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Serial distribution of airway diameters from input impedance and computed tomography.

Indirect measures of airway diameter such as respiratory system input impedance (Zin) have been widely used to infer or quantify bronchoconstriction, or bronchodilation. One such measure, Zin above 100 Hz has been shown to be primarily influenced by airway geometry and airway walls but not by lung and chest wall tissues. We used a recently developed method based on a complex asymmetrically branched network of tubes with nonrigid walls to analyze Zin from 100 to 2,000 Hz in control and bronchoconstricted (histamine injection) dogs. The resulting estimates of airway diameters indicated that peripheral airways were constricted far more (approximately 30% of their control diameters) than central airways (i.e., 0% in the trachea). Separate measurements of changes in airway diameters were made in an excised dog lung using high resolution computed tomography. The observed changes in airway diameter between lung volumes of total lung capacity (TLC) and functional residual capacity (FRC) were quantitatively consistent with those obtained from Zin data in our control dogs at FRC. We conclude that this systems identification method can be used to estimate the distribution of airway diameters from Zin.

Airway Resistance↗

The effect of peritoneal dialysate on pulmonary function and blood gasses in C.A.P.D. patients.

There have been many reports showing diminished vital capacity (VC), total lung capacity (TLC), and functional residual capacity (FRC), after the infusion of peritoneal dialysate in patients on continuous ambulatory peritoneal dialysis (C.A.P.D.) for chronic renal failure. We also examined the effects of the infusion of two litres of dialysate on airways resistance (Raw) using total body plethysmography and on arterial blood gasses. Ten patients on C.A.P.D. were selected. The mean results of dialysate infused (in) and dialysate drained (out) are as follows: FVC 3.66 l (in) and 3.73 l (out) (not significant); VC 3.81 l (in) and 3.99 l (out) (p less than 0.05); FEV1 3.02 l (in) and 2.94 (out) (n.s.); TLC 5.89 l (in) and 6.33 l (out) (p less than 0.05); FRC 3.56 l (in) and 3.78 l (out) (p less than 0.05); Raw 4.79 cmsH21/l/s (in) and 4.72 cmsH20/l/s (out) (n.s.); Pa02 11.03 kPA (in) and 11.35 kPA (out) (p less than 0.001). We conclude that two litre dialysate causes significant reduction of TLC, VC and FRC, and a reduction in Pa02 and A-a02 but has no effect on airways resistance.

Airway Resistance↗

Effect of intensive swimming training on lung volumes, airway resistance and on the maximal expiratory flow-volume relationship in prepubertal girls.

The aim of the present study was to analyse the effect of 1 year of intensive swimming training on lung volumes, airway resistance and on the flow-volume relationship in prepubertal girls. Five girls [9.3 (0.5) years old] performing vigorous swimming training for 12 h a week were compared with a control group of 11 girls [9.3 (0.5) years old] who participated in various sport activities for 2 h per week. Static lung volumes, maximal expiratory flows (MEF) at 75, 50 and 25% of vital capacity, 1-s forced expiratory volume (FEV1.0) and airway resistance (R(aw)) were measured by means of conventional body plethysmograph techniques. Prior to the training period there were no significant differences between the two groups for any of the parameters studied. Moreover, for both groups, all parameters were within the normal range for children of the corresponding age. After 1 year of training, vital capacity (VC), total lung capacity (TLC) and functional residual capacity (FRC) were larger (P < 0.05) in the girl swimmers than in the control group, while physical development in terms of height and weight was similar. FEV1.0 (P < 0.01), MEF25, MEF50 (P < 0.05) and MEF75 as well as the ratio MEF50/TLC (P < 0.05) had increased in the girl swimmers but were unchanged in the control group. R(aw) tended to be lower in the girl swimmers and higher in the control group. The results indicate that intensive swimming training prepuberty enhances static and dynamic lung volumes and improves the conductive properties of both the large and the small airways. As to the causative mechanism, it can be speculated that at prepuberty intensive swimming training promotes isotropic lung growth by harmonizing the development of the airways and of alveolar lung spaces.

Airway Resistance↗

Comparison of computed tomographic lung density with haemodynamic data of the pulmonary circulation.

Computed tomographic (CT) lung density measurements were prospectively correlated with pulmonary haemodynamic data in 33 patients with chronic heart disease. Cardiac catheterisation and five specific computed tomographic scans (three at nearly total lung capacity, one at functional residual capacity, and one at residual volume) were performed. There was a significant correlation between anterior lung density and mean pulmonary artery pressure (r = 0.86), pulmonary vascular resistance (r = 0.80), and pulmonary artery wedge pressure (r = 0.65). Lung density, as measured by CT, thus provides a valuable estimate of pulmonary arterial pressure and pulmonary vascular resistance, but is affected by other pathological conditions, such as emphysema and congestional or post-inflammatory fibrosis.

Adult↗

Contribution of the closure of pulmonary units to impaired oxygenation during anesthesia.

Associations between airway closure, alveolar-arterial oxygen tension difference (A-aDO2), and positive end-expiratory pressure (PEEP) were investigated in anesthetized, paralyzed, artifically ventilated patients. The difference between closing capacity (CC) and functional residual capacity (FRC) was measured with a modified standard technique using a bolus of N2 to detect airway closure in denitrogenated patients. At FIO2 = 0.4 during anesthesia before application of PEEP, A-aDO2 was larger than expected in comparable conscious subjects and increased at about 1 mmHg/yr of age. CC was below FRC in young subjects but above FRC in older subjects, the two coinciding at about age 43 yr. Thus, during anesthesia both A-aDO2 and CC-FRC increased with age. The proximity and point of coincidence of CC and FRC suggested that CC is reduced during anesthesia. In patients whose CC exceeded FRC, imposition of PEEP estimated to be sufficient to elevate FRC above CC decreased A-aDO2 to a level comparable to that in patients exhibiting airway closure below FRC without PEEP. Patients in whom CC was initially below FRC failed to improve oxygenation with PEEP. At least half of the decrease in A-aDO2 associated with application of PEEP persisted for 20-30 min after the withdrawal of PEEP, although the withdrawal resulted in an immediate recurrence of airway closure above FRC. The authors conclude that closure of pulmonary units operates in some circumstances to contribute to pulmonary dysfunction in anesthetized patients but is neither the only nor necessarily the most important such mechanism.

Anesthesia, General↗

Scoliosis and pulmonary function.

The effect on pulmonary function of all three dimensions of the scoliotic deformity was analyzed with computer tomography in 33 patients with thoracic idiopathic scoliosis. Both static (total lung capacity [TLC], vital capacity [VC] and functional residual capacity [FRC] ) and dynamic volumes (forced expiratory volumes in one second [FEV-1]) were negatively correlated to the lateral deformity and, to a lesser degree, to rotation. Of the computer tomography variables reflecting kyphosis, the sagittal diameter was correlated positively to all lung volumes though negatively to the quotient FRC/TLC while the KLi was correlated positively to VC and FEV1. The conclusion is drawn that the Cobb angle gives the most accurate estimation of lung volume compromise and that operative treatment should aim of reducing the lateral dislocation of the vertebrae and at maintaining normal sagittal thoracic curve.

Adolescent↗

Direct measurement of subglottic air pressure while swallowing.

OBJECTIVE: The subglottic pressure theory for swallowing asserts that laryngeal mechanoreceptors have a role in the regulation of swallowing function. The primary purpose of this study was to determine if subglottic air pressure is generated during swallowing in a healthy, nontracheostomized person. METHODS: This pilot investigation used a prospective, repeated-measures design in a single subject. Direct measurement of subglottic air pressure was obtained through percutaneous puncture of the cricothyroid membrane. Swallows were timed with four randomly assigned lung volumes: total lung capacity, tidal volume, functional residual capacity (FRC), and residual volume. RESULTS: Lung volumes above FRC generated positive subglottic pressure during the swallow, whereas lung volumes below FRC generated consistently negative subglottic pressures. The degree and polarity of the pressure was directly related to lung volume at the time of the swallow. CONCLUSION: These findings illustrate that during normal swallowing, positive subglottic air pressure is likely present. Previously, subglottic air pressure during swallowing had been measured in tracheostomy patients only.

Adult↗

Effect of salbutamol on lung function and chest wall volumes at rest and during exercise in COPD.

BACKGROUND: Inhaled bronchodilators can increase exercise capacity in chronic obstructive pulmonary disease (COPD) by reducing dynamic hyperinflation, but treatment is not always effective. This may reflect the degree to which the abdomen allows dynamic hyperinflation to occur. METHOD: A double blind, randomised, crossover trial of the effect of 5 mg nebulised salbutamol or saline on endurance exercise time was conducted in 18 patients with COPD of mean (SD) age 67.1 (6.3) years and mean (SD) forced expiratory volume in 1 second (FEV1) of 40.6 (15.0)% predicted. Breathing pattern, metabolic variables, dyspnoea intensity, and total and regional chest wall volumes were measured non-invasively by optoelectronic plethysmography (OEP) at rest and during exercise. RESULTS: Salbutamol increased FEV1, forced vital capacity (FVC) and inspiratory capacity and reduced functional residual capacity (FRC) and residual volume significantly. OEP showed the change in resting FRC to be mainly in the abdominal compartment. Although the mean (SE) end expiratory chest wall volume was 541 (118) ml lower (p<0.001) at the end of exercise, the endurance time was unchanged by the bronchodilator. Changes in resting lung volumes were smaller when exercise duration did not improve, but FEV1 still rose significantly after active drug. After the bronchodilator these patients tried to reduce the end expiratory lung volume when exercising, while those exercising longer continued to allow end expiratory abdominal wall volume to rise. The change to a more euvolumic breathing pattern was associated with a lower oxygen pulse and a significant fall in endurance time with higher isotime levels of dyspnoea. CONCLUSIONS: Nebulised salbutamol improved forced expiratory flow in most patients with COPD, but less hyper-nflated patients tried to reduce the abdominal compartmental volume after active treatment and this reduced their exercise capacity. Identifying these patients has important therapeutic implications, as does an understanding of the mechanisms that control chest wall muscle recruitment.

Aged↗

Pulmonary mechanical and immunologic dysfunction in a murine model of AIDS.

Human immunodeficiency virus-infected patients occasionally exhibit alveolar septal wall thickening and decreases in gas diffusion capacity, but the mechanism underlying these abnormalities is unknown. The present study evaluated septal wall thickness and gas exchange properties in a murine model of the acquired immunodeficiency syndrome and determined whether there were alterations in lung lymphocyte deposition and activation that could contribute to changes in respiratory structure and function. Although alveolar septal wall thickness did not differ from control at 1, 2, and 4 wk postimmunosuppressive virus infection, at 8 wk after infection, septal wall thickness was substantially increased. Immunohistochemical evaluation at this time revealed marked increases in the septal wall deposition of fibronectin and collagen type IV. Pulmonary function tests on anesthetized mice with virus-induced septal wall thickening demonstrated that, although total lung capacity, compliance, and functional residual capacity were unaltered, diffusion capacity for carbon monoxide was significantly impaired. A diffuse nonspecific interstitial pneumonitis was present in lungs of immunodeficient mice, and flow cytometry indicated that both lymphocytes and macrophages were activated. Reverse transcriptase-polymerase chain reaction analysis of lung lymphocytes demonstrated enhanced mRNA expression for several cytokines known to affect lung structure. These results show that impaired gas exchange occurs in a murine model of acquired immunodeficiency syndrome and suggest that such alterations may be mediated by elaboration of cytokines from activated lung lymphocytes and macrophages.

Acquired Immunodeficiency Syndrome↗

Changing effect of lung volume on respiratory drive in man.

Experiments were conducted on human subjects to study the effect of lung inflation during breath holding on respiratory drive. Two series of experiments were performed: the first to examine respiratory drive during a single breath hold, the second designed to examine the sustained effect of lung inflation on subsequent breath holds. The experiments involved breath holding begun either at the end of a normal expiration or after a maximum inspiration. When breath holding was repeated at 10-min intervals, the increase in BHT produced by lung inflation was greater in short breath holds (after CO2 rebreathing) than in long breath holds (after hyperventilation). If breath holds were made in rapid succession, the first breath hold was much longer when made at total lung capacity than at functional residual capacity, but this effect of lung inflation diminished in subsequent breath holds. It is concluded that the inhibitory effect of lung inflation decays during breath holding and is regained remarkably slowly during the period of breathing immediately after breath holding.

Adult↗

Hysteresis in the relation between diffusing capacity of the lung and lung volume.

The diffusing capacity of the lung for carbon monoxide (DLCO) varies directly with lung volume (VA) when measured during a breath-holding interval. DLCO measured during a slow exhalation from total lung capacity (TLC) to functional residual capacity (FRC) does not vary as VA changes. Since VA is reached by inhaling during breath holding and by exhaling during the slow exhalation maneuver, we hypothesized that the variability in the relation between DLCO and VA was due to hysteresis. To test this hypothesis, breath-holding measurements of DLCO were made at three lung volumes, both when VA was reached by inhaling from residual volume (RV) and when Va was reached by exhaling from TLC. At 72% TLC, DLCO was 22% higher when VA was reached by exhalation compared to inhalation (P < 0.02). At 52% TLC, DLCO was 19% higher when VA was reached by exhalation compared to exhalation (P < 0.005). DCLO measured during a slow exhalation fell on the exhalation limb of the CLCO/VA curve. these data indicate that there is hysteresis in DLCO with respect to lung volume.

Adult↗

Geometry and kinematics of dog ribs.

Five anesthetized supine beagle dogs were scanned using a fast, multislice computed tomographic X-ray technique to determine the orientation of the ribs at total lung capacity (TLC) and functional residual capacity (FRC). A plane was fit to each rib using a coordinate system in which the z-axis was aligned approximately cephalocaudally and the x-z-plane coincided with the sagittal midplane. The orientation of each plane was described by "pump-handle" and "bucket-handle" angles. The ribs rotated downward and inward during a passive deflation of the lungs from TLC to FRC. Rib displacement was not uniform: bucket-handle motion was predominant in the upper ribs, and pump- and bucket-handle motions were equal in the lower ribs. The change in the pump-handle angles between TLC and FRC was approximately 6 degrees for ribs 3-8, and the change in the bucket-handle angles decreased with rib number from 16 degrees for rib 3 to 6 degrees for rib 8. Rib shape was described by fitting an ellipse to the data for each rib; the ribs became larger and more circular with increasing rib number.

Animals↗

Shape of the chest wall in the prone and supine anesthetized dog.

The shape of the passive chest wall of six anesthetized dogs was determined at total lung capacity (TLC) and functional residual capacity (FRC) in the prone and supine body positions by use of volumetric-computed tomographic images. The transverse cross-sectional areas of the rib cage, mediastinum, and diaphragm were calculated every 1.6 mm along the length of the thorax. The changes in the volume and the axial distribution of transverse area of the three chest wall components with lung volume and body position were evaluated. The decrease of the transverse area within the rib cage between TLC and FRC, as a fraction of the area at TLC, was uniform from the apex of the thorax to the base. The volume of the mediastinum increased slightly between TLC and FRC (14% of its TLC volume supine and 20% prone), squeezing the lung between it and the rib cage. In the transverse plane, the heart was positioned in the midthorax and moved little between TLC and FRC. The shape, position, and displacement of the diaphragm were described by contour plots. In both postures, the diaphragm was flatter at FRC than at TLC, because of larger displacements in the dorsal than in the ventral region of the diaphragm. Rotation from the prone to supine body position produced a lever motion of the diaphragm, displacing the dorsal portion of the diaphragm cephalad and the ventral portion caudad. In five of the six dogs, bilateral isovolume pneumothorax was induced in the supine body position while intrathoracic gas volume was held constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Effects of fatigue, fiber length, and aminophylline on human diaphragm contractility.

The clinical relevance of methylxanthines as therapeutic agents for improving diaphragmatic contractility is controversial. In a double-blind, placebo-controlled trial, we investigated the effect of aminophylline on the contractility of fresh and fatigued human diaphragm at different lung volumes, and therefore as a function of fiber length. The diaphragmatic contractility of normal subjects was assessed by measurements of transdiaphragmatic pressure changes (Pdi,T) in response to single, bilateral, supramaximal phrenic-nerve shocks during relaxation from total lung capacity (TLC) to functional residual capacity (FRC). Fatigue was induced by resistive breathing. Therapeutic levels of theophylline were reached in all subjects. Under fresh (i.e., nonfatigue) conditions, aminophylline significantly increased Pdi,T at lung volumes above 75% of the inspiratory capacity (IC). Fatigue in the absence of aminophylline caused a disproportionately greater reduction of Pdi,T at high than at low lung volume (J. Appl. Physiol. 1992; 72:1064), which was rapidly reversible with rest. With aminophylline, the disproportionate decrease in diaphragmatic contractility at short fiber lengths was not observed. Aminophylline potentiates diaphragmatic contractility to a proportionately greater extent at short than at long fiber lengths, under both fresh and fatigued conditions. We explain these findings by known effects of muscle shortening, fatigue, and methylxanthines on excitation-contraction coupling mechanisms.

Adult↗

Mechanical constraints on exercise hyperpnea in a fit aging population.

We studied 12 physically fit (VO2 max = 44 ml.kg-1.min-1) older subjects (age = 63 to 77 yr) who showed the usual age-related declines in lung function (i.e., reduced maximal expiratory flow rates, vital capacity and increased functional residual capacity, closing capacity, and residual volume). We measured the optimal transpulmonary pressures for maximal expiratory airflow and the capacity of the muscles of inspiration for developing pleural pressure (taking into account the effects of lung volume and flow rate). Within these mechanical constraints to ventilation we plotted tidal pleural pressure-volume loops for mild through maximal exercise according to a measured end-expiratory lung volume (EELV). We found EELV to decrease a mean of 0.26 +/- 0.09 L and maximal effective pleural pressures to be reached in nine subjects near EELV with only light to moderate exercise intensities, whereas peak inspiratory pressure was only 45% of the capacity for pressure generation. With progressive increases in exercise intensity, EELV increased, and pleural pressures encroached to a greater extent on the maximal effective pressures; however, they remained effective in the majority of subjects. During maximal exercise EELV was 0.13 +/- 0.10 L greater than resting values, 20% of the Vt reached maximal effective pressures, and 83% of the capacity for inspiratory pressure was achieved. Three subjects significantly surpassed their maximal effective expiratory pressures, and four subjects achieved 95 to 100% of the capacity for inspiratory pressure generation. These subjects also showed no further increase in ventilation while breathing 0.02 to 0.05 FICO2 at maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[End inspiratory lung volumes as the limiting factor in PEEP ventilation].

In 17 patients requiring artificial ventilation expiratory pressure-volume curves (VPE) were plotted all over the inspiratory capacity (IC) between total lung capacity (TLC) and functional residual capacity (FRC). Then patients were ventilated with PEEP of 0, 5, 10 and 15 cmH2O for 30 min. The volume excursions with known PEEP were displayed graphically into the VPE to determine the position of end-inspiratory volume within the IC. The steep, quasi-linear part of each VPE was flattening exponentially against TLC in the upper part of the curve. This "overdistension range" was found to be identical with the upper 40% of IC. Heavy side-effects of PEEP ventilation were never seen before the inspiratory volume excursion had reached this upper 40% of IC. If this was the case, the following observations were made: 1. Static compliance (Cst) decreased by more than 10% in all cases. 2. Pulmonary vascular resistance (PVR) increased by more than 20% in 12 cases. 3. Cardiac index (CI) decreased by more than 15% in 12 cases. 4. The alterations observed in Cst, PVR and CI increased rapidly, when the lungs were further distended, and were well correlated parabolically to the position of end-inspiratory volume within IC. --5 patients failed to show important circulatory alterations. It is concluded that overdistension-related side-effects of PEEP on respiratory mechanics and circulation do not occur before the linear part of the pressure-volume curve has been exceeded by hyperinflation. For the first adjustment of controlled ventilation at least the upper third of IC should be avoided.

Adolescent↗

Peak or plateau maximal inspiratory mouth pressure: which is best?

There is no clear evidence as to how maximal inspiratory mouth pressure (PI,max) should be measured, although plateau pressures sustained for 1 s and measured at residual volume (RV) are usually recommended. Peak and plateau PI,max were measured at RV and at functional residual capacity (FRC) in 533 healthy subjects (aged 10-90 yrs) in order to comparably test all PI,max measurements for their predictors, reproducibility and normal values. Plateau pressures accounted for 82.0-86.3%, of peak pressures. Peak and plateau pressures measured at FRC accounted for 84.3-90.5% of pressures at RV, and were highly correlated. Age was negatively predictive and weight and body mass index positively predictive of PI,max, but regression parameters were low. All PI,max measurements were comparable when calculating regression parameters, between-subject variability and reproducibility. In conclusion, peak and plateau maximal inspiratory mouth pressure are comparably useful for the assessment of inspiratory muscle strength and can be reliably measured at functional residual capacity and at residual volume. Regression equations are of low impact in predicting normal values due to the weak influence of demographic and anthropometric factors and to the high unexplained between-subject-variability. Age-related 5th percentiles can indicate the lower limit of the normal range.

Adolescent↗

Influence of vagal activity on the neonatal ventilatory response to hypoxemia.

The sustained increase in ventilation (V1) that occurs during acute hypoxemia in adults is not characteristic of the neonate as V1 falls to or below baseline values soon after onset of the hypoxic stimulus. Associated with this decline in V1 is a decrease in tidal volume, lung compliance, inspiratory duration, and an increase in functional residual capacity and respiratory frequency. We hypothesized that hypoxemia induced small airway constriction and pulmonary time constant inequalities resulting in a frequency dependent fall in lung compliance and tidal volume and retention of lung volume. In seven newborn subhuman primates, responses to acute hypoxemia were measured prior to and after administration of atropine methyl bromide to prevent vagally mediated narrowing of peripheral airways. The increase in frequency and fall in inspiratory duration characteristic of the ventilatory decline during hypoxemia was eliminated by the drug but functional residual capacity and lung compliance were unaffected. Also, the initial rise in V1 was blunted or blocked in all subjects. Bilateral vagotomy caused V1 to fall significantly requiring oxygen supplementation but responses to hypoxemia were still biphasic in nature. These findings suggest that cholinergically mediated mechanisms in the airways do not alter effective lung distensibility related to respiratory rate. Acetylcholine may be important at the peripheral chemosensor since cholinergic blockade eliminated the initial ventilatory increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗