Abstracts
Symptoms of sleep-disordered breathing, especially obstructive sleep apnea syndrome (OSAS), are common in asthma patients and have been associated with asthma severity. It is known that asthma symptoms tend to be more severe at night and that asthma-related deaths are most likely to occur during the night or early morning. Nocturnal symptoms occur in 60-74% of asthma patients and are markers of inadequate control of the disease. Various pathophysiological mechanisms are related to the worsening of asthma symptoms, OSAS being one of the most important factors. In patients with asthma, OSAS should be investigated whenever there is inadequate control of symptoms of nocturnal asthma despite the treatment recommended by guidelines having been administered. There is evidence in the literature that the use of continuous positive airway pressure contributes to asthma control in asthma patients with obstructive sleep apnea and uncontrolled asthma.
Apnea; Sleep apnea, obstructive; Asthma
Tem-se observado que sintomas dos distúrbios respiratórios do sono, especialmente a síndrome da apneia obstrutiva do sono (SAOS), são comuns em asmáticos; além disso, associam-se com a gravidade da asma. Sabe-se que durante a noite tende a haver maior gravidade dos sintomas da asma, assim como uma maior proporção de mortalidade durante a noite e as primeiras horas da manhã. Sintomas noturnos ocorrem entre 60-74% dos pacientes com asma e são marcadores de controle inadequado da doença. Vários mecanismos fisiopatológicos são relacionados a esse agravamento. A SAOS está incluída entre os fatores mais importantes. A investigação da SAOS em pacientes com asma deve ser realizada sempre que não houver um controle adequado dos sintomas noturnos da asma com o tratamento recomendado por diretrizes. Há evidências da literatura que sugerem que o uso de pressão positiva contínua nas vias aéreas pode contribuir para o controle da asma, quando o paciente asmático tem apneia obstrutiva do sono e sua asma não está controlada.
Apneia; Apneia do sono tipo obstrutiva; Asma
Asthma
Asthma is a chronic inflammatory disease with multiple phenotypes related to genetic
predisposition and various environmental interactions, and there is still a major gap in
the understanding of its complex causality and, consequently, in the primary prevention
of the disease.(
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) It is estimated that the annual cost of asthma in the USA is 11 billion
dollars, and hospitalizations account for half of these expenditures in that
country.(
22. Smith DH, Malone DC, Lawson KA, Okamoto LJ, Battista C, Saunders WB.
A national estimate of the economic costs of asthma. Am J Respir Crit Care Med.
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) Although patients with severe asthma account for less than 20% of all
asthma patients, they consume 80% of all funds allocated for the treatment of
asthma.(
22. Smith DH, Malone DC, Lawson KA, Okamoto LJ, Battista C, Saunders WB.
A national estimate of the economic costs of asthma. Am J Respir Crit Care Med.
1997;156(3 Pt 1):787-93. http://dx.doi.org/10.1164/ajrccm.156.3.9611072 PMid:9309994
http://dx.doi.org/10.1164/ajrccm.156.3.9...
) Asthma is the fourth leading cause of hospitalization via the Brazilian
Unified Health Care System.(
33. Ministério da Saúde. Secretaria Nacional de Ações Básicas de Saúde.
Estatísticas de Mortalidade. Brasília: Ministério da Saúde; 2000.
) A multicenter study showed that Brazil ranks eighth, the mean prevalence of
asthma in the country being 20%.(
44. Worldwide variations in the prevalence of asthma symptoms: the
International Study of Asthma and Allergies in Childhood (ISAAC). Eur Respir J.
1998;12(2):315-35. http://dx.doi.org/10.1183/09031936.98.12020315
http://dx.doi.org/10.1183/09031936.98.12...
) Approximately 45% of all adults with asthma have another chronic disease,
such as hypertension, diabetes, and depression.(
55. Franco R, Nascimento HF, Cruz AA, Santos AC, Souza-Machado C, Ponte
EV, et al. The economic impact of severe asthma to low-income families. Allergy.
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) In addition, approximately 2,500 people die each year because of
asthma.(
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Saúde. [cited 2013 Jan 11]. Farmácia Popular terá remédio de graça para asma.
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) In 2011, of the 177,800 patients who were hospitalized for asthma via the
Brazilian Unified Health Care System, 77,100 were children.(
66. Portal da Saúde [homepage on the Internet]. Brasília: Ministério da
Saúde. [cited 2013 Jan 11]. Farmácia Popular terá remédio de graça para asma.
Available from:
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)
Obstructive sleep apnea syndrome
Obstructive sleep apnea syndrome (OSAS) is characterized by episodes of complete or
partial upper airway obstruction during sleep.(
77. Yoursleep [homepage on the Internet]. Darien: American Academy of
Sleep Medicine. [cited 2013 Jan 11]. Understanding Sleep Apnea: Know All of the
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) It is known that OSAS induces hypoxemia, carbon dioxide retention, changes
in the normal autonomic structure, and hemodynamic responses during sleep.(
88. Wiggert GT, Faria DG, Castanho LA, Dias PA, Greco OT. Apnéia
obstrutiva do sono e arritmias cardíacas. Relampa. 2010;23(1):5-11.
) According to Young et al.,(
99. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The
occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med.
1993;328(17):1230-5. http://dx.doi.org/10.1056/NEJM199304293281704 PMid:8464434
http://dx.doi.org/10.1056/NEJM1993042932...
) OSAS affects 4% of males and 2% of females. In Brazil, it affects 32.9% of
adults, affecting 40.6% of males and 26.1% of females.(
1010. Tufik S, Santos-Silva R, Taddei JA, Bittencourt LR. Obstructive
sleep apnea syndrome in the Sao Paulo Epidemiologic Sleep Study. Sleep Med.
2010;11(5):441-6. http://dx.doi.org/10.1016/j.sleep.2009.10.005 PMid:20362502
http://dx.doi.org/10.1016/j.sleep.2009.1...
) According to Kapur et al.,(
1111. Kapur V, Blough DK, Sandblom RE, Hert R, de Maine JB, Sullivan SD,
et al. The medical cost of undiagnosed sleep apnea. Sleep. 1999;22(6):749-55.
PMid:10505820
) the average annual medical costs for patients with undiagnosed OSAS is US$
2,720, being approximately twice as high as those for patients diagnosed with and
undergoing treatment for sleep-disordered breathing. If not diagnosed and treated
appropriately, OSAS generates an additional annual expenditure of 3.4 billion dollars in
the USA.(
1111. Kapur V, Blough DK, Sandblom RE, Hert R, de Maine JB, Sullivan SD,
et al. The medical cost of undiagnosed sleep apnea. Sleep. 1999;22(6):749-55.
PMid:10505820
) The lack of diagnosis in cases of severe OSAS is alarming because of the
comorbidities and the risk of sudden death.(
1212. Weiss JW, Launois SH, Anand A, Garpestad E. Cardiovascular morbidity
in obstructive sleep apnea. Prog Cardiovasc Dis. 1999;41(5):367-76.
http://dx.doi.org/10.1053/pcad.1999.0410367 PMid:10406330
.
http://dx.doi.org/10...
)
Patients with OSAS tend to have circular upper airways, whereas normal individuals have
elliptical upper airways.(
1313. Schwab RJ, Gefter WB, Hoffman EA, Gupta KB, Pack AI. Dynamic upper
airway imaging during awake respiration in normal subjects and patients with sleep
disordered breathing. Am Rev Respir Dis. 1993;148(5):1385-400.
http://dx.doi.org/10.1164/ajrccm/148.5.1385 PMid:8239180
http://dx.doi.org/10.1164/ajrccm/148.5.1...
) In adult patients with upper airway obstruction, the most common types of
obstruction are velopharyngeal narrowing, in 78%; oropharyngeal narrowing, in 35%; and
hypopharyngeal narrowing, in 54%. Obstruction at a single level was observed in 48%,
whereas obstruction at multiple levels was observed in 52%.(
1414. Rabelo FA, Küpper DS, Sander HH, dos Santos Júnior V, Thuler E,
Fernandes RM, et al. A comparison of the Fujita classification of awake and
drug-induced sleep endoscopy patients. Braz J Otorhinolaryngol. 2013;79(1):100-5.
http://dx.doi.org/10.5935/1808-8694.20130017 PMid:23503915
http://dx.doi.org/10.5935/1808-8694.2013...
) A disproportionate oral cavity anatomy due to increased soft tissue (in
particular, increased tongue volume) or underdeveloped maxilla and mandible can be
evaluated by applying the modified Mallampati classification.(
1515. Bittencourt LA, Haddad FM, Fabbro CD, Cintra FD, Rios L. Abordagem
geral do paciente com síndrome da apneia obstrutiva do sono. Rev Bras Hipertens.
2009;16(3):158-63.
) The Mallampati classification was modified by Samsoon and Young (Figure 1).(
1616. Samsoon GL, Young JR. Difficult tracheal intubation: a retrospective
study. Anaesthesia. 1987;42(5):487-90.
http://dx.doi.org/10.1111/j.1365-2044.1987.tb04039.x
http://dx.doi.org/10.1111/j.1365-2044.19...
,
1717. Wikimedia Commons [homepage on the Internet]. San Francisco:
Wikimedia Foundation. [cited 2013 Jan 11]. File: Mallampati.svg. Available from:
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Available from:
htt...
) The pharyngeal structures are now classified into four types: class I: the
soft palate, palatine tonsils, uvula, and anterior and posterior pillars of the fauces
are visible; class II: all class I structures are visible, except the pillars of the
fauces; class III: only the base of the uvula is visible; and class IV: the uvula cannot
be seen, and only the hard palate is visible.(
1616. Samsoon GL, Young JR. Difficult tracheal intubation: a retrospective
study. Anaesthesia. 1987;42(5):487-90.
http://dx.doi.org/10.1111/j.1365-2044.1987.tb04039.x
http://dx.doi.org/10.1111/j.1365-2044.19...
)
Modified Mallampati score.(17) Author Jmarchn, January 11, 2013. Permission is granted to copy, distribute, and/or modify this document under the terms of the GNU Free Documentation License - Version 1.2 or any later version published by the Free Software Foundation.
OSAS-asthma
Introduction
The first study examining asthma and OSAS was a case report by Hudgel & Shrucard,
in 1979.(
1818. Hudgel DW, Shucard DW. Coexistence of sleep apnea and asthma
resulting in severe sleep hypoxemia. JAMA. 1979;242(25):2789-90.
http://dx.doi.org/10.1001/jama.1979.03300250045031
http://dx.doi.org/10.1001/jama.1979.0330...
) Ekici et al.(
1919. Ekici A, Ekici M, Kurtipek E, Keles H, Kara T, Tunckol M, et al.
Association of asthma-related symptoms with snoring and apnea and effect on
health-related quality of life. Chest. 2005;128(5):3358-63.
http://dx.doi.org/10.1378/chest.128.5.3358 PMid:16304284
http://dx.doi.org/10.1378/chest.128.5.33...
) conducted a study involving 7,469 adults; of those, 2,713 had a history
of asthma. The authors found that snoring (OR = 1.7) and self-reported apnea (OR =
2.7) were more prevalent in patients who had a history of asthma than in those who
did not. Larsson et al.(
2020. Larsson LG, Lindberg A, Franklin KA, Lundbäck B. Symptoms related to
obstructive sleep apnoea are common in subjects with asthma, chronic bronchitis and
rhinitis in a general population. Respir Med. 2001;95(5):423-9.
http://dx.doi.org/10.1053/rmed.2001.1054 PMid:11392586
http://dx.doi.org/10.1053/rmed.2001.1054...
) evaluated 46 patients with a history of chronic cough, expectoration, or
periodic wheezing. Of those 46 patients, 52% had a history of snoring and an
apnea-hypopnea index (AHI) ≥ 10 events/hour of sleep. In that study, OSAS was
associated with wheezing in 21% of the cases, and asthma was associated with OSAS in
17% of the cases.(
2020. Larsson LG, Lindberg A, Franklin KA, Lundbäck B. Symptoms related to
obstructive sleep apnoea are common in subjects with asthma, chronic bronchitis and
rhinitis in a general population. Respir Med. 2001;95(5):423-9.
http://dx.doi.org/10.1053/rmed.2001.1054 PMid:11392586
http://dx.doi.org/10.1053/rmed.2001.1054...
) Byun et al.(
2121. Byun MK, Park SC, Chang YS, Kim YS, Kim SK, Kim HJ, et al.
Associations of moderate to severe asthma with obstructive sleep apnea. Yonsei Med J.
201;54(4):942-8.
) selected 176 adults with the following complaints: habitual snoring;
excessive daytime sleepiness (EDS); choking during sleep; sleep fragmentation;
nonrestorative sleep; daytime fatigue; and difficulty concentrating. Those patients
were referred for clinical evaluation and polysomnography. Of the 176 patients, 111
(66%) had 10 > AHI > 5 events/h, and 72 (43%) had an AHI > 15 events/h. Of
the patients who had an AHI > 5 events/h, 37 (33.6%) had been diagnosed with
moderate to severe asthma.(
2121. Byun MK, Park SC, Chang YS, Kim YS, Kim SK, Kim HJ, et al.
Associations of moderate to severe asthma with obstructive sleep apnea. Yonsei Med J.
201;54(4):942-8.
)
Both OSAS and asthma can result in fragmented sleep and EDS.(
2222. Calhoun SL, Vgontzas AN, Fernandez-Mendoza J, Mayes SD, Tsaoussoglou
M, Basta M, et al. Prevalence and risk factors of excessive daytime sleepiness in a
community sample of young children: the role of obesity, asthma, anxiety/depression,
and sleep. Sleep. 2011;34(4):503-7. PMid:21461329 PMCid:3065261
) Calhoun et al.(
2222. Calhoun SL, Vgontzas AN, Fernandez-Mendoza J, Mayes SD, Tsaoussoglou
M, Basta M, et al. Prevalence and risk factors of excessive daytime sleepiness in a
community sample of young children: the role of obesity, asthma, anxiety/depression,
and sleep. Sleep. 2011;34(4):503-7. PMid:21461329 PMCid:3065261
) studied 700 children and found that 13.3% of those who had EDS also had
a diagnosis of asthma. The independent predictors of EDS were waist circumference (OR
= 1.4), self-reported anxiety/depressive symptoms (OR = 2.9), difficulty falling
asleep (OR = 1.7), and a history of asthma (OR = 2.4). In another study, impaired
sleep quality was found to be far more common in children with asthma than in
controls (33 vs. 0; p < 0.01).(
2323. Stores G, Ellis AJ, Wiggs L, Crawford C, Thomson A. Sleep and
psychological disturbance in nocturnal asthma. Arch Dis Child. 1998;78(5):413-9.
http://dx.doi.org/10.1136/adc.78.5.413 PMid:9659086 PMCid:1717552
http://dx.doi.org/10.1136/adc.78.5.413...
) In addition, EDS was more common in the children with asthma than in
those in the control group (19 vs. 14; p < 0.05).(
2323. Stores G, Ellis AJ, Wiggs L, Crawford C, Thomson A. Sleep and
psychological disturbance in nocturnal asthma. Arch Dis Child. 1998;78(5):413-9.
http://dx.doi.org/10.1136/adc.78.5.413 PMid:9659086 PMCid:1717552
http://dx.doi.org/10.1136/adc.78.5.413...
) This EDS can be explained by recurrent episodes of coughing and dyspnea
during sleep, which are characteristic of asthma.(
2323. Stores G, Ellis AJ, Wiggs L, Crawford C, Thomson A. Sleep and
psychological disturbance in nocturnal asthma. Arch Dis Child. 1998;78(5):413-9.
http://dx.doi.org/10.1136/adc.78.5.413 PMid:9659086 PMCid:1717552
http://dx.doi.org/10.1136/adc.78.5.413...
) It should be taken into consideration that both asthma and OSAS involve
frequent awakenings associated with airflow limitation and increased respiratory
effort, with consequent desaturation during sleep.(
1919. Ekici A, Ekici M, Kurtipek E, Keles H, Kara T, Tunckol M, et al.
Association of asthma-related symptoms with snoring and apnea and effect on
health-related quality of life. Chest. 2005;128(5):3358-63.
http://dx.doi.org/10.1378/chest.128.5.3358 PMid:16304284
http://dx.doi.org/10.1378/chest.128.5.33...
)
Sleep-disordered breathing vs. asthma control
In patients with asthma, OSAS acts as a mechanism that contributes to the lack of
asthma control,(
2424. Gutierrez MJ, Zhu J, Rodriguez-Martinez CE, Nino CL, Nino G.
Nocturnal phenotypical features of obstructive sleep apnea (OSA) in asthmatic
children. Pediatr Pulmonol. 2013;48(6):592-600. http://dx.doi.org/10.1002/ppul.22713
PMid:23203921
http://dx.doi.org/10.1002/ppul.22713...
) because the reduction in airway caliber in nocturnal asthma is often
associated with sleep fragmentation, early morning awakening, difficulty maintaining
sleep, and EDS.(
2525. Shigemitsu H, Afshar K. Nocturnal asthma. Curr Opin Pulm Med.
2007;13(1):49-55. Erratum in: Curr Opin Pulm Med. 2007;13(2):156-7.
http://dx.doi.org/10.1097/MCP.0b013e328010a890 PMid:17133125
http://dx.doi.org/10.1097/MCP.0b013e3280...
) Increased abdominal pressure during periods of OSAS contributes to
gastroesophageal reflux (GER), bronchial hyperreactivity, and bronchial
inflammation.(
2626. Lewis DA. Sleep in patients with asthma and chronic obstructive
pulmonary disease. Curr Opin Pulm Med. 2001;7(2):105-12.
http://dx.doi.org/10.1097/00063198-200103000-00008 PMid:11224731
http://dx.doi.org/10.1097/00063198-20010...
) Patients with difficult-to-control asthma can have an increase in the
number of episodes of OSAS and oxyhemoglobin desaturation, especially during rapid
eye movement sleep.(
2424. Gutierrez MJ, Zhu J, Rodriguez-Martinez CE, Nino CL, Nino G.
Nocturnal phenotypical features of obstructive sleep apnea (OSA) in asthmatic
children. Pediatr Pulmonol. 2013;48(6):592-600. http://dx.doi.org/10.1002/ppul.22713
PMid:23203921
http://dx.doi.org/10.1002/ppul.22713...
) Because of the aforementioned reasons, the US National Asthma Education
and Prevention Program recommends that patients with difficult-to-control asthma be
screened for OSAS.(
2727. National Heart, Lung, and Blood Institute [homepage on the
Internet]. Bethesda: National Institutes of Health. [cited 2013 Mar 15]. Expert Panel
Report 3 Guidelines for the Diagnosis and Management of Asthma. [Adobe Acrobat
document, 440p.]. Available from:
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf
Available
from: htt...
)
Teodorescu et al.(
2828. Teodorescu M, Polomis DA, Hall SV, Teodorescu MC, Gangnon RE,
Peterson AG, et al. Association of obstructive sleep apnea risk with asthma control
in adults. Chest. 2010;138(3):543-50. http://dx.doi.org/10.1378/chest.09-3066
PMid:20495105 PMCid:2940069
http://dx.doi.org/10.1378/chest.09-3066...
) found that individuals with OSAS were 3.6 times as likely to have
uncontrolled asthma. Janson et al.(
2929. Janson C, De Backer W, Gislason T, Plaschke P, Björnsson E, Hetta J,
et al. Increased prevalence of sleep disturbances and daytime sleepiness in subjects
with bronchial asthma: a population study of young adults in three European
countries. Eur Respir J. 1996;9(10):2132-8.
http://dx.doi.org/10.1183/09031936.96.09102132 PMid:8902479
http://dx.doi.org/10.1183/09031936.96.09...
) found an association of bronchial hyperreactivity with daytime fatigue,
EDS, early awakening, higher percentage of time awake during the night, and decreased
sleep efficiency. The use of theophylline was associated with an increased prevalence
of difficulty initiating sleep and decreased sleep efficiency.(
2929. Janson C, De Backer W, Gislason T, Plaschke P, Björnsson E, Hetta J,
et al. Increased prevalence of sleep disturbances and daytime sleepiness in subjects
with bronchial asthma: a population study of young adults in three European
countries. Eur Respir J. 1996;9(10):2132-8.
http://dx.doi.org/10.1183/09031936.96.09102132 PMid:8902479
http://dx.doi.org/10.1183/09031936.96.09...
) A negative correlation was found between FEV1 and daytime
fatigue, and a positive correlation was found between PEF and duration of insomnia
and between PEF and sleep efficiency.(
2929. Janson C, De Backer W, Gislason T, Plaschke P, Björnsson E, Hetta J,
et al. Increased prevalence of sleep disturbances and daytime sleepiness in subjects
with bronchial asthma: a population study of young adults in three European
countries. Eur Respir J. 1996;9(10):2132-8.
http://dx.doi.org/10.1183/09031936.96.09102132 PMid:8902479
http://dx.doi.org/10.1183/09031936.96.09...
)
Julien et al.(
3030. Julien JY, Martin JG, Ernst P, Olivenstein R, Hamid Q, Lemière C, et
al. Prevalence of obstructive sleep apnea-hypopnea in severe versus moderate asthma.
J Allergy Clin Immunol. 2009;124(2):371-6.
http://dx.doi.org/10.1016/j.jaci.2009.05.016 PMid:19560194
http://dx.doi.org/10.1016/j.jaci.2009.05...
) found that greater asthma severity translated to a higher AHI; that is,
patients with severe asthma had an AHI of 23.6 events/h, those with moderate asthma
had an AHI of 19.5 events/h, and those with mild asthma had an AHI of 9.9 events/h (p
< 0.001). When the authors investigated OSAS in those with an AHI ≥ 15 events/h,
they found that 23 (88%) of the 26 patients with severe asthma had been diagnosed
with OSAS, as had 15 (58%) of the 26 patients with moderate asthma and 8 (31%) of the
26 controls without asthma. Mean nocturnal SaO2 was significantly lower in
the patients with severe asthma than in the controls.(
3030. Julien JY, Martin JG, Ernst P, Olivenstein R, Hamid Q, Lemière C, et
al. Prevalence of obstructive sleep apnea-hypopnea in severe versus moderate asthma.
J Allergy Clin Immunol. 2009;124(2):371-6.
http://dx.doi.org/10.1016/j.jaci.2009.05.016 PMid:19560194
http://dx.doi.org/10.1016/j.jaci.2009.05...
) The high prevalence of OSAS in patients with severe asthma suggests that
recognition and treatment of OSAS play an important role in improving asthma
control.(
3030. Julien JY, Martin JG, Ernst P, Olivenstein R, Hamid Q, Lemière C, et
al. Prevalence of obstructive sleep apnea-hypopnea in severe versus moderate asthma.
J Allergy Clin Immunol. 2009;124(2):371-6.
http://dx.doi.org/10.1016/j.jaci.2009.05.016 PMid:19560194
http://dx.doi.org/10.1016/j.jaci.2009.05...
) Approximately 63% of children with severe asthma have OSAS.(
3131. Kheirandish-Gozal L, Dayyat EA, Eid NS, Morton RL, Gozal D.
Obstructive sleep apnea in poorly controlled asthmatic children: effect of
adenotonsillectomy. Pediatr Pulmonol. 2011;46(9):913-8.
http://dx.doi.org/10.1002/ppul.21451 PMid:21465680 PMCid:3156307
http://dx.doi.org/10.1002/ppul.21451...
)
Teodorescu et al.(
3232. Teodorescu M, Consens FB, Bria WF, Coffey MJ, McMorris MS,
Weatherwax KJ, et al. Predictors of habitual snoring and obstructive sleep apnea risk
in patients with asthma. Chest. 2009;135(5):1125-32.
http://dx.doi.org/10.1378/chest.08-1273 PMid:18849401
http://dx.doi.org/10.1378/chest.08-1273...
) found that asthma patients who were using low-dose inhaled
corticosteroids regularly, those who were using medium-dose inhaled corticosteroids
regularly, and those who were using high-dose inhaled corticosteroids regularly were,
respectively, 2.29 times, 3.67 times, and 5.43 times as likely to develop OSAS as
were those who were not using inhaled corticosteroids. In addition, an inverse
association was found between OSAS and FEV1.(
3232. Teodorescu M, Consens FB, Bria WF, Coffey MJ, McMorris MS,
Weatherwax KJ, et al. Predictors of habitual snoring and obstructive sleep apnea risk
in patients with asthma. Chest. 2009;135(5):1125-32.
http://dx.doi.org/10.1378/chest.08-1273 PMid:18849401
http://dx.doi.org/10.1378/chest.08-1273...
) Teodorescu et al.(
3232. Teodorescu M, Consens FB, Bria WF, Coffey MJ, McMorris MS,
Weatherwax KJ, et al. Predictors of habitual snoring and obstructive sleep apnea risk
in patients with asthma. Chest. 2009;135(5):1125-32.
http://dx.doi.org/10.1378/chest.08-1273 PMid:18849401
http://dx.doi.org/10.1378/chest.08-1273...
) reported that the association between OSAS and the doses of inhaled
corticosteroids can be associated with the known adverse effects of corticosteroids.
The authors reported that inhaled corticosteroids can compromise the upper airway
dilator muscles in asthma patients and therefore act as facilitators of
OSAS.(
3232. Teodorescu M, Consens FB, Bria WF, Coffey MJ, McMorris MS,
Weatherwax KJ, et al. Predictors of habitual snoring and obstructive sleep apnea risk
in patients with asthma. Chest. 2009;135(5):1125-32.
http://dx.doi.org/10.1378/chest.08-1273 PMid:18849401
http://dx.doi.org/10.1378/chest.08-1273...
33. Williams AJ, Baghat MS, Stableforth DE, Cayton RM, Shenoi PM,
Skinner C. Dysphonia caused by inhaled steroids: recognition of a characteristic
laryngeal abnormality. Thorax. 1983;38(11):813-21.
http://dx.doi.org/10.1136/thx.38.11.813 PMid:6648863 PMCid:459669
http://dx.doi.org/10.1136/thx.38.11.813...
-
3434. DelGaudio JM. Steroid inhaler laryngitis: dysphonia caused by
inhaled fluticasone therapy. Arch Otolaryngol Head Neck Surg. 2002;128(6):677-81.
http://dx.doi.org/10.1001/archotol.128.6.677 PMid:12049563
http://dx.doi.org/10.1001/archotol.128.6...
)
It has been reported that 60-74% of patients with asthma have nocturnal symptoms,
which function as markers of inadequate control of the disease.(
2525. Shigemitsu H, Afshar K. Nocturnal asthma. Curr Opin Pulm Med.
2007;13(1):49-55. Erratum in: Curr Opin Pulm Med. 2007;13(2):156-7.
http://dx.doi.org/10.1097/MCP.0b013e328010a890 PMid:17133125
http://dx.doi.org/10.1097/MCP.0b013e3280...
) In 1988, Guilleminault et al.(
3535. Guilleminault C, Quera-Salva MA, Powell N, Riley R, Romaker A,
Partinen M, et al. Nocturnal asthma: snoring, small pharynx and nasal CPAP. Eur
Respir J. 1988;1(10):902-7. PMid:3066641
) studied patients with nocturnal asthma and OSAS and noted that episodes
of nocturnal asthma exacerbation were inhibited by the recommended treatment for
OSAS, i.e., continuous positive airway pressure (CPAP). The authors suggested that
patients with OSAS have an increased vagal tone during sleep, which can increase the
chance of having nocturnal bronchoconstriction, which in turn can be inhibited by
CPAP. Subsequently, Ciftci et al.(
3636. Ciftci TU, Ciftci B, Guven SF, Kokturk O, Turktas H. Effect of nasal
continuous positive airway pressure in uncontrolled nocturnal asthmatic patients with
obstructive sleep apnea syndrome. Respir Med. 2005;99(5):529-34.
http://dx.doi.org/10.1016/j.rmed.2004.10.011 PMid:15823448
http://dx.doi.org/10.1016/j.rmed.2004.10...
) conducted polysomnographic studies in asthma patients who had nocturnal
symptoms despite using the medications recommended by the Global Initiative for
Asthma. In addition to nocturnal symptoms, those patients had a history of snoring
for at least 6 months. Polysomnography showed that 21 (48.83%) of the 43 patients had
OSAS, i.e., an AHI ≥ 5 events/h, and 19 of the 21 patients with OSAS had an AHI ≥ 15
events/h; therefore, they were referred for CPAP treatment, the recommended treatment
having improved the symptoms of nocturnal asthma.(
3636. Ciftci TU, Ciftci B, Guven SF, Kokturk O, Turktas H. Effect of nasal
continuous positive airway pressure in uncontrolled nocturnal asthmatic patients with
obstructive sleep apnea syndrome. Respir Med. 2005;99(5):529-34.
http://dx.doi.org/10.1016/j.rmed.2004.10.011 PMid:15823448
http://dx.doi.org/10.1016/j.rmed.2004.10...
)
Hypotheses for the interaction between OSAS and asthma
OSAS-obesity-asthma
Obesity is considered one of the causal factors for OSAS. Peppard et al.(
3737. Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal
study of moderate weight change and sleep-disordered breathing. JAMA.
2000;284(23):3015-21. http://dx.doi.org/10.1001/jama.284.23.3015 PMid:11122588
http://dx.doi.org/10.1001/jama.284.23.30...
) evaluated adults at two different time points (at baseline and 4 years
later). Initial data showed that individuals with body mass index (BMI) ≥ 30
kg/m2 (n = 268) had an AHI of 7.4 events/h; those with 30 < BMI ≥ 25
kg/m2 (n = 241) had an AHI of 2.6 events/h; and those with BMI < 25
kg/m2 (n = 181) had an AHI of 1.2 events/h. After 4 years, 39 of the
patients who did not have moderate to severe OSAS (AHI ≥ 15 events/h) had a 3.9 kg
increase in weight. Of the 46 participants who had moderate to severe OSAS, 17 gained
an average of 3.1 kg, although there was no significant change in the AHI; among
those whose AHI was normal, there was an average increase in weight of 2.2 kg. The
authors found that the increase in weight was positively correlated with the AHI;
that is, patients who gain 10% of their body weight tend to show an increase of
approximately 32% in the AHI, and a 10% reduction in weight resulted in a 26%
reduction in the AHI. A 10% increase in body weight increased the chance of
developing moderate to severe OSAS by 6 times.(
3737. Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal
study of moderate weight change and sleep-disordered breathing. JAMA.
2000;284(23):3015-21. http://dx.doi.org/10.1001/jama.284.23.3015 PMid:11122588
http://dx.doi.org/10.1001/jama.284.23.30...
)
The high prevalence of OSAS in patients with asthma appears to be associated with
obesity. Cottrell et al.(
3838. Cottrell L, Neal WA, Ice C, Perez MK, Piedimonte G. Metabolic
abnormalities in children with asthma. Am J Respir Crit Care Med. 2011;183(4):441-8.
http://dx.doi.org/10.1164/rccm.201004-0603OC PMid:20851922 PMCid:3056222
http://dx.doi.org/10.1164/rccm.201004-06...
) conducted a cross-sectional study involving 17,994 children (in the 4-12
year age bracket), 14% of whom had a diagnosis of asthma. The prevalence of asthma
was directly proportional to the BMI percentile. The prevalence of asthma is higher
in obese children and even higher in morbidly obese children. It has been suggested
that, beyond a certain threshold of obesity, metabolic factors become involved in the
pathophysiology of upper airway inflammation, as well as in bronchial
hyperreactivity, being able to interfere with the clinical manifestations of
asthma.(
3838. Cottrell L, Neal WA, Ice C, Perez MK, Piedimonte G. Metabolic
abnormalities in children with asthma. Am J Respir Crit Care Med. 2011;183(4):441-8.
http://dx.doi.org/10.1164/rccm.201004-0603OC PMid:20851922 PMCid:3056222
http://dx.doi.org/10.1164/rccm.201004-06...
) It seems that the association between asthma and OSAS worsens the
clinical picture of asthma, given that OSAS can stimulate weight gain, playing a
significant role in the severity of asthma.(
3939. Alkhalil M, Schulman E, Getsy J. Obstructive sleep apnea syndrome
and asthma: what are the links?. J Clin Sleep Med. 2009;5(1):71-8. PMid:19317386
PMCid:2637171
) It is known that OSAS interferes with lipid homeostasis and systemic
inflammation and, when associated with obesity, affects glycemic regulation,
interfering with insulin sensitivity, independently of the BMI.(
4040. Gozal D, Capdevila OS, Kheirandish-Gozal L. Metabolic alterations
and systemic inflammation in obstructive sleep apnea among nonobese and obese
prepubertal children. Am J Respir Crit Care Med. 2008;177(10):1142-9.
http://dx.doi.org/10.1164/rccm.200711-1670OC PMid:18276939 PMCid:2383995
http://dx.doi.org/10.1164/rccm.200711-16...
) Komakula et al.(
4141. Komakula S, Khatri S, Mermis J, Savill S, Haque S, Rojas M, et al.
Body mass index is associated with reduced exhaled nitric oxide and higher exhaled
8-isoprostanes in asthmatics. Respir Res. 2007;8:32.
http://dx.doi.org/10.1186/1465-9921-8-32 PMid:17437645 PMCid:1855924
http://dx.doi.org/10.1186/1465-9921-8-32...
) found an association of BMI, leptin levels, and adiponectin levels with
decreased levels of exhaled nitric oxide in patients with asthma.
OSAS-systemic inflammation-asthma
It is known that OSAS has a negative effect on proatherogenic lipid levels and
promotes inflammatory responses, which are evidenced by a reversible increase in
C-reactive protein (CRP).(
4040. Gozal D, Capdevila OS, Kheirandish-Gozal L. Metabolic alterations
and systemic inflammation in obstructive sleep apnea among nonobese and obese
prepubertal children. Am J Respir Crit Care Med. 2008;177(10):1142-9.
http://dx.doi.org/10.1164/rccm.200711-1670OC PMid:18276939 PMCid:2383995
http://dx.doi.org/10.1164/rccm.200711-16...
) Gozal et al.(
4040. Gozal D, Capdevila OS, Kheirandish-Gozal L. Metabolic alterations
and systemic inflammation in obstructive sleep apnea among nonobese and obese
prepubertal children. Am J Respir Crit Care Med. 2008;177(10):1142-9.
http://dx.doi.org/10.1164/rccm.200711-1670OC PMid:18276939 PMCid:2383995
http://dx.doi.org/10.1164/rccm.200711-16...
) noted that triglyceride levels decreased after adenotonsillectomy,
although only in the group of obese children. In both groups, serum levels of apoB
decreased remarkably after adenotonsillectomy, and the effect was slightly higher in
the group of nonobese children. Similarly, serum levels of CRP, which were higher in
the pre-adenotonsillectomy period, decreased proportionally to the AHI, the reduction
being more significant in the group of nonobese children. By means of hypoxemia,
hypercapnia, and sleep fragmentation, OSAS can cause or aggravate proinflammatory
states through effects on sympathetic hyperreactivity, oxidative stress, or
both.(
4242. Mehra R, Redline S. Sleep apnea: a proinflammatory disorder that
coaggregates with obesity. J Allergy Clin Immunol. 2008;121(5):1096-102.
http://dx.doi.org/10.1016/j.jaci.2008.04.002 PMid:18466782 PMCid:2720266
http://dx.doi.org/10.1016/j.jaci.2008.04...
)
TNF-α is considered a marker of sleep-disordered breathing.(
4242. Mehra R, Redline S. Sleep apnea: a proinflammatory disorder that
coaggregates with obesity. J Allergy Clin Immunol. 2008;121(5):1096-102.
http://dx.doi.org/10.1016/j.jaci.2008.04.002 PMid:18466782 PMCid:2720266
http://dx.doi.org/10.1016/j.jaci.2008.04...
) Vgontzas et al.(
4343. Vgontzas AN, Zoumakis E, Lin HM, Bixler EO, Trakada G, Chrousos GP.
Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor
necrosis factor-alpha antagonist. J Clin Endocrinol Metab. 2004;89(9):4409-13.
http://dx.doi.org/10.1210/jc.2003-031929 PMid:15356039
http://dx.doi.org/10.1210/jc.2003-031929...
) demonstrated that TNF-α inhibition can decrease the severity of OSAS.
Gozal et al.(
4444. Gozal D, Serpero LD, Kheirandish-Gozal L, Capdevila OS, Khalyfa A,
Tauman R. Sleep measures and morning plasma TNF-alpha levels in children with
sleep-disordered breathing. Sleep. 2010;33(3):319-25. PMid:20337189 PMCid:2831425
) noted that children with moderate to severe OSAS had elevated levels of
TNF-α in the early hours of the morning and that children with adenotonsillar
hypertrophy showed a reduction in the levels of TNF-α after surgical treatment. In
patients with OSAS, CPAP therapy results in an improvement in the levels of CRP,
TNF-α, and IL-6.(
4545. Baessler A, Nadeem R, Harvey M, Madbouly E, Younus A, Sajid H, et
al. Treatment for sleep apnea by continuous positive airway pressure improves levels
of inflammatory markers - a meta-analysis. J Inflamm (Lond). 2013;10(1):13.
http://dx.doi.org/10.1186/1476-9255-10-13 PMid:23518041 PMCid:3637233
http://dx.doi.org/10.1186/1476-9255-10-1...
) TNF-α is a potent proinflammatory cytokine that plays an important role
in the pathogenesis of asthma; that is, it interferes with airway smooth muscle
contractility.(
4545. Baessler A, Nadeem R, Harvey M, Madbouly E, Younus A, Sajid H, et
al. Treatment for sleep apnea by continuous positive airway pressure improves levels
of inflammatory markers - a meta-analysis. J Inflamm (Lond). 2013;10(1):13.
http://dx.doi.org/10.1186/1476-9255-10-13 PMid:23518041 PMCid:3637233
http://dx.doi.org/10.1186/1476-9255-10-1...
)
OSAS-leptin-asthma
The treatment of OSAS can reduce circulating leptin levels as a result of the
reduction in the AHI.(
4646. Sanner BM, Kollhosser P, Buechner N, Zidek W, Tepel M. Influence of
treatment on leptin levels in patients with obstructive sleep apnoea. Eur Respir J.
2004;23(4):601-4. http://dx.doi.org/10.1183/09031936.04.00067804 PMid:15083761
http://dx.doi.org/10.1183/09031936.04.00...
) Sanner et al.(
4646. Sanner BM, Kollhosser P, Buechner N, Zidek W, Tepel M. Influence of
treatment on leptin levels in patients with obstructive sleep apnoea. Eur Respir J.
2004;23(4):601-4. http://dx.doi.org/10.1183/09031936.04.00067804 PMid:15083761
http://dx.doi.org/10.1183/09031936.04.00...
) noted that adults with OSAS treated with CPAP showed a reduction in the
AHI, from 29 events/h before CPAP treatment to 1.6 events/h after CPAP treatment, as
well as showing a reduction in leptin levels, from 8.5 ng/mL before CPAP treatment to
7.4 ng/mL after CPAP treatment. Circulating leptin levels are directly proportional
to the amount of adipose tissue; therefore, obese children and adults have elevated
circulating leptin levels.(
4646. Sanner BM, Kollhosser P, Buechner N, Zidek W, Tepel M. Influence of
treatment on leptin levels in patients with obstructive sleep apnoea. Eur Respir J.
2004;23(4):601-4. http://dx.doi.org/10.1183/09031936.04.00067804 PMid:15083761
http://dx.doi.org/10.1183/09031936.04.00...
) Mai et al.(
4747. Mai XM, Böttcher MF, Leijon I. Leptin and asthma in overweight
children at 12 years of age. Pediatr Allergy Immunol. 2004;15(6):523-30.
http://dx.doi.org/10.1111/j.1399-3038.2004.00195.x PMid:15610366
http://dx.doi.org/10.1111/j.1399-3038.20...
) showed that leptin levels are higher in obese children than in nonobese
children (mean, 18.1 ng/mL vs. 2.8 ng/mL). In addition, children with asthma are
twice as likely to have elevated leptin levels as are those without. Guler et
al.(
4848. Guler N, Kirerleri E, Ones U, Tamay Z, Salmayenli N, Darendeliler F.
Leptin: does it have any role in childhood asthma? J Allergy Clin Immunol.
2004;114(2):254-9. http://dx.doi.org/10.1016/j.jaci.2004.03.053 PMid:15316499
http://dx.doi.org/10.1016/j.jaci.2004.03...
) compared children with asthma and healthy children in terms of leptin
levels, which were found to be 3.53 ng/mL and 2.26 ng/mL, respectively. A logistic
regression showed that leptin acted as a predictive factor for asthma.
OSAS-GER-asthma
It is believed that the significant increase in negative intrathoracic pressure
caused by upper airway obstruction can predispose to retrograde movement of gastric
contents.(
4949. Orr WC, Robert JJ, Houck JR, Giddens CL, Tawk MM. The effect of acid
suppression on upper airway anatomy and obstruction in patients with sleep apnea and
gastroesophageal reflux disease. J Clin Sleep Med. 2009;5(4):330-4. PMid:19968010
PMCid:2725251
) One study showed that 71.4% of patients with OSAS had GER (as measured
by pH monitoring); of those, 10.4% reported no symptoms.(
5050. Samelson CF. Gastroesophageal reflux and obstructive sleep apnea.
Sleep. 1989;12(5):475-6. PMid:2799220
) Guda et al.(
5151. Guda N, Partington S, Vakil N. Symptomatic gastro-oesophageal
reflux, arousals and sleep quality in patients undergoing polysomnography for
possible obstructive sleep apnoea. Aliment Pharmacol Ther. 2004;20(10):1153-9.
http://dx.doi.org/10.1111/j.1365-2036.2004.02263.x PMid:15569118
http://dx.doi.org/10.1111/j.1365-2036.20...
) suggested that patients with GER have more episodes of OSAS than do
those without symptoms of GER. It has been reported that OSAS-induced GER can play an
important role in asthma symptoms.(
3939. Alkhalil M, Schulman E, Getsy J. Obstructive sleep apnea syndrome
and asthma: what are the links?. J Clin Sleep Med. 2009;5(1):71-8. PMid:19317386
PMCid:2637171
) Kiljander et al.(
5252. Kiljander TO, Laitinen JO. The prevalence of gastroesophageal reflux
disease in adult asthmatics. Chest. 2004;126(5):1490-4.
http://dx.doi.org/10.1378/chest.126.5.1490 PMid:15539717
http://dx.doi.org/10.1378/chest.126.5.14...
) studied 90 patients with asthma and reported that 32 (36%) had a
diagnosis of GER. However, this prevalence can be as high as 84%.(
5353. Sontag SJ, O'Connell S, Khandelwal S, Greenlee H, Schnell T,
Nemchausky B, et al. Asthmatics with gastroesophageal reflux: long term results of a
randomized trial of medical and surgical antireflux therapies. Am J Gastroenterol.
2003;98(5):987-99. PMid:12809818
,
5454. Harding SM, Richter JE, Guzzo MR, Schan CA, Alexander RW, Bradley
LA. Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma
outcome. Am J Med. 1996;100(4):395-405.
http://dx.doi.org/10.1016/S0002-9343(97)89514-9
http://dx.doi.org/10.1016/S0002-9343(97)...
) Sontag et al.(
5353. Sontag SJ, O'Connell S, Khandelwal S, Greenlee H, Schnell T,
Nemchausky B, et al. Asthmatics with gastroesophageal reflux: long term results of a
randomized trial of medical and surgical antireflux therapies. Am J Gastroenterol.
2003;98(5):987-99. PMid:12809818
) studied 62 patients with asthma and GER; of those, 24 were on antacids
(control group), 22 were on ranitidine (150 mg), and 16 underwent fundoplication.
Those who underwent surgical treatment showed an immediate reduction in nocturnal
exacerbation of wheezing, cough, and dyspnea. After 2 years, there was an improvement
in asthma in 74.5% of the patients who underwent surgical treatment, in 9.1% of those
in the ranitidine group, and in 4.2% of those in the control group. In the group of
patients who underwent surgical treatment, asthma symptom scores increased by 43%,
whereas, in the ranitidine and control groups, asthma symptom scores increased by
less than 10%.(
5353. Sontag SJ, O'Connell S, Khandelwal S, Greenlee H, Schnell T,
Nemchausky B, et al. Asthmatics with gastroesophageal reflux: long term results of a
randomized trial of medical and surgical antireflux therapies. Am J Gastroenterol.
2003;98(5):987-99. PMid:12809818
)
OSAS-upper airways-asthma
The current trend is to regard the nose and bronchi as parts of a single
airway.(
5555. Bousquet J, Van Cauwenberge P, Khaltaev N; Aria Workshop Group;
World Health Organization. Allergic rhinitis and its impact on asthma. J Allergy Clin
Immunol. 2001;108(5 Suppl):S147-334. http://dx.doi.org/10.1067/mai.2001.118891
PMid:11707753
http://dx.doi.org/10.1067/mai.2001.11889...
) Rhinitis is considered an independent risk factor for
asthma.(
5656. Cruz AA. The 'united airways' require an holistic approach to
management. Allergy. 2005;60(7):871-4.
http://dx.doi.org/10.1111/j.1398-9995.2005.00858.x PMid:15932375
http://dx.doi.org/10.1111/j.1398-9995.20...
) The proportion of asthma patients who have symptoms of rhinitis can be
as high as 100%.(
5757. Linneberg A, Henrik Nielsen N, Frølund L, Madsen F, Dirksen A,
Jørgensen T, et al. The link between allergic rhinitis and allergic asthma: a
prospective population-based study. The Copenhagen Allergy Study. Allergy.
2002;57(11):1048-52. http://dx.doi.org/10.1034/j.1398-9995.2002.23664.x PMid:12359002
http://dx.doi.org/10.1034/j.1398-9995.20...
) Kiely et al.(
5858. Kiely JL, Nolan P, McNicholas WT. Intranasal corticosteroid therapy
for obstructive sleep apnoea in patients with co-existing rhinitis. Thorax.
2004;59(1):50-5. PMid:14694248 PMCid:1758841
) noted that, after four weeks of treatment with a corticosteroid
(fluticasone propionate), the AHI was lower in the group of patients who used
fluticasone than in the control group. Kheirandish-Gozal et al.(
5959. Kheirandish-Gozal L, Gozal D. Intranasal budesonide treatment for
children with mild obstructive sleep apnea syndrome. Pediatrics. 2008;122(1):e149-55.
http://dx.doi.org/10.1542/peds.2007-3398 PMid:18595959
http://dx.doi.org/10.1542/peds.2007-3398...
) used intranasal budesonide for six weeks in children with moderate OSAS
and noted a significant improvement in the polysomnographic variables, 54.1% of the
children having reached the normal range. There was also a reduction in adenoid size.
The discontinuation of the nasal corticosteroid did not affect the results. However,
in the placebo group, there were no changes in the investigated data.(
5959. Kheirandish-Gozal L, Gozal D. Intranasal budesonide treatment for
children with mild obstructive sleep apnea syndrome. Pediatrics. 2008;122(1):e149-55.
http://dx.doi.org/10.1542/peds.2007-3398 PMid:18595959
http://dx.doi.org/10.1542/peds.2007-3398...
)
In children with OSAS, the most common upper airway obstruction sites are as follows:
adenoid, in 57%; hard palate, in 29%; and palatine tonsils, in 14%.(
6060. Isono S, Shimada A, Utsugi M, Konno A, Nishino T. Comparison of
static mechanical properties of the passive pharynx between normal children and
children with sleep-disordered breathing. Am J Respir Crit Care Med. 1998;157(4 Pt
1):1204-12. http://dx.doi.org/10.1164/ajrccm.157.4.9702042 PMid:9563740
http://dx.doi.org/10.1164/ajrccm.157.4.9...
) Donnelly et al.(
6161. Donnelly LF, Casper KA, Chen B. Correlation on cine MR imaging of
size of adenoid and palatine tonsils with degree of upper airway motion in
asymptomatic sedated children. AJR Am J Roentgenol. 2002;179(2):503-8.
http://dx.doi.org/10.2214/ajr.179.2.1790503 PMid:12130463
http://dx.doi.org/10.2214/ajr.179.2.1790...
) studied the upper airways using magnetic resonance imaging and found
hypopharyngeal collapse in 81% of the children with OSAS, having found no collapse in
the control group (composed of healthy children). Fregosi et al.(
6262. Fregosi RF, Quan SF, Morgan WL, Goodwin JL, Cabrera R, Shareif I, et
al. Pharyngeal critical pressure in children with mild sleep-disordered breathing. J
Appl Physiol. 2006;101(3):734-9. http://dx.doi.org/10.1152/japplphysiol.01444.2005
PMid:16709652
http://dx.doi.org/10.1152/japplphysiol.0...
) noted that the palatine tonsils, pharyngeal tonsils, and hard palate
account for 74.3% of all cases of upper airway obstruction in children. However,
Guilleminault et al.(
6363. Guilleminault C, Huang YS, Glamann C, Li K, Chan A.
Adenotonsillectomy and obstructive sleep apnea in children: a prospective survey.
Otolaryngol Head Neck Surg. 2007;136(2):169-75.
http://dx.doi.org/10.1016/j.otohns.2006.09.021 PMid:17275534
http://dx.doi.org/10.1016/j.otohns.2006....
) noted that OSAS persisted in 45% of the children who underwent
adenotonsillectomy. Therefore, adenotonsillar hypertrophy is only one of the causes
of OSAS in children. Other triggering factors, such as rhinopathy, turbinate
hypertrophy, septal deviation, and micrognathia, should be taken into
consideration.(
6464. Rizzi M, Onorato J, Andreoli A, Colombo S, Pecis M, Marchisio P, et
al. Nasal resistances are useful in identifying children with severe obstructive
sleep apnea before polysomnography. Int J Pediatr Otorhinolaryngol. 2002;65(1):7-13.
http://dx.doi.org/10.1016/S0165-5876(02)00119-2
http://dx.doi.org/10.1016/S0165-5876(02)...
)
Regarding the inflammatory process of the upper airways, Almendros et al.(
6565. Almendros I, Carreras A, Ramírez J, Montserrat JM, Navajas D, Farré
R. Upper airway collapse and reopening induce inflammation in a sleep apnoea model.
Eur Respir J. 2008;32(2):399-404. http://dx.doi.org/10.1183/09031936.00161607
PMid:18448490
http://dx.doi.org/10.1183/09031936.00161...
) conducted an experimental study in rats submitted to recurrent episodes
of negative pressure alternating with positive pressure and inducing upper airway
collapse and reopening, similar to what occurs in OSAS. They concluded that there was
a high expression of pro-inflammatory biomarkers, such as TNF-α, IL-1, and
macrophages, in the laryngeal and soft palate tissue. Puig et al.(
6666. Puig F, Rico F, Almendros I, Montserrat JM, Navajas D, Farre R.
Vibration enhances interleukin-8 release in a cell model of snoring-induced airway
inflammation. Sleep. 2005;28(10):1312-6. PMid:16295217
) examined human bronchial epithelial cells placed on a vibrating
platform. After 12 h and 24 h of exposure to vibration, the cells exhibited high
levels of IL-8 in comparison with those in the control group. The authors concluded
that vibration applied to epithelial cells can trigger inflammatory processes,
similar to what occurs in snoring and OSAS.(
6666. Puig F, Rico F, Almendros I, Montserrat JM, Navajas D, Farre R.
Vibration enhances interleukin-8 release in a cell model of snoring-induced airway
inflammation. Sleep. 2005;28(10):1312-6. PMid:16295217
)
Trudo et al.(
6767. Trudo FJ, Gefter WB, Welch KC, Gupta KB, Maislin G, Schwab RJ.
State-related changes in upper airway caliber and surrounding soft-tissue structures
in normal subjects. Am J Respir Crit Care Med. 1998;158(4):1259-70.
http://dx.doi.org/10.1164/ajrccm.158.4.9712063 PMid:9769290
http://dx.doi.org/10.1164/ajrccm.158.4.9...
) used magnetic resonance imaging in order to evaluate the upper airways
of 15 healthy adults during induced sleep and noted changes in and around the upper
airways. The air space at the level of the retropalatal region was reduced by 19%
during sleep, with an anteroposterior and laterolateral reduction in the pharynx. In
the retroglossal region, no significant reduction was observed. Schwab et
al.(
6868. Schwab RJ, Pasirstein M, Pierson R, Mackley A, Hachadoorian R, Arens
R, et al. Identification of upper airway anatomic risk factors for obstructive sleep
apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med.
2003;168(5):522-30. http://dx.doi.org/10.1164/rccm.200208-866OC PMid:12746251
http://dx.doi.org/10.1164/rccm.200208-86...
) compared patients with OSAS and healthy individuals in terms of the
dimensions of the upper airways. The chance of upper airway structures being
associated with OSAS was 6.01 for the lateral pharyngeal wall, 4.66 for tongue
volume, and 6.95 for soft tissues. The volume of the tongue and lateral pharyngeal
walls proved to be an independent factor for OSAS. Studies have shown fat deposition
in upper airway tissues in patients with OSAS.(
6969. Stauffer JL, Buick MK, Bixler EO, Sharkey FE, Abt AB, Manders EK, et
al. Morphology of the uvula in obstructive sleep apnea. Am Rev Respir Dis.
1989;140(3):724-8. http://dx.doi.org/10.1164/ajrccm/140.3.724 PMid:2782743
http://dx.doi.org/10.1164/ajrccm/140.3.7...
,
7070. Zohar Y, Sabo R, Strauss M, Schwartz A, Gal R, Oksenberg A.
Oropharyngeal fatty infiltration in obstructive sleep apnea patients: a histologic
study. Ann Otol Rhinol Laryngol. 1998;107(2):170-4. PMid:9486913
)
Prospects for intervention in OSAS-asthma
Patients with severe uncontrolled asthma seek emergency room treatment 15 times as often
as do those with moderate asthma and are hospitalized 20 times as often.(
7171. Jardim JR. Pharmacological economics and asthma treatment. J Bras
Pneumol. 2007;33(1):iv-vi. http://dx.doi.org/10.1590/S1806-37132007000100002
PMid:17568859
http://dx.doi.org/10.1590/S1806-37132007...
72. Ponte E, Franco RA, Souza-Machado A, Souza-Machado C, Cruz AA.
Impact that a program to control severe asthma has on the use of Unified Health
System resources in Brazil. J Bras Pneumol. 2007;33(1):15-9.
http://dx.doi.org/10.1590/S1806-37132007000100006 PMid:17568863
http://dx.doi.org/10.1590/S1806-37132007...
-
7373. Serra-Batlles J, Plaza V, Morejón E, Comella A, Brugués J. Costs of
asthma according to the degree of severity. Eur Respir J. 1998;12(6):1322-6.
http://dx.doi.org/10.1183/09031936.98.12061322 PMid:9877485
http://dx.doi.org/10.1183/09031936.98.12...
) It is speculated that OSAS plays an important role in asthma exacerbations
and that the use of CPAP can decrease exacerbations, improve quality of life, and reduce
the number of cases of difficult-to-control asthma.(
7474. Alkhalil M, Schulman ES, Getsy J. Obstructive sleep apnea syndrome
and asthma: the role of continuous positive airway pressure treatment. Ann Allergy
Asthma Immunol. 2008;101(4):350-7. http://dx.doi.org/10.1016/S1081-1206(10)60309-2
http://dx.doi.org/10.1016/S1081-1206(10)...
) Chan et al.(
7575. Chan CS, Woolcock AJ, Sullivan CE. Nocturnal asthma: role of snoring
and obstructive sleep apnea. Am Rev Respir Dis. 1988;137(6):1502-4.
http://dx.doi.org/10.1164/ajrccm/137.6.1502 PMid:3059864
http://dx.doi.org/10.1164/ajrccm/137.6.1...
) noted that the mean pre-bronchodilator and post-bronchodilator
FEV1 were higher during CPAP therapy than during two control periods
(i.e., without CPAP therapy). The authors reported that CPAP treatment improved asthma
control, and, in particular, nocturnal exacerbations of asthma. Guilleminault et
al.(
3535. Guilleminault C, Quera-Salva MA, Powell N, Riley R, Romaker A,
Partinen M, et al. Nocturnal asthma: snoring, small pharynx and nasal CPAP. Eur
Respir J. 1988;1(10):902-7. PMid:3066641
) studied patients with asthma and craniomandibular abnormalities, with a
narrow retrolingual space. They found that the use of CPAP eliminated snoring, apnea,
hypopnea, and nocturnal asthma exacerbations. Nasal CPAP had no effect on daytime
asthma.(
3535. Guilleminault C, Quera-Salva MA, Powell N, Riley R, Romaker A,
Partinen M, et al. Nocturnal asthma: snoring, small pharynx and nasal CPAP. Eur
Respir J. 1988;1(10):902-7. PMid:3066641
) The use of CPAP, when appropriate, is beneficial for asthma-OSAS, having
favorable effects on bronchial and systemic inflammation, reducing bronchial
hyperreactivity, improving sleep architecture, reducing body weight, suppressing
lecithin production by adipose tissue, improving cardiac function, and significantly
reducing GER.(
7474. Alkhalil M, Schulman ES, Getsy J. Obstructive sleep apnea syndrome
and asthma: the role of continuous positive airway pressure treatment. Ann Allergy
Asthma Immunol. 2008;101(4):350-7. http://dx.doi.org/10.1016/S1081-1206(10)60309-2
http://dx.doi.org/10.1016/S1081-1206(10)...
) Therefore, bronchial asthma and OSAS are two public health problems, whose
interrelationship is being recognized.(
7676. Cabral MM, Mueller Pde T. Sleep and chronic lung diseases: diffuse
interstitial lung diseases, bronchial asthma, and COPD [Article in Portuguese]. J
Bras Pneumol. 2010;36 Suppl 2:53-6. http://dx.doi.org/10.1590/S1806-37132010001400014
PMid:20944983
http://dx.doi.org/10.1590/S1806-37132010...
) It is expected that an understanding of this process can provide the basis
for the development of new treatment strategies.(
7676. Cabral MM, Mueller Pde T. Sleep and chronic lung diseases: diffuse
interstitial lung diseases, bronchial asthma, and COPD [Article in Portuguese]. J
Bras Pneumol. 2010;36 Suppl 2:53-6. http://dx.doi.org/10.1590/S1806-37132010001400014
PMid:20944983
http://dx.doi.org/10.1590/S1806-37132010...
)
Final considerations
Although the association between OSAS and asthma is common, it is poorly investigated. If left untreated, OSAS can contribute to the lack of control of asthma, especially nocturnal asthma symptoms. In patients with asthma, OSAS should be investigated whenever there is inadequate control of nocturnal asthma symptoms despite the treatment recommended by guidelines having been administered. There is evidence in the literature that CPAP therapy is effective in terms of symptom remission and contributes to asthma control in asthma patients with OSAS and uncontrolled asthma.
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*
Study carried out under the auspices of the Graduate Program in Health Sciences, Federal University of Bahia, Salvador, Brazil.
Publication Dates
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Publication in this collection
Sep-Oct 2013
History
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Received
27 Mar 2013 -
Accepted
14 June 2013