The physiology of small airways.
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Airway Obstruction↗
Biomedical subjects
P T Macklem
Publications and source records attributed to P T Macklem.
Urban-rural differences in questionnaire-derived markers of asthma in Kenyan school children.
Grade 4 Kenyan children attending 10 randomly selected public primary schools in Nairobi (urban) and the Muranga District (rural) were surveyed to establish the prevalence of symptom markers of asthma and to assess the impact of urbanization. A respiratory health and home environment questionnaire was administered at school to parents or guardians. The questionnaire response rates were 94.2% (568/ 603) for Nairobi and 89.6% (604/674) for Muranga. The prevalence rates for asthma, defined as "attacks of shortness of breath with wheeze", were 9.5% for urban and 3.0% for rural children (odds ratio (OR) urban versus rural: 3.42; 95% confidence interval (CI): -1.96-5.91). This urban-rural gradient persisted after adjusting for urban-rural differences in host factors (including duration of breastfeeding and family history of asthma and/or allergy), but was largely explained by urban-rural differences in environmental factors, including indoor animals, sharing a bedroom with a smoker, parental education, house ventilation and exposure to motor vehicle fumes en route to school (adjusted OR: 1.59; 95% CI: 0.70-3.55). Similar results were obtained for all other symptoms. These findings confirm the clinical impression that asthma is an important illness in Kenya and underline the need for the further study of environmental factors amenable to intervention, particularly in urban areas.
Adolescent↗
Measurement of elastic properties of Xenopus oocytes.
Elastic properties of Xenopus oocytes were examined by measuring intracellular pressure (Pic) and cell volume (Vc) in cells undergoing osmotic swelling. Pic was measured by micropuncture, using the servo-null technique. Vc was obtained by analyzing images acquired from a microscope having a video camera attachment. During osmotic swelling, Pic increased from 61 +/- 17 to 500 +/- 59 Pa (mean +/- SE), but the relationship with volume was not linear. In cells that underwent sequential swelling and shrinking, Pic was always lower on shrinking and the cells showed hysteresis. Cells with vitelline envelope (VE) removed had Pic-Vc curves similar in shape to those of intact cells; however, Pic values were significantly lower. Specific elastance[delta Pic/(delta Vc/Vc)] was reduced by removal of the VE. The data indicate that oocytes are weakly elastic and that a large part of their resistance to expansion resides in the VE.
Animals↗
Respiratory effort sensation during exercise with induced expiratory-flow limitation in healthy humans.
Nine healthy subjects (age 31 +/- 4 yr) exercised with and without expiratory-flow limitation (maximal flow approximately 1 l/s). We monitored flow, end-tidal PCO2, esophageal (Pes) and gastric pressures, changes in end-expiratory lung volume, and perception (sensation) of difficulty in breathing. Subjects cycled at increasing intensity (+25 W/30 s) until symptom limitation. During the flow-limited run, exercise performance was limited in all subjects by maximum sensation. Sensation was equally determined by inspiratory and expiratory pressure changes. In both runs, 90% of the variance in sensation could be explained by the Pes swings (difference between peak inspiratory and peak expiratory Pes). End-tidal PCO2 did not explain any variance in sensation in the control run and added only 3% to the explained variance in the flow-limited run. We conclude that in healthy subjects, during normal as well as expiratory flow-limited exercise, the pleural pressure generation of the expiratory muscles is equally related to the perception of difficulty in breathing as that of the inspiratory muscles.
Adult↗
Rib cage mechanics during quiet breathing and exercise in humans.
During exercise, large pleural, abdominal, and transdiaphragmatic pressure swings might produce substantial rib cage (RC) distortions. We used a three-compartment chest wall model (J. Appl. Physiol. 72: 1338-1347, 1992) to measure distortions of lung- and diaphragm-apposed RC compartments (RCp and RCa) along with pleural and abdominal pressures in five normal men. RCp and RCa volumes were calculated from three-dimensional locations of 86 markers on the chest wall, and the undistorted (relaxation) RC configuration was measured. Compliances of RCp and RCa measured during phrenic stimulation against a closed airway were 20 and 0%, respectively, of their values during relaxation. There was marked RC distortion. Thus nonuniform distribution of pressures distorts the RC and markedly stiffens it. However, during steady-state ergometer exercise at 0, 30, 50, and 70% of maximum workload, RC distortions were small because of a coordinated action of respiratory muscles, so that net pressures acting on RCp and RCa were nearly the same throughout the respiratory cycle. This maximizes RC compliance and minimizes the work of RC displacement. During quiet breathing, plots of RCa volume vs. abdominal pressure were to the right of the relaxation curve, indicating an expiratory action on RCa. We attribute this to passive stretching of abdominal muscles, which more than counterbalances the insertional component of transdiaphragmatic pressure.
Abdomen↗
Human respiratory muscle actions and control during exercise.
We measured pressures and power of diaphragm, rib cage, and abdominal muscles during quiet breathing (QB) and exercise at 0, 30, 50, and 70% maximum workload (Wmax) in five men. By three-dimensional tracking of 86 chest wall markers, we calculated the volumes of lung- and diaphragm-apposed rib cage compartments (Vrc,p and Vrc,a, respectively) and the abdomen (Vab). End-inspiratory lung volume increased with percentage of Wmax as a result of an increase in Vrc,p and Vrc,a. End-expiratory lung volume decreased as a result of a decrease in Vab. DeltaVrc,a/DeltaVab was constant and independent of Wmax. Thus we used DeltaVab/time as an index of diaphragm velocity of shortening. From QB to 70% Wmax, diaphragmatic pressure (Pdi) increased approximately 2-fold, diaphragm velocity of shortening 6.5-fold, and diaphragm workload 13-fold. Abdominal muscle pressure was approximately 0 during QB but was equal to and 180 degrees out of phase with rib cage muscle pressure at all percent Wmax. Rib cage muscle pressure and abdominal muscle pressure were greater than Pdi, but the ratios of these pressures were constant. There was a gradual inspiratory relaxation of abdominal muscles, causing abdominal pressure to fall, which minimized Pdi and decreased the expiratory action of the abdominal muscles on Vrc,a gradually, minimizing rib cage distortions. We conclude that from QB to 0% Wmax there is a switch in respiratory muscle control, with immediate recruitment of rib cage and abdominal muscles. Thereafter, a simple mechanism that increases drive equally to all three muscle groups, with drive to abdominal and rib cage muscles 180 degrees out of phase, allows the diaphragm to contract quasi-isotonically and act as a flow generator, while rib cage and abdominal muscles develop the pressures to displace the rib cage and abdomen, respectively. This acts to equalize the pressures acting on both rib cage compartments, minimizing rib cage distortion.
Abdominal Muscles↗
Inspiratory muscle dysfunction as a cause of death in COPD patients.
Although fatigue of the inspiratory muscles has been well documented, its prevalence in patients with chronic obstructive pulmonary disease (COPD) and its influence on mortality are unknown, because of the lack of a simple, clinically available diagnostic test. The hypothesis and experimental evidence relating inspiratory muscle dysfunction to the development of hypercapnia and hypercapnic ventilatory failure are reviewed. Since a poor prognosis in COPD is associated with carbon dioxide retention, inspiratory muscle weakness and/or fatigue may have an association with survival in these patients.
Cause of Death↗
Exercise-induced bronchospasm: a pilot survey in Nairobi school children.
Exercise-induced bronchospasm (EIB), a common feature of asthma in children, has been used as the outcome measure in community-based surveys of childhood asthma to circumvent difficulties arising from relative lack of objectivity in the use of questionnaires in communities with different cultural and language orientations. We report here the results of the first community-based study of childhood asthma in Kenya using EIB as the outcome measurement. The data was collected in a pilot study to develop methodology for a larger subsequent study. The survey targeted grade four children in five Nairobi City Council school each representing a neighbourhood social economic status (SES). Out of 597 eligible, 408 children took part in the study (68% participation rate). EIB defined as decline in FEV1 of 15% or more, post-exercise was found in 10.5% (95% CI; 10.3, 10.7) of the children studied, the highest rate reported so far in Africa. While boys were more likely to exhibit EIB compared to girls, the prevalence of EIB tended to decrease with age, especially among children residing in low SES neighbourhoods where the EIB prevalence rates tended to be lower compared to those among children from higher SES neighbourhoods. However, none of these differences was statistically significant. This study confirms the feasibility of undertaking exercise challenge tests in the African context and we recommend that additional studies of similar nature be carried out in other populations of Africa to explore the potential of using an exercise test as a marker of asthma in epidemiologic studies.
Age Distribution↗
Intracellular pressure is a motive force for cell motion in Amoeba proteus.
The cortical filament layer of free-living amoebae contains concentrated actomyosin, suggesting that it can contract and produce an internal hydrostatic pressure. We report here on direct and dynamic intracellular pressure (P(ic)) measurements in Amoeba proteus made using the servo-null technique. In resting apolar A. proteus, P(ic) increased while the cells remained immobile and at apparently constant volume. P(ic) then decreased approximately coincident with pseudopod formation. There was a positive correlation between P(ic) at the onset of movement and the rate of pseudopod formation. These results are the first direct evidence that hydrostatic pressure may be a motive force for cell motion. We postulate that contractile elements in the amoeba's cortical layer contract and increase P(ic) and that this P(ic) is utilized to overcome the viscous flow resistance of the intracellular contents during pseudopod formation.
Amoeba↗
Invited editorial on "airflow effects on amplitude and spectral content of normal breath sounds".
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Air Pressure↗
Influence of global inspiratory muscle fatigue on breathing during exercise.
We evaluated the effect of global inspiratory muscle fatigue (GF) on respiratory muscle control during exercise at 30, 60, and 90% of maximal power output in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. Esophageal and gastric pressures, anteroposterior displacement of the rib cage and abdomen, breathing pattern, and perceived breathlessness were measured. Induction of GF had no effect on the ventilatory parameters during mild and moderate exercise. It altered, however, ventilatory response to heavy exercise by increasing breathing frequency and minute ventilation, with minor changes in tidal volume. This was accompanied by an increase in perceived breathlessness. GF significantly increased both the tonic and phasic activities of abdominal muscles that allowed 1) the diaphragm to maintain its function while developing less pressure, 2) the same tidal volume with lesser shortening of the rib cage inspiratory muscles, and 3) relaxation of the abdominal muscles to contribute to lung inflation. The increased work performed by the abdominal muscles may, however, lead to a reduction in their strength. GF may impair exercise performance in some healthy subjects that is probably not related to excessive breathlessness or other ventilatory factors. We conclude that the respiratory system is remarkably adaptable in maintaining ventilation during exercise even with impaired inspiratory muscle contractility.
Adult↗
Human rib cage distortability.
In five normal men, we divided the rib cage into lung-apposed [pulmonary rib cage (RCp)] and diaphragm-apposed [abdominal rib cage (RCab)] compartments and calculated their absolute cross-sectional areas (Arc,p and Arc,ab) by anteroposterior and lateral dimensions measured by magnetometry. Distortion was quantified as the displacement of RCp and RCab produced by diaphragmatic twitches away from the relaxed configuration. We measured transdiaphragmatic pressure as the difference between gastric and esophageal pressures. Distortability was expressed as percent distortion per transdiaphragmatic pressure and varied among individuals from 0.02 to 0.23%/cmH2O. The pressure acting to restore the distorted rib cage back to its relaxed shape (Plink) varied from 0.1 to 31.3 cmH2O/%distortion. Distortion correlated positively (r = 0.92) and Plink per percent distortion negatively (r = -0.90) with RCab compliance during the relaxation maneuver (delta Arc, ab/delta gastric pressure). We conclude that rib cage distortability varies widely among normal subjects and is closely linked to RCab compliance.
Abdomen↗
Association of chest wall motion and tidal volume responses during CO2 rebreathing.
The purpose of this study is to investigate the effect of chest wall configuration at end expiration on tidal volume (VT) response during CO2 rebreathing. In a group of 11 healthy male subjects, the changes in end-expiratory and end-inspiratory volume of the rib cage (delta Vrc,E and delta Vrc,I, respectively) and abdomen (delta Vab,E and delta Vab,I, respectively) measured by linearized magnetometers were expressed as a function of end-tidal PCO2 (PETCO2. The changes in end-expiratory and end-inspiratory volumes of the chest wall (delta Vcw,E and delta Vcw,I, respectively) were calculated as the sum of the respective rib cage and abdominal volumes. The magnetometer coils were placed at the level of the nipples and 1-2 cm above the umbilicus and calibrated during quiet breathing against the VT measured from a pneumotachograph. The delta Vrc,E/delta PETCO2 slope was quite variable among subjects. It was significantly positive (P < 0.05) in five subjects, significantly negative in four subjects (P < 0.05), and not different from zero in the remaining two subjects. The delta Vab,E/delta PETCO2 slope was significantly negative in all subjects (P < 0.05) with a much smaller intersubject variation, probably suggesting a relatively more uniform recruitment of abdominal expiratory muscles and a variable recruitment of rib cage muscles during CO2 rebreathing in different subjects. As a group, the mean delta Vrc,E/delta PETCO2, delta Vab,E/delta PETCO2, and delta Vcw,E/delta PETCO2, slopes were 0.010 +/- 0.034, -0.030 +/- 0.007, and -0.020 +/- 0.032 1/Torr, respectively; only the delta Vab,E/delta PETCO2, slope was significantly different from zero. More interestingly, the individual delta VT/delta PETCO2 slope was negatively associated with the delta Vcr,E/delta PETCO2 (r = 0.68, P = 0.021) and delta Vcw,E/delta PETCO2 slopes (r = 0.63, P = 0.037) but was not associated with the delta Vab,E/delta PETCO2 slope (r = 0.40, P = 0.223). There was no correlation of the delta Vrc,E/delta PETCO2 and delta Vcw,E/delta PETCO2 slopes with age, body size, forced expiratory volume in 1 s, or expiratory time. The group delta Vab,I/delta PETCO2 slope (0.004 +/- 0.014 1/Torr) was not significantly different from zero despite the VT nearly being tripled at the end of CO2 rebreathing. In conclusion, the individual VT response to CO2, although independent of delta Vab,E, is a function of delta Vrc,E to the extent that as the delta Vrc,E/delta PETCO2 slope increases (more positive) among subjects, the VT response to CO2 decreases. These results may be explained on the basis of the respiratory muscle actions and interactions on the rib cage.
Abdominal Muscles↗
Chest wall and lung volume estimation by optical reflectance motion analysis.
Estimation of chest wall motion by surface measurements only allows one-dimensional measurements of the chest wall. We have assessed on optical reflectance system (OR), which tracks reflective markers in three dimensions (3-D) for respiratory use. We used 86 (6-mm-diameter) hemispherical reflective markers arranged circumferentially on the chest wall in seven rows between the sternal notch and the anterior superior iliac crest in two normal standing subjects. We calculated the volume of the entire chest wall and compared inspired and expired volumes with volumes obtained by spirometry. Marker positions were recorded by four TV cameras; two were 4 m in front of and two were 4 m behind the subject. The TV signals were sampled at 100 Hz and combined with grid calibration parameters on a personal computer to obtain the 3-D coordinates of the markers. Chest wall surfaces were reconstructed by triangulation through the point data, and chest wall volume was calculated. During tidal breathing and vital capacity maneuvers and during CO2-stimulated hyperpnea, there was a very close correlation of the lung volumes (VL) estimated by spirometry [VL(SP)] and OR [VL(OR)]. Regression equations of VL(OR) (y) vs. VL(SP) (x, BTPS in liters) for the two subjects were given by y = 1.01x-0.01 (r = 0.996) and y = 0.96x + 0.03 (r = 0.997), and by y = 1.04x + 0.25 (r = 0.97) and y = 0.98x + 0.14 (r = 0.95) for the two maneuvers, respectively. We conclude spirometric volumes can be estimated very accurately and directly from chest wall surface markers, and we speculate that OR may be usefully applied to calculations of chest wall shape, regional volumes, and motion analysis.
Humans↗
A theoretical analysis of the effect of airway smooth muscle load on airway narrowing.
We used published data for the elastic properties of a 2-mm outer-diameter canine bronchus and assumed values for the thickness of the wall components and lung parenchymal shear modulus to estimate the load on airway smooth muscle and its effect on airway narrowing. The following relationships were calculated: (1) luminal and smooth muscle radii of curvature and transmural pressure; (2) the isovolume, transmural pressures developed by the smooth muscle to narrow the lumen at distending pressures of 20, 10, 5, and 2 cm H2O; (3) the equilibrium tension developed by, and thus the load on, the airway smooth muscle as a function of smooth muscle length during isovolume bronchoconstriction. From these calculations a smooth muscle length-tension diagram was drawn allowing the interactions between submucosal thickening, peribronchial thickening, load, and smooth muscle contractility to be analyzed. The analysis indicates that: (1) the load on smooth muscle decreases by more than an order of magnitude between a distending pressure of 20 and 2 cm H2O; (2) increasing smooth muscle contractility has more effect at large rather than at small distending pressures; (3) peribronchial inflammation decreases both load and the slope of the relationship between peribronchial and pleural pressures. Decreases in load may be an important mechanism producing excessive bronchoconstriction in asthma.
Animals↗
Detection of excessive bronchoconstriction in asthma.
Airway hyperresponsiveness is easily assessed by measuring the concentration or dose of an inhaled agonist that produces a defined response, e.g., PC20 or PD20. However, this measure does not assess excessive bronchoconstriction. We report the results of analyzing bronchial dose-response curves by measuring percent fall in vital capacity (delta FVC%) as the response rather than the PC20. In our analysis, delta FVC% was measured at the PC20, and therefore it was the dependent variable, whereas the concentration of agonist was the independent variable, in contrast to the usual bronchoprovocation tests in which the response is the independent variable and the dose is the dependent variable. We reasoned that a dose-dependent increase in gas trapping with histamine would detect excessive bronchoconstriction as a decrease in FVC; in contrast, PC20 measures only the ease of bronchoconstriction. In 10 patients with mild asthma the reproducibility of delta FVC% when FEV1 fell by 20%, i.e., at the PC20 concentration of histamine, taken from a greater than 6-s FVC on an otherwise standard histamine challenge test was comparable to that of PC20. In 10 healthy asymptomatic subjects there were only trivial falls (0.3%) in FVC to as much as 16 mg/ml histamine. In a retrospective study of 146 patients with mild asthma, the delta FVC% was normally distributed (13.2 +/- 5.5 SD%) and did not correlate with the number of beta 2-agonist prescriptions or the PC20, but it did correlate with the number of prescriptions written per month for oral prednisone (r = 0.55, p < 0.02). We conclude that delta FVC% when FEV1 falls by 20% is a safe method of detecting excessive bronchoconstriction, and it reveals that different asthmatics react in fundamentally different ways to the same agonist. This may be useful in detecting the asthmatic at risk for serious disease.
Adult↗
Nutritional status and mortality in chronic obstructive pulmonary disease.
The role of nutritional status in the prognosis of subjects with severe chronic obstructive pulmonary disease was studied in a cohort of Canadian men and women followed for 3 to 5 yr. A total of 348 subjects who were recruited for a study of negative pressure ventilation were evaluated for lung function and body weight, and a subset who entered hospital for the study (n=184) had baseline measures of diffusing capacity, maximal inspiratory and expiratory mouth pressure (PImax and PEmax), and blood gases. Predictors of survival were analyzed using Cox regression models. In the total cohort, low body mass index (BMI) and use of home oxygen were independently associated with reduced survival. In the hospitalized group, predictors of respiratory mortality were elevated PaCO2 and low BMI, PImax, and diffusing capacity. PaO2 (measured on oxygen therapy), FEV1, PEmax, age, smoking behavior, and gender were not associated with survival. The predictors of total mortality were similar, except that BMI was no longer significant. In conclusion, low body weight, a potentially modifiable factor, was associated with respiratory mortality, but whether it has a casual effect or is a marker of declining health can only be resolved through an intervention trial.
Adult↗