The changes in esophageal propulsive characteristics during maturation are not known. Our aim was to define the effects of postnatal maturation on esophageal peristaltic characteristics in preterm human neonates. We tested the hypotheses that: (i) maturation modifies esophageal bolus propulsion characteristics, and (ii) the mechanistic characteristics differ between primary and secondary peristalsis.
Esophageal motility in 10 premature neonates (mean 27.5 weeks gestational age) was evaluated twice at 33.8 weeks (time 1, earlier study) and 39.2 weeks (time 2, later study) mean postmenstrual age. Esophageal manometry waveform characteristics (amplitude and duration, peristaltic velocity, and intrabolus pressure domains) were analyzed during spontaneous primary peristalsis and infusion-induced secondary peristalsis. Repeated-measures and unstructured variance–covariance or compound symmetry matrixes were used for statistical comparison. Values stated as least squares means±s.e.m. or percent.
A total of 200 primary peristalsis and 227 secondary peristalsis events were evaluated. Between time 1 and time 2: (i) proximal esophageal waveform amplitude increased (P < 0.02), with primary peristalsis (38±6 vs. 48±7 mm Hg) and with secondary peristalsis (34±6 vs. 46±5 mm Hg); (ii) distal esophageal waveform amplitude was similar (P = NS), with primary peristalsis (42±4 vs. 43±4 mm Hg) and secondary peristalsis (29±3 vs. 32±4 mm Hg); (iii) proximal esophageal waveform onset to peak duration decreased (P = 0.02) with primary (2.6±0.3 vs. 1.9±0.1 s, P < 0.003) and with secondary peristalsis (2.2±0.2 vs. 1.8±0.1 s); (iv) distal esophageal waveform onset to peak duration decreased (P = 0.01) with primary (2.4±0.3 vs. 1.8±0.1 s) and with secondary peristalsis (1.9±0.2 vs. 1.5±0.1 s); (v) effects of identical stimulus volume on intrabolus pressure were similar (P = NS); however, greater infusion volumes (2 vs. 1 ml) generated higher intrabolus pressure at both time 1 and time 2 (both Ps < 0.05). Between primary and secondary peristalsis (mechanistic variable): (i) no differences were noted at either period, with proximal esophageal waveform amplitudes (P = NS); (ii) differences were noted with distal esophageal waveform amplitudes at each time period (P = 0.0002); (iii) no differences were noted with both esophageal waveforms duration at either period (P = NS); (iv) peristaltic velocity was faster with secondary peristalsis than with primary peristalsis at either period (at earlier study, 7.9±1.4 vs. 2.5±1.4 cm/s and at later study 6.2±1.6 vs. 1.2±1.5 cm/s, both Ps < 0.01).
In preterm neonates, longitudinal maturation modulates the characteristics of primary and secondary peristalsis. Differences in proximal striated muscle and distal smooth muscle activity during peristalsis are evident. Peristaltic velocity is faster with secondary peristalsis. These findings may represent maturation of central and peripheral neuromotor properties of esophageal bolus propulsion in healthy preterm human neonates.
Pulmonary aspiration is the consequence of abnormal entry of fluid, particulate material, or endogenous secretions into the airway. The two main types of aspiration scenarios include anterograde aspiration, which occurs during swallowing, and retrograde aspiration, which can occur during gastroesophageal reflux (GER) events. The important structures that protect against aspiration include the aerodigestive apparatus: pharynx, upper esophageal sphincter, esophageal body, glottis and vocal cords, and airway. In this article we review the neuroanatomy, physiology, and pathophysiology pertinent to glottic reflexes and airway aspiration across the age spectrum from neonates to adults. We also discuss recent advances in our understanding of glottal reflexes and the relationship of these reflexes to developmental anatomy and physiology, the pathophysiology of aspiration, and aerodigestive interactions.
Pharyngoglottal closure reflex; esophagoglottal closure reflex; laryngeal adductor reflex; upper esophageal sphincter; gastroesophageal reflux
Glottal relationships during swallowing dominate the etiology of dysphagia. We investigated the pharyngo-glottal relationships during basal and adaptive swallowing.
Temporal changes in glottal closure kinetics (frequency, response latency, and duration) with spontaneous and adaptive pharyngeal swallows were defined in 12 infants using concurrent pharyngoesophageal manometry and ultrasonography of the glottis.
Frequency, response latency, and duration of glottal closure with spontaneous swallows (n = 53) were 100%, 0.27±0.1 s, and 1±0.22 s, respectively. The glottis adducted earlier (P < 0.0001 vs. upper esophageal sphincter relaxation) within the same respiratory phase as swallow (P = 0.03). With pharyngeal provocations (n = 41), glottal adduction (pharyngo-glottal closure reflex (PGCR)) was noted first and then again with pharyngeal reflexive swallow (PRS). The frequency, response latency, and duration of glottal closure with PGCR were 100%, 0.56±0.13 s, and 0.52±0.1 s, respectively. Response latency to PRS was 3.24±0.33 s; the glottis adducted 97% within 0.36±0.08 s in the same respiratory phase (P = 0.03), and remained adducted for 3.08±0.71 s. Glottal adduction was the quickest with spontaneous swallow (P = 0.04 vs. PGCR), and the duration was the longest during PRS (P < 0.005 vs. PGCR or spontaneous swallow).
Glottal adduction during basal or adaptive swallowing reflexes occurs in either respiratory phase, thus ensuring airway protection against pre-deglutitive or deglutitive aspiration. The independent existence and magnitude (duration of adduction) of PGCR suggests a hypervigilant state of the glottis in preventing aspiration during swallowing or during high gastroesophageal reflux events. Investigation of pharyngeal–glottal relationships with the use of noninvasive methods may be more acceptable across the age spectrum.
Asymptomatic subjects volunteering for research studies are generally stratified as healthy based on a questionnaire, medical interviewing, and physical examination. The aim of this study was to evaluate the prevalence of upper GI abnormalities in healthy asymptomatic volunteers using unsedated transnasal esophago-gastro-duodenoscopy (T-EGD) with an ultrathin endoscope as an additional screening tool.
This is a prospective study from one academic medical center with extensive experience in T-EGD. Consecutive 150 subjects volunteering for research studies were initially screened by using a gastroesophageal reflux disease (GERD) questionnaire, interviewing, and examination. Based on these, they were stratified as healthy asymptomatic volunteers or with GERD. Unsedated T-EGD was then performed by a faculty who was blinded to the results of the initial assessment.
On initial assessment using GERD questionnaire, medical interviewing, and physical examination, of the total 150 consecutive research volunteers, 83 (33±16, 46 females, 37 males) subjects were healthy asymptomatic volunteers and 67 (36±15, 35 females, 32 males) had symptoms of GERD. On T-EGD, gastrointestinal pathology was found in 15 of 83 (18%) healthy asymptomatic volunteers as compared to 24 of 67 (36%) stratified as having GERD (p <0.01). The esophageal abnormalities found in healthy asymptomatic volunteers were esophagitis (13.3%), Barrett’s esophagus (2.4%), hiatus hernia (2.4%) and gastritis (2.4%).
A small but significant number of asymptomatic subjects have abnormal upper GI findings. Hence, transnasal unsedated endoscopy can be considered as a screening tool to stratify subjects as healthy especially when considering them for research studies.
Transnasal endoscopy; unsedated endoscopy; ultrathin endoscope; gastroesophageal reflux disease; Barretts esophagus
Background & Aims
Studies of the pressure response of the upper esophageal sphincter (UES) to simulated or spontaneous gastroesophageal reflux have shown conflicting results. These discrepancies could result from uncontrolled influence of variables such as posture, volume, and velocity of distension. We characterized in humans the effects of these variables on UES pressure response to esophageal distension.
We studied 12 healthy volunteers (average 27±5 years old, 6 male) using concurrent esophageal infusion and high-resolution manometry to determine UES, lower esophageal sphincter, and intraesophageal pressure values. Reflux events were simulated by distal esophageal injections of room-temperature air and water (5, 10, 20, and 50 ml) in individuals in 3 positions (upright, supine and semi-supine). Frequencies of various UES responses were compared using χ2 analysis. Multinomial logistical regression analysis was used to identify factors that determine the UES response.
UES contraction and relaxation were the overriding responses to esophageal water and air distension, respectively, in a volume-dependent fashion (P<.001). Water-induced UES contraction and air-induced UES relaxation were the predominant responses among individuals in supine and upright positions, respectively (P<.001). The prevalence of their respective predominant response significantly decreased in the opposite position. Proximal esophageal dp/dt significantly and independently differentiated the UES response to infusion with water or air.
The UES response to esophageal distension is affected by combined effects of posture (spatial orientation of the esophagus), physical properties, and volume of refluxate, as well as the magnitude and rate of increase in intraesophageal pressure. The UES response to esophageal distension can be predicted using a model that incorporates these factors.
esophagus; stomach; airway; GERD
Irritable bowel syndrome (IBS) is a common health issue that is characterized by abdominal pain, abnormal bowel movements and altered visceral perception. The complexity and variability in symptoms pose serious challenges in treating IBS. Current therapy for IBS is primarily focused on reducing the abdominal pain, thereby improving the quality of life to a significant extent. Although the use of fiber rich diet is widely recommended in treating IBS, some studies have questioned its use. Intracolonic butyrate, a short chain fatty acid, is primarily produced by the fermentation of dietary fibers in the colon. In the existing literature there are conflicting reports about the function of butyrate. In rats it is known to induce visceral hypersensitivity without altered pathology, whereas in humans it has been reported to reduce visceral pain. Understanding the molecular mechanisms responsible for this contrasting effect of butyrate is important before recommending fiber rich diet to IBS patients.
Inflammatory bowel syndrome; colonic hypersensitivity; short chain fatty acids; sodium butyrate
BACKGROUND & AIMS
Direct evidence to support the airway protective function of aerodigestive reflexes triggered by pharyngeal stimulation was previously demonstrated by abolishing these reflexes by topical pharyngeal anesthesia in normal subjects. Studies have also shown that these reflexes deteriorate in cigarette smokers. Aim of this study was to determine the influence of defective pharyngeal aerodigestive reflexes on airway protection in cigarette smokers.
Pharyngoglottal Closure reflex; PGCR, Pharyngo-UES Contractile reflex; PUCR, and Reflexive Pharyngeal Swallow; RPS were studied in 15 healthy non-smokers (24.2 ± 3.3 SD y, 7 males) and 15 healthy chronic smokers (27.3 ± 8.1, 7 males). To elicit these reflexes and to evaluate aspiration, colored water was perfused into the hypopharynx at the rate of 1 mL/min. Maximum volume of water that can safely dwell in the hypopharynx before spilling into the larynx (Hypopharyngeal Safe Volume; HPSV) and the threshold volume to elicit PGCR, PUCR, and RPS were determined in smokers and results compared with non-smokers.
At baseline, RPS was elicited in all non-smokers (100%) and in only 3 of 15 smokers (20%; P < .001). None of the non-smokers showed evidence of laryngeal spillage of water, whereas 12 of 15 smokers with absent RPS had laryngeal spillage. Pharyngeal anesthesia abolished RPS reflex in all non-smokers resulting in laryngeal spillage. The HPSV was 0.61 ± 0.06 mL and 0.76 ± 0.06 mL in non-smokers and smokers respectively (P = .1).
Deteriorated reflexive pharyngeal swallow in chronic cigarette smokers predispose them to risks of aspiration and similarly, abolishing this reflex in non-smokers also results in laryngeal spillage. These observations directly demonstrate the airway protective function of RPS.
Cigarette Smoking; Airway Protection; Reflux; UES
Background & Aims
The cingulate cortex (CC) has been reported to be involved in processing pain of esophageal origin. However, little is known about molecular changes and cortical activation that arise from early-life, esophageal acid reflux. Excitatory neurotransmission via activation of the N-methyl-D-aspartate (NMDA) receptor and its interaction with post-synaptic density protein-95 (PSD-95) at the synapse appears to mediate neuronal development and plasticity. We investigated the effect of early-life esophageal acid exposure on NMDA receptor subunits and PSD-95 expression in the developing CC.
We assessed NMDA receptor subunits and PSD-95 protein expression in rostral CC (rCC) tissues of rats exposed to esophageal acid or saline (control), either during post-natal days 7–14 (P7–P14) and/or acutely, at adult stage (P60), using immunoblot and immunoprecipitation analyses.
Compared with controls, acid exposure from P7 to P14 significantly increased expression of NR1, NR2A, and PSD-95, measured 6 weeks after exposure. However, acute exposure at P60 caused a transient increase in expression of NMDA receptor subunits. These molecular changes were more robust in animals exposed to acid neonatally and rechallenged, acutely, at P60. Esophageal acid exposure induced calcium calmodulin kinase II-mediated phosphorylation of the subunit NR2B at Ser1303.
Esophageal acid exposure during early stages of life has long-term effects, because of phosphorylation of the NMDA receptor and overexpression in the rCC. This molecular alteration in the rCC might mediate sensitization of patients with acid-induced esophageal disorders.
brain; developmental neuroscience; pain processing; CamKII
The objective of this study was to determine if neonatal cystitis alters colonic sensitivity later in life and to investigate the role of peripheral mechanisms.
Neonatal rats received intravesical zymosan, normal saline, or anesthesia only for three consecutive days (postnatal days 14th–16th). The estrous cycle phase was determined prior to recording the visceromotor response (VMR) to colorectal distension (CRD) in adult rats. Eosinophils and mast cells were examined from colon and bladder tissue. CRD or urinary bladder distension (UBD)-sensitive pelvic nerve afferents (PNAs) were identified and their responses to distension were examined. The relative expression of N-methyl-D-aspartic acid (NMDA) NR1 subunit in the L6-S1 spinal cord was examined using Western blot.
The VMR to CRD (≥10mmHg) in the neonatal zymosan group was significantly higher than control in both the diestrus, estrus phase and in all phases combined. There was no difference in the total number of eosinophils, mast cells or number of degranulated mast cells between groups. The spontaneous firing of UBD, but not CRD-sensitive PNAs from the zymosan rats was significantly higher than the control. However, the mechanosensitive properties of PNAs to CRD or UBD were no different between groups (p > 0.05). The expression of spinal NR1 subunit was significantly higher in zymosan-treated rats compared to saline treated rats (p <0.05).
Neonatal cystitis results in colonic hypersensitivity in adult rats without changing tissue histology or the mechanosensitive properties of CRD-sensitive PNAs. Neonatal cystitis does results in overexpression of spinal NR1 subunit in adult rats.
cystitis; visceral hyperalgesia; neonatal; viscero-visceral convergence
Esophageal mechanorecptors, i.e. muscular slowly adapting tension receptors and mucosal rapidly adapting touch receptors, mediate different sets of reflexes. The aim of this study was to determine the medullary vagal nuclei involved in the reflex responses to activation of these receptors. Thirty-three cats were anesthetized with alpha-chloralose and the esophagus was stimulated by slow balloon or rapid air distension. The physiological effects of the stimuli (N=4) were identified by recording responses from the pharyngeal, laryngeal, and hyoid muscles, esophagus, and the lower esophageal sphincter (LES). The effects on the medullary vagal nuclei of the stimuli: slow distension (N=10), rapid distension (N=9), and in control animals (N=10) were identified using the immunohistochemical analysis of c-fos. The experimental groups were stimulated 3 times per minute for 3 hours. After the experiment, the brains were removed and processed for c-fos immunoreactivity or thioinin. We found that slow balloon distension activated the esophago-UES contractile reflex and esophago LES relaxation response, and rapid air injection activated the belch and its component reflexes. Slow balloon distension activated the NTSce, NTSdl, NTSvl, DMNc, DMNr and NAr; and rapid air injection primarily activated AP, NTScd, NTSim, NTSis, NTSdm, NTSvl, NAc and NAr. We concluded that different sets of medullary vagal nuclei mediate different reflexes of the esophagus activated from different sets of mechanoreceptors. The NTScd is the primary NTS subnucleus mediating reflexes from the mucosal rapidly adapting touch receptors, and the NTSce is the primary NTS subnucleus mediating reflexes from the muscular slowly adapting tension receptors. The AP may be involved in mediation of belching.
nucleus tractus solitarius; dorsal motor nucleus; nucleus ambiguus; esophageal mechanoreceptors; pharynx; larynx; belching
The objective of this study was to determine the brain stem nuclei and physiological responses activated by esophageal acidification. The effects of perfusion of the cervical (ESOc), or thoracic (ESOt) esophagus with PBS or HCl on c-fos immunoreactivity of the brain stem or on physiological variables, and the effects of vagotomy were examined in anesthetized cats. We found that acidification of the ESOc increased the number of c-fos positive neurons in the area postrema (AP), vestibular nucleus (VN), parabrachial nucleus (PBN), nucleus ambiguus (NA), dorsal motor nucleus (DMN), and all subnuclei of the nucleus tractus solitarius (NTS), but one. Acidification of the ESOt activated neurons in the central (CE), caudal (CD), dorsomedial (DM), dorsolateral (DL), ventromedial (VM) subnuclei of NTS, and the DMN. Vagotomy blocked all c-fos responses to acid perfusion of the whole esophagus (ESOw). Perfusion of the ESOc or ESOt with PBS activated secondary peristalsis (2P), but had no effect on blood pressure, heart rate, or respiratory rate. Perfusion of the ESOc, but not ESOt, with HCL activated pharyngeal swallowing (PS), profuse salivation, or physiological correlates of emesis. Vagotomy blocked all physiological effects of ESOw perfusion. We conclude that acidification of the ESOc and ESOt activate different sets of pontomedullary nuclei and different physiological responses. The NTSce, NTScom, NTSdm, and DMN are associated with activation of 2P, the NTSim and NTSis, are associated with activation of PS, and the AP, VN, and PBN are associated with activation of emesis and perhaps nausea. All responses to esophageal fluid perfusion or acidification are mediated by the vagus nerves.
medulla; pons; esophagus; hydrochloric acid; c-fos; cat
Kinematic analysis, also commonly referred to as biomechanical analysis, of the swallow is used to measure movement of oropharyngeal structures over time. Two laboratory directors who have used kinematic analysis in their research collaborated to determine the feasibility of establishing agreement between two separate laboratories on measures of structural movements of the swallow. This report describes the process that was followed toward the goal of establishing measurement agreement. Under the direction of the laboratory directors, one research technician from each laboratory participated in a process that included initial meetings, training sessions, and pre- and post-training evaluation of reproducibility.
Because agreement on initial measures of structural movement demonstrated weak correlation on some measures, the research technicians trained together for approximately 6 hours. After training, statistical analyses indicated that (a) most Pearson correlations for measures of structural movements were greater than 0.80 and were highly statistically significant; (b) most percentages of absolute deviation were under 25%; and (c) most concordance coefficients were above .70. These statistics indicate that the two laboratories were able to increase their level of agreement in measuring selected structural movements of the swallow after a brief amount of training.
Factors affecting measurement agreement include image quality, establishment of rules for measuring, and the opportunity for regular discussions among research assistants and investigators from both laboratories.
Background and Aims
Several types of gastric surgeries have been associated with early satiety, dyspepsia and food intolerances. We aimed to examine alterations in gastric vagal afferents following gastric surgery-fundus ligation.
Six week old, male Sprague-Dawley rats underwent chronic ligation (CL) of the gastric fundus. Sham rats underwent surgery, but without ligation. Another group of rats underwent acute ligation (AL) immediately prior to experiments. Animals were allowed to grow to age 3–4 months. Food intake and weights were recorded post-operatively. Gastric compliance and gastric wall thickness was measured at baseline and during gastric distension (GD). Extracellular recordings were made to examine response characteristics of vagal afferent fibers to GD and to map the stomach receptive field (RF). The morphological structures of afferent terminals in the stomach were examined with retrograde tracings from the nodose ganglion.
The CL group consumed significantly less food and weighed less than control. The mean compliance of CL group was significantly less than control, but higher than the AL. The spontaneous firing and responses to GD of afferent fibers from the CL rats were significantly higher than AL rats. There was a marked expansion of the gastric RF in the CL rats with significant reorganization and regeneration of intramuscular array (IMA) terminals. There was no difference in total wall or muscle thickness among the groups.
CL results in aberrant remodeling of IMAs with expansion of the gastric RF and alters the mechanotransduction properties of vagal afferent fibers. These changes could contribute to altered sensitivity following gastric surgery.
Vagal Afferents; Stomach; Satiety; Fundus ligation; Gastric surgery
Seven institutions participated in this small clinical trial that included 19 patients who exhibited oropharyngeal dysphagia on videofluorography (VFG) involving the upper esophageal sphincter (UES) and who had a 3-month history of aspiration. All patients were randomized to either traditional swallowing therapy or the Shaker exercise for 6 weeks. Each patient received a modified barium swallow pre- and post-therapy, including two swallows each of 3 ml and 5 ml liquid barium and 3 ml barium pudding. Each videofluorographic study was sent to a central laboratory and digitized in order to measure hyoid and larynx movement as well as UES opening. Fourteen patients received both pre-and post-therapy VFG studies. There was significantly less aspiration post-therapy in patients in the Shaker group. Residue in the various oral and pharyngeal locations did not differ between the groups. With traditional therapy, there were several significant increases from pre- to post-therapy, including superior laryngeal movement and superior hyoid movement on 3-ml pudding swallows and anterior laryngeal movement on 3-ml liquid boluses, indicating significant improvement in swallowing physiology. After both types of therapy there is a significant increase in UES opening width on 3-ml paste swallows.
Dysphagia; Shaker exercise; Upper esophageal sphincter; Deglutition; Deglutition disorders
Earlier studies of the effect of 6 weeks of the Shaker Exercise have shown significant increase in UES opening and anterior excursion of larynx and hyoid during swallowing in patients with upper esophageal sphincter (UES) dysfunction, resulting in elimination of aspiration and resumption of oral intake. This effect is attributed to strengthening of the suprahyoid muscles, as evidenced by comparison of electromyographic changes in muscle fatigue before and after completion of the exercise regime. The effect of this exercise on thyrohyoid muscle shortening is unknown. Therefore the aim of this study was to determine the effect of the exercise on thyrohyoid muscle shortening. We studied 11 dysphagic patients with UES dysfunction. Six were randomized to traditional swallowing therapy and five to the Shaker Exercise. Videofluoroscopy was used to measure deglutitive thyrohyoid shortening before and after completion of assigned therapy regimen. Maximum thyrohyoid muscle shortening occurred at close temporal proximity to the time of maximal thyroid cartilage excursion. The percent change in thyrohyoid distance from initiation of deglutition to maximal anterior/superior hyoid excursion showed no statistically significant difference between the two groups prior to either therapy (p = 0.54). In contrast, after completion of therapy, the percent change in thyrohyoid distance in the Shaker Exercise group was significantly greater compared to the traditional therapy (p = 0.034). The Shaker Exercise augments the thyrohyoid muscle shortening in addition to strengthening the suprahyoid muscles. The combination of increased thyrohyoid shortening and suprahyoid strengthening contributes to the Shaker Exercise outcome of deglutitive UES opening augmentation.
Deglutition; UES dysfunction; Thyrohyoid muscle; Shaker exercise; Dysphagia; Videofluoroscopy; Deglutition disorders
To test the hypothesis that the sensory-motor characteristics of the reflexes evoked upon stimulation with air and water infusions differ, we studied the effect of pharyngeal stimulation on the pharyngeal-upper esophageal sphincter (UES) interactions in healthy neonates
Pharyngo-UES-esophageal manometry was recorded in 10 neonates at 39 ± 4 wk postmenstrual age. Pharyngeal infusions (n=155) of air (0.1–2.0 ml) and sterile water (0.1–0.5 ml) were given. Two types of reflexes were recognized: Pharyngeal reflexive swallowing (PRS) and pharyngo-UES-contractile reflex (PUCR). Frequency occurrence, distribution of reflexes, threshold volume, response time, and stimulus-response relationship were evaluated.
The reflex response rate for air was 30% and was 76% for water (P<0.001). The frequency occurrence of PRS was greater than PUCR with air and water (P<0.05), although the stimulation thresholds and response latency were similar. Graded volumes of water but not air resulted in an increased frequency of PRS (P<0.01).
PRS is the most frequent response, and characteristics of the reflexes are distinct between air vs. water stimuli. These methods have implications for the evaluation of swallowing in infants.
Pharyngeal reflexive swallowing; upper esophageal sphincter; pharyngo-UES-contractile reflex; neonates
Rationale: Recent studies have reported acidification of exhaled breath condensate (EBC) in inflammatory lung diseases. This phenomenon, designated “acidopnea,” has been attributed to airway inflammation.
Objectives: To determine whether salivary acids and bases can influence EBC pH in chronic obstructive pulmonary disease (COPD).
Methods: Measurements were made of pH, electrolytes, and volatile bases and acids in saliva and EBC equilibrated with air in 10 healthy subjects and 10 patients.
Results: The average EBC pH in COPD was reduced (normal, 7.24 ± 0.24 SEM; range, 6.11–8.34; COPD, 6.67 ± 0.18; range, 5.74–7.64; p = 0.079). EBCs were well buffered by NH4+/NH3 and CO2/HCO3− in all but four patients, who had NH4+ concentrations under 60 μmol/L, and acetate concentrations that approached or exceeded those of NH4+. Saliva contained high concentrations of acetate (∼ 6,000 μmol/L) and NH4+ (∼ 12,000 μmol/L). EBC acetate increased and EBC NH4+ decreased when salivary pH was low, consistent with a salivary source for these volatile constituents. Nonvolatile acids did not play a significant role in determining pH of condensates because of extreme dilution of respiratory droplets by water vapor (∼ 1:12,000). Transfer of both acetic acid and NH3 from the saliva to the EBC was in the gas phase rather than droplets.
Conclusions: EBC acidification in COPD can be affected by the balance of volatile salivary acids and bases, suggesting that EBC pH may not be a reliable marker of airway acidification. Salivary acidification may play an important role in acidopnea.
acetate; ammonium; bicarbonate; buffer; exhaled breath condensate