Circulating KL-6, a biomarker of lung injury, in obstructive sleep apnoea.

In obstructive sleep apnoea (OSA), oxidative stress contributes to endothelial dysfunction in the peripheral circulation. In the lung, oxidative stress can lead to alveolar injury. The present authors hypothesised that patients with OSA would have biomarker evidence of increased alveolar wall permeability. Sleep characteristics, brachial artery flow-mediated dilation and plasma KL-6 levels were observed in 11 otherwise healthy patients with OSA and 10 controls. Median (interquartile range) plasma KL-6 levels were higher in patients with OSA compared with controls: 317 (232-506) U.mL(-1) versus 226 (179-257) U.mL(-1), respectively. Higher plasma KL-6 levels were associated with greater time spent asleep with an oxyhaemoglobin saturation <90%, lower nadir saturation, more frequent desaturation of >4% during sleep and lower brachial artery flow-mediated dilation. Adjustment for nadir saturation or flow-mediated dilation attenuated the association between plasma KL-6 levels and OSA. Circulating KL-6 levels are elevated in some patients with obstructive sleep apnoea, possibly reflecting increased alveolar wall permeability.

Respiratory and electrocortical responses to acoustic stimulation.

Although sleep-related obstructive apnea is most often associated with transient arousal, the impact of this arousal on respiratory control remains unclear. We employed binaural tone bursts (.5 second duration) to elicit repetitive transient arousals from sleep during polygraphic recordings in 5 adult volunteers. By this method, we elicited repetitive transient arousals with a mean duration of approximately 10 seconds from all stages of sleep. With respect to the 3 pre-stimulus breaths, acoustic stimulation was associated with increased tidal volume and decreased inspiratory duration for at least 4 breaths. These respiratory responses to acoustic stimulation were not significantly influenced by either presence of transient arousal from sleep or the sleep state from which arousal occurred. We conclude that transient electro-cortical state changes may be repeatedly evoked from all sleep stages by transient acoustic stimulation in normal sleepers. This sensory stimulation represents a significant respiratory stimulus even when generalized arousal from sleep does not occur.

Respiratory and arousal responses to acoustic stimulation.

STUDY OBJECTIVES: Although sleep-related obstructive apnea is most often associated with transient arousal, the impact of this arousal on respiratory control remains unclear. We tested the hypotheses that acoustic arousing stimulation can generate a significant respiratory response during sleep in healthy subjects and that the magnitude or timing of this response is affected by the presence of electrocortical arousal or inhaled carbon dioxide. DESIGN: We employed binaural tone bursts (0.5-s duration, 4-KHz center frequency, 99-s interstimulus interval) to elicit repetitive transient arousals from sleep during nocturnal polysomnographic recordings beginning at 10 PM and ending at 6 AM. PARTICIPANTS: Recordings were conducted in five healthy adult volunteers aged 24 to 37 years. INTERVENTIONS: Inspired gas was alternated between room air and 3% to 7% CO2 (titrated to yield an approximate 50% increase in minute ventilation) at 1-h intervals. MEASUREMENTS AND RESULTS: Each 30-s epoch was scored for sleep/wake stage according to standard criteria. Only results obtained during nonrapid eye movement sleep are presented herein. Tone-evoked arousals were detected by computer analysis as increased EEG frequency occurring within 3 s of acoustic stimulation. For each tone, respiratory parameters for each of three prestimulus and four poststimulus breaths were normalized to the overall mean of prestimulus breaths measured during room air breathing for each subject. Tone bursts elicited repetitive transient arousals with a mean duration of approximately 10 s from all stages of sleep. With respect to the three prestimulus breaths, acoustic stimulation was associated with increased tidal volume and decreased inspiratory duration for at least four breaths. These respiratory responses to acoustic stimulation were not significantly influenced by either presence of transient arousal from sleep or inspired gas. CONCLUSIONS: We conclude that transient EEG arousal may be repeatedly evoked from nonrapid eye movement sleep by transient acoustic stimulation in normal sleepers. This sensory stimulation is associated with augmented ventilation, a response that is not significantly affected by inspired hypercapnia or the presence of generalized EEG arousal.

Acoustically induced cortical arousal increases phasic pharyngeal muscle and diaphragmatic EMG in NREM sleep.

Six healthy subjects (3 males, 3 females) were studied to assess phasic inspiratory responses of upper airway (UA) and diaphragm muscles to electrocortical arousal independent of other potential respiratory stimulation. Transient electroencephalographic (EEG) arousal (abrupt EEG frequency shift > or = 3 s without awakening) was induced during supine stage 2 non-rapid-eye-movement (NREM) sleep with binaural tone bursts (0.5 s, 4 kHz, 25-95 dB). Electromyograms (EMG) of levator veli palatini (EMGlvp) and genioglossus (EMGgg) were obtained with intramuscular electrodes, and EMG of diaphragm (EMGdi) was obtained with esophageal electrodes. EMG signals were processed as moving time-averaged inspiratory activity over 100-ms windows. For each arousal, each of five consecutive postarousal breaths (R1-R5) was scored for peak inspiratory phasic EMG and normalized as percent averaged EMG of the three prearousal breaths for all muscles. After arousal, EMGlvp was increased for R1-R5 and EMGgg and EMGdi were increased for R1-R4. The increase in EMGlvp was greater than those of EMGgg and EMGdi for all response breaths. There was a significant increase in EMGlvp in all subjects, and EMGgg and EMGdi were significantly increased in three and two subjects, respectively. These data indicate that isolated transient electrocortical arousal is generally associated with phasic inspiratory recruitment of UA and diaphragm muscles in normal humans during NREM sleep; velopharyngeal muscle recruitment appears to be more consistent and of greater magnitude and duration than that of oropharyngeal muscle or diaphragm. We speculate that transient arousal from sleep may contribute to UA patency independent of chemical and mechanical respiratory stimuli.

Breathing route influences upper airway muscle activity in awake normal adults.

Both nasal obstruction and nasal anesthesia result in disordered breathing during sleep in humans, and bypassing the nasal route during tidal breathing in experimental animals produces decreased electromyographic activity of upper airway (UA) dilating muscles. To investigate UA responses to breathing route in normal awake humans, we studied eight healthy males (ages 21-38 yr) during successive trials of voluntary nose breathing (N), voluntary mouth breathing (M), and mouth breathing with nose occluded (MO). We measured genioglossus electromyographic activity (EMGgg) with perorally inserted bipolar electrodes, alae nasi (EMGan) and diaphragm EMG activity (EMGdi) with surface electrodes, and minute ventilation (VE) with a pneumotachograph. Mean phasic inspiratory EMG activity of both UA muscles was significantly greater during N than during M or MO, even when a 2.5-cmH2O.l-1.s inspiratory resistance was added to MO (P less than 0.01). In contrast, neither EMGdi nor VE was consistently affected by breathing route. EMGgg during N was significantly decreased after selective topical nasal anesthesia (P less than 0.002); a decrease in EMGan did not achieve statistical significance. These data suggest that peak UA dilating muscle activity may be modulated by superficial receptors in the nasal mucosa sensitive to airflow.

Effect of induced transient arousal on obstructive apnea duration.

Six untreated male patients (age 19-55 yr) with obstructive sleep apnea underwent nocturnal polysomnography with acoustic stimulation to determine the effect of transient arousal on obstructive apneas during sleep. Binaural tone bursts (25-95 dB) were delivered in late expiration during the second obstructive apnea of a cycle consisting of four consecutive apneas. For the group, stimulated apneas were significantly shorter (P < 0.05, Fisher's protected least significant difference test) than were the unstimulated apneas when transient electrocortical arousal was elicited in both non-rapid-eye-movement (non-REM) sleep [mean 17 +/- 7 (SD) vs. 26 +/- 9, 23 +/- 10, and 26 +/- 12 s for 2nd vs. 1st, 3rd, and 4th apnea, respectively, of each cycle] and REM sleep (mean 19 +/- 10 vs. 35 +/- 15, 45 +/- 18, and 39 +/- 20 s). Without electrocortical arousal, the stimulated apnea was significantly shortened in non-REM (23 +/- 9 vs. 25 +/- 7, 24 +/- 8, and 26 +/- 8 s) but not in REM (32 +/- 16 vs. 37 +/- 12, 32 +/- 15, and 30 +/- 16 s). Tones delivered relatively early and late in the apnea were equally likely to be associated with resolution of the apnea. The nadir of arterial oxygen saturation of hemoglobin was inversely proportional to apnea length, with higher saturation nadirs associated with the stimulated apneas. These data indicate that transient arousal, induced by nonrespiratory stimulation, influences the resolution of obstructive apneas during sleep.

Effect of inspired air temperature on genioglossus activity during nose breathing in awake humans.

Experimental data suggest the presence of sensory receptors specific to the nasopharynx that may reflexly influence respiratory activity. To investigate the effects of inspired air temperature on upper airway dilator muscle activity during nose breathing, we compared phasic genioglossus electromyograms (EMGgg) in eight normal awake adults breathing cold dry or warm humidified air through the nose. EMGgg was measured with peroral bipolar electrodes during successive trials of cold air (less than or equal to 15 degrees C) and warm air (greater than or equal to 34 degrees C) nasal breathing and quantified for each condition as percent activity at baseline (room temperature). In four of the subjects, the protocol was repeated after topical nasal anesthesia. For all eight subjects, mean EMGgg was greater during cold air breathing than during baseline (P less than 0.005) or warm air breathing (P less than 0.01); mean EMGgg during warm air breathing was not significantly changed from baseline. Nasal anesthesia significantly decreased the mean EMGgg response to cold air breathing. Nasal airway inspiratory resistance, measured by posterior rhinomanometry in six subjects under similar conditions, was no different for cold or warm air nose breathing [cold 1.4 +/- 0.7 vs. warm 1.4 +/- 1.1 (SD) cmH2O.l-1.s at 0.4 l/s flow]. These data suggest the presence of superficially located nasal cold receptors that may reflexly influence upper airway dilating muscle activity independently of pressure changes in awake normal humans.

Hypoxemia alone does not explain blood pressure elevations after obstructive apneas.

In patients with obstructive sleep apnea (OSA), substantial elevations of systemic blood pressure (BP) and depressions of oxyhemoglobin saturation (SaO2) accompany apnea termination. The causes of the BP elevations, which contribute significantly to nocturnal hypertension in OSA, have not been defined precisely. To assess the relative contribution of arterial hypoxemia, we observed mean arterial pressure (MAP) changes following obstructive apneas in 11 OSA patients during non-rapid-eye-movement (NREM) sleep and then under three experimental conditions: 1) apnea with O2 supplementation; 2) hypoxemia (SaO2 80%) without apnea; and 3) arousal from sleep with neither hypoxemia nor apnea. We found that apneas recorded during O2 supplementation (SaO2 nadir 93.6% +/- 2.4; mean +/- SD) in six subjects were associated with equivalent postapneic MAP elevations compared with unsupplemented apneas (SaO2 nadir 79-82%): 18.8 +/- 7.1 vs. 21.3 +/- 9.2 mmHg (mean change MAP +/- SD); in the absence of respiratory and sleep disruption in eight subjects, hypoxemia was not associated with the BP elevations observed following apneas: -5.4 +/- 19 vs. 19.1 +/- 7.8 mmHg (P less than 0.01); and in five subjects, auditory arousal alone was associated with MAP elevation similar to that observed following apneas: 24.0 +/- 8.1 vs. 22.0 +/- 6.9 mmHg. We conclude that in NREM sleep postapneic BP elevations are not primarily attributable to arterial hypoxemia. Other factors associated with apnea termination, including arousal from sleep, reinflation of the lungs, and changes of intrathoracic pressure, may be responsible for these elevations.

Phenylephrine-induced hypertension acutely decreases genioglossus EMG activity in awake humans.

To investigate the relationship between systemic blood pressure (BP) and upper airway dilator muscle activity, we recorded genioglossus electromyograms (EMGgg) during pharmacologically induced acute increases in BP in five healthy humans (ages 27-40 yr). EMGgg was measured with perorally placed fine-wire electrodes; phasic EMGgg was expressed as percentage of baseline activity. Subjects were studied supine, awake, and breathing through a face mask with their mouths taped. End-tidal PCO2 was monitored with a mass spectrometer; minute ventilation was measured with a pneumotachograph. Digital BP was monitored continuously with the Penaz method (Finapres, Ohmeda). Mean arterial pressure (MAP) at baseline was 89 +/- 6 (SD) mmHg. Phenylephrine was infused until MAP reached 15-25 mmHg above baseline (107 +/- 7 mmHg). Recording was continued until MAP returned to baseline (90 +/- 7 mmHg). Elevated BP was associated with a significantly decreased phasic EMGgg (P less than 0.005). With return of MAP to baseline, phasic EMGgg returned toward normal (P less than 0.01). Minute ventilation and end-tidal PCO2 did not differ among conditions. Genioglossus activity appears to be influenced by acute changes in systemic BP. We speculate that BP elevations accompanying obstructive apneas during sleep may decrease upper airway tone and facilitate subsequent apneas.

Upper airway anesthesia delays arousal from airway occlusion induced during human NREM sleep.

Six healthy subjects (5 males and 1 female, 26-40 yr old) were studied during non-rapid-eye-movement (NREM) sleep to assess the role of upper airway (UA) afferents in the arousal response to induced airway occlusion. Subjects wore an airtight face mask attached to a low-resistance one-way valve. A valve in the inspiratory circuit allowed instantaneous inspiratory airway occlusion and release; the expiratory circuit remained unoccluded at all times. Each subject was studied during two nights. On one night, occlusions were created during stable stage 2 NREM sleep before and after application of 4% lidocaine to the oral and nasal mucosa. On the other night, the protocol was duplicated with saline ("sham anesthesia") rather than lidocaine. The order of nights was randomized. Occlusions were sustained until electroencephalographic arousal. Three to 12 occlusions were performed in each subject for each of the four parts of the protocol (pre- and post-lidocaine, pre- and post-saline). The auditory threshold for arousal (1,500-Hz tone beginning at 30 dB) was also tested before and after UA lidocaine. For the group, arousal time after UA anesthesia was prolonged compared with preanesthesia arousal time (P less than 0.001); arousal time after sham anesthesia did not significantly increase from before sham anesthesia (P = 0.9). The increase in arousal time with UA anesthesia was greater than the increase with sham anesthesia (P less than 0.001). The auditory arousal threshold did not increase after UA anesthesia. Inspiratory mask pressure, arterial O2 saturation of hemoglobin, and end-tidal PCO2 during occlusions were similar before and after UA anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemo- and baroresponses differ in African-Americans and Caucasians in sleep.

To determine sleep effects on baro- and ventilatory responses to transient chemo- and barostimulation in African-Americans and Caucasians, 26 nonobese normotensive young subjects (13 African-Americans and 13 Caucasians) were studied awake and in non-rapid-eye movement (NREM) and rapid-eye-movement sleep during induced transient hypoxemia (N2), hypertension (phenylephrine, PE), and concomitant hypoxemia and hypertension (N2 + PE). Arterial blood pressure was recorded by plethysmographic volume clamp, minute ventilation by pneumotachograph, and arterial O2 saturation by pulse oximeter. For all subjects, chronotropic baroresponse (Deltapulse interval/Deltasystolic blood pressure, where Delta is change) increased with NREM sleep (P = 0.007). Baroresponse slope was greater in Caucasians than in African-Americans (ANOVA, P = 0.02). Hypoxemic ventilatory response (Deltaminute ventilation/Deltaarterial O2 saturation) was greater in African-Americans than in Caucasians in NREM sleep (P = 0.01), as was hypoxemic attenuation of baroresponse (N2 + PE, P = 0.03). These data suggest sleep-related differences in arterial chemo- and baroreceptor responses in normal young African-Americans and Caucasians, which may have implications concerning development of systemic hypertension.

An assessment of pulmonary function testing and ventilatory kinematics by optoelectronic plethysmography.

New advances in computer processing and imaging have allowed the development of innovative techniques to assess lung function. A promising methodology is optoelectronic plethysmography (OEP). OEP evaluates ventilatory kinematics through the use of infrared imaging. Markers are placed, and images read on the chest, back and abdomen of subjects. Currently, this system is used mainly in research settings, but in the future may have broad applicability to patient populations such as very young children, patients with neuromuscular disease and patients who cannot be tested with classical spirometry testing. This paper presents the history and development of OEP, along with a summary of the OEP methodology, a discussion of research findings and results to date, as well as application and limitations.

Patient-ventilator asynchrony with nocturnal noninvasive ventilation in ALS.

BACKGROUND: American Academy of Neurology (AAN) practice parameters for amyotrophic lateral sclerosis (ALS) include noninvasive positive pressure ventilation (NIV) for a forced vital capacity (FVC) ≤50%predicted. Despite the limited ability of NIV systems to deliver adequate ventilation synchronous with patient demand, nocturnal patient-ventilator asynchrony has not been systematically studied in patients with ALS prescribed such NIV. METHODS: Twenty-three consecutively recruited patients with ALS reporting consistent use of nocturnal NIV (nNIV) prescribed for FVC ≤50% or orthopnea underwent home nocturnal polysomnography (PSG) on their current nNIV regimen (all used bilevel positive airway pressure). PSG recorded airflow, NIV pressures, thoracic and abdominal respiratory effort, and O(2) saturation by pulse oximetry (SpO(2)). Patient-ventilator asynchrony was calculated as an asynchrony index (AI), the number of episodes of asynchrony per hour of nocturnal recording time (RT). RESULTS: Nineteen patients had an adequate PSG. Their mean AI was 69 ± 46 SD (range 15-146/hour). Mean asynchrony time as a percent of RT was 17% ± 19%. Mean nadir SpO(2) was 85% ± 7%. In multiple regression analysis, no demographic, functional severity (including FVC and ALS Revised Functional Rating Scale), or NIV (including pressure levels and duration of NIV prescription) variables were significantly predictive of degree of patient-ventilator asynchrony. CONCLUSIONS: These findings document frequent nocturnal patient-ventilator asynchrony in patients with ALS consistently using nNIV prescribed as per current AAN practice parameters, and suggest that use of nNIV per these parameters is unlikely to provide patients with ALS optimal nocturnal ventilatory support.

Racial and ethnic disparities in survival in lung transplant candidates with idiopathic pulmonary fibrosis.

Minority patients have worse outcomes than nonminority patients in a variety of pulmonary diseases. We aimed to compare the survival of Black and Hispanic patients to that of others with idiopathic pulmonary fibrosis (IPF). We performed a retrospective cohort study of patients with IPF who were evaluated for lung transplantation at our center. Kaplan-Meier survival curves and Cox proportional hazards models were used to compare survival between groups. Black and Hispanic patients had spirometry, lung volumes and diffusion capacity that were similar to others, but had worse exercise capacity. Minority patients had a significantly increased risk of death compared to others independent of transplantation status (hazard ratio = 3.3, 95% CI 1.2-8.9, p = 0.02). Differences in exercise capacity, pulmonary hemodynamics and socioeconomic factors appeared to account for some of the differences in survival. Black and Hispanic patients with IPF had an increased risk of death following referral for lung transplantation. This finding may be due to differences in disease progression and/or differences in access to medical care among minority patients. Future studies should confirm our findings in a larger cohort. The elimination of racial and ethnic disparities in outcome should be a priority for clinicians and researchers in this field.

Phasic electromyographic activity of the genioglossus increases in normals during slow-wave sleep.

Obstructive apneas occur infrequently during Stage 3-4 NREM sleep (SWS), even in patients with severe obstructive sleep apnea. To investigate whether upper airway (UA) dilator muscle activity preferentially increases during SWS as a partial explanation for this phenomenon, we measured phasic electromyogram activity of the genioglossus muscle (EMGgg) during continuous Stage 2 NREM sleep and SWS in 5 healthy males. Subjects were studied supine during a complete cycle of nocturnal NREM sleep after partial sleep deprivation. EMGgg was measured with perorally inserted bipolar electrodes, and quantified as peak phasic inspiratory activity during all continuous epochs of NREM sleep. We found EMGgg to be increased during SWS relative to stage 2 sleep by a mean of 58% among all subjects (P = 0.02); neither end-tidal PCO2 nor inspired minute ventilation varied between these sleep stages. Upper airway resistance, measured in 3 of the subjects on a separate study night, was not different between SWS and Stage 2 sleep. We speculate that the increase in phasic EMGgg during SWS in our normal subjects may reflect a mechanism whereby UA patency tends to be preserved during this stage.

Systemic blood pressure elevation after airway occlusion during NREM sleep.

Increases in arterial pressure follow obstructive sleep apneas even in the absence of hypoxemia. These blood pressure (BP) elevations could be caused by arousal from sleep, resumption of ventilation, or abrupt changes of intrathoracic pressure (ITP). To better define the relative contributions of each of these factors to the BP elevations, we designed two protocols employing six normal subjects isolating the effects of arousal from those of ventilation and ITP. BP (Penaz method), sleep stage, air flow, and esophageal pressure (Pes) were monitored. Episodically, a stopcock was closed, occluding the inspiratory circuit. In Experiment 1, data were recorded on tape. Occlusions were initiated during Stage 2 NREM sleep and released coincident with arousal. Subjects were than awakened and instructed to trace the displayed, taped Pes profile creating occlusions of identical duration to those recorded during sleep. In five subjects, the mean BP elevation (preocclusion to peak) associated with occlusion release upon arousal was 19.0 +/- 5.1 mm Hg, whereas the analogous rise for matched awake occlusions was 5.4 +/- 4.8 mm Hg (p = 0.027). In Experiment 2, occlusion release was delayed 6 to 12 s after arousal. In five subjects, these occlusions were associated with BP elevations that peaked coincident with arousal, not with resumption of ventilation (mean increase, 18.0 +/- 10.4 mm Hg). We conclude that under the conditions of these experiments, BP elevations after airway occlusion during sleep are attributable more to arousal than to resumption of ventilation.

Palatal muscle electromyogram activity in obstructive sleep apnea.

Eight subjects (5 men, 3 women, ages 27 to 55) with obstructive sleep apnea syndrome (OSAS) were studied to quantify and compare electromyographic (EMG) activity of levator veli palatini (LVP) and palatoglossus (PG), two velopharyngeal muscles, and genioglossus (GG) during obstructive apnea cycles in non-rapid eye movement (NREM) sleep. EMG activity of three successive preapneic breaths, first and last apneic efforts, and three successive postapneic breaths was quantified for each muscle as peak phasic inspiratory EMG normalized as percent activity of the last preapneic breath. In all subjects, apnea onset coincided with simultaneous inspiratory EMG nadir of all three muscles (LVP = 63 +/- 40%, PG = 74 +/- 53%. GG = 83 +/- 48%. mean +/- SD activity of last preapneic breath). Apnea resolution did not occur until inspiratory EMG of all three muscles simultaneously reached maximal activity, at levels significantly greater than preapneic activity as well as activity of the last preapneic effort (LVP = 215 +/- 205%, PG = 227 +/- 240+, GG = 235 +/- 202%, mean +/- SD activity of last preapneic breath, p < 0.05, Fisher's partial least-squares difference [PLSD] test for each muscle). The presence or absence of electroencephalographic arousal at apnea resolution did not influence these patterns of EMG activity. Inspiratory recruitment of velopharyngeal as well as oropharyngeal muscles appears to be associated with upper airway patency during sleep in patients with OSAS.

Predictors of the new onset of wheezing among middle-aged and older men. The Normative Aging Study.

Characteristics potentially associated with the development of wheeze symptoms were examined in a prospective cohort study of 624 middle-aged and older men who initially denied any history of wheezing or asthma. Initial evaluation included spirometry, methacholine challenge testing, allergy skin testing with common aeroallergens, serum total IgE concentration, blood leukocyte count, blood eosinophil count, and postural heart rate change (standing minus supine). The presence or absence of wheezing symptoms at follow-up 3 yr later was assessed by questionnaire. Multiple logistic regression was used to examine initial characteristics as predictors of subsequent wheezing. Current smoking was the strongest independent predictor of the new onset of wheezing (adjusted OR, 14.3; 95% confidence interval (CI), 3.9 to 52.3). The risk of developing new wheezing also increased with age (adjusted OR, 1.6; 95% CI, 0.9 to 2.9 comparing individual subjects 10 yr apart) and postural heart rate change at the initial examination (adjusted OR, 1.8; 95% CI, 1.1 to 3.0 comparing individual subjects differing by 10 beats/min). A significant association between greater methacholine airway responsiveness (PD20FEV1 < or = 16.8 mumol versus PD20FEV1 > 16.8 mumol) and the subsequent development of wheezing was observed among nonsmokers (adjusted OR, 5.2; 95% CI, 2.0 to 13.6) but not among current smokers. Other baseline variables were not independently related to the risk of developing wheezing symptoms. These data suggest that current smoking, age, nonspecific airway responsiveness, and altered autonomic function are independently related to the risk of developing wheezing symptoms in middle-aged and older men.

Oral mucosal stimulation modulates intensity of breathlessness induced in normal subjects.

Patients with chronic obstructive pulmonary disease (COPD) often report an increase in breathlessness when they breathe through a mouthpiece. We hypothesized that stimulation of receptors in the oral mucosa modulates the sensation of breathlessness. We studied 10 normal naive volunteers in whom breathlessness was induced by having them breathe for 4 min with an inspiratory resistive load (18 cm H2O/L/s) while breathing was stimulated by CO2 inhalation (end-tidal PCO2 maintained at 55 mm Hg). Initially, subjects breathed with a tight-fitting face mask and inspiratory flow was displayed on a storage oscilloscope. In subsequent trials, the subjects were asked to match this trace, which controlled ventilation and the pattern of breathing. Subjects performed eight trials, four with the tight-fitting mask only (M) and four with a mouthpiece and the mask (MM). M and MM were alternated; the initial condition was chosen at random. Following each of the trials, subjects rated the intensity of their breathlessness by choosing a number from a modified Borg scale. On the average, subjects were more breathless while breathing with the mask and mouthpiece than with the mask alone (mean ratings of breathlessness 6.6 +/- 1.1 and 5.6 +/- 1.8 units, p less than 0.01). Six subjects repeated the protocol on 2 additional days: 1 day with inhalation of warm (34 degrees C), humidified air and 1 day after topical application of 4% lidocaine to the oral mucosa. Both these interventions abolished the differences in breathlessness between mask and mouthpiece and mask alone. We conclude that afferent information from oral mucosal stimulation influences the intensity of breathlessness.