Utility of maximum inspiratory and expiratory pressures as a screening method for respiratory insufficiency in slowly progressive neuromuscular disorders

Highlights

• MIP and MEP can serve as a screening parameter for patients with neuromuscular disorders.

• Parallel testing of both MIP and MEP needs to be performed to increase the positive prediction probability across disease groups.

• Predicted values of MIP and MEP should be calculated for a more comprehensive interpretation of manometry results.

• Disease-specific cut-offs of MIP and MEP did not increase the prediction rate of patients with abnormal FVC and FEV1.

Abstract

The aim of this study was to assess whether different cut-offs of maximum inspiratory and/or expiratory pressure (MIP/MEP) are valuable screening parameters to detect restrictive respiratory insufficiency. Spirometry, MIP, MEP and capillary blood gas analysis were obtained from patients with confirmed neuromuscular disorders. We calculated regression analysis, sensitivity, specificity and predictive values. We enrolled 29 patients with myotonic dystrophy type 1 (DM1), 19 with late-onset Pompe disease (LOPD), and 24 with spinal muscular atrophy type 3. Moderate to high reduction in manometry was exclusively found in LOPD and DM1 patients. Significant associations were found between manometry and spirometry. Highest adjusted r² was found for MIP % predicted and forced vital capacity (FVC) % predicted. Manometry predicted abnormal FVC and forced expiratory volume 1 s (FEV1). MEP > 80 cmH₂O predicted normal FVC and FEV1, regardless of cut-off values. MIP and MEP did not positively predict alterations in capillary blood gas analysis. Disease-specific cut-offs of manometry did not increase the prediction rate of patients with abnormal FVC and FEV1. Predicted values should be calculated for a more comprehensive interpretation of manometry results. MIP and MEP can serve as a screening parameter for patients with neuromuscular disorders, but parallel testing of both MIP and MEP needs to be performed to increase the positive prediction probability across disease groups.

Introduction

Maximum inspiratory and expiratory pressures (MIP and MEP) are quick, easy and noninvasive tests for the direct measurement of the strength of respiratory muscles. MIP primarily reflects the strength of the diaphragm and secondary chest wall muscles and elasticity, whereas MEP reflects a group of expiratory muscles, primarily abdominal and chest wall muscles [1], [2], [3]. In neuromuscular disorders (NMDs), a variable affection of respiratory muscles may occur during the disease course. With a few exceptions, most of the NMDs are characterized by a slowly progressive restrictive respiratory insufficiency, caused by weakness of inspiratory and expiratory muscles in a variable degree (respiratory muscle weakness, RMW) [4]. Untreated, chronic hypercapnia and hypoxaemia lead to a decreased quality of life and increased morbidity and early mortality [[5], [6], [7]]. For evaluation of respiratory insufficiency, recommendations include spirometry (forced vital capacity, FVC and forced expiratory volume in 1 s, FEV1) as well as blood gas analysis (esp. carbon dioxide, pCO₂ and oxygen, pO₂) [8]. MIP and MEP are recommended as an additional standard diagnostic assessment in NMDs as they may detect respiratory insufficiency earlier than FVC and show a high association with early mortality [[9], [10], [11]]. As a result of this, assessments of respiratory muscle strength have been broadly used in longitudinal studies on the decline of RMW in amyotrophic lateral sclerosis, Duchenne muscular dystrophy and Pompe disease [2,3,12,13]. They serve as clinically meaningful outcome measures in various clinical trials [14]. Commonly, MIP and MEP are expressed as absolute values in cmH₂O or kPa, while measurements in spirometry are expressed both as absolute values and % predicted of normal and sometimes as % of the lower limit of normal (LLN). In clinical practice, FVC and FEV1 as the % predicted of normal as well as FCV/FEV1-ratio are commonly used for interpretation of restrictive respiratory insufficiency and treatment decisions [8,[15], [16], [17], [18]]. Although there is no generally accepted value for the definition of reduced FVC % predicted, values <75% of predicted are commonly associated with restrictive respiratory insufficiency for patients with NMDs [16]. In NMDs with a restrictive respiratory pattern, FEV1/FVC ratio typically remains normal as FEV1 is reduced proportionally to FVC. A value of FVC/FEV1-ratio below 70% predicted suggests an obstructive process [19]. Values for MIP < −40 cmH₂O and MEP < 80 cmH₂O are defined as clearly pathologic [20] as defined by analysis of large cohort studies in healthy and COPD patients [9,[21], [22], [23], [24], [25]]. As these cut-offs may be imprecise or sometimes inaccurate, there is some debate about a meaningful cut-off. Several regression equations have been published for a more precise interpretation of the results including ethnicity, gender and age, and some also included height into their equations [1,[8], [9], [10],21,22]. In NMDs, most longitudinal studies for the assessment and interpretation of respiratory strength were performed for MIP, primarily in patients with ALS, Duchenne, and Pompe disease. By contrast, reports on assessments of maximum respiratory pressures, especially for MEP, in NDMs like myotonic dystrophy or SMA3 are rare [26].

This study aimed to assess whether disease-specific cut-offs of MIP and/or MEP are a better screening parameter for early detection of restrictive respiratory insufficiency compared to the commonly used outcome measures like FVC, FEV1 or alterations in blood gas analysis.