Bronchial Hyperresponsiveness After Cervical Spinal Cord Injury

      Cervical spinal cord injury results in interruption of sympathetic airway innervation, which originates from the upper thoracic spine, whereas parasympathetic nerve supply, arising in the vagal nuclei of the brainstem, remains intact. To assess the effect of such an altered neural environment on airway reactivity, bronchoprovocation testing was performed on eight subjects with nonacute traumatic lesions of the cervical spine, all of whom were lifetime nonsmokers without history of respiratory symptoms prior to their injury. Bronchial challenge was subsequently repeated after pretreatment with the anticholinergic agent, ipratropium bromide, an inhibitor of airway muscarinic receptors. All subjects demonstrated hyperresponsiveness to methacholine (the concentration of methacholine producing a fall in FEV1 of 20 percent from baseline [PC20]= 1.42 ± 1.61 [SD] mg/ml). Airway hyperreactivity was completely blocked by pretreatment with inhaled ipratropium bromide (mean PC20 >25 mg/ml [p<0.0001]). The bronchial hyperresponsiveness observed in this population most likely reflects the loss of sympathetic airway innervation and resultant unopposed cholinergic bronchoconstrictor tone which results from transection of the cervical spine. Blockade of methacholine hyperresponsiveness with ipratropium bromide suggests a muscarinic receptor-mediated phenomenon.
      PC20 (concentration of methacholine producing a fall in FEV1 of 20 percent from baseline)
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        • Mansel JK
        • Norman JR
        Respiratory complications and management of spinal cord injuries?.
        Chest. 1990; 97: 1446-1452
        • Bergofsky EH
        Mechanism for respiratory insufficiency after cervical cord injury?.
        Ann Intern Med. 1964; 61: 435-447
        • Ohry A
        • Molho M
        • Rozin R
        Alterations of pulmonary function in spinal cord injured patients?.
        Paraplegia. 1975; 13: 101-108
        • Forner JV
        • Llonbart RL
        • Valleder MCV
        The flow-volume loop in tetraplegics?.
        Paraplegia. 1977; 15: 245-251
        • McMichan JC
        • Michel L
        • Westbrook PR
        Pulmonary dysfunction following traumatic quadriplegia?.
        JAMA. 1980; 243: 528-531
        • Ledsome JR
        • Sharp JM
        Pulmonary function in acute cervical cord injury?.
        Am Rev Respir Dis. 1981; 124: 41-44
        • Polatty RC
        • McElaney MA
        • Marcelino V
        Pulmonary complications in the spinal cord injury patient?.
        Arch Phys Med Rehabil. 1987; 1: 353-373
        • Barnes PJ
        Neural control of human airways in health and disease?.
        Am Rev Respir Dis. 1986; 134: 1289-1314
        • Marlin GE
        • Thompson PJ
        • Reddell HK
        • Chow CM
        • Cheng S
        Bronchodilator activity of prazozin in patients with allergic rhinitis and asthma?.
        Br J Clin Pharmacol. 1982; 13: 445-448
        • American Thoracic Society
        Lung function testing: selection of reference values and interpretative strategies?.
        Am Rev Respir Dis. 1991; 144: 1202-1218
        • Morris JF
        • Koski A
        • Johnson LC
        Spirometric standards for healthy nonsmoking adults?.
        Am Rev Respir Dis. 1971; 103: 57-67
        • Juniper EF
        • Frith PA
        • Dunnett C
        • Cockcroft DW
        • Hargreave FE
        Reproducibility and comparison of responses to inhaled histamine and methacholine?.
        Thorax. 1978; 33: 705-710
        • Malo JL
        • Pineau L
        • Cartier A
        • Martin RR
        Reference values of the provocative concentrations of methacholine that cause 6% and 20% changes in forced expiratory volume in one second in a normal population?.
        Am Rev Respir Dis. 1983; 128: 8-11
        • Vincent NJ
        • Knudson R
        • Leith DE
        • Macklem PT
        • Mead J
        Factors influencing pulmonary resistance?.
        J Appl Physiol. 1970; 29: 236-243
        • DeTroyer A
        • Yernault JC
        • Rodenstein D
        Effects of vagal blockade on lung mechanics in normal man?.
        J Appl Physiol. 1979; 46: 217-226
        • Douglas NJ
        • Sudlow MF
        • Flenley DC
        Effect of an inhaled atropinelike agent on normal airway function?.
        J Appl Physiol. 1979; 46: 256-262
        • Banner NR
        • Heaton R
        • Hollingshead L
        • Guz A
        • Yacoub MH
        Bronchial reactivity to methacholine after combined heart-lung transplantation?.
        Thorax. 1988; 43: 955-959
        • Maurer JR
        • McLean PA
        • Cooper JD
        • Chamberlain DW
        • Grossman RF
        • Zamel N
        • et al.
        Airway hyperreactivity in patients undergoing lung and heart/lung transplantation?.
        Am Rev Respir Dis. 1989; 139: 1038-1041
        • Higgenbottam T
        • Jackson M
        • Rashdi T
        • Stewart S
        • Coutts C
        • Wallwork J
        Lung rejection and bronchial hyperresponsiveness to methacholine and ultrasonically nebulized distilled water in heart-lung transplantation patients?.
        Am Rev Respir Dis. 1989; 140: 52-57
        • Glanville AR
        • Theodore J
        • Baldwin JC
        • Robin ED
        Bronchial responsiveness after human heart-lung transplantation?.
        Chest. 1990; 97: 1360-1366
        • Zaid G
        • Beall GN
        Bronchial response to beta-adrenergic blockade?.
        N Engl J Med. 1966; 275: 580-584
        • Tattersfield AE
        • Leaver DG
        • Pride NB
        Effect of beta adrenergic blockade and stimulation on normal human airways?.
        J Appl Physiol. 1973; 35: 613-619
        • Richardson PS
        • Sterling GM
        Effects of beta-adrenergic receptor blockade on airway conductance and lung volume in normal and asthmatic subjects?.
        BMJ. 1969; 3: 143-145
        • Richardson JB
        • Ferguson CC
        Neuromuscular structure and function in the airways?.
        Fed Proc. 1979; 38: 202-208
        • Dicpinigaitis PV
        • Spungen AM
        • Bauman WA
        Reversible airway obstruction in quadriplegic nonsmokers [abstract]?.
        Am Rev Respir Dis. 1992; 145: A379
        • Barnes PJ
        The third nervous system in the lung: physiology and clinical perspectives?.
        Thorax. 1984; 39: 561-567
        • Richardson J
        • Beland J
        Nonadrenergic inhibitory nervous system in human airways?.
        J Appl Physiol. 1976; 41: 764-771
        • Ichinose M
        • Inoue H
        • Miura M
        • Takishima T
        Nonadrenergic bronchodilation in normal subjects?.
        Am Rev Respir Dis. 1988; 138: 31-34
        • Lammers JJ
        • Minette P
        • McCusker MT
        • Chung KF
        • Barnes PJ
        Nonadrenergic bronchodilator mechanisms in normal human subjects in vivo.
        J Appl Physiol. 1988; 64: 1817-1822
        • Barnes PJ
        Muscarinic receptor subtypes: implications for lung disease?.
        Thorax. 1989; 44: 161-167