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International audience; SETTING: Occupational asthma (OA) is most likely to develop in the very early years of exposure. OBJECTIVE: To describe the early incidence of OA among bakers/pastry-makers (BP) and hairdressers and to explore the role of atopy. DESIGN: Following a retrospective follow-up design, subjects were invited to undergo telephone interviews. Those who declared work-related respiratory or rhinitis symptoms and a sample group of others were offered a medical visit for OA investigations. Data from interviews and from medical visits were used to estimate the incidence of OA according to increasing durations of exposure. RESULTS: A total of 866 subjects were interviewed (mean age 25.3 years, 43.8% females), of whom 282 underwent a medical visit. Total estimated incidence rates of 'confirmed or probable' OA during the first 12 years of exposure were high in BP (2.63 per 100 person-years [py]) and in hairdressers (0.58/100 py), particularly in the first 4 years. Atopy is a strong risk factor for incidence among BP but, irrespective of the occupational sector, it does not influence the timing of OA symptoms. CONCLUSION: OA symptoms occur soon after the start of exposure. Our results suggest that atopy does not precipitate the occurrence of symptoms in two different allergen exposure settings.

Resume Introduction Nous avons analyse la prevalence et les facteurs de risque du ronflement habituel dans un echantillon de sujets masculins de la population active de Lorraine. Methodes Les 850 sujets, âges de 22 et 66 ans, ont repondu a un questionnaire sur la frequence du ronflement, leur mode de vie, leurs antecedents personnels et familiaux. Des mesures anthropometriques ont ete completees par un examen non invasif de permeabilite de voies aeriennes superieures. Resultats La prevalence du ronflement habituel etait de 34,6 % ; augmentant avec l’âge, le poids et ses indices derives. Nous avons identifie (par regression logistique) les variables independamment associees au ronflement habituel : l’âge, le poids, l’obstruction nasale nocturne, le diagnostic d’apnees du sommeil par un medecin, et l’hypertrophie du voile du palais et de la luette. Le resultat original a ete la mise en evidence d’un effet « protecteur » d’une grande taille ; l’exercice de loisir n’apparait significatif qu’a l’analyse univariee. Conclusions Cette etude rapporte une prevalence du ronflement habituel similaire a d’autres etudes utilisant les memes methodes. Elle confirme le risque lie a l’âge, au poids, a l’obstruction nasale, et aux modifications nasopharyngees. Un effet protecteur d’une haute taille apparait comme element original, jamais signale par les enquetes precedentes.

SummaryThe aim of the study was to evaluate the prevalence, the covariates and determinants of respiratory pauses during sleep in a sample of French middle-aged males.Study subjects were 850 active males, aged 22–66 years; 88.4% of them answered the question on breathing pauses during sleep from a structured, validated sleep questionnaire.Forty-one (=5.4%) subjects reported breathing pauses at least once a week; these “positive responders” were older, heavier and had larger neck- and waist girths as compared to subjects with negative answers. Loud habitual snoring, various sleep disturbances, excessive daytime sleepiness, a doctor diagnosis of sleep apnoea, history of stroke and hypertension were significantly more frequent among subjects with breathing pauses during sleep.The prevalence found in this survey was close to that reported from the UK (5.2%). However, by logistic regression, we identified novel determinants of breathing pauses i.e. habitual snoring, loud snoring, and excessive sleepiness, factors well known in clinical setting, but never previously reported in epidemiologic studies.

Background: No data on snoring prevalence obtained with a standard questionnaire exist for France. Major nose-throat abnormalities have been demonstrated in cases with obstructive sleep apnea; evidence of ‘minor’ abnormalities in community studies is scarce. Objectives: The fist objective of our study was to estimate the prevalence of habitual snoring in a sample of middle-aged active males in France. The second objective was to test the hypothesis that ‘minor’ nose-throat abnormalities could be associated with habitual snoring in a field survey. Methods: Three hundred thirty-four male employees of a local university volunteered for the study (93.6% of those contacted by mail); 300 returned a sleep questionnaire. The protocol also included anthropometry and a noninvasive nose-throat examination. Results: Complete data were obtained in 299 subjects aged 23–63 years. When ‘habitual snorers’ (= 32%) were compared with never-snorers, significant differences were found for all anthropometric variables, except height. In univariate analysis, habitual snoring was associated with a large number of variables, including a large soft palate, a large uvula, and altered nose patency. A logistic regression model retained 8 factors independently associated with snoring: age, neck circumference, tobacco consumption, breathing pauses during sleep, not feeling rested during the day, need for coffee to stay awake, blocked or running nose at night and a large soft palate. Conclusions: The prevalence of habitual snoring in this sample of middle-aged French males was 32%. We confirmed the significant association of habitual snoring with age, weight excess, and tobacco smoking, and identified two further factors: blocked nose at night and a large soft palate.

Sleep-disordered breathing (SDB) and lower socio-professional status have in common a series of risk factors for ill health such as sedentary lifestyle, weight excess, heavy alcohol and tobacco consumption. We hypothesised that SDB will be more prevalent in lower socio-professional groups. A total of 496 male middle aged subjects (23–66 years) were tested with a protocol including a self-completed structured sleep questionnaire (translation of the Madison sleep cohort study form), anthropometry (including neck, waist and hip girth) and a simple, non-invasive nose–throat examination by a specialist physician. The subjects were classified according to the 10 major groups of the ISCO-88 classification (International Labour Office). Our sampling base did not contain subjects in the major groups 1 (senior officials, legislators), 6 (fishery and agricultural workers), and zero (armed forces), thus these groups were not represented in the analysis. To improve the power of the statistical analysis, groups 3 and 4, 5 and 7, 8 and 9 were merged, the analysis thus including four categories. The differences in demographic data were negligible; as expected, smoking was more prevalent in low socio-occupational groups (difference non-significant). A history of chronic bronchitis was more frequent in low socio-occupational groups, while a low physical job labour was more frequent in higher occupational groups. We did not find any differences in the prevalence of sleep-related respiratory disturbances (snoring, sleep apnoeas). This first study of the possible association between socio-occupational factors and sleep disordered breathing was negative, but we believe further studies, on larger samples, with a more homogeneous distribution of social groups are warranted.

International audience; BACKGROUND: Exposure to pollutants in bakeries and hairdressing salons can cause airway syndromes varying from bronchial irritation to asthma. Workplace respiratory health surveillance aims to identify possible cases requiring further investigation. AIMS: To compare the performance of fractional exhaled nitric oxide (FE(NO)) and spirometry for health surveillance of apprentice bakers (ABs) and apprentice hairdressers (AHDs). Determinants of FE(NO) were also identified. METHODS: Symptoms and physician-diagnosed asthma were evaluated by questionnaire. FE(NO) was measured and spirometry was carried out. Subjects with elevated FE(NO) (FE(NO) > upper limit normal), airway obstruction [forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) < 95th percentile] and atopy (history of allergies) were identified. RESULTS: A total of 126 apprentices (59 ABs and 67 AHDs) participated. Twenty-nine (23%) apprentices had abnormal tests: 4 had associated high FE(NO) and airway obstruction, while 25 had either high FE(NO) (n = 15) or airway obstruction (n = 10) alone. Compared with ABs (n = 16), AHDs (n = 13) had more asthma (38 versus 0%; P < 0.05) and atopy (62 versus 6%; P < 0.05). There was no difference in symptoms, smoking FE(NO) or airways obstruction. Among 97 subjects with normal tests, no differences existed between ABs (n = 53) and AHDs (n = 44). Average FE(NO) was increased in atopic non-smokers compared with atopic smokers and non-atopic subjects (P < 0.05). Smoking, a history of allergies, FEV(1)/FVC % observed and respiratory symptoms were the main determinants of FE(NO). CONCLUSIONS: FE(NO) and spirometry were not overlapping dimensions in ABs and hairdressers, each test contributing unique information on the physiological status of the respiratory system. FE(NO) may provide added information on airway inflammation not provided by spirometry.

In a previous study, it has been shown that bolus injections of dopamine could either stimulate or inhibit the carotid chemosensory discharge in the kitten (Marchal et al., 1992a). To further characterize dopaminergic mechanisms in the carotid body during development, the effects of a continuous infusion of dopamine on carotid chemosensory activity in air, hypoxia (8% O2 in N2) and hyperoxia (100% O2) were studied in ten anesthetized, paralyzed and artificially ventilated kittens, aged 1 to 21 days and in three adult cats. One carotid sinus nerve was prepared for recording the activity of a single or a few chemosensory afferents. In the kittens, the immediate effect of dopamine at the onset of infusion (10 micrograms/kg/min) was an inhibition of the discharge in five kittens, a progressive excitation in four and no change in one. Four minutes after the onset of dopamine infusion, there was a significant increase in chemosensory activity both in room air (from 4.5 +/- 0.8 impulse/sec to 8.8 +/- 1.4 impulse/sec, mean +/- SEM, P0.05) and in hypoxia (from 24.6 +/- 3.7 impulse/sec to 33.4 +/- 5.3 impulse/sec, P0.05) but not in hyperoxia (0.5 +/- 0.2 impulse/sec vs 0.7 +/- 0.3 impulse/sec). The adult cats received four successive dopamine infusions at the rate of 2.5, 5, 7.5 and 10 micrograms/kg/min, in an attempt to establish a dose-response relationship. The effects of dopamine infusions were consistent within, but variable between, cats. The onset of dopamine infusion was associated with an inhibition of the discharge in two cats, at all infusion rates. In one of them, chemosensory activity returned quickly to control and the response to hypoxia was enhanced. In the other cat, the inhibition of the discharge persisted for the duration of the infusion, and the response to hypoxia was inhibited. In the third cat, dopamine had no effect on the chemosensory discharge. The patterns of chemosensory responses evoked by dopamine are qualitatively similar in kittens and cats, but the excitatory type of response appear to be more readily elicited in the kitten.

Pregnancy increases ventilatory and carotid body neural output (CBNO) responsiveness to hypoxia in cats (J. Appl. Physiol. 67: 797-803, 1989). To determine whether progesterone and estrogen stimulated hypoxic ventilatory and CBNO responsiveness, we studied 24 castrated male cats before and after 1 wk of placebo, estrogen, progesterone, or estrogen plus progesterone treatment. Estrogen plus progesterone treatment decreased end-tidal PCO2 (-3.8 +/- 0.8 Torr) and increased hypoxic ventilatory responsiveness, whereas estrogen or progesterone alone had no effect. Animals receiving progesterone alone or in combination with estrogen had higher CBNO responsiveness than placebo or estrogen-treated animals (shape parameter A = 45 +/- 7 vs. 27 +/- 4, P less than 0.05). However, the group treated with estrogen plus progesterone did not have greater CBNO responsiveness to hypoxia than the group receiving progesterone alone. The cross plot of the simultaneously measured CBNO and ventilation during progressive hypoxia revealed a greater slope in the estrogen-treated than in the placebo animals, suggesting that estrogen treatment increased central nervous system transduction of CBNO into ventilation. Thus the data taken together suggested that progesterone and estrogen had a combination of peripheral (carotid body) and central sites of action such that the administration of both hormones together had a more consistent stimulatory effect on hypoxic ventilatory responsiveness than either hormone alone.

Background: Most studies on habitual snoring have focused on its prevalence. However, from the clinical point of view, the intensity of snoring is of upmost importance, as it suggests the existence of sleep apnoeas. Objectives: The aim of the study was to assess the prevalence of loud snoring using a standard questionnaire and to evaluate the anthropometric and sleep characteristic differences between loud and light snorers in a sample of middle-aged males. Methods: The subjects were middle-aged active male employees. They completed a structured sleep questionnaire and had standard anthropometric measurements. Subjects reporting habitual snoring (≧3 nights/week) were further classified as loud or light snorers. Results: Of the 850 male subjects volunteering, 149 (17.5%) were habitual loud snorers. Loud snorers were older and had a greater waist-to-hip ratio as compared with light snorers. In univariate analysis, loud snoring was associated with gasping/snorting during sleep, breathing stops during sleep, waking up too early, excessive daytime sleepiness and falling asleep while watching TV. Logistic regression identified four independent associates of loud snoring: gasping during sleep, excessive daytime sleepiness, falling asleep watching TV and age. Conclusions: Loud snoring is present in a significant proportion of middle-aged men and is associated with central obesity and age. It disturbs sleep and elicits significant daytime sleepiness. Its association with breathing pauses (univariate) and its independent association with gasping during sleep suggests that loud snoring could be considered a clinical correlate of obstructive sleep apnoeas.

Study objectives: To assess the prevalence of occasional snoring in a group of middle-aged men, and to compare anthropometric variables and prevalence of sleep-related symptoms of subjects who occasionally snore with those of other snoring categories. Design: A field survey of a sample of middle-aged men in France. Participants: Male employees of a local university and subjects from the community attending a preventive medicine center. Participation rate was 93.5%. Measurements: Anthropometric variables were recorded in 499 subjects aged 23 to 66 years (mean, 44.3 years). The subjects completed a standard sleep questionnaire and were classified according to the snoring frequency as never, rarely, sometimes, occasional, several nights per week, and every night. The subjects who snore occasionally represented 8.6% of the total. Results: The anthropometric data of subjects who snore occasionally were similar to those of subjects who habitually snore. When compared with subjects who do not snore, older age and a larger neck girth were significant. Subjects who snore occasionally were also significantly more often subjects who snore loudly, and tended more frequently to have breathing stops during sleep. Conclusions: Our epidemiologic study shows that approximately 9% of a sample of middle-aged men snore occasionally. Subjects who snore occasionally have anthropometric characteristics close to those of subjects who snore habitually. The prevalence of the main sleep-related symptoms is between that of subjects who do not snore and of subjects who snore habitually. In an epidemiologic setting, inclusion of subjects who snore occasionally as subjects who do not snore or subjects who snore habitually will lead to bias. The present results suggest they should be identified and considered as a separate category. (CHEST 2002; 122:562–568)

Asthma has a tendency, to destabilize and get worse at night, probably due to a nocturnal increase in airiway inflammation and bronchial responsiveness. Nocturnal airway narrowing in asthma is often associated with sleep disorders, such as episodes of nocturnal and early morning awakening, difficulty in maintaining sleep, and day time sleepiness. On the other hand, an association has been documented between nocturnal sleep-disordered breathing and asthma. This review highlights the causes of nocturnal worsening of asthma and examines the evidence pointing toward a causal relationship between nocturnal asthma and sleep-disordered breathing.

In patients with obstructive sleep apnoea (OSA) anatomic and functional upper airway abnormalities are frequent and severe. Invasive methods are used to identify and quantitate the obstruction, to precisely locate its site, etc. as part of pre-treatment or of preoperative evaluations. These methods (lateral skull radiographs, computerized tomography, MRI, fibroscopies, etc) are too expensive and too invasive to be utilized in field surveys. To the classical sleep questionnaires and anthropometric measurements, some simple nose-throat examinations, easily accepted by the volunteers in a population study, could add useful information for the identification of the subjects at risk for sleep-disordered breathing. The present paper is a review of these examinations and of their utility.

The accuracy and precision of transcutaneous pressure measurements of oxygen (Ptc,O2) and carbon dioxide (Ptc,CO2) in the monitoring of nocturnal assisted ventilation in adult patients were evaluated. Transcutaneous measurements obtained with two analysers, Radiometer TINATCM3 (R) and Kontron MicroGas-7650 (K), were compared with arterial blood gases analysed in blood samples withdrawn simultaneously in 10 patients. Sensors were heated to 43 degrees C. Measurements of transcutaneous blood gases and arterial blood gases were collected six times at 1-h intervals. The data obtained with both instruments were similar and did not significantly change over the 5 h test period. Measurement of Ptc,O2 underestimated arterial oxygen tension (Pa,O2) and this underestimation increased with the level of Pa,O2 (p

Catecholamines, dopamine and norepinephrine, are present in a significant amount in the carotid body of many animal species (Fidone et al, 1980; Fitzgerald et al, 1983). Dopamine is synthesized in glomus cells since the presence of the rate limiting enzyme in catecholamine synthesis, tyrosine-hydroxylase (TH), has been clearly demonstrated. Moreover, hypoxia is known to increase dopamine release (Fidone et al, 1982), norepinephrine content (Hanbauer et al, 1981; Verna et al, 1993), and activity of TH in carotid body, and to induce the expression of TH-mRNA (Czyzyk-Krzeska et al, 1992). However, the presence of epinephrine in the carotid chemoreceptors remains controversial probably because of the difficulty in detecting small amounts of this substance.

Doxapram is a respiratory stimulant which acts on peripheral chemoreceptors and central respiratory neurons in a dose-dependent fashion in the adult cat. In the newborn, the mechanisms of action of doxapram are still unclear. To evaluate the effects of doxapram on the carotid chemosensory discharge and its relationship with dopaminergic mechanisms in the carotid body, two groups of kittens less than 13 days old, anesthetized, artificially ventilated and paralyzed, were prepared for the recording of a single or a few chemosensory afferents of the carotid sinus nerve. The chemosensory activity was recorded under five conditions of inspired gas mixtures (21 and 8% O2 in N2, 100% O2, 5 and 10% CO2 in O2). Group 1 (n = 9) received only doxapram and group 2 (n = 8) was pretreated with haloperidol (1 mg/kg), a dopamine D2-receptor blocker, before receiving doxapram. Doxapram significantly stimulated the discharge rate of the carotid chemoafferents under all conditions of inspired gas. The chemosensory discharge was increased by haloperidol, and was raised further after doxapram by an amount similar to group 1. For instance, in normoxia, the activity increased from 2.9 +/- 0.4 to 7.5 +/- 0.9 impulse/s (mean +/- SEM, p < 0.01) in group 1 and from 3.8 +/- 0.6 to 9.1 +/- 1.0 impulse/s (p < 0.01) in group 2. These results indicate that the mechanisms of response of carotid chemoreceptor to doxapram are developed in the newborn kitten and doxapram acts independent of the dopaminergic mechanisms in the carotid body.

In adult cats, peripheral chemoreceptors respond to a step increase in PCO2 by a rise in activity to a maximum and then adapt to a lower steady level within one minute. It has been shown that the transient peak response is entirely dependent on the catalyzed CO2 hydration and disappears after carbonic anhydrase inhibition (Black et al., 1971). In newborn kittens, the dynamics of response of peripheral chemoreceptors are different from that observed in adult cats (Marchal et al., 1992). It is known that neither the chemosensory activity (Hanson, 1986) nor the carbonic anhydrase activity (Maren, 1967) is mature at birth. However, the dynamics of the hypercapnic response of the peripheral chemoreceptors in newborns remains unknown.

The carotid body chemoreceptors are the main sensors for the level of arterial PO2 involved in the ventilatory control. It is well recognized that they also contribute to the ventilatory response to changes in PaCO2. Electrophysiological recordings of carotid chemoreceptor activity in adult animals show that they present a rapid response to sudden step rise of PCO2 in the arterial blood (Dutton et al., 1967; Fitzgerald et al., 1969; Black et al.,1971). It is still appreciable during hyperoxia and is enhanced by hypoxia (Fitzgerald and Parks, 1971;Lahiri et al., 1975, 1982). On the other hand, it has been established that an adaptation of the ventilatory response to CO2 occurs within seconds of a peak response (Dutton et al., 1967). Similarly, the carotid chemoreceptors appear to adapt (Black et al.,1971), at least in hypoxia or under specific stimulation (Lahiri et al. 1982, 1989). However, these results have only been observed in adult animals. In newborns, the weak chemosensory reactivity of carotid body is well documented (Blanco et al., 1984) but no information on the neonatal development either of the dynamic CO2- response of peripheral chemoreceptors or of the O2-CO2 interaction was available.

Hypoxic ventilatory response (HVR) is known to be increased by female as well as male sex hormones, but whether there are differences in HVR between men and women remains unclear. To determine whether gender differences exist in HVR, we undertook systematic comparisons of resting ventilation and HVR in awake male and female cats. Furthermore to explore the potential contribution of sex hormones to gender differences observed, we compared neutered and intact cats of both sexes. Resting ventilation differed among the four groups, but differences disappeared with correction for body weight. Intact females had a lower end-tidal PCO2 than intact male cats (females: 31.6 +/- 0.4 Torr vs. males: 33.6 +/- 0.4 Torr, P less than 0.05), indicating an increased alveolar ventilation per unit CO2 production. HVR expressed as the shape parameter A was similar among the four groups of animals. However, baseline (hyperoxic; end-tidal PO2 greater than 200 Torr) minute ventilation [VI(PO2 greater than 200)] differed among the groups. Therefore we normalized HVR by dividing the shape parameter A by VI(PO2 greater than 200) to compare the relative hypoxic chemosensitivity among the various groups of animals. In addition, we further normalized HVR for body weight, because body size influences ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Six pulse oximeters with finger probes were studied in three groups of 17 hypoxemic patients with COPD aged 50 to 75 years. Transcutaneous arterial oxygen saturation (SpO 2 ) was measured with the Nellcor N101 (oximeter 1a), the Ohmeda Biox III (oximeter 1b), the Nellcor N200 (oximeter 2a), the Critikon Oxyshuttle (oximeter 2b), the Radiometer Oxi100 (oximeter 3a), and the Ohmeda Biox 3700 (oximeter 3b). The SpO 2 was compared with SaO 2 measured in simultaneously withdrawn samples of arterial blood (Radiometer OSM2) at three 20-minute steady-state levels of Flo 2 ranging from 0.21 to 0.40 (SaO 2 , 62 to 100 percent). The bias (mean SpO 2 -SaO 2 difference) and the error in precision (SD of the differences) were both below 4 percent for instruments 1a and 1b and remained below 1.2 and 3 percent, respectively, for the others. A good agreement between SpO 2 and SaO 2 , as reflected by the Bartko intraclass correlation coefficient, was observed in instruments 2a, 3a, and 3b. The individual relationships between SpO 2 -SaO 2 differences and SaO 2 appeared to be linear and parallel. With four instruments (1a, 1b, 2a, and 2b), the mean slope of this relationship was negative, showing a systematic instrumental error: the lower the SaO 2 , the larger the overestimation of SaO 2 . The scattering of the data (precision) principally reflects a subject source of error. In most instruments a technical adjustment could greatly improve instrumental errors and accuracy. The correction of the errors due to between-subject variation would require a system of calibration adjustable by the users to each individual.

Pregnancy increases ventilation and ventilatory sensitivity to hypoxia and hypercapnia. To determine the role of the carotid body in the increased hypoxic ventilatory response, we measured ventilation and carotid body neural output (CBNO) during progressive isocapnic hypoxia in 15 anesthetized near-term pregnant cats and 15 nonpregnant females. The pregnant compared with nonpregnant cats had greater room-air ventilation [1.48 +/- 0.24 vs. 0.45 +/- 0.05 (SE) l/min BTPS, P less than 0.01], O2 consumption (29 +/- 2 vs. 19 +/- 1 ml/min STPD, P less than 0.01), and lower end-tidal PCO2 (30 +/- 1 vs. 35 +/- 1 Torr, P less than 0.01). Lower end-tidal CO2 tensions were also observed in seven awake pregnant compared with seven awake nonpregnant cats (28 +/- 1 vs. 31 +/- 1 Torr, P less than 0.05). The ventilatory response to hypoxia as measured by the shape of parameter A was twofold greater (38 +/- 5 vs. 17 +/- 3, P less than 0.01) in the anesthetized pregnant compared with nonpregnant cats, and the CBNO response to hypoxia was also increased twofold (58 +/- 11 vs. 29 +/- 5, P less than 0.05). The increased CBNO response to hypoxia in the pregnant compared with the nonpregnant cats persisted after cutting the carotid sinus nerve while recording from the distal end, indicating that the increased hypoxic sensitivity was not due to descending central neural influences. We concluded that greater carotid body sensitivity to hypoxia contributed to the increased hypoxic ventilatory responsiveness observed in pregnant cats.

'Conventional' (lung volumes, airway conductance, CO transfer factor) and 'small-airway dysfunction' (single-breath N2 washout, maximal expiratory flows with air and a helium-oxygen mixture) tests were performed in a group of asymptomatic male ex-smokers (n = 20) with normal spirometry and compared to those of a similar group of middle-aged nonsmokers (n = 41). The study group had a mean life-long consumption of 13.2 +/- (SD) 8.8 pack-years and had stopped smoking 1-21 years ago, mean 7.3 +/- (SD) 5.8 years. Among the conventional tests, a minimal increase in residual volume and residual volume/total lung capacity ratio was found. Ex-smokers had a steeper phase III slope, a higher closing volume/vital capacity ratio, lower forced flows with air and a higher volume of isoflow, but neither difference between the group means was significant. There was a trend to more abnormal small-airway tests as a function of increased smoking, but only the correlation between percent of predicted closing volume and pack-years reached significance (r = +0.51, p less than 0.05). We conclude that small-airway function normalizes in the long term in most ex-smokers if they become asymptomatic, with less than 10% still having abnormal results years after they stopped smoking.

To assess the actual sensitivity of forced expiration indices to changes in the resistance of peripheral airways, maximal expiratory flow-volume curves were obtained in 30 normal subjects breathing air and breathing an O2-Ne-SF6 gas mixture having the same density as air but a 45% larger viscosity. The measurements were made using a bag-in-box system to circumvent calibration problems, and the data were processed digitally. Besides the usual forced expiration indices, slope ratios, as described by Mead (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 156-165, 1978), and transit time indices were also computed. Breathing the viscous mixture, the largest changes were seen with the slope ratio measured at 60% forced vital capacity, followed by other slope ratios, the standard deviation of transit times, and maximal flows at low lung volumes. However, when the data were compared using the t test for paired measurements, the most significant changes were found with the forced expiratory volumes at 1 and 2 s, due to their low within-subject variability. These indices may therefore by considered as the most suitable for detecting changes in individuals.

A model was developed to interpret the difference between volume variations at the mouth and at the chest observed by body plethysmography during inspiration in normal subjects breathing ambient air. The mechanical phenomena were characterized, as usual, by a time constant alpha, the product of airway resistance and alveolar gas compressibility. In contrast to other models, the change in temperature and water vapor pressure of the inspired gaswas not considered to be instantaneous but rather a first-order process characterized by a thermal time constant tau. Experimental curves obtained in eight subjects were analyzed by use of parameter estimation techniques. Thevalues of alpha were in agreement with those obtained by conventional plethysmography and tau averaged 63+/-24 ms. The results of additional experiments devised to test the physical meaning of the coefficients and the influence of neglected factors support the validity of the model. It was shown that tau cannot be neglected when breathing air at room temperature.

Summary. The variability, short-term (1 hour) and long-term (2 weeks) reproducibility of the variables derived from the single-breath N2 test were evaluated in a group of 56 healthy children aged 10 to 16 years with a computerized system. The variability was low for vital capacity and total lung capacity (coefficient of variation less than 3%), moderate for residual volume and phase III N2 slope (9 and 13%) and very high for closing volume (more than 50%). A closing volume could not be identified by the computer algorithm in 18.3% of the trials. The reproducibility of the variables was satisfactory both at 1 hour and at 2 weeks, with the exception of the closing volume, whose increase at 2 weeks seemed to be due to methodological factors. We conclude that reliable results of static lung volumes and phase III N2 slope, but not of closing volume, may be obtained in children by a computerized system in epidemiological studies.