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1.
J Allergy Clin Immunol ; 138(4): 1183-1189.e4, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27056270

RESUMO

BACKGROUND: Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear. OBJECTIVE: The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. METHODS: Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. RESULTS: Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. CONCLUSION: Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease.


Assuntos
Candidíase/complicações , Quitinases/metabolismo , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Adolescente , Adulto , Asma/complicações , Candida albicans/isolamento & purificação , Candida albicans/metabolismo , Candidíase/enzimologia , Quitinases/sangue , Quitinases/deficiência , Quitinases/genética , Feminino , Humanos , Masculino , Regulação para Cima , Adulto Jovem
2.
J Cyst Fibros ; 15(3): 340-9, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26856310

RESUMO

With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern of bacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preserved lung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa. Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. Collectively, this study identified potentially protective and harmful microbial colonization patterns in adolescent CF patients. Further studies in different patient cohorts are required to evaluate these microbial patterns and to assess their clinical relevance.


Assuntos
Aspergillus fumigatus/isolamento & purificação , Fibrose Cística , Pulmão , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções por Pseudomonas , Pseudomonas aeruginosa/isolamento & purificação , Aspergilose Pulmonar , Infecções Estafilocócicas , Adolescente , Áustria/epidemiologia , Fibrose Cística/epidemiologia , Fibrose Cística/microbiologia , Fibrose Cística/fisiopatologia , Feminino , Alemanha/epidemiologia , Humanos , Pulmão/microbiologia , Pulmão/fisiopatologia , Masculino , Interações Microbianas , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/fisiopatologia , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/epidemiologia , Aspergilose Pulmonar/fisiopatologia , Testes de Função Respiratória/métodos , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/fisiopatologia , Estatística como Assunto
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