PURPOSE: Changes in symptoms and pulmonary function before a COPD exacerbation are not well defined. In this post hoc analysis of data from a study in patients with COPD, changes from baseline in symptoms and pulmonary function during the week preceding the initial COPD exacerbation were assessed.
METHODS: Data were from a randomized, double-blind, multicenter 12-month study (N=1964) (NCT00206167; Drugs. 2009;69:549) in patients with moderate to very severe COPD aged ≥40 years. Data were combined from all treatment groups: twice-daily budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler (pMDI) 320/9 μg, BUD/FM pMDI 160/9 μg, FM dry powder inhaler (DPI) 9 μg, and placebo. Exacerbations were defined as worsening of COPD requiring oral corticosteroids (OCS) and/or hospitalization. Patients recorded dyspnea, cough, and sputum scores (derived from the Breathlessness, Cough, and Sputum Scale [BCSS; each scored on a 0-4 scale with higher scores indicating worse symptoms]), peak expiratory flow (PEF; L/min), and nighttime rescue medication use (inhalations/night) via diary. Mean changes from baseline in those variables were assessed during the 7 days preceding the patient’ s first exacerbation.
RESULTS: Tattersfield plots showed progressive worsening from baseline in mean dyspnea scores during the 7 days preceding COPD exacerbation; similar results were observed for cough and sputum scores. Mean change in dyspnea score overall during the 7 days was approximately 0.35 units, exceeding the predefined criteria for a minimal important difference (≥0.2-unit difference). Similar patterns of worsening were observed for PEF and nighttime rescue medication use during the 7 days preceding COPD exacerbation.
CONCLUSION: The results from this analysis show that COPD exacerbations are preceded by at least 7 days of worsening COPD symptoms and pulmonary function.
CLINICAL IMPLICATIONS: Substantial worsening in COPD symptoms and pulmonary function is observed before occurrence of a COPD exacerbation based on OCS treatment and/or hospitalization. Further research is needed to determine the threshold for changes in symptom-related variables that may be associated with a COPD exacerbation and whether such changes may help in predicting COPD exacerbations.
DISCLOSURE: Donald Tashkin, Grant monies (from industry related sources) This study was funded by AstraZeneca LP. Stephen I Rennard has received grant monies from Almirall, AstraZeneca, Biomark, Centocor, GSK, IFSH, Lorillard, Novartis, Pfizer, Philip Morris, Roche.; Shareholder Ubaldo J. Martin is a shareholder of AstraZeneca stocks.; Employee Jennifer McElhattan and Ubaldo J. Martin are employees of AstraZeneca; Consultant fee, speaker bureau, advisory committee, etc. Stephen I Rennard is a consultant to Abbott, Able Associations, Almirall, Almirall/Forest, Altana, Anthera, APT Pharma/Britnall, Aradigm, AstraZeneca, Boehringer Ingelheim, Britnall and Nicolini, Defined Health, Dunn Group, Eaton Associates, Gerson, GSK, Infomed, Johnson & Johnson, KOL Connection, Leerink Swan, MedaCorp, Mpex, Novartis, Otsuka, Pfizer, Propagate, Pulmatrix, Quintiles, Roche, Scimed, TargeGen, Theravance, United Biosource, Vantage Point, VantagePoint Mgmt; and on the Advisory Board of Abbott, Almirall, Boehringer Ingelheim, COPDForum, Dey, GSK, Novartis, Nycomed, Nycomed/Strategicare, Pfizer, Pharmaxis, Schering-Plough, TargeGen.; Other Stephen I Rennard is a speaker for ACCP, AstraZeneca, Novartis, Network for Continuing Ed, Pfizer, SOMA, Creative Educational Concept, France Foundation. Donald P Tashkin has received grant support (administered through his university), fees for consulting/advisory boards, and/or honoraria for speaking from Boehringer Ingelheim, Pfizer, AstraZeneca, GSK, Schering-Plough, Novartis, Teva, and Dey Labs.; No Product/Research Disclosure Information