Nocturnal asthma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


The pathophysiology of nocturnal asthma is closely associated with the chronobiology and the science of biologic processes that have time-related rhythms.

  • Alterations in beta2-adrenergic[1][2] and glucocorticoid receptors[3] and hypothalamic-pituitary-adrenal axis function have shown to play a role in modulating the nocturnal asthma phenotype, and recent studies have suggested elevation and phase delay of peak serum melatonin,[4] a neurohormonal controller of circadian rhythms, to play an important role in the pathogenesis of nocturnal asthma.[5][6]
  • The increase of CD51 at night, in patients with nocturnal asthma, may be related to increased airway inflammation and repair processes in response to injury.[7]
  • Research has demonstrated that the greatest inflammation in nocturnal asthmatics occurs in the proximal alveolar tissue at 4 AM. Inflammatory mediators such as eosinophils, macrophages and CD4+ lymphocytic infiltration, were shown to accumulate in the proximal alveolar tissue and contribute to the variation in lung function.[8][9]
  • The development of nocturnal airway obstruction in asthma has been associated with the enhanced production of oxygen radicals by air-space cells. Because oxygen radicals can cause airway injury and thus enhance bronchial obstruction, it has been postulated that the release of these reactive compounds is causally associated with nocturnal asthma.[10][11][12]
  • Worsening of nocturnal asthma has been associated to the secondary increase in the levels of inflammatory mediators such as leukotrienes, interleukins, and histamine.[10][13][14][15][16][17]
  • Enhanced parasympathetic activity is associated with bronchial hyper-reactivity, which is characteristic of asthma. It is believed this increased cholinergic tone may be related to the pathogenesis of bronchial asthma.[18][19]


  1. Contopoulos-Ioannidis DG, Manoli EN, Ioannidis JP (2005) Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes. J Allergy Clin Immunol 115 (5):963-72. DOI:10.1016/j.jaci.2004.12.1119 PMID: 15867853
  2. Turki J, Pak J, Green SA, Martin RJ, Liggett SB (1995) Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype. J Clin Invest 95 (4):1635-41. DOI:10.1172/JCI117838 PMID: 7706471
  3. Kraft M, Vianna E, Martin RJ, Leung DY (1999) Nocturnal asthma is associated with reduced glucocorticoid receptor binding affinity and decreased steroid responsiveness at night. J Allergy Clin Immunol 103 (1 Pt 1):66-71. PMID: 9893187
  4. Sutherland ER, Ellison MC, Kraft M, Martin RJ (2003) Elevated serum melatonin is associated with the nocturnal worsening of asthma. J Allergy Clin Immunol 112 (3):513-7. PMID: 13679809
  5. Sutherland ER (2005) Nocturnal asthma. J Allergy Clin Immunol 116 (6):1179-86; quiz 1187. DOI:10.1016/j.jaci.2005.09.028 PMID: 16337443
  6. Sutherland ER, Ellison MC, Kraft M, Martin RJ (2003) Altered pituitary-adrenal interaction in nocturnal asthma. J Allergy Clin Immunol 112 (1):52-7. PMID: 12847479
  7. Kraft M, Striz I, Georges G, Umino T, Takigawa K, Rennard S et al. (1998) Expression of epithelial markers in nocturnal asthma. J Allergy Clin Immunol 102 (3):376-81. PMID: 9768576
  8. Kraft M, Djukanovic R, Wilson S, Holgate ST, Martin RJ (1996) Alveolar tissue inflammation in asthma. Am J Respir Crit Care Med 154 (5):1505-10. PMID: 8912772
  9. Kraft M, Martin RJ, Wilson S, Djukanovic R, Holgate ST (1999) Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma. Am J Respir Crit Care Med 159 (1):228-34. PMID: 9872843
  10. 10.0 10.1 Jarjour NN, Busse WW, Calhoun WJ (1992) Enhanced production of oxygen radicals in nocturnal asthma. Am Rev Respir Dis 146 (4):905-11. PMID: 1329592
  11. Martin RJ, Cicutto LC, Smith HR, Ballard RD, Szefler SJ (1991) Airways inflammation in nocturnal asthma. Am Rev Respir Dis 143 (2):351-7. PMID: 1990952
  12. Doi S, Murayama N, Inoue T, Takamatsu I, Kameda M, Omoto Y et al. (1996) CD4 T-lymphocyte activation is associated with peak expiratory flow variability in childhood asthma. J Allergy Clin Immunol 97 (4):955-62. PMID: 8655891
  13. Barnes P, FitzGerald G, Brown M, Dollery C (1980) Nocturnal asthma and changes in circulating epinephrine, histamine, and cortisol. N Engl J Med 303 (5):263-7. DOI:10.1056/NEJM198007313030506 PMID: 6247655
  14. Wenzel SE, Trudeau JB, Kaminsky DA, Cohn J, Martin RJ, Westcott JY (1995) Effect of 5-lipoxygenase inhibition on bronchoconstriction and airway inflammation in nocturnal asthma. Am J Respir Crit Care Med 152 (3):897-905. PMID: 7663802
  15. Jarjour NN, Busse WW (1995) Cytokines in bronchoalveolar lavage fluid of patients with nocturnal asthma. Am J Respir Crit Care Med 152 (5 Pt 1):1474-7. PMID: 7582279
  16. Szefler SJ, Ando R, Cicutto LC, Surs W, Hill MR, Martin RJ (1991) Plasma histamine, epinephrine, cortisol, and leukocyte beta-adrenergic receptors in nocturnal asthma. Clin Pharmacol Ther 49 (1):59-68. PMID: 1846332
  17. Bellia V, Bonanno A, Cibella F, Cuttitta G, Mirabella A, Profita M et al. (1996) Urinary leukotriene E4 in the assessment of nocturnal asthma. J Allergy Clin Immunol 97 (3):735-41. PMID: 8613628
  18. Morrison JF, Pearson SB, Dean HG (1988) Parasympathetic nervous system in nocturnal asthma. Br Med J (Clin Res Ed) 296 (6634):1427-9. PMID: 3132275
  19. Kallenbach JM, Webster T, Dowdeswell R, Reinach SG, Millar RN, Zwi S (1985) Reflex heart rate control in asthma. Evidence of parasympathetic overactivity. Chest 87 (5):644-8. PMID: 3987376

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