Fatigue and anxiety mediate the effect of dyspnea on quality of life in amyotrophic lateral sclerosis

Abstract

Introduction: Dyspnea (or breathlessness) due to progressive neuromuscular respiratory failure is common in amyotrophic lateral sclerosis (ALS). It is associated with anxiety, depression and reduced quality of life (QoL). For effective treatment, it is essential to understand the relationships between dyspnea, anxiety, depression and QoL.

Methods: The UK Trajectories of Outcomes in Neurological Conditions-ALS study (TONiC-ALS) collected self-report measures from patients with ALS. Ordinal scales were transformed to interval-scaled estimates by the Rasch Measurement model. They were subsequently included in a series of path models where the focal relationships were dyspnea to QoL and dyspnea to depression.

Results: Path analyses using 1022 participants showed that 60.5% of the variance of QoL was explained by fatigue, anxiety, dyspnea and disability. For depression, 54.1% of the variance was explained by a model of these factors. Dyspnea played an important but mostly indirect role in influencing QoL and depressive symptoms. Disability was dominated by all other factors in the model.

Discussion: Dyspnea in ALS influences quality of life and depression largely through indirect effects, principally acting via anxiety and fatigue. Recognition of this is essential for clinicians to understand where to intervene for greatest benefit. Researchers must be aware that studies of the effect of dyspnea on QoL and depression require path models, measuring both direct and indirect effects, as the impact of dyspnea is likely to be significantly miscalculated if only direct effects are assessed.

Keywords:

• Dyspnea
• Rasch
• patient reported outcome measure
• quality of life
• depression

Acknowledgments

The authors sincerely thank all the people with ALS/MND and their families who contributed to this study; staff from MND Care Centres in Basildon, Brighton, Cambridge, Cumbria, Dartford and Gravesham NHS Trust, Edinburgh, Exeter, Kings’ College London, Leicester, Liverpool, London North West, London, North East, Maidstone, Manchester, Newcastle, North Devon, Norwich, Oxford, Peterborough, Portsmouth, Plymouth, Preston, Sheffield, Shropshire, Southampton, South Wales MND Care Network (Cardiff, Swansea, Cwm Taf and Hywel Dda Clinics), Stoke on Trent, Swansea, West Suffolk, Worcester for identifying and caring for study patients; the research and clinical staff for recruitment and data collection; and the TONiC team.

The authors thank NIHR Clinical Research Network and the NIHR UK MND Clinical Studies Group for support.

Declaration of interest

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by the Motor Neurone Disease Association (UK) under grant Young/Jan15/929-794, and also received research support from the NIHR Clinical Research Network, and the Neurological Disability Fund 4530. AAC is an NIHR Senior Investigator and is supported through the following funding organizations under the egis of JPND - www.jpnd.eu (United Kingdom, Medical Research Council (MR/L501529/1; MR/R024804/1) and Economic and Social Research Council (ES/L008238/1)) and through the Motor Neurone Disease Association. This study represents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Center at South London and Maudsley NHS Foundation Trust and King’s College London. CJM and this research are supported by the NIHR Sheffield Biomedical Research Center and the NIHR Sheffield Clinical Research Facility. CAY and this research are supported by NIHR CRN NWC. No funding source had involvement in the study design, analysis, interpretation of data, or preparation of the manuscript.