Respiratory physiologic changes following spinal cord injury

INTRODUCTION — The majority of causes of traumatic spinal cord injury (SCI) in 2012 included vehicular accidents (31.0 percent), falls (40.4 percent), and firearm injuries (5.4 percent) based on a review of hospitalized patients with acute traumatic SCI in the United States [1]. The National Spinal Cord Injury Database in 2010 to 2014 reported acts of violence as an etiology in 13.5 percent and sports in 8.9 percent [2]. The percentage of SCI associated with falls increased significantly from 28 percent in 1997 through 2000 to 66 percent in 2010 through 2012 in persons aged 65 or older [1]. Causes of nontraumatic SCI include tumor, vascular disease, demyelinating spinal cord diseases, and spinal stenosis [3]. Respiratory failure is common after SCI and respiratory complications are among the most common causes of death [4,5], particularly in the years following acute injury [6] and in patients who have required mechanical ventilation [7,8]. Between 2010 and 2017, the highest mortality rate was for respiratory causes [9]. The percentage of persons discharged from a hospital ventilator dependent was 3.1 percent in the years 2010 to 2014 [2].

SCI results in physiologic changes that affect many organ systems. The changes in pulmonary physiology that occur following SCI will be reviewed here. The diagnosis and management of acute and chronic SCI and the management of the respiratory complications of SCI are discussed separately. (See "Acute traumatic spinal cord injury" and "Cervical spinal column injuries in adults: Evaluation and initial management" and "Chronic complications of spinal cord injury and disease" and "Disorders affecting the spinal cord" and "Respiratory complications in the adult patient with chronic spinal cord injury" and "Spinal column injuries in adults: Types, classification, and mechanisms".)

ASSESSMENT OF LEVEL AND COMPLETENESS OF SCI — Pulmonary physiologic changes due to spinal cord injury (SCI) are related to the extent of neurological impairment. The American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) have developed standards for documenting the neurological level and severity of a patient with SCI [10]. The ASIA/ISCoS exam is used to determine the degree of impairment using the American Spinal Injury Association Impairment Scale (AIS). This scale classifies the degree of impairment based on strength in key muscles and on a sensory exam (table 1) [11]. A motor and sensory exam guide and worksheet are available. (See "Acute traumatic spinal cord injury", section on 'Clinical presentation'.)

The patient’s strength in key muscle groups is assessed and graded. A muscle grade of 5/5 is normal, and a grade of 3/5 means the muscle can be moved against gravity. The motor level is defined as the most caudal key muscle that is graded 3/5 or 4/5 with the segment cephalad to that level graded 5/5. The sensory level is defined as the most caudal dermatome to have normal sensation for both pinprick and light touch. For areas that lack key muscles to test, such as between T2 and L1, sensory findings are used to estimate motor levels.

Complete motor SCI includes AIS A (no sensory or motor function preserved below the neurologic level) and AIS B (sensory but no motor function preserved below the neurologic level) (table 1). Incomplete motor SCI includes AIS C where motor function in less than half of the key muscles below the neurologic level have a muscle grade less than 3, and for AIS D more than half the key muscles below the neurologic level have a muscle grade of 3 or more. (See "Muscle examination in the evaluation of weakness", section on 'Manual muscle strength testing'.)

With tetraplegia, there is injury to at least one of the eight cervical segments of the spinal cord; with paraplegia, there is injury in the thoracic, lumbar, or sacral regions. Based on the National Spinal Cord Injury Database 2010 to 2014. 28.8 percent of SCI had cervical A, B, or C level of injury.

PULMONARY PHYSIOLOGIC CHANGES — Pulmonary physiologic changes following spinal cord injury (SCI) include: (1) impairment of ventilatory muscle performance; (2) changes in lung and chest wall compliance; (3) changes in ventilatory control; and (4) airflow limitation and bronchial hyperresponsiveness. In describing the occurrence of these changes, it is useful to consider SCI in three phases: (1) immediately following the injury; (2) during the year thereafter; and (3) more than one year after injury.

Timing of changes in ventilatory function — Immediately after SCI, flaccid paralysis occurs and affects all muscles caudal to the level of injury, a physiologic state is known as spinal shock. Subsequent improvements in pulmonary function are due primarily to functional descent of the neurologic injury level as spinal cord inflammation resolves, enhanced recruitment of accessory ventilatory muscles, retraining of deconditioned muscles, and the evolution from flaccid to spastic paralysis [12-16]. Starting from several days to up to four to six weeks, spinal reflexes return and eventually become exaggerated as the syndrome of spasticity develops. In a study of 54 patients (mean age 65 years old) who experienced mainly incomplete cervical spinal cord damage as a result of a hyperextension injury and no accompanying bone fracture, mean vital capacity improved substantially from 57.7 percent predicted at admission to 78.9 percent predicted at 12 weeks [17]. In more severely injured patients with complete motor and sensory loss at presentation, the vital capacity increased from a mean of 31.1 percent predicted (11 patients) to 44.9 percent predicted (9 patients) at three months [13]. (See "Acute traumatic spinal cord injury", section on 'Transient paralysis and spinal shock' and "Chronic complications of spinal cord injury and disease", section on 'Spasticity'.)

The timing of respiratory failure was examined in 72 patients with traumatic cervical SCI [18]. Among those who required mechanical ventilation, 90 percent of the episodes of respiratory failure occurred within the first three days after SCI. Improvement in respiratory muscle performance after SCI largely occurs in the first year following injury [16,19-21].

Impairment of ventilatory muscle function — The extent of ventilatory muscle impairment depends upon the degree and location of the injury, as well as the duration of time since the injury. The higher the level and more complete the injury, the more likely that there will be respiratory muscle dysfunction. Ventilatory muscles innervated below the level of a complete SCI are completely nonfunctional (AIS A or B), while the degree of ventilatory muscle compromise is variable in patients with incomplete injuries (AIS C or D) (table 1). (See 'Assessment of level and completeness of SCI' above and "Acute traumatic spinal cord injury", section on 'Clinical presentation' and "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Clinical manifestations'.)

Muscles of respiration — The most important muscle that mediates inspiration is the diaphragm, which is innervated by the phrenic nerves (third to fifth cervical roots). The other principal muscles of inspiration are the external intercostals innervated by thoracic nerve roots [22]. Accessory muscles of inspiration include the pectoralis major and minor, scalenes, serratus anterior, serratus posterior superior, levator scapulae, trapezius, and sternocleidomastoids. The scalenes are innervated by cervical nerve roots C4 to C8 and the sternocleidomastoid and trapezius muscles are innervated via C1 to C4 and also cranial nerve XI. Patients with high SCI can sometimes utilize oral, pharyngeal, and laryngeal muscles for short-term ventilation by projecting boluses of air past the glottis (glossopharyngeal breathing), although these muscles are not traditionally thought of as muscles of respiration. (See "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction", section on 'Glossopharyngeal breathing'.)

The muscles of expiration are the abdominal wall muscles (rectus abdominus, obliques, and transversus abdominus), innervated by the lower thoracic and lumbar nerve roots, and the internal intercostals, innervated by the thoracic nerve roots. Normally, expiration is passive and does not require use of these muscles. However, these muscles are crucial when forced exhalation is needed, such as during exercise or coughing. When the ability to generate forced exhalation for coughing is impaired, removal of airway secretions is ineffective. In addition, these muscles contribute to normal function of the diaphragm in three important ways [23-27]:

●The intercostal muscles help to stabilize the rib cage, preventing inward collapse of the rib cage during diaphragmatic contraction for inspiration. In patients with cervical or thoracic SCI, paralysis of the intercostal muscles leads to inward motion of the rib cage during inspiration, thus decreasing the volume of air inspired for a given amount of diaphragmatic work.

●The integrated abdominal wall and thoracic cage musculature act as a fulcrum against which the diaphragm can contract. Loss of this fulcrum effect reduces the efficiency of the diaphragm.

●Flaccid paralysis of the abdominal wall muscles leads to relocation of the abdominal contents caudad, away from the diaphragm. The diaphragm is less steeply domed and, therefore, less efficient.

Injury above C3 — Complete injury above C3 produces near total ventilatory muscle paralysis because the phrenic nerve, which innervates the diaphragm, arises from the third to fifth cervical roots. In addition, the intercostal, abdominal muscles, sternocleidomastoid, and trapezius muscles are denervated. Due to complete paralysis of the respiratory muscles, patients with SCI above the C3 root have acute ventilatory failure and do not survive unless manual ventilation is rapidly instituted at the accident scene. (See "Respiratory complications in the adult patient with chronic spinal cord injury", section on 'Respiratory insufficiency'.)

In addition to ventilatory dysfunction, these patients are unable to cough without assistance.

Injury at C3 through C5 — Injuries involving C3 to C5 cause variable impairment of diaphragmatic strength and variable impairment of the accessory muscles of inspiration (eg, scalenes, sternocleidomastoid, trapezius and others). Respiratory failure requiring mechanical ventilation is common during the first few days to weeks after the injury, either due to respiratory muscle weakness and fatigue or precipitated by atelectasis or pneumonia. As the initial muscle flaccidity transitions to spasticity and accessory muscles are recruited and strengthened, spontaneous ventilation is often adequate for weaning from mechanical ventilation. (See "Respiratory complications in the adult patient with chronic spinal cord injury", section on 'Respiratory insufficiency' and "Respiratory complications in the adult patient with chronic spinal cord injury", section on 'Pulmonary infection'.)

In addition to ventilatory dysfunction, these patients have an impaired cough due to loss of expiratory muscle strength.

Injury at C6 through C8 — Patients with complete cervical SCI but with intact diaphragm function are able to inhale via the diaphragm and accessory muscles above the level of injury (such as muscles in the neck). Exhalation occurs primarily through the passive recoil of the chest wall and lungs, because the primary muscles of exhalation (internal intercostals and muscles of the abdominal wall) are paralyzed. When the arms are fixed, the clavicular portions of the pectoralis major muscles may contribute to exhalation; training of this muscle has been described but typically provides only a small contribution [28,29]. Thus, cough is impaired and even if these patients do not have initial respiratory failure, they are at an increased risk of respiratory muscle fatigue in the setting of respiratory system loading (eg, pneumonia or excess secretions) [22,26,27,30]. (See 'Muscles of respiration' above.)

Injuries of the thoracic spinal cord — Patients with injuries of the thoracic spinal cord have intact diaphragm function. Despite some loss of intercostal muscle strength and impaired stabilization of the rib cage due to abdominal wall paralysis, they have less impairment of overall ventilatory muscle function, as described below. (See 'Other etiologies of PFT abnormalities' below.)

The main respiratory impairment for these patients is an inefficient cough mechanism.

Changes in lung and chest wall compliance — Lung and chest wall compliance, when measured 1 to 12 months after SCI, is reduced in patients with tetraplegia, compared with normal subjects [31]. The decrease in compliance has been attributed to the accompanying reduction in lung volumes and possibly changes in surfactant that can occur with ventilation at reduced lung volumes [21]. Although the abdomen is highly compliant in quadriplegia, the rib cage compartment of the chest wall is stiff because of intercostal muscle spasticity and ankylosis of the rib articulations with the spine and sternum. It is believed that ankylosis of rib articulations results from an inability to inspire to total lung capacity due to inspiratory muscle weakness [21,31-34].

Airflow limitation and bronchial hyperresponsiveness — Subjects with tetraplegia demonstrate reversible expiratory airflow limitation, which is usually only apparent when a bronchodilator is administered, as the predominant abnormality is a restrictive ventilatory defect. Loss of postganglionic sympathetic innervation to the airways is a potential mechanism contributing to airflow limitation, although the functional significance of direct sympathetic airway innervation is thought to be minor or absent. The reversibility of this airflow limitation was demonstrated by the administration of inhaled ipratropium bromide, an anticholinergic agent, which caused an increase in expiratory airflow [35,36]. This reversibility suggests that unopposed vagal cholinergic (bronchoconstrictor) activity also contributes to airflow limitation. An alternate explanation is reduced airway smooth muscle relaxation secondary to lack of inhalation to a normal total lung capacity [35-39]. (See "Neuronal control of the airways", section on 'Innervation of the lower airways'.)

Abnormalities of sympathetic or parasympathetic nervous system activity may also be responsible for airway hyperresponsiveness noted after SCI causing quadriplegia [40]. (See 'Bronchial hyperresponsiveness and bronchodilator response' below.)

Changes in ventilatory control — Individuals with tetraplegia have an abnormally small increase in ventilatory drive in response to hypercapnia [41,42]. As an example, a study of nine tetraplegic subjects and eight able-bodied controls found that the ventilatory response to hypercapnia among quadriplegics was approximately one-fourth that of controls [42]. The mechanism for a blunted response to hypercapnia is not fully explained by respiratory muscle weakness, as patients with comparable respiratory muscle weakness due to other causes do not exhibit the same blunted response. (See "Control of ventilation".)

One hypothesis is that the blunted response is related to a decrease in blood pressure in the sitting position. This was examined in a study of 12 subjects with tetraplegia that found a normal ventilatory response to hypercapnia in the supine position and a reduced response in the sitting position [43]. The ventilatory response correlated better with blood pressure changes than with improved chest cage mechanics associated with the supine position.

Sleep-disordered breathing has been reported in individuals with SCI and is predominantly obstructive or a combination of obstructive and central. Sleep-disordered breathing following SCI is discussed separately. (See "Respiratory complications in the adult patient with chronic spinal cord injury", section on 'Sleep-disordered breathing'.)

ASSESSMENT OF PULMONARY FUNCTION — Some of the techniques for performing pulmonary function tests (PFTs) need to be modified in the presence of spinal cord injury (SCI). In addition, changes in respiratory muscle performance following SCI result in abnormal PFT results that can be predicted based on the level and completeness of SCI and other factors.

Technical considerations in measuring pulmonary function — Standardized techniques for performing PFTs and calculating predicted values need adjustment due to the practical challenges posed by SCI.

Measurement of height — Height is used to calculate predicted pulmonary function values in the able-bodied, but precise measurement of height in SCI patients can be problematic since most cannot stand. Since recalled height may be inaccurate, it is suggested that supine length, taking care to straighten contractures, be measured for use in the calculation of predicted pulmonary function values in SCI [44]. Arm span measurements appear less reliable than recalled height based on a study of 88 individuals with SCI; arm span was found to be less accurate and explained less variability in measured length (r² = 0.62) than recalled length (r² = 0.78) [44].

Use of modified ATS standards — Many SCI patients, particularly those with complete tetraplegia cannot meet the acceptability and reproducibility standards for spirometry set by the American Thoracic Society (ATS) [45]. ATS standards require that exhalation last for more than six seconds, but in a study of 278 adults with SCI, the most common reason for unacceptable trials was failure to exhale maximally for a minimum of six seconds [46]. (See "Office spirometry" and "Office spirometry", section on 'Forced expiratory volume in six seconds'.)

American Thoracic Society (ATS) criteria also require a prompt onset of exhalation, but subjects with complete quadriplegia are more likely than others with SCI to have a delay at the start of a forced expiratory maneuver, resulting in an excessive back-extrapolated volume (BEV). The BEV is the volume of gas that has already been expired from maximal lung volume before the start of exhalation using the slope of the steepest portion of the volume-time curve to determine time 0 [45,47]. ATS standards prior to 2019 were that the BEV had to be less than 5 percent of FVC or 150 mL, whichever is greater, in order to identify spirometry that did not represent maximal effort [45]. In 2019, the 150 mL limit was reduced to 100 mL [47]. As an example, in a study of 278 adults with SCI, those with excessive back-extrapolated volume had a back-extrapolated volume of 7.4 percent of the FVC, which is higher than the ATS criterion [46]. Patients with expiratory muscle weakness appear to have reduced acceleration of the respiratory system at the onset of a forced expiratory effort, causing the slight delay.

When ATS standards are modified to allow expiratory efforts less than six seconds, as long as a 0.5 second plateau is achieved (presumably at residual volume), and a greater degree of excessive back-extrapolated volume, as long as the volume-time curves and flow volume loops are otherwise acceptable, then the FVC and forced expiratory volume in one second (FEV₁) are reproducible [46]. This finding indicates that despite respiratory muscle weakness, the FVC and FEV₁ can be assessed longitudinally at all levels and neurologic completeness of SCI.

Mouthpiece for pressure measurements — In order to achieve accurate measurement of maximal inspiratory and expiratory static pressures, the mouthpiece may need to be adjusted. Measurement of maximal inspiratory pressure after SCI is generally acceptable using a conventional mouthpiece with a flange that fits inside the mouth (picture 1). However, measurement of maximal expiratory pressure muscle with a flange style mouthpiece may result in the underestimation of maximal expiratory respiratory muscle strength [48]. For reliable results, a tube style mouthpiece that fits outside and around the mouth should be substituted [48]. (See "Tests of respiratory muscle strength", section on 'Maximal inspiratory and expiratory pressure'.)

Effect of posture — Posture has a significant impact upon lung mechanics in the majority of patients with SCI. Typically, individuals with SCI have an increase in vital capacity (VC) when changing from a seated to supine position, whereas the normal response to recumbency is a slight decrease in VC. As examples:

●Among 14 patients with tetraplegia (C4-C7), the mean increase in VC was 0.41 L (16 percent of the seated value) [49].

●In a study of 74 patients with SCI, the FVC and forced expiratory volume in one second (FEV₁) were larger in the supine compared with the seated posture down to an injury level of T1 [50]. Smaller postural differences were observed in this study, possibly due to the inclusion of persons with both complete and incomplete SCI. Among those with quadriplegia, the mean FVC was 2.87 L when supine and 2.7 L when seated, and mean FEV₁ values were 2.41 L and 2.36 L, respectively. The expiratory reserve volume (ERV) decreased in the supine position and the inspiratory capacity (IC) increased proportionally more than the VC (2.21 L when seated and 2.56 L when supine).

●In eight patients with C4 to C7 motor complete tetraplegia, the mean IC increased significantly from the seated (1.34 L) to the tilted (1.61 L) and the supine (2.14 L) position, with no significant change in total lung capacity (TLC) [24]. Mean functional residual capacity (FRC) decreased progressively (by approximately 1 liter) from the seated (3.11 L) to the tilted (2.74 L) and the supine (2.15 L) position.

A change from the seated to the supine position results in a decrease in FRC because the abdominal contents push upon the diaphragm. However, the muscle fibers of the diaphragm are longer at end expiration when supine and, thus, at a more favorable portion of their length-tension curve, resulting in a greater downward (caudad) excursion of the diaphragm during inspiration. Together, these effects result in an improved IC and VC when supine. On the other hand, gas exchange abnormalities are more likely in the supine position due to airway closure and any atelectasis that could arise from tidal breathing at lower respiratory system volumes (at a reduced FRC). When choosing a position to optimize respiratory system function, the advantage of a greater VC and IC must be weighed against the possibility of gas exchange problems due to airway closure and atelectasis (eg, arising from tidal breathing at lower respiratory system volumes).

Expected values for spirometry — Three cross sectional studies of large cohorts have assessed spirometry in patients several years after SCI and temporally distant from any acute illness. These studies included 216 adults from the Bronx Veterans Affairs hospital, 239 from the Rancho Los Amigos National Rehabilitation Center in Los Angeles, and 339 veterans and nonveterans recruited from the surrounding community at the Boston Veterans Affairs Medical Center [51-53]. The results of these studies are summarized here. An additional study included 440 adults with SCI, but did not adjust for smoking history and included persons within six months after injury, so would not accurately represent the effects of chronic SCI on pulmonary function [54].

The VA Boston study assessed the cross-sectional effect of a wide range of clinical factors on FVC, FEV₁, and FEV₁/FVC ratio. In this study, adjusting for stature and neurologic level and completeness of SCI, lower FEV₁ values were significantly related to greater age, greater years since injury (-6 mL/year), greater lifetime cigarette smoking (pack years), previous chest injury or operation, a history of clinician-diagnosed asthma, self-report of wheeze (using a standardized respiratory symptom questionnaire), and a lower maximum inspiratory pressure. The cross-sectional effect of age on FEV₁ was similar to that observed in studies describing the effects of age in the able-bodied. The effect of years since injury on FEV₁ was greatest in the weakest persons with tetraplegia (ASIA A and C, -12 mL/year). In addition, a reduction in FEV₁/FVC was associated with older age, greater lifetime cigarette smoking (pack years), previous chest injury or operation, self-report of wheeze, and a greater body mass index [53].

In the Bronx VA study, smoking resulted in a reduction in FEV₁/FVC in patients with quadriplegia and paraplegia [51,52]. In the Los Angeles cohort, a consistent effect of current smoking was not observed, but a greater number of years since injury was associated with a reduction in FEV₁ [52].

After determining the factors other than SCI that affect spirometry results following SCI, the mean values for FEV₁, FVC, and FEV₁/FVC in the Boston cohort were adjusted to determine the expected impairment based on neurologic level and completeness of SCI [53]. The adjusted mean values (95% confidence intervals) for the FEV₁ and FVC were the following:

●C4 to C5 complete motor cervical SCI – 55 percent (49 percent to 61 percent) and 53 percent (47 percent to 59 percent) of predicted values, respectively

●C6 to C8 complete motor cervical SCI – 65 percent (60 percent to 70 percent) and 64 percent (59 percent to 68 percent) of predicted values, respectively  

●T1 to T6 paraplegia – 80 percent (76 percent to 84 percent) and 78 percent (74 percent to 81 percent) of predicted values, respectively

The FEV₁/FVC ratio decreased with lower SCI levels in complete injury. Similar to the Los Angeles and Bronx cohorts, the FEV₁/FVC was greater in quadriplegics than in paraplegics. The relationship between FEV₁/FVC and SCI level in complete SCI may be attributed to a reduction in expiratory flow during a forced exhalation due to weaker expiratory muscles and a lower driving pressure causing less dynamic compression of airways and subsequently less increase in resistance. Therefore, the FEV₁/FVC in persons with the weakest expiratory muscles (such as in tetraplegia and high paraplegia) is expected to be less sensitive to factors usually associated with changes in airway size (such as smoking) and may not reliably detect the severity of airflow obstruction.

Expected values for lung volumes — Most patients with complete cervical motor SCI will have a restrictive ventilatory defect (decreased TLC and FVC). The FRC and ERV are also reduced, but the residual volume (RV) is increased. The decreases in TLC, FRC, and ERV are attributable to inspiratory muscle weakness, while the increase in RV is due to expiratory muscle weakness. (See "Overview of pulmonary function testing in adults" and "Selecting reference values for pulmonary function tests".)

In the VA Boston study described above, the values for TLC, FRC, RV, and ERV were assessed and compared with the neurologic level and completeness of SCI [55]. These data may be used to estimate the expected average effects of SCI on lung volumes for individuals with SCI:

●Among subjects with complete SCI, the mean percent-predicted values for high and low cervical SCI were 74 to 78 for TLC, 75 to 79 for FRC, 106 to 112 for RV, and 31 to 32 for ERV, respectively.

●Among subjects with incomplete cervical SCI, the mean percent-predicted values for TLC, FRC, and RV were normal, but ERV was moderately reduced.

●Among subjects with complete or incomplete thoracic SCI, the mean percent-predicted values for TLC, FRC, and RV were normal, but ERV was mildly reduced.

Greater body mass index (BMI) was significantly associated with a linear decrease in TLC, FRC, RV, and ERV [55]. Greater time since injury was also associated with decreases in TLC, FRC, RV, and ERV (range, -8 to -18 mL/year). Age was not a significant predictor of TLC once time since injury was included in the multivariate regression model. Greater lifetime smoking was associated with increased FRC and RV, and a history of chronic obstructive pulmonary disease (COPD) was associated with a greater RV.

Longitudinal assessment of pulmonary function — Several case series have observed that after SCI, the greatest rate of improvement in pulmonary function occurs in the first three months and is followed by further more gradual improvement up to about one year following the initial injury [15,16,20,22]. Over the next many years, a gradual decline in pulmonary function is observed.

●Among 36 subjects with tetraplegia, the greatest rate of improvement in VC occurred during the first three months with slower subsequent improvement up to 10 months; the overall increase was from 45 to 58 percent of predicted [15].

●In 12 subjects with motor complete injuries (including eight cervical), there was a mean improvement in FEV₁ from 1.82 L to 2.54 L and in FVC from 2.03 L to 2.69 L between 90 days and 210 days after injury [20].

●Among five subjects with motor complete tetraplegia studied within 47 days of injury and followed for up to a year, there was an increase inspiratory capacity (1.84 L to 2.71 L) and expiratory reserve volume (0.11 L to 0.27 L) [21].

Longitudinal change in FEV₁ and FVC in chronic SCI appears to be related to age and potentially modifiable factors, such as cigarette smoking and a greater body mass index [56]. In order to directly assess factors associated with longitudinal changes pulmonary function, 174 patients with chronic SCI in the VA Boston cohort described above underwent repeated measurement of FVC and FEV₁ over an average follow-up time of 7.5 years (range: 4 to 14 years) [56]. Neurologic level and completeness of SCI was not a direct determinant of longitudinal decline in FVC and FEV₁. However, declines in FVC and FEV₁ were related to continued smoking, persistent wheeze, an increase in body mass index, a greater degree of respiratory muscle weakness (assessed by measurement of maximal inspiratory pressure), and the effects of aging. The effects of aging were similar to those noted in the able-bodied. A greater body mass index was also associated with a longitudinal decline in FEV₁/FVC.

A borderline effect of greater injury duration on decline in FEV₁ was noted in persons with more severe injury, ie, cervical SCI that was motor complete (AIS A and B) or motor incomplete AIS C. It has been hypothesized that the effect of greater injury duration on pulmonary function is attributable to a slow but progressive decrease in lung and rib cage compliance [53,55,56]. In contrast to the effect of injury duration noted in the cross-sectional assessment of FEV₁ described above, the borderline significance of this effect in the longitudinal study may be caused by the slow rate of change of lung and rib cage compliance relative to the duration of follow-up testing. An additional study in 173 persons also reported no effects of injury severity on longitudinal change in FVC [57]. These results suggest a model in which neurological completeness and level of injury account for a reduction in the level of FEV₁ and FVC (ie, assessed cross-sectionally), but do not appreciably influence longitudinal decline.

Maximal inspiratory and expiratory pressures — In general, when the level of SCI is below C5 and thus spares the phrenic nerve, maximal expiratory force is impaired more than maximal inspiratory pressure, which remains within the normal range. In the VA Boston study, a greater maximal inspiratory pressure (MIP), as an indicator of respiratory muscle performance, was associated with greater TLC and was inversely related to RV [55]. (See "Tests of respiratory muscle strength" and 'Impairment of ventilatory muscle function' above.)

Bronchial hyperresponsiveness and bronchodilator response — Individuals with tetraplegia, but not with low paraplegia, demonstrate airways hyperreactivity on bronchoprovocation testing with methacholine, histamine, and ultrasonically nebulized distilled water [58-60]. The clinical significance of this finding remains unclear. For example, in an epidemiological survey of 343 persons with chronic SCI, there was no association between level and severity of SCI and report of wheeze [61]. However, in the 2010 cycle of the Canadian Community Health Survey, patients with SCI had an increased risk of also reporting asthma (odds ratio [OR] 1.59; 95% CI 1.11-2.26) and COPD (OR 1.87, 95% CI 1.20-2.91), adjusting for age, sex, and smoking [62]. Therefore, it is possible that patients with SCI may be more likely to be diagnosed with conditions that may be associated with airways hyperreactivity. (See "Bronchoprovocation testing" and 'Airflow limitation and bronchial hyperresponsiveness' above.)

Approximately, 40 to 50 percent of SCI patients exhibit significant responses to bronchodilator administration, even in the absence of demonstrable airflow limitation at baseline [35,37]. However, the clinical benefit of routine use of bronchodilators to maximize the pulmonary function of individuals with tetraplegia, but no history of asthma or COPD, has not been established.

Other etiologies of PFT abnormalities — When interpreting pulmonary function test (PFT) results in an individual with SCI, it is important to remember that factors other than neurologic level and completeness of injury can affect pulmonary function. These other factors include cigarette smoking, obesity, other chest trauma sustained at the time of the SCI, and co-morbidities such as asthma, COPD, and tracheal stenosis from prior intubation [51-53].

SUMMARY AND RECOMMENDATIONS

●Pulmonary physiologic changes due to spinal cord injury (SCI) are related to the extent of neurological impairment. The American Spinal Injury Association Impairment Scale (AIS) is used to classify the degree of impairment that is based on strength in key muscles and on a sensory exam (table 1). An exam guide and worksheet for assessing SCI is available through the American Spinal Cord Injury Association. (See 'Assessment of level and completeness of SCI' above.)

●Immediately after SCI, flaccid paralysis affects all muscles caudal to the level of injury (also known as spinal shock). Subsequent improvements in pulmonary function are due primarily to functional descent of the neurologic injury level as spinal cord inflammation resolves, enhanced recruitment of accessory ventilatory muscles, retraining of deconditioned muscles, and the evolution from flaccid to spastic paralysis. (See 'Timing of changes in ventilatory function' above.)

●The extent of ventilatory muscle impairment depends upon the degree and location of the injury, as well as the duration of time since the injury. The higher the level and more complete the injury, the more likely that there will be respiratory muscle dysfunction. Complete injury above C3 produces near total ventilatory muscle paralysis because the phrenic nerve, which innervates the diaphragm, arises from the third to fifth cervical roots. (See 'Impairment of ventilatory muscle function' above.)

●Posture has a significant impact upon lung mechanics in the majority of patients with SCI. Typically, individuals with SCI have an increase in vital capacity (VC) when changing from a seated to supine position, whereas the normal response to recumbency is a slight decrease in VC. (See 'Technical considerations in measuring pulmonary function' above.)

●Measurement of supine length is preferred over arm-span or recalled standing height for use in the calculation of predicted pulmonary function values for persons with SCI. (See 'Measurement of height' above.)

●When obtaining spirometry, American Thoracic Society (ATS) standards may need to be modified to accept expiratory efforts less than six seconds in duration, as long as a 0.5 second plateau is achieved (presumably at residual volume), and a greater degree of back-extrapolated volume (eg, ~7.5 percent of forced vital capacity), when volume-time curves and flow volume loops are otherwise acceptable. (See 'Use of modified ATS standards' above.)

●Among individuals with chronic cervical cord injury, spirometry typically shows a restrictive ventilatory defect with forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁) values approximately 55 percent of the values predicted for able-bodied subjects. (See 'Expected values for spirometry' above.)

●Lung volumes following complete cervical cord injury show a marked reduction in expiratory volume (ERV), a mild to moderate reduction in total lung capacity (TLC) and functional reserve volume (FRC), and preservation of residual volume (RV). The main lung volume abnormality after incomplete cervical or thoracic SCI is a moderate reduction in ERV. (See 'Expected values for lung volumes' above.)

●Longitudinal change in FEV₁ and FVC in chronic SCI appears to be related to age and potentially modifiable factors, such as cigarette smoking and a greater body mass index. Greater lifetime cigarette smoking (pack years) is associated with lower values for FVC and FEV₁ both initially after SCI and during long-term follow-up (see 'Expected values for spirometry' above and 'Longitudinal assessment of pulmonary function' above). A greater body mass index in SCI has been associated with reduced lung volumes, a reduced FEV₁/FVC, and longitudinal decline in FEV₁ and FEV₁/FVC.  

●In general, when the level of SCI is below C5 and thus spares the phrenic nerve, maximal expiratory force is impaired more than maximal inspiratory pressure, which remains near or within the normal range. (See 'Maximal inspiratory and expiratory pressures' above.)

●Pulmonary function testing in persons with weaker respiratory muscles (ie, cervical A, B, or C tetraplegia) may not reliably detect airflow limitation. Airflow limitation may only become apparent during reversibility testing with inhaled bronchodilators such as beta2-agonists and the anticholinergic agent ipratropium bromide. Report of wheeze in SCI is also associated with a reduction in FEV_1. However, the clinical benefit regarding the routine use of bronchodilators in quadriplegia for purposes of maximizing pulmonary function has not been established. (See 'Airflow limitation and bronchial hyperresponsiveness' above and 'Bronchial hyperresponsiveness and bronchodilator response' above.)