James D Chalmers1, Stefano Aliberti2,3, Anna Filonenko4, Michal Shteinberg5, Pieter C Goeminne6,7, Adam T Hill8,9, Thomas C Fardon1, Dusanka Obradovic10, Christoph Gerlinger4,11, Giovanni Sotgiu12, Elisabeth Operschall4, Robert M Rutherford13, Katerina Dimakou14, Eva Polverino15, Anthony De Soyza16,17, Melissa J McDonnell13,17. 1. 1 Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom. 2. 2 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 3. 3 Internal Medicine Department, Respiratory Unit, and Cystic Fibrosis Adult Center, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 4. 4 Bayer AG, Berlin, Germany. 5. 5 Pulmonary Institute, Carmel Medical Center, Haifa, Israel. 6. 6 Respiratory Medicine, University Hospital Gasthuisberg, Leuven, Belgium. 7. 7 Respiratory Disease, AZ Nikolaas, Sint-Niklaas, Belgium. 8. 8 Royal Infirmary of Edinburgh, Edinburgh, United Kingdom. 9. 9 University of Edinburgh, Edinburgh, United Kingdom. 10. 10 Institute for Pulmonary Diseases of Vojvodina Sremska Kamenica and Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. 11. 11 Gynecology, Obstetrics, and Reproductive Medicine, University of Saarland Medical School, Homburg/Saar, Germany. 12. 12 Clinical Epidemiology and Medical Statistics Unit, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy. 13. 13 Department of Respiratory Medicine, Galway University Hospitals, Galway, Ireland. 14. 14 5th Department of Pulmonary Medicine, "Sotiria" Chest Diseases Hospital, Athens, Greece. 15. 15 Servei de Pneumologia, Hospital Clinic, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedade Respiratorias (CIBERES), Barcelona, Spain. 16. 16 Adult Bronchiectasis Service and Sir William Leech Centre for Lung Research, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Heaton, United Kingdom; and. 17. 17 Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Abstract
RATIONALE: Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described. OBJECTIVES: To establish if there is a "frequent exacerbator phenotype" in bronchiectasis and the impact of exacerbations on long-term clinical outcomes. METHODS: We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality. MEASUREMENTS AND MAIN RESULTS: A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype. The incident rate ratios for future exacerbations were 1.73 (95% confidence interval [CI], 1.47-2.02; P < 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70-3.66; P < 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27-6.78; P < 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV1, radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during follow-up. Mortality over up to 5 years of follow-up increased with increasing exacerbation frequency. CONCLUSIONS: The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow-up.
RATIONALE: Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described. OBJECTIVES: To establish if there is a "frequent exacerbator phenotype" in bronchiectasis and the impact of exacerbations on long-term clinical outcomes. METHODS: We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality. MEASUREMENTS AND MAIN RESULTS: A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype. The incident rate ratios for future exacerbations were 1.73 (95% confidence interval [CI], 1.47-2.02; P < 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70-3.66; P < 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27-6.78; P < 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV1, radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during follow-up. Mortality over up to 5 years of follow-up increased with increasing exacerbation frequency. CONCLUSIONS: The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow-up.
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