Skip to main content
SpringerLink
Log in

Nocturnal asthma: underlying mechanisms and treatment

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Nocturnal asthma is defined by a drop in forced expiratory volume in 1 second (FEV1) of at least 15% between bedtime and awakening in patients with clinical and physiologic evidence of asthma. Nocturnal symptoms are a common part of the asthma clinical syndrome; up to 75% of asthmatics are awakened by asthma symptoms at least once per week, and approximately 40% experience nocturnal symptoms on a nightly basis. An extensive body of research has demonstrated that nocturnal symptoms such as cough and dyspnea are accompanied by increases in airflow limitation, airway hyperresponsiveness, and airway inflammation. Treatment strategies in nocturnal asthma are similar to those used in persistent asthma, although dosing of medications to target optimum delivery during periods of nocturnal worsening is beneficial.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Turner-Warwick M: Epidemiology of nocturnal asthma. Am J Med 1988, 85:6–8.

    Article  PubMed  CAS  Google Scholar 

  2. Hetzel MR, Clark TJ, Branthwaite MA: Asthma: analysis of sudden deaths and ventilatory arrests in hospital. Br Med J 1977, 1:808–811.

    PubMed  CAS  Google Scholar 

  3. Martin RJ: Location of airway inflammation in asthma and the relationship to circadian change in lung function. Chronobiol Int 1999, 16:623–630.

    Article  PubMed  CAS  Google Scholar 

  4. Van Keimpema AR, Ariaansz M, Tamminga JJ, et al.: Nocturnal waking and morning dip of peak expiratory flow in clinically stable asthma patients during treatment: occurrence and patient characteristics. Respiration 1997, 64:29–34.

    PubMed  Google Scholar 

  5. Martin RJ, Cicutto LC, Ballard RD: Factors related to the nocturnal worsening of asthma. Am Rev Respir Dis 1990, 141:33–38.

    PubMed  CAS  Google Scholar 

  6. Kraft M, Djukanovic R, Wilson S, et al.: Alveolar tissue inflammation in asthma. Am J Respir Crit Care Med 1996, 154:1505–1510.

    PubMed  CAS  Google Scholar 

  7. Dethlefsen U, Repgas R: Ein neues Therapieprinzip bei Nachtlichen Asthma. Klin Med 1985, 80:44–47.

    Google Scholar 

  8. Cochrane GM, Clark JH: A survey of asthma mortality in patients between ages 35 and 64 in the Greater London hospitals in 1971. Thorax 1975, 30:300–305.

    PubMed  CAS  Google Scholar 

  9. Irvin CG, Pak J, Martin RJ: Airway-parenchyma uncoupling in nocturnal asthma. Am J Respir Crit Care Med 2000, 161:50–56.

    PubMed  CAS  Google Scholar 

  10. Kharitonov SA, Yates D, Robbins RA, et al.: Increased nitric oxide in exhaled air of asthmatic patients. Lancet 1994, 343:133–135.

    Article  PubMed  CAS  Google Scholar 

  11. ten Hacken NH, van der Vaart H, van der Mark TW, et al.: Exhaled nitric oxide is higher both at day and night in subjects with nocturnal asthma. Am J Respir Crit Care Med 1998, 158:902–907.

    PubMed  Google Scholar 

  12. Georges G, Bartelson BB, Martin RJ, Silkoff PE: Circadian variation in exhaled nitric oxide in nocturnal asthma. J Asthma 1999, 36:467–473.

    PubMed  CAS  Google Scholar 

  13. Silkoff PE, McClean PA, Slutsky AS, et al.: Exhaled nitric oxide and bronchial reactivity during and after inhaled beclomethasone in mild asthma. J Asthma 1998, 35:473–479.

    PubMed  CAS  Google Scholar 

  14. 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, 159:228–234. Biopsy study describing circadian changes in alveolar tissue inflammation in nocturnal asthma.

    PubMed  CAS  Google Scholar 

  15. Djukanovic R, Roche WR, Wilson JW, et al.: Mucosal inflammation in asthma. Am Rev Respir Dis 1990, 142:434–457.

    PubMed  CAS  Google Scholar 

  16. Szefler SJ, Ando R, Cicutto LC, et al.: Plasma histamine, epinephrine, cortisol, and leukocyte beta-adrenergic receptors in nocturnal asthma. Clin Pharmacol Ther 1991, 49:59–68.

    Article  PubMed  CAS  Google Scholar 

  17. Turki J, Pak J, Green SA, et al.: Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma: evidence that Gly16 correlates with the nocturnal phenotype. J Clin Invest 1995, 95:1635–1641.

    PubMed  CAS  Google Scholar 

  18. Kraft M, Vianna E, Martin RJ, Leung DYM: Nocturnal asthma is associated with reduced glucocorticoid receptor binding affinity and decreased steroid responsiveness at night. J Allergy Clin Immunol 1999, 103:66–71. A study describing the role of glucocorticoid receptor beta as a possible mechanism of steroid resistance in asthma.

    Article  PubMed  CAS  Google Scholar 

  19. Kraft M, Leung DYM, Martin RJ, Hamid QA: Reduced steroid responsiveness at night in asthma is due to increased glucocorticoid receptor beta expression in lung macrophages. Am J Respir Crit Care Med 1999, 159:A632.

    Google Scholar 

  20. Sutherland ER, Ellison MC, Kraft M, Martin RJ: Altered pituitaryadrenal interaction in nocturnal asthma. J Allergy Clin Immunol 2003, 112:52–57. Study describing altered adrenal response to corticotrophin in nocturnal asthma.

    Article  PubMed  CAS  Google Scholar 

  21. Sutherland ER, Martin RJ, Ellison MC, Kraft M: Immunomodulatory effects of melatonin in asthma. Am J Respir Crit Care Med 2002, 166:1055–1061.

    Article  PubMed  Google Scholar 

  22. Sutherland ER, Ellison MC, Kraft M, Martin RJ: Elevated serum melatonin is associated with the nocturnal worsening of asthma. J Allergy Clin Immunol 2003, 112:513–517.

    Article  PubMed  CAS  Google Scholar 

  23. Guidelines for the diagnosis and management of asthma: Report No. 97-4051. Bethesda, MD: National Heart, Lung and Blood Institute; 1997.

  24. Wempe JB, Tammeling EP, Postma DS, et al.: Effects of budesonide and bambuterol on circadian variation of airway responsiveness and nocturnal symptoms of asthma. J Allergy Clin Immunol 1992, 90:349–357.

    Article  PubMed  CAS  Google Scholar 

  25. Toogood JH, Baskerville JC, Jennings B, et al.: Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid, budesonide. J Allergy Clin Immunol 1982, 70:288–298.

    Article  PubMed  CAS  Google Scholar 

  26. Malo JL, Cartier A, Merland N, et al.: Four-times-a-day dosing frequency is better than a twice-a-day regimen in subjects requiring a high-dose inhaled steroid, budesonide, to control moderate to severe asthma. Am Rev Respir Dis 1989, 140:624–628.

    PubMed  CAS  Google Scholar 

  27. Horn CR, Clark TJ, Cochrane GM: Inhaled therapy reduces morning dips in asthma. Lancet 1984, 1:1143–1145.

    Article  PubMed  CAS  Google Scholar 

  28. 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, 95:1172–1178.

    Article  PubMed  CAS  Google Scholar 

  29. 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, 100:771–774.

    Article  PubMed  CAS  Google Scholar 

  30. Reinberg A, Gervais P, Chaussade M, et al.: Circadian changes in effectiveness of corticosteroids in eight patients with allergic asthma. J Allergy Clin Immunol 1983, 71:425–433.

    Article  PubMed  CAS  Google Scholar 

  31. Reinberg A, Halberg F, Falliers CJ: Circadian timing of methylprednisolone effects in asthmatic boys. Chronobiologia 1974, 1:333–347.

    PubMed  CAS  Google Scholar 

  32. Beam WR, Weiner DE, Martin RJ: Timing of prednisone and alterations of airways inflammation in nocturnal asthma. Am Rev Respir Dis 1992, 146:1524–1530.

    PubMed  CAS  Google Scholar 

  33. Fitzpatrick MF, Mackay T, Driver H, Douglas NJ: Salmeterol in nocturnal asthma: a double blind, placebo controlled trial of a long acting inhaled beta 2 agonist. BMJ 1990, 301:1365–1368.

    PubMed  CAS  Google Scholar 

  34. Lockey RF, DuBuske LM, Friedman B, et al.: Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes. Chest 1999, 115:666–673.

    Article  PubMed  CAS  Google Scholar 

  35. Barnes PJ, Greening AP, Neville L, et al.: Single-dose slowrelease aminophylline at night prevents nocturnal asthma. Lancet 1982, 1:299–301.

    Article  PubMed  CAS  Google Scholar 

  36. Goldenheim PD, Conrad EA, Schein LK: Treatment of asthma by a controlled-release theophylline tablet formulation: a review of the North American experience with nocturnal dosing. Chronobiol Int 1987, 4:397–408.

    PubMed  CAS  Google Scholar 

  37. Martin RJ, Cicutto LC, Ballard RD, et al.: Circadian variations in theophylline concentrations and the treatment of nocturnal asthma. Am Rev Respir Dis 1989, 139:475–478.

    PubMed  CAS  Google Scholar 

  38. Elias-Jones AC, Higenbottam TW, Barnes ND, Godden DJ: Sustained release theophylline in nocturnal asthma. Arch Dis Child 1984, 59:1159–1161.

    Article  PubMed  CAS  Google Scholar 

  39. Coe CI, Barnes PJ: Reduction of nocturnal asthma by an inhaled anticholinergic drug. Chest 1986, 90:485–488.

    PubMed  CAS  Google Scholar 

  40. Chan CS, Woolcock AJ, Sullivan CE: Nocturnal asthma: role of snoring and obstructive sleep apnea. Am Rev Respir Dis 1988, 137:1502–1504.

    PubMed  CAS  Google Scholar 

  41. Martin RJ, Pak J: Nasal CPAP in nonapneic nocturnal asthma. Chest 1991, 100:1024–1027.

    PubMed  CAS  Google Scholar 

  42. Martin RJ, Kraft M: Nocturnal asthma: therapeutic considerations. Clin Immunother 1996, 6:443–453.

    Google Scholar 

  43. Tan WC, Martin RJ, Pandey R, Ballard RD: Effects of spontaneous and simulated gastroesophageal reflux on sleeping asthmatics. Am Rev Respir Dis 1990, 141:1394–1399.

    PubMed  CAS  Google Scholar 

  44. Brugman SM, Larsen GL, Henson PM, et al.: Increased lower airways responsiveness associated with sinusitis in a rabbit model. Am Rev Respir Dis 1993, 147:314–320.

    PubMed  CAS  Google Scholar 

  45. Shturman-Ellstein R, Zeballos RJ, Buckley JM, Souhrada JF: The beneficial effect of nasal breathing on exercise-induced bronchoconstriction. Am Rev Respir Dis 1978, 118:65–73.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Jewish Medical and Research Center and University of Colorado Health Sciences Center, 1400 Jackson Street, Room J-217, 80206, Denver, CO, USA

    E. Rand Sutherland MD, MPH

Authors
  1. E. Rand Sutherland MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sutherland, E.R. Nocturnal asthma: underlying mechanisms and treatment. Curr Allergy Asthma Rep 5, 161–167 (2005). https://doi.org/10.1007/s11882-005-0091-z

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-005-0091-z

Keywords

Search

Navigation