Asthmatics are known to have a high prevalence of GER and GER is known to trigger asthma [19
]. Initial episodes of reflux may induce acute esophageal injury resulting in lowered LES pressure, delayed acid clearing and more reflux [20
]. As reflux continues, aspiration may follow causing the first asthmatic episode. Sensitization of the pulmonary tree may cause the airways to become reactive to other stimuli resulting in bronchospasm through a vagal mechanism [1
Factors that may promote GER in asthma include, physical characteristics of the individuals (age, gender and body mass index), disruption of LES mechanism (related to asthma severity and presence of hiatal hernia), reduced LES pressure and increased esophageal acid contact times (effect of asthma medication) [21
] and autonomic dysregulation [7
]. Increasing age [22
], the male sex [23
] and increased body mass index [24
] predispose towards increased GER. The population of asthmatics and controls in the present study was comparable in these characteristics; hence any confounding influence of these factors would have been minimal.
In this study, the asthmatics demonstrated a high use of oral medication (Table ). Regression analysis revealed that the use of asthma medication (overall and oral versus inhaled) did not seem to influence the difference in oesophageal function parameters between asthmatics and controls.
The asthmatics were recruited from medical clinics. In their history on recruitment it was clarified that these were patients who had been having asthma for a considerable period of time and even childhood asthma. They did not have long term symptoms of gastro-oesophageal reflux disease. The classification regarding presence or absence of GERD symptoms was based on a questionnaire with a recall period of 4 weeks. However, there is no possibility of excluding ‘silent gastro-oesphageal reflux’. So there is a possibility that some may have had GERD as their primary pathology.
The present study revealed that 10 of 27 asthmatics (37%) had evidence of esophagitis. The average prevalence of erosive esophagitis in asthmatics reported in a recent systematic review was also 37% [19
]. Most studies report that the severity of esophagitis has a positive correlation with the degree of asthma severity [8
]. The fact that our population of asthmatics had less severe asthma may have contributed to the low prevalence of esophagitis in them. We did not perform UGI endoscopy on the controls. We considered it unethical to do so, when they scored negative for GERD on a previously validated GERD screening questionnaire [12
] which was shown to have good correlation with reflux status as determined by 24 hour pH monitoring.
Twenty two (73.3%) asthmatics had abnormally high acid exposure of the distal esophagus and 20 (66.7%) of the proximal esophagus. Individual pH monitoring parameters were significantly higher (both proximal and distal) in asthmatics compared to controls. The acid exposure values were higher in asthmatics that scored positive for GERD symptoms compared to those with lower values. Other studies in similar settings to ours (cross-sectional surveys in secondary care units sampling consecutive asthmatics) have reported high acid exposure values ranging from 14.8-81.8%. A systematic review of these studies revealed a pooled sample-size weighted average prevalence of 50.9% [19
]. Of the studies describing dual-sensor pH monitoring, abnormally high proximal acid exposure was reported as 46% in 56 asthmatics [27
] and abnormally high distal acid exposure was reported in 78% of 54 asthmatics [28
]. Gustafsson et al.
reported pathological reflux in 50% of asthmatic children in the proximal esophagus and in 16% in the proximal esophagus [29
]. DeMeester et al. reported that 50% of patients with chronic respiratory symptoms with proximal reflux had esophageal dysmotility [30
The anti-reflux barriers that protect against reflux are the gastresophageal junction (LES function), esophageal body motor function and acid clearance and the UES [31
Asthmatics have been shown to have lower LES pressures [1
]. The present study showed that only 2 asthmatics had LES hypotension and that the LES pressure value did not differ between asthmatics (with or without reflux) and controls significantly. A previous study reported similar findings [33
]. Two studies involving patients with suspected laryngeal reflux have also revealed the same results [34
]. Stationary pull-through method was employed according to the available facilities in our unit. The gold standard for measurement of LES pressure is use of a Dent Sleeve [36
]. However this technique was not available to us at the time of the study. Hence interpretation of data regarding LES pressure is done with caution. Failure to demonstrate a relationship between LES pressure and LES events with the severity of GERD could be attributed to the inferior technique employed. This is a severe limitation of the study. With proper and better techniques, a repeated study would enable a more thorough and accurate assessment of actual LES events during reflux episodes in asthmatics.
Another disadvantage in our methodology and hence a major limitation in our study is that stationary pull-through manometry does not record LES pressure continuously, hence fails to capture sphincter relaxations and intermittent reflux episodes.
The UES parameters in our study were similar in asthmatics and controls. Ours was not an ideal setup to measure UES pressure. This is a major limitation in our study, hence data on UES measurement is not discussed here.
Esophageal peristalsis [38
] and amplitude of peristaltic contractions [39
] play a major role in esophageal acid clearance following GER episodes. Esophageal motility disturbances could contribute to or result from pathological GER. We compared esophageal motility parameters between asthmatics and controls, between asthmatics who had positive GERD symptom scores with those with negative scores and each of these groups separately with controls. When individual esophageal motility parameters were compared [40
], asthmatics differed from controls only by a significantly lower proportion of peristaltic waves. Asthmatics with higher GERD symptom scores had lower peristaltic activity.
In the present study the asthmatics demonstrated low peristaltic activity but otherwise normal esophageal manometry. Hence, it is likely that these asthmatics do not have an intrinsic esophageal motility abnormality leading to GER. Therefore, rather than vagal hypofunction contributing to the esophageal dysmotility, as is currently accepted, it may be vagal-hyperreactivity that leads to esophageal dysmotility. Our results lead us to speculate whether this is due to vagal hyperreactivity-induced increased secretion. Whether the reduced esophageal motility is secondary to increased GER due to vagal hyperreactivity and resulting reduced acid clearance warrants further study.
When esophageal parameters were grouped according to motility patterns, asthmatics were found to have a higher frequency of abnormal motility patterns. The most common motility pattern among asthmatics was ineffective esophageal motility (IEM) 44.4% of 29 asthmatics). IEM has previously been described as the commonest motility pattern in subjects with reflux-associated respiratory symptoms [3
]. Campo et al. described esophageal dysmotility in 68% of asthmatics with reflux symptoms [2
]. Abnormal esophageal motility has been described in patients with chronic cough [41
]. Patti et al. found non-specific esophageal motility abnormalities in patients with pulmonary aspiration and GERD [42
]. A study from Taiwan reported that out of 56 clinically stable asthmatics, 23 had IEM and 12 had non-specific motility disorder [43
]. There are however some studies contradicting this relationship, and these have reported that IEM has no association with GERD or extra-esophageal GERD [44
IEM is associated with increased acid clearance times in the distal esophagus [46
]. Esophageal acid clearance time is the amount of time necessary to return the esophagus to a neutral pH following an acidic reflux event [34
]. It is one of the important mechanisms that prevent GERD [29
]. Initially there is rapid clearance of the refluxate by gravity and primary or secondary peristalsis, followed by slow neutralization of the acid by the swallowed saliva. It is generally assumed that the latter is constant among subjects [34
]; hence acid clearance is considered a good measure of esophageal function. Peristaltic dysfunction could delay esophageal acid clearance. This would keep acid in the esophagus for a longer duration and promote acid reaching a higher level [45
Vagal hypofunction is known to contribute to esophageal hypomotility [5
]. Studies have reported that in GERD patients, there is no correlation between autonomic function state and esophageal motility or esophageal acid exposure [5
]. In the present study, asthmatics did not have evidence of vagal hypofunction, but rather showed a vagal hyper-reactivity. We could not demonstrate correlation between a derived vagal function score and esophageal motility, increased acid exposure or the presence of esophagitis.
The current Montreal consensus on GERD states that though frequency and severity of symptoms have been shown to have a moderate correlation with severity of endoscopic findings in several studies, symptoms cannot accurately predict endoscopic findings of an individual patient [48
]. In this context there is difficulty in diagnosing pathological GER by either symptoms or investigation alone. The present study too failed to demonstrate an association of reflux status with upper GI endoscopy findings, symptom severity or esophageal motility pattern among asthmatics.
From the present study findings it seems that hyper-vagal response and prolonged esophageal acid exposure are the more likely reasons for the esophageal peristaltic dysfunction. Increased vagal stimulation increases rate and amount of acid secretion and could therefore augment the damaging effects of GER in these subjects [49
]. Acid also inhibits the vagal low threshold mechano-sensors in the esophagus that are responsible for the reflex regulation of esophageal motor functions. This inhibition could result in reduced esophageal clearance or reduced LOS function, thereby favouring further GER [50