[Clinical application of portable spirometry in asthma].

OBJECTIVE: To investigate the clinical applications of portable spirometry in asthma. METHODS: Twenty patients with asthma were recruited from Peking Union Medical College Hospital. Flow-volume loop, simultaneous asthma symptoms, and mood were monitored three times a day for consecutive 14 days. RESULTS: In patients with a normal daytime spirometry, marked decline of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were observed at night and/or in the early morning. A within subject correlation analysis between FEV1, PEF, and asthma symptoms showed that the correlation between symptoms and airway obstruction was found only in seven out of twenty patients (35%). Four patients (20%) reported many symptoms with nearly normal portable spirometry. Accordingly, their symptoms were not correlated with FEV1 and PEF. This group of patients was defined as over-perceivers. On the contrary, another two patients (10%) did not report any symptoms while obvious airways obstruction was recorded by a portable spirometry. These patients were defined as under-perceivers. CONCLUSIONS: Dynamic monitoring of flow-volume loop with a portable spirometry is more accurate than routine lung function test in assessment of asthma severity. In addition, combined with simultaneous monitoring of symptoms, it would be of particularly helpful in identifying two specific types of asthma patients, e.g. over-perceivers and under-perceivers.

[Medically unexplained dyspnea in children: a review of 34 cases].

OBJECTIVE: Medically unexplained dyspnea is common in adult and accounts for 14% patients complaining of dyspnea. Its occurrence in children is seldom recognized. In the present paper, 34 children with medically unexplained dyspnea (age 10 to 18 years) seen in Peking Union Medical College Hospital from 1996 to 2002 are reported. METHODS: The diagnosis of medically unexplained dyspnea was clinical: it was based on the presence of dyspnea and other complaints which cannot be explained by an organic disease. The patients answered Nijmegen questionnaire and state and trait anxiety (STAI), and performed hyperventilation provocation test. Twenty sessions of breathing therapy were applied and 13 out of 34 children were followed up after the therapy. RESULTS: Among the children, 75% started to have symptoms at the age of 13 to 16 years, though the age of first episode could be as early as 8 years. In most of the cases, the course was chronic clinically. In addition to marked dyspnea, their clinical profile included symptoms of hyperventilation i.e. blurred vision, dizziness, tingling, stiff fingers or arm. The symptoms of anxiety were less frequent in children and accordingly the level of anxiety evaluated by means of STAI was lower in children compared to adult patients. The precipitating psychological factors appeared to be related to middle school competition. Pressure from exams, reprimand from stern and unsympathetic teachers coupled with high parental expectation could be emotionally damaging to psychologically susceptible children. Thirteen patients were followed up after 2-3 months of breathing therapy with emphasis on abdominal breathing and slowing down of expiration. After therapy, the sum score of the Nijmegen Questionnaire was markedly decreased. Dyspnea and symptoms of hyperventilation were improved. The level of anxiety was minimally modified. CONCLUSION: The cases illustrated the need for careful diagnostic evaluation and treatment because of the high rate of chronicity of the disorder.

Medically unexplained dyspnea: psychophysiological characteristics and role of breathing therapy.

BACKGROUND: Medically unexplained dyspnea occurs commonly in medical settings and remains poorly understood. This study was conducted to investigate the psychophysiological characteristics of medically unexplained dyspnea and the efficacy of breathing retraining for these patients. METHODS: A group of patients with medically unexplained dyspnea were compared to patients with a variety of organic lung diseases and healthy subjects. In another group of patients, the influence of breathing therapy on complaints, anxiety, and breath-holding was evaluated for an average of 1.5 years. RESULTS: Patients with medically unexplained dyspnea reported more intense dyspnea than patients with a variety of organic lung diseases. Additionally, they were anxious and presented a broad range of symptoms in daily life and under challenge, for instance voluntary hyperventilation. More than one third of them qualified for panic disorder. They had shorter breath-holding time at rest, less increase in breath-holding time and higher chances of showing a "paradoxical" decrease of breath-holding time after hyperventilation. A combination of PaO2, forced expiratory volume in one second (FEV1), and anxiety measures distinguished them from organic dyspnea. Breathing retraining profoundly improved their symptoms and decreased the level of state and trait anxiety. Moreover, they better tolerated the voluntary hyperventilation and the symptoms induced were also markedly decreased after therapy. Breath-holding time was prolonged and PetCO2 in a representative group of patients increased. CONCLUSIONS: Patients with medically unexplained dyspnea appear to have the feature of a "psychosomatic" patient: an anxious patient with a wide variety of symptoms of different organ systems that do not have an organic basis. They can be distinguished from organic dyspnea using a small set of physiological and psychological measures. Breathing retraining turns out to be an effective therapy for those "difficult to treat patients".

Critical conditions for hyperventilation responses. The role of autonomic response propositions during emotional imagery.

Hyperventilation is often conceived of as part of a fight-or-flight response, triggered by situations with high arousal and negative valence. However, a previous study using emotional imagery found hyperventilation responses during imagery of high-arousal scenes regardless of their valence. Those imagery scripts contained suggestions of autonomic activity, which may have partly induced or enhanced the hyperventilatory responsivity. The present study used four emotional scripts--depicting relaxing, fearful, depressive, and pleasant situations--without suggestions of autonomic or respiratory responses. After each imagery trial, participants rated their imagery for valence, arousal, and vividness. Fractional end-tidal carbon dioxide (FetCO2), inspiratory and expiratory time, tidal volume, and pulse rate were measured in a non-intrusive way. Results showed significant FetCO2 drops during the fearful and pleasant scripts. However, this effect was much smaller compared to imagery scripts with autonomic response propositions. Participants imagining scripts without autonomic response information found it harder to imagine the scripts vividly and reported lower levels of subjective arousal.

Hyperventilation beyond fight/flight: respiratory responses during emotional imagery.

Hyperventilation (HV) is often considered part of a defense response, implying an unpleasant emotion (negative valence) combined with a strong action tendency (high arousal). In this study, we investigated the importance of arousal and valence as triggers for HV responses. Forty women imagined eight different scripts varying along the arousal and valence dimensions. The scripts depicted relaxation, fear, depressive, action, and desire situations. After each trial, the imagery was rated for valence, arousal, and vividness. FetCO2, inspiratory and expiratory time, tidal volume, and pulse rate were measured in a nonintrusive way. FetCO2 drops and decreases in inspiratory and expiratory time occurred in all but the depressive and the relaxation scripts, suggesting that a defense conceptualization of hyperventilation is not always appropriate.

Acquiring symptoms in response to odors: a learning perspective on multiple chemical sensitivity.

In this chapter, a learning account is discussed as a potential explanation for the symptoms in multiple chemical sensitivity. Clinical evidence is scarce and anecdotal. A laboratory model provides more convincing results. After a few breathing trials containing CO2-enriched air as an unconditioned stimulus in a compound with harmless odor substances as conditioned stimuli, subjective symptoms are elicited and respiratory behavior is altered by the odors only. Also, mental images can become conditioned stimuli to trigger subjective symptoms. The learning effects cannot be explained by a response bias or by conditioned arousal, and they appear to involve basic associative processes that do not overlap with aware cognition of the relationship between the odors and the CO2 inhalation. Learned symptoms generalize to new odors and they can be eliminated in a Pavlovian extinction procedure. In accordance with clinical findings, neurotic subjects and psychiatric cases are more vulnerable to learning subjective symptoms in response to odors. Consistent with a learning account, cognitive-behavioral treatment techniques appear to produce beneficial results in clinical cases. Several criticisms and unresolved questions regarding the potential role of learning mechanisms are discussed.

Maximal inspiratory flow rates in patients with COPD.

OBJECTIVES: To assess the relevance of maximal inspiratory flow rates (MIFR) in the assessment of airway obstruction in COPD. SETTING: University teaching hospital. PARTICIPANTS: Ten consecutive COPD patients (O group; mean [+/- SD] age, 58.5+/-8.3 years) and 10 matched healthy subjects (H group; mean age, 58.7+/-7.4 years). MEASUREMENTS: Lung volumes, FEV(1), specific airway conductance, single-breath lung diffusing capacity, MIFR, and maximal expiratory flow rates (MEFR). RESULTS: Mean FEV(1)/vital capacity (VC) was 74.7% in the H group and 37.8% in the O group (p<0.001). Total lung capacity was higher (p<0.001) in the O group compared with the H group. Lung diffusing capacity was less than half in the O group compared with the H group (p<0.001). MEFR at all lung volumes were lower in the O group (p<0.001). MIFR were comparable in the two groups, except at 25% inspired VC, where MIFR were lower in the O group (p< 0.05). CONCLUSION: MIFR are less sensitive than MEFR to detect airway obstruction in COPD patients. Yet, the interest of MIFR lay in the possibility to separate intrinsic from extrinsic involvement of airways. A normal MIFR associated with low MEFR, as in the present study, suggests either a lack of parenchymal support, an increased collapsibility of the airways, or a reversible peripheral airway narrowing. A fixed, generalized airway narrowing would be associated with a decrease of both MIFR and MEFR.

Hyperventilation and attention: effects of hypocapnia on performance in a stroop task.

This study aimed to investigate the effect of hypocapnia on attentional performance. Hyperventilation, producing hypocapnia, is associated with physiological changes in the brain and with subjective symptoms of dizziness, concentration problems and derealization. In this study (N=42), we examined cognitive performance on a Stroop-like task, following either 3 min of hypocapnic or normocapnic overbreathing. Both overbreathing trials were run on separate days, each preceded by a baseline trial with the same task during normal breathing. More and other symptoms were reported after hypocapnia compared to normocapnia. Also, more errors were made and progressively slower reaction times (RT's) were observed during recovery from hypocapnia. These performance deficits were only found in participants characterized by apneas. The number of symptoms did not correlate with RT's or errors. The pattern of data suggested that hypoxia, as a result of apneas during recovery from hypocapnia, caused the cognitive performance deficit.

Mechanisms for isolated volume response to a bronchodilator in patients with COPD.

We hypothesized that an altered effect of lung inflation on airway caliber may in part explain the isolated volume response to bronchodilators, i.e., an increase of forced vital capacity (FVC) without change in 1-s forced expiratory volume (FEV(1)). Small-airway caliber was measured by high-resolution computed tomography at functional residual capacity and total lung capacity in five chronic obstructive pulmonary disease patients with an isolated increase of FVC (FVC responders) and five with an increase of both FVC and FEV(1) (FVC-FEV(1) responders) after inhalation of salbutamol. In FVC-FEV(1) responders, the airway diameter increased with the cube root of increase in lung volume but was unchanged or even decreased in four of five FVC responders. FVC responders had more severe emphysema, as inferred from lung function and imaging studies, than FVC-FEV(1) responders. We speculate that longitudinal traction or space competition (Verbeken EK, Cauberghs M, and Van de Woestijne KP, J Appl Physiol 81: 2468-2480, 1996) are possible underlying mechanisms. We conclude that the isolated volume response to bronchodilators is associated with severe emphysema and likely results from an altered effect of lung inflation on airway caliber.

Psychosomatic symptoms and breathing pattern.

OBJECTIVE: Study of the links between breathing pattern, negative affectivity, and psychosomatic complaints at rest and following hyperventilation. METHODS: In 819 patients with anxiety and somatoform disorders and 159 healthy subjects, self-reported symptoms, breathing pattern, and end-tidal CO(2) concentration (FetCO(2)) were recorded during rest and following a hyperventilation provocation test (HVPT). The relationship between disorder category, symptoms, age, and score of STAI-trait (as a measure of negative affectivity) on the one hand, and breathing pattern on the other was investigated, separately in men and women. RESULTS: Anxiety disorders, and to a lesser extent, somatoform disorders, were characterized by breathing instability (progressive decrease of FetCO(2) at rest during mouthpiece breathing, delayed recovery of FetCO(2) following HVPT), the mean values of respiratory frequency, and FetCO(2) being modulated by STAI-trait. After grouping the symptoms into independent factors, links were observed between symptoms and breathing pattern, independently from the presence of an anxiety or somatoform disorder. CONCLUSION: Some symptom factors appeared to be related to a lower FetCO(2) during hyperventilation, others likely directly influenced the breathing pattern. Among those, mainly respiratory symptoms were accompanied by a reduction of FetCO(2) at rest, with slower recovery of FetCO(2) following HVPT. The latter was observed also in the presence of marked anxiety. In contrast, subjects complaining of dizziness, fainting, and paresthesias in daily life presented higher values of FetCO(2) following HVPT, probably due to a voluntary braking of ventilation during HVPT.

Influence of upper airway shunt on total respiratory impedance in infants.

When input impedance is determined by means of the forced oscillation technique, part of the oscillatory flow measured at the mouth is lost in the motion of the upper airway wall acting as a shunt. This is avoided by applying the oscillations around the subject's head (head generator) rather than at the mouth (conventional technique). In seven wheezing infants, we compared both techniques to estimate the importance of the upper airway wall shunt impedance (Zuaw) for the interpretation of the conventional technique results. Computation of Zuaw required, in addition, estimation of nasal impedance values, which were drawn from previous measurements (K. N. Desager, M. Willemen, H. P. Van Bever, W. De Backer, and P. A. Vermeire. Pediatr. Pulmonol. 11: 1-7, 1991). Upper airway resistance and reactance at 12 Hz ranged from 40 to 120 and from 0 to -150 hPa. l(-1). s, respectively. Varying nasal impedance within the range observed in infants did not result in major changes in the estimates of Zuaw or lung impedance (ZL), the impedance of the respiratory system in parallel with Zuaw. The conventional technique underestimated ZL, depending on the value of Zuaw. The head generator technique slightly overestimated ZL, probably because the pressure gradient across the upper airway was not completely suppressed. Because of the need to enclose the head in a box (which is not required with the conventional technique), the head generator technique is difficult to perform in infants.

Acquisition and extinction of somatic symptoms in response to odours: a Pavlovian paradigm relevant to multiple chemical sensitivity.

OBJECTIVES: Multiple chemical sensitivity is a poorly understood syndrome in which various symptoms are triggered by chemically unrelated, but often odorous substances, at doses below those known to be harmful. This study focuses on the process of pavlovian acquisition and extinction of somatic symptoms triggered by odours. METHODS: Diluted ammonia and butyric acid were odorous conditioned stimuli (CS). The unconditioned stimulus (US) was 7.4% CO2 enriched air. One odour (CS+) was presented together with the US for 2 minutes (CS+ trial), and the other odour (CS-) was presented with air (CS-trial). Three CS+ and three CS-exposures were run in a semi-randomised order; this as the acquisition (conditioning) phase. To test the effect of the conditioning, each subject then had one CS+ only--that is, CS+ without CO2--and one CS- test exposure. Next, half the subjects (n = 32) received five additional CS+ only exposures (extinction group), while the other half received five exposures to breathing air (wait group). Finally, all subjects got one CS+ only test exposure to test the effect of the extinction. Ventilatory responses were measured during and somatic symptoms after each exposure. RESULTS: More symptoms were reported upon exposure to CS+ only than to CS-odours, regardless of the odour type. Altered respiratory rate was only found when ammonia was CS+. Five extinction trials were sufficient to reduce the level of acquired symptoms. CONCLUSION: Subjects can acquire somatic symptoms and altered respiratory behaviour in response to harmless, but odorous chemical substances, if these odours have been associated with a physiological challenge that originally had caused these symptoms. The conditioned symptoms can subsequently be reduced in an extinction procedure. The study further supports the plausibility of a pavlovian conditioning hypothesis to explain the pathogenesis of MCS.

Fear-relevant images as conditioned stimuli for somatic complaints, respiratory behavior, and reduced end-tidal pCO2.

Two fear-relevant imagery scripts were used as conditioned stimuli (CSs) in a differential learning paradigm with 5.5% CO2-enriched air as unconditioned stimulus (US). In another condition, 2 neutral scripts were used as CSs (N = 56). Within each condition, one script was imagined while breathing the CO2-enriched air (CS+/US trial), the other while breathing room air (CS- trial). Three CS+ and 3 CS- trials were run in an acquisition phase, followed by 2 CS+ and 2 CS- test trials (imagining the scripts while breathing air). Respiratory behavior, end-tidal CO2, and heart rate were measured throughout the experiment; subjective symptoms were measured after each trial. The type of imagery had strong effects on symptoms and physiological responses. A selective conditioning effect was also observed: CS+ imagery produced more symptoms and altered respiratory behavior compared with CS- imagery, but only in the fear-relevant script condition. The findings are discussed as to their relevance for panic and agoraphobic anxiety.

Physical performance of patients with numerous psychosomatic complaints suggestive of hyperventilation.

In some patients exercise induces numerous complaints which cannot be attributed to an organic disorder, and which are suggestive of hyperventilation. The study was designed to investigate in this type of patient: 1) exercise capacity and muscle force; 2) breathing pattern and symptoms during maximal exercise and recovery; 3) relationships between symptoms and breathing pattern. Twenty-four patients were compared with 20 healthy subjects. They performed a maximal incremental cycle ergometer test and peripheral and respiratory muscle strength were measured. Patients tended to have a decreased exercise capacity and presented with moderately reduced muscle strength. At comparable minute ventilation, breathing frequency was higher (mean: 24 versus 21 per minute) and tidal volume smaller (mean: 1.42 versus 1.67 L). End-tidal partial pressure of carbon dioxide (PET,CO2) was not significantly different. A significant relation was observed between PET,CO2 and respiratory frequency during recovery in patients, suggesting a reduced flexibility of the ventilatory response to exercise. In patients respiratory complaints and paresthesias were weakly correlated to PET,CO2 at moderate exercise. It is suggested that the physical deconditioning observed in those patients is rather a consequence than a cause of the response to exercise. The link between symptoms and breathing pattern might be explained by a psychological conditioning process.

Subjective symptoms and breathing pattern at rest and following hyperventilation in anxiety and somatoform disorders.

The purpose of the present study was to investigate the diagnostic specificity of bodily symptoms and respiratory behavior at rest and after a hyperventilation provocation test (HVPT) in patients that were either grouped according to the DSM classification or diagnosed as suffering from hyperventilation syndrome. Nine hundred three anxiety and somatoform patients, showing symptoms supposedly caused by psychogenic hyperventilation, and 170 healthy subjects, were studied. Breathing pattern and end-tidal CO2 concentration were recorded during breathing at rest and following a HVPT. Subjective symptoms in daily life and after HVPT were measured. A principal-components analysis was performed on both the symptoms and breathing variables and their specificity levels were compared in the two classifications of patients. Some symptoms in daily life were grouped together with the same symptoms after the HVPT, other symptoms were not. This suggests that the HVPT elicited partly specific symptoms, and partly reproduced the symptoms experienced in daily life. Similar findings were observed with respect to the breathing variables. Patients with panic differed from other patients with anxiety disorders by an increased level of symptoms and a FETCO2 decline at rest. The HVPT may be informative for diagnosis because it provokes some of the typical somatic and psychological symptoms, and it identifies the breathing instability that is characteristic of both patients with HVS and with anxiety. The same symptoms and breathing variables characterized the patients, whatever their classification. Overall, the specificity of breathing variables is rather low.

Negative affect, respiratory reactivity, and somatic complaints in a CO2 enriched air inhalation paradigm.

Subjects scoring high on negative affectivity (NA) are known to report more psychosomatic complaints than subjects scoring low. According to the symptom perception hypothesis, high NA subjects attend more to somatic sensations and interpret these as more threatening. We investigated the relationship between NA and psychosomatic complaints in a group of high and low NA subjects (N = 72) in, (a) a questionnaire study, and (b) in a laboratory setting. The latter involved the inhalation of three different gas mixtures (room air, 5.5% and 7.5% CO2-enriched air) while respiratory responses were registered. Subjective complaints were measured after each trial. High NA subjects reported more complaints than low NA subjects in the questionnaire study. However, NA had no main effects on complaints in the laboratory study and did not interact with the effects of gas mixture on complaints. During room air trials, NA correlated only with general arousal complaints when a strong respiratory challenge had not been given before. The pattern of results suggests that experimental inductions of complaints may largely wipe out NA-related differences in attentional/interpretative processes that may mediate the NA complaints link.

Memory effects on symptom reporting in a respiratory learning paradigm.

With odors as conditioned stimuli (CSs) and CO2-enriched air as the unconditioned stimulus, participants learned to exhibit respiratory responses and somatic complaints on presentation of only the odor CS+. Studied was whether complaints during CS+-only trials were inferred from the conditioned somatic responses or were based on activated memory of the complaints during acquisition. Participants (N = 56) were either attentionally directed away or not from the complaints during acquisition, and the effects on somatic complaints during test were studied. Respiratory responses, heart rate, and somatic complaints were measured. No physiological conditioning effects were found. However, more complaints were reported to the CS+ than to the CS- odor, but only when the CS+ was foul smelling. This effect was modulated by the attention manipulation, showing that the learned complaints during the test phase were based on memory of the acquisition complaints and not on physiological responses during the test.

Short-term ventilatory effects in workers exposed to fumes containing zinc oxide: comparison of forced oscillation technique with spirometry.

Following the occurrence of metal fume fever in some subjects after the installation of an electric furnace in a steel plant, a survey was undertaken to examine whether subjects exposed to fumes containing zinc oxide would exhibit a detectable impairment in ventilatory function, and whether a forced oscillation technique (FOT) was more suited for this detection than conventional spirometry. Pulmonary function measurements were made in 57 exposed workers (production or maintenance) and 55 nonexposed workers (maintenance or strandcasting department) at the beginning and near the end of a work shift (day or night). Maximal expiratory volumes and flows were measured by means of a pneumotachograph, and respiratory resistance (Rrs) and reactance at various frequencies by means of a FOT. These measurements were repeated 1 day later. During the day shift, there were no significant differences in pulmonary function between exposed and control workers. However, during the night shift, an influence of exposure on pulmonary function was revealed both by spirometry and by FOT: workers exposed at night showed a slight decrease in vital capacity (VC) and in forced expiratory volume in one second (FEV1), and a decline in respiratory resistance (Rrs) with oscillation frequency, that were more marked than in unexposed subjects. In contrast to the frequency dependence of Rrs, the changes of lung volumes and expiratory flows were related to differences in initial values between exposed and nonexposed workers. The decrease in FEV1 was maintained the day after exposure. The forced oscillation technique proved at least as sensitive as spirometry to detect small across-shift changes in ventilatory function. Although the effects on pulmonary function were small, it is likely that they represent a subclinical response to the inhalation of small quantities of zinc oxide.

Influence of awareness of the recording of breathing on respiratory pattern in healthy humans.

This study was designed to test whether awareness of the measurement of breathing influences the breathing pattern in healthy subjects under routine laboratory conditions. Seventy four subjects (40 females and 34 males), aged 21-63 yrs, were studied under three different conditions whilst their breathing was being recorded for 5 min by means of inductance plethysmography (Respitrace): 1) subjects were misled into believing that their breathing was not being recorded but that they had to wait for 5 min whilst equipment was calibrated; 2) subjects were instructed that their breathing pattern was being recorded for 5 min; 3) the subject's breathing was recorded for 5 min with mouthpiece and pneumotachograph. The first two conditions were randomized. The Respitrace was calibrated by means of multiple linear regression carried out during the 5 min period of quiet breathing through a mouthpiece. Awareness of the recording of breathing caused prolongation of inspiratory (tI) and expiratory time (tE). Breathing through the mouthpiece resulted in an increase of tI, tE and tidal volume (VT). The breathing irregularities (sighs and end-expiratory pauses) decreased when subjects were aware of the recording of breathing and nearly disappeared when subjects breathed through the mouthpiece. The end-tidal carbon dioxide concentration was not significantly different between the three conditions. Mouthpiece breathing often induced some respiratory discomfort and even anxiety, particularly in females. Awareness by the subject that his or her breathing was being recorded altered the spontaneous breathing pattern, mainly the breathing frequency. In addition, use of a mouthpiece markedly increased tidal volume, particularly in females in whom mouthpiece breathing induced more complaints than in males.

Unsteadiness of breathing in patients with hyperventilation syndrome and anxiety disorders.

The breathing pattern of 399 patients with hyperventilation syndrome (HVS) and/or with anxiety disorders and that of 347 normal controls was investigated during a 5 min period of quiet breathing and after a 3 min period of voluntary hyperventilation. The diagnosis of HVS was based on the presence of several suggestive complaints occurring in the context of stress, and reproduced by voluntary hyperventilation. Organic diseases as a cause of the symptoms were excluded. The anxiety disorders were diagnosed by means of an abbreviated version of the Anxiety Disorders Interview Schedule (ADIS). There was a large overlap between the two diagnoses. Simply breathing via a mouthpiece and pneumotachograph made end-tidal CO2 fractional concentration (FET,CO2) decrease progressively both in hyperventilators and in patients with anxiety disorders, but not in normals. At the start of the measurement the FET,CO2 was not different between patients and healthy subjects. In patients < or = 28 yrs, the decrease of FET,CO2 resulted from a higher tidal volume, and in patients > or = 29 years from an increase in frequency. After voluntary hyperventilation, the recovery of FET,CO2, was delayed in patients, due to a slower normalization of respiratory frequency in females and in older males, and of tidal volume in younger males, and also due to less frequent end-expiratory pauses. When breathing was recorded first by means of inductive plethysmography (Respitrace), the progressive decline of FET,CO2 seen in patients was not observed: from the onset of the recording, FET,CO2 was reduced in patients. It did not change further when, immediately afterwards, the subject switched to mouthpiece breathing. The finding that breathing through a mouthpiece induces hyperventilation in patients and that recovery of FET,CO2 is delayed after voluntary hyperventilation, suggests that the respiratory control system is less resistant to challenges (mouthpiece or voluntary hyperventilation) in those patients. On the other hand, the lower values of FET,CO2 measured during recording by means of a Respitrace probably result from a challenge, prior to the recordings, induced by the fitting of the measuring device to the patient. This unsteadiness of breathing characterizes patients with hyperventilation syndrome and those with anxiety disorders, but is not sufficiently sensitive to be used for individual diagnosis.