Elevated End-expiratory Lung Volume Research Articles

A new approach for the detection of obesity-related airway obstruction in lung-healthy individuals

BackgroundSubjects with obesity show an increased prevalence of airway obstruction but it is not clear in each case whether this reflects genuine lung disease. Via intentional increase in end-expiratory lung volume we studied the detection of obesity-induced airway obstruction in lung-healthy obese subjects. MethodsThe primary study population comprised 66 lung-healthy obese subjects and 23 normal weight subjects. Measurements were performed in a body plethysmograph allowing for recording and quantification of breathing loops in terms of specific airway resistance at both normal and intentionally elevated end-expiratory lung volume. The change in volume was documented by a shutter maneuver. ResultsThe voluntary increase of lung volume led to a significant reduction of expiratory airway resistance in 11 of the 66 obese subjects. This reduction could be quantified by a change of total expiratory resistance (sRtEX) of >1 kPa*s but was also clearly visible in the breathing loops. sRtEX showed the largest change among all resistance parameters. The loops of normal weight subjects remained virtually unaffected by the change in lung volume. Moreover, those of 5 obese patients with COPD who were measured for comparison partially showed a reduction of resistance but airway obstruction remained. ConclusionThe proposed breathing maneuver was simple to perform and allowed for a quantitative and qualitative detection of obesity-induced airway obstruction. This might help in reducing the likelihood of misdiagnosis and overtreatment of obese patients.

Effect of end-expiratory lung volume on upper airway collapsibility in sleeping men and women.

The relationship between changes in absolute end-expiratory lung volume (EELV) and collapsibility has not been rigorously quantified. We hypothesized that pharyngeal collapsibility varies inversely with absolute lung volume in sleeping humans during 1) conventional and 2) isovolume measurements of passive critical pressure (Pcrit). Eighteen healthy subjects (11 male, 7 female) slept in a negative pressure ventilator for measurements of pharyngeal collapsibility (Pcrit) during non-rapid eye movement sleep. EELV was 1) allowed to vary with changes in nasal pressure for conventional Pcrit measurements and 2) controlled by maintaining a fixed pressure difference across the respiratory system (P(RS)) from the nose to the body surface for isovolume Pcrit measurements at elevated EELV (P(RS) = +10 cmH(2)O), reduced EELV (P(RS) = -5 cmH(2)O), and functional residual capacity (FRC; P(RS) = 0 cmH(2)O). In each condition, the absolute EELV was determined and the corresponding Pcrit was derived from upper airway pressure-flow relationships. In the entire group, Pcrit varied inversely with EELV (P < 0.001). Pcrit decreased as EELV increased from the conventional to the FRC isovolume condition by -3.5 ± 1.0 cmH(2)O/l (P < 0.003). Subjects with a conventional Pcrit below -2 cmH(2)O exhibited greater reductions in EELV and correspondingly greater decreases in the FRC isovolume compared with the conventional Pcrit (P < 0.001). The overall response, ΔPcrit/ΔEELV, was -2.0 ± 0.2 cmH(2)O/l (P < 0.001) and did not differ between men and women (P = 0.16). Nevertheless, men and women differed significantly in FRC (2.63 ± 0.16 vs. 1.88 ± 0.13 liters, P <0.05) and FRC isovolume Pcrit (-2.3 ± 0.8 vs. -7.2 ± 1.2 cmH(2)O, P < 0.05), implying that the men had larger lungs and more collapsible airways than the women. The ΔPcrit/ΔEELV response was independent of sex, conventional Pcrit, body mass index, and neck, waist, and hip circumferences. We conclude that Pcrit varies inversely with absolute EELV, which may lead to 1) an underestimation of the magnitude of quantitative differences in Pcrit across the spectrum from health (negative Pcrit) to disease (positive Pcrit) and 2) increases in sleep apnea susceptibility in obesity.

Refining Ventilatory Treatment for Acute Lung Injury and Acute Respiratory Distress Syndrome

ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) IS the clinical manifestation of inflammatory lung edema originating from a variety of insults. Since its first description 40 years ago, the mainstays of management have been institution of mechanical ventilation to ventilate the incompliant lungs, inspired oxygen for hypoxemia, and when hypoxemia is severe, the addition of positive end-expiratory pressure (PEEP) to increase end-expiration lung volume, which facilitates O2 gas exchange. Early on, physicians recognized that the high intrathoracic pressures of mechanical ventilation caused parenchymal stress or rupture, known as barotrauma. However, it took several years to identify the local injury resulting from intratidal opening and closing of parts of the lung (atelectrauma) and the inflammatory reaction of the lung to nonphysiological stress (biotrauma). Subsequently computed tomographic scanning showed that the lung fraction open to gas exchange in ARDS is small, equivalent in size to that of a young child (baby lung model). This observation provided the anatomical basis for the concept of volutrauma, focused on the excessive strain within the baby lung induced by tidal ventilation. Taken together, these multiple potentially damaging factors are now called ventilatorinduced lung injury (VILI). In the last decade, prevention of VILI through gentle lung treatment, by adjusting either tidal volume or PEEP, has become the major goal of mechanical ventilatory support not just for ARDS but for the broader population of patients with acute lung injury (ALI). With regard to tidal volume, this line of reasoning and research was most conclusively supported by the National Heart, Lung, and Blood Institute ARDS Network trial demonstrating an improvement in survival for patients with ALI or ARDS who were ventilated with low tidal volumes (6 mL/kg of predicted body weight) compared with those ventilated with higher tidal volumes (12 mL/kg of predicted body weight). Although many argued that the tidal volume in the control group might have been higher than existing practice, the tidal volume in the interventional group marked a stark departure from usual care and has resulted in a dramatic change in the approach to tidal volume setting for ALI and ARDS. The optimal PEEP strategy, however, has remained unresolved. Evidence from animal studies suggested that higher PEEP (in the range of 10-15 cm H2O) could prevent VILI. Thus, many clinicians were surprised when the first large randomized clinical trial comparing higher levels of PEEP with lower levels of PEEP in patients with ALI and ARDS, the National Heart, Lung, and Blood Institute’s ARDS Network Assessment of Low Tidal Volume and Elevated EndExpiratory Lung Volume to Obviate Lung Injury (ALVEOLI) study, was stopped for futility. In this issue of the JAMA, 2 new large international randomized trials examining the effects of PEEP on outcome in patients with ALI and ARDS are presented. In the Lung Open Ventilation (LOV) trial, the level of PEEP administered, either lower or higher, was selected according to an oxygenation scale conceptually similar to the one used in the previous ALVEOLI study. In the Expiratory Pressure (Express) trial, PEEP selection was based on a more subtle and refined approach, using bedside assessment of lung mechanics instead of gas exchange. This method identified a minimal distention strategy (lower level of PEEP) and an increased recruitment strategy (higher level of PEEP). Despite the different criteria used for PEEP selection, the PEEP levels tested were similar in the 2 studies. In the LOV study, mean PEEP levels on day 1 were 15.6 cm H2O and 10.1 cm H2O, and the subsequent hospital mortality rates were 36.4% and 40.4%. In the Express study, mean PEEP levels on day 1 were 15.8 cm H2O and 8.4 cm H2O, and the

"Tightness" sensation of asthma does not arise from the work of breathing.

Asthma evokes several uncomfortable sensations including increased "effort to breathe" and chest "tightness." We have tested the hypotheses that "effort" and "tightness" are due to perception of increased work performed by the respiratory muscles. Bronchoconstriction was induced by inhaled methacholine in 15 subjects with mild asthma (FEV(1)/FVC baseline = 81.9% +/- 5.8; bronchoconstriction = 64.0% +/- 8.6). To relieve the work of breathing, and thereby minimize activation of respiratory muscle afferents and motor command, subjects were mechanically ventilated. Subjects separately rated effort to breathe and tightness during mechanical ventilation and during spontaneous breathing. Bronchoconstriction produced elevated end-expiratory lung volume (279 +/- 62 ml); in a control study, end-expiratory lung volume was increased equally in the absence of bronchoconstriction by increasing end-expiratory pressure. During bronchoconstriction, ratings of effort were greater during spontaneous breathing than during mechanical ventilation (p < 0.05). Ratings of tightness were unchanged by the absence of respiratory muscle activity (p = 0.12). Hyperinflation alone did not produce tightness or effort. We conclude that tightness is not related to the increase in respiratory work during bronchoconstriction.

Enhanced ventilatory and exercise performance in athletes with slight expiratory resistive loading.

We determined the cardiorespiratory and performance effects of slight (1.5-3.0 cmH2O) expiratory resistive loading (ERL). Twenty-eight highly fit [peak O2 uptake (VO2 peak) = 63.6 +/- 1.3 ml . kg-1 . min-1] athletes (age = 33.5 +/- 1.3 yr) performed paired VO2 peak cycle ergometer tests (control vs. ERL). End-expiratory lung volume was separately determined in a subset of subjects (n = 12) at steady-state 75% maximum power output (POmax) and was found to increase (0.67 +/- 0.29 liter) with ERL. In the VO2 peak tests, peak expiratory pressure at the mouth, mean inspiratory flow, minute ventilation, and O2 pulse were greater with ERL at every intensity level (i.e., 75, 80, 85, and 90% POmax). Increased minute ventilation was largely due to a trend toward increased tidal volume (P < 0.05 at 80% POmax). O2 uptake was greater at 90% POmax with ERL. Increased O2 pulse with ERL at comparative workloads suggests that stroke volume was augmented with ERL. Also, with ERL, athletes attained higher VO2 peak (63.0 +/- 1.4 vs. 60.1 +/- 1.3 ml . kg-1 . min-1) and greater POmax (352.0 +/- 9.9 vs. 345.7 +/- 9.5 W). We conclude that elevated end-expiratory lung volume in response to slight ERL during strenuous exercise served to attenuate both airflow and blood flow limitations, which enhanced exercise capacity.

Effects of hyperinflation and CPAP on work of breathing and respiratory failure in dogs

Increased end-expiratory lung volume (EELV) and airway resistance are both characteristic features of obstructive lung disease. Increased EELV alone loads the respiratory muscles and may cause respiratory failure, changes that could be reversed by continuous positive airway pressure (CPAP). To study the effects of elevated EELV on respiration without increased airway resistance, we used a mechanical analogue of airway closure to increase EELV in six spontaneously breathing anesthetized dogs. Hyperinflation of 0.84 +/- 0.11 liter for 30 min decreased minute ventilation from 4.8 +/- 0.37 to 3.5 +/- 0.21 l/min and increased arterial PCO2 from 40.3 +/- 1.5 to 73.2 +/- 8.1 Torr (both P < 0.01). Inspiratory work per breath increased 3-fold, work per liter increased 3.7-fold, and work per minute increased 2.8-fold (all P < 0.01). CPAP at 15 cmH2O restored minute ventilation to 4.3 +/- 0.3 l/min and reduced arterial PCO2 to 54 +/- 6.6 Torr (NS vs. baseline). All measurements of inspiratory work were also restored to baseline, but cardiac output was reduced (baseline 3.09 +/- 0.36, hyperinflation 2.71 +/- 0.36, hyperinflation + CPAP 1.94 +/- 0.29 l/min; P < 0.05, baseline vs. hyperinflation + CPAP). We conclude that increases in EELV mimic important features of airway obstruction, increase inspiratory work, and can cause respiratory failure independent of increased airway resistance. This respiratory failure is reversed by CPAP at the potential expense of hemodynamic compromise.

Hypercapnia increases expiratory braking in preterm infants

In contrast to adults, newborn infants breathe from an elevated end-expiratory lung volume, determined by the interaction of airflow retardation (braking) by the diaphragm and larynx, and expiratory duration. To determine the effect of hypercapnia on this strategy, we examined changes in respiratory muscle activity and the ventilatory response to CO2 breathing in eight premature infants 33-34 wk gestational age in the first 3 postnatal days. We recorded tidal volume, airflow, and electromyograms (EMG) of the laryngeal abductor [posterior cricoarytenoid (PCA)], which abducts the vocal cords, and diaphragm during behaviorally determined quiet sleep in room air and during steady-state inhalation of 2% CO2 in air. As expected, tidal volume increased (P < 0.0005) without a change in inspiratory duration with hypercapnia. Unexpectedly, in all subjects, expiratory duration was longer during CO2 inhalation (P < 0.001), accompanied by marked changes in expiratory flow patterns consistent with increased expiratory braking. Diaphragm post-inspiratory EMG activity increased with hypercapnia (P < 0.005) with no change in baseline diaphragm or PCA EMG activity. Peak inspiratory EMG activity of the diaphragm and PCA increased with CO2 (10 and 37%, respectively; P < 0.05). We conclude that the mechanisms used to elevate end-expiratory lung volume are enhanced during hypercapnia in premature infants. This breathing strategy may be important in maintaining gas exchange in infants with lung disease.

Preservation of sustainable inspiratory muscle pressure at increased end-expiratory lung volume.

Previous studies in isolated muscles have shown that decreases in muscle length reduce the loss of force resulting from fatigue in response to repeated maximal stimulations. However, increases in end-expiratory lung volume (EEV), which presumably decrease the length of the inspiratory muscles, appear to make the inspiratory muscles more susceptible to fatigue. To address this paradox, we studied the influence of changes in EEV on inspiratory muscle fatigue resulting from repeated maximal voluntary inspirations for 15 min in normal humans. Tidal volume and breath timing were constant between runs. Fatigue runs were compared with atmospheric, positive or negative pressures applied to the mouth, sufficient to change EEV by approximately +30% or -20% of inspiratory capacity. Although the maximal initial pressure-time product for the inspiratory muscles (PTmus) was reduced by increased EEV, sustainable PTmus was not significantly affected. In contrast, both initial and sustainable pressure-time products for the diaphragm were reduced at elevated EEV. The rate at which the fatigue process developed was also reduced at increased EEV. There were no significant effects of decreased EEV on any measured pressures. We conclude that when EEV is elevated, within a moderate range, sustainable inspiratory muscle pressure is preserved. However, the contribution of the diaphragm to inspiratory pressure development during fatigue may be uniquely compromised by increased EEV.

Effects of increased end-expiratory lung volume on breathing in awake ponies

We studied the changes in breathing and respiratory muscle electromyograms (EMG) during passively induced increases in end-expiratory lung volume (EELV) in awake normal (N), hilar nerve-denervated (HND), carotid body-denervated (CBD), and HND + CBD ponies. EELV was increased by applying continuous negative pressure (-10 and -20 cmH2O) around the torso of the standing pony. In all groups, negative pressure produced sustained increases in EELV that were linearly related to the degree of negative pressure. Elevated EELV decreased breathing frequency (f) in N and CBD ponies but increased f in HND and HND + CBD ponies. When EELV was increased, tidal volume was unchanged or above control in N ponies but was below or near control in the other groups. In all groups during elevated EELV, arterial PCO2 initially decreased but then increased relative to control with isocapnia achieved after approximately 1.5 min. In all groups, the elevated EELV was accompanied by increased stimulation of the diaphragm as indicated by increased rate of rise of the integrated EMG (P less than 0.05). During elevated EELV, the duration of diaphragm EMG was reduced, but only in HND ponies was this reduction significant (P less than 0.05). In N ponies, the major effect of elevated EELV on the expiratory transversus abdominis (TA) muscle was an increase (P less than 0.05) in duration of activity and therefore total activity. The work of breathing was thus presumably shifted more to this muscle during elevated EELV. These changes in TA timing were not observed in HND and HND + CBD ponies during elevated EELV. We conclude that elevation of EELV, which presumably places the diaphragm on a less favorable portion of its length-tension relationship, results in compensatory increased stimulation of the diaphragm that is not critically dependent on hilar and carotid chemoreceptor afferents. However, hilar afferents do contribute to the changes in diaphragm and TA duration of activity during elevated EELV.

Inductance plethysmography measurement of CPAP-induced changes in end-expiratory lung volume

The respiratory inductance plethysmograph (RIP) has recently gained popularity in both the research and clinical arenas for measuring tidal volume (VT) and changes in functional residual capacity (delta FRC). It is important however, to define the likelihood that individual RIP measurements of VT and delta FRC would be acceptably accurate (+/- 10%) for clinical and investigational purposes in spontaneously breathing individuals on continuous positive airway pressure (CPAP). Additionally, RIP accuracy has not been compared in these regards after calibration by two commonly employed techniques, the least squares (LSQ) and the quantitative diagnostic calibration (QDC) methods. We compared RIP with pneumotachographic (PTH) measurements of delta FRC and VT during spontaneous mouth breathing on 0-10 cmH2O CPAP. Comparisons were made after RIP calibration with both the LSQ (6 subjects) and QDC (7 subjects) methods. Measurements of delta FRC by RIPLSQ and RIPQDC were highly correlated with PTH measurements (r = 0.94 +/- 0.04 and r = 0.98 +/- 0.01 (SE), respectively). However, only an average of 30% of RIPQDC determinations per subject and 31.4% of RIPLSQ determinations per subject were accurate to +/- 10% of PTH values. An average of 55.2% (QDC) and 68.8% (LSQ) of VT determinations per subject were accurate to +/- 10% of PTH values. We conclude that in normal subjects, over a large number of determinations, RIP values for delta FRC and VT at elevated end-expiratory lung volume correlate well with PTH values. However, regardless of whether QDC or LSQ calibration is used, only about one-third of individual RIP determinations of delta FRC and one-half of two-thirds of VT measurements will be sufficiently accurate for clinical and investigational use.

Phrenic afferents and ventilatory control at increased end-expiratory lung volumes in cats

The role of phrenic afferents in controlling inspiratory duration (TI) at elevated end-expiratory lung volume (EEV) has been studied in pentobarbital-anesthetized, spontaneously breathing cats with intact vagi. Responses to increases in EEV, induced by imposition of an expiratory threshold load (ETL) of 10 cmH2O, were monitored before and after section of cervical dorsal roots C3-C7. The immediate (first-breath) effect of application of ETL was a prolongation of both TI and expiratory duration (TE). After 10 min of breathing against the ETL, average TI returned to control values but TE remained prolonged. Abolishing feedback from the diaphragm did not affect these responses. When steady-state responses to ETL were compared with those elicited by inhalation of 5-6% CO2 in O2, changes in EEV had, on average, no independent effect on respiratory drive (rate of rise of integrated phrenic activity), although phrenic activity increased greatly in some cats despite little or no change in arterial partial pressure of CO2. These data indicate that diaphragmatic receptors do not contribute to either the immediate (first-breath) or steady-state responses of phrenic motoneurons to increases in EEV in intact cats.

Influence of the upper airway on breathing pattern and expiratory time constant in unanesthetized dog pups

Unanesthetized dog pups (2 to 31 days old) respond to sudden opening of a tracheal cannula to atmospheric pressure with a marked increass in breathing frequency. This response is achieved with a 25% decrease in inspiratory and 40% decrease in expiratory times. Expiratory thyroarytenoid muscle activity increased concomitantly, while inspiratory diaphragmatic and posterior cricoarytenoid muscle activities were reduced. These responses are interpreted as a compensatory mechanism for maintenance of an elevated end-expiratory lung volume with functional loss of the upper airway. The changes in expiratory time and thyroarytenoid muscle activity were not observed when positive pressure was applied at the trachea. The expiratory time constant was assessed during spontaneous breathing. The mean value was twice as long during nasal breathing than during tracheal breathing. The nasal value was substantially increased when the thyroarytenoid muscle was active during expiration.

Laryngeal muscle and diaphragmatic activities n conscious dog pups

A new chronic animal preparation ( i.e. puppies) for the study of respiratory laryngeal muscle acitivity is described. Posterior cricoarytenoid (PCA), thyroarytenoid (TA) and diaphragmatic activities were monitored in conscious puppies (13–43 days old) using chronically implanted electrodes. PCA activity was prominent during inspiration in all behavioral states. TA and post-inspiratory diaphragmatic activities were consistently high during expiration in quiet wakefulness and quiet sleep, but expiratory TA activity decreased dramatically and post-inspiratory diaphragmatic activity became highly variable in rapid eye movement sleep. There was also a tendency for these expiratory muscle activities to become less pronounced with increasing postnatal age. When a chronically implanted, low resistnace T-tube tracheal cannula was suddenly opened, thus effectively eliminating the effects of upper airway resistance on airflow, respiratory frequency dramatically increased. These results indicate that the exhibits muscle activities consistent with the maintenance of an elevated end-expiratory lung volume achieved by the retardation of expiratory airflow using the larynx and diaphragm.