Variance components analysis of forced expiration in families

Familial aggregation of forced expiration (as measured by forced expiratory volume in 1 sec (FEV1) and the ratio of this to total forced vital capacity (FEV1/FVC) was analyzed in 439 adult members of 108 families ascertained through control patients who had participated in a genetic and epidemiologic study of chronic obstructive pulmonary disease. Residual values for both FEV1 and FEV1/FVC obtained from regression on age, sex, race, and cigarette smoking (and height for FEV1) were used in a variance components analysis to assess the relative importance of genetic and nongenetic factors influencing familial aggregation of pulmonary function among adults. For both residual FEV1 and residual FEV1/FVC, the "best" model among a series of genetic and nongenetic models was a simple additive genetic model. A modified score test, which is robust to the assumption of multivariate normality, was used to test the significance of these estimated components. Under the most parsimonious model, additive genetic variation accounted for 28% of the variation in residual FEV1 in 108 families and 24% of the variation in residual FEV1/FVC. After outlying individuals were identified by examining goodness-of-fit statistics, the simple genetic model still gave the best fit to these data. There was little indication of non-normality in FEV1 in these families; however, FEV1/FVC did show evidence of non-normality when examining goodness-of-fit statistics. This genetic component contributing to the distribution of forced expiration may be a factor in the familial aggregation of certain respiratory diseases.     

Experiments on flow limitation during forced expiration in a monoalveolar lung model

To understand the mechanism of flow limitation during forced expiration, flow properties were studied using a rubber model made up of two elements in series: a balloon and a thin-walled collapsible tube. This elastic model was inserted into a rigid box and flow was provided by pressure ramps in the box. Flow rate and transmural pressures were then measured; wave speed and fluid velocity were calculated from the area-pressure law. For a sufficiently high flow rate, a flow-limiting segment was observed. The flow became supercritical relative to the small amplitude pressure wave speed and a choke flow occurred. Then the tube collapsed. Consequently, the fluid velocity decreased and the flow became subcritical throughout the entire tube. Thus the flow rate appeared to be limited by viscous effects.     

The measurement of air flow in a forced expiration using a pressure-sensitive transistor

A pressure-sensitive transistor has been tested as a pneumotachograph transducer for the measurement of forced expirations. A venturi head is used, as it is shown that, over most of the flow range, it has a better signal/drift ratio than a linear-resistance flowmeter of comparable resistance. Preliminary measurements on normal subjects show that f.e.v.₁ can be measured to an accuracy of 3% and the peak flow to approximately 5%. The accuracy of f.v.c. values is not as good, as it is limited by a threshold at the input of the venturi square-rooting circuit. Simple ways of overcoming this difficulty are suggested.     

Experimental and theoretical models of flow during forced expiration: pressure and pressure history dependence of flow rate

Flow characteristics have been studied in elastic mono- and bialveolar lung models made from tubes and balloons in series. Flow rate variation is explained on the basis of two successive limiting factors governed by the mutual interaction of tube mechanical properties and flow characteristics, i.e. wave-speed and viscous limitations induced by the tube collapse. A numerical model of flow in an elastic monoalveolar structure has been developed. It is generally admitted that a remarkable feature of forced expiration is that the flow rate is ‘effort independent’ for approximately the lower 80 per cent of vital capacity. The present results, which describe a continuous process, suggest that the flow rate depends mostly on the external pressure and pressure history. between the 15th August 1987 and the 31st August 1988, and at other periods to him at INSERM U. 296, Faculté de Médecine, 8 av Gl Sarrail, 94010 Creteil Cedex, France.     

Calculation of dynamic error for maximum volume velocity during forced expiration measured by the PT-1 pneumotachometer

Conclusions 1. The dynamic error of pneumotachometric measurements can be determined theoretically by simulating the forced-expiration process.2. The type PT-1 pneumotachometers have a significant dynamic measuring error that understates appreciably the true values of the maximum volumetric air velocity.3. The calculated value of dynamic error for pneumotachometric measurements is inversely proportional to the time interval t_o for the volume-velocity buildup during forced expiration. Since the value of t_o varies over a substantial range and is not known before-hand, it is impossible to correct the readings of a pneumotachometer with a specific correction factor.4. For the experimental determination and rating of dynamic measuring error in pneumotachometric instruments it will be necessary to introduce into the practice of medical instrument building standard metrological arrangements that produce calibrated, rapidly varying air flows.Kiev Production Union Medapparatura. Translated from Meditsinskaya Tekhnika, No. 1, pp. 28–35, January–February, 1982.     

Potentiating effect of spirometric maneuver on bronchial responsiveness to methacholine in asthmatic subjects--the role of deep inspiration and forced expiration

We previously reported that spirometric maneuver (SM) had potentiating effect on bronchial responsiveness (BR) in asthmatic subjects but not in normal subjects. SM consists of deep inspiration to TLC (DI) and forced expiration to RV (FE). In this study, we examined the effect of SM, DI and FE on BR in 9 asthmatic subjects. Provocative concentration of methacholine producing a 35% fall in respiratory conductance (PC35-Grs) was significantly (p less than 0.02 and p less than 0.025) decreased from 0.34 mg/ml (GSEM, 1.51) to 0.16 mg/ml (GSEM, 1.45) and 0.14 mg/ml (GSEM, 1.51) by SM and DI, respectively but it was not altered by FE. These findings indicate that potentiating effect of SM on BR which is characteristic of asthma may be due to DI effect.     

Forced expiration index, signal and noise

Although forced expiration measurements are extensively used, there is no general agreement concerning the best way to quantify the data. In this context, it may be of interest to examine indices from the point of view of their signal/noise ratio. The signal depends upon the actual sensitivity of the index to the kind of abnormality which is to be detected. In general, the relationship between signal and degree of abnormality is strongly non-linear, so that sensitivity is not a constant. The noise depends upon the kind of investigation which is made. When a subject is compared to himself (bronchomotor challenge, follow-up studies, etc.), it is mainly due to intraindividual variability. FEV1 is an example of index with a low sensitivity to peripheral airway abnormality, but a high reproducibility, so that its signal/noise ratio for paired measurements is comparatively good. When two groups are to be compared, the relevant noise is interindividual variability. Coefficient of variation of transit times and slope ratios are quite effective in detecting abnormalities in young smokers, probably because their sensitivity to mild peripheral airway disease is large compared to their interindividual variability. It follows that, according to the type of study, as well as to the nature and extent of abnormality, many indices may qualify as being the best.     

Reflex prolongation of stage I of expiration

Experiments were performed on anesthetized cats to test the theory that the interval between phrenic bursts is comprised of two phases, stage I and stage II of expiration. Evidence that these represent two separate neural phases of the central respiratory rhythm was provided by the extent to which stage duration is controlled individually when tested by superior laryngeal, vagus and carotid sinus nerve stimulation. Membrane potential trajectories of bulbar postinspiratory neurons were used to identify the timing of respiratory phases.Stimulation of the superior laryngeal, vagus and carotid sinus nerves during stage I of expiration prolonged the period of depolarization in postinspiratory neurons without significantly changing the durations of either stage II expiratory or inspiratory inhibition, indicating a fairly selective prolongation of the first stage of expiration. Changes in subglottic pressure, insufflation of smoke into the upper airway, application of water to the larynx or rapid inflation of the lungs produced similar effects. Sustained tetanic stimulation of superior laryngeal and vagus nerves arrested the respiratory rhythm in stage I of expiration. Membrane potentials in postinspiratory, inspiratory and expiratory neurons were indicative of a prolonged postinspiratory period. Thus, such an arrhythmia can be described as a postinspiratory apneic state of the central oscillator. The effects of carotid sinus nerve stimulation reversed when the stimulus was applied during stage II expiration. This was accompanied by corresponding changes in the membrane potential trajectories in postinspiratory neurons.The results manifest a ternary central respiratory cycle with two individually controlled phases occurring between inspiratory bursts.     

Lateral parabrachial nucleus mediates shortening of expiration during hypoxia

Acute hypoxia elicits complex time-dependent responses including rapid augmentation of inspiratory drive, shortening of inspiratory and expiratory durations (T(I), T(E)), and short-term potentiation and depression. The central pathways mediating these varied effects are largely unknown. Here, we show that the lateral parabrachial nucleus (LPBN) of the dorsolateral pons specifically mediates T(E)-shortening during hypoxia and not other hypoxic response components. Twelve urethane-anesthetized and vagotomized adult Sprague-Dawley rats were exposed to 1-min poikilocapnic hypoxia before and after unilateral kainic acid or bilateral electrolytic lesioning of the LPBN. Bilateral lesions resulted in a significant increase in baseline T(E) under hyperoxia. After unilateral or bilateral lesions, the decrease in T(E) during hypoxia was markedly attenuated without appreciable changes in all other hypoxic response components. These findings add to the mounting evidence that the central processing of peripheral chemoafferent inputs is segregated into parallel integrator and differentiator (low-pass and high-pass filter) pathways that separately modulate inspiratory drive, T(I), T(E) and resultant short-term potentiation and depression.     

Determination of rate-constants as a method to describe passive expiration

To describe the relaxed expiration by a two-compartment model, we introduced a gas/energy transfer between the lung compartment (V₁) and a second one (V₂). If V₂ were a real volume, the rate-constants (i.e. the flow/volume ratios) of the compartments would describe a real gas-exchange. Alternatively, if a viscoelastic behaviour of the lung or an energy-exchange between compartments was simulated, V₂ would become a "pseudo-volume". We studied nine mechanically ventilated subjects. Changes in volume were transduced by respiratory inductive plethysmography. The rate-constants were assumed (together with the initial volumes of the compartments) as parameters to fit the total volume [V₁(t)+V₂(t)]. Once the best fitting was performed using these "physiological" parameters, the system was directly identified and the compartments were independently analysed. The time profile of the second compartment showed a maximum that depended on the value of the rate-constants. Appropriate tests confirmed the reliability of our procedure. In conclusion, our analysis demonstrated that the energy/volume of the second compartment may increase at the beginning of expiration and then decrease, showing a maximum, even though the total curve can only be a decreasing one. In other words, the slowing down of the curve representing expiratory volume is due not only to the longer emptying of the second compartment, but also to the interaction between the two compartments. As presently proposed, this interaction can be represented by either a gas exchange between two actual volumes, or a mechanical energy transfer between the lung and the tissue compartment.     

Distinct rhythm generators for inspiration and expiration in the juvenile rat

Inspiration and active expiration are commonly viewed as antagonistic phases of a unitary oscillator that generates respiratory rhythm. This view conflicts with observations we report here in juvenile rats, where by administration of fentanyl, a selective μ-opiate agonist, and induction of lung reflexes, we separately manipulated the frequency of inspirations and expirations. Moreover, completely transecting the brainstem at the caudal end of the facial nucleus abolished active expirations, while rhythmic inspirations continued. We hypothesize that inspiration and expiration are generated by coupled, anatomically separate rhythm generators, one generating active expiration located close to the facial nucleus in the region of the retrotrapezoid nucleus/parafacial respiratory group, the other generating inspiration located more caudally in the preBötzinger Complex.