title: Changes in airway inflammation during pulmonary exacerbations in patients with cystic fibrosis and primary ciliary dyskinesia.
abstract: Lung disease in patients with both primary ciliary dyskinesia (PCD) or cystic fibrosis (CF) is associated with impaired mucociliary clearance; however, clinical outcomes are typically worse in CF patients. We assessed whether CF and PCD patients differ in inflammatory response in the airways during pulmonary exacerbation.We first studied clinically stable PCD patients with a spectrum of bacterial pathogens to assess inflammatory response to different pathogens. Subsequently, PCD and CF patients with similar bacterial pathogens were studied at the time of a pulmonary exacerbation and after 21 days of antibiotics treatment. Qualitative and quantitative microbiology, cell counts, interleukin-8 concentrations, and neutrophil elastase activity were assessed in sputum samples obtained before and after treatment.In stable PCD patients, no significant differences were found in sputum inflammatory markers between individuals colonised with different bacterial pathogens. Pulmonary exacerbation severity assessed by a pulmonary exacerbation score and lung function decline from their previous baseline did not differ between CF and PCD patients. Bacterial density for Staphylococcus aureus and Haemophilus influenzae was higher in CF versus PCD (p<0.05), but absolute neutrophil counts were higher in PCD patients (p=0.02). While sputum elastase activity was similar in PCD and CF at the time of exacerbation, it decreased with antibiotic therapy in PCD (p<0.05) but not CF patients.PCD patients differ from those with CF in their responses to treatment of pulmonary exacerbations, with higher neutrophil elastase activity persisting in the CF airways at the end of treatment.
authors.affiliation: Division of Respiratory Medicine, Department of Paediatrics, Hospital for Sick Children, Toronto, Canada University of Toronto, Toronto, Canada Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada felix.ratjen@sickkids.ca.
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
authors.affiliation: Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada Division of Infectious Diseases, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Waters
authors.affiliation: Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Klingel
authors.affiliation: Division of Respiratory Medicine, Department of Paediatrics, Hospital for Sick Children, Toronto, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: McDonald
authors.affiliation: Division of Respiratory Medicine, Department of Paediatrics, Hospital for Sick Children, Toronto, Canada University of Toronto, Toronto, Canada Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Sharon
authors.initials: S
authors.lastname: Dell
authors.affiliation: Division of Infectious Diseases, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Timothy Ronan
authors.initials: TR
authors.lastname: Leahy
authors.affiliation: University of Toronto, Toronto, Canada Division of Microbiology, Dept of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Yau
authors.affiliation: Division of Respiratory Medicine, Department of Paediatrics, Hospital for Sick Children, Toronto, Canada University of Toronto, Toronto, Canada Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Grasemann
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D002648:Child; D003550:Cystic Fibrosis / Q000382:microbiology / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006193:Haemophilus influenzae / Q000302:isolation & purification; D006801:Humans; D007249:Inflammation / Q000382:microbiology*; D016209:Interleukin-8 / Q000097:blood; D007619:Kartagener Syndrome / Q000382:microbiology / Q000503:physiopathology*; D008168:Lung / Q000503:physiopathology*; D008297:Male; D009504:Neutrophils / Q000166:cytology; D009864:Ontario; D012129:Respiratory Function Tests; D013183:Sputum / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000302:isolation & purification
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D016209:Interleukin-8