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Biomedical subjects

J Milic-Emili

Publications and source records attributed to J Milic-Emili.

At least 19 recordsLinked to original sources

Expiratory flow limitation during exercise in competition cyclists.

In some trained athletes, maximal exercise ventilation is believed to be constrained by expiratory flow limitation (FL). Using the negative expiratory pressure method, we assessed whether FL was reached during a progressive maximal exercise test in 10 male competition cyclists. The cyclists reached an average maximal O2 consumption of 72 ml. kg-1. min-1 (range: 67-82 ml. kg-1. min-1) and ventilation of 147 l/min (range: 122-180 l/min) (88% of preexercise maximal voluntary ventilation in 15 s). In nine subjects, FL was absent at all levels of exercise (i.e., expiratory flow increased with negative expiratory pressure over the entire tidal volume range). One subject, the oldest in the group, exhibited FL during peak exercise. The group end-expiratory lung volume (EELV) decreased during light-to-moderate exercise by 13% (range: 5-33%) of forced vital capacity but increased as maximal exercise was approached. EELV at peak exercise and at rest were not significantly different. The end-inspiratory lung volume increased progressively throughout the exercise test. The conclusions reached are as follows: 1) most well-trained young cyclists do not reach FL even during maximal exercise, and, hence, mechanical ventilatory constraint does not limit their aerobic exercise capacity, and 2) in absence of FL, EELV decreases initially but increases during heavy exercise.

Adolescent

Tension-time index of inspiratory muscles in COPD patients: role of airway obstruction.

Inspiratory muscle function has been shown to be related to general muscle weakness, weight loss, blood gas tensions, airway obstruction and hyperinflation. The aim of this study was to define (1) the factor that is the main determinant of the tension-time index of the inspiratory muscles (TTmus), and which this increases the risk of inspiratory muscle fatigue; and (2) whether a breathing strategy is adopted to avoid inspiratory muscle fatigue. Twenty-seven normal volunteers and 35 stable COPD outpatients (FEV1% predicted, range: 21-89%; and FRC/TLC, range: 49-77%) were studied. The TTmus was determined as follows: TTmus = PI/PImax.TI/Ttot, where Pi is the mean inspiratory pressure calculated from the mouth occlusion pressure (P0.1), PImax is the maximal inspiratory pressure, TI is the inspiratory time, and Ttot is the total time of the breathing cycle. COPD patients showed significantly lower PImax and higher P0.1, PI, PI/PImax, and TTmus than normal subjects. No patient had a TTmus value higher than the inspiratory muscle fatigue threshold of 0.33. The FEV1 was significantly correlated with TTmus and all its components in the patients. The FRC/TLC was also correlated with all components except PI. Body weight was only correlated with PImax. In a forward and backward stepwise regression analysis, FEV1 appeared to be the only significant factor explaining the variance of log (PI/PImax) and log (TTmus), whereas FRC/TLC was the principal determinant of PImax. In COPD patients, a non-linear relationship was found between TI and P0.1. A negative linear relationship was found between TI/Ttot and PI/PImax. In conclusion, although hyperinflation predominantly affected inspiratory muscle strength in a group of stable COPD patients with a wide range of severity, airway obstruction was the principal factor determining the magnitude of TTmus. In addition, in order to remain below the inspiratory muscle fatigue threshold, as the severity of airway obstruction increased, patients adopted a breathing strategy characterized by decreased TI/Ttot as inspiratory pressure demand increased.

Adaptation, Physiological

Effect of inverse I:E ratio ventilation on pulmonary gas exchange in acute respiratory distress syndrome.

BACKGROUND: It is not known whether inverse I:E ratio ventilation (IRV) offers any real benefit over conventional mechanical ventilation with positive end-expiratory pressure (CMV-PEEP) at similar levels of end-expiratory pressure. METHODS: The effects of volume-controlled and pressure-controlled IRV (VC-IRV and PC-IRV, respectively) on VA/Q inequality were compared with those of CMV-PEEP at a similar level of end-expiratory pressure and with CMV without PEEP (CMV) in eight patients in the early stages of acute respiratory distress syndrome (ARDS). Respiratory blood gases, inert gases, lung mechanics, and hemodynamics were measured 30 min after the onset of each ventilatory mode. RESULTS: Recruitment of nonventilated, poorly ventilated (or both) but well-perfused alveoli increased the partial pressure of oxygen (PaO2) during CMV-PEEP (+13 mmHg) and IRV-VC (+10 mmHg; P < 0.05) compared with CMV. In contrast, PC-IRV did not affect PaO2 but caused a decrease in PaCO2 (-7 mmHg; P < 0.05). The latter was due to a concomitant decrease in dead space (P < 0.01) and shift to the right of VA/Q distributions. During PC-IRV, the increase in the mean of blood flow distribution (mean Q; P < 0.01) without a change in the dispersion (log SD Q) did not result in an increase in PaO2, probably because it reflected redistribution of blood flow within well-ventilated areas. CONCLUSIONS: Short-term PC-IRV improved carbon dioxide clearance, but the lung became less efficient as an oxygen exchanger. Furthermore, based on mean airway and plateau pressures, the risk of barotrauma was not reduced with this type of ventilation.

Adult

Application of negative expiratory pressure during expiration and activity of genioglossus in humans.

The application of negative expiratory pressure (NEP) at end expiration has been shown to cause reflex-mediated activation of the genioglossus muscle in awake humans. To test whether a reflex contraction of pharyngeal dilator muscles also occurs in response to NEP applied in early expiration, the effect on genioglossus muscle reflex activity of NEP pulses of 500 ms, given 0.2 s after the onset of expiration and during the end-expiratory pause, was assessed in 10 normal awake subjects at rest. The raw and integrated surface electromyogram of the genioglossus (EMGgg) was recorded with airflow and mouth pressure under control conditions and with NEP ranging from -3 to -10 cmH2O. Intraoral EMGgg was also recorded under the same experimental conditions in two subjects. The application of NEP at the end-expiratory pause elicited a consistent reflex response of EMGgg in seven subjects with a mean latency of 68 +/- 5 ms. In contrast, when NEP was applied at the onset of expiration, EMGgg reflex activity was invariably observed in only one subject. No relationship was found between steady increase or abrupt fall in expiratory flow and the presence or the absence of a reflex activity of genioglossus during sudden application of NEP at the beginning of expiration. Our results show that a reflex activity of genioglossus is elicited much more commonly during application of NEP at the end rather than at the onset of expiration. These findings also suggest that when NEP is applied in early expiration to detect intrathoracic flow limitation the absence of upper airways narrowing does not imply the occurrence of a reflex-mediated activation of genioglossus and vice versa.

Adult

Mechanical work of breathing during maximal voluntary ventilation.

With the use of the esophageal balloon technique, the working capacity of the respiratory muscles was assessed in four normal subjects by measuring the work per breath (W) and respiratory power (W) during maximal voluntary ventilation with imposed respiratory frequencies (f) ranging from 20 to 273 cycles/min. Measurements were made in a body plethysmograph to assess the work wasted as a result of alveolar gas compressibility (Wg'). In line with other types of human voluntary muscle activity, W decreased with increasing f, whereas W exhibited a maximum at f of approximately 100 cycles/min. Up to this f value, Wg' was small relative to W. With further increase in f, the Wg'/W ratio increased progressively, amounting to 8-22% of W at f of 200 cycles/min.

Adult

Effect of salbutamol on dynamic hyperinflation in chronic obstructive pulmonary disease patients.

Expiratory flow limitation (EFL), which promotes dynamic hyperinflation and increased work of breathing, often occurs in chronic obstructive pulmonary disease (COPD). The purpose of this study was to assess the effect of bronchodilators on EFL and end-expiratory lung volume in patients with moderate-to-severe COPD. EFL was assessed by applying negative expiratory pressure (NEP) at the mouth during tidal expiration. EFL was present when expiratory flow did not increase or increased only in the early phase of expiration with NEP. In 18 patients (age 65+/-2 yrs; forced expiratory volume in one second (FEV1)=45+/-4% predicted) pulmonary function tests and a series of NEP (-3.5 cmH2O) test breaths were performed at rest in a sitting position before and 20 min after inhalation of 400 microg of salbutamol. EFL was detected in 11 patients and persisted after salbutamol in all of these flow-limited (FL) patients. After bronchodilator administration FL patients exhibited a significant decrease in functional residual capacity (FRC) associated with an increase in inspiratory capacity (IC). In contrast, no changes in FRC and IC were observed in the seven non flow-limited (NFL) patients after administration of salbutamol. Except for one NFL patient, the other 17 patients (six NFL and 11 FL) had no reversibility of their bronchial obstruction (delta FEV1 <10% pred). In conclusion, patients with chronic obstructive pulmonary disease and expiratory flow limitation, even if nonresponders in terms of forced expiratory volume in one second, may benefit from bronchodilators because they can breathe, still in a flow-limited manner, at a lower lung volume.

Administration, Inhalation

Single-breath method for assessing the viscoelastic properties of the respiratory system.

In order to explain the time dependency of resistance and elastance of the respiratory system, a linear viscoelastic model (Maxwell body) has been proposed. In this model the maximal viscoelastic pressure (Pvisc.max) developed within the tissues of the lung and chest wall at the end of a constant-flow (V') inflation of a given time (tI) is given by: Pvisc,max = R2V'(1-e(-tI/tau2), where R2 and tau2 are, respectively, the resistance and time constant of the Maxwell body. After rapid airway occlusion at t1, tracheal pressure (Ptr) decays according to the following function: Ptr(t) = Pvisc(t) + Prs,st = Pvisc,max(etocc/tau2)+ Prs,st, where tocc/is time after occlusion and Prs,st is static re-coil pressure of the respiratory system. By fitting Ptr after occlusion to this equation, tau2 and Pvisc,max are obtained. Using these values, together with the V' and tI pertaining to the constant-flow inflation preceding the occlusion, R2 can be calculated from the former equation. Thus, from a single breath, the constants tau2, R2 and E2 (R2/tau2) can be obtained. This method was used in 10 normal anaesthetized, paralysed, mechanically ventilated subjects and six patients with acute lung injury. The results were reproducible in repeated tests and similar to those obtained from the same subjects and patients with the time-consuming isoflow, multiple-breath method described previously.

Adult

Exercise limitation in obstructive lung disease.

OBJECTIVE: To study the relationship of resting pulmonary function to maximal exercise power output (Wmax) in obstructive lung disease (OLD). SETTING: University Hospital Pulmonary Function Laboratory. SUBJECTS: Twenty-five patients with OLD (6 with asthma and 19 with COPD). METHODS: Measurement of pulmonary lung function, resting arterial blood gases, and maximal symptom-limited exercise on a cycle ergometer. RESULTS AND CONCLUSIONS: In OLD, the only significant contributor to Wmax was the inspiratory capacity (r2 = 0.66; p < 0.001).

Blood Gas Analysis

Detection of expiratory flow limitation during exercise in COPD patients.

The negative expiratory pressure (NEP) method was used to detect expiratory flow limitation at rest and at different exercise levels in 4 normal subjects and 14 patients with chronic obstructive pulmonary disease (COPD). This method does not require performance of forced expirations, nor does it require use of body plethysmography. It consists in applying negative pressure (-5 cmH2O) at the mouth during early expiration and comparing the flow-volume curve of the ensuing expiration with that of the preceding control breath. Subjects in whom application of NEP does not elicit an increase in flow during part or all of the tidal expiration are considered flow limited. The four normal subjects were not flow limited up to 90% of maximal exercise power output (Wmax). Five COPD patients were flow limited at rest, 9 were flow limited at one-third Wmax, and 12 were flow limited at two-thirds Wmax. Whereas in all patients who were flow limited at rest the maximal O2 uptake was below the normal limits, this was not the case in most of the other patients. In conclusion, NEP provides a rapid and reliable method to detect expiratory flow limitation at rest and during exercise.

Adult

Expiratory flow limitation in COPD patients after single lung transplantation.

Expiratory flow limitation and dyspnea during resting breathing are common in patients with severe chronic obstructive pulmonary disease (COPD). Although single lung transplantation (SLT) is used to treat end-stage COPD, its effects on flow limitation and dyspnea are not well established. We assessed expiratory flow-limitation and dyspnea in 13 COPD patients after SLT at rest in the sitting and supine positions by applying negative pressure at the mouth during tidal expiration (negative expiratory pressure [NEP] technique). If NEP increases flow throughout the control tidal volume (VT), flow limitation is absent (not flow limited [NEL]). If NEP does not increase flow during part of the control VT, flow limitation is present. After SLT, lung function improved in all but one patient. Twelve patients were NFL during resting breathing in both positions studied. The patient whose lung function did not improve after SLT was flow-limited (FL) both when seated and supine. This patient also exhibited moderately severe chronic dyspnea (Medical Research Council [MRC] score = 3). In the nine other patients in whom dyspnea was assessed, it was slight (MRC score = 1). In conclusion, after SLT for end-stage COPD, expiratory flow limitation at rest is uncommon in both the seated and supine positions. This is consistent with the finding that after SLT the degree of chronic dyspnea is generally slight.

Dyspnea

Small airway closure and positive end-expiratory pressure in mechanically ventilated patients with chronic obstructive pulmonary disease.

The effects of positive end-expiratory pressure (PEEP) on alveolar recruitment and closing volume were studied in ten supine, sedated, and paralyzed patients with chronic obstructive respiratory disease and acute respiratory failure. We applied PEEP (0, 5, 10, and 15 cm H2O) and constructed inflation static volume-pressure (V-P) curves. In all patients, the static V-P curves obtained at different PEEP levels were superimposed on each other, indicating that with PEEP there was no recruitment of previously atelectatic lung units. However, the static V-P curves exhibited an inflection point, which should reflect the critical pressure (Po) required to reopen all closed airways, whilst the corresponding lung volume (Vo) reflects the opening volume. On average, Vo was 0.71 L above the relaxation volume of the respiratory system (Vr). All patients, however, exhibited dynamic hyperinflation, i.e., with zero PEEP (ZEEP) the end-expiratory lung volume (EELV) was 0.54 L above Vr. Nevertheless, in seven patients the EELV on ZEEP was below Vo, resulting in cyclic reopening and closure of small airways with each breathing cycle, with concomitant mechanical stresses on the peripheral airways that may lead to low-volume barotrauma. Such barotrauma may be prevented by increasing with PEEP the EELV to Vo.

Acute Disease

Expiratory flow limitation in stable asthmatic patients during resting breathing.

Application of negative pressure at the mouth during tidal expiration (NEP) provides a simple, rapid, noninvasive method for detecting expiratory flow limitation during spontaneous breathing. Patients in whom NEP elicits an increase in flow throughout expiration are not flow-limited (FL). In contrast, patients in whom application of NEP does not elicit an increase in flow during most or part of tidal expiration are considered FL. We have used the NEP technique to assess the prevalence of expiratory flow limitation during resting breathing in sable asthmatic patients in both the seated and supine positions. In patients in the sitting position, we have also assessed flow limitation with the conventional method, based on comparison of tidal and maximal expiratory flow-volume (MEFV) curves. We studied 13 patients (FEV1 range: 48 to 94% predicted) with both the NEP and conventional techniques. According to the NEP technique, none of the patients was FL in the seated and only two were FL in the supine position. By contrast, on the basis of the conventional method, six of the patients would have been classified as FL in the sitting position. We conclude that: (1) most stable asthmatic patients do not exhibit tidal expiratory flow limitation during resting breathing; and (2) the conventional method for assessing flow limitation may lead to erroneous conclusions.

Adolescent

Lung and chest wall mechanics in patients with acquired immunodeficiency syndrome and severe Pneumocystis carinii pneumonia.

The aim of this study was to assess the mechanical characteristics of the respiratory system in patients with acquired immune deficiency syndrome (AIDS) and acute respiratory distress syndrome (ARDS) caused by Pneumocystis carinii pneumonia (PCP). In 12 mechanically ventilated patients, total respiratory system mechanics was assessed using the technique of rapid airway occlusion during constant flow inflation, and was partitioned into lung and chest wall components using the oesophageal balloon technique. We measured interrupter resistance (Rint), which mainly reflects airway resistance, additional resistance (deltaR) due to viscoelastic behaviour and time constant inequalities, and static elastance (Est). In addition, the static inflation volume-pressure (V-P) curve was assessed. In eight patients, computed tomography scans were performed within 2 days of the assessment of respiratory mechanics. Compared to values reported in the literature for normal subjects, Est and deltaR were markedly increased in AIDS patients with PCP, whilst Rint exhibited a relatively smaller increase. These changes, which involved only the lung and airways, were mainly due to the reduction of ventilated lung units, but additional factors were involved to cause independent modifications of lung stiffness, airway calibre, and viscoelastic properties. The changes in Rint, deltaR, and Est were similar to those observed in other studies on patients with ARDS of different aetiologies. At variance with common observations in the latter patients, none of the AIDS patients with PCP exhibited an inflection point on the static inflation V-P curve, suggesting little or no alveolar recruitment during lung inflation. This finding could be related to the distinctive histopathology of Pneumocystis carinii pneumonia. Indeed, computed tomography revealed homogeneous diffuse interstitial and alveolar infiltration rather than the dense, dependent opacities observed in other studies on acute respiratory distress syndrome of different aetiologies.

AIDS-Related Opportunistic Infections

Dependence of forced vital capacity manoeuvre on time course of preceding inspiration in patients with restrictive lung disease.

In normal subjects and patients with airway obstruction, flows during a forced vital capacity (FVC) manoeuvre are higher after a fast inspiration without an end-inspiratory pause (manoeuvre 1) as compared to a slow inspiration with an end-expiratory pause of approximately 5 s (manoeuvre 2). In this study, we investigated the influence of these manoeuvres on maximal expiratory volume-time and flow-volume curves in patients with restrictive lung disease. Eleven patients with restrictive lung disease were studied. Their average (+/-SD) lung function test results were: FVC=55+/-12% predicted value, forced expiratory volume in one second (FEV1) 52+/-20% pred, FEV1/FVC 85+/-6%, total lung capacity 55+/-8% pred, and carbon monoxide transfer factor 47+/-18% pred. The patients performed the two FVC manoeuvres in random order. We compared the ensuing spirograms and maximal expiratory flow-volume curves from which peak expiratory flow, FEV1, FEV1/FVC, maximal mid-expiratory flow, and maximal flows were computed. All spirometric indices were significantly higher with manoeuvre 1 than 2. Maximal expiratory flows at the same lung volume were also significantly higher with manoeuvre 1 than 2, in all patients. Routine spirometric indices, obtained during a forced vital capacity manoeuvre depend on the time course of the preceding inspiration in patients with restrictive lung disease. Therefore, the forced vital capacity manoeuvre should be standardized if used in clinical, epidemiological and research studies.

Adult

Effects of inspiratory flow waveforms on arterial blood gases and respiratory mechanics after open heart surgery.

The clinical usefulness of inspiratory flow pattern manipulation during mechanical ventilation remains unclear. The aim of this study was to investigate the effects of different inspiratory flow waveforms, i.e. constant, sinusoidal and decelerating, on arterial blood gases and respiratory mechanics, in mechanically ventilated patients. Eight patients recovering after open heart surgery for valvular replacement and/or coronary bypass were studied. The ventilator inspiratory flow waveform was changed according to a randomized sequence, keeping constant the other variables of the ventilator settings. We measured arterial blood gases, flow, volume and pressure at the proximal (airway opening pressure (Pao)) and distal (Ptr) ends of the endotracheal tubes before and after 30 min of mechanical ventilation with each inspiratory flow waveform. We computed breathing pattern, respiratory mechanics (pressures and dynamic elastance) and inspiratory work, which was then partitioned into its elastic and resistive components. We found that: 1) arterial oxygen tension (Pa,O2) and arterial carbon dioxide tension (Pa,CO2) were not affected by changes in the inspiratory flow waveform; and 2) peak Pao and Ptr were highest with sinusoidal inspiratory flow, whilst mean Pao and Ptr and total work of breathing were least with constant inspiratory flow, mainly because of a concomitant decrease in resistive work during constant flow inflation. The effects of the inspiratory flow profile on Pao, Ptr and total inspiratory work performed by the ventilator were mainly due to the resistive properties of the endotracheal tubes. We conclude that the ventilator inspiratory flow waveform can influence patients' respiratory mechanics, but has no impact on arterial oxygen and arterial carbon dioxide tension.

Adult

Expiratory flow limitation during spontaneous breathing: comparison of patients with restrictive and obstructive respiratory disorders.

BACKGROUND AND STUDY OBJECTIVES: Comparison of tidal and forced expiratory flow-volume (V-V) curves has inherent technical problems in the characterization of expiratory flow limitation. In addition, patients with neuromuscular disorders may be unable to perform forced expiratory maneuvers because of muscle weakness or poor coordination. A recently developed simple, noninvasive technique that avoids these problems was used to detect expiratory flow limitation at rest in 19 seated patients with restrictive respiratory (13 with musculoskeletal) disorders (RD) and 20 with chronic obstructive airway disease (COAD). SETTING: A large rehabilitation hospital for the care of patients with chronic musculoskeletal and respiratory disorders. INTERVENTIONS AND MEASUREMENTS: The method consisted of applying negative pressure of about 5 cm H2O at the airway opening during expiration and comparing the ensuing V-V curve to the preceding tidal V-V curve. RESULTS: While nine patients with COAD demonstrated flow limitation, only one patient with RD did so. Patients with expiratory flow limitation exhibited various contours of the control tidal expiratory V-V curve. Thus, inspection of the tidal V-V curve is not a reliable means of detecting expiratory flow limitation. CONCLUSIONS: We conclude that expiratory flow limitation during resting breathing is common in patients with COAD but not in patients with RD.

Adult