Pulmonary Pharmacology & Therapeutics xxx (2015) 1e3
Contents lists available at ScienceDirect
Pulmonary Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/ypupt
Cough in obstructive sleep apnoea Kevin Chan a, Alvin Ing b, Surinder S. Birring c, * a
Campbelltown Hospital, University of Western Sydney, Campbelltown, New South Wales, Australia Concord Repatriation General Hospital, University of Sydney, Sydney, New South Wales, Australia c King's College London, Division of Asthma, Allergy and Lung Biology, Denmark Hill Campus, London, United Kingdom b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 17 January 2015 Accepted 31 May 2015 Available online xxx
Obstructive Sleep Apnoea (OSA) has recently been reported to be a cause of chronic cough. It should be considered when cough remains unexplained following investigations and treatments for common causes. The presence of nocturnal cough, snoring and gastro-oesophageal reflux may be helpful in identifying patients who require further investigation. Daytime somnolence is often absent. Continuous positive airway pressure (CPAP) therapy has been reported to be effective in alleviating cough. Therapy for gastro-oesophageal reflux disease, if present, should be optimised. The mechanism of the association between OSA and cough is not clear, but airway inflammation, gastro-oesophageal reflux disease, increased cough reflex sensitivity and tracheobronchomalacia are possible explanations. Further studies should identify clinical predictors of OSA-cough, establish mechanisms and the optimal therapy. Crown Copyright © 2015 Published by Elsevier Ltd. All rights reserved.
Keywords: Obstructive sleep apnoea Gastro-oesophageal reflux Cough hyper sensitivity syndrome Chronic cough
1. Introduction
2. Prevalence
Unexplained chronic cough is a common condition referred to respiratory out-patient clinics. The assessment of patients initially focuses on asthma, gastro-oesophageal reflux and rhinitis as they are the most frequent causes [1]. In a significant number of patients, the cough remains unexplained despite extensive investigations and treatment trials [2]. They are known as ‘idiopathic chronic cough’. Obstructive Sleep Apnoea (OSA) was reported as a potential cause of chronic cough by Birring, S et al., in 2007, in a case series of four patients [3]. Cough was the sole presenting feature of OSA. The diagnosis of OSA was, in some cases, established many years following the initial presentation with cough. The cough improved in all four patients with continuous positive airways pressure (CPAP) therapy. Since 2007, OSA has been reported as a cause or association with chronic cough by a number of investigators (see Table 1). This review will discuss the presenting features of OSAassociated cough, assessment, management and potential mechanisms of cough.
Few studies have investigated the prevalence of OSA in patients with chronic cough. Sundar et al. reported a prevalence of 44% and 68% in patients presenting with chronic cough in two studies [4,5]. The very high prevalence may reflect the high body mass index (BMI) in the general population in Utah, United States of America [6]. It is also possible that some patients had other causes for their cough. Chan et al. and Wang et al. reported a prevalence of chronic cough in patients with a confirmed diagnosis of OSA of 33% and 39% respectively compared to 12.5% in those in whom OSA was excluded [7,8].
* Corresponding author. Division of Asthma, Allergy and Lung Biology, Denmark Hill Campus, King's College London, Denmark Hill, London, SE5 9RS, United Kingdom. E-mail address: [email protected] (S.S. Birring).
3. Clinical manifestations It is difficult to identify patients with OSA-cough at initial presentation from the history alone as the cough is usually indistinguishable from other causes. The published case series do suggest some presenting features that should alert the clinician to the possibility of OSA-cough. These include the presence of snoring, nocturnal cough, nocturnal heartburn and symptoms of rhinitis [3,7]. Nocturnal cough is unusual in patients with unexplained chronic cough and therefore its presence may indicate a sleep related disorder. Chan et al. reported that patients with OSA-cough are twice as likely to be female compared to OSA patients without cough, and more likely to have symptoms of nocturnal heartburn and rhinitis [7]. It would also be reasonable to consider the
http://dx.doi.org/10.1016/j.pupt.2015.05.008 1094-5539/Crown Copyright © 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: K. Chan, et al., Cough in obstructive sleep apnoea, Pulmonary Pharmacology & Therapeutics (2015), http:// dx.doi.org/10.1016/j.pupt.2015.05.008
2
K. Chan et al. / Pulmonary Pharmacology & Therapeutics xxx (2015) 1e3
Table 1 Obstructive sleep apnoea-cough case series. Author
Country
Year
Number patients
Female (%)
CPAP responders
Birring Chan Faruqui Sundar Wang Yokohori
UK Australia UK USA Taiwan Japan
2007 2010 2012 2013 2013 2014
4 18 1 19 39 2
50 61 0 71 23 100
Y na Y Y Y Y
CPAP: continuous positive airway pressure. Number patients: Number of patients with co-existing cough and obstructive sleep apnoea.
diagnosis of OSA in a patient with a raised BMI and clinical features of OSA. A common theme in reported cases of OSA-cough is that the patients did not have excessive daytime somnolence, and their Epworth Sleepiness Scores were often normal. The authors suggest that the patients with an unexplained chronic cough should be initially investigated for common causes of cough, such as asthma, gastro-oesophageal reflux and rhinitis, before evaluating for OSA unless there are obvious features of OSA, such as daytime somnolence and snoring in a patient with a raised BMI (see Table 2). 4. Investigation The investigation of OSA in patients with chronic cough in published case series varies between the use of overnight oximetry and full polysomnography. There are no comparative studies. In the author's opinion, it is reasonable to investigate patients initially with an ambulatory sleep study with EEG recording capacity (Level 2 sleep study) [12] or an overnight oximetry (Level 4 sleep study) [12] because these are cost-effective options and convenient for the patient, and diagnosis can be reached in many cases. Full polysomnography can be requested if the diagnosis is still unclear following such studies. In the study reported by Wang et al., the apnoea-hypoapnoea index was associated with cough in a univariate analysis, but was subsequently not confirmed as an independent predictor in a multivariate analysis [8]. 5. CPAP therapy CPAP therapy has been reported to be effective for OSA-cough [3,8e11]. It should however be noted that these studies were uncontrolled, and the chance of bias is high. Improvement in cough appears to be apparent within one month of initiation of CPAP. In the author's opinion, CPAP therapy should be used with humidification to avoid further exacerbation of cough associated with airway dryness. Furthermore, therapy for gastro-oesophageal reflux and rhinitis should be optimised. The success of CPAP therapy on cough should only be judged once CPAP has been titrated to optimal pressures and compliance established. In the study reported by Sundar et al., 93% of patients with OSA-associated cough
Table 2 Clinical features of OSA. Clinical features that may be present in OSA-cough Snoring Nocturnal cough Nocturnal heartburn Rhinitis Raised body mass index Daytime somnolence often absent OSA: obstructive sleep apnoea.
improved following CPAP therapy [9]. In the study by Wang et al., cough resolved in 67% of patients following CPAP therapy [8]. By comparison, cough resolved in only 10% of subjects with OSAcough who did not undergo CPAP therapy [8]. The effectiveness of other OSA treatment modalities such as the mandibular advancement splints is not known and should be investigated. 6. Mechanisms of OSA-cough The mechanism of the association between OSA and cough is not known. However, several mechanisms are possible, and discussed below. Patients with OSA are likely to have upper airway inflammation resulting from snoring and frequent episodes of airway obstruction. In patients with OSA, increased concentrations of inflammatory mediators such as interleukin-6, interferongamma and interleukin-8 have been reported [6]. Furthermore, an increase in exhaled nitric oxide from the upper airways and sputum neutrophilia has been reported in OSA [13]. It is therefore possible that a mechanism for OSA-cough may be an increase in the sensitivity of the cough reflex associated with airway inflammation, as seen in other causes of cough, such as eosinophilic bronchitis [14]. Faruqi et al. have reported desensitisation of the cough reflex following CPAP therapy in a patient with OSA-associated cough [11]. Another possibility may be a loss or reduction of central inhibition on cough reflex sensitivity due to frequent arousals at night associated with episodes of airflow obstruction. Gastro-oesophageal reflux is another plausible explanation for the association between OSA and cough. Patients with OSA have an increased prevalence of gastro-oesophageal reflux and a study by Ing et al. reported that CPAP effectively treats gastro-oesophageal reflux in patients with OSA [15]. Both Chan et al. and Wang et al. have reported a higher prevalence of gastro-oesophageal reflux in patients with OSA and cough compared to those without cough [7,8]. Furthermore, Wang et al. reported gastro-oesophageal reflux was an independent predictor of cough in patients with OSA [8]. It is therefore important that patients with OSA-cough undergo optimal treatment for gastro-oesophageal reflux according to cough guidelines [16]. The association between OSA and cough may have a mechanical basis. Bonnet et al. reported five patients with an unexplained nocturnal cough that improved following CPAP therapy [17]. All had tracheobronchomalacia, a condition characterised by flaccidity of the tracheal support cartilage which leads to tracheal collapse extending to the bronchi. The diagnosis is usually established by direct visualisation during bronchoscopy. In adults, it is usually acquired, often of unknown origin. Causes include previous mechanical ventilation, trauma and external compression. The cough often has a striking, barking quality, and is typically not responsive to corticosteroids or bronchodilators. 7. Conclusion There is emerging evidence that OSA may be a cause of chronic cough. This diagnosis should be considered in patients with negative investigations and treatment trials for chronic cough. The presence of nocturnal cough and snoring may be helpful in identifying patients. A small number of uncontrolled studies report that CPAP is effective in reducing symptoms of cough. The mechanism of cough is unclear, and should be investigated further. Further studies should also evaluate the effectiveness of CPAP therapy in controlled studies. References [1] S.S. Birring, Controversies in the evaluation and management of chronic
Please cite this article in press as: K. Chan, et al., Cough in obstructive sleep apnoea, Pulmonary Pharmacology & Therapeutics (2015), http:// dx.doi.org/10.1016/j.pupt.2015.05.008
K. Chan et al. / Pulmonary Pharmacology & Therapeutics xxx (2015) 1e3 cough, Am. J. Respir. Crit. Care Med. 183 (6) (2011 March 15) 708e715. [2] S.S. Birring, C.E. Brightling, F.A. Symon, S.G. Barlow, A.J. Wardlaw, I.D. Pavord, Idiopathic chronic cough: association with organ specific autoimmune disease and bronchoalveolar lymphocytosis, Thorax 58 (12) (2003 December) 1066e1070. [3] S.S. Birring, A.J. Ing, K. Chan, G. Cossa, S. Matos, M.D. Morgan, et al., Obstructive sleep apnoea: a cause of chronic cough, Cough 3 (2007) 7. [4] K.M. Sundar, S.E. Daly, M.J. Pearce, W.T. Alward, Chronic cough and obstructive sleep apnea in a community-based pulmonary practice, Cough 6 (1) (2010) 2. [5] K.M. Sundar, S.E. Daly, Chronic cough and OSA: a new association? J. Clin. Sleep. Med. 7 (6) (2011 December 15) 669e677. [6] K.M. Sundar, S.E. Daly, Chronic cough and OSA: an underappreciated relationship, Lung 192 (1) (2014 February) 21e25. [7] K.K. Chan, A.J. Ing, L. Laks, G. Cossa, P. Rogers, S.S. Birring, Chronic cough in patients with sleep-disordered breathing, Eur. Respir. J. 35 (2) (2010 February) 368e372. [8] T.Y. Wang, Y.L. Lo, W.T. Liu, S.M. Lin, T.Y. Lin, C.H. Kuo, et al., Chronic cough and obstructive sleep apnoea in a sleep laboratory-based pulmonary practice, Cough 9 (1) (2013) 24. [9] K.M. Sundar, S.E. Daly, A.M. Willis, A longitudinal study of CPAP therapy for patients with chronic cough and obstructive sleep apnoea, Cough 9 (1) (2013) 19.
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[10] N. Yokohori, M. Hasegawa, A. Sato, H. Katsura, Utility of continuous positive airway pressure therapy for treating chronic coughs in patients with obstructive sleep apnea, Intern Med. 53 (10) (2014) 1079e1082. [11] S. Faruqi, A. Fahim, A.H. Morice, Chronic cough and obstructive sleep apnoea: reflux-associated cough hypersensitivity? Eur. Respir. J. 40 (4) (2012 October) 1049e1050. [12] M. Ahmed, N. Patel, I. Rosen, Portable monitors in the diagnosis of obstructive sleep apnoea, Chest 132 (2007) 1672e1677. [13] A.M. Fortuna, R. Miralda, N. Calaf, M. Gonzalez, P. Casan, M. Mayos, Airway and alveolar nitric oxide measurements in obstructive sleep apnea syndrome, Respir. Med. 105 (4) (2011 April) 630e636. [14] R.J. Kimoff, E. Sforza, V. Champagne, L. Ofiara, D. Gendron, Upper airway sensation in snoring and obstructive sleep apnea, Am. J. Respir. Crit. Care Med. 164 (2) (2001 July 15) 250e255. [15] A.J. Ing, M.C. Ngu, A.B. Breslin, Obstructive sleep apnea and gastroesophageal reflux, Am. J. Med. 108 (Suppl. 4a) (2000 March 6) 120Se125S. [16] R.S. Irwin, M.H. Baumann, D.C. Bolser, L.P. Boulet, S.S. Braman, C.E. Brightling, et al., Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines, Chest 129 (1 Suppl) (2006 January) 1Se23S. [17] R. Bonnet, R. Jorres, R. Downey, H. Hein, H. Magnussen, Intractable cough associated with the supine body position. Effective therapy with nasal CPAP, Chest 108 (2) (1995) 581e585.
Please cite this article in press as: K. Chan, et al., Cough in obstructive sleep apnoea, Pulmonary Pharmacology & Therapeutics (2015), http:// dx.doi.org/10.1016/j.pupt.2015.05.008
Contents lists available at ScienceDirect
Pulmonary Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/ypupt
Cough in obstructive sleep apnoea Kevin Chan a, Alvin Ing b, Surinder S. Birring c, * a
Campbelltown Hospital, University of Western Sydney, Campbelltown, New South Wales, Australia Concord Repatriation General Hospital, University of Sydney, Sydney, New South Wales, Australia c King's College London, Division of Asthma, Allergy and Lung Biology, Denmark Hill Campus, London, United Kingdom b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 17 January 2015 Accepted 31 May 2015 Available online xxx
Obstructive Sleep Apnoea (OSA) has recently been reported to be a cause of chronic cough. It should be considered when cough remains unexplained following investigations and treatments for common causes. The presence of nocturnal cough, snoring and gastro-oesophageal reflux may be helpful in identifying patients who require further investigation. Daytime somnolence is often absent. Continuous positive airway pressure (CPAP) therapy has been reported to be effective in alleviating cough. Therapy for gastro-oesophageal reflux disease, if present, should be optimised. The mechanism of the association between OSA and cough is not clear, but airway inflammation, gastro-oesophageal reflux disease, increased cough reflex sensitivity and tracheobronchomalacia are possible explanations. Further studies should identify clinical predictors of OSA-cough, establish mechanisms and the optimal therapy. Crown Copyright © 2015 Published by Elsevier Ltd. All rights reserved.
Keywords: Obstructive sleep apnoea Gastro-oesophageal reflux Cough hyper sensitivity syndrome Chronic cough
1. Introduction
2. Prevalence
Unexplained chronic cough is a common condition referred to respiratory out-patient clinics. The assessment of patients initially focuses on asthma, gastro-oesophageal reflux and rhinitis as they are the most frequent causes [1]. In a significant number of patients, the cough remains unexplained despite extensive investigations and treatment trials [2]. They are known as ‘idiopathic chronic cough’. Obstructive Sleep Apnoea (OSA) was reported as a potential cause of chronic cough by Birring, S et al., in 2007, in a case series of four patients [3]. Cough was the sole presenting feature of OSA. The diagnosis of OSA was, in some cases, established many years following the initial presentation with cough. The cough improved in all four patients with continuous positive airways pressure (CPAP) therapy. Since 2007, OSA has been reported as a cause or association with chronic cough by a number of investigators (see Table 1). This review will discuss the presenting features of OSAassociated cough, assessment, management and potential mechanisms of cough.
Few studies have investigated the prevalence of OSA in patients with chronic cough. Sundar et al. reported a prevalence of 44% and 68% in patients presenting with chronic cough in two studies [4,5]. The very high prevalence may reflect the high body mass index (BMI) in the general population in Utah, United States of America [6]. It is also possible that some patients had other causes for their cough. Chan et al. and Wang et al. reported a prevalence of chronic cough in patients with a confirmed diagnosis of OSA of 33% and 39% respectively compared to 12.5% in those in whom OSA was excluded [7,8].
* Corresponding author. Division of Asthma, Allergy and Lung Biology, Denmark Hill Campus, King's College London, Denmark Hill, London, SE5 9RS, United Kingdom. E-mail address: [email protected] (S.S. Birring).
3. Clinical manifestations It is difficult to identify patients with OSA-cough at initial presentation from the history alone as the cough is usually indistinguishable from other causes. The published case series do suggest some presenting features that should alert the clinician to the possibility of OSA-cough. These include the presence of snoring, nocturnal cough, nocturnal heartburn and symptoms of rhinitis [3,7]. Nocturnal cough is unusual in patients with unexplained chronic cough and therefore its presence may indicate a sleep related disorder. Chan et al. reported that patients with OSA-cough are twice as likely to be female compared to OSA patients without cough, and more likely to have symptoms of nocturnal heartburn and rhinitis [7]. It would also be reasonable to consider the
http://dx.doi.org/10.1016/j.pupt.2015.05.008 1094-5539/Crown Copyright © 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: K. Chan, et al., Cough in obstructive sleep apnoea, Pulmonary Pharmacology & Therapeutics (2015), http:// dx.doi.org/10.1016/j.pupt.2015.05.008
2
K. Chan et al. / Pulmonary Pharmacology & Therapeutics xxx (2015) 1e3
Table 1 Obstructive sleep apnoea-cough case series. Author
Country
Year
Number patients
Female (%)
CPAP responders
Birring Chan Faruqui Sundar Wang Yokohori
UK Australia UK USA Taiwan Japan
2007 2010 2012 2013 2013 2014
4 18 1 19 39 2
50 61 0 71 23 100
Y na Y Y Y Y
CPAP: continuous positive airway pressure. Number patients: Number of patients with co-existing cough and obstructive sleep apnoea.
diagnosis of OSA in a patient with a raised BMI and clinical features of OSA. A common theme in reported cases of OSA-cough is that the patients did not have excessive daytime somnolence, and their Epworth Sleepiness Scores were often normal. The authors suggest that the patients with an unexplained chronic cough should be initially investigated for common causes of cough, such as asthma, gastro-oesophageal reflux and rhinitis, before evaluating for OSA unless there are obvious features of OSA, such as daytime somnolence and snoring in a patient with a raised BMI (see Table 2). 4. Investigation The investigation of OSA in patients with chronic cough in published case series varies between the use of overnight oximetry and full polysomnography. There are no comparative studies. In the author's opinion, it is reasonable to investigate patients initially with an ambulatory sleep study with EEG recording capacity (Level 2 sleep study) [12] or an overnight oximetry (Level 4 sleep study) [12] because these are cost-effective options and convenient for the patient, and diagnosis can be reached in many cases. Full polysomnography can be requested if the diagnosis is still unclear following such studies. In the study reported by Wang et al., the apnoea-hypoapnoea index was associated with cough in a univariate analysis, but was subsequently not confirmed as an independent predictor in a multivariate analysis [8]. 5. CPAP therapy CPAP therapy has been reported to be effective for OSA-cough [3,8e11]. It should however be noted that these studies were uncontrolled, and the chance of bias is high. Improvement in cough appears to be apparent within one month of initiation of CPAP. In the author's opinion, CPAP therapy should be used with humidification to avoid further exacerbation of cough associated with airway dryness. Furthermore, therapy for gastro-oesophageal reflux and rhinitis should be optimised. The success of CPAP therapy on cough should only be judged once CPAP has been titrated to optimal pressures and compliance established. In the study reported by Sundar et al., 93% of patients with OSA-associated cough
Table 2 Clinical features of OSA. Clinical features that may be present in OSA-cough Snoring Nocturnal cough Nocturnal heartburn Rhinitis Raised body mass index Daytime somnolence often absent OSA: obstructive sleep apnoea.
improved following CPAP therapy [9]. In the study by Wang et al., cough resolved in 67% of patients following CPAP therapy [8]. By comparison, cough resolved in only 10% of subjects with OSAcough who did not undergo CPAP therapy [8]. The effectiveness of other OSA treatment modalities such as the mandibular advancement splints is not known and should be investigated. 6. Mechanisms of OSA-cough The mechanism of the association between OSA and cough is not known. However, several mechanisms are possible, and discussed below. Patients with OSA are likely to have upper airway inflammation resulting from snoring and frequent episodes of airway obstruction. In patients with OSA, increased concentrations of inflammatory mediators such as interleukin-6, interferongamma and interleukin-8 have been reported [6]. Furthermore, an increase in exhaled nitric oxide from the upper airways and sputum neutrophilia has been reported in OSA [13]. It is therefore possible that a mechanism for OSA-cough may be an increase in the sensitivity of the cough reflex associated with airway inflammation, as seen in other causes of cough, such as eosinophilic bronchitis [14]. Faruqi et al. have reported desensitisation of the cough reflex following CPAP therapy in a patient with OSA-associated cough [11]. Another possibility may be a loss or reduction of central inhibition on cough reflex sensitivity due to frequent arousals at night associated with episodes of airflow obstruction. Gastro-oesophageal reflux is another plausible explanation for the association between OSA and cough. Patients with OSA have an increased prevalence of gastro-oesophageal reflux and a study by Ing et al. reported that CPAP effectively treats gastro-oesophageal reflux in patients with OSA [15]. Both Chan et al. and Wang et al. have reported a higher prevalence of gastro-oesophageal reflux in patients with OSA and cough compared to those without cough [7,8]. Furthermore, Wang et al. reported gastro-oesophageal reflux was an independent predictor of cough in patients with OSA [8]. It is therefore important that patients with OSA-cough undergo optimal treatment for gastro-oesophageal reflux according to cough guidelines [16]. The association between OSA and cough may have a mechanical basis. Bonnet et al. reported five patients with an unexplained nocturnal cough that improved following CPAP therapy [17]. All had tracheobronchomalacia, a condition characterised by flaccidity of the tracheal support cartilage which leads to tracheal collapse extending to the bronchi. The diagnosis is usually established by direct visualisation during bronchoscopy. In adults, it is usually acquired, often of unknown origin. Causes include previous mechanical ventilation, trauma and external compression. The cough often has a striking, barking quality, and is typically not responsive to corticosteroids or bronchodilators. 7. Conclusion There is emerging evidence that OSA may be a cause of chronic cough. This diagnosis should be considered in patients with negative investigations and treatment trials for chronic cough. The presence of nocturnal cough and snoring may be helpful in identifying patients. A small number of uncontrolled studies report that CPAP is effective in reducing symptoms of cough. The mechanism of cough is unclear, and should be investigated further. Further studies should also evaluate the effectiveness of CPAP therapy in controlled studies. References [1] S.S. Birring, Controversies in the evaluation and management of chronic
Please cite this article in press as: K. Chan, et al., Cough in obstructive sleep apnoea, Pulmonary Pharmacology & Therapeutics (2015), http:// dx.doi.org/10.1016/j.pupt.2015.05.008
K. Chan et al. / Pulmonary Pharmacology & Therapeutics xxx (2015) 1e3 cough, Am. J. Respir. Crit. Care Med. 183 (6) (2011 March 15) 708e715. [2] S.S. Birring, C.E. Brightling, F.A. Symon, S.G. Barlow, A.J. Wardlaw, I.D. Pavord, Idiopathic chronic cough: association with organ specific autoimmune disease and bronchoalveolar lymphocytosis, Thorax 58 (12) (2003 December) 1066e1070. [3] S.S. Birring, A.J. Ing, K. Chan, G. Cossa, S. Matos, M.D. Morgan, et al., Obstructive sleep apnoea: a cause of chronic cough, Cough 3 (2007) 7. [4] K.M. Sundar, S.E. Daly, M.J. Pearce, W.T. Alward, Chronic cough and obstructive sleep apnea in a community-based pulmonary practice, Cough 6 (1) (2010) 2. [5] K.M. Sundar, S.E. Daly, Chronic cough and OSA: a new association? J. Clin. Sleep. Med. 7 (6) (2011 December 15) 669e677. [6] K.M. Sundar, S.E. Daly, Chronic cough and OSA: an underappreciated relationship, Lung 192 (1) (2014 February) 21e25. [7] K.K. Chan, A.J. Ing, L. Laks, G. Cossa, P. Rogers, S.S. Birring, Chronic cough in patients with sleep-disordered breathing, Eur. Respir. J. 35 (2) (2010 February) 368e372. [8] T.Y. Wang, Y.L. Lo, W.T. Liu, S.M. Lin, T.Y. Lin, C.H. Kuo, et al., Chronic cough and obstructive sleep apnoea in a sleep laboratory-based pulmonary practice, Cough 9 (1) (2013) 24. [9] K.M. Sundar, S.E. Daly, A.M. Willis, A longitudinal study of CPAP therapy for patients with chronic cough and obstructive sleep apnoea, Cough 9 (1) (2013) 19.
3
[10] N. Yokohori, M. Hasegawa, A. Sato, H. Katsura, Utility of continuous positive airway pressure therapy for treating chronic coughs in patients with obstructive sleep apnea, Intern Med. 53 (10) (2014) 1079e1082. [11] S. Faruqi, A. Fahim, A.H. Morice, Chronic cough and obstructive sleep apnoea: reflux-associated cough hypersensitivity? Eur. Respir. J. 40 (4) (2012 October) 1049e1050. [12] M. Ahmed, N. Patel, I. Rosen, Portable monitors in the diagnosis of obstructive sleep apnoea, Chest 132 (2007) 1672e1677. [13] A.M. Fortuna, R. Miralda, N. Calaf, M. Gonzalez, P. Casan, M. Mayos, Airway and alveolar nitric oxide measurements in obstructive sleep apnea syndrome, Respir. Med. 105 (4) (2011 April) 630e636. [14] R.J. Kimoff, E. Sforza, V. Champagne, L. Ofiara, D. Gendron, Upper airway sensation in snoring and obstructive sleep apnea, Am. J. Respir. Crit. Care Med. 164 (2) (2001 July 15) 250e255. [15] A.J. Ing, M.C. Ngu, A.B. Breslin, Obstructive sleep apnea and gastroesophageal reflux, Am. J. Med. 108 (Suppl. 4a) (2000 March 6) 120Se125S. [16] R.S. Irwin, M.H. Baumann, D.C. Bolser, L.P. Boulet, S.S. Braman, C.E. Brightling, et al., Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines, Chest 129 (1 Suppl) (2006 January) 1Se23S. [17] R. Bonnet, R. Jorres, R. Downey, H. Hein, H. Magnussen, Intractable cough associated with the supine body position. Effective therapy with nasal CPAP, Chest 108 (2) (1995) 581e585.
Please cite this article in press as: K. Chan, et al., Cough in obstructive sleep apnoea, Pulmonary Pharmacology & Therapeutics (2015), http:// dx.doi.org/10.1016/j.pupt.2015.05.008
