Abstract
Purpose
Hypoxia/reoxygenation episodes in obstructive sleep apnea (OSA) results in the alteration of the oxidative balance, leading to the development of inflammation. Airway wall thickening and inflammatory changes are suggested as a primary cause of the airway hyperresponsiveness in asthmatics. Bronchial hyperreactivity (BH) may also occur in patients with OSA. We investigated the presence of BH and airway wall thickness in OSA and correlations with inflammatory markers.
Materials and methods
Sixteen OSA patients and ten controls without allergic diseases were prospectively studied. Plasma pro-B-type natriuretic peptide (pro-BNP), fibrinogen, D-dimer, α1-antitrypsin, and high-sensitive C-reactive protein levels were measured. Airway wall thickness was evaluated with high-resolution CT, and BH was assessed by giving each subject a methacholine challenge test.
Results
In OSA patients, bronchial wall thickness, fibrinogen, D-dimer, α1-antitrypsin, high sensitive C-reactive protein, and pro-BNP levels were significantly greater than those in control subjects. Among the 16 patients, three had BH on methacholine challenge. Bronchial wall thickness(mm) was positively correlated with apnea–hypopnea index (AHI: number of apneas + hypopneas/hour of sleep), BMI, respiratory arousal index, nocturnal oxygen desaturation (NOD) duration (time in minutes with a nocturnal arterial oxygen saturation of <90% during sleep), and α1-antitrypsin levels. NOD duration also correlated with pro-BNP and fibrinogen levels.
Conclusions
In OSA patients, walls of central airways were thicker than normal subjects. BH may have occurred in OSA patients. NOD duration correlated with inflammatory parameters and oxygen desaturation index 3% had an effect on the thickness of bronchial walls. But overall, AHI was found to be the only independent predictor of bronchial wall thickness.
Similar content being viewed by others
Abbreviations
- AHI:
-
Apnea–hypopnea index
- BMI:
-
Body mass index
- hsCRP:
-
Highly sensitive C-reactive protein
- pro-BNP:
-
pro-B-type natriuretic peptide
- NOD:
-
Nocturnal oxygen desaturation
- OSA:
-
Obstructive sleep apnea
- BH:
-
Bronchial hyperreactivity
- HRCT:
-
High-resolution computed tomography
References
Young T, Peppard E, Gottlieb DJ (2002) Epidemiology of obstructive sleep apnea. A population health perspective. Am J Respir Crit Care Med 165:1217–1239
Friedlander AH, Walker LA, Friedlander IK (2000) Diagnosing and comanaging patients with obstructive sleep apnea syndrome. JADA 131:1178–1184
Sabato R, Guido P, Salerno FG, Resta O, Spanevello A (2006) Airway inflammation in patients affected by obstructive sleep apnea. Monaldi Arch Chest Dis 65:102–105
Hatipoglu U, Rubinstein I (2003) Inflammation and obstructive sleep apnea syndrome pathogenesis: a working hypothesis. Respiration 70:665–671
Rubinstein I (1995) Nasal inflammation is present in patients with obstructive sleep apnea. Laryngoscope 105:175–177
Sekosan M, Zakkar M, Wenig BL, Olopade CO, Rubinstein I (1996) Inflammation in the uvula mucosa of patients with obstructive sleep apnea. Laryngoscope 106:1018–1020
Brown RH, Zerhouni EA, Mitzner W (1995) Airway edema potentiates airway reactivity. J Appl Physiol 79:1242–1248
Alkhalil M, Schulman E, Getsy J (2009) Obstructive sleep apnea syndrome and asthma: what are the links? J Clin Sleep Med 5:71–78
Rechtschaffen A, Kales A (1968) A manual of standardized terminology, techniques and scoring system for sleep stages in human subjects. Brain Information Service, VCLA, Los Angeles, CA
American Academy of Sleep Medicine (1999) Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 22:667–689
Iber C, Ancoli-Israel S, Chesson AL, Quan SF (2007) The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Respiratory rules for adults.VII.4.B Hypopnea rules. American Academy of Sleep Medicine, Westchester, IL, p 46
American Thoracic Society (2000) American Thoracic Society guidelines for methacholine and exercise challenge testing—1999. Am J Respir Crit Care Med 161:309–329
Niimi A, Matsumoto H, Takemura M, Ueda T, Chin K, Mishima M (2003) Relationship of airway wall thickness to airway sensitivity and airway reactivity in asthma. Am J Respir Crit Care Med 168:983–988
Harmancı E, Kebapcı M, Metintas M, Ozkan R (2002) High-resolution computed tomography findings are correlated with disease severity in asthma. Respiration 69:420–426
Aysola RS, Hoffman EA, Gierada D, Wenzel S, Cook-Granroth J (2008) Airway remodeling measured by multidetector CT is increased in severe asthma and correlates with pathology. Chest 134:1183–1191
Beigelman-Aubry C, Brillet PY, Grenier PA (2009) MDCT of the airways: technique and normal results. Radiol Clin N Am 47:185–201
Thalhofer S, Dorow P, Meissner P, Luding K (1997) Change in bronchial hyperreactivity with nCPAP respiration in patients with sleep related respiratory disorders. Pneumologie 51:767–769
Lin CC, Lin CY (1995) Obstructive sleep apnea syndrome and bronchial hyperreactivity. Lung 173:117–126
Malerba M, Radaeli A, Ceriani L, Tantucci C, Grassi V (2003) Airway hyperresponsiveness in a large group of subjects with α1-antitrypsin deficiency: a cross-sectional controlled study. J Int Med 253:351–358
Quan SF, Gersh BJ (2004) Cardiovascular consequences of sleep-disordered breathing: past, present and future. Circulation 109:951–957
Ryan S, Nolan MG, Hannigan E, Cunningham S, Taylor C, McNicholas WT (2007) Cardiovascular risk markers in obstructive sleep apnea syndrome and correlation with obesity. Thorax 62:509–514
Ridker PM (2007) C-reactive protein and the prediction of cardiovascular events among those at intermediate risk. Moving an inflammatory hypothesis towards consensus. J Am Coll Cardiol 49:2129–2138
Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro MP, Gramiccioni E, Barnes PJ (2003) 8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy. Chest 124:1386–1392
Olopade CO, Christon JA, Zakkar M, Hua C, Swedler WI, Scheff PA, Rubinstein I (1997) Exhaled penthane and nitric oxide levels in patients in patients with obstructive sleep apnea. Chest 111:1500–1504
Salerno FG, Carpagnano E, Guido P, Bonsignore MR, Roberti A, Aliani M, Vignola AM, Spanevello A (2004) Airway inflammation in patients affected by obstructive sleep apnea. Respir Med 98:25–28
Devouassoux G, Le´vy P, Rossini E, Pin I, Fior-Gozlan M, Henry M, Seigneurin D, Pe´pin JL (2007) Sleep apnea is associated with bronchial inflammation and continuous positive airway pressure–induced airway hyperresponsiveness. J Allergy Clin Immunol 119:597–603
Boudjeltia KZ, Meerhaeghe AV, Doumit S, Guillaume M, Cauche P, Brohee D (2006) Sleep apnoea–hypopnoea index is an independent predictor of high sensitivity C-reactive protein elevation. Respiration 73:243–246
Von Kanel R, Loredo JS, Powell FL, Adler KA, Dimsdale JE (2005) Short-term isocapnic hypoxia and coagulation in patients with sleep apnea. Clin Hemorheol Microcirc 33:369–377
Chin K, Ohi M, Kita H, Noguchi T, Otsuka N, Tsuboi T, Mishima M, Kuno K (1996) Effects of nCPAP therapy on fibrinogen levels in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 153:1972–1976
Von Känel R, Dimsdale JE (2003) Hemostatic alteration in patients with obstructive sleep apnea and the implications for cardiovascular disease. Chest 124:1956–1967
Sánchez A, Schwartz AR, Sánchez PL, Fernández JL, Ramos J, Herrero FM, Celador RF, Ruano R, Bregon I, Luengo CM, Gómez FP (2008) Hemodynamic and inflammatory markers of sleep apnea–hypopnea syndrome and nocturnal hypoxemia: effects of treatment with nasal continuous positive airway pressure. Arch Bronchoneumol 44:531–539
Mehra R, Redline S (2008) Sleep apnea: a proinflammatory disorder that coaggregates with obesity. J Allergy Clin Immunol 121:096–1102
Sutherland ER (2008) Obesity and asthma. Immunol Allergy Clin North Am 28(3):589–602
Guerra S, Sherrill DL, Bobadilla A, Martinez FD, Barbee RA (2002) The relation of body mass index to asthma, chronic bronchitis, and emphysema. Chest 122:1256–1263
Delgado J, Barranco P, Quirce S (2008) Obesity and asthma. J Investig Allergol Clin Immunol 18:420–425
Sulit LG, Storfer-Isser A, Rosen CL, Kirchner HL, Redline S (2005) Associations of obesity, sleep-disordered breathing, and wheezing in children. Am J Respir Crit Care Med 171:659–664
Litonjua AA, Sparrow D, Celedon JC, DeMolles D, Weiss ST (2002) Association of body mass index with the development of methacholine airway hyperresponsiveness in men: the Normative Aging Study. Thorax 57:581–585
Arnardottir ES, Mackiewicz M, Gislason T, Teff KL, Pack AI (2009) Molecular signatures of obstructive sleep apnea in adults: a review and perspective. Sleep 32:447–470
Coxson HO, Lam S (2009) Quantitative assessment of the airway wall using computed tomography and optical coherence tomography. Proc Am Thorac Soc 6:439–443
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sarıman, N., Levent, E., Çubuk, R. et al. Bronchial hyperreactivity and airway wall thickening in obstructive sleep apnea patients. Sleep Breath 15, 341–350 (2011). https://doi.org/10.1007/s11325-010-0387-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11325-010-0387-7