Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects.

BACKGROUND: Obesity is associated with increased prevalence and incidence of asthma, but the mechanism is unknown. Obesity reduces lung volumes, which can increase airway responsiveness, and increases resistive and elastic work of breathing, which can increase dyspnea. OBJECTIVE: To determine if the intensity of dyspnea due to airway narrowing or if airway responsiveness is increased in obese, non-asthmatic subjects. SUBJECTS: Twenty-three obese (BMI (body mass index) > or =30 kg m(-2)) and 26 non-obese (BMI <30 kg m(-2)) non-asthmatic subjects, aged between 18 and 70 years. METHODS: High-dose methacholine challenge was used to determine the sensitivity and the maximal response to methacholine. Respiratory system resistance (Rrs) and reactance were measured, using the forced oscillation technique, as indicators of resistive and elastic loads during challenge. Perception of dyspnea was measured by the Borg score during challenge. Static lung volumes were measured by body plethysmography. RESULTS: Static lung volumes were reduced in the obese subjects. There were no significant differences in the sensitivity or maximal response to methacholine between obese and non-obese subjects. The magnitude of change in Rrs was similar in both groups, but obese subjects had more negative reactance after challenge (P=0.002) indicating a greater elastic load. The intensity of dyspnea was greater in obese subjects (P=0.03). CONCLUSIONS: Obesity reduces lung volumes, but does not alter the sensitivity or maximal response to methacholine. However, obese subjects have enhanced perception of dyspnea, associated with greater apparent stiffness of the respiratory system, and may therefore be at greater risk of symptoms.

The effects of body weight on airway calibre.

Increased wheeze and asthma diagnosis in obesity may be due to reduced lung volume with subsequent airway narrowing. Asthma (wheeze and airway hyperresponsiveness), functional residual capacity (FRC) and airway conductance (Gaw) were measured in 276 randomly selected subjects aged 28-30 yrs. Data were initially adjusted for smoking and asthma before examining relationships between weight and FRC (after adjustment for height), and between body mass index (BMI = weight.height(-2)) and Gaw (after adjustment for FRC) by multiple linear regression, separately for females and males. For males and females, BMI (+/-95% confidence interval) was 27.0+/-4.6 kg.m(-2) and 25.6+/-6.0 kg.m(-2) respectively, Gaw was 0.64+/-0.04 L.s(-1).cmH2O(-1) and 0.57+/-0.03 L.s(-1).cmH2O(-1), and FRC was 85.3+/-3.4 and 84.0+/-2.9% of predicted. Weight correlated independently with FRC in males and females. BMI correlated independently and inversely with Gaw in males, but only weakly in females. In conclusion, obesity is associated with reduced lung volume, which is linked with airway narrowing. However, in males, airway narrowing is greater than that due to reduced lung volume alone. The mechanisms causing airway narrowing and sex differences in obesity are unknown.

Airway re-narrowing following deep inspiration in asthmatic and nonasthmatic subjects.

After bronchoconstriction, deep inspiration (DI) causes dilatation followed by airway re-narrowing. Re-narrowing may be faster in asthmatic than nonasthmatic subjects. This study investigated the relationship between re-narrowing and the magnitude of both DI-induced dilatation and the volume-dependence of respiratory system resistance (Rrs) during tidal breathing. In 25 asthmatic and 18 nonasthmatic subjects the forced oscillation technique was used to measure Rrs at baseline and after methacholine challenge, during 1 min of tidal breathing, followed by DI to total lung capacity (TLC) and passive return to functional residual capacity (FRC). Dilatation was measured as the decrease in Rrs between end tidal inspiration and TLC, re-narrowing as Rrs at FRC immediately after DI, as per cent Rrs at end-tidal expiration, and volume dependent tidal fluctuation as the difference between mean Rrs at end-expiration and end-inspiration. Asthmatic subjects had greater re-narrowing, less dilatation, and greater tidal fluctuations both at baseline and after challenge. Re-narrowing correlated with baseline tidal fluctuation and inversely with dilatation. Both baseline tidal fluctuation and dilatation were significant independent predictors of re-narrowing. Following deep inspiration-induced dilatation, faster airway re-narrowing in asthmatic than nonasthmatic subjects is associated not only with reduced deep inspiration-induced dilatation but also with some property of the airways that is detectable prior to challenge as an increased volume dependence of resistance.

The Autosow raised miniature swine as a model for assessing the effects of dietary soy trypsin inhibitor.

Toxicological effects of dietary soy trypsin inhibitor (TI) were assessed in male miniature swine, a model chosen for its similarities to human digestive physiology and anatomy. The TI preparation was extracted from defatted raw soy flour. From 1 through 5 weeks of age, piglets were automatically fed either a TI liquid diet [Autosow TI group (ASTI)] or a control liquid diet [Autosow control group (ASC)]. From 6 to 39 weeks of age, these animals received either swine chow and TI or swine chow and control article. The TI diets were formulated to contain a TI activity of approximately 500 mg TI/100 g dry matter. A sow control (SC) group suckled from birth to 6 weeks of age and then fed as the ASC group with swine chow plus control article from 6 to 39 weeks of age. The SC piglets grew faster than ASC piglets during postnatal weeks 1 and 2; however, the ASC piglets were significantly heavier than the SC piglets (P=0.001) at 6 weeks of age. Compared with the ASC group, TI caused a moderate decrease in feed consumption and a moderate but reversible decrease in growth from 2 to 5 weeks of age, but not thereafter. Some control and TI-fed Autosow-reared piglets had loose stools until 6 weeks of age; the effect was significantly greater in the TI-fed group. Otherwise, all swine were active and had normal appearance and behavior.

Patterns of breath support in projection of the singing voice.

Recordings of the rib cage and abdominal motions and acoustic output were obtained from five professional opera singers during performance of an aria recorded with two levels of voice projection. The condition of greater projection resulted in a significant increase in the acoustic power in the frequency band 2-4 kHz, relative to the power in the 0-2 kHz band, and a decrease in the mean expiratory flow, implying a move to more efficient vocalization with the greater projection. Also, the condition of greater projection resulted in a larger rib cage, particularly in the lateral dimension, but only a small decrease in the abdominal lateral dimension, suggesting that the greater abdominal support required for a larger projection is obtained by increased activation of abdominal muscles acting medially.

Respiratory function in operatic singing: effects of emotional connection.

The respiratory patterns of five professional operatic singers when performing with "emotional connection" (EC) as if communicating to an audience were compared with "technical" (T) singing as if rehearsing. Recordings of the performances were played to experienced listeners to provide independent confirmation of the singers' intentions. The findings show that, in comparison with T singing, EC singing, especially in the aria task, used more air with a greater percentage of vital capacity (VC) expired per second, but without a simple association with sound pressure level (SPL) or breath (phrase) duration. These findings suggest that the performing state of mind itself can effect technical results in operatic singing. Pedagogical implications are discussed.

Automatic control of pressure support mechanical ventilation using fuzzy logic.

There is currently no universally accepted approach to weaning patients from mechanical ventilation, but there is clearly a feeling within the medical community that it may be possible to formulate the weaning process algorithmically in some manner. Fuzzy logic seems suited this task because of the way it so naturally represents the subjective human notions employed in much of medical decision-making. The purpose of the present study was to develop a fuzzy logic algorithm for controlling pressure support ventilation in patients in the intensive care unit, utilizing measurements of heart rate, tidal volume, breathing frequency, and arterial oxygen saturation. In this report we describe the fuzzy logic algorithm, and demonstrate its use retrospectively in 13 patients with severe chronic obstructive pulmonary disease, by comparing the decisions made by the algorithm with what actually transpired. The fuzzy logic recommendations agreed with the status quo to within 2 cm H(2)O an average of 76% of the time, and to within 4 cm H(2)O an average of 88% of the time (although in most of these instances no medical decisions were taken as to whether or not to change the level of ventilatory support). We also compared the predictions of our algorithm with those cases in which changes in pressure support level were actually made by an attending physician, and found that the physicians tended to reduce the support level somewhat more aggressively than the algorithm did. We conclude that our fuzzy algorithm has the potential to control the level of pressure support ventilation from ongoing measurements of a patient's vital signs.

Effect of stochastic heterogeneity on lung impedance during acute bronchoconstriction: a model analysis.

In a previous study (J. H. T. Bates, A. M. Lauzon, G. S. Dechman, G. N. Makaym, and T. F. Schuessler. J. Appl. Physiol. 76: 616-626, 1994), we investigated the acute changes in isovolume lung mechanics immediately after a bolus injection of histamine. We found that dynamic resistance and elastance increased progressively in the 80-s period after injection, whereas the estimated tissue hysteresivity reached a stable plateau after approximately 25 s. In the present study, we developed a computer model of the lung to investigate the mechanisms responsible for these observations. The model conforms to Horsfield's morphometry, with the addition of compliant airways and structural damping tissue units. Using this model, we simulated the time course of acute bronchoconstriction after intravenous administration of a bolus of bronchial agonist. Heterogeneity was induced by randomly varying the values of the maximal airway smooth muscle contraction and the tissue response to the agonist. Our results demonstrate that much of the increase in lung impedance observed in our previous study can be produced purely by the effects of airway heterogeneity. However, we were only able to reproduce the plateauing of hysteresivity by assigning a minimum radius to each airway, beyond which it would immediately snap completely shut. We propose that airway closure played an important role in our experimental observations.

Towards a quantitative description of asthmatic cough sounds.

This study describes a method of quantitatively characterizing cough sounds using digital signal processing techniques. Differences between asthmatic and non-asthmatic cough sounds are presented. Coughs from 12 asthmatic and 5 non-asthmatic subjects were analysed. Cough sounds and flows were digitized, at a sampling rate of 5 kHz, before and after a free-running exercise test. Individual coughs were divided into two or three phases, corresponding to the initial glottal opening burst, the quieter middle phase, and (sometimes) the final closing burst. Standard signal processing techniques were then invoked to characterize the spectral and temporal shapes of the first two phases. Factor analysis indicated that the spectral shapes of the two phases are independent, with each being largely described by the degree of "peakedness" in the spectrum, and by the balance of energy between low and high frequencies. Both the duration of the initial burst and zero-crossing rates of the cough waveform (which indicates the "spectral balance") during each of the first two phases were smaller for asthmatic than for non-asthmatic coughs. Fewer asthmatic coughs contained a final burst. Discriminant analysis between the two groups gave classification error rates of 20-30%. The peak flow recorded during the cough was significantly smaller for asthmatics, and correlated very well with the peak flow recorded during forced expiration. Thus, significant differences exist between asthmatic and non-asthmatic cough sounds. An effective representation of the temporal structure of the cough sound is required to successfully characterize the cough.

Intrinsic echolocation capability of Hector's dolphin, Cephalorhynchus hectori.

A sonar system's echolocation capabilities can be inferred from the ambiguity distribution (defined here in terms of the conventional signal response function) of each of its transmitted signals. Several records of sounds emitted by Hector's dolphin are analyzed. The computed ambiguity distributions indicate that the sonar clicks of Hector's dolphins should be capable of resolving the ranges of targets as close together as 2 cm apart, but that target velocities cannot be resolved to any useful degree from a single echo.

A microcomputer-based interactive cough sound analysis system.

The occurrence and nature of cough sounds, especially those occurring in asthma in young children, is of considerable interest to workers in paediatrics and general practice. To facilitate our research into the characteristics of such sounds, we have developed a microcomputer-based analysis system, which we call COFF. In this paper we discuss the design and implementation of the system, emphasising its user-friendly, interactive features, and the manner in which it efficiently manages the large amounts of data that research into sounds incurs. We illustrate the operation of the system with examples of spectrograms computed from cough sounds recorded simultaneously at the mouth and through the chest wall.

Mycotoxin methodology.

The development of methods with high specificity and low limits of determination, as well as screening methods that are convenient for detection and rough quantitation of mycotoxins, has proceeded at an accelerating rate over the past few years. Of particular interest has been the widespread application of high performance liquid chromatographic and immunoassay techniques in mycotoxin methodology. An overview of the latest developments in mycotoxin methodology is presented with emphasis on the need for attention to sampling and sample preparation, the basic principles supporting the analytical methodology, the need for techniques to confirm analyte identification, and the requirement for high-quality reference materials.

A portable system for the spectral analysis of cough sounds in asthma.

A practical and portable method is described to analyze the sound spectra of coughs. The system is based upon a personal computer and simultaneously collects the sounds of cough heard both at the mouth and through the chest wall together with the airflow at the mouth produced during the cough. Subsequent analysis produce spectrographs of the cough sound linked to the corresponding airflow. The system will be used initially to examine the effects of exercise on the sound of cough in asthma. Further study of cough spectra in this way may be useful in the management of asthma either diagnostically or in the assessment of therapeutic interventions.

Cough sound analysis: a new tool for the diagnosis of asthma?

A method of computerized cough sound analysis is described. The sounds of nocturnal and post-exercise coughs from a child with asthma were compared with those from a child without asthma. The spectrographic patterns of voluntary cough at rest from the two children were similar. The pattern seen after exercise from the asthmatic child was different from the resting cough but similar to that seen during recorded nocturnal cough. In contrast the post-exercise cough from the non-asthmatic child was similar to the cough seen at rest. Refinement of this method of cough sound analysis may be useful in the diagnosis of asthma in young children.

Thin layer chromatographic method for determination of deoxynivalenol in wheat: collaborative study.

A collaborative study of a rapid method for the determination of deoxynivalenol (DON) in winter wheat was successfully completed. The method involves sample extraction with acetonitrile-water (84 + 16), cleanup using a disposable column of charcoal, Celite, and alumina, and detection by thin layer chromatography after spraying with an aluminum chloride solution. Each of the 15 collaborators analyzed 12 samples, 2 of which were naturally contaminated, and 10 to which DON was added, in duplicate, at levels of 0, 50, 100, 300, and 1000 ng/g. Average recoveries of DON ranged from 78 to 96% with repeatabilities of 30-64% and reproducibilities of 33-87%. The results of the study show that false positives were not a problem and that all of the analysts could detect DON at the 300 ng/g level or higher. The method has been adopted official first action.

Deoxynivalenol in winter wheat: thin layer chromatographic method and survey.

A rapid method for the determination of deoxynivalenol (DON) in wheat was used to analyze 57 wheat samples collected from 4 midwestern states where the winter wheat crop was contaminated with Fusaria. The method involves sample extraction with acetonitrile-water (84 + 16), cleanup by charcoal-alumina column chromatography, and determination by thin layer chromatography (TLC), using an AlCl3 solution spray and heat to form a fluorescent derivative. Recoveries of DON added to wheat at levels as low as 0.2 micrograms/g averaged greater than 80%. DON was detected at an average level of 3.6 micrograms/g; the levels ranged from 0.2 to 9.0 micrograms/g in 54 of 57 of the wheat samples. The quantity of DON was, in general, proportional to the percentage of total damaged kernels (grade). The chemical identity of DON was confirmed by mass spectrometry after isolation with preparative TLC.

High pressure liquid chromatographic determination of xanthomegnin in grains and animal feeds.

A high pressure liquid chromatographic (HPLC) method is described for the determination of xanthomegnin in grains and mixed animal feeds at levels ranging from 150 to 1200 ng/g. This is equivalent to actual amounts of xanthomegnin injected on the HPLC system at from 15 to 120 ng/injection. Xanthomegnin is extracted with chloroform and 0.1M phosphoric acid. An aliquot of the crude extract is purified by column chromatography using a commercially available silica gel cartridge. Xanthomegnin is then separated from the remaining interferences by HPLC with a reverse phase C-8 column, and subsequently determined by absorbance detection at 405 nm. Elapsed time for the method from initial extraction to final HPLC determination is approximately 1 h. Recoveries of xanthomegnin added to grains and animal feeds at levels from 150 to 1200 ng/g averaged 82% with a coefficient of variation of 10.2%.

Is the low-dose pill always preferable?

PIP: Response to a previous article which provided an assessment of the oral contraceptive pill after 20 years. The author notes that the article did not adequately address the problem of patient compliance. While supporting the proposition that women should use the lowest dose pill consistent with efficacy, the author notes that several of his clinic patients became pregnant after missing 3 or 4 pills in a monthly cycle while on a 35-mcg estrogen pill, and that fewer became pregnant after missing several pills, when they were on 50 mcg pills. More instances of breakthrough bleeding and amenorrhea among women using low-dose pills were also encountered. The author emphasizes the need for physicians to consider the needs of each individual patient before prescribing an oral contraceptive.^ieng