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Bronchodilation and bronchoprotection by deep inspiration and their relationship to bronchial hyperresponsiveness

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Abstract

Bronchial hyperresponsiveness (BHR) is a cardinal feature of asthma. Airway inflammation and BHR are probably linked, but the mechanisms underlying this relationship remain elusive. BHR is closely associated with defects in the beneficial responses to lung inflation. These responses, which become apparent by the fact that healthy individuals can develop severe airway obstruction if they are exposed to methacholine in the absence of deep inspirations, include bronchodilation and bronchoprotection. Bronchodilation refers to the effect of lung inflation after the induction of airway smooth muscle tone, while bronchoprotection is used to indicate the effect prior to inhalation of a spasmogen. Mild asthmatics who manifest BHR lack bronchoprotection by lung inflation. In contrast, many of them are able to bronchodilate. In more severe disease, both functions are impaired. The lack of bronchoprotection is also found in individuals with rhinitis and BHR, but no asthma. These and other observations suggest that the mechanisms of bronchodilation and bronchoprotection may be distinct, although overlap is possible. We believe that the loss of bronchoprotection is pertinent to the phenomenon of hyperresponsiveness, but that both the bronchodilatory and bronchoprotective functions of deep inspiration interact to produce the asthmatic phenotype. In this review, we describe the phenomena of lung inflation-induced bronchodilation and bronchoprotection and detail potential mechanical and neurohumoral mechanisms accounting for these physiologic functions. In addition, possible mechanisms leading to the impairment of these functions in subjects with BHR are discussed.

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References

  1. Horowitz, E. and Busse, W. (1995) Inflammation and asthma. Clinics in Chest Medicine 16, 583–602.

    Google Scholar 

  2. Nadel, J. and Tierney, D. (1961), Effect of a previous deep inspiration on airway resistance in man. J. Appl. Physiol. 16, 717–719.

    PubMed  CAS  Google Scholar 

  3. Fish, J., Ankin, M., Kelly, J., and Peterman, V. (1981), Regulation of bronchomotor tone by lung inflation in asthmatic and nonasthmatic subjects. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 50, 1079–1086.

    CAS  Google Scholar 

  4. Jensen, A., Atileh, H., Suki, B., Ingenito, E., and Lutchen, K. (2001), Airway caliber in healthy and asthmatic subjects: effects of bronchial challenge and deep inspirations. J. Appl. Physiol. 91, 506–515.

    PubMed  CAS  Google Scholar 

  5. Gayrard, P., Orehek, J., Grimaud, C., and Charpin, J. (1975) Bronchoconstrictor effects of a deep inspiration in patients with asthma. Am. Rev. Respir. Dis. 111, 433–439.

    PubMed  CAS  Google Scholar 

  6. Orehek, J., Charpin, D., Velardocchio, J., and Grimaud, C. (1980), Bronchomotor effect of a bronchoconstriction-induced deep inspiration in asthmatics. Am. Rev. Respir. Dis. 121, 297–305.

    PubMed  CAS  Google Scholar 

  7. Malmberg, P., Larsson, K., and Zhiping, S. (1993), Importance of the time interval between FEV1 measurements in a methacholine provocation test. Eur. J. Resp. Dis. 6, 680–686.

    CAS  Google Scholar 

  8. Kapsali, T., Permutt, S., Laube, B., Scichilone, N., and Togias, A. (2000), The potent bronchoprotective effect of deep inspiration and its absence in asthma. J. Appl. Physiol. 89, 711–720.

    PubMed  CAS  Google Scholar 

  9. Skloot, G., Permutt, S., and Togias, A. (1995), Airway hyperresponsiveness in asthma: a problem of limited smooth muscle relaxation with inspiration. J. Clin. Investig. 96, 2393–2403.

    PubMed  CAS  Google Scholar 

  10. Moore, B., Verburgt, L., King, G., and Pare, P. (1997), The effect of deep inspiration on methacholine dose-response curves in normal subjects. Am. J. Respir. Crit. Care Med. 156, 1278–1281.

    PubMed  CAS  Google Scholar 

  11. King, G., Moore, B., Seow, C., and Pare, P. (1999), Time course of increased airway narrowing caused by inhibition of deep inspiration during methacholine challenge. Am. J. Respir. Crit. Care Med. 160, 454–457.

    PubMed  CAS  Google Scholar 

  12. Brusasco, V., Crimi, E., Barisione, G., Spanevello, A., Rodarte, J., and Pellegrino, R. (1999), Airway responsiveness to methacholine: effects of deep inhalations and airway inflammation. J. Appl. Physiol. 87, 567–573.

    PubMed  CAS  Google Scholar 

  13. Brown, R. H., Croisille, P., Mudge, B., Diemer, F., Permutt, S., and Togias, A. (2000), Airway narrowing in healthy humans inhaling methacholine without deep inspirations demonstrated by HRCT. Am. J. Respir. Crit. Care Med. 161, 1256–1263.

    PubMed  CAS  Google Scholar 

  14. Pyrgos, G., Michalopoulou, P., Proud, D., Kotanidou, A., Diemer, F., Permutt, S., et al. (2002). Bronchoconstriction from bradykinin is not modified by deep inspirations. Submitted.

  15. Pyrgos, G., Kapsali, T., Permutt, S., and Togias, A. (2002), Absence of deep inspiration-induced bronchoprotection against inhaled allergen. Submitted.

  16. Kesler, B., Canning, B., and Togias, A. (2001), Inhibition of cholinergic nerve activity in healthy humans minics the bronchoprotective effect of deep inspiration (DI). Am. J. Crit. Care Med. 163, A829.

    Google Scholar 

  17. Ding, D., Martin, J., and Macklem, P. (1987), Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans. J. Appl. Physiol. 62, 1324–1330.

    PubMed  CAS  Google Scholar 

  18. Duggan, C., Chan, J., Whelan, A., and Berend, N. (1990), Bronchodilation induced by deep breaths in relation to transpulmonary pressure and lung volume. Thorax 45, 930–934.

    PubMed  CAS  Google Scholar 

  19. Scichilone, N., Kapsali, T., Permutt, S., and Togias, A. (2000), Deep inspiration-induced bronchoprotection is stronger than bronchodilation. Am. J. Respir. Crit. Care Med. 162, 910–916.

    PubMed  CAS  Google Scholar 

  20. Pichurko, B. and Ingram, R. (1987), Effects of airway tone and volume history on maximal expiratory flow in asthma. J. Appl. Physiol. 62, 1133–1140.

    PubMed  CAS  Google Scholar 

  21. Orehek, J., Nicoli, M., Delpierre, S., and Beaupre, A. (1981), Influence of the previous deep inspiration on the spirometric measurement of provoked bronchoconstriction in asthma. Am. Rev. Respir. Dis. 123, 269–272.

    PubMed  CAS  Google Scholar 

  22. Scichilone, N., Permutt, S., and Togias, A. (2001), The lack of the bronchoprotective and not the bronchodilatory ability of deep inspiration is associated with airways hyperresponsiveness. Am. J. Respir. Crit. Care Med. 163, 413–419.

    PubMed  CAS  Google Scholar 

  23. Lim, T., Pride, N., and Ingram, R. J. (1987), Effects of volume history during spontaneous and acutely induced air-flow obstruction in asthma. Am. Rev. Respir. Dis. 135, 591–596.

    PubMed  CAS  Google Scholar 

  24. Lim, T., Pride, N., and Ingram, R. (1989), the effects of deep inhalation on maximal expiratory flow during intensive treatment of spontaneous asthmatic episodes. Am. Rev. Respir. Dis. 140, 340–343.

    PubMed  CAS  Google Scholar 

  25. Pellegrino, R., Violante, B., Crimi, E., and Brusasco, V. (1990), Effects of deep inhalation during early and late asthmatic reactions to antigen. Am. Rev. Respir. Dis. 142, 822–825.

    PubMed  CAS  Google Scholar 

  26. Brown, R., Scichilone, N., Mudge, B., Diemer, F., Permutt, S., and Togias, A. (2001), High-resolution computed tomographic evaluation of airway distensibility and the effects of lung inflation on airway caliber in healthy subjects and individuals with asthma. Am. J. Respir. Crit. Care Med. 163(4), 994–1001.

    PubMed  CAS  Google Scholar 

  27. Scichilone, N., Kapsali, J., Pyrgos, G., Anderlind, C., Permutt, S., and Togias, A. (2001), The distribution of deep inspiration (DI)-induced bronchoprotection (BP). Am. J. Crit. Care Med. 163, A289.

    Google Scholar 

  28. Wheatley, J., Pare, P., and Engel, L. (1989), Reversibility of induced bronchoconstriction by deep inspiration in normal and asthmatic subjects. Eur. Respir. J. 2, 331–339.

    PubMed  CAS  Google Scholar 

  29. Pellegrino, R., Violante, B., Selleri, R., and Brusasco, V. (1994), Changes in residual volume during induced bronchoconstriction in healthy and asthmatic subjects. Am. J. Respir. Crit. Care Med. 150, 363–368.

    PubMed  CAS  Google Scholar 

  30. Burns, G. and Gibson, G. (1998), Airway hyperresponsiveness in asthma: not just a problem of smooth muscle relaxation with inspiration. Am. J. Respir. Crit. Care Med. 158, 201–206.

    Google Scholar 

  31. Skloot, G., Jourdy, D., Shpak, I., Mrejen, K., and Schachter, E. (2001), Increasing time without deep inspiration enhances methacholine reactivity in nonasthmatics but not in asthmatics. Am. J. Respir. Crit. Care Med. 163, A828.

    Google Scholar 

  32. Anderlind, C., Kuroda, N., Permutt, S., and Togias, A. (2001), Validation of inspiratory vital capacity (IVC) as an outcome of single dose bronchoprovocation when deep inspiration (DI) is prohibited. Am. J. Crit. Care Med. 163(5), A829.

    Google Scholar 

  33. Fredberg, J., Inouye, D., Miller, B., Nathan, M., Jafari, S., Raboudi, S., et al. (1997), Airway smooth muscle, tidal stretches, and dynamically determined contractile states. Am. J. Respir. Crit. Care Med. 156, 1752–1759.

    PubMed  CAS  Google Scholar 

  34. Fredberg, J., Inouye, D., Srboljub, M., Mijailovich, M., and Butler, J. (1999), Perturbed equilibrium of myosin binding in airway smooth muscle and its implications in bronchospasm. Am. J. Respir. Crit. Care Med. 159, 959–967.

    PubMed  CAS  Google Scholar 

  35. Gunst, S. and Wu, M. (2001), Plasticity of airway smooth muscle stiffness and extensibility: role of length-adaptive mechanisms. J. Appl. Physiol. 90, 741–749.

    PubMed  CAS  Google Scholar 

  36. Hughes, R., May, A., and Widdicome, J. (1959), Stress relaxation in rabbits' lungs. J. Physiol. (Lond.) 146, 85–97.

    CAS  Google Scholar 

  37. Thulesius, O. and Mustafa, S. (1994), Stretch-induced myogenic responses of airways after histamine and carbachol. Clin. Physiol. 14, 135–143.

    PubMed  CAS  Google Scholar 

  38. Gunst, S., Stropp, J., and Service, J. (1990), Mechanical modulation of pressure-volume characteristics of contracted canine airways in vitro. J. Appl. Physiol. 68, 2223–2229.

    PubMed  CAS  Google Scholar 

  39. Sasaki, H. and Hoppin, F. (1979), Hysteresis of contracted airway smooth muscle. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 47, 1251–1262.

    CAS  Google Scholar 

  40. Gunst, S. and Mitzner, W. (1981), Mechanical properties of contracted canine bronchial segments in vitro. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 50, 1236–1247.

    CAS  Google Scholar 

  41. Shen, X., Wu, M., Tepper, R., and Gunst, S. (1997), Mechanisms for the mechanical response of airway smooth muscle to length oscillation. Amer. J. Physiol. 83, 731–738.

    CAS  Google Scholar 

  42. Gunst, S. and Russell, J. (1982), Contractile force of canine tracheal smooth muscle during continuous stretch. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 52, 655–663.

    CAS  Google Scholar 

  43. Shen, X., Ramchandani, R., Gunst, S., and Tepper, R. (1999), Effect of timing of deep inspiration on airway response to methacholine challenge in mature and immature rabbits. Am. J. Respir. Crit. Care Med. 159, A469.

    Google Scholar 

  44. Gunst, S., Meiss, R., Wu, M., and Rowe, M. (1995), Mechanisms for the mechanical plasticity of tracheal smooth muscle. Am. J. Physiol. 268, C1267-C1276.

    PubMed  CAS  Google Scholar 

  45. Pratusevich, V., Seow, C., and Ford, L. (1995), Plasticity in canine airway smooth muscle. J. Gen. Physiol. 105, 73–94.

    PubMed  CAS  Google Scholar 

  46. Wang, L., Pare, P., and Seow, C. (2000), Effects of length oscillation on the subsequent force development in swine tracheal smooth muscle. J. Appl. Physiol. 88, 2246–2250.

    PubMed  CAS  Google Scholar 

  47. Scichilone, N., Prygos, G., Kapsali, T., Anderlind, C., Brown, R., Permutt, S., et al. (2001), Airways hyperresponsiveness and the effects of lung inflation. Intl. Arch. Allergy Immunol. 124, 262–266.

    CAS  Google Scholar 

  48. Huxley, A. (1957), Muscle structure and theories of contraction. Prog. Biophys. Biophys. Chem. 7, 255–318.

    PubMed  CAS  Google Scholar 

  49. Gunst, S. (1983), Contractile force of canine airway smooth muscle during cyclical length changes. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 55, 759–769.

    CAS  Google Scholar 

  50. Davis, H., Fowler, W., and Lambert, E. (1956), Effect of volume and rate inflation and deflation on transpulmonary pressure and response of pulmonary stretch receptors. Am. J. Physiol. 187, 558–566.

    PubMed  CAS  Google Scholar 

  51. Hida, W., Arai, M., Shindoh, C., Liu, Y.-N., Sasaki, H., and Takishima, T. (1984), Effect of inspiratory flow rate on bronchomotor tone in normal and asthmatic subjects. Thorax 39, 86–92.

    PubMed  CAS  Google Scholar 

  52. Chandy, D., Carillo-Bislick, R., Schachter, E., and Skloot, G. (1999), Differences between the bronchoprotective effect of fast and slow deep inspirations. Am. J. Respir. Crit. Care Med. 159, A468.

    Google Scholar 

  53. Kesler, B. S. and Canning, B. J. (1999), Regulation of baseline cholinergic tone in guinea-pig airway smooth muscle. J. Physiol. 518, 843–855.

    PubMed  CAS  Google Scholar 

  54. Drazen, J., Loring, S., Jackson, A., Snapper, J., and Ingram, R. (1979), Effects of volume history on airway changes induced by histamine or vagal stimulation. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 47, 657–665.

    CAS  Google Scholar 

  55. Ellis, J. L. and Undem, B. J. (1992), Inhibition by L-NG-nitro-L-arginine of nonadrenergic-noncholinergic-mediated relaxations of human isolated central and peripheral airway. Am. Rev. Respir. Dis. 146(6), 1543–1547.

    PubMed  CAS  Google Scholar 

  56. Fischer, A. and Hoffman, B. (1996), Nitric oxide synthase in neurons and nerve fibers of lower airways and in vagal sensory Ganglia of man—correlation with neuropeptides. Am. J. Respir. Crit. Care Med. 154, 209–216.

    PubMed  CAS  Google Scholar 

  57. Hogman, M., Frostell, C., Arnberg, H., and Hedenstierna, G. (1993), Inhalation of nitric oxide modulates methacholine-induced bronchoconstriction in the rabbit. Eur. Respir. J. 6, 177–180.

    PubMed  CAS  Google Scholar 

  58. Hogman, M., Frostell, C., Hedenstrom, H., and Hedenstierna, G. (1993), Inhalation of nitric oxide modulates adult human bronchial tone. Am. Rev. Respir. Dis. 148, 1474–1478.

    PubMed  CAS  Google Scholar 

  59. Kacmarek, R., Ripple, R., Cockrill, B., Bloch, K., Zapol, W., and Johnson, D. (1996), Inhaled nitric oxide; a bronchodilator in mild asthmatics with methacholine-induced bronchospasm. Am. J. Respir. Crit. Care Med. 153, 128–135.

    PubMed  CAS  Google Scholar 

  60. Nijkamp, F., Van Der Linde, H., and Folkerts, G. (1993), Nitric oxide synthesis inhibitors induce airway hyperresponsiveness in the guinea pig in vivo and in vitro: the role of the epithelium. Am. Rev. Respir. Dis. 148, 727–734.

    PubMed  CAS  Google Scholar 

  61. Aizawa, H., Takata, S., Inoue, H., Matsumoto, K., Koto, H., and Hara, N. (1999), Role of nitric oxide released from iNANC neurons in airway responsiveness in cats. Eur. Respir. J. 13, 775–780.

    PubMed  CAS  Google Scholar 

  62. De Sanctis, G., MacLean, J., Hamada, K., Mehta, S., Scott, J., Jiao, A., et al. (1999), Contribution of nitric oxide synthases 1,2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma. J. Exp. Med. 189.

  63. Ricciardolo, F. L. M., Geppetti, P., Mistretta, A., Nadel, J. A., Sapienza, M. A., Bellofiore, S., et al. (1996), Randomised double-blind placebo-controlled study of the effect of inhibition of nitric oxide synthesis in bradykinin-induced asthma. Lancet 348, 374–377.

    PubMed  CAS  Google Scholar 

  64. Ricciardolo, F., Timmers, M., Geppetti, P., van Schadewijk, A., Brahim, J., Sont, J., et al. (2001), Allergen-induced impairment of bronchoprotective nitric oxide synthesis in asthma. J. Allergy Clin. Immunol. 108, 198–204.

    PubMed  CAS  Google Scholar 

  65. Bannenberg, G. and Gustafsson, L. (1997), Stretch-induced stimulation of lower airway nitric oxide formation in the guinea-pig: inhibition by gadolinium chloride. Pharmacol. Toxicol. 81(1), 13–18.

    PubMed  CAS  Google Scholar 

  66. Groneberg, D., Springer, J., and Fischer, A. (2001), Vasoactive intestinal polypeptide as mediator of asthma. Pulm. Pharm. Therap. 14, 391–401.

    CAS  Google Scholar 

  67. Barnes, P. and Dixon, C. (1984), The effect of inhaled vasoactive intestinal peptide on bronchial reactivity to histamine in humans. Am. Rev. Respir. Dis. 130, 162–166.

    PubMed  CAS  Google Scholar 

  68. Altiere, R., Kung, M., and Diamond, L. (1984), Comparative effects of inhaled isoproterenol and vasoactive intestinal peptide on histamine-induced bronchoconstriction in human subjects. Chest 86, 153–154.

    PubMed  CAS  Google Scholar 

  69. Wirtz, H. and Dobbs, L. (1990), Calcium mobilization and exocytosis after one mechanical stretch of lung epithelial cells. Science 250, 1266–1269.

    PubMed  CAS  Google Scholar 

  70. Macklem, P., Proctor, D., and Hogg, J. (1970), The stability of peripheral airways. Respir. Physiol. 9, 191–203.

    Google Scholar 

  71. Enhorning, G., Yarussi, A., and Rao, P. I. V. (1996) Increased airway resistance due to surfactant dysfunction can be alleviated with aerosol surfactant. Can. J. Physiol. Pharmacol. 74, 687–691.

    PubMed  CAS  Google Scholar 

  72. James, A., Pearce-Pinto, G., and Hillman, D. (1994), Effects of lung volume and surface forces on maximal airway smooth muscle shortening. J. Appl. Physiol. 77, 1755–1762.

    PubMed  CAS  Google Scholar 

  73. Berry, E., Edmonds, J., and Wyllie, J. (1971), Release of prostaglandins E2 and unidentified factors from ventilated lungs. Br. J. Surg. 58, 189–192.

    PubMed  CAS  Google Scholar 

  74. Said, S., Kitamura, S., Yoshida, T., Preskitt, J., and Holden, L. (1974), Humoral control of airways. Ann. NY Acad. Sci. 221, 103–114.

    PubMed  CAS  Google Scholar 

  75. Shore, S., Austen, K., and Drazen, J. (1989), Eicosanoids and the lung. In: Massaro, D. (ed) Lung Cell Biology. New York: Marcel Dekker, 1989, 1011–1089.

    Google Scholar 

  76. Shore, S., Powell, W., and Martin, J. (1985) Endogenous prostaglandins modulate histamine induced contraction in canine tracheal smooth muscle. J. Appl. Physiol. 58, 859–868.

    PubMed  CAS  Google Scholar 

  77. Hulks, G., Jardine, A., Connell, J., and Thomson, N. (1991), Influence of elevated plasma levels of atrial natriuretric factor on bronchial reactivity in asthma. Am. Rev. Respir. Dis. 143, 775–782.

    Google Scholar 

  78. Hulks, G., Jardine, A., Connell, J., and Thomson, N. (1990), Effect of atrial natriuretic peptide on bronchomotor tone in normal subjects. Clin. Sci. 79, 51–55.

    PubMed  CAS  Google Scholar 

  79. Barnes, P., Fitzgerald, G., Brown, M., and Dollery, C. (1980), Nocturnal asthma and changes in circulating epinephrine, histamine, and cortisol. N. Engl. J. Med. 303, 263–267.

    PubMed  CAS  Google Scholar 

  80. Warren, J. and Dalton, N. (1983), A comparison of the bronchodilator and vasopressor effects of exercise levels of adrenaline in man. Clin. Sci. (Lond.) 64, 475–479.

    CAS  Google Scholar 

  81. Gunst, S. and Wu, M. (1996), Canine tracheal smooth muscle stiffness increases with duration of contraction. Am. J. Respir. Crit. Care Med. 153, A841 (abstract).

    Google Scholar 

  82. Seow, C., Pratusevich, V., and Ford, L. (2000), Series-to-parallel transition in the filament lattice of airway smooth muscle. J. Appl. Physiol. 89, 869–876.

    PubMed  CAS  Google Scholar 

  83. Macklem, P. (1996), A theoretical analysis of the effect of airway smooth muscle load on airway narrowing. Am. J. Respir. Crit. Care Med. 153, 83–89.

    PubMed  CAS  Google Scholar 

  84. Schellenberg, R., Pare, P., Hards, J., and Ishida, K. (1991), Smooth muscle mechanics: implications for airway hyperresponsiveness. Int. Arch. Allergy Appl. Immunol. 94, 291–292.

    PubMed  CAS  Google Scholar 

  85. Mead, J., Takishima, T., and Leith, D. (1970), Stress distribution in lungs: a model of pulmonary elasticity. J. Appl. Physiol. 28, 596–608.

    PubMed  CAS  Google Scholar 

  86. Lai-Fook, S., Hyatt, R., and Rodarte, J. (1978), Effect of parenchymal shear modulus and lung volume on bronchial pressure-diameter behavior. J. Appl. Physiol. 44, 859–868.

    PubMed  CAS  Google Scholar 

  87. Gunst, S., Warner, D., Wilson, T., and Hyatt, R. (1988), Parenchymal interdependence and airway response to methacholine in excised dog lobes. J. Appl. Physiol. 65, 2490–2497.

    PubMed  CAS  Google Scholar 

  88. Macklem, P. (1989), Mechanical factors determining maximum bronchoconstriction. Eur. Respir. J. 2, 516S-519S.

    Google Scholar 

  89. Pyrgos, G., Scichilone, N., Mintz, M., Permutt, S., Togias, A., and Brown, R. (2001), Deep inspiration-induced bronchodilation in asthma is dependent on airways distensibility assessed by HRCT. Am. J. Crit. Care Med. 163, A830.

    Google Scholar 

  90. Pyrgos, G., Scichilone, N., Mintz, M., Liu, M., Togias, A., and Brown, R. (2001), Decreased airway relaxation by a beta agonist is associated with decreased distensibility by lung inflation in asthma. Am. J. Crit. Care Med., A421.

  91. Marthan, R. and Woolcock, A. (1989), Is a myogenic response involved in deep inspiration-induced bronchoconstriction in asthmatics?. Am. Rev. Respir. Dis. 140, 1354–1358.

    PubMed  CAS  Google Scholar 

  92. Antonissen, L., Mitchell, R., Koreger, E., Kepron, W., Tse, K., and Stephens, N. (1979), Mechanical alterations of airway smooth muscle in a canine asthmatic model. J. Appl. Physiol. 46, 681–687.

    PubMed  CAS  Google Scholar 

  93. Gayrard, P., Orehek, J., Grimaud, C., and Charpin, J. (1979), Mechanisms of the bronchoconstrictor effects of deep inspiration in asthmatic patients. Thorax 34, 234–240.

    PubMed  CAS  Google Scholar 

  94. Gaston, B., Drazen, J., Loscalzo, J., and Stamler, J. (1994), The biology of nitrogen oxides in the airways. Am. J. Respir. Crit. Care Med. 149, 538–551.

    PubMed  CAS  Google Scholar 

  95. Alving, K., Weitzberg, E., and Lundberg, J. (1993), Increased amount of nitric oxide in exhaled air of asthmatics. Eur. Respir. J. 6, 1368–1370.

    PubMed  CAS  Google Scholar 

  96. Sanders, S. (1999), Nitric oxide in asthma; pathogenic, therapeutic, or diagnostic?. Am. J. Respir. Cell Mol. Biol. 21, 147–149.

    PubMed  CAS  Google Scholar 

  97. Sapienza, M., Kharitonov, S., Horvath, I., Chung, K., and Barnes, P. (1998), Effect of inhaled L-arginine on exhaled nitric oxide in normal and asthmatic subjects. Thorax 53, 172–175.

    PubMed  CAS  Google Scholar 

  98. Scichilone, N., Liu, M., Pyrgos, G., Sylvester, J., Togias, A., and Permutt, S. (2001), Role of airway NO diffusion in the pathogenesis of asthma. Am. J. Crit. Care Med. 163, A757.

    Google Scholar 

  99. Silkoff, P., Sylvester, J., Zamel, N., and Permutt, S. (2000), Airway nitric oxide diffusion in asthma. Role in pulmonary function and bronchial responsiveness. Am. J. Respir. Crit. Care Med. 161, 1218–1228.

    PubMed  CAS  Google Scholar 

  100. Liu, M. C., Sylvester, J. T., and Permutt, S. (2000), Effect of allergen challenge on airway nitric oxide diffusion. Am. J. Respir. Crit. Care Med. 161, A743.

    Google Scholar 

  101. Takata, M., Filippov, G., Liu, H., Ichinose, F., Janssens, S., Bloch, D., et al. (2001), Cytokines decrease sGC in pulmonary artery smooth muscle cells via NO-dependent and NO-independent mechanisms. Am. J. Physiol. Lung Cell Mol. Physiol. 280, L272-L278.

    PubMed  CAS  Google Scholar 

  102. DeFronzo, R. (1988), Lilly Lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37, 667–687.

    PubMed  CAS  Google Scholar 

  103. Kroegel, C., Liu, M., Hubbard, W., Lichtenstein, L., and Bochner, B. (1994), Blood and bronchoalveolar eosinophils in allergic subjects after segmental antigen challenge: surface phenotype, density heterogeneity, and prostanoid production. J. Allergy Clin. Immunol. 93, 725–734.

    PubMed  CAS  Google Scholar 

  104. Proud, D., Togias, A., Naclerio, R., Crush, S., Norman, P., and Lichtenstein, L. (1983), Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen. J. Clin. Investig. 72, 1678–1685.

    PubMed  CAS  Google Scholar 

  105. Creticos, P., Peters, S., Adkinson, N. J., Naclerio, R., Hayes, E., Norman, P., et al. (1984), Peptide leukotriene release after antigen challenge in patients sensitive to ragweed. N. Engl. J. Med. 310, 1626–1630.

    PubMed  CAS  Google Scholar 

  106. Adelroth, E., Morris, M., Hargreave, F., and O'Byrne, P. (1986), Airway responsiveness to leukotrienes C4 and D4 and to methacholine in patients with asthma and normal controls. N. Engl. J. Med. 315, 480–484.

    PubMed  CAS  Google Scholar 

  107. Kern, R., Smith, L., Patterson, R., Krell, R., and Bernstein, P. (1986), Characterization of the airway response to inhaled leukotriene D4 in normal subjects. Am. Rev. Respir. Dis. 133, 1127–1132.

    PubMed  CAS  Google Scholar 

  108. Thomson, R., Bramley, A., and Schellenberg, R. (1996), Airway muscle stereology: implications for increased shortening in asthma. Am. J. Respir. Crit. Care Med. 154, 749–757.

    PubMed  CAS  Google Scholar 

  109. Solway, J. and Fredberg, J. (1997), Perhaps airway smooth muscle dysfunction contributes to asthmatic bronchial hyperresponsiveness after all. Am. J. Resp. Cell Molec. Biol. 17, 144–147.

    CAS  Google Scholar 

  110. Fredberg, J. (1999), Airway smooth muscle in asthma: flirting with disaster. Eur. Respir. J. 12, 1252–1256.

    Google Scholar 

  111. Pliss, L., Ingenito, E., and Ingram, R. (1989), Responsiveness, inflammation, and effects of deep breaths on obstruction in mild asthma. J. Appl. Physiol. 66, 2298–2304.

    PubMed  CAS  Google Scholar 

  112. Bel, E., Tamaka, W., Spector, R., Friedman, B., Veen, H., Dijkman, J., et al. (1990), An effective oral leukotriene biosynthesis inhibitor on antigen-induced early and late asthmatic reactions in man. Am. Rev. Respir. Dis. 141, A31.

    Google Scholar 

  113. Scichilone, N., Permutt, S., and Togias, A. (2002), Inhaled steroids and the beneficial effects of deep inspiration (DI) in asthma. Am. J. Respir. Crit. Care Med. 165, A123.

    Google Scholar 

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mount Sinai School of Medicine, New York, NY

    Gwen Skloot

  2. Divisions of Clinical Immunology and Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD

    Alkis Togias

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  1. Gwen Skloot
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  2. Alkis Togias
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Correspondence to Gwen Skloot.

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Skloot, G., Togias, A. Bronchodilation and bronchoprotection by deep inspiration and their relationship to bronchial hyperresponsiveness. Clinic Rev Allerg Immunol 24, 55–71 (2003). https://doi.org/10.1385/CRIAI:24:1:55

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