[Clinical study of the month: the TORCH study (TOwards a Revolution in COPD Health)]. / L'étude clinique du mois. L'étude TORCH (TOwards a Revolution in COPD Health): vers une révolution de la santé des patients souffrant de BPCO.

The TORCH study (Towards a Revolution in COPD Health) was a double-blind, randomised, placebo-controlled clinical trial, investigating the combination of salmeterol/fluticasone propionate for 3 years in COPD. The primary end point was on all-cause mortality. Secondary end points included COPD exacerbation rate, lung function and health status. More than 6000 patients were randomised. In this article, we briefly report the most significant results of the study. The efficacy on mortality (reduction of the risk of death of 17.5%) was near the predetermined level of statistical significance (p = 0.052); the combination had a significant effect on the three pillars of COPD management, that is: improvement of quality of life and respiratory function, and reduction of the rate of exacerbations. In addition to being effective, the combination salmeterol/fluticasone (50/500 microg 2x/day) is well tolerated in COPD and had a favourable benefit/risk ratio.

Randomized controlled trial of salbutamol aerosol therapy via metered dose inhaler-spacer vs. jet nebulizer in young children with wheezing.

The jet nebulizer is a common device used for administering aerosol medication in young children. However, compared to a metered dose inhaler-spacer (MDI-spacer), it takes more time and personnel. This study aimed to compare the efficacy of salbutamol aerosol therapy given via these two devices in young wheezing children. A prospective randomized, double-blind, placebo-controlled trial was performed in children up to 5 years old who had acute wheezing and were admitted to the Department of Pediatrics, King Chulalongkorn Memorial Hospital. Patients were randomly divided into two groups. The first group received 2 puffs of placebo via MDI-spacer, followed by 0.15 mg/kg salbutamol respiratory solution via jet nebulizer. The second group received 2 puffs (100 microg/puff) of salbutamol via MDI-spacer, followed by placebo via jet nebulizer. Clinical scores and tidal breathing pulmonary function test were evaluated before and after treatment. Pulmonary function parameters included those derived from flow volume loops (volume to peak tidal expiratory flow over total expiratory volume, V(PTEF)/V(E); time to peak tidal expiratory flow over total expiratory time, T(PTEF)/T(E); and ratio of tidal expiratory flow at 25% remaining expiration to peak expiratory flow, 25/PF), compliance (Crs), and resistance (Rrs) of the respiratory system. The efficacy of both methods was compared by using analysis of covariance. Forty-seven wheezing children were studied (24 received salbutamol via MDI-spacer, and 23 received it via jet nebulizer). There was no statistical difference between the two groups regarding clinical scores and all pulmonary function parameters. However, heart rate was significantly increased after treatment in the jet nebulizer group when compared to those in the MDI-spacer group (P = 0.004). In conclusion, the efficacy of salbutamol aerosol therapy via MDI-spacer compared to jet nebulizer in young wheezing children was not different in terms of clinical score and postbronchodilator pulmonary function parameters. However, salbutamol aerosol therapy via jet nebulizer significantly increased the heart rate when compared to the MDI-spacer.

Nedocromil sodium inhibits the increase in airway reactivity induced by platelet activating factor in humans.

To investigate the effect of nedocromil sodium on changes in airway reactivity to methacholine induced by platelet activating factor, we studied 12 nonasthmatic, nonatopic subjects (24 to 41 years) in a double-blind trial. The FEV1 and airflow at 30 percent of vital capacity from a partial forced expiration (V30p) were used to assess changes in airway caliber. Two concentration-response curves to doubling concentrations of MCh (from 0.3 mg/ml) were performed 48 h apart. The concentrations of MCh causing a 20 percent fall in FEV1 (PC20FEV1) or a 40 percent fall in V30p (PC40V30p) were calculated. After the first MCh challenge, subjects were matched by airway reactivity and randomly assigned to nedocromil sodium (two puffs qid 2 mg/puff) or placebo treatment. Two days after the second MCh challenge, PAF was inhaled, and changes in airway caliber were recorded. Administration of either nedocromil sodium or placebo was ended at this time and airway response to MCh was assessed two days after PAF. The two concentration-response curves to MCh obtained before PAF exposure were superimposable. The PAF caused a dose-related bronchoconstriction in both groups; the maximal fall in V30p was 27.6 +/- 6.6 percent (mean +/- SE) in the nedocromil sodium group and 37.4 +/- 4.6 percent in the placebo group. Two days after PAF, the PC20FEV1 did not change in subjects who received nedocromil sodium (4.86 vs 4.32 mg/ml; geometric mean), but it fell from 6.59 to 1.12 mg/ml (p less than 0.05) in placebo-treated subjects. These results indicate that nedocromil sodium inhibits PAF-induced increase in airway reactivity.

Hyperresponsiveness of the extrathoracic airway in patients with captopril-induced cough.

It has been suggested that cough from captopril may originate from an increased sensitivity of receptors in the extrathoracic airway (EA). To explore this hypothesis, we assessed the responsiveness of EA and bronchi and the cough sensitivity to inhaled histamine in nine hypertensive patients with captopril-induced cough (group 1) during treatment and one month after withdrawal of the drug treatment. Nine patients who were asymptomatic while receiving captopril (group 2) and nine patients receiving no current treatment (group 3) served as controls. The EA responsiveness was assessed by using the maximal midinspiratory flow (MIF50) as an arbitrary index of EA constriction and was expressed as the histamine concentration causing a 25 percent decrease in MIF50 (PC25MIF50). PC15FEV1 was the index of bronchial responsiveness and PCcough (dose causing five or more coughs) was that of cough sensitivity. Airway hyperresponsiveness (EA-HR or BHR) was diagnosed when PC25MIF50 or PC15FEV1 were 8 mg/ml or lower. Patients with captopril-cough, as compared with controls, had significantly lower values of PC25MIF50, PC15FEV1, and PCcough; EA-HR and BHR were found, respectively, in seven and three of these patients and in none of the control subjects. In all the patients of group 1, cough and EA-HR resolved after withdrawal of captopril treatment, while BHR persisted in one. PC25MIF50, PC15FEV1, and PCcough were all significantly improved. Our findings suggest that cough during captopril therapy may originate from receptors in the EA.

A survey of the current use and methods of analysis of bronchoprovocational challenges.

The purpose of this study was to survey the current techniques and methods of analysis in bronchoprovocational challenges currently in use. A questionnaire was sent to 94 investigators who had recently published an article in which a bronchoprovocational technique was used. They were asked to answer questions regarding the techniques used in challenge procedures and to calculate the results of ten histamine challenges which had previously been performed in our laboratory. Forty-four responded; 32 of these gave specific results for the histamine challenge. The most common provocative agent utilized was methacholine (62 percent), and that most used delivery mode was a dosimeter for delivery (55 percent). The most common provocative agent utilized was methacholine (62 percent) and the most used delivery mode was a dosimeter (55 percent).

A prospective study of pulmonary function in patients receiving mitomycin.

Mitomycin is a chemotherapeutic agent that is used to treat a variety of solid tumors. Pulmonary toxic reactions from this agent can be life threatening. We prospectively investigated the utility of pulmonary function tests (PFTs) in monitoring for the occurrence of pulmonary toxicity due to mitomycin. PFTs were obtained at baseline and after three cycles of mitomycin therapy. We analyzed the clinical course, radiologic studies, and PFT results in 133 patients with metastatic squamous cell carcinoma of the lung randomized to treatment with either mitomycin, vinblastine, and cisplatin or mitomycin alone as part of a prospective treatment protocol of the North Central Cancer Treatment Group (NCCTG). The diffusing capacity (DCO) was available in only 40 patients after the third cycle due to a high rate of progression and death from their underlying disease. After three cycles of chemotherapy, there was an average decline in the DCO of 14% (p<0.0001) and no changes were observed in expiratory flows. No differences were noted between treatment arms. A significant decline in the DCO (defined as a >20% change after correcting for hemoglobin) was noted in 11 of 40 patients (28%). This decline in the DCO was not associated with a worse prognosis (p=0.77). Seven patients (5%) developed severe pulmonary toxic reactions attributed to chemotherapy, including noncardiogenic pulmonary edema, interstitial pneumonitis, and pleural effusions. Corticosteroid therapy resulted in temporary subjective improvement in three patients. The Dco did not correlate with the development of pulmonary toxic reactions in these seven patients. In conclusion, (1) the incidence of clinically significant pulmonary toxic reactions from mitomycin is relatively low (5%), (2) mitomycin therapy resulted in a greater than 20% decline in the DCO in approximately one-fourth of patients receiving three cycles of chemotherapy, and (3) the use of serial PFTs in patients receiving mitomycin was not shown to be predictive of pulmonary toxicity.

Pentoxifylline improves pulmonary gas exchange.

Pentoxifylline is a xanthine derivative with hemorrheologic and vascular properties that may improve gas exchange in patients with chronic obstructive pulmonary disease (COPD). We tested this hypothesis in 12 patients with COPD (mean FEV1 = 40 percent predicted; mean DCO, 8.6 ml/min/mm Hg) randomly divided into a treatment and control group and six healthy volunteers. Following establishment of baseline DCO and maximum expiratory flow volume (MEFV) curve values, each subject in the treatment and healthy groups took 400 mg of pentoxifylline three times a day for 12 weeks. Weekly DCO and MEFV curves were measured before treadmill exercise in both COPD groups and before and after exercise in the healthy group. The MEFV curve parameters from the final three weeks of therapy did not differ significantly from baseline values. During this time, however, the treatment COPD group's resting DCO rose by 8.2 +/- 2.4 percent over baseline level (p less than 0.01). Treadmill walk time increased from 17.7 +/- 2.9 minutes to 23.2 +/- 2.9 minutes (p less than 0.02). This was accompanied by improved exercise oxygen saturation measured by oximetry (SoxiO2). Premedication SoxiO2 fell from 92.8 +/- 1.2 percent to 88.6 +/- 2.5 percent during exercise, and from 94.4 +/- 1.1 percent to only 91.8 +/- 1.0 percent after 12 weeks of medication (p less than 0.05). No such improvement was noted in the control COPD group. Although the healthy group's resting SoxiO2 and DCO did not change during treatment, their exercise DCO increased significantly from 36.3 +/- 3.1 ml/min/mm Hg to 41.8 +/- 3.5 ml/min/mm Hg (p less than 0.001). These data demonstrate that pentoxifylline improves gas exchange, possibly by increasing cardiac output, and/or by raising mixed venous PO2, and/or by improving blood flow to underperfused alveoli.

Effects of increasing doses of beta-agonists on airway and parenchymal hysteresis.

We examined the effects of a deep inhalation on airway caliber before and after increasing doses of a beta-agonist in eight subjects, including one former and two current but mild asthmatics. With bronchodilation the increase in maximal flow on the partial flow-volume curve (P), initiated from functional residual capacity, exceeded that seen on the maximal curve (M), initiated from total lung capacity, such that isovolumic maximal flows diminished after a deep inhalation; i.e., M/P ratios fell with bronchodilation, as we and others have found. Five of eight reversed this downward trend in M/P ratios at higher cumulative doses. Quasistatic pressure-volume curves (QSPV) were simultaneously performed on two of these five and demonstrated a decrease in pressure-volume hysteresis (PVH) at the higher doses associated with a rising M/P ratio. Three of eight had continuing low and diminishing M/P ratio up to the highest dose given. QSPV were performed in two of these three and indicated no change in PVH at any of the doses. One of these two had a repeat study using a subcutaneous beta-agonist after the inhaled drug was given, and the M/P ratio rose as QSPV PVH fell. These data support the relative hysteresis analysis of airway and parenchyma as an explanation for volume history effects on airway caliber.

The dose-response slope: a useful method for expressing the results of methacholine provocation tests in healthy subjects?

In order to study the reproducibility of different indices of airway responsiveness, two bronchial provocations with increasing methacholine concentrations up to 256 mg ml-1 were performed within 2 weeks on 30 healthy volunteers. The dose-response slope [DRS = maximal fall (%) in pulmonary function/maximal non-cumulative methacholine dose (mumol)] was calculated from forced expiratory volume in 1 s (FEV1) and from area under the expiratory flow-volume curve (AEFV). DRS reproducibility within 2 weeks in responsive (decline in FEV1 greater than 20%) and non-responsive subjects (decline in FEV1 less than 20%) was assessed. After log-transformation of the data the reproducibility was assessed with intraclass correlations (ICC) [with 95% confidence intervals (CIicc)], mean difference with limits of agreement (delta +/- SD), 95% confidence intervals for a single measurement (CIsm), and the absolute difference of the observations of the two days from each other (zero = ideal reproducibility). Provocative doses (PD20FEV1) could be calculated for 14 subjects on both occasions. In this responsive group the reproducibility of all the parameters used (PD20FEV1, DRSFEV1 and DRSAEFV) was high. In the non-responsive group, DRSFEV1 demonstrated a slightly, but not clearly, lower ICC than DRSAEFV. However, DRSFEV1 had clearly wider limits of agreement and CIsm than DRSAEFV. Also, with DRSFEV1 the observations of the two days differed significantly more from each other than with DRSAEFV (P less than 0.05).

Reproducibility of methacholine induced bronchoconstriction in healthy subjects: the use of area under the expiratory flow-volume curve to express results.

The usefulness of the pulmonary function variable, area under the expiratory flow-volume curve (AEFV), in methacholine provocation (MP) studies in normal subjects was evaluated. The baseline coefficients of variation (CV), maximal fall from post-saline values (MAX) and dose-response slope [DRS = maximal percentage fall in pulmonary function/maximal noncumulative methacholine dose (mumol)] were calculated for AEFV, and were compared to those of forced expiratory volume in one second (FEV1), maximum expiratory flow at 50% (MEF50%) and at 25% (MEF25%). Also the repeatability after 2 and 8 weeks was assessed. The rank order of CVs was FEV1 less than AEFV less than MEF50% approximately MEF25% all differences, except MEF50% vs. MEF25%, being significant (P less than 0.05). The order of sensitivities (estimated with MAX and DRS) was FEV1 less than AEFV less than MEF50% less than MEF25%. Again, all differences were significant (AEFV vs. MEF50% P less than 0.01, others P less than 0.001). After two weeks the correlation coefficients for MAX- and DRS-values of AEFV were 0.84 and 0.94 (P less than 0.001), respectively. After an eight week period the correlations were still high, 0.86 and 0.92 (P less than 0.001), respectively, but the actual MAX- and DRS-values tended to be smaller than eight weeks before. The repeatability of MAX of AEFV was not quite as high as that of FEV1. On the other hand, the correlations of DRS-value derived from AEFV were markedly better than those derived from FEV1. In conclusion, MP in normal subjects is well repeatable at least within two weeks, but after an eight week period disturbing factors may intervene reducing repeatability. AEFV can be considered at least as good a pulmonary function variable as FEV1 in demonstrating bronchoconstriction during MPs in normal subjects, and it might even be a better variable to obtain DRS-values than other variables tested.

Can asthma treatment in sports be doping? The effect of the rapid onset, long-acting inhaled beta2-agonist formoterol upon endurance performance in healthy well-trained athletes.

Inhaled beta2-agonists have been subject to restrictions in relationship to sports due to fear of possible improvement in endurance performance. According to the international doping regulations only inhaled salbutamol, terbutaline and salmeterol are allowed for use in sports. Formoterol is a recently introduced rapid onset-long-acting inhaled beta2-agonist. The main aim of the present randomized, double-blind placebo-controlled study was to investigate possible improvement in endurance performance of inhaled formoterol in 24 healthy well-trained competitive male athletes, 21-29 years old. Lung function (flow-volume loops) was measured before, 15 min after each inhaled study drug and before and repeatedly after exercise. On day 1, maximum oxygen uptake (VO2max), peak ventilation (VEpeak) and running time till exhaustion were measured and used to determine the exercise load on days 2 and 3. On days 2 and 3 the subjects inhaled the study drugs, rested for 1 h, then exercised, and VO2max, VEpeak and running time until exhaustion were determined. Inhaled formoterol did not improve any parameter of endurance performance. On the other hand a statistically significant, although not clinically significant (0.05 ml(-1) min kg(-1)), change was found in estimated difference of VO2max between formoterol and placebo in favour of placebo. Lung function increased significantly after inhaled formoterol, and after exercise also for placebo, but without differences between the beta2-agonist and placebo after exercise. In conclusion, inhaled formoterol did not improve endurance performance compared to placebo.

Inhaled platelet-activating factor increases airway sensitivity but not maximal airway narrowing to methacholine in normal subjects.

To examine the effect of inhaled platelet-activating factor (PAF) on airway sensitivity and on maximal airway narrowing, we measured airway response to doubling concentrations of methacholine (MCh) 48 h before and 48 h after inhalation of 10, 50 and 100 micrograms of PAF in six nonatopic, nonasthmatic subjects. The forced expiratory volume in one second (FEV1) and airflow at 30 percent of vital capacity (V30) from partial forced expiration were used to assess changes in airway calibre. Inhalation of PAF caused only minor changes in FEV1. In contrast, inhalation of 100 micrograms of PAF caused a significant fall in V30 from 2.64 +/- 0.35 to 1.35 +/- 0.43 l.min-1 (p < 0.05). Two days after PAF inhalation a leftward shift of the concentration-response curve to MCh was observed. The MCh concentration causing a 20% fall in FEV1 (PC20FEV1) was 11.25 +/- 1.78 and 2.38 +/- 1.29 mg.ml-1 (geometric mean +/- GSEM; p < 0.05) before and after PAF inhalation, respectively. PAF did not affect the maximal airway response to MCh. The maximum percentage fall in FEV1 was 36.2 +/- 1.9% at baseline and 37.6 +/- 1.8% after PAF inhalation. Likewise, maximum percentage change in V30 was 72.8 +/- 3.7% at baseline and 73.6 +/- 3.4% after PAF inhalation. The results of this study show that PAF inhalation increases airway sensitivity without altering the maximal bronchoconstrictive response to MCh in normal subjects.

[The effect of inhaled salbutamol on pulmonary gas exchange in patients with chronic obstructive bronchopneumopathy]. / Effet du salbutamol inhalé sur les échanges gazeux pulmonaires de patients atteints de BPCO.

The aim of this study is to establish whether or not the inhalation of a puff of salbutamol (Ventoline, 100 micrograms) could induce hypoxemia. Twenty-five chronic obstructive pulmonary disease (COPD) patients were investigated. In a first group of 20 patients arterial blood gases and related indices were measured before and 5, 10, 30, 60 and 90 minutes after inhalation of salbutamol. The oxyhemoglobin dissociation curve was traced before and 90 minutes after the drug intake. Except in two subjects in whom salbutamol dramatically improves arterial blood gases, the drug had no effect on the investigated parameters. It is concluded that salbutamol does not affect the blood gases in COPD patients. In this respect the behaviour of COPD patients differs from that of asthmatics in whom salbutamol generally induced hypoxemia.

[The control of respiration in pulmonary fibrosis. The effect of O2 and CO2]. / Contrôle de la respiration dans les fibroses pulmonaires. Effets de l'O2 et du CO2.

We have studied the mode of ventilation and chemosentivity in 10 patients suffering from pulmonary fibrosis. The total lung capacity was on average 63.5 +/- 8% of the predicted. Their static compliance was 0.078 +/- 0.05 l.cm of water. The patients were studied in the prone position breathing ambient air then on hyperoxia. The response to CO2 was assessed according to the rebreathing method of Read. The results of these patients were compared with those of 11 normal subjects. The ventilation at rest was normal, with a shortened respiratory time and a Ti/Ttot ratio which was lowered. The occlusion pressure (P0.1) was very much higher than that in normal subjects. This rise was correlated with an increase in pulmonary elastance and a reduction in vital capacity. The correction of hypoxia was without effect on the respiratory parameters. In relation to normal subjects the ventilatory response to carbon dioxide in fibrotics was decreased whilst the response of the P0.1 was increased expressing central hyperactivity. In conclusion, fibrotic patients have normal ventilation in spite of an increase in inspiratory work. This normal ventilation results from hyperactivity of the respiratory centre, as in the hyperventilation induced by carbon dioxide when at rest.

[Delayed-release salbutamol, a new beta-mimetic with prolonged action. Results of a comparative study against theophylline L.A]. / Salbutamol à libération prolongée, un nouveau bêta 2 mimétique à action prolongée. Résultats d'une étude comparative versus théophylline L.A.

Salbutamol controlled-release (CR), a new salbutamol formulation, was compared in asthmatic patients to another long-acting bronchodilator, theophylline L.A., in a randomized (2 salbutamol, 1 theophylline), multicentre, parallel-group study. Among the 83 patients who met the inclusion criteria (mean age 41 years), 55 received salbutamol CR and 28 received theophylline L.A. during 6 weeks. At the end of the study, there was a significant difference (p less than 0.05) in favour of salbutamol CR for FEV1 (2.53 l versus 2.13 l) and VC (4.23 l versus 3.50 l). FEF25-75 and PEF were higher with salbutamol CR, respectively 2.06 l sec-1 versus 1.86 l sec-1 and 6.03 l sec-1 versus 5.03 l sec-1. PEFR, measured by the patient, improved more with salbutamol CR than with theophylline L.A., with a significant difference as from the third week. There was a significant difference at the end of the study too, both morning (408 l min-1 versus 350.1 l min-1, p less than 10(-3] and evening (408.9 l min-1 versus 353 l min-1, p less than 10(-3]. Salbutamol CR and theophylline L.A. were considered as well tolerated, respectively by 95.5% of the patients in the salbutamol group and 92.3% of the patients in the theophylline group. There were equal numbers of minor and usual adverse events in the two groups. Salbutamol CR showed a better efficacy in airways obstruction without systemic safety problems. It is therefore an excellent treatment for patients requiring bronchodilator maintenance therapy.

[Effect of salbutamol inhalation on small airways function in patients with sarcoidosis]. / Wplyw inhalacji salbutamolu na stan czynnosciowy drobnych dróg oddechowych u chorych na sarkoidoze.

The effect of Salbutamol (Polfa) inhalation on small airway function was studied in 20 patients with stage II sarcoidosis and 8 healthy volunteers. MEFV values and dynamic compliance were assessed. A significant statistical increase of FEV1, MEF50, Cdyn20 and Cdyn60 were seen only in healthy volunteers. In patients with sarcoidosis the assessed parameters were not effected by the Salbutamol inhalation.

[Standards in evaluating the test of obstruction reversibility based on the flow-volume curves]. / Standardy oceny testu odwracalnosci obturacji na podstawie krzywej przeplyw--objetosc.

The study analyzed the changes in the shape of the flow-volume curve after fenoterol (Berotec) inhalation in school age healthy children. Significant increase of FEF25-75%, FEF50%, FEF25% values were seen. The authors demonstrated that bronchodilatation was not related to sex, height, weight and children's age, but it's value is indirectly proportional to the at-rest state of the airways. It seems, basing on results of this study, that FEV1 and FEF25-75% are the best indexes of dilatation tests. Increases of 10% and 30% are significant of bronchodilatation.

[Bronchial hyperreactivity to the inhalation of hypo- and hyperosmolar aerosols and its correction by halotherapy]. / Giperreaktivnost' bronkhov na ingalatsii gipo- i giperosmoliarnykh aérozolei i ee korrektsiia metodom galoterapii.

18 bronchial asthma (BA) patients (12 with mild and 6 with moderate disease) were examined before and after halotherapy (HT) for airways reactivity using provocative tests with ultrasonic inhalations of purified water (UIPW) and hypertonic salt solution (HSS). Bronchial hyperreactivity (BHR) to UIPW and HSS before treatment occurred in 13 and 11 patients (72 and 69%, respectively). HT reduced BHR in 2/3 and 1/2 of the patients, respectively. In the rest patients BHR was unchanged or increased, being so to UIPW only in patients with atopic asthma in attenuating exacerbation. Clinical efficacy of HT and initial BHR to UIPW correlated (r = 0.56; p < 0.05). No correlation was found between HT efficacy and initial BHR to HSS.

[High density respiratory syndrome: I. Oscillations of flow-volume curves during forced respiration in dense gas media]. / Dykhatel'nyi sindrom vysokoi plotnosti: I. Ostsilliatsiia na kryvykh "potok-ob''em" vo vremia forsirovannogo dykhaniia v plotnykh gazovykh sredakh.

33 divers exposed to high pressure have been examined in three series. The dynamics of the forced breathing parameters has been studied: I--helio or neon-oxygen medium under pressure of 1.078-3.53 MPa (11-36 kg/m2) with density to 32.7 kg/m3; II--nitrogen-oxygen medium under 0.274-0.882 MPa (2.8-9.0 kg/m2) with density of 11.7 kg/m3; III--under the same conditions, as II, but using bronchospasmolytics (stimulators of 2-adrenoreceptors: astompent, salbutamol, berotec) under hyperbaria. A new phenomenon: high-density breathing syndrome is revealed. It includes appearance of oscillations of respiratory flows against the background of a decrease of forced breathing rate in dense gas medium and has a common mechanism of appearance both during inhale and exhale. High hydrostatic pressure and narcotic qualities of inert gases can have a modulating effect. Evidences are obtained that tremor phenomena observed during high pressure nervous syndrome can influence the biomechanics of forced breathing at hyperbaria. A high correlation between amplitude modulation of electromyograms of breathing muscles and pneumotachogram oscillations within the range, corresponding to the frequency of physiological tremor, allowed assuming that tremor of breathing muscles induced by high-density gas medium action is one of factors responsible for appearance of respiratory flows oscillations.

[High density respiratory syndrome: III. The functional role of oscillation of respiratory flow during respiration in dense gas media]. / Dykhatel'nyi sindrom vysokoi plotnosti: III. Funktsional'noe znachenie ostsilliatsii respiratornykh potokov pri dykhanii v plotnykh gazovykh sredakh.

It is found out that when reaching critical density of gas medium (20.4-24.0 kg/m3), the relative power of oscillations on the "flow-volume" curves and pneumotachograms sharply increases. At the same time the maximal rate of exhale, rates of expiratory flows in large bronchi decrease significantly and the rates of expiratory flows in bronchi of middle and small calibers reduce to zero. Within the range of densities of different gas medium (from 1.3 to 32.7 kg/m3) the changes in the relative power of oscillations of respiratory flows correlate well with the changes in permeability of upper respiratory tracts (r = -0.932 +/- 0.054). A regression equation describing this dependence is obtained. A detailed description is given to symptoms of high-density breathing syndrome: a decrease in rates of gas flows in tracheobronchial tree, early development of dynamic compression of airway, tremor of breathing muscles and appearance of respiratory flow oscillations, pronounced dyspnea and hypoventilation of alveoli. A hypothetic scheme of its development is presented. The functional significance of respiratory flow oscillations as a mechanism improving gas exchange in gas media with extremely high density is under discussion.