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]

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[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 increased 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]

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.[20][21]
  • However, CPAP has not shown to be effective in patients with nocturnal asthma alone.[22]

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.[23][5]

Treatment

Indirect Therapy

  • Overnight nasal continuous positive airway pressure (nCPAP) abolishes nocturnal oxygen desaturation and offers improvement in nocturnal asthma control.[24][25][26]
  • Gastroesophageal reflux contributes little to the nocturnal worsening of asthma[27][28][29] 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.[30]

Direct Pharmacological Therapy

References

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  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. 5.0 5.1 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
  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
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  20. "Breathing disorders during sleep are common among asthmatics, may help predict severe asthma" (Press release). University of Michigan Health System. May 25, 2005.
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  22. 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)
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