Computerized method for analyzing maximum and partial expiratory flow-volume curves.

Computerized instrumentation and software have been developed to obtain maximum expiratory flow-volume (MEFV) and partial expiratory flow-volume (PEFV) curves. The computerized system calculates and prints out the flow at 25% and 40% of control vital capacity (VC), the expiratory volume, peak expiratory flow rate and expiratory volume at one second (FEV1) divided by VC, the latter expressed as a percent. The flow-volume curves can be displayed on an oscilloscope or plotter and stored on magnetic tape. A pilot study was completed to demonstrate the reliability and validity of the data obtained.     

Model of forced expiratory flows and airway geometry in infants.

Early measurements of autopsied lungs from infants, children, and adults suggested that the ratio of peripheral to central airway resistance was higher in infants than older children and adults. Recent measurements of forced expiration suggest that infants have high flows relative to lung volume. We employed a computational model of forced expiratory flow along with physiological and anatomic data to evaluate whether the infant lung is a uniformly scaled-down version of the adult lung. First, we uniformly scaled an existing computational model of adult forced expiration to estimate forced expiratory flows (FEF) and density dependence for an 18-mo-old infant. The values obtained for FEF and density dependence were significantly lower than those reported for healthy 18-mo-old infants. Next, we modified the model for the infant lung to reproduce standard indexes of expiratory flow [forced expiratory volume in 0.5 s (FEV(0.5)), FEFs after exhalation of 50 and 75% forced vital capacity, FEF between 25 and 75% expired volume] for this age group. The airway sizes obtained for the infant lung model that produced accurate physiological measurements were similar to anatomic data available for this age and larger than those in the scaled model. Our findings indicate that the airways in the infant lung model differ from those in the scaled model, i.e., middle and peripheral airway sizes are larger than result from uniform downscaling of the adult lung model. We show that the infant lung model can be made to reproduce individual flow-volume curves by adjusting lumen area generation by generation.     

Analysis of the configuration of maximum expiratory flow-volume curves

The ratios of the instantaneous tangent slopes to corresponding chord slopes are sensitive to curvatures of flow-volume curves; and these dimensionless slope ratios, SR, plotted against fractional volumes remaining to be expired, VCf, are sensitive to the shape of flow-volume curves but insenitive to flow or volume magnitudes. SR-VCf curves predicted for lungs which empty homogeneously differ substantially from those predicted for lungs which empty nonhomogeneously, the latter showing systematic increases in SR with VCf which may extend beyond the homogeneous range. SR-VCf curves for some 80 healthy subjects show systematic changes with age (range 6-64 yr), but all are consistent with advanced obstructive lung disease (chronic bronchitis, emphysema, asthma) are consistent with nonhomogeneous emptying, but it does not seem likely that SR-VCf curves will prove useful for detecting early stages of disease.     

Airway dynamics in transition between peak and maximal expiratory flow

Expiratory flow-volume curves with periodic interruption of flow showed flow transients exceeding maximal flow (Vmax) measured on the maximum expiratory flow-volume (MEFV) curve in a mechanical lung model and in five tracheotomized, vagotomized, open-chest, anesthetized dogs. Direct measurement of flow from the collapsing model airway showed that the volume of the flow transients in excess of the MEFV envelope was greater than that from the collapsing airway. Determination of wave-speed flows from local airway transmural pressure-area curves (J. Appl. Physiol. 52: 357-369, 1982) and photography of the airway led to the following conclusions. Flow transients exceeding Vmax are wave-speed flows determined by an initial and unstable configuration of the flow-limiting segment (FLS) with maximum compression in the midportion. The drop in flow from the peak to the following plateau is due to development of a more stable airway configuration with maximum compression at the mouthward end with a smaller area and a smaller maximal flow. When FLS jumps to a more peripheral position, the more distal airways may pass through similar configurational changes that are responsible for the sudden decrease of flow (the "knee") seen on most MEFV curves from dogs.     

Continuous measurements of a binding reaction using a capacitive biosensor

A capacitive biosensor with polyclonal antibodies raised against human serum albumin (HSA) immobilized on a gold transducer has been developed for continuous measurement of HSA in the muM-range. A mathematical model has been refined to describe integral HSA-binding curves assuming that (i) binding is essentially irreversible under the conditions used, (ii) the signal is scaled as the number of non-occupied binding sites and (iii) the rate of disappearance of available binding sites is scaled as the number of available binding sites and analyte concentration in solution. Deconvolution of the curves using the mathematical model indicates clearly that it is possible to retrieve concentration profiles (isocratic, linearly or exponentially increasing gradients) of the analyte in the continuous sample flow from the normalized integral binding (NIB) curves. The data presented constitutes the theoretical background and the first step towards the development of an analytical system allowing on-line detection of the concentration profile of the analyte from NIB-curves. Since the system can be used for extended time periods between regeneration steps, a low frequency of regeneration steps can be expected.     

Effect of maximal respiratory manoeuvres on bronchial sensitivity of asthmatic patients as compared to normal people.

Cumulative dose-response curves to carbachol given by aerosol were established using plethysmographic measurements of specific airways resistance (SRaw) in 10 patients with asthma and five healthy subjects. Two experiments were performed--a control test and one in which maximal respiratory manoeuvres (MRM) (two maximal inspirations and two maximal expirations) were made before each carbachol inhalation. MRM did not modify the dose-response curves in the normal subjects. In the patients these manoeuvres enhanced the bronchoconstrictor effect of carbachol: curves were shifted to the left and the mean dose of carbachol producing a twofold increase in initial SRaw was decreased from 0.373 mg to 0.189 mg (P less than 0.001). Bronchial provocation tests using methods which require MRM--for example, forced expiratory volume at one second--could overestimate the bronchial sensitivity of patients with asthma.     

Effects of deep inhalation in asthma: relative airway and parenchymal hysteresis

Asthmatic subjects were screened for the effects or volume history on the degree of induced airway obstruction with methacholine by comparing isovolumic maximal expiratory flows (Vmax) from partial expiratory flow-volume curves (P) begun near functional residual capacity (FRC) followed by maximal expiratory flow-volume (M) maneuvers begun from total lung capacity (TLC). The isovolumic Vmax values from M and P maneuvers defined two groups: one had a high M/P ratio (high group), indicating a large degree of reversal with deep inhalation, another had a low M/P ratio (low group), indicating minimal reversal. No differences were found between groups. A more complete study was later performed in which we measured specific airway conductance (sGaw) and anatomical dead space (VD) as indices of airway size and hysteresis before and after deep inhalation. The area of quasi-static transpulmonary pressure (Ptp) volume (V) curves from FRC to TLC and back to FRC was measured as an index of parenchymal hysteresis. At base line both groups showed a decrease in both sGaw and VD after a deep inhalation (DI). After constriction neither group changed VD after DI, whereas sGaw increased significantly in the high group after DI. This suggests that dilation of airways with DI occurred peripheral to those contributing to VD in the high group. The areas of the Ptp-V curves were equal at base line; yet the increase in areas with constriction in the low group was much greater.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyroarytenoid muscle activity during hypoxia in awake lambs

It is generally accepted that hypoxia in early life results in active laryngeal braking of expiratory airflow via the recruitment of glottic adductor muscles. We examined the electromyogram expiratory activity of the thyroarytenoid muscle in seven 11- to 18-day-old awake nonsedated lambs exposed to an inspired O2 fraction of 0.08 for 18 min. The lambs breathed through a face mask and a pneumotachograph. During baseline prehypoxic breathing, the thyroarytenoid muscle was largely inactive in each awake lamb. Unexpectedly, no recruitment of the thyroarytenoid muscle was recorded during hypoxia in any of the seven lambs; simultaneous examination of the flow-volume curves revealed an absence of expiratory airflow braking. Also unexpectedly, marked expiratory activity of the thyroarytenoid muscle was recorded, with each expiration occurring within less than 10 s after the return to room air. The resulting delay of expiration was apparent in the flow-volume loops. Thus, in awake 11- to 18-day-old lambs, 1) active expiratory glottic adduction is absent during hypoxia and 2) a return from hypoxia to room air results in prolonged expiration as well as active glottic adduction that controls end-expiratory lung volume.     

Smooth muscle dynamics and maximal expiratory flow in asthma.

A computational model for maximal expiratory flow in constricted lungs is presented. The model was constructed by combining a previous computational model for maximal expiratory flow in normal lungs and a previous mathematical model for smooth muscle dynamics. Maximal expiratory flow-volume curves were computed for different levels of smooth muscle activation. The computed maximal expiratory flow-volume curves agree with data in the literature on flow in constricted nonasthmatic subjects. In the model, muscle force during expiration depends on the balance between the decrease in force that accompanies muscle shortening and the recovery of force that occurs during the time course of expiration, and the computed increase in residual volume (RV) depends on the magnitude of force recovery. The model was also used to calculate RV for a vital capacity maneuver with a slow rate of expiration, and RV was found to be further increased for this maneuver. We propose that the measurement of RV for a vital capacity maneuver with a slow rate of expiration would provide a more sensitive test of smooth muscle activation than the measurement of maximal expiratory flow.     

Effect of age on changes in flow rates and airway conductance after a deep breath

The effects of aging on changes in maximal expiratory flow rates and specific airway conductance after a deep breath were evaluated in 64 normal subjects. Flow rates (Vp) on partial expiratory flow-volume curves (PEFV), initiated from 60-70% of the vital capacity (VC), were compared with those (Vc) on maximal flow-volume curves (MEFV), initiated from total lung capacity (TLC), at a lung volume corresponding to 25% of VC on the MEFV curves. Specific airway conductance was measured before (sGaw) and after a deep inspiration (sGawDI). Bronchodilation after inspiration to TLC was inferred by Vp/Vc less than 1 and sGaw/sGawDI less than 1. The mean Vp was less than Vc. However, the ratio Vp/Vc increased significantly with age (r = 0.75, P less than 0.001). Specific conductance also increased after a deep inspiration (sGaw less than sGawDI). The ratio sGaw/sGawDIj increased slightly but significantly with age (r = 0.28, P less than 0.02). Measurement of lung elastic recoil pressures before and after a deep breath in a subgroup of patients (n = 14) suggested that the age-related increase in Vp/Vc was secondary to a decrement in the ability of a deep breath to decrease the upstream airway resistance. These findings suggest that even though changes in airway size after a deep breath as measured by sGaw/sGawDI have minimal age dependence, aging diminishes expiratory flow rates of MEFV curves relative to PEFV curves because of a decrease in the ability of a deep breath to increase the size of the peripheral airways.     

Interaction between Bronchoconstrictor Stimuli on Human Airway Smooth Muscle

In healthy human subjects, the simultaneous aerosol administration of histamine and methacholine results in a pronounced decrease in maximum flow rates on partial expiratory flow-volume (PEFV) curves. When given alone in the same concentrations, these drugs produced no or minimal decreases in flow rates. The results suggest an interaction of histamine and cholinergic stimuli on airway smooth muscle (ASM). This mechanism might explain many experiments where vagal blockade diminished or abolished ASM response to histamine and other stimuli, simply by interfering with histamine-cholinergic interaction at the ASM level. These findings confirm similar findings of animal in vitro experiments. The experiments clearly confirm the sensitivity and value of assessing drug effects prior to a deep breath. Flow-rate changes after a full inspiration, taken from the maximum expiratory flow-volume (MEFV) curve, show either no relationship to the concentration of inhaled methacholine or significantly less effect than that seen on the PEFV curve.     

A mathematical analysis of mechanical factors in the forced expiration

A one compartment, mechanical model of the human lung-thorax system is presented and mathematically analyzed. The equation relating the thoracic muscular stress to the expired air volume is developed and investigated. Assuming that the pressure drop along the airways is a linear function of air flow rate and that the effective lung-thorax compliance is constant, a form for the muscular stress as a function of time is developed. This is used to predict volume-time and flow-volume curves, which are compared to those measured on a normal individual. It appears that these theoretical results have the essential characteristics of the experimental curves. These results, coupled with the one-to-one correspondence between the parameters of the model and those of the prototype, suggest that this model should have great utility in the study of ventilatory mechanics.     

Effects of airway tone and volume history on maximal expiratory flow in asthma

We assessed the difference between isovolumic maximal expiratory flows (Vmax) using maneuvers begun at mid-lung volumes, so-called partial expiratory flow-volume curves (P), vs. those begun at full inflation, so-called maximal expiratory flow-volume curves (M), in 10 asthmatic subjects before and following obstruction induced by isocapnic hyperpnea with cold air and before and after bronchodilation with a beta-agonist or antimuscarinic agent. Volume history effects were quantitated as an M-to-P ratio of Vmax at 30% vital capacity (M/P V30). Although M/P V30 was variable among patients at base line, there was a uniform increase in M/P V30 during constriction and a consistent decrease below base line after dilation. Blunting of induced obstruction with beta-agonists also diminished the increase in M/P V30. Antimuscarinics, despite equivalent bronchodilation, failed to alter the degree of obstruction induced by cold air or the increase in M/P V30 seen during obstruction. The level of airway tone, as indicated by specific resistance, related directly to the M/P V30. We conclude that the response of the asthmatic lung to a deep inhalation is relatively predictable when acute changes in airway tone are produced.     

Objective evaluation measures of genetic marker selection in large-scale SNP genotyping

High-throughput single nucleotide polymorphism (SNP) genotyping systems provide two kinds of fluorescent signals detected from different alleles. In current technologies, the process of genotype discrimination requires subjective judgments by expert operators, even when using clustering algorithms. Here, we propose two evaluation measures to manage fluorescent scatter data with nonclear plot aggregation. The first is the marker ranking measure, which provides a ranking system for the SNP markers based on the distance between the scatter plot distribution and a user-defined ideal distribution. The second measure, called individual genotype membership, uses the membership probability of each genotype related to an individual plot in the scatter data. In verification experiments, the marker ranking measure determined the ranking of SNP markers correlated with the subjective order of SNP markers judged by an expert operator. The experiment using the individual genotype membership measure clarified that the total number of unclassified individuals was remarkably reduced compared to that of manually unclassified ones. These two evaluation measures were implemented as the GTAssist software. GTAssist provides objective standards and avoids subjective biases in SNP genotyping workflows.     

Models of the turning and fast-start swimming dynamics of aquatic vertebrates

Two models for unpowered and powered turns and C-type fast-starts were developed and applied to four different manoeuvres: unpowered turns by a streamlined fish (yellowfin tuna Thunnus albacares ), powered turns by an unstreamlined fish (boxfish Ostracion meleagris ), fast-starts (sticklebacks Gasterosteus spp.) and a manoeuvre by a steller sea lion Eumetopias jubatus deploying control surfaces (flippers). The velocity at the end of manoeuvres (terminal velocity) was employed as the 'benchmark variable' for comparisons of predicted and actual performance. Good agreement was found in all cases. A log–log plot of available experimental data for turning radius v. mass shows that turning radius scales to the 0·37 power of mass ( r ²= 0·73), close to the predicted value of 0·33. Recent interests in highly manoeuvrable aquatic vertebrates as biomimetic models for automated underwater vehicles adds to the practical utility of the models presented here.     

Inhalation of adenosine 5'-monophosphate increases methacholine airway responsiveness

Airway hyperresponsiveness is a characteristic feature in asthmatic subjects, but the mechanism of the hyperresponsiveness is not known. The purpose of this study was to investigate whether methacholine airway responsiveness was increased 24 h after inhalation of adenosine 5'-monophosphate (AMP). Ten atopic asthmatic subjects and six atopic normal subjects were studied on 4 study days. On the 1st day, a methacholine inhalation test was performed, followed within 48 h by an AMP inhalation test. Seven days later the second AMP test was performed, and 24 h later the methacholine inhalation test was repeated. Response was measured using partial flow-volume curves, and the concentration required to cause a 40% fall in the partial flow-volume curve (PC40) was calculated. The geometric mean methacholine PC40 fell from 1.36 mg/ml on day 1 (before AMP inhalation) to 0.71 mg/ml on day 4 (24 h after AMP inhalation, P less than 0.01). There was no change in the mean PC40 for adenosine on the 2 study days (5.82 and 7.06 mg/ml, P greater than 0.1). These findings suggest that adenosine release may contribute to the increase in airway responsiveness after allergen challenge.     

Threshold of airway response to inhaled methacholine in healthy men and women

Threshold of airway response to inhaled methacholine was determined using maximum expiratory partial flow-volume curves in 21 men and 36 women with similar age distribution, all of them healthy nonsmokers. Mean threshold was on average 1.3 doubling dose lower in women than men. There were no sex differences in the increase of maximum expiratory flows after a full inspiration when the airways were constricted by methacholine.     

The influence of resprouting forest canopy species on richness in Southern Cape forests, South Africa

We investigated the relationship between species richness and numbers and types of individuals and species present in forests with different physiognomies in the southern Cape Province, South Africa. Data were collected from three different ‘plot’ types: 400 m², canopy‐scaled (plot length is directly proportional to canopy height) and per 100 individuals closest to a point. Plots were designed to control for the effect of scale on local richness. Canopy species richness was inversely proportional to the abundance of resprouting species. The strength of the relationship between the abundance of resprouters and canopy species richness increased progressively from the 400 m² plots to the canopy‐scaled plots and finally to the plots of 100 individuals. Resprouter abundance decreased, while canopy species richness increased, with increasing canopy height. Resprouters are able to retain their in situ position in the forests for longer periods of time than do reseeders. This reduces individual and species turnover, thus reducing species richness in resprouter‐dominated forests.     

Transthoracic echocardiographic imaging of coronary arteries: tips, traps, and pitfalls

Background

This study explores the feasibility of non-invasive evaluation of left ventricular (LV) flow-volume dynamics using 3-dimensional (3D) echocardiography, and the capacity of such an approach to identify altered LV hemodynamic states caused by valvular abnormalities.

Methods

Thirty-one patients with moderate-severe aortic (AS) and mitral (MS) stenoses (21 and 10 patients, respectively) and 10 healthy volunteers underwent 3D echocardiography with full volume acquisition using Philips Sonos 7500 equipment. The digital 3D data were post- processed using TomTec software. LV flow-volume loops were subsequently constructed for each subject by plotting instantaneous LV volume data sampled throughout the cardiac cycle vs. their first derivative representing LV flow. After correction for body surface area, an average flow-volume loop was calculated for each subject group.

Results

Flow-volume loops were obtainable in all subjects, except 3 patients with AS. The flow-volume diagrams displayed clear differences in the form and position of the loops between normal individuals and the respective patient groups. In patients with AS, an "obstructive" pattern was observed, with lower flow values during early systole and larger end-systolic volume. On the other hand, patients with MS displayed a "restrictive" flow-volume pattern, with reduced diastolic filling and smaller end-diastolic volume.

Conclusion

Non-invasive evaluation of LV flow-volume dynamics using 3D-echocardiographic data is technically possible and the approach has a capacity to identify certain specific types of alteration of LV flow-volume pattern caused by valvular abnormalities, thus reflecting underlying hemodynamic states specific for these abnormalities.