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The respiratory system as an exercise limiting factor in normal sedentary subjects.
The present study was undertaken to investigate the respiratory system as an exercise limiting factor. Breathing and cycle endurance (i.e. the time until exhaustion at a given performance level) as well as physical working capacity 170 (i.e. the exercise intensity corresponding to a heart rate of 170 beats.min-1 on a cycle ergometer) were determined in four healthy sedentary subjects. Subsequently, the subjects trained their respiratory system for 4 weeks by breathing daily about 90 l.min-1 for 30 min. Otherwise they continued their sedentary lifestyle. Immediately after the respiratory training and 18 months later, all performance tests carried out at the beginning of the study were repeated. The respiratory training increased breathing endurance from 4.2 (SD 1.9) min to 15.3 (SD 3.8) min. Cycle endurance was improved from 26.8 (SD 5.9) min to 40.2 (SD 9.2) min whereas physical working capacity 170 remained essentially the same. During the endurance cycling test in the respiratory untrained state, the subjects continuously increased their ventilation up to hyperventilation [ventilation at exhaustion = 96.9 (SD 23.6) l.min-1] while after the respiratory training they reached a respiratory steady-state without hyperventilation [ventilation at exhaustion = 63.3 (SD 14.5) l.min-1]. The absence of this marked hyperventilation was the cause of the impressive increase of cycle endurance in normal sedentary subjects after respiratory training. The effects gained by the respiratory training were completely lost after 18 months. Our results indicated that the respiratory system was an exercise limiting factor during an endurance test in normal sedentary subjects.
Measurement of effective elastance of the total respiratory system in ventilated patients by a computed method. Comparison with the static method.
We have studied 28 patients mechanically ventilated for acute respiratory failure at different levels of externally applied positive end-expiratory pressure (PEEPe). We describe and compare a computed method of measuring "effective" elastance of the total respiratory system (Ers,eff) with the static values of elastance of the total respiratory system (Ers,st), obtained with the end-inflation occlusion technique. Ers,eff was computed by an original device (Heres, R.P.A., Belgium), also the effective resistance of the total respiratory system was calculated. At zero end-expiratory pressure set by the ventilator (ZEEP). Ers,eff averaged 29.5 +/- 13.5 cm H2O x L-1 while Ers,st non-corrected for intrinsic PEEP (PEEPi) averaged 36.4 +/- 15.1 cm H2O x L-1 and Ers,st corrected for PEEPi averaged 28.2 +/- 13.4 cm H2O x L-1. The small difference between Ers,eff and Ers,st corrected for PEEPi was statistically significant and these two values were highly correlated (r = 0.98). This significant difference disappeared rapidly with PEEPe and probably reflects a frequency-dependance due to pendelluft. We also observed that PEEPi was present in 21 of 27 patients at ZEEP. Our results also indicate that low levels of PEEP may improve Ers in hyperinflated COPD patients, without inducing further hyperinflation. In conclusion, values of Ers,eff are very similar to static values corrected for PEEPi and permit an accurate and rapid approach to the management of ventilated patients.
[The respiratory system and safety pharmacology].
Many drugs affect respiration in man. The changes in respiratory function following their administration are due to a direct effect on the respiratory system or are the consequence of a central, metabolic (alteration of the acid-base balance) or vascular effect (pulmonary hypertension). Regulatory documents (CPMP, FDA and MHW drafts) are in agreement in considering the respiratory system as a vital function to explore during safety pharmacology studies. On the basis of these recommendations, the first studies to be performed should be on conscious unrestrained animals, in general the drug being administered as a single dose. The effects on the respiratory function are best studied by plethysmography in the guinea-pig or rat. The measurement of ventilatory parameters--respiratory rate, tidal volume, inspiratory time, expiratory time, peak inspiratory flow, peak exploratory flow and resistance--allow the differentiation between drugs affecting respiratory control and those altering lung mechanical properties. The pulmonary hypertension risk could be evaluated in the dog during haemodynamic studies. Finally, the study of the effects on blood gases should always be carried out in conscious animals, usually in the dog. For drugs belonging to pharmacological classes presenting a high respiratory risk, complementary studies should be considered. The extrapolation from healthy persons to ill patients (especially chronic respiratory insufficiency patients) of the incurred risk is often difficult. For this reason, it is very useful to study the effect of such drugs on the respiratory function of pathological animals.
Effect of occupational exposure to opiates on the respiratory system.
The authors discuss the effect of occupational exposure to opiates. A depressive influence of opiates on the respiratory system is well known. This effect results from stimulation of opioid kappa and delta receptors in the central nervous system leading to a decrease in spirometric parameters and degranulation of mast cells. The studies carried out in the USA indicated that 26% of the pharmaceutical industry workers, occupationally exposed to opiates suffer from bronchial asthma. Some of the cases can be explained by the effect of opiates on the respiratory system mentioned above, but this is not a full explanation. Contribution of immunological mechanisms is also possible. The presence of specific IgG and IgM antibodies was found in workers exposed to opiates. Changes in distribution of individual subpopulations of lymphocytes T were also observed. The question of asthma and other disorders of the respiratory system in persons exposed to opiates does not receive due recognition in Poland. In view of data presented in this paper this attitude should be changed as this problem is not only the subject of occupational medicine but also of some other fields, particularly in view of a recent increase in the number of users of drugs which also include opiates.
Respiratory system mechanics in patients treated with isotonic or hypertonic NaCl solutions.
Twenty-one patients who underwent elective surgery for coronary artery bypass were studied right after chest wall closure. They were anesthetized, paralyzed, and artificially ventilated with a constant-flow ventilator. Airflow, changes in lung volume, and tracheal pressure were measured. Respiratory system resistance (Rrs,max) was partitioned into its homogeneous (Rrs,min) and uneven (Rrs,u) components. Respiratory system elastance (Ers) was also measured. The subjects were randomly divided into two groups injected with test solutions just after chest wall closure: eleven patients received isotonic saline (0.9% NaCl solution), whereas the remaining ten were injected with hypertonic saline (7.5% NaCl solution). In all patients, mechanical parameters were measured at six different times: just before infusion, at 5 and 10 min (end of infusion); and at 15, 20, and 25 min after beginning of injection. No statistically significant differences were observed in respiratory system mechanical parameters between groups or between different times within each group. Our data suggest that hypertonic saline infusion does not result in significant changes in respiratory system mechanics in patients submitted to coronary artery bypass.
Statics of the respiratory system in newborn mammals.
The static mechanical properties of the respiratory system have been studied in newborn mammals within the first two weeks of life, ranging in body size from rat to piglet, and compared to the corresponding adult. Animals were supine, paralyzed, and passively ventilated. The pressure-volume curves of the respiratory system and of the lung have been constructed by changing volume a known amount and measuring the tracheal pressure before and after opening the rib cage. In the newborns, the mean elastic recoil pressure of the lung at functional residual capacity (PLFRC) is 1.9 cm H2O with no clear correlation with body weight. The dry lung weight (LW)/body weight (BW) ratio is greater in newborns than in adults and progressively decreases with age. FRC (measured directly with the saline displacement method) is proportional to LW1.09 and BW1.03. In newborns, lung compliance per lung weight (CL/LW) is similar between species (Cl alpha LW1.07). Chest wall compliance per body weight is also constant (CW alpha BW1.00). By comparing the newborns with the corresponding adults we found that PLFRC is 35-57% of the adult value. FRC/LW in the newborn is less than or equal to the adult value, while FRC/BW is generally larger in the newborn. CL/LW is usually smaller in the newborn than in the adult while CW/BW is larger.
Volume/pressure curve of total respiratory system in paralysed patients: artefacts and correction factors.
The volume/pressure (V/P) curve of the total respiratory system in paralysed patients is drawn assuming that volume changes of the respiratory system (delta V resp) equals volume displacement of the measuring apparatus (delta V syr), usually a supersyringe. However, in 93 VP curves we found that O2 removed from the lung-syringe system during the procedure (proportional to the time) largely exceeds the CO2 added to the lung-syringe system (delta V gas). This results in a net loss of volume from the system (delta V resp less than delta V-syr). Deflation compliance, hysteresis area and ratio are significantly affected by this phenomenon. Inflation compliance is less influenced by delta V gas, partially compensated by the intrapulmonary gas expansion due to the temperature changes. We conclude that the parameters computed on the deflation limb of V/P curve are misleading if proper correction of the volume scale is not introduced.
The effect of gestational age on the effective elastance of the respiratory system in neonates.
We measured the effective elastance of the respiratory system (E'RS) in 38 "healthy" neonates, gestational ages ranging from 28-42 weeks. E'RS was calculated by dividing the inspiratory pressure generated after nasal occlusion by the tidal volume of the breath preceding occlusion (E'RS = P/VT). E'RS decreased from 790 +/- 0.070 cm H2O/liter at 30.4 +/- 0.4 weeks of gestation to 520 +/- 0.030 at 34.5 +/- 0.3 weeks (P less than 0.01); then to 340 +/- 0.020 at 40 +/- 0.2 weeks (P less than 0.01). E'RS corrected for lung volume ("specific" E'RS) were 32 +/- 2,32 +/- 4, and 28 +/- 2 cm H2O at the above gestational ages, respectively (P greater than 0.05). We suggest: (1) the increased E'RS observed in preterm infants is lung volume dependent. Changes in lung volume may alter the geometry of the thorax, and therefore, the force/length characteristics of the respiratory muscles; (2) this increased E'RS is not of much benefit to preterm infants who have little respiratory stability when E'RS is maximum; and (3) if E'RS is an index of mechanical stability, apnea in preterm infants is independent of the mechanical properties of the respiratory system.
Man-made vitreous fibers and risk of respiratory system cancer: a review of the epidemiologic evidence.
Because asbestos has been demonstrated to cause lung cancer, the issue regarding safety of other fibers, including man-made vitreous fibers (MMVF), has been raised. We reviewed the available evidence, in particular the epidemiologic data, on MMVF and the risk of respiratory system cancer. Glass fibers (especially glass wool) have been studied most extensively. Taken together, the data indicate that among those occupationally exposed, glass fibers do not appear to increase risk of respiratory system cancer. Of six studies that specifically examined rock and slag wool workers, three reported excesses in respiratory system cancer among such workers. Two of these three studies, however, did not control for cigarette smoking, a powerful predictor of such cancers. There are no published studies, in humans, of refractory ceramic fibers. Future studies evaluating the potential of MMVF to increase risk of respiratory system cancer will not add to existing knowledge if investigators do not address potential confounding by cigarette smoking and other workplace carcinogens.
[Effect of cholinesterase (ChE) reactivators on hemodynamics in animals. I. Reactions of the circulatory and respiratory systems of rabbits after administration of ChE reactivators].
Studies on the dynamics of changes in the circulatory and respiratory system in rabbits were carried out after intravenous injection of ChE reactivators used in treatment of poisoning with phosphoorganic compounds (FO). Blood flow in the carotid artery, arterial pressure, frequency and amplitude of breathing were measured. From the above data pulse rate and coefficient of vesself resistance were calculated. The results obtained indicate that the reactions in the circulatory and respiratory system depend on the kind of the reactivator, the size of its dose and time of action. Pralidoxim--PAM (at a dose of 10, 20, 40 mg/kg) acts cholinergically on the muscular coat o blood vessels, causing their shrinkage, which is proved by decreased blood flow with simultaneous increase of vessel resistance. The increase of vessel resistance was directly proportional to the dose of pralidoxim and often caused an increase in arterial pressure. Pralidoxim did not show a larger effect on the function of the heart. The action of obidoxim--Toxogonin or Toxobidin--does not only depend on the size of the dose but on the time of action as well. At small doses (10 mg/kg), obidoxim increases blood flow after 15 min, then causes shrinkage of blood vessels and decreases blood flow with increased vessel resistance. At larger doses (20, 40 mg/kg) a constant increase of blood flow is maintained, despite frequently decreased arterial pressure with simultaneously decreased vessel resistance. This accounts for blood vessel dilatation. The reactivators studied stimulate the function of the respiratory system by increased frequency of breathing, but its amplitude was effected to a lesser extent. It was also shown that ChE activity in blood was not changed significantly. The action of the indoxims studied was similar to that of Toxobidin (Polfa) and Toxogonin (E. Merck).
Injury of the cell's respiratory system by heat and by formaldehyde. Thermokinetics and early molecular events.
This is a study of the manner in which the respiratory system of the cell is injured either by elevated temperature or by exposure to diluted formaldehyde. Molecular mechanisms were identified by thermokinetic measurements. The rates at which respiratory failure developed in mouse liver slices in an injurious environment were measured at various temperatures. The data were fitted to the Arrhenius equation, and the effective activation energies of the injury processes were calculated. These data show that (1) the thermokinetics of injury to the cell's respiratory system, whether by thermal or chemical means, follows the Arrhenius law. (2) Thermal injury of the cell's respiratory system has a high activation energy, indicating that the critical, rate-determining event is a protein denaturation. Other mechanisms such as imbalance of metabolic reaction rates and thermal liquefaction of membrane lipids can be ruled out. (3) Repression of cell respiration by diluted formaldehyde has an activation energy compatible with a chemical reaction but low enough to exclude protein denaturation as a mechanism.
[The respiratory system--its self-cleaning system. General mechanisms of clearance].
The behaviour of particles and deposition in different parts of respiratory system are described. Listed are factors which contribute to the deposition of particles in the lungs and upper areas of the respiratory system. The general mechanisms of lung clearance and their action such as cough, mucociliary transport, alveolar clearance and immunological system are reported. Particularly is stressed the necessity of coordination of all defense mechanisms in order to maintain normal respiratory function.
Effects of indoor environmental factors on respiratory systems of children.
Effects of indoor environmental factors on children's respiratory system and pulmonary function tests were investigated in this study. A total of 617 primary school children aged between 9-12 years were included. A standard questionnaire, which includes questions about respiratory symptoms and illness, indoor environmental determinants, family history of respiratory diseases, and smoking habits of the parents, was sent to homes of all children and information was obtained from parents. Children with a family history of asthma, bronchitis, or other chest troubles suffered morning and day/night coughs, shortness of breath, wheezing and asthma, bronchitis, or pneumonia more frequently. Children whose mothers smoked complained of blocked-runny nose and sinusitis more frequently. Pulmonary function levels were diminished in passive smokers and in children whose houses were heated by a wood-burning stove. As a result, passive smoking, using a wood-burning stove for heating, and family history of respiratory diseases are to be considered risk factors for the respiratory system.
Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.
Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment.
A new method for calculating total respiratory system compliance. Theory and model experiments.
A new method for calculating total respiratory system compliance is described, based on simple modelling of a ventilator-respiratory system circuit that assumes linear characteristics of the circuit parameters compliances and resistances. The method requires only that flow measurement be conducted continuously to obtain compliance, if the internal compliance of the circuit is known beforehand. Model experiments showed that the compliance of a child test lung, calculated from the flow recording, differed at most by 10% from the compliance obtained by separate measurements of pressure and volume under static conditions, over a wide range of respiratory flows and airway resistances.
[Allergy of the respiratory system].
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[Value of bronchoscopic examination in the diagnosis of diseases of the respiratory system. I. Neoplasms of the respiratory tract and tuberculosis].
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