Forced vital capacity and cross-domain late-onset Pompe disease outcomes: an individual patient-level data meta-analysis

Abstract

Background Late-onset Pompe disease (LOPD) is a rare, metabolic disease primarily affecting the musculoskeletal and respiratory systems. Forced vital capacity (FVC) is commonly used to measure pulmonary function; however, associations between FVC and other LOPD outcomes remain unclear. Methods A systematic literature review was conducted on November 2015, updated September 2016 and supplemented with clinical trial data from the sponsor. Outcomes included: 6-min walk test distance (6MWT), FVC, maximal inspiratory/expiratory pressure (MIP/MEP), Medical Research Council-skeletal muscle strength score (MRC), 36-item short-form survey-physical component score (SF-36), Rotterdam Handicap Scale (RHS), Fatigue Severity Scale (FSS) and survival. Individual patient data meta-analysis was used for cross-sectional analyses and longitudinal analyses to determine associations between percent of predicted FVC and LOPD measures and outcomes. Results Fifteen studies were selected. From cross-sectional analyses, FVC and MRC were most strongly associated. Specifically, patients with 10% higher FVC (a round number for illustrative purposes only) were associated with a 4.72% (95% confidence interval [CI]: 3.37, 6.07) higher MRC score, indicating a positive association. Similarly, slopes for the 6MWT and SF-36 relative to a 10% higher FVC were estimated at 33.2 meters (95% CI 24.0, 42.4) and 1.2% (95% CI 0.24, 2.16%), respectively. From longitudinal analyses, a 10% incremental increase in predicted FVC was associated with an average increase of 4.12% in MRC score (95% CI 1.29, 6.95), 35.6 m in the 6MWT (95% CI 19.9, 51.6), and 1.34% in SF-36 (95% CI 0.08, 2.60). There was insufficient data to conduct analyses for RHS, FSS and survival. Conclusions FVC is positively associated with LOPD measures and outcomes across multiple domains. Additionally, longitudinal changes in FVC are positively associated with changes in the 6MWT, MRC and SF-36. Electronic supplementary material The online version of this article (10.1007/s00415-019-09401-1) contains supplementary material, which is available to authorized users.

Magnetization Transfer Ratio in Lower Limbs of Late Onset Pompe Patients Correlates With Intramuscular Fat Fraction and Muscle Function Tests

“…We obtained forced vital capacity (FVC), both seated and lying down, using the Carefusion Microlab ML 3500 MK8 spirometer (Carefusion, Yorba Linda, CA, USA). These last two tests were added due their being commonly used in Pompe disease patients to measure their clinical status ( 9 ). Finally, Creatine kinase levels in serum were quantified in the HSCSP biochemistry laboratory following standard protocols.…”

Positive association between physical outcomes and patient-reported outcomes in late-onset Pompe disease: a cross sectional study

“…In an earlier study from our own group we had already reported the positive associations between participation in daily life (RHS) and the FVC and MRC [28]. Positive associations of the physical component of quality of life (PCS) with both FVC upright and the MRC were also described in an international meta-analysis [29]. This study corroborates the present results, as the individual level data used in the international study did not include the Dutch patients included in the present study.…”

Positive association between physical outcomes and patient-reported outcomes in late-onset Pompe disease: a cross sectional study

“…In an earlier study from our own group we had already reported the positive associations between participation in daily life (RHS) and the FVC and MRC (31). Positive associations of the physical component of quality of life (PCS) with both FVC upright and the MRC were also described in an international meta-analysis (32). This study corroborates the present results, as the individual level data used in the international study did not include the Dutch patients included in the present study.…”