- Email: [email protected]
The role of high resolution oesophageal manometry in occult respiratory symptoms
Respiratory Medicine 138 (2018) 47–49
Contents lists available at ScienceDirect
Respiratory Medicine journal homepage: www.elsevier.com/locate/rmed
Short communication
The role of high resolution oesophageal manometry in occult respiratory symptoms
T
Jennifer M. Burkea, Warren Jacksona, Alyn H. Moriceb,∗ a b
GI Physiology, Hull and East Yorkshire Hospitals NHS Trust, Castle Hill Hospital, Hull HU16 5JQ, United Kingdom Hull York Medical School, Castle Hill Hospital, Hull, HU16 5JQ, United Kingdom
A R T I C LE I N FO
A B S T R A C T
Keywords: Cough Manometry Respiratory hypersensitivity
Purpose: Cough Hypersensitivity Syndrome is the urge to cough following minimal stimulation, but its mechanism and method of provocation remain unexplained. 121 patients (44 males, 77 females; age range 18–81 years) were evaluated. Procedures: High resolution manometry was performed on consecutive patients presenting with unexplained respiratory symptoms (Respiratory Group 61). Data were compared with matched controls, i.e. dyspepsia without respiratory symptoms (Dyspepsia Group 60). Main findings: Results showed increased inspiratory gastro-oesophageal pressure gradient due to significantly lower intra-oesophageal pressure on inspiration (p = 0.001), and reduced oesophageal motility in the Respiratory Group. Conclusions: Further research in respiratory conditions characterised by decreased intrathoracic pressure during inspiration is needed.
1. Introduction Many patients present with unexplained respiratory symptoms despite normal chest radiograph and little evidence of airway inflammation. Studies using objective acoustic cough monitors demonstrate “idiopathic” chronic cough sufferers have frequent cough events and are sensitive to various external stimuli. Cough Hypersensitivity Syndrome [1] (vagal afferent hypersensitivity) is the urge to cough following minimal stimulation, but its mechanism and method of provocation remain unexplained. The long-established association of gastro-oesophageal reflux with chronic cough [2] suggests that abnormal oesophageal physiology may underlie some afferent sensations perceived by sufferers, e.g. classic reflux disease, non-acid gaseous reflux, or referred sensations from oesophageal vagal afferents. Abnormal oesophageal motor activity causes several complaints, e.g. dysphagia and chest pain [3], which may be investigated using oesophageal manometry via trans-nasal passage of a pressure-sensitive catheter. High resolution manometry (HRM) is a recent innovation employing closely spaced pressure sensors and continuous real-time recording that has resulted in sensitive, accurate, objective oesophageal physiology analysis [4]. A link between oesophageal dysmotility and chronic cough using oesophageal manometry has been demonstrated [5]. However, the
∗
dynamic physiological change seen during respiration in patients with respiratory disease has not be characterised. HRM allows determination of the pressure profile of thoracic and abdominal cavities during respiratory cycles in real-time and enables calculation of the gastro-oesophageal pressure gradient (GOPG) describing pressure profiles of the thorax and abdomen and their effect on trans-oesophago-gastric pressures. 2. Materials and methods The study was conducted in the Department of GI Physiology, Castle Hill Hospital. All patients provided written informed consent prior to participation. HRM was performed on consecutive patients presenting with unexplained respiratory symptoms (Respiratory Group) using a solid-state catheter (UniTip: UniSensor AG, Switzerland). Data from age- and sex-matched controls were collected from patients undergoing investigation for dyspepsia but without respiratory symptoms (Dyspepsia Group). Patients were instructed to stop proton pump inhibitor medications 7 days pre-investigation and histamine H2-receptor antagonist or drugs affecting gastrointestinal motility 3 days pre-investigation, and to remain nil-by-mouth from 4 h pre-investigation. All tests were performed according to the Association of GI Physiologists' national guidelines [6].
Corresponding author. E-mail addresses: [email protected] (J.M. Burke), [email protected] (W. Jackson), [email protected] (A.H. Morice).
https://doi.org/10.1016/j.rmed.2018.03.027 Received 5 January 2018; Received in revised form 15 March 2018; Accepted 24 March 2018 Available online 27 March 2018 0954-6111/ © 2018 Elsevier Ltd. All rights reserved.
Respiratory Medicine 138 (2018) 47–49
J.M. Burke et al.
scores.
Table 1 Dynamic pressures.
Inspiratory intra-oesophageal inspiratory pressure (mmHg) Intra-gastric inspiratory pressure (mmHg) Inspiratory GOPG
Respiratory Group
Dyspepsia Group
Mean
Range
Mean
Range
−11.5
−23 to 0
−8.7
−21 to 4
5.8
−3 to 18
5.8
5 to 19
17.3
6 to 35
14.1
1 to 29
4. Discussion Results showed increased inspiratory GOPG due to significantly lower intra-oesophageal pressure on inspiration and reduced oesophageal motility in those with unexplained respiratory symptoms compared to age- and sex-matched controls with suspected gastro-oesophageal reflux disease (GORD). Oesophageal dysmotility is common amongst classic acid-related GORD sufferers and appears more problematic in patients with “respiratory” symptomatology. Thus, the current Chicago Classification Criteria [8] defining abnormality regarding dyspeptic GORD may be insufficiently sensitive to demonstrate an association in respiratory disease. Because of an increased GOPG, physiological amounts of reflux ordinarily considered within normal limits may remain in the oesophagus because of inadequate peristalsis. Poorly cleared refluxate, i.e. as a gaseous mist, could passively traverse to the proximal oesophagus and pharynx into the airways, eliciting respiratory symptoms. Results showed that in the Respiratory Group, enhanced crural diaphragm contraction attempts to act as a barrier to reflux as LOS pressure is generally higher than the inspiratory GOPG. However, since any protection from the crural diaphragm is lost when its contraction is inhibited during transient LOS relaxations [9], those with a significantly higher inspiratory GOPG are particularly at risk of GORD during these events. Our patients demonstrated mild airflow obstruction, and, by extrapolation, decreasing intrathoracic pressure during inspiration may therefore underlie the known association of reflux disease with more severe COPD [10]. Further research in different respiratory conditions characterised by decreased intrathoracic pressure during inspiration is needed. Crural diaphragmatic barrier failure may be an important unrecognised mechanism in respiratory pathophysiology. Improved technology sufficiently sensitive to detect airway reflux in the pharynx and larynx is required to help understand the relationship between oesophageal function and respiratory disease.
Patients took an exaggerated inhalation to ensure the catheter had traversed the lower oesophageal sphincter entirely, confirmed by increased gastric pressure and decreased oesophageal pressure. The following procedures were then performed:
• 10x5mL swallows of water (each 5 mL water bolus separated by > 20 s enabling evaluation of each peristaltic sequence) • multiple rapid swallow of 5x2mL swallows of water (in rapid succession, allowing time to observe a ‘clearance contraction’) • 5 single swallows of bread separated by 20-s intervals Approximately 70% of Respiratory Group patients and all Dyspepsia Group patients underwent 24-h pH-metry immediately following HRM, using either Mk3 single-channel Digitrapper, (Synectics Medical, UK) or Orion II Ambulatory pH Measurement System (MMS, Enschede, the Netherlands). 2.1. Statistical analysis Variables were summarised using mean, median, minimum and maximum. Student's t-tests, chi-squared tests and a Mann-Whitney U test allowed assessment of the impact of the presenting complaint. Statistical analyses were performed using Microsoft Excel for Mac 2011, version 14.5.3. A p-value of < 0.05 was considered statistically significant.
Role of the funding source 3. Results This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
121 patients (44 males, 77 females; age range 18–81 years) were included (Respiratory Group 61, Dyspepsia Group 60). Primary complaints in the Respiratory Group were cough (50) and breathlessness (11); and heartburn (56) and regurgitation (4) in the Dyspepsia Group. In the Respiratory Group, the mean Hull Airways Reflux Questionnaire score [7] was 43 (a normal score is < 14). Mean FEV1 was 2.13L, comprising 71% of predicted. More oesophageal dysmotility was seen in the Respiratory Group. The percentage of intact primary contractions with a 5 mL water bolus was significantly lower (43% vs 58%, p = 0.03) compared with the Dyspepsia Group. The average number of intact peristaltic bread swallows was 3/5 (normal > 4) with no statistical difference between groups. Lower oesophageal sphincter (LOS) augmentation during inspiration was significantly higher in the Respiratory Group (46 mmHg vs 33 mmHg, p < 0.01) and inspiratory intra-oesophageal pressure was significantly lower in the Respiratory Group (p = 0.001). This resulted in a significantly higher inspiratory GOPG (intra-gastric pressure–intra oesophageal pressure) (p = 0.01) (Table 1). In the Respiratory Group, 4% of patients had an inspiratory GOPG higher than the augmentation of the LOS pressure during inspiration, compared to 3% of Dyspepsia Group patients. No difference was found in intra-gastric pressure during the inspiratory phase of tidal breathing (Table 1). Other results showed a higher percentage of acid exposure in the Dyspepsia Group (6.9% versus 4.4%, p = 0.03); there was no statistically significant difference between the groups regarding DeMeester
Competing interests None. Acknowledgements None. References [1] A.H. Morice, E. Millqvist, M.G. Belvisi, K. Bieksiene, S.S. Birring, K.F. Chung, R.W. Dal Negro, P. Dicpinigaitis, A. Kantar, L.P. McGarvery, A. Pacheco, R. Sakalauskas, J.A. Smith, Expert opinion on the cough hypersensitivity syndrome in respiratory medicine, Eur. Respir. J. 2014 (44) (2014) 1132–1148. [2] J.M. FitzGerald, C.J. Allen, M.A. Craven, M.T. Newhouse, Chronic cough and gastroesophageal reflux, CMAJ (Can. Med. Assoc. J.) 140 (1989) 520–524. [3] C. Daum, R. Sweis, E. Kaufman, A. Fuellemann, A. Anggiansah, M. Fried, M. Fox, Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro-esophageal reflux disease, Neuro Gastroenterol. Motil. 23 (2011) 517–e200. [4] Van Hoeij, A.J. Bredenoord, Clinical application of esophageal high-resolution manometry in the diagnosis of esophageal motility disorders, J. Neurogastroenterol. Motil. 22 (1) (2016) 6–13. [5] C. Almansa, J.A. Smith, J. Morris, M.D. Crowell, D. Valdramidou, A.S. Lee, K.R. Devault, L.A.A. Houghton, Weak peristalsis with large breaks in chronic cough: association with poor esophageal clearance, Neuro Gastroenterol. Motil. 27 (2015) 431–442. [6] AGIP Committee, Agreed AGIP Guidelines for Oesophageal High Resolution
48
Respiratory Medicine 138 (2018) 47–49
J.M. Burke et al.
57–65. [9] D.P. Hirsch, G.N.J. Tytgat, G.E.E. Boeckxstaens, Review article: transient lower oesophageal sphincter relaxations - a pharmacological target for gastro-oesophageal reflux disease? Aliment. Pharmacol. Ther. 16 (2002) 17–26. [10] J. Vestbo, W. Anderson, H.O. Coxson, C. Crim, F. Dawber, L. Edwards, G. Hagan, K. Knobil, D.A. Lomas, W. Macness, E.K. Silverman, R. Tal-SingerInvestigators, Evaluation of COPD longitudinally to identify predictive surrogate end-points (ECLIPSE), Eur. Respir. J. 31 (2008) 869–873.
Manometry, (January 2016) http://www.bsg.org.uk/images/stories/docs/ sections/agip/agip_hrm_guidelines_jan2016.pdf. [7] A.H. Morice, S. Faruqi, C.E. Wright, R. Thompson, J.M. Bland, Cough hypersensitivity syndrome: a distinct clinical entity, Lung 189 (2011) 73–79. [8] A.J. Bredenoord, M. Fox, P.J. Kahrilas, J.E. Pandolfino, W. Schwizer, A.J. SmoutInternational High Resolution Manometry Working Group, Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography, Neuro Gastroenterol. Motil. 24 (Suppl 1) (2012)
49
Contents lists available at ScienceDirect
Respiratory Medicine journal homepage: www.elsevier.com/locate/rmed
Short communication
The role of high resolution oesophageal manometry in occult respiratory symptoms
T
Jennifer M. Burkea, Warren Jacksona, Alyn H. Moriceb,∗ a b
GI Physiology, Hull and East Yorkshire Hospitals NHS Trust, Castle Hill Hospital, Hull HU16 5JQ, United Kingdom Hull York Medical School, Castle Hill Hospital, Hull, HU16 5JQ, United Kingdom
A R T I C LE I N FO
A B S T R A C T
Keywords: Cough Manometry Respiratory hypersensitivity
Purpose: Cough Hypersensitivity Syndrome is the urge to cough following minimal stimulation, but its mechanism and method of provocation remain unexplained. 121 patients (44 males, 77 females; age range 18–81 years) were evaluated. Procedures: High resolution manometry was performed on consecutive patients presenting with unexplained respiratory symptoms (Respiratory Group 61). Data were compared with matched controls, i.e. dyspepsia without respiratory symptoms (Dyspepsia Group 60). Main findings: Results showed increased inspiratory gastro-oesophageal pressure gradient due to significantly lower intra-oesophageal pressure on inspiration (p = 0.001), and reduced oesophageal motility in the Respiratory Group. Conclusions: Further research in respiratory conditions characterised by decreased intrathoracic pressure during inspiration is needed.
1. Introduction Many patients present with unexplained respiratory symptoms despite normal chest radiograph and little evidence of airway inflammation. Studies using objective acoustic cough monitors demonstrate “idiopathic” chronic cough sufferers have frequent cough events and are sensitive to various external stimuli. Cough Hypersensitivity Syndrome [1] (vagal afferent hypersensitivity) is the urge to cough following minimal stimulation, but its mechanism and method of provocation remain unexplained. The long-established association of gastro-oesophageal reflux with chronic cough [2] suggests that abnormal oesophageal physiology may underlie some afferent sensations perceived by sufferers, e.g. classic reflux disease, non-acid gaseous reflux, or referred sensations from oesophageal vagal afferents. Abnormal oesophageal motor activity causes several complaints, e.g. dysphagia and chest pain [3], which may be investigated using oesophageal manometry via trans-nasal passage of a pressure-sensitive catheter. High resolution manometry (HRM) is a recent innovation employing closely spaced pressure sensors and continuous real-time recording that has resulted in sensitive, accurate, objective oesophageal physiology analysis [4]. A link between oesophageal dysmotility and chronic cough using oesophageal manometry has been demonstrated [5]. However, the
∗
dynamic physiological change seen during respiration in patients with respiratory disease has not be characterised. HRM allows determination of the pressure profile of thoracic and abdominal cavities during respiratory cycles in real-time and enables calculation of the gastro-oesophageal pressure gradient (GOPG) describing pressure profiles of the thorax and abdomen and their effect on trans-oesophago-gastric pressures. 2. Materials and methods The study was conducted in the Department of GI Physiology, Castle Hill Hospital. All patients provided written informed consent prior to participation. HRM was performed on consecutive patients presenting with unexplained respiratory symptoms (Respiratory Group) using a solid-state catheter (UniTip: UniSensor AG, Switzerland). Data from age- and sex-matched controls were collected from patients undergoing investigation for dyspepsia but without respiratory symptoms (Dyspepsia Group). Patients were instructed to stop proton pump inhibitor medications 7 days pre-investigation and histamine H2-receptor antagonist or drugs affecting gastrointestinal motility 3 days pre-investigation, and to remain nil-by-mouth from 4 h pre-investigation. All tests were performed according to the Association of GI Physiologists' national guidelines [6].
Corresponding author. E-mail addresses: [email protected] (J.M. Burke), [email protected] (W. Jackson), [email protected] (A.H. Morice).
https://doi.org/10.1016/j.rmed.2018.03.027 Received 5 January 2018; Received in revised form 15 March 2018; Accepted 24 March 2018 Available online 27 March 2018 0954-6111/ © 2018 Elsevier Ltd. All rights reserved.
Respiratory Medicine 138 (2018) 47–49
J.M. Burke et al.
scores.
Table 1 Dynamic pressures.
Inspiratory intra-oesophageal inspiratory pressure (mmHg) Intra-gastric inspiratory pressure (mmHg) Inspiratory GOPG
Respiratory Group
Dyspepsia Group
Mean
Range
Mean
Range
−11.5
−23 to 0
−8.7
−21 to 4
5.8
−3 to 18
5.8
5 to 19
17.3
6 to 35
14.1
1 to 29
4. Discussion Results showed increased inspiratory GOPG due to significantly lower intra-oesophageal pressure on inspiration and reduced oesophageal motility in those with unexplained respiratory symptoms compared to age- and sex-matched controls with suspected gastro-oesophageal reflux disease (GORD). Oesophageal dysmotility is common amongst classic acid-related GORD sufferers and appears more problematic in patients with “respiratory” symptomatology. Thus, the current Chicago Classification Criteria [8] defining abnormality regarding dyspeptic GORD may be insufficiently sensitive to demonstrate an association in respiratory disease. Because of an increased GOPG, physiological amounts of reflux ordinarily considered within normal limits may remain in the oesophagus because of inadequate peristalsis. Poorly cleared refluxate, i.e. as a gaseous mist, could passively traverse to the proximal oesophagus and pharynx into the airways, eliciting respiratory symptoms. Results showed that in the Respiratory Group, enhanced crural diaphragm contraction attempts to act as a barrier to reflux as LOS pressure is generally higher than the inspiratory GOPG. However, since any protection from the crural diaphragm is lost when its contraction is inhibited during transient LOS relaxations [9], those with a significantly higher inspiratory GOPG are particularly at risk of GORD during these events. Our patients demonstrated mild airflow obstruction, and, by extrapolation, decreasing intrathoracic pressure during inspiration may therefore underlie the known association of reflux disease with more severe COPD [10]. Further research in different respiratory conditions characterised by decreased intrathoracic pressure during inspiration is needed. Crural diaphragmatic barrier failure may be an important unrecognised mechanism in respiratory pathophysiology. Improved technology sufficiently sensitive to detect airway reflux in the pharynx and larynx is required to help understand the relationship between oesophageal function and respiratory disease.
Patients took an exaggerated inhalation to ensure the catheter had traversed the lower oesophageal sphincter entirely, confirmed by increased gastric pressure and decreased oesophageal pressure. The following procedures were then performed:
• 10x5mL swallows of water (each 5 mL water bolus separated by > 20 s enabling evaluation of each peristaltic sequence) • multiple rapid swallow of 5x2mL swallows of water (in rapid succession, allowing time to observe a ‘clearance contraction’) • 5 single swallows of bread separated by 20-s intervals Approximately 70% of Respiratory Group patients and all Dyspepsia Group patients underwent 24-h pH-metry immediately following HRM, using either Mk3 single-channel Digitrapper, (Synectics Medical, UK) or Orion II Ambulatory pH Measurement System (MMS, Enschede, the Netherlands). 2.1. Statistical analysis Variables were summarised using mean, median, minimum and maximum. Student's t-tests, chi-squared tests and a Mann-Whitney U test allowed assessment of the impact of the presenting complaint. Statistical analyses were performed using Microsoft Excel for Mac 2011, version 14.5.3. A p-value of < 0.05 was considered statistically significant.
Role of the funding source 3. Results This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
121 patients (44 males, 77 females; age range 18–81 years) were included (Respiratory Group 61, Dyspepsia Group 60). Primary complaints in the Respiratory Group were cough (50) and breathlessness (11); and heartburn (56) and regurgitation (4) in the Dyspepsia Group. In the Respiratory Group, the mean Hull Airways Reflux Questionnaire score [7] was 43 (a normal score is < 14). Mean FEV1 was 2.13L, comprising 71% of predicted. More oesophageal dysmotility was seen in the Respiratory Group. The percentage of intact primary contractions with a 5 mL water bolus was significantly lower (43% vs 58%, p = 0.03) compared with the Dyspepsia Group. The average number of intact peristaltic bread swallows was 3/5 (normal > 4) with no statistical difference between groups. Lower oesophageal sphincter (LOS) augmentation during inspiration was significantly higher in the Respiratory Group (46 mmHg vs 33 mmHg, p < 0.01) and inspiratory intra-oesophageal pressure was significantly lower in the Respiratory Group (p = 0.001). This resulted in a significantly higher inspiratory GOPG (intra-gastric pressure–intra oesophageal pressure) (p = 0.01) (Table 1). In the Respiratory Group, 4% of patients had an inspiratory GOPG higher than the augmentation of the LOS pressure during inspiration, compared to 3% of Dyspepsia Group patients. No difference was found in intra-gastric pressure during the inspiratory phase of tidal breathing (Table 1). Other results showed a higher percentage of acid exposure in the Dyspepsia Group (6.9% versus 4.4%, p = 0.03); there was no statistically significant difference between the groups regarding DeMeester
Competing interests None. Acknowledgements None. References [1] A.H. Morice, E. Millqvist, M.G. Belvisi, K. Bieksiene, S.S. Birring, K.F. Chung, R.W. Dal Negro, P. Dicpinigaitis, A. Kantar, L.P. McGarvery, A. Pacheco, R. Sakalauskas, J.A. Smith, Expert opinion on the cough hypersensitivity syndrome in respiratory medicine, Eur. Respir. J. 2014 (44) (2014) 1132–1148. [2] J.M. FitzGerald, C.J. Allen, M.A. Craven, M.T. Newhouse, Chronic cough and gastroesophageal reflux, CMAJ (Can. Med. Assoc. J.) 140 (1989) 520–524. [3] C. Daum, R. Sweis, E. Kaufman, A. Fuellemann, A. Anggiansah, M. Fried, M. Fox, Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro-esophageal reflux disease, Neuro Gastroenterol. Motil. 23 (2011) 517–e200. [4] Van Hoeij, A.J. Bredenoord, Clinical application of esophageal high-resolution manometry in the diagnosis of esophageal motility disorders, J. Neurogastroenterol. Motil. 22 (1) (2016) 6–13. [5] C. Almansa, J.A. Smith, J. Morris, M.D. Crowell, D. Valdramidou, A.S. Lee, K.R. Devault, L.A.A. Houghton, Weak peristalsis with large breaks in chronic cough: association with poor esophageal clearance, Neuro Gastroenterol. Motil. 27 (2015) 431–442. [6] AGIP Committee, Agreed AGIP Guidelines for Oesophageal High Resolution
48
Respiratory Medicine 138 (2018) 47–49
J.M. Burke et al.
57–65. [9] D.P. Hirsch, G.N.J. Tytgat, G.E.E. Boeckxstaens, Review article: transient lower oesophageal sphincter relaxations - a pharmacological target for gastro-oesophageal reflux disease? Aliment. Pharmacol. Ther. 16 (2002) 17–26. [10] J. Vestbo, W. Anderson, H.O. Coxson, C. Crim, F. Dawber, L. Edwards, G. Hagan, K. Knobil, D.A. Lomas, W. Macness, E.K. Silverman, R. Tal-SingerInvestigators, Evaluation of COPD longitudinally to identify predictive surrogate end-points (ECLIPSE), Eur. Respir. J. 31 (2008) 869–873.
Manometry, (January 2016) http://www.bsg.org.uk/images/stories/docs/ sections/agip/agip_hrm_guidelines_jan2016.pdf. [7] A.H. Morice, S. Faruqi, C.E. Wright, R. Thompson, J.M. Bland, Cough hypersensitivity syndrome: a distinct clinical entity, Lung 189 (2011) 73–79. [8] A.J. Bredenoord, M. Fox, P.J. Kahrilas, J.E. Pandolfino, W. Schwizer, A.J. SmoutInternational High Resolution Manometry Working Group, Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography, Neuro Gastroenterol. Motil. 24 (Suppl 1) (2012)
49