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(Chest. 2000;118:1397-1404.)
© 2000 American College of Chest Physicians

Airway Hyperreactivity in Subjects With Tetraplegia Is Associated With Reduced Baseline Airway Caliber*

David R. Grimm, EdD; Dipak Chandy, MD; Peter L. Almenoff, MD, FCCP; Gregory Schilero, MD, FCCP and Marvin Lesser, MD

* From the Pulmonary/Critical Care Medicine Section (Drs. Chandy, Almenoff, Schilero, and Lesser), Bronx Veterans Affairs Medical Center, Bronx, NY; and the Department of Medicine (Dr. Grimm), The Mount Sinai School of Medicine, New York, NY.

Correspondence to: Marvin Lesser, MD, Pulmonary Section, VA Medical Center, 130 West Kingsbridge Rd, Bronx, NY


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objectives: We administered aerosolized histamine to 32 subjects with tetraplegia to determine whether there were differences in spirometric and/or lung volume parameters between responders and nonresponders.

Results: Baseline pulmonary function parameters revealed mild to moderate restrictive dysfunction. We found that 25 subjects (78%) were hyperreactive to histamine (mean provocative concentration of a substance causing a 20% fall in FEV1 [PC20], 1.77 mg/mL). Responders (PC20, < 8 mg/mL) had significantly lower values for forced expiratory flow between 25% and 75% of the outflow curve (FEF25–75), FEF25–75 percent predicted, and FEF25–75/FVC ratio. Among all 32 subjects, the natural logarithmic transformation performed on PC20 values (lnPC20) correlated with FEF25–75 percent predicted, FEV1 percent predicted, and FEF25–75/FVC ratio but not with FVC percent predicted. Responders with PC20 values < 2 mg/mL (n = 13) had significantly reduced values for FVC, FVC percent predicted, FEV1, and FEV1 percent predicted compared to those with PC20 values between 2 mg/mL and 8 mg/mL. In addition, among responders, there was a significant correlation between lnPC20 and FVC percent predicted. A significant relationship was found between maximal inspiratory pressure (PImax) and both FEV1 percent predicted and FEF25–75 percent predicted, but not between lnPC20 and either PImax or maximal expiratory pressure (PEmax).

Conclusions: These findings demonstrate that subjects with tetraplegia who exhibit airway hyperreactivity (AHR) have reduced baseline airway caliber and that lower values for lnPC20 are associated with parallel reductions in surrogate spirometric indexes of airway size (FEV1 percent predicted and FEF25–75 percent predicted) and airway size relative to lung size (FEF25–75/FVC ratio). The absence of an association between lnPC20 and FVC percent predicted for the entire group or between lnPC20 and either PImax or PEmax indicates that reduced lung volumes secondary to respiratory muscle weakness cannot explain the mechanism(s) underlying AHR. Among responders, however, a possible role for reduction in lung volume, as it pertains to increasing AHR, cannot be excluded. Proposed mechanisms for reduced baseline airway caliber relative to lung size in subjects with tetraplegia include unopposed parasympathetic activity secondary to the loss of sympathetic innervation to the lungs and/or the inability to stretch airway smooth muscle with deep inhalation.

Key Words: airway hyperresponsiveness • bronchoprovocation • pulmonary function • spinal cord injury


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The majority of subjects with tetraplegia display airway hyperreactivity (AHR) following the inhalation of methacholine, histamine, or ultrasonically nebulized distilled water.1 2 3 4 One explanation for exaggerated bronchoconstriction among these subjects is reduced resting airway caliber due to the loss of sympathetic innervation originating in the upper six thoracic segments of the spinal cord. Reduced airway caliber and increased airway resistance may play a pivotal role in AHR based on the mathematical theorem that resistance of laminar gas flow is inversely related to the fourth power of the radius. Accordingly, with narrowed airways, a given degree of further narrowing caused by a bronchoconstrictive agent will be associated with greater obstruction to flow than the same degree of narrowing occurring at normal patency.5 The specific goal of this investigation, therefore, was to determine the relationships between histamine responsiveness and spirometric/lung volume parameters among subjects with chronic tetraplegia.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Thirty-two subjects in clinically stable condition with chronic cervical spinal cord injury (tetraplegia) of at least 1-year duration participated in this study. None were receiving medications known to alter responsiveness to histamine. Subjects were selected who reported no preinjury history of pulmonary disease, atopy, or asthma. All denied recent or active pulmonary infections. The study was approved by the Institutional Review Board of the Bronx Veterans Affairs Medical Center, and informed consent was obtained prior to investigation.

Spirometric measurements were obtained while subjects were seated in their wheelchairs (model 2200 Automated Pulmonary Function Laboratory; SensorMedics; Yorba Linda, CA). Baseline values of FVC and FEV1 were obtained according to the recommendations of the American Thoracic Society.6 Accordingly, the best FVC and corresponding FEV1 values from three reproducible FVC maneuvers (± 5%), each of at least 6-s duration, were obtained. Spirometry results are expressed as absolute values and percent predicted based on the standards of Morris et al.7 Measures of respiratory muscle strength (ie, maximal inspiratory pressure [PImax] and maximal expiratory pressure [PEmax]) were obtained using an electronic portable mouth pressure meter (Vacu-Med; Ventura, CA) from the best of three maximum efforts, each beginning from residual volume (RV) and total lung capacity (TLC), respectively. Lung volumes were determined using the open-circuit nitrogen washout technique and were expressed as absolute values and as percent predicted based on the prediction equations of Crapo et al.8

Histamine challenge consisted of a series of maneuvers, each involving five slow inhalations (inspiratory time, 5 s) from functional residual capacity (FRC) to TLC. Subjects were instructed not to hold their breath at TLC and to exhale slowly. The time between each inhalation was approximately 10 s. Subjects demonstrating a < 10% response to normal saline solution were challenged with increasing concentrations (ie, 0.025, 0.25, 2.5, 10, and 25 mg/mL) of histamine diphosphate (Freeman Industries; Tuckahoe, NY). Aerosols were generated by a nebulizer (Salter 8900; Asthmakit, Diemolding Healthcare Division; Canastota, NY) driven by air at a flow rate of 8 L/min with an output of 0.35 mL/min. Particle size ranged from 1.6 to 3.4 µm. On initiation of each breath, nebulization was performed by manual occlusion of a thumb port for approximately 1.5 s. Spirometry was measured 2 to 3 min after each set of five inhalations, or sooner if dyspnea or chest tightness developed. The challenge was terminated either when the FEV1 decreased >= 20% from baseline (ie, a provocative concentration of a substance causing a 20% fall in FEV1 [PC20]) or when the maximal concentration of histamine (25 mg/mL) was administered. The PC20 was calculated using a computer program that generated the value by interpolation from a logarithmic dose-response curve. A PC20 of < 8 mg/mL defined AHR9 and separated responders from nonresponders. Subjects with a PC20 of < 8 mg/mL and/or symptoms were immediately given an inhaled ß2-agonist (ie, a 2.5-mL dose of a 0.6% solution of metaproterenol sulfate) and were observed until the symptoms abated and the FEV1 returned to within 5% of baseline. A PC20 value of 25 mg/mL was used in the calculations for subjects not responding to the maximal concentration of histamine.

A subgroup who had exhibited AHR underwent, on an alternate day, serial saline solution challenges (single-blind) employing the same protocol used for histamine bronchoprovocation.

All data are expressed as mean ± SD. A natural logarithmic transformation was performed on PC20 values (lnPC20). An unpaired Student’s t test was applied to determine differences between responders and nonresponders for pulmonary function and PC20 values and to assess differences between subjects responding with a PC20 of < 2 mg/mL and those responding with a PC20 between 2 and 8 mg/mL. Simple regression analysis was used to assess the relationships between PC20 values and baseline pulmonary function. Statistical significance for all analyses was established at a p value < 0.05.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Twenty-five of 32 subjects with tetraplegia demonstrated AHR (PC20, < 8 mg/mL) in response to aerosolized histamine (Table 1 ). Age, duration of injury, level of injury, and completeness of injury did not differ significantly between responders and nonresponders. Although six of seven nonresponders were never-smokers, eight responders were also never-smokers. Among responders, PC20 values for never-smokers (mean lnPC20, 0.36 mg/mL) were comparable to those of current smokers (mean lnPC20, 0.83 mg/mL).


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  		Table 1. Subject Characteristics and PC20 Values

 
The mean values for pulmonary function parameters demonstrated mild to moderate restrictive dysfunction as defined by decreases in TLC percent predicted, FVC percent predicted, and FEV1 percent predicted and a normal FEV1/FVC ratio (Table 2 ). Compared to nonresponders, responders had significantly lower values for forced expiratory flow between 25% and 75% of the outflow curve (FEF25–75), FEF25–75 percent predicted, and FEF25–75/FVC ratio (Table 2) . Regression analysis among all subjects demonstrated significant relationships between lnPC20 and FEF25–75 percent predicted (r = 0.49; p < 0.005; Fig 1 ), FEV1 percent predicted (r = 0.43; p < 0.01; Fig 2 ), and FEF25–75/FVC ratio (r = 0.47; p < 0.005; Fig 3 ) but not between lnPC20 and FVC percent predicted. Among responders, lnPC20 correlated with FVC percent predicted (r = 0.45; p < 0.01; Fig 4 ), and subjects with PC20 values < 2 mg/mL (n = 13) had significantly reduced FVC and FEV1 values (absolute values and percent predicted; Table 3 ). Regression analysis approached significance for PImax and FVC percent predicted (r = 0.46; p = 0.08) and reached significance for FEV1 percent predicted (r = 0.57; p = 0.03) and FEF25–75 percent predicted (r = 0.56; p = 0.03). No relationship was found between PEmax and any of the spirometric parameters. Neither PImax nor PEmax correlated with lnPC20. Other lung volume parameters did not differ significantly between responders and nonresponders (Table 2) or between responders with PC20 values < 2 mg/mL and those with PC20 values between 2 and 8 mg/mL (Table 3) .


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  		Table 2. Comparison of Mean Pulmonary Function Parameters*

 


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  		Figure 1. Relationship between lnPC20 and FEF25–75 among 32 subjects.

 


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  		Figure 2. Relationship between lnPC20 and FEV1 among 32 subjects.

 


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  		Figure 3. Relationship between lnPC20 and FEF25–75/FVC ratio among 32 subjects.

 


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  		Figure 4. Relationship between lnPC20 and FVC among 25 subjects responding to histamine.

 

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  		Table 3. Comparison of Mean Pulmonary Function Parameters Among Responders

 
Five responders had no demonstrable changes in FEV1 following serial saline solution challenges (Table 4 ).


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  		Table 4. Comparison of Percent Change in FEV1 After Administration of Histamine and Saline Solution Challenges

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
We found that 25 of 32 subjects in medically stable condition with chronic tetraplegia were hyperresponsive to aerosolized histamine, with a mean PC20 of 1.77 mg/mL among responders. The findings confirm previous observations involving fewer subjects that demonstrated that the majority of subjects with tetraplegia display exaggerated bronchoconstriction following inhalation of pharmacologically and physicochemically provocative agents.1 2 3 4 AHR cannot be attributed to asthma or atopy because subjects were closely screened, and those with a history of these conditions were excluded from study. Also, AHR cannot be ascribed to long-term cigarette use because eight responders were never-smokers, and because, among responders, PC20 values for never-smokers were comparable to those of current smokers. Moreover, in a previous study2 using methacholine it was demonstrated that PC20 values among subjects with tetraplegia were comparable among smokers, ex-smokers, and nonsmokers.

In the current study, a comparison of pulmonary function parameters revealed reductions of FEF25–75, FEF25–75 percent predicted, and FEF25–75/FVC ratio in responders compared to nonresponders, and reductions of FVC, FVC percent predicted, FEV1, and FEV1 percent predicted among responders with PC20 values of < 2 mg/mL. Regression analysis among all 32 subjects demonstrated the correlation of lnPC20 with FEF25–75 percent predicted, FEF25–75/FVC ratio, and FEV1 percent predicted, and among responders, the correlation of lnPC20 with FVC percent predicted. Although both responders and nonresponders manifested pulmonary function abnormalities that were consistent with neuromuscular disease marked by restrictive physiology, lnPC20 values among all subjects were associated with spirometric indexes of airway caliber (ie, FEV1 percent predicted and FEF25–75 percent predicted; Fig 1 , 2 ) and with a surrogate marker of airway size relative to lung size (ie, FEF25–75/FVC ratio; Fig 3 ) but not with lung volume (ie, FVC percent predicted; Fig 4 ). Furthermore, although significant relationships were found between PImax and both FEV1 percent predicted and FEF25–75 percent predicted, the absence of a relationship between lnPC20 and either PImax or PEmax indicates that AHR cannot be explained on the basis of reduced lung volumes secondary to respiratory muscle weakness. Nor can respiratory muscle fatigue induced by repeated spirometric maneuvers during histamine challenge account for our findings, since serial saline solution challenges in subjects demonstrating AHR documented no appreciable fall in FEV1 (Table 4) .

In a population-based study, a cross-sectional investigation demonstrated that FEF25–75/FVC ratio was significantly associated with airway responsiveness to methacholine after adjustment for age, height, initial FEV1 level, smoking, eosinophil count, and IgE level.10 An additional population-based study evaluating the response to eucapneic hyperventilation with cold air found that a low prechallenge FEF25–75/FVC ratio was a significant predictor of response.11 Similarly, random population studies of healthy children and adults have demonstrated that AHR associated with exposure to methacholine, histamine, or cold air correlated with baseline values of FEF25–75, FEF25–75 percent predicted, FEV1, FEV1 percent predicted, and/or FEV1/FVC ratio.12 13 14 15 16 17 In one study, AHR was an independent predictor of pulmonary function level after adjustment for age, sex, area of residence, respiratory symptom prevalence, and cigarette use.17 Furthermore, among subjects with asthma or chronic obstructive lung disease, AHR has been found to correlate with baseline values of FEV1, FEV1 percent predicted, FEF25–75 percent predicted, and/or FEV1/FVC ratio.18 19 20 21 It appears, therefore, that AHR among different population groups, including those with tetraplegia, is associated with parameters reflecting reduced baseline airway caliber of central and peripheral airways.

One explanation for reduced baseline airway caliber among subjects with tetraplegia is unopposed parasympathetic (cholinergic) activity due to the interruption of sympathetic innervation of the lung. The sympathetic nerve supply to the lung arises in the upper six thoracic segments of the spinal cord. Postganglionic fibers synapse in the middle and inferior cervical ganglia and in the upper four thoracic ganglia, and they enter the hilum to intermingle with cholinergic nerves that form dense plexuses around airways and vessels.22 Sympathetic fibers also innervate the smooth muscle layer of the human bronchial tree, with a few fibers reaching the level of secondary bronchi and terminal bronchioles.23 24 25 26 Sympathetic fibers may modulate airway tone indirectly through interaction with parasympathetic fibers in airway ganglia and directly through the local release of norepinephrine. Support for autonomic imbalance comes from findings that approximately 50% of subjects with chronic tetraplegia exhibited a significant bronchodilator response (ie, an increase in FEV1 of >= 12% and 200 mL) following inhalation of ipratropium bromide.27 In addition, there are observations that plasma levels of norepinephrine, which reflect overall sympathetic nerve activity,22 are significantly reduced.28 Of possible clinical relevance, among a series of patients who had undergone dorsal sympathectomy, subsequent concomitant decreases in midexpiratory flow and lung volume parameters were attributed to sympathetic denervation.29 With an increase in baseline resting airway tone due to uninhibited parasympathetic activity, even with a normal load, airway smooth muscle is shortened to lengths below the resting length.30

Epinephrine released from the adrenal medulla also may regulate baseline airway tone and may induce bronchodilation through interaction with airway smooth muscle adrenergic receptors.22 Of note, circulating levels of epinephrine among subjects with tetraplegia are significantly reduced, reflecting denervation of the adrenal glands.28 31 Among subjects with asthma, although baseline catecholamine levels are normal, the infusion of epinephrine producing circulating levels within the range found with exercise causes dose-related bronchodilation and attenuation of methacholine responsiveness.32 33 34 However, the effect of reduced circulating epinephrine levels on resting airway tone among subjects with tetraplegia is unknown, and it has not been determined whether the infusion of epinephrine modulates airway responsiveness to histamine or methacholine.

Additional factors may contribute to decreased baseline airway caliber. A decrease in resting "preload" due to softening of the cartilage in large airways, a loss of lung elastin and collagen, or a reduction in elastic recoil will contribute to airway narrowing.30 Although it is not known whether structural changes occur in the airways or parenchyma following spinal cord injury, subjects with tetraplegia have reduced elastic recoil pressure.35 Airway wall thickening or secretions within the airway lumen also could increase baseline resistance and maximal response to agonists.30 Subjects with tetraplegia have difficulty clearing mucus from their lungs and, in the acute phase, produce excessive amounts of thick airway secretions.36 Finally, it has been suggested that the failure of periodic inflation with deep inspiration may allow airway smooth muscle to become stiff and noncompliant, thereby contributing to exaggerated airway narrowing.37 38 Subjects with tetraplegia have reduced TLC and FVC,39 40 and, as observed in the current study, FVC was significantly reduced in those subjects exhibiting the greatest responses to histamine (ie, PC20, < 2 mg/mL), and lnPC20 among responders correlated with FVC percent predicted. Also, among subjects with amyotrophic lateral sclerosis who have intact sympathetic innervation to the lungs, there is a higher prevalence of AHR among those with reduced FVC.41 It has not been established, however, among subjects with tetraplegia whether an inability to inhale to the predicted TLC affects resting airway caliber or responsiveness to bronchoconstrictive agents.

The clinical significance of AHR among subjects with tetraplegia is unknown. In a study assessing the prevalence of pulmonary symptoms among subjects with spinal cord injury, 73% with high tetraplegia (ie, injury at C5 and above not requiring mechanical ventilation) and 58% with low tetraplegia (ie, injury at C6 to C8) reported that they regularly experienced shortness of breath at rest or with exertion.42 Presumably, respiratory muscle weakness is a major factor contributing to the sensation of breathlessness among these individuals. Findings among subjects with high tetraplegia, however, that breathlessness worsened following exposure to cold air, hot air, or secondary cigarette smoke suggest that AHR may contribute to breathlessness. In addition, findings that pretreatment with a ß-agonist (eg, metaproterenol sulfate) blocked hyperresponsiveness to methacholine or histamine43 and that metaproterenol sulfate or ipratropium bromide alone caused significant bronchodilation in subjects with tetraplegia (42% and 48%, respectively)27 44 suggest that long-term administration of a ß-agonist or anticholinergic agent might provide symptomatic benefit. To our knowledge, however, no prospective study has been performed among these individuals to assess the therapeutic value of bronchodilator therapy.


   Footnotes
 
Abbreviations: AHR = airway hyperreactivity; FEF25–75 = forced expiratory flow between 25% and 75% of the outflow curve; FRC = functional residual capacity; lnPC20 = natural logarithmic transformation performed on values of a provocative concentration of a substance causing a 20% fall in FEV1; PC20 = provocative concentration of a substance causing a 20% fall in FEV1; PEmax = maximal expiratory pressure; PImax = maximal inspiratory pressure; RV = residual volume; TLC = total lung capacity

Received for publication November 2, 1999. Accepted for publication May 2, 2000.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Dicpinigaitis, PV, Spungen, AM, Bauman, WA, et al (1994) Bronchial hyperresponsiveness after cervical spinal cord injury. Chest 105,1073-1076[Abstract/Free Full Text]
  2. Singas, E, Lesser, M, Spungen, AM, et al (1996) Airway hyperresponsiveness to methacholine in subjects with spinal cord injury. Chest 110,911-915[Abstract/Free Full Text]
  3. Fein, ED, Grimm, DR, Lesser, M, et al (1998) The effects of ipratropium bromide on histamine-induced bronchoconstriction in subjects with cervical spinal cord injury. J Asthma 35,49-55[ISI][Medline]
  4. Grimm, DR, Arias, E, Lesser, M, et al (1999) Airway hyperresponsiveness to ultrasonically nebulized distilled water in subjects with tetraplegia. J Appl Physiol 86,1165-1169[Abstract/Free Full Text]
  5. Benson, MK (1975) Bronchial hyperreactivity. Br J Dis Chest 69,227-239[ISI][Medline]
  6. . American Thoracic Society. (1995) Standardization of spirometry: 1994 update. Am Rev Respir Dis 152,1107-1136
  7. Morris, JF, Koski, A, Johnson, LC (1971) Spirometric standards for healthy nonsmoking adults. Am Rev Respir Dis 103,57-67[ISI][Medline]
  8. Crapo, RO, Morris, AH, Clayton, PD, et al (1982) Lung volumes in healthy nonsmoking adults. Bull Eur Physiopathol Respir 18,419-425[ISI][Medline]
  9. Juniper, EF, Frith, PA, Dunnett, C, et al (1978) Reproducibility and comparison of responses to inhaled histamine and methacholine. Thorax 33,705-710[Abstract]
  10. Litonjua, AA, Sparrow, D, Weiss, ST (1999) The FEF25–75/FVC ratio is associated with methacholine airway responsiveness: the normative aging study. Am J Respir Crit Care Med 159,1574-1579[Abstract/Free Full Text]
  11. Tager, IB, Weiss, ST, Munoz, A, et al (1986) Determinants of response to eucapneic hyperventilation with cold air in a population-based study. Am Rev Respir Dis 134,502-508[ISI][Medline]
  12. Britton, J, Pavord, I, Richards, K, et al (1994) Factors influencing the occurrence of airway hyperreactivity in the general population: the importance of atopy and airway calibre. Eur Respir J 7,881-887[Abstract]
  13. Sparrow, D, O’Connor, G, Colton, T, et al (1987) The relationship of nonspecific bronchial responsiveness to the occurrence of respiratory symptoms and decreased levels of pulmonary function. Am Rev Respir Dis 135,1255-1260[ISI][Medline]
  14. Forastiere, F, Corbo, GM, Dell’Orco, V, et al (1996) A longitudinal evaluation of bronchial responsiveness to methacholine in children: role of baseline lung function, gender, and change in atopic status. Am J Respir Crit Care Med 153,1098-1104[Abstract]
  15. Paoletti, P, Carrozzi, L, Viegi, G, et al (1995) Distribution of bronchial responsiveness in a general population: effect of sex, age, smoking, and level of pulmonary function. Am J Respir Crit Care Med 151,1770-1777[Abstract]
  16. Sparrow, D, O’Connor, GT, Rosner, B, et al (1991) The influence of age and level of pulmonary function on nonspecific airway responsiveness. Am Rev Respir Dis 143,978-982[ISI][Medline]
  17. Rijcken, B, Schouten, JP, Weiss, ST, et al (1988) The relationship between airway responsiveness to histamine and pulmonary function level in a random population sample. Am Rev Respir Dis 137,826-832[ISI][Medline]
  18. Ramsdell, JW, Nachtwey, FJ, Moser, KM (1982) Bronchial hyperreactivity in chronic obstructive bronchitis. Am Rev Respir Dis 126,829-832[ISI][Medline]
  19. Bahous, J, Cartier, A, Ouimet, G, et al (1984) Nonallergic bronchial hyperexcitability in chronic bronchitis. Am Rev Respir Dis 129,216-220[ISI][Medline]
  20. Yan, K, Salome, CM, Woolcock, AJ (1985) Prevalence and nature of bronchial hyperresponsiveness in subjects with chronic obstructive pulmonary disease. Am Rev Respir Dis 132,25-29[ISI][Medline]
  21. Ramsdale, EH, Roberts, RS, Morris, MM, et al (1985) Differences in responsiveness to hyperventilation and methacholine in asthma and chronic bronchitis. Thorax 40,422-426[Abstract]
  22. Barnes, PJ (1986) Neural control of human airways in health and disease. Am Rev Respir Dis 134,1289-1314[ISI][Medline]
  23. Pack, RJ, Richardson, PS (1984) The aminergic innervation of the human bronchus: a light and electron microscopic study. J Anat 138,493-502
  24. Laitinen, A, Partanen, M, Hervonen, A, et al (1985) Electron microscopic study on the innervation of the human lower respiratory tract: evidence of adrenergic nerves. Eur J Respir Dis 67,209-215[ISI][Medline]
  25. Laitinen, LA, Laitinen, A (1987) Innervation of airway smooth muscle. Am Rev Respir Dis 136,S38-S41[ISI][Medline]
  26. Partanen, M, Laitinen, A, Hervonen, A, et al (1982) Catecholamine- and acetylcholinesterase-containing nerves in human lower respiratory tract. Histochemistry 76,175-188[CrossRef][ISI][Medline]
  27. Almenoff, PL, Alexander, LR, Spungen, AM, et al (1995) Bronchodilatory effects of ipratropium bromide in patients with tetraplegia. Paraplegia 33,274-277[ISI][Medline]
  28. Mathias, CJ, Christensen, NJ, Corbett, JL, et al (1976) Plasma catecholamines during paroxysmal neurogenic hypertension in quadriplegic man. Circ Res 39,204-208[Abstract/Free Full Text]
  29. Molho, M, Kurchin, A, Ohry, A, et al (1977) Pulmonary functional abnormalities after upper dorsal sympathectomy. Am Rev Respir Dis 116,879-883[ISI][Medline]
  30. Moreno, RH, Hogg, JC, Pare, PD (1986) Mechanics of airway narrowing. Am Rev Respir Dis 133,1171-1180[ISI][Medline]
  31. Munro, AF, Robinson, R (1960) The catecholamine content of the peripheral plasma in human subjects with complete transverse lesions of the spinal cord. J Physiol 154,244-253
  32. Barnes, PJ, Ind, PW, Brown, MJ (1982) Plasma histamine and catecholamines in stable asthmatic subjects. Clin Sci 62,661-665[Medline]
  33. Berkin, KE, Inglis, GC, Ball, SG, et al (1986) Effect of low dose adrenaline and noradrenaline infusions on airway calibre in asthmatic patients. Clin Sci 70,347-352[Medline]
  34. Sands, MF, Douglas, FL, Green, J, et al (1985) Homeostatic regulation of bronchomotor tone by sympathetic activation during bronchoconstriction in normal and asthmatic humans. Am Rev Respir Dis 132,993-998[ISI][Medline]
  35. De Troyer, A, Heilporn, A (1980) Respiratory mechanics in quadriplegia: the respiratory function of the intercostal muscles. Am Rev Respir Dis 122,591-600[ISI][Medline]
  36. Bhaskar, KR, Brown, R, O’Sullivan, DD, et al (1991) Bronchial mucus hypersecretion in acute quadriplegia. Am Rev Respir Dis 143,640-648[ISI][Medline]
  37. Moore, BJ, Verburgt, LM, King, GG, et al (1997) The effect of deep inspiration on methacholine dose-response curves in normal subjects. Am J Respir Crit Care Med 156,1278-1281[Abstract/Free Full Text]
  38. Skloot, G, Permutt, S, Togias, A (1995) Airway hyperresponsiveness in asthma: a problem of limited smooth muscle relaxation with inspiration. J Clin Invest 96,2393-2403
  39. Almenoff, PL, Spungen, AM, Lesser, M, et al (1995) Pulmonary function survey in spinal cord injury: influences of smoking and level and completeness of injury. Lung 173,297-306[ISI][Medline]
  40. Anke, A, Aksnes, AK, Stanghelle, JK, et al (1993) Lung volumes in tetraplegic patients according to cervical spinal cord injury level. Scand J Rehabil Med 25,73-77[ISI][Medline]
  41. Linneman, N, Sivak, M, Grimm, DR, et al (1997) Assessment of airway hyperreactivity in subjects with amyotrophic lateral sclerosis [abstract]. Am J Respir Crit Care Med 155,A543
  42. Spungen, AM, Grimm, DR, Lesser, M, et al (1997) Self-reported prevalence of pulmonary symptoms in subjects with spinal cord injury. Spinal Cord 35,652-657[CrossRef][ISI][Medline]
  43. DeLuca, RV, Grimm, DR, Lesser, M, et al (1999) Effects of a ß2-agonist on airway hyperreactivity in subjects with cervical spinal cord injury. Chest 115,1533-1538[Abstract/Free Full Text]
  44. Spungen, AM, Dicpinigaitis, PV, Almenoff, PL, et al (1993) Pulmonary obstruction in individuals with cervical spinal cord lesions unmasked by bronchodilator administration. Paraplegia 31,404-407[ISI][Medline]



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G. J. Schilero, D. R. Grimm, W. A. Bauman, R. Lenner, and M. Lesser
Assessment of Airway Caliber and Bronchodilator Responsiveness in Subjects With Spinal Cord Injury
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Right arrow Articles by Lesser, M.

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