A new technique to fix tobacco smoke aerosols by methyl-2-cyanoacrylate vapor is applied to the study of the size distribution of sodium chloride droplets generated from a commercial inhalation nebulizer. The count mode diameter of the fixed droplets agrees well with the actual droplets calculated from known dried particles. The method allows direct visualization and measurement of droplets by light or electron microscopy, but it is limited to particles smaller than 2 μm in diameter. Further work is required to improve the fixation chamber design and sampling technique to ensure complete fixation and collection of droplets greater than 2 μm in diameter before the method can be used to characterize the polydisperse aerosol droplets from nebulizers. © 1979.

Accurate noninvasive methods are needed for determination of cardiac output. Current methods are generally complex or may be unreliable. A previously described method, based on absorption of acetylene gas during a constant exhalation that enables calculation of cardiac output by estimating pulmonary capillary circulation, is incorporated in a new, automated commercial product (SensorMedics 2200). In this study, cardiac output by single-breath acetylene blood flow measured with this device was compared with the standard thermodilution and direct Fick methods in 20 patients undergoing cardiac or pulmonary artery catheterization. Patients inhaled test gas mixture to total lung capacity and exhaled at a constant rate through an adjustable resistor. Lung volumes and noninvasive acetylene blood flow value were calculated automatically. Correlation between the automated single-breath technique and both thermodilution and Fick cardiac output determinations was very high (correlation coefficients were 0.90 and 0.92, respectively), regression slopes were close to identity (0.98 and 0.90), and bias (-0.39 and -0.79 liter/min) and precision (0.94 and 1.02) were good; when shunt correction was applied, bias was reduced to 0.06 and 0.35 liter/min, respectively. Rapid, accurate, noninvasive measurement of cardiac output was easily obtained using the automated device. This technique may have a wide applicability for noninvasive evaluation of patients with cardiac disease and for monitoring effects of therapeutic interventions.

Airway occlusion pressure correlates with central respiratory drive. The airway occlusion pressure (P0.1) may be an excellent predictor of the ability of patients with obstructive lung disease to wean from mechanical ventilation. We describe a new method for measuring P0.1 using digitized signals generated from standard respiratory equipment and a computer program to automatically determine P0.1 values. The accuracy of this new method was tested by comparison with standard analog recorder methods using a mechanical lung model, in ventilated patients in an intensive care unit, and in normal volunteers. In all settings, excellent correlation was obtained between P0.1 measurements by the digital Servo and standard analog methods (r = 0.99). This new method permits accurate and automatic determination of P0.1 in ventilated patients using standard respiratory equipment. The rapid response and ease of use of this method should enable evaluation of a number of physiologic variables involved in respiratory control in ventilated and nonventilated patients.

Introduction

Lung volume reduction surgery (LVRS) improves pulmonary function and dyspnea symptoms acutely in selected patients with heterogeneous emphysema. Limited data are available regarding long-term function following LVRS. We analyzed short-term (<6 months) and long-term rate of change of pulmonary function in 376 patients who underwent unilateral or bilateral LVRS using thoracoscopic or median sternotomy, staple, laser, or combined techniques. We hypothesized that the long-term rate of deterioration in lung function would be dependent on the surgical procedure used and would be greatest in those with the largest short-term postoperative improvement.

Methods

Pulmonary function was assessed preoperatively and at repeated intervals following LVRS. The change in pulmonary function over time was assessed for each patient by determining the individual change in FEV1 using linear regression analysis short and long term. Overall rate of change in pulmonary function was calculated for the composite group of patients and subgrouped by operative procedure.

Results

Lung function appears to improve in the first few months following LVRS in most patients, maximizing at approximately 3 to 6 months and declining thereafter. The short-term incremental improvement following staple procedures is superior to improvements following laser procedures or unilateral surgery: FEV1 increase (mean+/-SD) of 0.39+/-0.03 L for bilateral staple, 0.25+/-0.03 L for unilateral staple, 0.10+/-0.03 L for unilateral laser, and 0.22+/-0.1 L for mixed unilateral staple/laser procedures. However, the long-term rate of decline in FEV1 was greatest for bilateral staple LVRS procedures as well: 0.255+/-0.057 L/yr for bilateral staple, 0.107+/-0.068 L/yr for unilateral staple, 0.074+/-0.034 L/yr for unilateral laser, and 0.209+/-0.12 L/yr for mixed staple laser procedures. There was a general correlation between the magnitude of short-term incremental improvement and the rate of deterioration in FEV1 (r=0.292, p=0.003).

Conclusions

While bilateral staple LVRS procedures lead to greater short-term improvement in FEV1, the more rapid rate of FEV1 decline in these patients and the general association between greater short-term incremental improvement and higher rates of deterioration raise questions regarding optimal long-term procedures. Further studies will be needed to answer these important questions.

Pulmonary resistance may be assessed in ventilated patients by analysis of passive expiratory pressure and flow properties of the respiratory system. Such measurements are generally complex and require specialized equipment. To facilitate expiratory airway mechanics measurements, we have developed a method for automatically recording and analyzing expiratory pressure flow curves in mechanically ventilated patients using standard ventilatory equipment and a personal computer. Simultaneous digital pressure, flow, and volume recordings are obtained with this system during exhalation. These values allow continuous calculation of ventilator circuitry and total system resistance, which could be used for assessing expiratory airway resistance in intubated patients. The accuracy of these methods was tested by comparison to standard analog recorder pressure-flow methods using two lung models as well as by testing in normal volunteers ventilated through a mouthpiece. In all situations (flows, pressures, and volumes) there was excellent correlation between data generated from the automatic digital method and standard analog methods (all r values > .9, slopes 0.9 to 1.02, P < .001, flow bias -0.02 L/min, flow precision 0.08 L/min, volume bias 0.008 L, volume precision 0.027 L). Expiratory resistance (using expiratory time-constant cord methods) also correlated well between automatic digital and standard analog analyses (r = .9, slope 0.98, P < .001). We found that expiratory flow limb resistances (airway, tubing, filters, and valves) were substantial (range, 5.5 to 14.0 cm H2O/L/s) and are varied throughout the expiratory cycle. Therefore, measurement of expiratory-flow limb resistance is necessary for accurate clinical assessment of pulmonary resistance for any system analyzing expiratory flow mechanics in ventilated patients. We conclude that this simple and convenient method allows automatic and accurate construction of pulmonary expiratory flow properties and may enable measurement of passive expiratory resistance. Rapid and accurate measurements of expiratory lung mechanics may be possible at the bedside of ventilated patients using standard ventilatory equipment with these methods. © 1992.

Currently accepted techniques utilize the plateau concentration of nitric oxide (NO) at a constant exhalation flow rate to characterize NO exchange, which cannot sufficiently distinguish airway and alveolar sources. Using nonlinear least squares regression and a two-compartment model, we recently described a new technique (Tsoukias et al. J Appl Physiol 91: 477-487, 2001), which utilizes a preexpiratory breath hold followed by a decreasing flow rate maneuver, to estimate three flow-independent NO parameters: maximum flux of NO from the airways (J(NO,max), pl/s), diffusing capacity of NO in the airways (D(NO,air), pl x s(-1) x ppb(-1)), and steady-state alveolar concentration (C(alv,ss), ppb). In healthy adults (n = 10), the optimal breath-hold time was 20 s, and the mean (95% intramaneuver, intrasubject, and intrapopulation confidence interval) J(NO,max), D(NO,air), and C(alv,ss) are 640 (26, 20, and 15%) pl/s, 4.2 (168, 87, and 37%) pl x s(-1) x ppb(-1), and 2.5 (81, 59, and 21%) ppb, respectively. J(NO,max) can be estimated with the greatest certainty, and the variability of all the parameters within the population of healthy adults is significant. There is no correlation between the flow-independent NO parameters and forced vital capacity or the ratio of forced expiratory volume in 1 s to forced vital capacity. With the use of these parameters, the two-compartment model can accurately predict experimentally measured plateau NO concentrations at a constant flow rate. We conclude that this new technique is simple to perform and can simultaneously characterize airway and alveolar NO exchange in healthy adults with the use of a single breathing maneuver.

Background

Lung volume reduction surgery (LVRS) is being actively investigated for palliative treatment of severe emphysema. Considerable focus is directed toward patient selection and outcomes of LVRS. However, there is little information available regarding surgical methods to guide optimal extent of resection. We hypothesized that acute improvement and long-term survival after bilateral staple LVRS would be related to the extent of tissue resected.

Methods

The relationship between acute improvement in forced expiratory volume in 1 second and forced vital capacity was examined as a function of the total grams of lung tissue resected in 237 patients who underwent bilateral staple LVRS by a single group of surgeons. Overall survival was assessed based on extent of resection by quartiles of tissue weight resected using Kaplan-Meier survival methods.

Results

Improvement in forced expiratory volume in 1 second and forced vital capacity correlated with extent of tissue resected (p < 0.01), although there was considerable variability to individual response (r = 0.3). In contrast, there was no apparent relationship between the amount of tissue resected and overall postoperative survival (p = 0.7).

Conclusions

There is a correlation between the amount of tissue resected and improvement in forced expiratory volume in 1 second and forced vital capacity after bilateral staple LVRS, with generally greater postoperative improvement after larger volume resections. However, there does not appear to be greater long-term survival with larger volume resections despite greater improvement in spirometry. This study suggests that factors other than improvement in spirometric variables may govern optimal LVRS resection volumes and long-term outcome. Future studies will clearly be needed in this important area of LVRS emphysema research.

Study objectives

Despite numerous reports of short-term response to lung volume reduction surgery (LVRS) for treatment of emphysema, to our knowledge, longer-term survival has not been reported. We describe survival following LVRS in a large cohort of 256 patients treated with bilateral staple LVRS (n = 236 video-assisted thoracic surgery [VATS] approaches, n = 20 median sternotomy) by a single group of physicians over a 3 1/2-year period from April 1994 to November 1997.

Design

Prospective survival study. Overall survival, survival stratified by preoperative presentation, and acute postoperative response were investigated using Kaplan-Meier methods. The simultaneous effects of preoperative predictors and postoperative response variables on survival were examined using a Cox proportional hazards model.

Setting

Community hospital and university medical center.

Patients

We studied 256 consecutive patients with severe emphysema treated with LVRS.

Interventions

Bilateral staple LVRS by VATS.

Measurements and results

Overall survival information was known with certainty for 246 of 256 patients as of February 1, 1998. Median follow-up time was 623 days (range, 0 to 1,545 days). Mean FEV1 was 0.635L+/-0.015 L preoperatively and rose to 1.068L+/-0.029 L postoperatively. By standard analysis methods (missing patients censored at the time of last contact), 1-year survival was 85+/-2.3% compared with 83+/-2.4% 1-year survival with "worst case" analytic methods (assuming all missing patients died). Two-year survival averaged 81+/-2.7% by standard analysis vs 76+/-2.9% by worst case evaluation. Survival was significantly better for patients who were younger (< or = 70 years old, p = 0.02) and with higher baseline FEV1 (> 0.5, p < 0.03) and PO2 (> 54, p < 0.001). Patients who had greatest short-term improvement in FEV1 following surgery (> 0.56 L increase) also had significantly better longer-term survival following LVRS.

Conclusions

To our knowledge, this is the first longer-term survival analysis of a large series of patients who underwent bilateral staple LVRS for emphysema. Substantial long-term mortality is seen, particularly within identifiable high-risk subgroups. Careful comparison to comparably matched control patients will be needed to definitively assess the benefits and risks of LVRS. This study suggests that prospective, controlled trials may need to stratify patient randomization based on preoperative risk factors to obtain meaningful results.

Exhaled nitric oxide (NO) remains a promising noninvasive index for monitoring inflammatory lung diseases; however, the plateau concentration (C(NO,plat)) is nonspecific and requires a constant exhalation flow rate. We utilized a new technique that employs a variable flow rate to estimate key flow-independent parameters characteristic of NO exchange in a group (n = 9) of 10 to 14 yr-old healthy children and children with cystic fibrosis (CF): maximum flux of NO from the airways (J(NO,max'), pl s(-1)), diffusing capacity of NO in the airways (D(NO,air'), pl s(-1) ppb(-1)), steady-state alveolar concentration (C(alv,ss'), ppb), and mean tissue concentration of NO in the airways (C(tiss,air'), ppb). We determined the following mean (+/- SD) values in the healthy children and patients with CF for J(NO,max'), D(NO,air'), C(alv,ss'), and C(tiss,air'), respectively: 784 +/- 465 and 607 +/- 648 pl s(-1); 4.82 +/- 3.07 and 17.6 +/- 12.1 pl s(-1) ppb(-1); 4.63 +/- 3.59 and 1.96 +/- 1.18 ppb; and 198 +/- 131 and 38 +/- 25 ppb. D(NO,air) is elevated (p = 0.007), and both C(alv,ss) and C(tiss,air) are reduced (p = 0.05 and 0.002, respectively) in CF. In contrast, C(NO,plat) for healthy control subjects and patients with CF are not statistically different at both exhalation flow rates of 50 ml/s (17.5 +/- 11.5 and 11.5 +/- 8.97) and at 250 ml/s (7.11 +/- 5.36 and 4.28 +/- 3.43). We conclude that D(NO,air'), C(tiss,air'), and C(alv,ss) may be useful noninvasive markers of CF.

Clinical use of staple lung volume reduction surgery (LVRS) has proliferated for treatment of emphysema despite limited data regarding efficacy or optimal techniques. Recent studies in animal models of obstructive lung disease describe the decrease in lung compliance and increase in airway support as mechanisms of an improvement in pulmonary functions analogous to human data. We describe contrasting results in an animal model of bullous lung disease with a mixed but predominantly restrictive pattern of lung disease. Mixed restrictive and bullous lung disease was induced in 17 New Zealand white rabbits with i.v. Sephadex beads and endotracheally instilled carrageenan. Unilateral stapled lung volume reduction surgery was performed at 5 weeks postinduction of emphysema on the right lower lobe by lateral thoracotomy using a pediatric stapler. Static trans-pleural pressures were measured at 60, 40, and 20 cm3 inflation at preinduction (baseline), pre- and postoperatively, and 1 week postoperatively in anesthetized animals. Lungs were then harvested en bloc and examined histopathologically. The effects of volume reduction surgery on static lung compliance, lung conductance, and forced expiratory flows (FEF) were assessed. Five weeks after induction of lung disease, the animals had no significant change in static compliance and forced expiratory volume in 0.5 s (FEV0.5) or lung conductance compared to baseline. Immediately following LVRS, the animals showed a significant decrease in static compliance, FEV0.5, and conductance. One week postoperatively, compliance increased to approximately baseline levels along with a slight increase in FEFs and conductance toward preoperative levels. Histology examination revealed restrictive and bullous lung disease. Thus, we have demonstrated the feasibility of using an animal model for evaluation of volume reduction therapy for restrictive-obstructive lung disease. Physiologically, this model showed decrease conductance and decreased forced expiratory flows following lung volume reduction despite increased recoil. This is in contrast to increased conductance and flows seen in humans with severe emphysema following surgery and suggests that current criteria excluding patients with a significant restrictive component to their lung disease from LVRS surgery may be justified.