Prospective evaluation of pulmonary function in Parkinson's disease patients with motor fluctuations

Abstract

Background. Spirometry patterns suggesting restrictive and obstructive pulmonary dysfunction have been reported in Parkinson’s disease (PD). However, the patterns’ precise relation to PD pathophysiology remains unclear. Purpose/Aim. To assess ON- versus OFF-state pulmonary function, the quality of its spirometric evaluation, and the quality of longitudinal spirometric findings in a large sample of PD patients with motor fluctuations. Methods. During a placebo-controlled trial of an inhaled levodopa formulation, CVT-301, in PD patients with ≥2 h/d of OFF time, spirometry was performed by American Thoracic Society (ATS) guidelines at screening and throughout the 4-week treatment period. Results. Among 86 patients, mean motor impairment during an OFF state at screening was moderately severe. However, mean spirometry results at screening were within normal ranges, and in a mixed model for repeated measures (MMRM), the results at screening were not dependent on motor state (ON vs. OFF). In the placebo group (n = 43), 76% of ON-state and 81% of OFF-state examinations throughout the study met ATS quality metrics, and in an MMRM analysis, mean findings at these patients’ arrivals for treatment-period visits showed no significant 4-week change. Across all 86 patients, flow-volume curves prior to any study-drug administration showed only a 3% incidence of “sawtooth” morphology. Conclusions. In PD patients with motor fluctuations, longitudinal spirometry of acceptable quality was generally obtained. Although mean findings were normal, about a quarter of spirograms did not meet ATS quality criteria. Spirogram morphology may be less indicative of various forms of respiratory dysfunction than has previously been reported in PD.

KEYWORDS:

• pulmonary function
• spirometry
• Parkinson's disease
• levodopa
• CVT-301

Acknowledgements

The authors wish to acknowledge Tia DeFeo-Fraulini and Amanda Gentile for expert operational assistance in the conduct of the study and Jessica Roland of Acorda Therapeutics for editorial assistance. The authors would also like to acknowledge the efforts of the CVT-301-003 Study Group for their invaluable assistance in conducting this trial.

Declaration of Interest

The authors alone are responsible for the content and writing of this paper. Neil B. Hampson worked as a noncompensated pulmonary consultant to Civitas Therapeutics during the time of the study and has no conflicts to disclose; Karl D. Kieburtz is a consultant for the National Institutes of Health (NINDS), Acorda, Astellas Pharma, AstraZeneca, Auspex, Biotie, Britannia, Cangene, CHDI, Civitas, Clearpoint Strategy Group, Clintrex, Cynapsus, Intec, Isis, Lilly, Lundbeck, Medavante, Medivation, Melior Discovery, NeuroDerm, Nueromedix, Omeros, Otsuka, Pfizer, Pharm2B, Prothena/Neotope/Elan Pharmaceutical, Raptor Pharmaceuticals, Roche/Genentech, Sage Bionetworks, Serina, Stalth Peptides, Synagile, Teikoku Pharma, Titan, Turing Pharmaceuticals, Upsher-Smith, US WorldMeds, Vaccinex, Voyager, and Weston Brain Institute. He received grants/research support from the Michael J. Fox Foundation, the National Institutes of Health (NEI, NINDS, NIA, NICHD), and Teva; Peter A. LeWitt served as a consultant or advisor for Acorda, Biogen Idec, Britannia, Cynapsus, Depomed, Impax, Insightec, Intec, Kyowa Hakko, Lundbeck, Luye, NeuroDerm, Osmotica, Pfizer, ProStrakan, Prothena, SynAgile, Teva, UCB Pharma, and USWorldMeds, and has received speaker honoraria from The International Parkinson’s and Movement Disorders Society, Lundbeck, and USWorldMeds. He is compensated for services as Editor-in-Chief of Clinical Neuropharmacology and also serves without compensation on the editorial boards of Journal of Neural Transmission, Translational Neurodegeneration, and Journal of Parkinson’s Disease. The Parkinson’s Disease and Movement Disorders Program that Dr LeWitt directs has received clinical research grant support (for conducting clinical trials and other research) from AbbVie, Acorda, Adamas, Biotie, Kyowa Hakko, The Michael J. Fox Foundation for Parkinson’s Research, the Parkinson Study Group, Pharma 2B, UCB, and USWorldMeds; Mika Leinonen is a biostatistician at 4Pharma AB, a contract research organization that provided compensated statistical consultation services to Civitas Therapeutics and also provides similar services to Acorda Therapeutics; Martin I. Freed was an employee of Civitas Therapeutics, the study sponsor that was responsible for the conduct of the study. This study was funded in part from a grant from the Michael J Fox Foundation for Parkinson's Research. Editorial assistance was provided by The Curry Rockefeller Group, LLC, which was funded by Acorda Therapeutics.

Supplemental data

Supplemental data for this article can be accessed at http://dx.doi.org/10.1080/00207454.2016.1194274.

Additional information

Funding

This study was supported in part by a grant from the Michael J Fox Foundation for Parkinsonâε^TMs Research. The study was funded by Civitas Therapeutics, now wholly owned by Acorda Therapeutics, Inc.