The Effect of an Oral Beta-2 Agonist on Respiratory Muscle Strength in SCI

口服 Beta-2 激动剂对 SCI 呼吸肌力量的影响

• 批准号: 9132626
• 负责人: Gregory J. Schilero
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9132626
• 关键词: Abdominal Muscles; Acute; Adrenergic Agonists; Adverse effects; Agonist; Albuterol; Atelectasis; Attention; Breathing; Cervical; Chest; Chronic Phase; Coughing; Crossover Design; Data; Devices; Dose; Double-Blind Method; Effectiveness; Environmental air flow; Gases; Generations; Hand; Hour; Individual; Injury; Inspiratory Capacity; Intercostal Muscles; Intervention; Lead; Length; Lesion; Lung; Measurement; Measures; Metabolic; Morbidity - disease rate; Mucous body substance; Multicenter Trials; Muscle; Muscle Contraction; Muscle Fibers; Muscle Weakness; Muscle function; Oral; Oral Administration; Oral cavity; Paralysed; Paraplegia; Patients; Persons; Pharmaceutical Preparations; Placebo Control; Placebos; Pneumonia; Population; Property; Quadriplegia; Randomized; Research Design; Residual state; Resistance; Respiratory Diaphragm; Respiratory Muscles; Rest; Salmeterol; Spinal cord injury; Spinal cord injury patients; Subgroup; Testing; Thick; Thoracic spinal cord structure; Training; Translating; Ultrasonography; Vital capacity; Work; Work of Breathing; clinical application; design; discontinuation study; effective intervention; follow-up; improved; indexing; lung volume; mortality; muscle strength; pectoralis major muscle; pressure; public health relevance; pulmonary function; respiratory; thoracic pressure

 DESCRIPTION (provided by applicant): Spinal cord injury (SCI), especially involving the cervical and upper thoracic segments, can significantly compromise respiratory muscle function. Respiratory complications can ensue, including lung collapse and pneumonia, which are the primary cause for mortality in association with traumatic SCI both during the acute (< 12 months) and chronic phases post-injury. Lesions at the level of the cervical or high thoracic spinal cord result in respiratory muscle weakness, which is associated with ineffective cough, mucus retention, and mucus plugging. Residual expiratory pressure-generating capacity in persons with tetraplegia has been attributed to the clavicular portion of the pectoralis major muscle, with contraction of this muscle during cough necessary for generation of dynamic airway compression and expulsion of mucus. Inspiratory muscle function may also be compromised, as paralysis of intercostal and abdominal muscles can change the resting configuration and muscle fiber length of the diaphragm, the major muscle of inspiration, thereby impeding maximal force generation and contributing to reduction in vital capacity. Cough effectiveness is contingent upon both inspiratory and expiratory muscle strength; increasing the pressure-generating capacity of the inspiratory and expiratory muscles in persons with tetraplegia and high paraplegia may, therefore, translate to improved cough effectiveness and reduction in the propensity for atelectasis and, possibly, pneumonia. The work of breathing can be calculated by measuring change in intra-thoracic pressure due to inspiration, and the volume of gas displaced, and provides a way to determine if interventions reduce metabolic demand. Despite the fact that pulmonary complications are a major cause of morbidity and mortality in this population, there is a paucity of effective interventions in the SC population known to improve respiratory muscle strength. Respiratory muscle training, often utilizing simple hand-held portable resistive or threshold training devices, appears to have marginal effects on vital capacity and maximal static mouth inspiratory and expiratory pressures (MIP and MEP, respectively), although data is inconclusive. Pharmacologic intervention has comparatively received little attention. In a preliminary study, the inhaled long-acting beta-2 adrenergic agonist, salmeterol, was shown in a double-blind, placebo-controlled crossover design after four weeks of treatment to be associated with significant increases in lung volumes and maximal static mouth pressures suggestive of improvement in respiratory muscle strength. We recently completed a follow-up study using an oral form of a beta-2 agonist (sustained-release albuterol 4mg every 12 hours) in persons with tetraplegia and high paraplegia (injury T6 and above), that demonstrated significant improvement in MIP compared to placebo with minimal side effects. The improvements were most evident in the subgroup of SCI patients with the most profound inspiratory muscle weakness at baseline, as determined by baseline measurement of MIP, thereby identifying a subset of individuals who stand to potentially derive the greatest benefit from the intervention. Therefore, our primary aim is to identify persons with tetraplegia and high paraplegia who have significant baseline respiratory muscle weakness (baseline MIP of < 90 cmH2O) and by use of a randomized, double- blind, placebo-controlled, parallel group design determine if 16 weeks of treatment with sustained release albuterol improves: (1) inspiratory and expiratory muscle strength, (2) cough effectiveness, and (3) work of breathing. An exploratory aim will be to determine if there are sustained effects upon surrogate measures of respiratory muscle strength two weeks after discontinuation of study drug. We hypothesize that 16 weeks of oral beta-2 agonist use in SCI individuals with moderately to severely compromised respiratory muscle function will lead to a significant improvement in both inspiratory and expiratory muscle strength, as well as an improvement in cough effectiveness and decreased work of breathing compared to placebo.