Evaluating systemic lupus erythematosus patients for lung involvement.

INTRODUCTION: We set out to determine the frequency of respiratory symptoms, abnormal lung function, and shrinking lung syndrome (SLS) among patients with systemic lupus erythematosus (SLE) and to determine correlates of SLS. METHODS: Consecutive adult patients who fulfilled the American College of Rheumatology classification criteria for SLE were enrolled. Demographics, clinical, and serologic characteristics were recorded; all patients underwent pulmonary function tests (PFT) and had either a chest X-ray or computed tomography scan. SLS was defined as dyspnea with restrictive lung physiology (defined as a forced vital capacity (FVC) <80% predicted in the absence of obstruction) who did not have any evidence of interstitial lung disease on chest imaging; controls were symptomatic patients with no restrictive physiology and the absence of interstitial changes on chest imaging. RESULTS: Sixty-nine out of 110 (63%) patients had respiratory symptoms, 73 (66%) patients had abnormal lung function, and 11 (10%) patients met the definition for SLS. In a multivariate model controlling for disease duration, a history of pleuritis, modified American College of Rheumatology total score, seropositivity for dsDNA and RNP antibodies, increased disease duration (odds ratio (OR) = 1.2; 95% confidence interval (CI) of 1.0-1.3, p = 0.04), seropositivity for anti-RNP (OR = 24.4; 95% CI of 1.6-384.0, p = 0.02), and a history of serositis were significantly associated with SLS when compared with symptomatic controls. CONCLUSION: Respiratory symptoms, abnormal lung function, and SLS are common in SLE. Clinicians should consider evaluation for SLS among symptomatic patients with long-standing disease and a history of pleuritis.

Effects of pulmonary and intercostal denervation on the response of breathing frequency to varying inspiratory flow.

In mechanically ventilated awake and sleeping humans, it has been shown that increasing inspiratory flow rate (V'I) exerted a reflex excitatory effect on respiratory output. Mechanoreceptors located in intercostal muscles or within the lung have been suggested as possible pathways that may mediate the excitatory effect of V'I. To test this, five patients with bilateral lung transplantation (LTP) and eight quadriplegics with spinal cord transection at the level of C6-C7 (QP) were studied. Patients were connected to a volume cycle ventilator in the assist volume-control mode and V'I was randomly changed. V'I pattern was square and all breaths were patient-triggered. V'I values of 30, 60 and 90 L x min(-1) were studied. Each level of V'I was sustained for 15 breaths. Airway pressures, end-tidal partial pressure of carbon dioxide (PCO2), airflows and volumes were measured breath by breath. Thirty seven trials in LTP and sixty in QP, where V'I was randomly changed between 30 and 90 L x min(-1), were analysed. In both groups of patients, minute ventilation increased and total breath duration decreased significantly as V'I increased. These changes were complete in the first breath after V'I transition, without evidence of adaptation of the response. The magnitude of the response did not differ between the two groups of patients and was comparable to that observed previously in conscious normal subjects. We conclude that the excitatory effect of inspiratory flow rate on breathing frequency persists in patients who have pulmonary or intercostal denervation. These results do not favour receptors located within the lung (below the resection lines) or in the intercostal muscles to mediate the response of breathing frequency to flow rate.

Respiratory response to CO2 during pressure-support ventilation in conscious normal humans.

The respiratory response to CO2 during pressure-support ventilation (PSV) was studied in 16 conscious normal humans. The subjects breathed through a mouthpiece connected to a ventilator in PSV mode, with pressure set to the highest comfortable level for each subject (10.1 +/- 0.6 cm H2O, mean +/- SE). Compared with breathing spontaneously through the ventilator (CPAP mode with zero positive end-expiratory pressure), with PSV, tidal volume (VT) increased significantly (1.16 +/- 0.1 versus 0.85 +/- 0.04 L), whereas breathing frequency (f) remained stable (16.0 +/- 0.9 versus 15.6 +/- 1.1 breaths/min). As a result, the subjects hyperventilated, decreasing significantly end-tidal PCO2 (PETCO2, 23.5 +/- 1.2 versus 35.5 +/- 1.1 mm Hg). Fraction of inspired CO2 (FICO2) was then increased in steps, and changes in respiratory motor output were quantitated from changes in f, VT, ventilation (VI), peak inspiratory flow (Vpeak), and muscle pressure (Pmus). Pmus was calculated by the equation of motion, based on respiratory system mechanics, which were measured previously by airway occlusion at end-inspiration, VT, VI, and Pmus increased significantly with increasing PETCO2, and the response was detectable even below eupneic levels; f remained relatively stable over a wide range of PETCO2 (23 to 45 mm Hg) and increase significantly only when PETCO2 approached 50 mm Hg. These results indicate that in conscious normal humans during PSV, CO2 responsiveness extends well into hypocapnia and is expressed principally as an increase in intensity of respiratory motor output with little change in respiratory rate.

Effects of inspiratory muscle unloading on the response of respiratory motor output to CO2.

Inspiratory muscle output is downregulated when the mechanical load is reduced in awake humans. It is not known whether this is related to reduction in PCO2 or to removal of load-related neural responses. To address this issue, we did Read CO2 rebreathing tests in 13 normal subjects with and without unloading and compared respiratory output at identical end-tidal PCO2 (PET(CO2)) levels. Unloading was carried out with proportional assist ventilation (flow assist = 2 cm H2O/L/s plus volume assist = 4 cm H2O/L, representing approximately 50% reduction of the normal resistance and elastance). Ventilatory output (n = 13), total pressure of respiratory muscles (Pmus, n = 8), and transdiaphragmatic pressure (Pdi, n = 5) were computed at different PET(CO2) levels. Pmus was computed from esophageal pressure (Pes) using the Campbell diagram, and Pdi was measured from the difference between gastric pressure and Pes. Unloading caused an increase in ventilation (VI) and tidal volume (VT) at all PET(CO2) levels with no significant effect on slope (VI/PET(CO2) or VT/PET(CO2)) or respiratory rate. At low PET(CO2) (50 mm Hg), Pdi and Pmus waveforms did not differ with and without unloading. At high PET(C02) (59 mm Hg), peak Pdi and Pmus decreased by only 18.8 +/- 8.3% and 13.8 +/- 9.5%, respectively (NS, p > 0.05). Using a model that allows nonlinearity in the pressure-volume relation and for intrinsic muscle properties (force-length and force-velocity relations), we estimated the expected changes in mean VT and VI when the level of assist used in this study was applied in the absence of any change in neural output response to CO2. The predicted and observed changes in VT and VI were similar. We conclude that when chemical stimuli are rigorously controlled, unloading does not result in downregulation of respiratory muscle activation.

Effects of non-REM sleep on the response of respiratory output to varying inspiratory flow.

It has been shown in mechanically ventilated awake normal humans that increasing inspiratory flow rate (VI) exerts an excitatory effect on respiratory output. It is not known if this effect persists during sleep. To test this, seven normal adults were studied during wakefulness and non-rapid eye movement (non-REM) sleep. Subjects were connected through a nose mask to a volume-cycled ventilator in the assist/control mode, and VI was increased in steps (3 to 4 breaths each) from 30 to 70 L/min and then back to 30 L/min. VI pattern was square, and all breaths were subject-triggered. Forty-one trials during non-REM sleep and 10 during wakefulness were analyzed. Both during sleep and wakefulness minute ventilation increased and total breath duration (Ttot) decreased significantly in a graded and reversible manner as VI increased. These changes were complete in the first breath after VI transition. The response was significantly less during sleep than during wakefulness (p < 0.050; at 30 L/min Ttot, expressed as percent of that at 70 L/min, was 110.2 +/- 1.3% during sleep and 127.8 +/- 3.9% during wakefulness. During wakefulness, the rate of change in airway pressure before triggering the ventilator (dp/dt), an index of respiratory drive, increased significantly (p < 0.05) with increasing VI. During sleep dp/dt was not affected by VI changes. In four sleeping subjects the increase in VI was sustained for 1.5 to 2 min. There was no evidence for adaptation of the response; Ttot, averaged over the last three breaths, did not differ from that obtained with VI was sustained for only 3 to 4 breaths. We concluded that VI exerts an excitatory effect on respiratory output, mediated by a reflex neural mechanism, and the gain of this reflex is attenuated by sleep.

Effects of breathing route, temperature and volume of inspired gas, and airway anesthesia on the response of respiratory output to varying inspiratory flow.

The determinants of the response of the respiratory output to inspiratory flow rates (VI) were examined in awake normal subjects. Subjects were connected to a volume-cycle ventilator in the assist/control mode, and VI was increased in steps from 30 to 90 L/min and then back to 30 L/min. VI pattern was square, and all breaths were subject-triggered. In six subjects the effects of breathing route (nasal or mouth) and temperature and volume of inspired gas (Protocol A) and in 8 subjects the effects of airway anesthesia (upper and lower airways; Protocol B) on the response of respiratory output to varying VI were studied. In Protocol B, in order to calculate muscle pressure during inspiration (Pmus), respiratory system mechanics were measured using the interrupter method at end-inspiration. Independent of conditions studied, breathing frequency increased significantly and end-tidal concentration of CO2 decreased as VI increased. The response was graded and reversible and not affected by breathing route, temperature and volume of inspired gas, and airway anesthesia. With and without airway anesthesia (Protocol B), neural inspiratory and expiratory time and neural duty cycle, estimated from Pmus waveform, decreased significantly as VI increased. At all conditions studied, the rate of change in airway pressure prior to triggering the ventilator tended to increase as VI increased. The changes in timing and drive were nearly complete within the first two breaths after transition, with no evidence of adaptation during a given VI period. We conclude that VI exerts an excitatory effect on respiratory output which is independent of breathing route, temperature and volume of inspirate, and airway anesthesia. The response most likely is neural in origin, mediated through receptors not accessible to anesthesia, such as those located in the chest wall or below the airway mucosa.

Effect of breathing pattern and level of ventilation on pulmonary fluid filtration in dog lung.

The effect of breathing pattern and level of ventilation on fluid filtration in the lung under edema forming conditions was studied in an in situ left upper lobe (LUL) canine preparation. LUL weight was continuously monitored. In Group 1, rate of edema formation (delta W/delta t) was measured In seven dogs at two vascular pressures (35 and 45 mm Hg) while the LUL was randomly ventilated under six conditions. At equivalent vascular pressures and mean airway pressures (Paw) (and hence, mean operating lung volume), increasing respiratory frequency (f) enhanced delta W/delta t. This was reversed when minute ventilation (VE) was returned to baseline by reducing tidal volume (VT), even when Paw were matched to baseline. Increasing VT also enhanced delta W/delta t whether VE was increased (J Appl Physiol 1988; 64:1900) or not (present study) and whether Paw was matched to baseline. In Group 2 delta W/delta t was measured at fixed VT and f while inspiratory/expiratory time ratio (TI/TE) was switched from 1:1 to 1:6. Shortening inspiratory time by increasing inspiratory flow rate had no effect on delta W/delta t. We conclude that increasing VE, whether by raising VT or f, promotes greater edema formation by mechanisms that are independent of vascular pressure or operating lung volume. Increasing VT appears to have an additional adverse effect over and above that of increased VE.

Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans.

After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the "afterdischarge." Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing.

Distensibility and pressure-flow relationship of the pulmonary circulation. I. Single-vessel model.

To ascertain the relative contributions of vascular distensibility and nonhomogeneous behavior within the pulmonary circulation to the distinctive nonlinear relationship between inflow pressure (Pin) and flow [pressure-flow (P-F) relationship] and between Pin and outflow pressure (Pout) at constant flow (Pin-Pout relationship), we developed a multibranched model in which the elastic behavior of, and forces acting on, individual branches can be varied independently. The response of the multibranched model is described in the companion article (J. Appl. Physiol. 68: 1514-1527, 1990). Here we describe the methods used and the responses of single components of the larger model. Perivascular pressure is modeled as a function of intravascular and transpulmonary pressures (Pv and Ptp, respectively) and vessel length as a function of lung volume. These and the relationship between vascular area (A) and transmural pressure (Ptm) were modeled primarily from the dog data of Smith and Mitzner (J. Appl. Physiol. 48: 450-467, 1980). Vasomotor tone is modeled as a radial collapsing pressure (Pt) in the same plane as Ptm. In view of lack of information about the relationship between Pt and A for a given active state, different patterns were assumed that span a wide range of possible relationships. The P-F and Pin-Pout relationships of single vessels were very similar to those reported for the entire intact circulation. Of note, the slope of the Pin-Pout relationship in the low Pout range (0-5 Torr) was very low (less than 0.25) and increased gradually with Pout toward unity. Vasomotor tone caused an apparent parallel shift in the P-F relationship in the physiological flow range of the dog (2-8 l/min) regardless of the pattern used to model the Pt vs. A relationship; different patterns affected the P-F relationship only over the low flow range before the parallel shift was established.

Distensibility and pressure-flow relationship of the pulmonary circulation. II. Multibranched model.

The contribution of distensibility and recruitment to the distinctive behavior of the pulmonary circulation is not known. To examine this question we developed a multibranched model in which an arterial vascular bed bifurcates sequentially up to 8 parallel channels that converge and reunite at the venous side to end in the left atrium. Eight resistors representing the capillary bed separate the arterial and venous beds. The elastic behavior of capillaries and extra-alveolar vessels was modeled after Fung and Sobin (Circ. Res. 30: 451-490, 1972) and Smith and Mitzner (J. Appl. Physiol. 48: 450-467, 1980), respectively. Forces acting on each component are modified and calculated individually, thus enabling the user to explore the effects of parallel and longitudinal heterogeneities in applied forces (e.g., gravity, vasomotor tone). Model predictions indicate that the contribution of distensibility to nonlinearities in the pressure-flow (P-F) and atrial-pulmonary arterial pressure (Pla-Ppa) relationships is substantial, whereas gravity-related recruitment contributes very little to these relationships. In addition, Pla-Ppa relationships, obtained at a constant flow, have no discriminating ability in identifying the presence or absence of a waterfall along the circulation. The P-F relationship is routinely shifted in a parallel fashion, within the physiological flow range, whenever extra forces (e.g., lung volume, tone) are applied uniformly at one or more branching levels, regardless of whether a waterfall is created. For a given applied force, the magnitude of parallel shift varies with proportion of the circulation subjected to the added force and with Pla.

Effect of alveolar hypoxia on pulmonary fluid filtration in in situ dog lungs.

We have studied the effect of alveolar hypoxia on fluid filtration characteristics of the pulmonary microcirculation in an in situ left upper lobe preparation with near static flow conditions (20 ml/min). In six dogs (group 1), rate of edema formation (delta W/delta t, where W is weight and t is time) was assessed over a wide range of vascular pressures under two inspired O2 fraction (FIO2) conditions (0.95 and 0.0 with 5% CO2-balance N2 in both cases). delta W/delta t was plotted against vascular pressure, and the best-fit linear regression was obtained. There was no significant difference (paired t test) in either threshold pressure for edema formation [18.3 +/- 1.8 and 17.1 +/- 1.2 (SE) mmHg, respectively] or the slopes (0.067 +/- 0.008 and 0.073 +/- 0.017 g.min-1. mmHg-1.100g-1, respectively). In another seven dogs (group 2), delta W/delta t was obtained at a constant vascular pressure of 40 mmHg under four FIO2 conditions (0.95, 0.21, 0.05, and 0.0, with 5% CO2-balance N2). Delta W/delta t for the four conditions averaged 0.60 +/- 0.11, 0.61 +/- 0.11, 0.61 +/- 0.10, and 0.61 +/- 0.10 (SE) g.min-1.mmHg-1.100g-1, respectively. No significant differences (ANOVA for repeated measures) were noted. We conclude that alveolar hypoxia does not alter the threshold for edema formation or delta W/delta t at a given microvascular pressure.

Effect of tidal volume and PEEP on rate of edema formation in in situ perfused canine lobes.

The effects of raising tidal volume and positive end-expiratory pressure (PEEP) on rate of edema formation were studied in in situ canine left upper lobe preparations. Edema was induced by increasing blood flow to the left upper lobe (4-8 times normal). In the same animal, at equivalent flows and microvascular hydrostatic pressures, rate of edema formation observed with larger tidal volumes was significantly higher than that observed with smaller tidal volumes (0.73 +/- 0.29 vs. 0.58 +/- 0.30, P less than 0.001). Edema was also induced under static conditions (i.e., flow = 0) over a wide range of vascular pressures. Rate of edema formation was plotted against pressure and the best-fit linear regression was obtained. The slopes (g.min-1.mmHg-1.100 g-1) of the regression lines were significantly higher with larger tidal volumes compared with smaller tidal volumes [0.106 +/- 0.010 (SE) vs. 0.081 +/- 0.009, P less than 0.01]. The pressure intercepts were not different (16.1 +/- 1.6 vs. 15.7 +/- 1.8). When mean airway pressures were increased to levels equivalent to those obtained with larger tidal volumes, but by raising end-expiratory pressures, rate of edema formation dropped to levels below base line. We conclude that increasing the amplitude of cyclic changes in lung volume increases edema formation through mechanisms that are independent of changes in operating (i.e., mean) lung volume.

Arterial occlusion versus isofiltration pulmonary capillary pressures during very high flow.

Pressure in the compliant middle segment of the pulmonary vascular bed (PM), as determined by arterial occlusion, was compared with pressure at the filtration site (effective filtration pressure, EFP), determined by the isofiltration technique, at very high (7-10 times normal) pulmonary flow in six in situ perfused canine left upper lobes. At these flow rates inflow and left atrial pressures averaged 41.9 +/- 1.3 and 2.5 +/- 0.5 (SE) mmHg, respectively. PM was 30.9 +/- 1.6 mmHg, and EFP was 32.3 +/- 1.9 mmHg with no significant difference between the two measurements by paired t test. The results indicate that the arterial occlusion technique yields a pressure that is equivalent to EFP even during very high pulmonary blood flow where the longitudinal distribution of resistance is quite different from that obtained during normal flow.

Longitudinal distribution of pulmonary vascular resistance with very high pulmonary blood flow.

Dog left upper lobes (LUL) were perfused in situ via the left lower lobe artery. Lobe weight was continuously monitored. Increasing lobar flow from normal to 10 times normal had little effect on left atrial pressure, which ranged from 1 to 5 mmHg. There was a flow threshold (Qth) below which lobar weight was stable. Qth ranged from 1.1 to 1.55 l/min (mean 1.27) corresponding to four times normal LUL blood flow. Above Qth, step increases in lobar flow resulted in progressive weight gain at a constant rate that was proportional to flow. The effective pressure at the filtration site (EFP) at different flow rates was estimated from the static vascular pressure that resulted in the same rate of weight gain. From this value and from mean pulmonary arterial (PA) and left atrial (LA) pressures, we calculated resistance upstream (Rus) and downstream (Rds) from filtration site. At Qth, Rds accounted for 60% of total resistance. This fraction increased progressively with flow, reaching 83% at Q of 10 times normal. We conclude that during high pulmonary blood flow EFP is closer to PA pressure than it is to LA pressure, and that this becomes progressively more so as a function of flow. As a result, the lung accumulates water at flow rates in excess of four times normal despite a normal left atrial pressure.

The importance of the balloon reservoir volume of a CPAP system in reducing the work of breathing.

We have previously reported, that the work of breathing in spontaneously breathing patients on CPAP could be significantly reduced by increasing the volume of the balloon reservoir in the circuit of a CPAP system from 3 to 23 l. We now report a study designed to determine the optimum balloon reservoir volume for the minimization of the work of breathing. Twenty intubated, spontaneously breathing patients were connected to a CPAP system with interchangeable balloon reservoirs. In each patient the work of breathing was measured for reservoir volumes of 3, 6, 12, 18, and 24 l attached in random order, while the positive airway pressure was held constant at 10 cm H2O. The balloons were constructed of the same material and had similar compliance. Rebreathing was prevented with use of one-way valves. Significant (p less than 0.001) decreases in the work of breathing were found on increasing reservoir volumes from 3 to 6, 6 to 12, and 12 to 18 l. A less significant (p less than 0.01) decrease in the work of breathing was found between reservoirs of 18 and 24 l. Rebreathing did not occur with significantly (p less than 0.001) lower flow rates when large reservoirs were used. We conclude that a balloon reservoir of 18 l represents the best compromise between reduction in the work of breathing, utilization of low source flow, and convenience of clinical use.

Percutaneous peritoneal dialysis as an early treatment of acute necrotic hemorrhagic pancreatitis.

In this study, 8 years experience of early percutaneous peritoneal dialysis (PPD) in the treatment of acute necrotic hemorrhagic pancreatitis (ANHP) are presented. The introduction of methemalbuminemia and the presence of specific ascites rich in amylase, lipase and methemalbumin as early indicators of the presence of ANHP enabled us to confirm the diagnosis in 53 patients, after which early institution of PPD was possible. Thirty patients survived by PPD alone and 9 patients survived by the combination of PPD and surgery, giving an overall mortality rate of 26.4%. A better survival rate of patients having a high Ranson prognostic score was obtained. The introduction of computerized axial tomography (CAT), in 1980 into our hospital allowed us to use this technique for followup. This change and the fact that we were more experienced with PPD, divided our study into two periods: 1976 to 1979, 22 patients; 1980 to 1983, 31 patients. A more aggressive medical approach to treating ANHP was observed during the second period. Surgery was delayed compared to the first period and confined to treating late complications, such as infections, by drainage procedures. Despite the fact that the results were not statistically different, a trend towards a lower mortality rate (19.3%) in the second period compared to the first period (36%) was obtained.

Crush syndrome: experience from the Lebanon War, 1982.

Eight patients with crush syndrome were treated in our department during the Lebanon War, 1982. They arrived after having been trapped under fallen masonry for 4 to 28 h. They all had injuries of the lower limbs, with neurological deficiency and myoglobinuria. The local and general aspects of the syndrome are presented and discussed and a successful treatment protocol outlined.

Crush syndrome : Experience from the Lebanon war, 1982

Crush syndrome experience from the Lebanon war, 1982: Eight patients with crush syndrome were threated in the department during the Lebanon war 1982. They arrived after having been trapper under fallen masonry for 4 to 28h. They all had injuries of the lower limbs, with newrological deficiency and myoglpbinuria. The local and general aspects of the syndrome are presented and discussed and a successful treatment protocol, outlined (AU)