Skip to main content
Log in

Nocturnal Asthma

Therapeutic Considerations

  • Disease Management
  • Published:
Clinical Immunotherapeutics Aims and scope Submit manuscript

Summary

Nocturnal asthma is an important part of asthma and must be considered in regard to therapy. The majority of patients with asthma have nocturnal worsening in lung function. The aetiology of this process is multifactorial and interactive. There are many naturally occurring circadian rhythms, which for the normal individual have only a minor effect on lung function. However, in the asthmatic patient, these day to night alterations in circadian rhythm produce increased airway inflammation and worsening of asthma.

Therapy should be approached from 2 viewpoints. First, there are indirect interventions which can improve nocturnal asthma. These include treatment of sleep apnoea, if it exists in an asthma patient, high-gastroesophageal reflux and rhinosinusitis, as well as inspiratory muscle training. The second treatment option focuses on direct pharmacological approaches using the new concept of chronotherapy. That is, instead of viewing a patient as being in homeostasis and administering medication in equally divided doses, treatment should be focused on delivering higher doses of medication at the time of day when the disease process is at its most severe.

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

Access this article

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

  1. Turner-Warwick M. Epidemiology of nocturnal asthma. Am J Med 1988; 86 Suppl. 1B: 6–8

    Article  Google Scholar 

  2. Robertson CE, Rubinfeld AR, Bowej G. Deaths from asthma in Victoria: a 12-month study. Med J Aust 1990; 152: 511–7

    PubMed  CAS  Google Scholar 

  3. Dethlefsen U, Repgas R. Ein neues therapieprinzip bei nachtlichen asthma. Klin Med 1985; 80: 44–7

    Google Scholar 

  4. Heztel MR, Clark TJH. Comparison of normal and asthmatic circadian rhythms in peak expiratory flow rate. Thorax 1980; 35: 732–8

    Article  Google Scholar 

  5. Martin RJ, Cicutto LC, Ballard RD. Factors related to the nocturnal worsening of asthma. Am Rev Respir Dis 1990; 141: 33–8

    PubMed  CAS  Google Scholar 

  6. Martin RJ, Cicutto LC, Ballard RD, et al. Airways inflammation in nocturnal asthma. Am Rev Respir Dis 1991; 143: 351–7

    PubMed  CAS  Google Scholar 

  7. Jarjour NN, Busse WW, Calhoun WJ. Enhanced production of oxygen radicals in nocturnal asthma. Am Rev Respir Dis 1992; 146: 905–11

    PubMed  CAS  Google Scholar 

  8. Barnes P, FitzGerald G, Brown M, et al. Nocturnal asthma and changes in circulatory epinephrine, histamine and cortisol. N Engl J Med 1980; 303: 263–7

    Article  PubMed  CAS  Google Scholar 

  9. Morrison JFJ, Pearson SB, Dean HG. Parasympathetic nervous system in nocturnal asthma. BMJ 1988; 296: 1427–9

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. Turki J, Pak J, Sa G, et al. Genetic polymorphisms of the β-2 adrenergic receptor in nocturnal and nonnocturnal asthma. J Clin Invest 1995; 95: 1635

    Article  PubMed  CAS  Google Scholar 

  12. Chan CS, Woolcock AJ, Sullivan CE. Nocturnal asthma: role of snoring and obstructive sleep apnea. Am Rev Respir Dis 1988; 137: 1502–4

    PubMed  CAS  Google Scholar 

  13. Martin RJ, Pak J. Nasal CPAP in non-apneic nocturnal asthma. Chest 1991; 100: 1024–7

    Article  PubMed  CAS  Google Scholar 

  14. Moore JG, Wolfe M. The relation of plasma gastrin to the circadian rhythm of gastric acid secretion in man. Digestion 1073; 9: 97–105

  15. Tan WC, Martin RJ, Pandey R, et al. Effects of spontaneous and simulated gastroesophageal reflux on sleeping asthmatics. Am Rev Respir Dis 1990; 141: 1394–9

    PubMed  CAS  Google Scholar 

  16. Weiner P, Azgad Y, Ganum R. Specific inspiratory muscle training in patients with bronchial asthma. Chest 1992; 102: 1357–61

    Article  PubMed  CAS  Google Scholar 

  17. Chen WY, Horton DJ, Weiser PC. Airway obstruction induced by body cooling in asthmatics. Physiology 1977; 20: 16

    Google Scholar 

  18. Chen WY, Horton DJ. Airways obstruction in asthmatics induced by body cooling. Scand J Respir Dis 1978; 59: 13–20

    PubMed  CAS  Google Scholar 

  19. Petersdorf RA. Disturbance of heat regulation. In: Wintrobe MM, Thorn GW, Adams RD, et al, editors. Harrison’s principles of internal medicine. 7th ed. New York: McGraw-Hill, 1974

    Google Scholar 

  20. Chen WY, Chai H. Airway cooling and nocturnal asthma. Chest 1982; 81: 675–80

    Article  PubMed  CAS  Google Scholar 

  21. Shturman-Ellstein R, Zeballos RJ, Buckley JM, et al. The beneficial effect of nasal breathing on exercise-induced broncho-constriction. Am Rev Respir Dis 1978; 118: 65–73

    PubMed  CAS  Google Scholar 

  22. 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: 314–20

    PubMed  CAS  Google Scholar 

  23. Postma DS, Koeter 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 Chronopharmacol 1984; 1: 101–4

    Google Scholar 

  24. Köeter GH, Postma DS, Keyzer JJ, et al. Effect of oral slow release terbutaline on early morning dyspnea. Eur J Clin Pharmacol 1995; 28: 159–62

    Article  Google Scholar 

  25. Moore-Gillon J. Volmax (salbuterol CR 8mg) in the management of nocturnal asthma: a placebo-controlled study [abstract]. Eur Respir J 1988; 1 Suppl. 2: 306S

    Google Scholar 

  26. Storms VVW, Nathan RA, Bodman SF, et al. The effect of repeat action albuterol sulfate (Proventil ‘Repetabs’) in nocturnal symptoms of asthma. J Asthma 1992; 29: 206–12

    Article  Google Scholar 

  27. Ullman A, Svedmyr N. Salmeterol, a new long-acting inhaled beta2-adrenoreceptor agonist: comparison with salbutamol in adult asthmatic patients. Thorax 1988; 43: 674–8

    Article  PubMed  CAS  Google Scholar 

  28. Fitzpatrick MF, Mackay T, Driver H, et al. Salmeterol in nocturnal asthma: a double blind, placebo controlled trial of a long acting inhaled β2 agonist. BMJ 1990; 301: 1365–8

    Article  PubMed  CAS  Google Scholar 

  29. 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: 1178–84

    PubMed  CAS  Google Scholar 

  30. 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: 716–22

    Article  PubMed  CAS  Google Scholar 

  31. 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: 476–9

    Article  PubMed  CAS  Google Scholar 

  32. D’Alonzo GE, Smolensky MH, Feldman S, et al. Twenty-four hour lung function in adult patients with asthma. Am Rev Respir Dis 1990; 142: 84–90

    PubMed  Google Scholar 

  33. Darrow P, Steinijans VW. Therapeutic advantage of unequal dosing of theophylline in patients with nocturnal asthma. Chronobiol Int 1987; 4: 349–57

    Article  Google Scholar 

  34. Bruguerolle B, Philip-Joet R, Parrel M, et al. Unequal twice-daily, sustained-release theophylline dosing in chronic obstructive pulmonary disease. Chronobiol Int 1987; 4: 381–6

    Article  PubMed  CAS  Google Scholar 

  35. Schultz H-U, Frercks H-J, Hypa F. Vergleichende theophyllinserum-speigel messungen uber 24 stunden nach knoventioneller dosierung eines theophyllin-retard-praparation uber 4 tage. Therapiewoche 1984; 34: 536–43

    Google Scholar 

  36. Rhind GB, Connaughton JJ, McFie J, et al. Sustained release choline theophyllinate in nocturnal asthma. BMJ 1985; 291: 1605–7

    Article  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: 475–8

    Article  PubMed  CAS  Google Scholar 

  38. 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: 1098–102

    Article  PubMed  CAS  Google Scholar 

  39. 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: 387–408

    Article  Google Scholar 

  40. Arkinstall WW. Review of the North American experience with evening administration of Uniphyl tablets, a once-daily theophylline preparation, in the treatment of nocturnal asthma. Am J Med 1988; 85 Suppl. 1B: 60–3

    Article  PubMed  CAS  Google Scholar 

  41. Rivington RD, Calcutt L, Child S, et al. Comparison of morning versus evening dosing with a new once-daily oral theophylline formulation. Am J Med 1985; 79 Suppl. 6A: 67–72

    Article  PubMed  CAS  Google Scholar 

  42. Busse WW, Busch RK. Comparison of morning and evening dosing with a 24-hour sustained-release theophylline, Uniphyl, for nocturnal asthma. Am J Med 1985; 79 Suppl. 6A: 62–9

    Article  PubMed  CAS  Google Scholar 

  43. Arkinstall WVV, Atkins ME, Harrison D, et al. Once-daily sustained-release theophylline reduces diurnal variation in spirometry and symptomology in adult asthmatics. Am Rev Respir Dis 1987: 135: 475–8

    Google Scholar 

  44. Reinberg A. Chronopharmacology: cellular and biochemical interactions. In: Lemmer B, editor. Chronopharmacology of corticosteroids and ACTH. New York: Marcel-Dekker, 1989: 137–67

    Google Scholar 

  45. Reinberg AE. Circadian timing of methylprednisolone effects in asthmatic boys. Chronobiologia 1974; 1: 333–47

    PubMed  CAS  Google Scholar 

  46. 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: 425–33

    Article  PubMed  CAS  Google Scholar 

  47. Reinberg A, Guillet P, Gervais P, et al. One month chronocorticotherapy: control of the asthmatic condition without adrenal suppression and circadian rhythm alterations. Chronobiologia 1977; 4: 295–312

    PubMed  CAS  Google Scholar 

  48. Beam WR, Weiner DE, Martin RJ. Timing of prednisone and alterations of airways inflammation in nocturnal asthma. Am Rev Respir Dis 1992; 146: 1524–30

    PubMed  CAS  Google Scholar 

  49. Malo JL, Cortier A, Merland N, et al. Four times a day dosing frequency is better than 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: 6214–8

    Google Scholar 

  50. Horn CB, Clark TJH, Cochrane GM. Inhaler therapy reduces morning dips in asthma. Lancet 1984; I: 1143–5

    Article  Google Scholar 

  51. Toogood JH, Baskerville JC, Jennings B, et al. Influence of dosing frequency and schedule on the response of chronic asthmatics to aerosol steroid, budesonide. J Allergy Clin Immunol 1982; 70: 288–98

    Article  PubMed  CAS  Google Scholar 

  52. Pincus DJ, Szefler SJ, Ackerson LM, et al. Chronotherapy of asthma with inhaled steroids: the effect of dosage timing on drug efficacy. J Allergy Clin Immunol 1995; 95: 1172–8

    Article  PubMed  CAS  Google Scholar 

  53. Berntstein IL, Siegel SC, Brandon ML, et al. A controlled study of cromolyn sodium sponsored by the Drug Committee of the American Academy of Allergy. J Allergy Clin Immunol 1972; 50: 235–345

    Article  Google Scholar 

  54. Hetzel MR, Clarke JH, Gilliam SJ, et al. Is sodium cromoglycate effective in nocturnal asthma? Thorax 1985; 40: 793–4

    Article  PubMed  CAS  Google Scholar 

  55. Morgan AD, Connaughton JJ, Caterall JR, et al. Sodium cromoglycate in nocturnal asthma. Thorax 1986; 41: 39–41

    Article  PubMed  CAS  Google Scholar 

  56. Ruffin R, Alpers JH, Kromer DK, et al. A 4-week Australian multicentre study of nedocromil sodium in asthmatic patients. Eur J Respir Dis 1986; 69 Suppl. 147: 336–9

    Google Scholar 

  57. Williams AJ, Stableforth D. The addition of nedocromil sodium to maintenance therapy in the management of patients with bronchial asthma. Eur J Respir Dis 1986; 69 Suppl. 147: 340–3

    Google Scholar 

  58. Coe CI, Barnes PJ. Reduction of nocturnal asthma by an inhaled anticholinergic drug. Chest 1986; 90: 486–8

    Article  Google Scholar 

  59. Fisher LE, Ludwig EA, Wald JA, et al. Pharmacokinetics and pharmacodynamics of methylprednisolone when administered at 8 AM versus 4 PM. Clin Pharmacol Ther 1992; 51: 677–88

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, R.J., Kraft, M. Nocturnal Asthma. Clin. Immunother. 6, 443–453 (1996). https://doi.org/10.1007/BF03259366

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03259366

Keywords

Navigation