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patient in that the former had evidence of parenchymal disease (abscess with or without pneumonitis) as well as empyema at the time of his admission. However, the electrolyte disorder persisted until the loculated empyema was adequately drained by surgery, and only then did the electrolytes return to normal. Also, only one anaerobe was isolated from the pleural fluid, in contrast to our earlier patient who was infected with 3 anaerobes. This may have been due to difficulties in handling and processing the specimen, since most anaerobic infections are due to more than a single organism. Nevertheless, in both of these cases Bacteroides species were isolated, and perhaps this genus is responsible for the pathologic changes which cause the syndrome of inappropriate ADH secretion to occur in this setting. As more cases become recognized, the validity of this assumption can be tested, and perhaps more insight into the mechanism of this abnormality can be obtained. Finally, the appearance of another case at our hospital suggests that the association may be more common than originally supposed. BRENT G. PETTY

The Johns Hopkins Hospital Baltimore, Md. 21205 June 29, 1977

A T R O P I N E E F F E C T S ON A N T I G E N - M E D I A T E D A I R W A Y CONSTRICTION

To the

Editor:

Various aspects of the bronchial response of asthmatics to allergens and cholinergic drugs have been documented by 2 recent articles (Am Rev Respir Dis, March 19771-5). However, the results of such studies should be interpreted with caution as the mechanisms involved are complex and sometimes ill-known. Fish and associatesi observed that atropine had a rather weak protective effect against antigen-induced airway obstruction and they suggested that iFish, J. E., Rosenthal, R. R., Summer, W. R., Menkes, H. H., Norman, P. S., and Permutt, S.: Am Rev Respir Dis, 1977,115, 371. 2 Orehek, J., Gayrard, P., Grimaud, C., and Charpin, J.: Bull Physiopath Resp (Nancy), 1975, 11, 193. 3 Clement, J., and Van de Woestijne, K. P.: J Appl Physiol, 1971,30,437. 4 Gayrard, P., Orehek, J., and Charpin, J.: Respiration, 1975, 32, 294. 5Rubinfeld, A. R., and Pain, M. C. F.: Am Rev Respir Dis, 1977,275,381.

the cholinergic nervous system does not play a major role in human allergic asthma. However, it is apparent from their study that the protective effect of atropine was quite noticeable in some subjects. For example, after atropine, a dose of allergen 10 times higher was required in one subject (BS in table 2) to achieve a decrease in FEVj^ comparable to that observed without atropine. As we ignore the amount of allergen that reaches the airways during exposure to natural concentrations of allergens, it might be erroneous to state that the cholinergic nervous system is not of clinical importance in asthma. For example, if in natural conditions the above-mentioned subject (BS) were exposed to a lesser amount of allergen than that eliciting a bronchospasm after atropine, his or her disease could be considered cured by atropine. Furthermore, these authors have examined only 6 subjects and other studies, including our own2, have shown that the protective effect of anticholinergic drugs varies largely among asthmatics (7 of 10 subjects were strongly protected against grass pollen challenge in our study). Finally, it must be pointed out that in studies involving changes in baseline values, the results might be biased by the use of specific airway conductance (SGaw)3,4. Thus, a minor decrease in airway resistance, as observed after atropine, results in a major increase in SGaw. This bias renders questionable the use of percentages for calculating the dose of allergen causing a given change of SGaw before and after atropine. Rubinfeld and Pain5 found no relationship between the baseline value of SGaw and the degree of bronchial reactivity to methacholine within and among patients with asthma. In their study, the use of SGaw might also have complicated the results. In addition, these authors gave methacholine aerosol as a vital capacity inhalation. We have observed that, in asthmatics, deep inspiration from functional residual capacity or maximal respiratory maneuvers has a variable but often marked bronchomotor effect of their own, and that they are able to modify the airway response to a large extent6,T,8. Thus, these authors have in fact evaluated 3 variable factors in their work: the initial airway caliber, the bronchial reactivity, and the effect of deep inspiration. This could explain the lack of correlation that they reported, in contrast to our observations.9

6 Gayrard, P., Orehek, J., Grimaud, C , and Charpin, J.: Am Rev Respir Dis, 1975, 111, 433. 7 Orehek, J., Gayrard, P., Grimaud, C , and Charpin, J.: Br Med J, 1975,1, 123. 8 Gayrard, P., Orehek, J., Charpin, J.: Rev Fr Mai Respir, 1976, 4t15. 9 Gayrard, P., Orehek, J., Charpin, J.: Rev Fr Mai Respir, 1976, (4 SuppL) 1, 51.

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Another possible explanation for this discrepancy is that these authors have assessed the bronchial response by determining only the slope of the doseresponse curves to methacholine. We have indeed shown that the slope does not completely characterize the airway response to a bronchoconstrictor agentio. J. OREHEK P. GAYRARD

Hopital Salvator 249, chemin de Sainte Marguerite 13009 Marseille France May 6, 1977 10 Orehek, J., Gayrard, P., Smith, A. P., Grimaud, C., and Charpin, J.: Am Rev Respir Dis, 1977, 155, 937.

To the

Editor:

The comments by Drs. Orehek and Gayrard highlight a controversy in the interpretation of bronchial challenge tests. Does one plot dose-response relationships in absolute units or in relation to the initial values? Were it possible to define the maximum bronchial response of an individual, graphic representation could be made according to classic pharmacologic format. For obvious reasons this is impossible. Much of the contention, however, is more apparent than real. In figure 1 in our paperi, Linear decreases in SGaw are related to doses of methacoline, in both absolute and proportional terms. If SGaw were transposed to Raw, the response would become hyperbolic and almost identical to the graphs obtained by Dr. Orehek and co-workers2. Similarly, we have attempted to replot their data using our format and have found that their curves in most cases become well linearized. One point must be emphasized, however. In attempting to maintain a format as close as possible to dose-response curves of classical pharmacological experiments, our abscissa is not linear, as is that of Drs. Orehek, Gayrard, and others, but exponential. It seems, then, that we are each considering fairly small portions of an individual's total possible range of bronchial response, and that the graphic differences may well be minor. In our subjects and in theirs, changes in slope of dose-response curves were usually seen under the described circumstances; parallel shifts were generally not seen. Our iRubinfeld, A. R.: Am Rev Respir Dis, 1977, U5, 381. 2 Gayrard, P., Orehek, J., and Charpin, J.: Rev Fr Mai Resp 1976 (4 Suppl.) 1, 51.

analysis possibly tends to underinterpret such graphic alterations, and perhaps we erred on the side of excessive caution in utilizing such statistical methods. Similarly, the data of the above authors 2 show that in some of their subjects, changes in slope did not reach statistical significance. On the other hand, one subject showed gross changes in dose-response characteristics despite only minimal differences in initial airway caliber. Furthermore, in their interpretation of a doubling dose of Carbachol, the changes in many individuals were less than a factor of 2, a differences that is minor in pharmacological terms (but possibly not in clinical terms). While not detracting from the trends shown in their elegant data, we believe that both extremes of interpretation are worthy of consideration. Finally, with respect to our use of vital capacity inhalations as a means of administering aerosols, we are aware of the data demonstrating that such manoeuvers may temporarily alter the lung mechanics of asthmatics and may also affect their dose-response characteristics. T h e mechanical effects of such manoeuvers have usually disappeared by 3 minutes^. The fact that a vital capacity manoeuver affects a subject's dose-response characteristics does not make this a variable factor if, in fact, it has been constant in all tests. A. R . RUBINFELD

Respiratory Laboratory Royal Melbourne Hospital Victoria 3050 Australia June 24, 1977 3 Lloyd, J. C.: J Appl Physiol, 1967,18, 114.

From the

Authors:

Doctors Orehek and Gayrard have raised several points which deserve clarification. In the clinical setting the degree of protection provided by anticholinergic drugs will undoubtedly vary among asthmatic patients. For this reason we selected a relatively homogeneous group of ragweed sensitive asthmatics so we could specifically define the effect of cholinergic blockade on the antigen-induced response. What emerged from our study is the following. We demonstrated that atropine improved baseline pulmonary function in those asthmatics who already had airway obstruction, that the threshold dose of antigen at which impairment of function occurred was the same with or without atropine pretreatment, and that significant changes in

Atropine effects on antigen-mediated airway constriction.

792 C O R R E S P O N D E N CE patient in that the former had evidence of parenchymal disease (abscess with or without pneumonitis) as well as empye...
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