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Nocturnal asthma

INTRODUCTION

Nocturnal worsening of asthma has become a recognized and important problem that must be considered in the management of this disorder. It is quite common, as a survey of almost 8000 patients with varying degrees of asthma found that approximately 75 percent of asthmatics awaken at least once a week with symptoms, 64 percent three times per week, and 39 percent every night [1]. In one allergy specialty practice, a 67 percent prevalence of nocturnal asthma symptoms was found [2]. Eleven percent awakened every night, 16 percent three to six nights per week, 20 percent one to two nights per week, and 20 percent one night per month.

The occurrence of these symptoms is also reflected in mortality statistics. As an example, over a one-year period, 53 percent of asthma deaths in one report occurred at night [3]. However, the time of death does not completely reflect when asthma worsened; 79 percent of these patients had premortem complaints of asthma affecting their sleep, which occurred every night in 42 percent.

The high incidence of nocturnal asthma does not simply represent the waning of medication through the night. The vast majority of dyspneic episodes without medication still occur between 10 PM and 7 AM (graph 1) [4]. An overview of nocturnal asthma will be presented here; the general management of asthma is discussed separately. (See "An overview of asthma management".)

CIRCADIAN RHYTHMS AND ASTHMA

The chronobiology of asthma has been summarized in a 1998 NHLBI workshop [5]. Asthma is associated with a circadian pattern in lung function, with best function occurring at approximately 4 PM, and a worst at around 4 AM (graph 2). The normal population also experiences this circadian change in lung function, but the peak-to-trough swings in peak expiratory flow rate are only 5 to 8 percent compared to a variation which can reach 50 percent or more in asthmatics [6].

Bronchial responsiveness to inhaled bronchoconstrictors is also markedly increased at night in asthmatic subjects [7,8]. Larger circadian change in bronchial reactivity predicts a greater overnight fall in peak expiratory flow rates [9].
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References Top
  1. Turner-Warwick, M. Epidemiology of nocturnal asthma. Am J Med 1988; 85:6.
  2. Storms, WW, Bodman, SF, Nathan, RA, Byer, P. Nocturnal asthma symptoms may be more prevalent than we think. J Asthma 1994; 31:313.
  3. Robertson, CF, Rubinfeld, AR, Bowes, G. Deaths from asthma in Victoria; a 12-month survey. Med J Aust 1990; 152:511.
  4. Dethlefsen, U, Repgas, R. Ein neues therapieprinzip bei nachtlichen asthma. Clin Med 1985; 80:44.
  5. Martin, RJ, Banks-Schlegel, S. Chronobiology of asthma. Am J Respir Crit Care Med 1998; 158:1002.
  6. Hetzel, MR, Clark, TJH. Comparison of normal and asthmatic circadian rhythms in peak expiratory flow rate. Thorax 1980; 35:732.
  7. Barnes, PJ, Chung, KF, Page, CP. Inflammatory mediators and asthma. Pharmacol Rev 1988; 40:49.
  8. deVries, K, Goei, JT, Booy-Noord, H, et al. Changes during 24 hours in the lung function and histamine hyperactivity of the bronchial tree in asthmatic and bronchitic patients. Arch Allergy Appl Immunol 1962; 20:93.
  9. Martin, RJ, Cicutto, LC, Ballard, RD. Factors related to the nocturnal worsening of asthma. Am Rev Respir Dis 1990; 141:33.
  10. D'Alonzo, GE, Steinigans, VW, Keller, A. Measurement of morning and evening airflow grossly underestimate the circadian variability of FEV1 and peak expiratory flow rate in asthma. Am J Respir Crit Care Med 1995; 152:1097.
  11. Sutherland, ER. Nocturnal asthma: underlying mechanisms and treatment. Curr Allergy Asthma Rep 2005; 5:161.
  12. Sutherland, ER. Nocturnal asthma. J Allergy Clin Immunol 2005; 116:1179.
  13. Kraft, M, Djukanovic, R, Wilson, S, et al. Alveolar tissue inflammation in asthma. Am J Respir Crit Care Med 1996; 154:1505.
  14. Kraft, M, Striz, I, Georges, G, et al. Expression of epithelial markers in nocturnal asthma. J Allergy Clin Immunol 1998; 102:376.
  15. Kraft, M, Martin, RJ, Wilson, S, et al. Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma. Am J Respir Crit Care Med 1999; 159:228.
  16. Irvin, CG, Pak, J, Martin, RJ. Airway-parenchyma uncoupling in nocturnal asthma. Am J Respir Crit Care Med 2000; 161:50.
  17. Sutherland, ER, Martin, RJ, Bowler, RP, et al. Physiologic correlates of distal lung inflammation in asthma. J Allergy Clin Immunol 2004; 113:1046.
  18. Martin, RJ, Cicutto, LC, Smith, HR, et al. Airways inflammation in nocturnal asthma. Am Rev Respir Dis 1991; 143:351.
  19. Jarjour, NN, Calhoun, WJ, Busse, WW. Enhanced metabolism of oxygen radicals in nocturnal asthma. Am Rev Respir Dis 1992; 146:905.
  20. Doi, S, Murayama, H, Inoue, T, et al. CD4 T-lymphocyte activation is associated with peak expiratory flow variability in childhood asthma. J Allergy Clin Immunol 1996; 97:955.
  21. Beam, WR, Weiner, DE, Martin, RJ. Timing of prednisone and alterations of airways inflammation in nocturnal asthma. Am Rev Respir Dis 1992; 146:1524.
  22. Kraft, M, Vianna, E, Martin, RJ, et al. Nocturnal asthma is associated with reduced glucocorticoid receptor binding affinity and decreased steroid responsiveness at night. J Allergy Clin Immunol 1999; 103:66.
  23. Barnes, P, FitzGerald, G, Brown, M, Dollery, C. Nocturnal asthma and changes in circulating epinephrine, histamine, and cortisol. N Engl J Med 1980; 303:263.
  24. Sutherland, ER, Ellison, MC, Kraft, M, Martin, RJ. Altered pituitary-adrenal interaction in nocturnal asthma. J Allergy Clin Immunol 2003; 112:52.
  25. Sutherland, ER, Ellison, MC, Kraft, M, Martin, RJ. Elevated serum melatonin is associated with the nocturnal worsening of asthma. J Allergy Clin Immunol 2003; 112:513.
  26. Sutherland, ER, Martin, RJ. Airway inflammation in chronic obstructive pulmonary disease: comparisons with asthma. J Allergy Clin Immunol 2003; 112:819.
  27. Wenzel, SE, Trudeau, JB, Kaminsky, DA, et al. Effect of 5-lipoxygenasse inhibition on bronchoconstriction and airway inflammation in nocturnal asthma. Am J Respir Crit Care Med 1995; 152:897.
  28. Jarjour, NN, Bussee, WW. Cytokines in bronchoalveolar lavage fluid of patients with nocturnal asthma. Am J Respir Crit Care Med 1995; 152:1474.
  29. Szefler, SJ, Ando, R, Cicutto, LC, et al. Plasma histamine, epinephrine, cortisol, and leukocyte beta-adrenergic receptors in nocturnal asthma. Clin Pharmacol Ther 1991; 49:59.
  30. Bellia, V, Bonanno, A, Cibella, F, et al. Urinary leukotriene E4 in the assessment of nocturnal asthma. J Allergy Clin Immunol 1996; 97:735.
  31. Desjardin, JA, Sutarik, MJ, Sah, BY, Ballard, RD. Influence of sleep on pulmonary capillary volume in normal and asthmatic subjects. Am J Respir Crit Care Med 1995; 152:193.
  32. Morrison, JFJ, Pearson, SB, Dean, HG. Parasympathetic nervous system in nocturnal asthma. Br Med J 1988; 296:1427.
  33. Kallenbach, JM, Webster, T, Dowdeswell, R, et al. Reflex heart rate control in asthma: Evidence of parasympathetic over activity. Chest 1985; 87:644.
  34. Contopoulos-Ioannidis, DG, Manoli, EN, Ioannidis, JP. Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes. J Allergy Clin Immunol 2005; 115:963.
  35. Turki, J, Pak, J, Green, SA, et al. Genetic polymorphisms of the beta-2 adenergic receptor in nocturnal and nonnocturnal asthma. J Clin Invest 1995; 95:1635.
  36. Boezen, HM, Postma, DS, Schouten, JP, et al. PEF variability, bronchial responsiveness and their relation to allergy markers in a random population (20-70 yr). Am J Respir Crit Care Med 1996; 154:30.
  37. Epton, MJ, Martin, IR, Graham, P, et al. Climate and aeroallergen levels in asthma: A 12 month prospective study. Thorax 1997; 52:528.
  38. Chan, CS, Woolcock, AJ, Sullivan, CE. Nocturnal asthma: Role of snoring and obstructive sleep apnea. Am Rev Respir Dis 1988; 137:1502.
  39. Nadel, JA, Widdicombe, JG. Reflex effects of upper airway irritation on total lung resistance and blood pressure. J Appl Physiol 1962; 17:861.
  40. Martin, RJ, Pak, J. Nasal CPAP in non-apneic nocturnal asthma. Chest 1991; 100:1024.
  41. Tan, WC, Martin, RJ, Pandey, R, Ballard, RD. Effects of spontaneous and simulated gastroesophageal reflux on sleeping asthmatics. Am Rev Respir Dis 1990; 141:1394.
  42. Ford, GA, Oliver, JS, Prior, JS, et al. Omeprazole in the treatment of asthmatics with nocturnal symptoms and gastro-oesophageal reflux: a placebo-controlled cross-over study. Postgrad Med J 1994; 70:350.
  43. Harding SM, Schan, CA, Guzzo, MR. Gastroesophageal reflux-induced bronchoconstriction. Chest 1995; 108:1220.
  44. Weiner, P, Azgad, Y, Ganum, R. Specific inspiratory muscle training in patients with bronchial asthma. Chest 1992; 102:1357.
  45. Sullivan, CE, Murphy, E, Kozar, LF, et al. Waking and ventilatory responses to laryngeal stimulation in sleeping dogs. J Appl Physiol 1978; 45:681.
  46. Brugman, SM, Larsen, GL, Henson, PM, et al. Increased lower airways responsiveness associated with sinusitis in a rabbit model. Am Rev Respir Dis 1993; 147:314.
  47. Fitzpatrick, MF, Mackay, T, Driver, H, Douglas, NJ. Salmeterol in nocturnal asthma: A double-blind, placebo controlled trial of a long acting inhaled ß2-agonist. BMJ 1990; 301:1365.
  48. Dahl, R, Earnshaw, JS, Palmer, JBD. Salmeterol: A four week study of a long-acting beta-adrenoceptor agonist for the treatment of reversible airways disease. Eur Respir J 1991; 4:1178.
  49. Holimon, TD, Chafin, CC, Self, TH. Nocturnal asthma uncontrolled by inhaled corticosteroids: theophylline or long-acting beta2 agonists?. Drugs 2001; 61:391.
  50. Lockey, RF, DuBuske, LM, Friedman, B, et al. Nocturnal asthma: Effect of salmeterol on quality of life and clinical outcomes. Chest 1999; 115:666.
  51. Postma, DS, Köeter, GH, Meurs, H, et al. Slow release terbutaline in nocturnal bronchial obstruction: Relation of terbutaline dosage and blood levels with circadian changes in peak flow values. Annu Rev Chronopharmocol 1984; 1:101.
  52. Moore-Gillon, J. Volmax (salbuterol CR 8 mg) in the management of nocturnal asthma: A placebo-controlled study (abstract). Eur Res J 1988; 1(Suppl 2):306S.
  53. Crompton, GK, Ayres, JG, Basran, G. Comparison of oral bambuterol and inhaled salmeterol in patients with symptomatic asthma and using inhaled corticosteroids. Am J Respir Crit Care Med 1999; 159:824.
  54. Martin, RJ, Kraft, M, Beaucher, WN, et al. A comparative study of extended release albuterol sulfate and long-acting inhaled salmeterol xinafoate in the treatment of nocturnal asthma. Ann Allergy Asthma Immunol 1999; 83:121.
  55. Smolensky, MH, Scott, PH, Kramer, WG. Clinical significance of day-night differences in serum theophylline concentration with special reference to Theo-Dur®. J Allergy Clin Immunol 1986; 78:716.
  56. Scott, PH, Tabachnik, E, MacLeod, S, et al. Sustained-release theophylline for childhood asthma: Evidence for circadian variation of theophylline pharmacokinetics. J Pediatr 1981; 99:476.
  57. D'Alonzo, GE, Smolensky, MH, Feldman, S, et al. Twenty-four hour lung function in adult patients with asthma: Chronoptimized theophylline therapy once-daily dosing in evening versus conventional twice-daily dosing. Am Rev Respir Dis 1990; 142:84.
  58. Martin, RJ, Cicutto, LC, Ballard, RD, et al. Circadian variations in theophylline concentrations and the treatment of nocturnal asthma. Am Rev Respir Dis 1989; 139:475.
  59. Welsh, PW, Reed, CE, Conrad, E. Timing of one-a-day theophylline dose to match peak blood level with diurnal variation in severity of asthma. Am J Med 1986; 80:1098.
  60. Kraft, M, Torvik, JA, Trudeau, JB, et al. Theophylline: Potential antiinflammatory effects in nocturnal asthma. J Allergy Clin Immunol 1996; 97:1242.
  61. Selby, C, Engleman, HM, Fitzpatrick, MF, et al. Inhaled salmeterol or oral theophylline in nocturnal asthma? Am J Respir Crit Care Med 1997; 155:104.
  62. Reinberg, AE, Halberg, F, Falliers, CJ. Circadian timing of methylprednisolone effects in asthmatic boys. Chronobiologia 1974; 1:333.
  63. Reinberg, AE, Gervais, P, Ghaussade, M, et al. Circadian changes in effectiveness of corticosteroids in eight patients with allergic asthma. J Allergy Clin Immunol 1983; 71:425.
  64. Reinberg, AE, Guillet, P, Gervais, P, et al. One month chronocorticotherapy. Control of the asthmatic condition without adrenal suppression and circadian rhythm alterations. Chronobiologia 1977; 4:295.
  65. Horn, CR, Clark, TJ, Cochrane, GM. Inhaled therapy reduces morning dips in asthma. Lancet 1984; 1:1143.
  66. Petty, TL, Rollins, DR, Christopher, K. Cromolyn sodium is effective in adult chronic asthma. Am Rev Respir Dis 1989; 139:694.
  67. Pincus, DJ, Szefler, SJ, Ackerson, LM, Martin, RJ. Chronotherapy of asthma with inhaled steroids: the effect of dosage timing on drug efficacy. J Allergy Clin Immunol 1995; 95:1172.
  68. Pincus, DJ, Humeston, TR, Martin, RJ. Further studies on the chronotherapy of asthma with inhaled steroids: the effect of dosage timing on drug efficacy. J Allergy Clin Immunol 1997; 100:771.
  69. Spector, SL, Smith, LJ, Glass, M, and Accolate Asthma Trialists Group. Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. Am J Respir Crit Care Med 1994; 150:618.
  70. Malmstrom, K, Rodriguez-Gomez, G, Guerra, J, et al. Oral montelukast, inhaled beclamethasone, and placebo for chronic asthma. A randomized, controlled trial. Ann Intern Med 1999; 130:487.
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