Nocturnal asthma
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]
Overview
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.[1] The pathophysiology of nocturnal asthma is closely associated with the chronobiology and the science of biologic processes that have time-related rhythms. Hence, understanding the circadian rhythm is important to interpret the changes in pulmonary function that occurs in sleeping asthmatics. A large population based study reported dyspneic episodes without therapy in asthmatics occurred between 10 P.M. and 7 A.M.[2] Another population based survey that assessed 7729 patients, reported approximate 74% patients woke-up at least once a week with symptoms, 64% woke-up three times per week and 39% patients woke-up every night with symptoms.[3]
Epidemiology and Demographics
- Nocturnal worsening of asthma is very common clinical finding in asthmatics affecting approximately 75% of asthmatics who awaken at least once per week because of symptoms, and approximately 40% experience nocturnal symptoms on a nightly basis.[1][4]
Pathophysiology
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 [5][6] and glucocorticoid receptors [7] 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,[8] a neurohormonal controller of circadian rhythms, to play an important role in the pathogenesis of nocturnal asthma.[4][9]
- The increased of CD51 at night, in patients with nocturnal asthma, may be related to increased airway inflammation and repair processes in response to injury.[10]
- 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.[11][12]
- 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.[13][14][15]
- Worsening of nocturnal asthma has been associated to the secondary increase in the levels of inflammatory mediators such as leukotrienes, interleukins, and histamine.[13][16][17][18][19][20]
- 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.[21][22]
Asthma and Obstructive Sleep Apnea
- It is recognized with increasing frequency, that patients who have both obstructive sleep apnea and bronchial asthma, often improve tremendously when the sleep apnea is diagnosed and treated.[23][24]
- However, CPAP has not shown to be effective in patients with nocturnal asthma alone.[25]
Treatment
Indirect Therapy
- Overnight nasal continuous positive airway pressure (nCPAP) abolishes nocturnal oxygen desaturation and offers improvement in nocturnal asthma control.[26][27][28]
- Gastroesophageal reflux contributes little to the nocturnal worsening of asthma [29][30][31] and hence, should be based upon symptoms of reflux and not based upon the worsening of asthma. However, if a patient complained of metallic taste in the mouth or unexplained infiltrates on chest x-ray, the possibility of reflux with aspiration should be considered.
- Specific inspiratory muscle training improves the inspiratory muscle strength and endurance. This can result in the improvement of asthmatic symptoms and medication consumption by asthmatics.[32]
Direct Pharmacological Therapy
- Inhaled long-acting bronchodilator such as salmeterol has shown to improve sleep quality and may be beneficial for patients who remain symptomatic despite anti-inflammatory therapy and environmental control.[33][34][35][36]
- Similar bronchodilation and good symptomatic control of nocturnal asthma may be achieved by both oral beta2 agonists such as extended release albuterol tablet and inhaled long-acting bronchodilator such as inhaled salmeterol.[37][38]
- Sustained-release theophylline preparations alter the inflammatory cell number and function secondary to the leukotriene B4-mediated mechanism. Research has demonstrated this can provide better bronchial airflow levels overnight and stabilize nocturnal pulmonary function.[39][40][41][42][43][44] Among the drugs, inhaled salmeterol and oral theophylline, only a small benefit in sleep quality, quality of life, and daytime cognitive function was observed with salmeterol; however, no major clinical advantage was noted.[45]
- In patients with nocturnal asthma, the timing and dose of steroid alters both the inflammatory milieu and spirometric decline that is associated with nocturnal worsening of asthma.[46] Long-term administration of corticosteroids at 8 A.M. and 3 P.M. was found to be more effective to control asthma and enhance peak expiratory flow rate values.[47][48][49]
- Inhalation method of administration of steroids, cromolyn and nedocromil has shown to be beneficial in reducing the morning dips and improving the mean peak expiratory flow rate value.[50][51][52][53]
- 5-lipoxygenase inhibitors such as zafirlukast and montelukast, have shown to significantly decrease the levels of LTB4 and improve FVE1 that is usually worsened in patients with nocturnal asthma.[17][54][55]
- Inhaled short-acting anticholinergic drugs, that affect vagal blockade have shown to provide little benefit on the overnight fall in pulmonary function seen in patients with nocturnal asthma.[21]
References
- ↑ 1.0 1.1 Sutherland ER (2005) Nocturnal asthma: underlying mechanisms and treatment. Curr Allergy Asthma Rep 5 (2):161-7. PMID: 15683618
- ↑ Martin RJ (1993) Nocturnal asthma: circadian rhythms and therapeutic interventions. Am Rev Respir Dis 147 (6 Pt 2):S25-8. PMID: 8494197
- ↑ Turner-Warwick M (1988) Epidemiology of nocturnal asthma. Am J Med 85 (1B):6-8. PMID: 3400687
- ↑ 4.0 4.1 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 13.0 13.1 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 17.0 17.1 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 21.0 21.1 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
- ↑ 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
- ↑ "Breathing disorders during sleep are common among asthmatics, may help predict severe asthma" (Press release). University of Michigan Health System. May 25, 2005.
- ↑ Teodorescu M, Consens FB, Bria WF, Coffey MJ, McMorris MS, Weatherwax KJ et al. (2009) Predictors of habitual snoring and obstructive sleep apnea risk in patients with asthma. Chest 135 (5):1125-32. DOI:10.1378/chest.08-1273 PMID: 18849401
- ↑ Basner, Robert C. "Asthma and OSA". ASAA Resources > Publications. American Sleep Apnea Association. Unknown parameter
|accessyear=ignored (|access-date=suggested) (help); Unknown parameter|accessmonthday=ignored (help) - ↑ Chan CS, Woolcock AJ, Sullivan CE (1988) Nocturnal asthma: role of snoring and obstructive sleep apnea. Am Rev Respir Dis 137 (6):1502-4. PMID: 3059864
- ↑ NADEL JA, WIDDICOMBE JG (1962) Reflex effects of upper airway irritation on total lung resistance and blood pressure. J Appl Physiol 17 ():861-5. PMID: 13937041
- ↑ Martin RJ, Pak J (1991) Nasal CPAP in nonapneic nocturnal asthma. Chest 100 (4):1024-7. PMID: 1914551
- ↑ Tan WC, Martin RJ, Pandey R, Ballard RD (1990) Effects of spontaneous and simulated gastroesophageal reflux on sleeping asthmatics. Am Rev Respir Dis 141 (6):1394-9. PMID: 2350084
- ↑ Ford GA, Oliver PS, Prior JS, Butland RJ, Wilkinson SP (1994) Omeprazole in the treatment of asthmatics with nocturnal symptoms and gastro-oesophageal reflux: a placebo-controlled cross-over study. Postgrad Med J 70 (823):350-4. PMID: 8016006
- ↑ Harding SM, Schan CA, Guzzo MR, Alexander RW, Bradley LA, Richter JE (1995) Gastroesophageal reflux-induced bronchoconstriction. Is microaspiration a factor? Chest 108 (5):1220-7. PMID: 7587420
- ↑ Weiner P, Azgad Y, Ganam R, Weiner M (1992) Inspiratory muscle training in patients with bronchial asthma. Chest 102 (5):1357-61. PMID: 1424851
- ↑ Fitzpatrick MF, Mackay T, Driver H, Douglas NJ (1990) Salmeterol in nocturnal asthma: a double blind, placebo controlled trial of a long acting inhaled beta 2 agonist. BMJ 301 (6765):1365-8. PMID: 1980220
- ↑ Dahl R, Earnshaw JS, Palmer JB (1991) Salmeterol: a four week study of a long-acting beta-adrenoceptor agonist for the treatment of reversible airways disease. Eur Respir J 4 (10):1178-84. PMID: 1687131
- ↑ Holimon TD, Chafin CC, Self TH (2001) Nocturnal asthma uncontrolled by inhaled corticosteroids: theophylline or long-acting beta2 agonists? Drugs 61 (3):391-418. PMID: 11293649
- ↑ Lockey RF, DuBuske LM, Friedman B, Petrocella V, Cox F, Rickard K (1999) Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes. Chest 115 (3):666-73. PMID: 10084473
- ↑ Crompton GK, Ayres JG, Basran G, Schiraldi G, Brusasco V, Eivindson A et al. (1999) Comparison of oral bambuterol and inhaled salmeterol in patients with symptomatic asthma and using inhaled corticosteroids. Am J Respir Crit Care Med 159 (3):824-8. PMID: 10051257
- ↑ Martin RJ, Kraft M, Beaucher WN, Kiechel F, Sublett JL, LaVallee N et al. (1999) Comparative study of extended release albuterol sulfate and long-acting inhaled salmeterol xinafoate in the treatment of nocturnal asthma. Ann Allergy Asthma Immunol 83 (2):121-6. DOI:10.1016/S1081-1206(10)62622-1 PMID: 10480584
- ↑ Kraft M, Torvik JA, Trudeau JB, Wenzel SE, Martin RJ (1996) Theophylline: potential antiinflammatory effects in nocturnal asthma. J Allergy Clin Immunol 97 (6):1242-6. PMID: 8648019
- ↑ D'Alonzo GE, Smolensky MH, Feldman S, Gianotti LA, Emerson MB, Staudinger H et al. (1990) Twenty-four hour lung function in adult patients with asthma. Chronoptimized theophylline therapy once-daily dosing in the evening versus conventional twice-daily dosing. Am Rev Respir Dis 142 (1):84-90. PMID: 2195936
- ↑ Martin RJ, Cicutto LC, Ballard RD, Goldenheim PD, Cherniack RM (1989) Circadian variations in theophylline concentrations and the treatment of nocturnal asthma. Am Rev Respir Dis 139 (2):475-8. PMID: 2913892
- ↑ Welsh PW, Reed CE, Conrad E (1986) Timing of once-a-day theophylline dose to match peak blood level with diurnal variation in severity of asthma. Am J Med 80 (6):1098-102. PMID: 3728507
- ↑ Smolensky MH, Scott PH, Kramer WG (1986) Clinical significance of day-night differences in serum theophylline concentration with special reference to Theo-Dur. J Allergy Clin Immunol 78 (4 Pt 2):716-22. PMID: 3771961
- ↑ Scott PH, Tabachnik E, MacLeod S, Correia J, Newth C, Levison H (1981) Sustained-release theophylline for childhood asthma: evidence for circadian variation of theophylline pharmacokinetics. J Pediatr 99 (3):476-9. PMID: 7264813
- ↑ Selby C, Engleman HM, Fitzpatrick MF, Sime PM, Mackay TW, Douglas NJ (1997) Inhaled salmeterol or oral theophylline in nocturnal asthma? Am J Respir Crit Care Med 155 (1):104-8. PMID: 9001297
- ↑ Beam WR, Weiner DE, Martin RJ (1992) Timing of prednisone and alterations of airways inflammation in nocturnal asthma. Am Rev Respir Dis 146 (6):1524-30. PMID: 1456570
- ↑ Reinberg A, Halberg F, Falliers CJ (1974) Circadian timing of methylprednisolone effects in asthmatic boys. Chronobiologia 1 (4):333-47. PMID: 4468878
- ↑ Reinberg A, Gervais P, Chaussade M, Fraboulet G, Duburque B (1983) Circadian changes in effectiveness of corticosteroids in eight patients with allergic asthma. J Allergy Clin Immunol 71 (4):425-33. PMID: 6339595
- ↑ Reinberg A, Guillet P, Gervais P, Ghata J, Vignaud D, Abulker C (1977) One month chronocorticotherapy (Dutimelan 8 15 mite). Control of the asthmatic condition without adrenal suppression and circadian rhythm alteration. Chronobiologia 4 (4):295-312. PMID: 614119
- ↑ Horn CR, Clark TJ, Cochrane GM (1984) Inhaled therapy reduces morning dips in asthma. Lancet 1 (8387):1143-5. PMID: 6144875
- ↑ Petty TL, Rollins DR, Christopher K, Good JT, Oakley R (1989) Cromolyn sodium is effective in adult chronic asthmatics. Am Rev Respir Dis 139 (3):694-701. PMID: 2493760
- ↑ Pincus DJ, Szefler SJ, Ackerson LM, Martin RJ (1995) Chronotherapy of asthma with inhaled steroids: the effect of dosage timing on drug efficacy. J Allergy Clin Immunol 95 (6):1172-8. PMID: 7797785
- ↑ Pincus DJ, Humeston TR, Martin RJ (1997) Further studies on the chronotherapy of asthma with inhaled steroids: the effect of dosage timing on drug efficacy. J Allergy Clin Immunol 100 (6 Pt 1):771-4. PMID: 9438485
- ↑ Spector SL, Smith LJ, Glass M (1994) Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. ACCOLATE Asthma Trialists Group. Am J Respir Crit Care Med 150 (3):618-23. PMID: 8087328
- ↑ Malmstrom K, Rodriguez-Gomez G, Guerra J, Villaran C, Piñeiro A, Wei LX et al. (1999) Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group. Ann Intern Med 130 (6):487-95. PMID: 10075616