The Effect of Levodopa on Pulmonary Function in Parkinson’s Disease: A Systematic Review and Meta-Analysis Larissa Monteiro, MD, MSc 1 ; Adelmir Souza-Machado, MD, PhD 2 ; Silvia Valderramas, PT, PhD 1 ; and Ailton Melo, MD, PhD 1 1 Division of Neurology and Epidemiology, Federal University of Bahia, Salvador-Bahia, Brazil; and 2 Division of Biomorphology–Institute of Health Sciences, Federal University of Bahia, Salvador-Bahia, Brazil ABSTRACT Background: Levodopa is considered the gold stan- dard therapy for Parkinson’s disease (PD). Aspiration pneumonia is the most frequent cause of death among PD patients. Asymptomatic respiratory impairment can be detected even in the initial stages of the disease course; however, there is no conclusive evidence regarding the efficacy of levodopa, the main therapeutic drug for PD, to enhance pulmonary function in these patients. Objective: The aim of this systematic review and meta-analysis was to evaluate the effects of levodopa therapy on respiratory parameters in patients with PD. Methods: After a comprehensive and systematic lit- erature search in the electronic databases MEDLINE, Embase, the Cochrane Library, and Web of Science, all trials referring to levodopa and respiratory function that met the eligibility criteria were included in the analysis. Considered outcomes were forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1 ), the ratio between FEV 1 and FVC (FEV 1 /FVC), and peak expira- tory flow (PEF). The fixed effects model was used to as- sess the weighted mean difference, and heterogeneity be- tween studies was calculated with the I 2 test. Results: Four clinical trials comprising 73 patients and assessing the effects of levodopa on pulmonary function in patients with PD were included in the anal- ysis. Pooled data showed that levodopa significantly improved FVC (SMD, 0.40; P = 0.02) and PEF (stan- dard mean difference, 0.39; P = 0.03). No significant change was observed with FEV 1 (SMD, 0.34; P = 0.05) or the FEV 1 /FVC ratio (standard mean differ- ence, -0.08; P = 0.66) after levodopa therapy. Conclusions: The results of this systematic review suggest that levodopa therapy improved FVC and PEF, whereas no changes were observed in FEV 1 and FEV 1 / FVC. These findings may provide some indirect evi- dence regarding the efficacy of levodopa in restrictive parameters of pulmonary function. (Clin Ther. 2012; 34:1049 –1055) © 2012 Elsevier HS Journals, Inc. All rights reserved. Key words: levodopa, Parkinson’s disease, pulmo- nary dysfunction, respiratory function, therapeutics. INTRODUCTION Since its discovery in the early 1960s, levodopa has been considered the gold standard treatment for Par- kinson’s disease (PD). 1,2 Initially, data suggested that all PD manifestations could be relieved by administra- tion of the drug. Cardinal motor symptoms such as bradykinesia, rigidity, and tremor do improve with levodopa therapy. However, data regarding the effi- cacy of levodopa in the treatment of autonomic dys- function, including respiratory disorders, in PD pa- tients still reach inconclusive results. 3 Although there is evidence of pulmonary dysfunc- tion even in the initial clinical stages, patients with PD commonly do not report respiratory symptoms until late in the disease course, generally in advanced clinical stages. 4 Increasing evidence suggests that impairment in pulmonary function can be detected even when the first motor symptoms of PD appear, probably due to dysfunction in respiratory accessory muscles and bra- dykinesia. 5–7 Aspiration pneumonia and other compli- cations due to respiratory dysfunction remain the most frequent causes of death among PD patients, 5 and it seems clear that penetration and aspiration are related to dysfunction of the protective systems in the superior airways. 8 Furthermore, several abnormalities have been associated with pulmonary impairment in PD patients, Accepted for publication March 7, 2012. doi:10.1016/j.clinthera.2012.03.001 0149-2918/$ - see front matter © 2012 Elsevier HS Journals, Inc. All rights reserved. Clinical Therapeutics/Volume 34, Number 5, 2012 May 2012 1049