A center's experience: pulmonary function in spinal cord injury.

Traumatic spinal cord injury (SCI) is associated with significant psychological and physical challenges. A multidisciplinary approach to management is essential to ensure recovery during the acute phase, and comprehensive rehabilitative strategies are necessary to foster independence and quality of life throughout the chronic phase of injury. Complications that beset these individuals are often a unique consequence of SCI, and knowledge of the effects of SCI upon organ systems is essential for appropriate management. According to the National SCI Statistical Center (NSCISC), as of 2010 there were an estimated 265,000 persons living with SCI in the United States, with approximately 12,000 incidence cases annually. Although life expectancy for newly injured individuals with SCI is markedly reduced, persons with chronic SCI are expected to live about as long as individuals without SCI; however, longevity varies inversely with level of injury. Since 2005, 56 % of persons with SCI are tetraplegic, and due to paralysis of respiratory muscles, these individuals may be especially prone to pulmonary complications, which remain a major cause of mortality among persons with chronic SCI. We at the VA Rehabilitation Research and Development Center of Excellence for the Medical Consequences of SCI at the James J. Peters VA Medical Center have devoted more than 25 years to the study of secondary medical conditions that complicate SCI. Herein, we review pulmonary research at the Center, both our past and future endeavors, which form an integral part of our multidisciplinary approach toward achieving a greater understanding of and improving care for veterans with SCI.

Reproducibility and effect of posture on impulse oscillation parameters in persons with spinal cord injury.

BACKGROUND: The impulse oscillation system (IOS) offers significant value in the assessment of airway dynamics in persons with spinal cord injury (SCI) because of minimal patient effort but measurement reproducibility in SCI is unknown. OBJECTIVE: To evaluate between-day reproducibility and the effect of posture on airway resistance [respiratory resistances at 5 Hz (R5) and 20 Hz (R20)] in subjects with tetraplegia, paraplegia and able-bodied controls. METHODS: Ten subjects with tetraplegia, 10 subjects with paraplegia and 11 able-bodied individuals were evaluated using IOS. Three 30 second trials were obtained in each while in the seated and supine position on Day 1, and repeated on Day 2. RESULTS: The within-day coefficient of variation (CV%) for R5 and R20 were comparable in the 3 study groups in the seated and supine positions. Compared to controls, the between-day CV% for the combined data was higher in subjects with tetraplegia and paraplegia for R5 seated, and was higher in subjects with tetraplegia for R5 supine. CONCLUSIONS: IOS has applicability to the study of within-day respiratory resistance in SCI. However, performing longer-term studies in subjects with tetraplegia and paraplegia may be problematic because of the greater variability for R5 when compared to able-bodied individuals.

Breathing pattern and ventilatory control in chronic tetraplegia.

Blunted ventilatory responses to carbon dioxide indicate that respiratory control is impaired when ventilation is stimulated in individuals with tetraplegia; however, respiratory control during resting breathing has not been extensively studied in this population. Our objective was to evaluate respiratory control and sigh frequency during resting breathing in persons with tetraplegia. A prospective, two-group comparative study was performed. Breathing pattern was assessed in ten outpatients with chronic tetraplegia and eight age- and gender-matched able-bodied controls. Subjects were noninvasively monitored for 1 h, while seated and at rest. Tidal volume (V(T)) was calculated from the sum of the anteroposterior displacements of the rib cage and abdomen and the axial displacement of the chest wall. Inspiratory time (T(I)), V(T), and the ratio of V(T) to inspiratory time (V(T)/T(I)) were calculated breath by breath. A sigh was defined as any breath greater than two or more times an individual's mean V(T). Minute ventilation, V(T)/T(I), and sigh frequency were reduced in tetraplegia compared with controls (5.24 +/- 1.15 vs. 7.16 +/- 1.29 L/min, P < 0.005; 208 +/- 45 vs. 284 +/- 47 ml/s, P < 0.005; and 11 +/- 7 vs. 42 +/- 19 sighs/h, P < 0.0005, respectively). V(T)/T(I) was associated with sigh frequency in both groups (tetraplegia: R = 0.88; P = 0.001 and control: R = 0.70; P < 0.05). We concluded that reductions in minute ventilation, V(T)/T(I), and sigh frequency suggest that respiratory drive is diminished during resting breathing in subjects with tetraplegia. These findings extend prior observations of disordered respiratory control during breathing stimulated by CO(2) in tetraplegia to resting breathing.

Pulmonary function and spinal cord injury.

Injury to the cervical and upper thoracic spinal cord disrupts function of inspiratory and expiratory muscles, as reflected by reduction in spirometric and lung volume parameters and static mouth pressures. In association, subjects with tetraplegia have decreased chest wall and lung compliance, increased abdominal wall compliance, and rib cage stiffness with paradoxical chest wall movements, all of which contribute to an increase in the work of breathing. Expiratory muscle function is more compromised than inspiratory muscle function among subjects with tetraplegia and high paraplegia, which can result in ineffective cough and propensity to mucus retention and atelectasis. Subjects with tetraplegia also demonstrate heightened vagal activity with reduction in baseline airway caliber, findings attributed to loss of sympathetic innervation to the lungs. Significant increase in airway caliber following inhalation of ipratropium bromide, an anticholinergic agent, suggests that reduction in airway caliber is not due to acquired airway fibrosis stemming from repeated infections or to abnormal hysteresis secondary to chronic inability of subjects to inhale to predicted total lung capacity. Reduced baseline airway caliber possibly explains why subjects with tetraplegia exhibit airway hyperresponsiveness to methacholine and ultrasonically nebulized distilled water. While it has been well demonstrated that bilateral phrenic nerve pacing or stimulation through intramuscular diaphragmatic electrodes improves inspiratory muscle function, it remains unclear if inspiratory muscle training improves pulmonary function. Recent findings suggest that expiratory muscle training, electrical stimulation of expiratory muscles and administration of a long-acting beta(2)-agonist (salmeterol) improve physiological parameters and cough. It is unknown if baseline bronchoconstriction in tetraplegia contributes to respiratory symptoms, of if the chronic administration of a bronchodilator reduces the work of breathing and/or improves respiratory symptoms. Less is known regarding the benefits of treatment of obstructive sleep apnea, despite evidence indicating that the prevalence of this condition in persons with tetraplegia is far greater than that encountered in able-bodied individuals.

Airflow obstruction and reversibility in spinal cord injury: evidence for functional sympathetic innervation.

OBJECTIVES: The first objective was to assess group differences for specific airway conductance (sGaw) among subjects with tetraplegia, high paraplegia (HP: T2-T6), and low paraplegia (LP: T10-L4). The second objective was to determine the significance of responsiveness to ipratropium bromide (IB) by the assessment of the inherent variability of baseline measurements for impulse oscillation (IOS), body plethysmography, and spirometry. DESIGN: Prospective cross-sectional intervention study. SETTING: James J. Peters Veterans Administration Medical Center. PARTICIPANTS: Subjects (N=43): 12 with tetraplegia (C4-8), 11 with HP, 11 with LP, and 9 controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measurement of IOS, body plethysmography, and spirometry parameters at baseline and 30 minutes after IB. RESULTS: Baseline sGaw was significantly lower in tetraplegia (0.14+/-0.03) compared with HP (0.19+/-0.05) and LP (0.19+/-0.04) patients. By use of minimal difference to evaluate IB responsiveness in tetraplegia, 4 of 12 and 12 of 12 subjects had significant increases in forced expiratory volume in 1 second and sGaw, respectively, whereas 11 of 12 and 10 of 12 subjects had significant decreases in respiratory resistances measured at 5 and 20 Hz (R5 and R20), respectively. CONCLUSIONS: The finding of group differences for baseline sGaw supports the hypothesis that human lung contains functional sympathetic innervation. Body plethysmography and IOS were comparable in detecting IB-induced bronchodilation in tetraplegia and significantly more sensitive than spirometry.

Salmeterol improves pulmonary function in persons with tetraplegia.

beta(2)-Adrenergic agonists are known to improve muscle strength because of anabolic properties. The purpose of this study was to determine if long-term administration of a long-acting beta(2)-adrenergic agonist to subjects with tetraplegia is associated with improvement in pulmonary function parameters and maximal static inspiratory and expiratory mouth pressures (MIP and MEP, respectively), measures of respiratory muscle strength. The study was a randomized, prospective, double-blind, placebo-controlled, crossover trial and conducted at the James J. Peters Veterans Affairs Medical Center. Thirteen subjects who had complete or incomplete tetraplegia for more than one year participated in the study. Eleven subjects completed the study. All were clinically stable outpatients without any history of asthma or use of inhaled bronchodilators. Following baseline measurements, patients were randomized to receive salmeterol or placebo from identically marked Diskus containers for 4 weeks. Following a 4-week washout period, the subjects were randomized to receive the alternate preparation for 4 weeks. Pulmonary function parameters and static mouth pressure were measured during baseline and during the fourth week of the two study periods. During the 4-week period of salmeterol administration, forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, MIP, and MEP improved significantly compared with placebo and baseline. Expiratory reserve volume increased significantly compared to baseline. Increases in MIP and MEP during salmeterol administration suggest improvement in respiratory muscle strength. However, this cannot be stated with certainty because MIP and MEP are dependent on volume parameters at which they are measured. Regardless of the mechanism, improvement in static mouth pressures indicates that salmeterol should benefit these individuals by improving cough effectiveness.

Assessment of airway caliber and bronchodilator responsiveness in subjects with spinal cord injury.

STUDY OBJECTIVES: Previous spirometric findings among subjects with chronic tetraplegia that reduction in FEV1 and maximal forced expiratory flow, mid-expiratory phase (FEF(25-75%)) correlated with airway hyperresponsiveness to histamine, and that many of these subjects exhibited significant bronchodilator responsiveness, suggested that baseline airway caliber was low in this population. To better evaluate airway dynamics in patients with spinal cord injury, we used body plethysmography to determine specific airway conductance (sGaw), a less effort-dependent and more reflective surrogate marker of airway caliber. DESIGN: Cohort study. SETTING: Veterans Affairs medical center. PARTICIPANTS: Thirty clinically stable subjects with chronic spinal cord injury, including 15 subjects with tetraplegia (injury at C4-C7) and 15 subjects with low paraplegia (injury below T7), participated in the study. Fifteen able-bodied individuals served as a control group. INTERVENTIONS: Subjects underwent baseline assessment of spirometric and body plethysmographic parameters. Repeat measurements were performed among subjects with tetraplegia and paraplegia before and 30 min after receiving aerosolized ipratropium bromide (2.5 mL 0.02% solution; 12 subjects) or normal saline solution (2.5 mL; 6 subjects). MEASUREMENTS AND RESULTS: We found that subjects with tetraplegia had significantly reduced mean values for sGaw (0.16 cm H2O/s), total lung capacity, FVC, FEV1, and FEF(25-75%) compared to subjects in the other two groups. Subjects with tetraplegia who received ipratropium bromide experienced significant increases in sGaw (135%), FEV1 (12%; 260 mL), and FEF(25-75%) (27%). Significant, though far smaller, increases in sGaw (19%) were found among subjects with paraplegia. No discernable change in any pulmonary function parameter was found following the administration of normal saline solution. CONCLUSIONS: Subjects with tetraplegia, as opposed to those with low paraplegia, have reduced baseline airway caliber due to heightened vagomotor airway tone, which we hypothesize is the result of the interruption of sympathetic innervation to the lungs, and/or from low circulating epinephrine levels.

Effects of neostigmine and glycopyrrolate on pulmonary resistance in spinal cord injury.

Preliminary findings in subjects with spinal cord injury (SCI) suggest that neostigmine administered intravenously increases colonic tone, increases colonic contractions, and facilitates bowel evacuation. Of concern are potential pulmonary side effects, including an increase in airway secretions and bronchospasm. The objectives of the study were to determine the effects of intravenously administered neostigmine or neostigmine combined with glycopyrrolate on forced oscillation indices in persons with SCI. Pulmonary resistances at 5 Hz (R5) and 20 Hz (R20) were measured with the use of an impulse oscillation system (IOS) in 11 subjects with SCI. Values were obtained before and after the intravenous administration of 2 mg of neostigmine alone and, on a separate day, before and after the administration of 2 mg of neostigmine combined with 0.4 mg of glycopyrrolate. Baseline R5 and R20 values before neostigmine correlated significantly with baseline values before neostigmine combined with glycopyrrolate. Following neostigmine, mean R5 values increased 25% and mean R20 values increased 18%. Following neostigmine combined with glycopyrrolate, mean R5 values fell 9% and mean R20 values fell 7%. In summary, baseline IOS values obtained on 2 different days were highly reproducible in this population. Neostigmine alone induced significant bronchoconstriction, whereas neostigmine combined with glycopyrrolate caused bronchodilation.

Bronchodilator responses to metaproterenol sulfate among subjects with spinal cord injury.

A previous study using spirometric methods demonstrated that 42% of subjects with tetraplegia experienced significant bronchodilation following inhalation of metaproterenol sulfate (MS). Comparative studies involving subjects with paraplegia were not performed and none has been performed in this population using body plethysmography, a more sensitive method used to assess airway responsiveness. Stable subjects with tetraplegia (n = 5) or paraplegia (n = 5) underwent spirometry and determination of specific airway conductance (sGaw) by body plethysmography at baseline and 30 minutes after nebulization of MS (0.3 mL of a 5% solution). Among subjects with tetraplegia, inhaled MS resulted in significant increases in spirometric indices and sGaw. Among subjects with paraplegia, only sGaw increased significantly, although this increase was considerably less than that seen in subjects with tetraplegia. Our findings indicate that subjects with tetraplegia exhibit greater bronchodilation in response to inhaled MS than do subjects with paraplegia and that sGaw measurements may confer greater sensitivity for assessing bronchodilator responsiveness in tetraplegia.

Comparison of lung volume measurements in individuals with spinal cord injury by two different methods.

BACKGROUND/OBJECTIVE: Few detailed studies have been performed among subjects with spinal cord injury (SCI) using whole body plethysmography for measurement of static lung volumes. Because abdominal gas volumes and respiratory patterns among subjects with varying levels of SCI may differ significantly from able-bodied individuals, methodological concerns related to this technique could conceivably lead to inaccuracies in lung volume measurements. The purpose of this study was to compare lung volume parameters obtained by whole body plethysmography with those determined by the commonly used nitrogen washout technique among individuals with SCI. PARTICIPANTS: Twenty-nine clinically stable men, 14 with chronic tetraplegia (injury C4-C7) and 15 with paraplegia (injury below T5) participated in the study. METHODS: Lung volumes were obtained using whole body plethysmography and the open-circuit nitrogen washout technique. Within both study groups, data were evaluated by the paired Student's t test and by determination of correlation coefficients. RESULTS: No statistically significant differences for any lung volume parameter were found within either group. In subjects with tetraplegia on paraplegia, respectively, strong correlation coefficients were found for measurements of total lung capacity (.86 and .97), functional residual capacity (.87 and .96), and residual volume (.77 and .85). CONCLUSION: These findings indicate that body plethysmography is a valid technique for determining lung volumes among subjects with SCI. Because airway resistance measurements can also be obtained during same study sessions for assessment of airway caliber and bronchial responsiveness, body plethysmography is a useful tool for examining multiple aspects of pulmonary physiology in this population.

Recovery of cell wall-deficient organisms from blood does not distinguish between patients with sarcoidosis and control subjects.

STUDY OBJECTIVE: To determine if cell wall-deficient forms (CWDF) of mycobacteria can be grown in culture of blood from subjects with sarcoidosis. DESIGN: A special multicenter study of sarcoidosis (A Case Control Etiologic Study of Sarcoidosis), supported by the National Heart, Lung, and Blood Institute. PATIENTS AND CONTROL SUBJECTS: PATIENTS AND CONTROL SUBJECTS were recruited at 10 institutions in the United States. Control subjects (controls) were of the same gender and race, and within 5 years of age as matching patients with sarcoidosis (cases). RESULTS: Cultures were incubated from 347 blood specimens (197 cases, 150 controls). Two investigators trained to recognize CWDF mycobacteria examined material obtained from culture tubes after 3 weeks. Structures thought to be CWDF were seen with equal frequency in cases (38%) and controls (41%). Thirty-nine percent of cases and 37% of controls were read as negative for CWDF. CONCLUSION: This study fails to confirm earlier reports that CWDF mycobacteria can be grown from the blood of patients with sarcoidosis, but not from control subjects.

Relationship of respiratory symptoms with smoking status and pulmonary function in chronic spinal cord injury.

OBJECTIVE: The relationship of respiratory symptoms to pulmonary function parameters and smoking status was assessed in subjects with chronic (>1 year) spinal cord injury (SCI). METHODS AND PARTICIPANTS: As part of their annual physical examination, subjects were queried regarding respiratory symptoms and underwent pulmonary function studies. The 180 patients who successfully completed pulmonary function testing were evaluated, including 79 subjects with tetraplegia (56 nonsmokers and 23 smokers) and 101 subjects with paraplegia (78 nonsmokers and 23 smokers). FINDINGS: Logistic-regression analysis revealed the following independent predictors of breathlessness: level of injury (tetraplegia, paraplegia, odds ratio = 3.5, P < 0.0015), cough combined with phlegm and/or wheeze (CPWZ, odds ratio = 3.1, P < 0.015), total lung capacity percentage predicted (TLC <60%, odds ratio = 3.9, P < 0.02), and expiratory reserve volume (ERV < 0.6 L, odds ratio = 2.5, P < 0.05). Independent predictors of CPWZ were current smoking (odds ratio = 3.3, P < 0.004), breathlessness (odds ratio = 2.9, P < 0.03), and forced expiratory volume in 1 second (FEV1 <60%, odds ratio = 3.2, P < 0.01). CONCLUSION: Altered respiratory mechanics associated with tetraplegia contribute to breathlessness, restrictive ventilatory impairment (low TLC%), and reduced expiratory muscle strength (low ERV). These factors apparently overshadow adverse effects caused by smoking. Conversely, smoking and reduction of airflow (low FEV1%) were predictive of CPWZ, symptoms commonly associated with cigarette use.

Hemoptysis: diagnosis and management.

Hemoptysis is a frightening and potentially life-threatening symptom. However, most cases can be approached effectively with conservative management. Bronchial artery embolization should be attempted when bleeding is refractory to medical therapy, and surgery may be needed in severe hemorrhage.