To the Editor: I am writing concerning the recent paper by Matthay and WienerKronish (1). I am wondering why they chose to group patients with hydrostatic and permeability pulmonary edema in one group for their statistical analysis. One would expect the patients with hydrostatic pulmonary edema to have lower total protein and albumin concentrations than the permeability pulmonary edema subgroup. Thus, this population of patients would be expected to have a bimodal distribution with one mean for the hydrostatic patients and a separate mean for the permeability patients. As concerns the group who made clinical improvement, the distribution is skewed by the fact that there are more hydrostatic pulmonary edema patients in this group than permeability edema patients. In the group of patients who did not make improvement, the distribution is skewed by the greater frequency of permeability pulmonary edema. A single mean does not adequately represent either group. I am not sure that this makes a difference with performing a paired Student's t test. It may, however, influence an unpaired t test. A z-distribution is a theoretical probability distribution that is symmetrical and bell-shaped and is similar to a normal distribution, but more spread out. I am not sure that one can apply this to a group that has a bimodal distribution and may be skewed towards one end as in the present case.

Because the rise in edema fluid/plasma protein ratio correlated with improved clinical indices in all patients, the statistical test used for analyzing the data is not crucial. We hope that this explanation clarifies the issue. MICHAEL




Cardiovascular Research Institute University of California San Francisco, CA 1. Matthay MA, Landolt CC, Staub NC. Differential liquid and protein clearance from the alveoli of anesthetized sheep. J Appl Physiol 1982; 53:96-104. 2. Matthay MA, Berthiaume Y, Staub NC. Long term clearance of liquid and protein from the lungs of unanesthetized sheep. J Appl Physiol1985; 59:928-34. 3. Berthiaume Y,Broaddus VC, Gropper MA, Tanita T, Matthay MA. Alveolar liquid and protein clearance from normal dog lungs. J Appl Physiol 1988; 65:585-93. 4. Smedira N, Gates L, Hastings R, Jayr C, Sakuma T, Matthay MA. Alveolar and lung liquid clearance in anesthetized rabbits. J Appl Physioll991; 70:1827-35. 5. Matthay MA, Weiner-Kronish JP. Intact epithelial barrier function is critical for the resolution of alveolar edema in humans. Am Rev Respir Dis 1990; 142:1250-7.


Pulmonary Associates of New Haven, RC New Haven, CT 1. Matthay MA, Wiener-Kronish JP. Intact epithelial barrier function is

critical for the resolution of alveolar edema in humans. Am Rev Respir Dis 1990; 142:1250-7.

From the Authors: In reply to Dr. Rogol's letter, we grouped patients with hydrostatic or increased permeability pulmonary edema together because we were interested in determining if a rise in the edema fluid/plasma protein ratio correlated with clinical improvement independent of the type of edema. In several of our experimental studies (1-4), a rise in alveolar fluid protein concentration has correlated well with net alveolar liquid clearance. In order to test this hypothesis in a clinical study, we needed to determine whether a rise-in edema fluid protein concentration would occur in patients in whom there was evidence of clinical improvement (improved oxygenation and decreased edema on chest radiograph). Therefore, the patients were grouped together, independent of the type of pulmonary edema. In the study, every patient who had a rise in edema fluid/plasma protein concentration in the second sample had evidence of improved oxygenation. However, we did analyze the data for the two types of edema separately as well.For example, there were 18patients with hydrostatic pulmonary edema, 15 of whom had an increase in the edema fluid/plasma protein concentration ratio and each patient had improvement in their oxygenation, whereas the three patients who had no change in the edema fluid/plasma protein concentration ratio had no improvement in oxygenation. Similarly, there were 16 patients with increased permeability pulmonary edema, and nine of those patients showed a rise in their edema fluid/plasma protein concentration ratio, which correlated in each patient with improved clinical indices (5). 468


To the Editor: I am puzzled by the methods used to determine static air P-Vcurves and the interpretation of results in the report by Lamm and Albert (1) in the December 1990 issue of the Review. Why was surfactant instilled in degassed lungs? Degassing, if done correctly, will render the lungs airless and fully collapsed. Injecting gas or liquid in such a lung would require substantial pressure and would result in a very inhomogenous distribution of the material used due to opening pressure and recruitment phenomena. The pressure-volume (P-V) curves of the control and the HCl groups, which were determined in degassed lungs, cannot be compared with that of Hel and surfactant group, which was not done in the degassed state (because of surfactant instillation). How could the volume of the liquid surfactant instilled be added to the volume of the gas injected for lung inflation? This would have been acceptable if saline, not air, P-V curves were done. In any case, how could the addition of the surfactant volume underestimate the true TLC? Lungs were inflated to 25 and 40 em H 2 0 in in vitro and in vivo studies, respectively. Figures 1 and 2, however, show only pressures up to approximately 15 and 25 em H 20 in the two preparations, respectively. Did the P-V curves reach the plateau, and if so, why are not the entire scope of P-V relationships presented in the figures? The P-Vmeasurements were done by inflating and deflating the lungs in to-ml steps and recording pressure at each point, which would have been different for each lung according to its mechanical characteristics. Thus, how could one normalize pressures at exact percent TLC points? This could only be done accurately if lungs are deflated by stepwise withdrawal of exact percent TLC (90, 80, 70, etc.) rather than standard 10-ml volumes with pressure recordings at each point. Or, more conventionally, the P-V curves are constructed by stepwise inflation and deflation, to predetermined pressures, and recording the volume.


Because the purpose of the P-V measurements was to study surface elastic forces in the lung, determination of the inflation limb of the P-V relationships would have provided very useful information regarding the opening pressure and the hysteresis phenomena. Accurate determination and interpretation of P-V measurements in this study are of critical importance because they represent the only difference among various groups in the study. HAMID SAHEBJAMI, M.D. Department of Veterans Affairs Medical Center Cincinnati, OH

1. Lamm WJE, Albert RK. Surfactant replacement improves lung recoil in rabbit lungs after acid aspiration. Am Rev Respir Dis 1990; 142:1279-83.

From the Authors: We thank Dr. Sahebjami for his interest in our article describing the effects of surfactant replacement in the setting of the HCl aspiration model of acute lung injury (1). Weelected to degas the lungs so that the subsequently determined lung pressure-volume (P-V) relationships could be obtained with knowledge of the absolute lung volumes. Weagreethat inhomogeneous opening pressures might have been present, hence we presented data collected only on the deflation limb. We know of no reason why P-V curves of the control and HCltreated lungs cannot be compared as long as absolute lung gas volume and the volume of surfactant instilled are known. As stated, TLC was defined as that lung volume present at alveolar pressures of 25 and 40 em H 2 0 in the in vitro and in vivo studies, respectively. In absence of surfactant, all of the lung volume would represent air. When surfactant was added, some of the lung was filled with liquid such that the lung-gas volume would underestimate the true degree of lung distension (although only a 1-4070 correction was necessary). Our P-V curves did indeed reach a plateau in both the in vitro and in vivo studies. The scales used on the figures were selected to expand the graphs and facilitate comparison of the data. Our data were normalized to the percent TLC by constructing P-V curves in to-ml volume steps, connecting the points with straight lines, and then readingthe appropriate pressure for each percent TLC. We agree that interesting information might be present in the inflation limbs of our P-V data. However, for the very reasons alluded to by Dr. Sahebjami, the deflation limb is the one most classically used to describe lung mechanics. We also.agree that the method used for determining the P-V relationships is critical to the interpretation of our study. Accordingly, the technique weemployed was carefully considered and represents the most accurate one available. WAYNE LAMM


M.D. University of Washington Medical Center Seattle, WA RICHARD


1. Lamm WJE, Albert RK. Surfactant replacement improves lung recoil in rabbit lungs after acid aspiration. Am Rev Respir Dis 1990; 142:1279-83.

scale, controlled, prospective studies is inconsistent (1). Furthermore, Mycobacterium tuberculosis infections may be difficult to detect by the tuberculin test in populations where nonspecific tuberculin sensitivity (induced by BCG) is frequent. In Austria, general BCG vaccination of the newborn was introduced in 1952. At the end of 1989, it was recommended to restrict vaccination to babies with an "elevated risk of infection with tuberculosis." The main reason for abandoning the practice of general BCG vaccination of the newborn was a report presented to the vaccination committee of the Federal Board of Health, concerning 14 cases of severe complications after vaccination between 1970 and 1986. In Austria, BCG vaccine is ordered directly by the ministry of health. From 1980 to 1989, BCG sec Berna vaccine (strain Kopenhagen, 0.1 ml administered intradermally) was used. In 1990,however, due to the cost-benefit risk, this vaccine is no longer available from the Austrian distributor. The reasons given were the uncertainty of demand, in view of the introduction of restricted vaccination, as well as the (costly and time-consuming) official batch control tests introduced in 1989. Since March 1990, 60,000 doses of BCG vaccine Merieux (strain Kopenhagen, 0.1 ml administered intradermally) wereordered from another source. Within a surprisingly short period of time the entire batch had been distributed to physicians. In 1990, no reports of undesirable side effects reached the distributor of this vaccine. Because of a subsequent shortage of supplies from August 1990 onward, 7,540 ampoules of BCG Pasteur i.d. vaccineweredistributed (Pasteur strain, 0.05 ml given intradermally). Because of the occur. reneeof suppurative lymphadenitis in vaccinated newborns, the product was withdrawn from the market by official order from November 28, 1990.Apart from the increased reactogeneity ofthe Pasteur strain, erroneous application (0.1 ml instead of 0.05 ml) was also held responsible for the numerous side effects, for which, by March 15, 1991, 63 children had received surgical treatment at the University Hospital, Innsbruck. Of 659 babies vaccinated at the University Hospital, (department of obstetrics), 28 (4.2070) underwent surgery. At the present time, no BCG vaccine is available in Austria. The recommendation of vaccinating infants at high risk has also been cancelled. According to the World Health Organization, all complaints received from different countries concerning outbreaks of suppurative lymphadenitis in the last 20 yr were connected with a change of vaccine (2). This most recent outbreak of lymphadenitis associated with BCG vaccination also substantiates that the Pasteur strain is more reactogenic than the Kopenhagen strain. FRANZ ALLERBERGER, M.D. Federal Public Health Laboratory Innsbruck, Austria

1. Houston S, Fanning A, Soskolne C, Fraser N. The effectiveness of bacillusCalmette-Guerin (BCG) vaccination against tuberculosis. A case-control study in Traty Indians, Alberta, Canada. Am J Epidemiol1990; 131:340-8. 2. Anonymous. Lymphadenitis associated with BCG immunization. Wkly Epidem Rec 1988; 50:381-3.



To the Editor: Bacillus Calmette-Guerin (BCG) vaccination against tuberculosis has been used around the world for 70 yr; yet its efficacy in large-

Mortal complications accompanying Nd-YAGlaser photoresection (LPR) of endobronchial lesions include systemic air embolism, hemorrhage from either the lesion itself or from laser induced perforation of disrupted "normal" vascular structures, and fire. Inadvertent airway perforation leading to mediastinal emphysema is another potential major complication. Distorted mediastinal anatomy produced by resectional lung surgery, tumor infiltration, and radiation therapy contribute to such complications during LPR. Combination of distortion of the anatomy and perforation of air-

Surfactant replacement improves lung recoil in rabbit lungs after acid aspiration.

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