Airway hyperresponsiveness to ultrasonically nebulized distilled water in subjects with tetraplegia.

The majority of otherwise healthy subjects with chronic cervical spinal cord injury (SCI) demonstrate airway hyperresponsiveness to aerosolized methacholine or histamine. The present study was performed to determine whether ultrasonically nebulized distilled water (UNDW) induces airway hyperresponsiveness and to further elucidate potential mechanisms in this population. Fifteen subjects with SCI, nine with tetraplegia (C4-7) and six with paraplegia (T9-L1), were initially exposed to UNDW for 30 s; spirometry was performed immediately and again 2 min after exposure. The challenge continued by progressively increasing exposure time until the forced expiratory volume in 1 s decreased 20% or more from baseline (PD20) or the maximal exposure time was reached. Five subjects responding to UNDW returned for a second challenge 30 min after inhalation of aerosolized ipratropium bromide (2.5 ml of a 0.6% solution). Eight of nine subjects with tetraplegia had significant bronchoconstrictor responses to UNDW (geometric mean PD20 = 7.76 +/- 7.67 ml), whereas none with paraplegia demonstrated a response (geometric mean PD20 = 24 ml). Five of the subjects with tetraplegia who initially responded to distilled water (geometric mean PD20 = 5.99 +/- 4.47 ml) were not responsive after pretreatment with ipratropium bromide (geometric mean PD20 = 24 ml). Findings that subjects with tetraplegia are hyperreactive to UNDW, a physicochemical agent, combined with previous observations of hyperreactivity to methacholine and histamine, suggest that overall airway hyperresponsiveness in these individuals is a nonspecific phenomenon similar to that observed in patients with asthma. The ability of ipratropium bromide to completely block UNDW-induced bronchoconstriction suggests that, in part, airway hyperresponsiveness in subjects with tetraplegia represents unopposed parasympathetic activity.     

Time-dependent variations of transcutaneous PCO2 level in normal subjects

Transcutaneous PCO2 (PtcCO2), which is linearly related to arterial PCO2, was continuously recorded in healthy, adult, normal volunteers for 8-h periods. Recording this variable with the apparatus employed permits measurement of changes in the level of ventilation while subjects are freely ambulant and unencumbered by invasive and flow-resistive respiratory apparatus. The time series obtained exhibited marked periodicities. The frequencies and amplitudes varied between subjects. Peak-to-peak variation was 10-20% of mean values. There was no apparent association between fluctuations in PCO2 and activity other than formal exercise. Visual inspection of the time series and preliminary statistical analysis of digitally converted data suggested that the time-dependent changes of PtcCO2 were normally distributed. However, more rigorous statistical examination revealed that in no case was PtcCO2 actually normally distributed.     

Metabolic and respiratory effects of flow-resistive loading in preterm infants

Oxygen consumption (VO2) was measured during hypoventilation induced by moderate-sized flow-resistive loading in 12 preterm infants, and the results were compared with those obtained under basal conditions immediately before and after the loaded run, each of which lasted for 7-10 min. Loading was performed with a continuous flow-resistive load (inspiratory and expiratory), which was approximately threefold greater in magnitude than the intrinsic resistance of preterm infants. VO2, minute ventilation (VE), transcutaneous oxygen tension (PtCO2), and transcutaneous carbon dioxide tension (PtcCO2) were continuously monitored. Results revealed that VE decreased significantly with loading, from 336 +/- 103 to 231 +/- 58 (SD) ml.min-1.kg-1 (P less than 0.001), while returning to basal levels of 342 +/- 59 ml.min-1.kg-1 after discontinuation of the load. VO2 decreased from 7.2 +/- 1.2 to 5.9 +/- 0.9 ml.min-1.kg-1 with loading (P less than 0.001) and returned to 7.2 +/- 1.2 ml.min-1.kg-1 at the second basal measurement. PtcCO2 remained unchanged with loading, and PtcCO2 only increased from 39 +/- 8 to 41 +/- 9 Torr (P less than 0.05) with loading, while returning to 40 +/- 9 Torr at the second basal measurement. Results indicate a decrease in the metabolic rate and ventilation with loading, with relatively little increase in PtcCO2. These data can explain prior observations that minimal disturbances in oxygen and carbon dioxide tensions occur with hypoventilation during flow-resistive loading in neonates, although the precise mechanism for this reduction remains to be determined.     

Total lung capacity does not change during methacholine-stimulated airway narrowing

The accurate measurement of changes in flow rates from partial flow-volume curves depends on their measurement at the same lung volume. This lung volume can be standardized from total lung capacity (TLC) if this does not change at the same time. We examined the effect of methacholine-stimulated maximal airway narrowing [change in mean forced expiratory volume in 1 s (delta FEV1) = 26.4%] on TLC, measured by whole-body plethysmography, in 10 normal subjects and of moderate airway narrowing (mean delta FEV1 = 34.9%) in 10 asthmatics. The TLC changed from 5.88 to 6.03 liters in normal subjects (P greater than 0.05) and from 6.92 to 6.95 liters (P greater than 0.5) in asthmatics. The results of this study suggest that TLC does not change significantly after methacholine-stimulated maximal airway narrowing in normal subjects and after moderate narrowing in asthmatics.     

Airways responsiveness determined by consecutive histamine challenges in asymptomatic asthmatics

The effect of two consecutive histamine inhalation challenges on airways responsiveness was assessed in a group of eight nonsmoking nonmedicated asthmatics aged 19-27 yr. All subjects had a base-line forced expiratory volume in 1 s (FEV1) of greater than 80% of their predicted normal value before the initial challenge and were allowed to recover to greater than 95% of the initial base-line FEV1 value before the second challenge was initiated. The average airways recovery time after the first challenge was 44 min but ranged between 30 and 90 min. The mean +/- SD values of cumulative histamine dose units provoking a 20% decrease of the FEV1 from the buffer control value (PD20FEV1) were 10.79 +/- 5.95 determined with the first and 30.50 +/- 46.36 with the second challenge (P greater than 0.05). We conclude that sequential histamine challenges performed in mild asthmatics with closely controlled prechallenge airways function are well tolerated. Although some variance does exist in intersubject airways recovery time and in intra-subject histamine airways responsiveness determined by sequential challenges, our data do not support recent observations (J. Appl. Physiol. 63: 1572-1577, 1987) that histamine tolerance is a characteristic finding associated with bronchial asthma.     

Airway reactivity and lung function in triiodothyronine-induced thyrotoxicosis

To evaluate the possible relationship between asthma and hyperthyroidism, airway reactivity and lung function were prospectively compared in healthy volunteers before, during, and after liothyronine (triiodothyronine, T3)-induced hyperthyroidism. Base-line evaluation of the 10 subjects included clinical evaluation, thyroid and pulmonary function tests, and airway reactivity assessed by methacholine inhalational challenge (MIC). All studies were normal. During T3-induced hyperthyroidism, no subject developed respiratory symptoms or changes in pulmonary function or airway reactivity. The mean percent change in forced expiratory volume at 1 s from base line (delta FEV1) of -2.4 +/- 3.0 after MIC was not significantly different from that obtained before T3 administration (-1.4 +/- 1.5, P greater than 0.2). When all serum T3 concentrations and delta FEV1 values before, during and after T3-induced hyperthyroidism were compared, there was no significant correlation. We conclude that T3-induced hyperthyroidism of 3-wk duration has no effect on airway reactivity or lung function in normal volunteers.     

Changes in flow-volume curve configuration with bronchoconstriction and bronchodilation

Changes in the configuration of maximum expiratory flow-volume (MEFV) curves following mild degrees of bronchodilation or bronchoconstriction were studied in five normal and five asthmatic subjects. In a volume-displacement plethysmograph, MEFV curves were performed before and after inhalation of aerosolized isoproterenol (I) or histamine (H). Five filtered MEFV curves were averaged, and slope ratio vs. volume (SR-V) plots were obtained from averaged curves. Following I, maximal flows at 75% of the vital capacity (VC) were decreased in asthmatics but not in normal subjects. Flows at 50 and 25% of the VC increased in normal subjects and asthmatics, whereas VC's were unchanged. In asthmatics, sudden large decreases in flow (bumps) occurred at lower lung volumes following I. H reduced flows over the entire VC, with greater reductions occurring in asthmatics than in normals, particularly at low lung volumes. In asthmatics, VC was slightly reduced, and bumps in MEFV curve configuration occurred at higher lung volumes or were abolished entirely following H. A reduction in the amount of configurational detail appreciable in MEFV curves following histamine in asthmatics was best seen in SR-V plots. Following H, SR's decreased regularly with decreasing lung volume in all the asthmatics but in none of the normals. This was the single most striking finding of this study. Mild I- and H-induced perturbations of airway bronchomotor tone produced small but consistent changes in MEFV curve configuration.(ABSTRACT TRUNCATED AT 250 WORDS)     

No involvement of lipid mediators in a guinea pig model of ultrasonically nebulized distilled water-induced bronchoconstriction

An inhalation of ultrasonically nebulized distilled water (UNDW) induces bronchoconstriction only in asthmatics, but the mechanism underlying the response is not fully understood. We have reported that bronchoconstriction occurs immediately after UNDW is inhaled 20 min after an antigen challenge in guinea pigs. Our aim was to examine the role of lipid mediators in this response. Passively sensitized guinea pigs were anesthetized and artificially ventilated. A sulfidopeptide leukotriene receptor antagonist, KCA-757, and platelet-activating factor antagonists, Y-24180 and E6123, were administered i.v. 15 min after an aerosolized antigen challenge, and UNDW was inhaled 5 min later. KCA-757, Y-24180, or E6123 did not, significantly alter the UNDW-induced bronchoconstriction. Together with our previous data that thromboxane A2 receptor antagonists did not influence the UNDW-induced bronchoconstriction, the present results suggest that lipid mediators are not involved in the UNDW-induced bronchoconstriction in our guinea pig model.     

Allergen inhalation challenge induces decrease of serum neutral endopeptidase (NEP) in asthmatics

There is accumulating evidence that tachykinins are implicated in inflammation, including asthma. Therefore, we hypothesized that the neutral endopeptidase (NEP), under challenge conditions, could be affected. Serum from 21 asthmatics and six healthy volunteers was sampled before, 30, and 120 min after allergen challenge. NEP-IR was determined using an ELISA and was found in all subjects. Compared to prechallenge, no difference was seen between asthmatics and controls; however, under challenge conditions, NEP-IR in asthmatics was significantly lower (30 min, P = 0.058; 120 min, P = 0.0017, respectively). This finding supports indirectly the hypothesis that tachykinins are released during allergen exposure, and suggests a regulatory role of NEP.     

Mechanism of action of ozone on the human lung

Fourteen healthy normal volunteers were randomly exposed to air and 0.5 ppm of ozone (O3) in a controlled exposure chamber for a 2-h period during which 15 min of treadmill exercise sufficient to produce a ventilation of approximately 40 l/min was alternated with 15-min rest periods. Before testing an esophageal balloon was inserted, and lung volumes, flow rates, maximal inspiratory (at residual volume and functional residual capacity) and expiratory (at total lung capacity and functional residual capacity) mouth pressures, and pulmonary mechanics (static and dynamic compliance and airway resistance) were measured before and immediately after the exposure period. After the postexposure measurements had been completed, the subjects inhaled an aerosol of 20% lidocaine until response to citric acid aerosol inhalation was abolished. All of the measurements were immediately repeated. We found that the O3 exposure 1) induced a significant mean decrement of 17.8% in vital capacity (this change was the result of a marked fall in inspiratory capacity without significant increase in residual volume), 2) significantly increased mean airway resistance and specific airway resistance but did not change dynamic or static pulmonary compliance or viscous or elastic work, 3) significantly reduced maximal transpulmonary pressure (by 19%) but produced no changes in inspiratory or expiratory maximal mouth pressures, and 4) significantly increased respiratory rate (in 5 subjects by more than 6 breaths/min) and decreased tidal volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of gas exchange to slope of phase III of the single-breath nitrogen test

To study the influence of gas exchanges on the slope of phase III, single-breath nitrogen tests (SB-N2) and reversed tests (SB-R) were performed with 10 normal volunteers at expiratory flows of 100 ml.s-1, 500 ml.s-1,11.s-1, and 21.s-1. During the prolonged expiration required for the SB-N2 test, more O2 is consumed that CO2 eliminated. This factor could contribute to the rising slope of phase III. However, if one obtains a reversed slope of phase III (by having O2 as the residual gas and room air as the inspired gas), factors increasing N2 concentration with time of expiration should decrease the steepness of this reversed slope. Our data show that, at an expiratory flow of 100 ml.s-1, the slope of phase III was steeper in SB-N2 than in SB-R by 0.92 +/- 0.31% N2 1-1 (mean +/- SD, p less than 0.01). As the expiratory flow was increased to 500 ml.s-1, this difference decreased to 0.33 +/- 0.19% N2 1-1, and both slopes became similar in magnitude but opposite in direction at an expiratory flow of 1 1.s-1. These data suggest that active gas exchange has a significant influence on the slope of phase III of the SB-N2 test.     

Potent bronchoprotective effect of deep inspiration and its absence in asthma.

In the absence of deep inspirations, healthy individuals develop bronchoconstriction with methacholine inhalation. One hypothesis is that deep inspiration results in bronchodilation. In this study, we tested an alternative hypothesis, that deep inspiration acts as a bronchoprotector. Single-dose methacholine bronchoprovocations were performed after 20 min of deep breath inhibition, in nine healthy subjects and in eight asthmatics, to establish the dose that reduces forced expiratory volume in 1 s by >15%. The provocation was repeated with two and five deep inspirations preceding methacholine. Additional studies were carried out to assess optimization and reproducibility of the protocol and to rule out the possibility that bronchoprotection may result from changes in airway geometry or from differential spasmogen deposition. In healthy subjects, five deep inspirations conferred 85% bronchoprotection. The bronchoprotective effect was reproducible and was not attributable to increased airway caliber or to differential deposition of methacholine. Deep inspirations did not protect the bronchi of asthmatics. We demonstrated that bronchoprotection is a potent physiologic function of lung inflation and established its absence, even in mild asthma. This observation deepens our understanding of airway dysfunction in asthma.     

Dynamics of the duration of tracheal forced expiratory noises during long-term isolation in the Mars-500 experiment

The dynamics of the duration of tracheal forced expiratory noises in a group of volunteers were studied before, during, and after a 520-day confinement. The duration did not change in most volunteers. Two volunteers exhibited significant changes in the duration of tracheal sounds and some spirometric parameters. The increase in the duration of tracheal forced expiratory noises and the decrease in spirometric parameters reveal ventilation impairment of the obstructive type. Analysis of the duration of tracheal forced expiratory noise dynamics during prolonged confinement has proven to be a sensitive technique to test ventilation function changes.     

Effect of raised alveolar pressure on leukocyte retention in the human lung

To determine whether an increase in alveolar pressure delays the passage of leukocytes (WBCs) through the lung by compressing the lung capillaries, we measured the concentration of WBC across the lung in response to a forced expiratory maneuver. In 20 human subjects, blood was sampled from catheters placed in the pulmonary artery (PA) and left ventricle (LV) before, during, and after a forced expiratory maneuver held for greater than or equal to 20 s against an occluded airway. Pressures were recorded at the mouth and from both catheters. A significant fall in LV WBC (P less than 0.01) but not in PA WBC occurred during or immediately after the maneuver in 18 subjects, with a mean maximum decrease of 26 +/- 12% (SD) from base line (range 9-46%). Between 1 and 3 min after the maneuver, there was an increase in LV and PA WBC (P less than 0.01) above base line. The neutrophil and lymphocyte counts showed similar changes, but erythrocyte and platelet counts remained unchanged. The degree of fall in LV WBC correlated closely (r = 0.68, P less than 0.01) with the changes from lung zone 3 to zone 2 and 1 conditions, as determined from the pressure changes. We conclude that WBCs are retained in the lung during a forced expiratory maneuver because of alveolar capillary compression.     

Influence of changed gas media on acoustic parameters of human forced exhalation

In previous study it was shown that duration of tracheal forced expiratory noises is promising to reveal negative changes of lung function after dive. The objective is a study of parameters of tracheal forced expiratory noises in changed gas media. The first experiment involved 25 volunteers (22-60 years), performed forced exhalation under normal pressure with air, oxygen-helium and oxygen-krypton mixtures. The second experiment in the chamber involved 6 volunteers (25-46 years), which performed forced exhalation with air under normal pressure (0.1 MPa), and under elevated pressure 0.263 MPa with air and oxygen-helium mixture. In the first experiment the direct linear dependence on gas density was found for forced expiratory noises common duration in the band of 200-2000 Hz and for its durations in narrow 200-Hz bands, excluding high frequency range 1400-2000 Hz. In the second experiment a significant reversed dependence of high frequency durations and spectral energies in 200-Hz bands (1600-2000 Hz) on adiabatic gas compressibility. Individual dynamics of common duration of tracheal forced expiratory noises under model dive of 16.3 m (0.263 MPa) is more then the diagnostic threshold of this parameter for lung function decrease, previously obtained for divers under normal pressure.     

Breathing during exercise in subjects with mild-to-moderate airflow obstruction: effects of physical training.

In this study we explored the effects of physical training on the response of the respiratory system to exercise. Eight subjects with irreversible mild-to-moderate airflow obstruction [forced expiratory volume in 1 s of 85 +/- 14 (SD) % of predicted and ratio of forced expiratory volume in 1 s to forced vital capacity of 68 +/- 5%] and six normal subjects with similar anthropometric characteristics underwent a 2-mo physical training period on a cycle ergometer three times a week for 31 min at an intensity of approximately 80% of maximum heart rate. At this work intensity, tidal expiratory flow exceeded maximal flow at control functional residual capacity [FRC; expiratory flow limitation (EFL)] in the obstructed but not in the normal subjects. An incremental maximum exercise test was performed on a cycle ergometer before and after training. Training improved exercise capacity in all subjects, as documented by a significant increase in maximum work rate in both groups (P < 0.001). In the obstructed subjects at the same level of ventilation at high workloads, FRC was greater after than before training, and this was associated with an increase in breathing frequency and a tendency to decrease tidal volume. In contrast, in the normal subjects at the same level of ventilation at high workloads, FRC was lower after than before training, so that tidal volume increased and breathing frequency decreased. These findings suggest that adaptation to breathing under EFL conditions does not occur during exercise in humans, in that obstructed subjects tend to increase FRC during exercise after experiencing EFL during a 2-mo strenuous physical training period.     

Fluctuations in plantar flexion force are reduced after prolonged tendon vibration.

The purpose of the study was to examine the effect of prolonged vibration on the force fluctuations during a force-matching task performed at low-force levels. Fourteen young healthy men performed a submaximal force-matching task of isometric plantar flexion before and after Achilles tendon vibration (n = 8, vibration subjects) or lying without vibration (n = 6, control subjects) for 30 min. The target forces were 2.5-10% of the previbration maximal voluntary contraction force. The standard deviation of force decreased by a mean of 29 +/- 20% across target forces after vibration, whereas it did not decrease significantly in control subjects (-5 +/- 12%). This change was significantly greater compared with control subjects (P < 0.01 for both). Power spectral density of the force was predominantly composed of signals of low-frequency bandwidth (相似文献   

Adrenergic airway vascular smooth muscle responsiveness in healthy and asthmatic subjects.

The purpose of the present study was to determine the responsiveness of airway vascular smooth muscle (AVSM) as assessed by airway mucosal blood flow (Qaw) to inhaled methoxamine (alpha(1)-agonist; 0.6-2.3 mg) and albuterol (beta(2)-agonist; 0.2-1.2 mg) in healthy [n = 11; forced expiratory volume in 1 s, 92 +/- 4 (SE) % of predicted] and asthmatic (n = 11, mean forced expiratory volume in 1 s, 81 +/- 5%) adults. Mean baseline values for Qaw were 43.8 +/- 0.7 and 54.3 +/- 0.8 microl. min(-1). ml(-1) of anatomic dead space in healthy and asthmatic subjects, respectively (P < 0.05). After methoxamine inhalation, the maximal mean change in Qaw was -13.5 +/- 1.0 microl. min(-1). ml(-1) in asthmatic and -7.1 +/- 2.1 microl. min(-1). ml(-1) in healthy subjects (P < 0.05). After albuterol, the mean maximal change in Qaw was 3.0 +/- 0.8 microl. min(-1). ml(-1) in asthmatic and 14.0 +/- 1.1 microl. min(-1). ml(-1) in healthy subjects (P < 0.05). These results demonstrate that the contractile response of AVSM to alpha(1)-adrenoceptor activation is enhanced and the dilator response of AVSM to beta(2)-adrenoceptor activation is blunted in asthmatic subjects.     

Attenuation of induced bronchoconstriction in healthy subjects: effects of breathing depth.

The effects of breathing depth in attenuating induced bronchoconstriction were studied in 12 healthy subjects. On four separate, randomized occasions, the depth of a series of five breaths taken soon (approximately 1 min) after methacholine (MCh) inhalation was varied from spontaneous tidal volume to lung volumes terminating at approximately 80, approximately 90, and 100% of total lung capacity (TLC). Partial forced expiratory flow at 40% of control forced vital capacity (V(part)) and residual volume (RV) were measured at control and again at 2, 7, and 11 min after MCh. The decrease in V(part) and the increase in RV were significantly less when the depth of the five-breath series was progressively increased (P < 0.001), with a linear relationship. The attenuating effects of deep breaths of any amplitude were significantly greater on RV than V(part) (P < 0.01) and lasted as long as 11 min, despite a slight decrease with time when the end-inspiratory lung volume was 100% of TLC. In conclusion, in healthy subjects exposed to MCh, a series of breaths of different depth up to TLC caused a progressive and sustained attenuation of bronchoconstriction. The effects of the depth of the five-breath series were more evident on the RV than on V(part), likely due to the different mechanisms that regulate airway closure and expiratory flow limitation.     

Refractoriness for ultrasonically nebulized distilled water and histamine after histamine challenge

Refractoriness for bronchial provocation frequently occurs after different challenge tests used to assess bronchial hyperresponsiveness in asthmatic patients. We investigated whether histamine inhalation could cause refractoriness for bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) and whether histamine causes tachyphylaxis for a subsequent histamine challenge in nine stable asthmatic patients. Preinhalation of histamine induced a significant diminished bronchoconstrictor response to UNDW cumulative dose of inhaled UNDW causing a 20% fall in forced expired volume in 1 s. The mean increased from 3.5 +/- 0.8 to 11.8 +/- 2.6 (SE) ml after histamine challenge (P less than 0.01). However, repeated inhalation of histamine did not change the bronchoconstrictor response to histamine within 1 h after rechallenge (P greater than 0.5). The magnitude of refractoriness for UNDW inhalation after preinhalation of histamine was correlated to the bronchoconstrictor response to histamine (r = 0.73, P less than 0.05). We conclude that inhaled histamine can induce refractoriness for UNDW, which seems to be related to the degree of bronchial hyperresponsiveness.