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.