormalities including elevated IgE, enhanced Th2 cytokines such as IL-4, IL-5, and IL-13 (3), eosinophilic inflammation, and profound airway remodeling (4,5).…”

mentioning

confidence: 99%

Enhanced Pulmonary Allergic Responses toAspergillusin CCR2−/− Mice

Blease¹,

Mehrad

Standiford

et al. 2000

The Journal of Immunology

147

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Allergic responses to Aspergillus species exacerbate asthma and cystic fibrosis. The natural defense against live Aspergillus fumigatus spores or conidia depends on the recruitment and activation of mononuclear and polymorphonuclear leukocytes, events that are dependent on chemotactic cytokines. In this study, we explored the relative contribution of the monocyte chemoattractant protein-1 receptor, CCR2, in the pulmonary response to A. fumigatus conidia. Following sensitization to soluble A. fumigatus Ags, mice lacking CCR2 due to targeted deletion were markedly more susceptible to the injurious effects of an intrapulmonary challenge with live conidia compared with mice that expressed CCR2 or CCR2+/+. CCR2−/− mice exhibited a major defect in the recruitment of polymorphonuclear cells, but these mice also had significantly more eosinophils and lymphocytes in bronchoalveolar lavage samples. CCR2−/− mice also had significant increases in serum levels of total IgE and whole lung levels of IL-5, IL-13, eotaxin, and RANTES compared with CCR2+/+ mice. Airway inflammation, hyper-responsiveness to spasmogens, and subepithelial fibrosis were significantly enhanced in CCR2−/− mice compared with CCR2+/+ mice after the conidia challenge. Thus, these findings demonstrate that CCR2 plays an important role in the immune response against A. fumigatus, thereby limiting the allergic airway inflammatory and remodeling responses to this fungus.

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“…The CFTR has a central role in regulation of salt and water translocation and mutations in the CFTR gene lead to an altered mucus composition in affected lungs causing impaired mucociliary clearance. In patients with CF, an increasing prevalence of ABPA has been reported and can vary between 0.9% and 13% [1,8,9,13,14,16,18,21,27,30,31,35]. In two recent analyses of epidemiological registries, the reported prevalence of ABPA was 2.0% in North America among 14210 eligible patients older than 5 years of age [10] and 7.8% in nine European countries among 12447 patients [19].…”

Section: Introductionmentioning

confidence: 99%

“…Fluctuations in clinical presentation due to viral or bacterial pulmonary infections further limit the accurate diagnosis [8,30]. Recently, the IgE response towards recombinant A. fumigatus allergens (rAsp f) has been proposed to improve diagnosis of allergic diseases related to A. fumigatus in CF patients.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for allergic bronchopulmonary aspergillosis and sensitisation to Aspergillus fumigatus in patients with cystic fibrosis

Ritz¹,

Ammann²,

Aebischer³

et al. 2006

Eur J Pediatr

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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.

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Clinical and Serological Survey of Pulmonary Aspergillosis in Patients with Cystic Fibrosis

Cited by 30 publications

References 16 publications

Microbiology of airway disease in patients with cystic fibrosis

Microbiology of airway disease in patients with cystic fibrosis

Enhanced Pulmonary Allergic Responses toAspergillusin CCR2−/− Mice

Risk factors for allergic bronchopulmonary aspergillosis and sensitisation to Aspergillus fumigatus in patients with cystic fibrosis

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