Respiratory mechanics and dust exposure in byssinosis.

Acute exposures to hemp dust, in healthy subjects as well as hemp workers with byssinosis, resulted in two different responses. Men with symptoms (chest tightness, coughing, and wheezing) after exposure showed decreases of forced expiratory volumes (FEV(1.0)), flow rates on maximum expiratory flow-volume (MEFV) curves, and of vital capacity (VC), while airway conductance (Gaw: TGV ratio) did not decrease significantly ("flow rate response"). Men without symptoms after exposure showed no changes of VC, FEV(1.0), and MEFV curves, but had a significantly decreased airway conductance ("conductance response"). The flow rate response is attributed to a pharmacological bronchoconstrictor effect of hemp dust on small airways, the conductance response to a mechanical or reflex effect of hemp dust on large airways. Both responses were abolished by a bronchodilator drug. The type of response reflects a difference between individuals and is not related to age, smoking habits, or prior exposure history. Men with normal control function data had either a flow rate or a conductance response. All men with abnormal control data had a flow rate response.Long-term hemp dust exposure causes irreversible obstructive lung disease, in particular among men who respond to acute dust exposure with symptoms and flow rate decreases. The detection of this response, with FEV(1.0) measurements and MEFV curves, is essential in the study of byssinosis. Decreases of airway conductance after dust exposure have no consistent relation to the development of clinical symptoms. The relative value of measurements of maximum expiratory flow rates and of airway conductance in other lung diseases needs to be reassessed.

[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.

Total resistance and reactance in patients with respiratory complaints with and without airways obstruction.

A comparison was made of the frequency dependence of total respiratory resistance, (Rrs), and reactance (Xrs), determined by a forced oscillation technique in 442 healthy subjects and in 126 patients with respiratory complaints, with or without slight airways obstruction. The comparison was performed by means of a discriminant analysis. The latter demonstrated that the Rrs and Xrs data, measured between 8 and 24 Hz, of patients differ from those of healthy subjects primarily by a decrease of Rrs with frequency associated with more negative Xrs (and thus with an increase in resonant frequency). This probably also applies to patients with more advanced airways obstruction. The addition of the FEV1 values to the analysis provides only a small amount of independent information. The forced oscillation technique thus appears to be a sensitive tool to separate healthy subjects (smokers and nonsmokers) from patients with respiratory complaints associated or not with a reduced FEV1.

Normal values of total respiratory resistance and reactance determined by forced oscillations: influence of smoking.

In 407 healthy male subjects, smokers and nonsmokers, the resistance and reactance of the respiratory system were determined between 4 and 24 Hz, using a forced oscillation technique. The values are significantly correlated with age, weight, height, FEV1, and vital capacity. After standardization of the data for the latter variables, there are no differences between smokers and nonsmokers. The technique thus lacks sensitivity for the detection of the effects of smoking.

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.

Variations of respiratory impedance with lung volume in bronchial hyperreactivity.

The total respiratory impedance was measured at various frequencies (4 to 52 Hz) with a pseudo-random-noise forced oscillation technique (FOT). The apparatus (Oscillaire) was connected with a spirometer forming a closed respiratory circuit in which gas concentrations were kept constant. Measurements were made in 15 healthy subjects (group 1) and in 30 asthmatic patients with bronchial hyperreactivity, subdivided into group 2 treated only with inhaled beta 2-mimetics (n = 15) and in group 3 using both beta 2-mimetics and steroids in inhalation (n = 15). No significant differences were found between the impedance data obtained with the Oscillaire alone and those obtained with the Oscillaire connected with the spirometer circuit. The impedance was measured at FRC level, and at FRC +1 L and -1 L. The relative changes of the resistance at 8 Hz were -23.2 percent (13.8) at FRC +1 L and +40.9 percent (29.3) at FRC -1 L relative to the values at resting FRC. This inverse relation between airway resistance and lung volume was similar in all groups. The average reactance decreased at FRC -1 L in all groups. However, at FRC +1 L the average reactance increased 50.6 percent in group 2 and 94.2 percent in group 3, but decreased in group 1. Concomitant changes were observed in the resonant frequency and in the frequency dependence of resistance. Because of these qualitatively different responses of the impedance data to changes in lung volume (both for the whole group and for each individual) between healthy subjects and asthmatic patients, this test might be useful for the diagnosis of bronchial hyperreactivity.

Comparison of dynamic lung function indices during forced and quiet breathing in upper airway obstruction, asthma, and emphysema.

We compared the dynamic lung function indices in patients with asthma (n = 27), emphysema (n = 20), and UAO (n = 18), with the purpose being to examine whether different patterns of abnormalities could be found and which tests were most discriminative among the three groups. Forced expiratory indices were measured (FEV1; PEF; MEF50%), as well as indices obtained during quiet breathing (Raw; Gaw; Gaw/VL). The three groups were comparable as far as PEF was concerned (about 60 +/- 20 percent of predicted, yet the group with UAO showed significantly larger FEV1 (84 percent of predicted vs 55 percent and 57 percent of predicted in asthma and emphysema respectively), and larger MEF50% (71 percent of predicted vs 25 percent and 23 percent of predicted in the other groups), and the group with asthma had the largest Raw (0.37 +/- 0.18 kPa.s.L-1 vs 0.24 +/- 0.13 in UAO and 0.22 +/- 0.10 in emphysema). From these functional tests, several ratios were derived which were discriminative among the three groups. Upper airway obstruction could be recognized by a significantly lower PEF/MEF50% ratio and higher FEV1/PEF ratio than in the other conditions. Furthermore, a distinction between asthma and emphysema could be made by comparing airway patency during forced and quiet breathing, ie, the MEF50%/Gaw ratio. This ratio was, in fact, significantly different for all three groups, having the lowest value in emphysema (0.19 +/- 0.08 kPa vs 0.44 +/- 0.23 kPa and 0.63 +/- 0.34 kPa in asthma and UAO, respectively). Within the group with UAO, those with variable intrathoracic obstruction showed the least difference from asthma and emphysema for the measured indices.

Total respiratory resistance and reactance in patients with upper airway obstruction.

In 18 patients with upper airway obstruction, we measured dynamic lung volumes, maximal flows, airway resistance (Raw), and total respiratory resistance (Rrs) and reactance (Xrs) at various frequencies by means of a forced oscillation method. Patients were classified according to the site and the type of the obstruction. The values of Raw, Rrs and Xrs were tightly correlated and reflected the overall importance of the obstruction. In comparison with patients with chronic obstructive pulmonary disease the values of Rrs tend to be higher and to be influenced more by support of the cheeks during the measurement. These differences are not diagnostic, however.

The senile lung. Comparison with normal and emphysematous lungs. 1. Structural aspects.

As part of a study of the structural-functional correlations of excised human lungs obtained at autopsy, the parenchyma and peripheral airways were examined by means of morphometric techniques. Among the 30 lungs characterized by the absence of fibrosis, ten differed from the normal and emphysematous lungs by a homogeneous dilatation of the airspaces, in excess of the dimensions predicted on the basis of age. Study of the standard deviations of the mean linear intercepts showed that the airspace dilatation was more regular than in emphysematous lungs; in addition, there was no clear-cut destruction, as estimated from the number of alveolar attachments. These lungs were characterized in addition by an increased thickening of alveolar septa, without inflammation or fibrosis, normal size of the diameter, and reduced density of the membranous bronchioles. Since these lungs were from people older than 60 years, it is assumed that they represent cases of exaggerated airspace enlargement of the aging lung, differing from emphysema by the absence of destruction of alveolar walls. The term "senile lung" is proposed or this condition.

The senile lung. Comparison with normal and emphysematous lungs. 2. Functional aspects.

Senile lungs are characterized by a homogeneous enlargement of the alveolar airspaces, without fibrosis or destruction of their walls. Study of the functional characteristics of excisea senile lungs showed an increase in minimal air and a shift to the left of the elastic recoil pressure-volume curves, less pronounced than in emphysematous lungs. Maximal expiratory volumes and flows were normal. Total lung capacity was not significantly increased, but this may be a consequence of preagonal edema. Comparison of normal, senile, and emphysematous lungs showed a close relationship between recoil pressures and mean linear intercept, Lm, and between forced expiratory volume in 1 s and diameter and density of the membranous bronchioles. It is concluded that airspace enlargement may precede emphysema and may be responsible for changes in lung elasticity. In this respect, senile lungs are an example of the functional changes caused by an isolated airspace enlargement.

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.

Effect of upper airway shunt and series properties on respiratory impedance measurements.

Because of the contradictory statements published about the influence of the shunt properties of the upper airway on the measurements of the respiratory impedence by means of the forced oscillation technique, this influence has been reevaluated. In healthy adults and children and in patients with obstructive lung disease, the total respiratory impedance was measured by applying oscillations at the mouth (conventional technique) or around the head (head generator technique), with the cheeks either supported by the hands or not. In healthy adults the two techniques (conventional cheeks supported and head generator) yield similar results for respiratory resistance (Rrs) and a more pronounced increase of respiratory reactance (Xrs) with frequency with the head generator. In children and in patients with moderate airway obstruction, the negative frequency dependence of Rrs observed with the conventional technique tends to disappear with the head generator. This is not observed in patients with severe airway obstruction. The differences between the two techniques can be explained by the influence of the shunt impedance of the upper airway on Rrs and Xrs. Correction for this influence by subtracting the impedance measured during a Valsalva maneuver is not satisfactory, since the Valsalva maneuver itself modifies the upper airway shunt. The head generator technique reduces the influence of the upper airway shunt but does not suppress it altogether; the residual error is small, however.

Changes of respiratory input impedance during breathing in humans.

Changes of total respiratory resistance (Rrs) and reactance (Xrs) were studied between 8 and 32 Hz at five moments during the respiratory cycle in healthy adults (group A) and children (group B) and in patients with chronic obstructive lung disease (group C) and with upper airway obstruction (group D). Two forced oscillation techniques were used: the conventional one and the head generator, with the oscillations applied at the mouth and around the head of the subject, respectively. Both techniques yielded similar results. Rrs is lowest during the transition from inspiration to expiration and highest in the course of expiration, except in group D. Mean Xrs is highest at the transitions from inspiration to expiration or vice versa and lowest during expiration, except in group D. In groups C and D, the increases of Rrs are accompanied by a more pronounced negative frequency dependence of Rrs. The variations of Rrs and Xrs appear to be markedly flow dependent and may be a consequence of the interaction of breathing with oscillatory flows.

Shunt properties of large intrathoracic airways.

The impedance of the wall of human intrathoracic trachea and central airways was measured by submitting preparations of excised airways to forced oscillations at various frequencies from 2 to 32 Hz. Both real (resistance) and imaginary (reactance) parts of wall impedance demonstrate a marked frequency dependence, varying with transmural pressure. These variations of resistance and reactance are related and are linked to the static elastic properties of the airways. The data allow us to calculate the total shunt impedance of the central intrathoracic airways. When the latter shunt values are used to correct measurements of impedance values of excised emphysematous lungs, it turns out that the shunt does not modify markedly the observed frequency dependence of resistance and compliance of those lungs, at least at transpulmonary pressures > 0.2 kPa. A model study suggests, in addition, that the latter frequency characteristics cannot be explained satisfactorily by parallel mechanical inhomogeneities. We submit that the frequency dependence of resistance and compliance of excised emphysematous lungs is determined mainly by the visco- and/or plastoelastic properties of lung tissue itself.

Membranous bronchioles and connective tissue network of normal and emphysematous lungs.

Three-dimensional reconstructions of the septal system of normal human lungs revealed that airways course within the interlobular septa, i.e., between the two blades formed by the peripheral boundaries of adjacent lobuli of whatever order, and enter the supplied pulmonary unit at its side. This is not in keeping with the classic view of a peripheral airway in the center of a lung unit and submitted to radial traction by attached alveolar septa. The basic design of the lung fibrous scaffold appears to be in conformity with the laws of fractal geometry. Similar reconstructions in centrilobular emphysema disclosed tortuosities of both intra-acinar and interlobular septa, with consequent distortions of the corresponding intraseptal bronchioles and collapse of lung units of different sizes. It is suggested that in centrilobular emphysema competition for space, besides intrinsic airways narrowing because of inflammation and loss of elastic recoil, is a cause of flow limitation.

Resistance and reactance of the excised human larynx, trachea, and main bronchi.

We investigated the impedance of excised preparations of the human larynx before and after resection of the vocal cords and of the trachea whether or not in connection with the main bronchi for steady (75-700 ml.s-1) and oscillatory flows (4-64 Hz). To simulate the influence of respiratory flow on oscillatory resistance (Rosc), oscillatory and steady flow were superimposed. This resulted in a marked increase of Rosc, dependent on the value of steady flow, a change of the frequency dependence of Rosc, and a decrease of the reactance. The latter effects were particularly pronounced in the preparations of the larynx, especially with a narrow glottis opening. The influence of steady flow on oscillatory resistances is probably the expression of interactions of steady and oscillatory flow regimes in the larynx. Similar but less pronounced interactions are also met in the trachea. These effects lead to a systematic overestimation of upper airway resistance when measured during spontaneous breathing by means of a forced oscillation technique.

Influence of posture on lung volumes and impedance of respiratory system in healthy smokers and nonsmokers.

In 105 adults we investigated the influence of the body positions, sitting with respect to supine, on lung volumes and on the input resistance, (Rrs) and reactance (Xrs) of the respiratory system. Rrs and Xrs were measured between 2 and 26 Hz by means of a forced oscillation technique. Vital capacity (VC) and expiratory reserve volume (ERV) are smaller in the supine position; this reduction decreases with age and is less for ERV in male smokers than in nonsmokers. The Rrs values are larger in the supine position, and the slope of the Rrs-frequency curves tends to become less positive or negative, depending on sex, age, and smoking habits. Xrs decreases at lower frequencies. The changes in Rrs due to posture are larger in young smokers than in young nonsmokers. This is not explained by changes in ERV and may reflect changes in the intrinsic properties of the airways induced by smoking.

Anatomy of membranous bronchioles in normal, senile and emphysematous human lungs.

Serial reconstructions of the membranous bronchioles (MB) were performed in randomly selected tissue blocks cut parallel to the pleural surface in fixated human lungs. Two to four normal, senile, and emphysematous lungs were examined. Three (2 in senile lungs) orders of MB were observed with a dichotomous branching pattern. Emphysematous lungs are characterized by an overall decrease in airway diameter with localized stenoses. Comparison with mean airway diameter (d) and density [n (no. of MBs per cm2 of lung tissue)] of MBs obtained using standard morphometric techniques (random sections approximately 1 cm from the pleura) showed that the values of d and n are biased because of the inclusion in the measurements of a number of respiratory bronchioles and bronchi. When these misclassifications are corrected for, it appears that d corresponds quite well to the mean diameter of the terminal bronchioles (TB) and n to approximately twice the density of TBs. After correction, n is not significantly reduced in emphysematous lungs (the grossly destroyed areas being excluded) compared with normal lungs. The estimate of the number of TBs obtained from the present data is markedly less than that calculated by Weibel (Morphometry of the Human Lung. Berlin: Springer-Verlag, 1963), which suggests that the number of bronchi was overestimated by Weibel by at least one generation. Finally, values of peripheral airway resistance computed from the present anatomic data correspond quite well to direct measurement performed on the same lungs before fixation (Verbeken et al., J. Appl. Physiol. 72:2343-2353, 1992).

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.

Effect of rib cage and abdominal restriction on total respiratory resistance and reactance.

In 14 healthy male subjects we studied the effects of rib cage and abdominal strapping on lung volumes, airway resistance (Raw), and total respiratory resistance (Rrs) and reactance (Xrs). Rib cage, as well as abdominal, strapping caused a significant decrease in vital capacity (respectively, -36 and -34%), total lung capacity (TLC) (-31 and -27%), functional residual capacity (FRC) (-28 and -28%), and expiratory reserve volume (-40 and -48%) and an increase in specific airway conductance (+24 and +30%) and in maximal expiratory flow at 50% of control TLC (+47 and +42%). The decrease of residual volume (RV) was significant (-12%) with rib cage strapping only. Abdominal strapping resulted in a minor overall increase in Rrs, whereas rib cage strapping produced a more marked increase at low frequencies; thus a frequency dependence of Rrs was induced. A similar pattern, but with lower absolute values, of Rrs was obtained by thoracic strapping when the subject was breathing at control FRC. Xrs was decreased, especially at low frequencies, with abdominal strapping and even more with thoracic strapping; thus the resonant frequency of the respiratory system was shifted toward higher frequencies. Partitioning Rrs and Xrs into resistance and reactance of lungs and chest wall demonstrated that the different effects of chest wall and abdominal strapping on Rrs and Xrs reflect changes mainly of chest wall mechanics.