Is Ethanol a Bronchoconstrictor?

Path 1973; 111:149-53 4 McFarlane DE, Gardner S, Lipson C, Mills DC. Malondialdehyde producti on by platelets during secondary aggregation. Thromb Haemastas 1977; 38:1002-009 5 McMillan RM, McIntyre DE, Booth A, Gordon JL. Malondialdehyde formation in intact platelets is catalyzed by thromboxane synthetase. Biochem J 1978; 176:595-98 6 Vladutiu AO Brason FW Adler RH. Differential diagnosis of pleu;al effusions. Chest 1981; 79:297-301

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MALIGNANT

PLEURAL

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EFFUSIONS

EFFUSIONS

FIGURE 1. Malond ialdehyd s levels in benign and maligna nt pleural effusions. benign causes known to be associated with pleural fluids. In some patients , more than one sample was tested (Fig 1). The mean value of MDA in the benign group (630 /kM/L ± 302) significantly exceeds that of the cancer group (222 /kM/L ± 197). The arbitrari ly taken cut-off value of 400 ...M /L correctly classifies six of eight cancer patients (24 of 27 samples ) and 19 out of 23 patients with benign disease. The discriminative power of this test for malignancy is compara ble to that of other marker assays." The MDA techniqu e proved to be reprodu cible since the values of serial measure ments in the cancer group fell within the same range. The low MDA levels in the cancer group suggest that prostagl andins are not involved in the producti on of pleural fluids of tumors, contrary to the seemingly prostaglandin -depend ent benign pleural effusions. Our limited study leads us to suppose that the difference in MDA levels between maligna nt and benign pleural effusions may be useful for diagnostic purposes.

Andras Pdl, M.D., Bela Fekete, M.D., Istvan Forrai, M.D., National Institute for Tuberculosis and Pulmonology; and Zoltdn Torma, M.D., National Institute for Physical Education, Budapest, Hungary REFERE NCES

1 Bragt PC, Schenke laars EPM, Bonta IL. Dissociation between prostagl andin and malondi aldehyd e formation in exudate and increase d levels of malondialdehvde in plasma and liver during granulomatous inflammation in rat. Prostaglandins and Medicine 1979; 2:51-61 2 Stuart MJ, Scott MBS, Oski FA. A simple nonradioisotope techniqu e for the determi nation of platelet life span. N Engl J Med 1975; 208:1310-13 3 Velo SP, Dunn CJ, Giroud JP, Timsit J. Willoug hby DA. Distribu tion of prostaglandins in inflammatory exudate. J

CHEST, 81: 6, JUNE, 1982

Is Ethanol a Bronchoconstrictor? To the Editor: We were interested to read the article by Gong et al in the August issue of Chest (1981; 80:167-173). Geppert and Boushey- and Hieks'' before them have both claimed that ethyl alcohol itself is a cause of wheeze. Unfortunately, in these studies ethanol was mixed with a "soft drink" (eg, apple juice) and was not given mixed solely with water. If ethanol itself is a cause of wheeze, why did intravenous ethanol (albeit at a lower dose of 5 ml in a 10 percent solution) cause only an insignificant fall in airways conductance? Ten percent ethanol IV is not far below the concentration (15 percent) which can cause severe vasovagal reactions presumably due to venous irritation (persona l observation) and any fall in airflow following its administration might be due to vagal overactivity because of this effect. Tufts suggested in 1934 that ethanol given orally might increase intestinal permeability to ingested proteins or protein breakdo wn products, although there is no evidence for this. Was the apple juice used by Gong et al fresh or from a can or carton? Food stuff preservatives such as sulphur dioxide and coloring substances such as tartrazine are well known to cause wheeze- and, if present in apple juice, may, in combination with ethanol, be more likely to be absorbed, thus causing wheeze. Until the patient of Gong et al has been studied with oral ethanol in water, the statemen t that ethanol causes bronchoconstriction cannot be made. Jon Ayres, M.B., MRCP, Registrar, and T. J. H. Clark, M.D., FRCP, Professor, Guy's Hospital, London, England REFERE NCES

1 Geppert EF, Boushey HA. An investigation of the mechanism of ethanol-induced bronchoconstriction. Am Rev Respir Dis 1978; 118:135-39 2 Hicks R. Ethanol, a possible allergen. Ann Allergy 1968; 26:641-43 3 Tuft L. In: Clinical allergy. Philadelphia: WB Saunders 1937; 170 4 Freedm an BJ. Asthma induced by sulphur dioxide, benzoate and tartrazine. Clin Allergy 1977; 7:407-15

To the Editor: We thank Drs. Ayres and Clark for their interest in our report about alcohol-induced bronchospasm in an asthmatic patient. Intravenous infusion of normal saline solution (via an indwelling intravenous catheter ) did not produce symptoms or measure d bronchospasm. The saline solution was followed by a small amount of 10 percent intravenous ethanol and the ethanol infusion produce d short-lasting mild symptoms and measurable bronchoconstriction. The patient tolerated both infusions very well and did not

COMMUNICATIONS TO THE EDITOR 773

exhibit any symptoms to suggest a vasovagal reaction such as pallor, diaphoresis, hypotension, or syncope. It is possible that the intravenous ethanol was too dilute or given for too short a time to elicit the marked bronchoconstriction observed during oral administration of ethanol. Apple juice was chosen as a suitable, palatable, nonreactive vehicle with which to mix the ethanol for oral administration. The plain apple juice used in our experiments was obtained from commercially bottled containers labelled as "pure unsweetened apple juice" made from Washington state apples. Although there was no listing of ingredients (eg, preservatives) on the bottles, we do not believe that sulfur dioxide or tartrazine was added to this noncarbonated beverage. If these preservatives were present and if our patient were sensitive to these agents, then one would have expected the apple juice alone to cause bronchospasm. However, we clearly demonstrated that plain apple juice did not cause bronchoconstriction in the control experiment. In addition, neither inhaled nor ingested cromolyn sodium protected our patient, unlike four other patients- with asthma exacerbated by ingested sulfur dioxide, sodium benzoate, or tartrazine. Finally, we recently retested the same patient with the ingestion of 30 ml of 95 percent ethanol in 170 ml distilled water. The same protocol (as previously reported) was followed, using spirometric and plethysmographic tests before and serially after ingestion of the ethanol in water. The results in absolute values are as follows: FEVl , L

SGaw, L/sec/cm H 20/L

3.86

0.22

Immediately after oral ethanol

3.73

0.12

10 min post ethanol

3.29

0.05

15 min post ethanol

3.48

0.06

30 min post ethanol

3.05*

0.05t

60 min post ethanol

3.62

0.07

90 min post ethanol

3.73

0.08

120 min post ethanol

3.86

0.11

Baseline Oral ethanol in water

*21 percent reduction compared to baseline value t77 percent reduction compared to baseline value The subject developed generalized flushing and tightness of the chest immediately after ingestion of the ethanol. The chest tightness subjectively peaked 30 minutes postingestion (without wheezes or rhonchi on auscultation) and improved spontaneously 90 minutes after ingestion. We believe that the reported data strongly support our conclusions that ethanol alone was responsible for this patient's bronchoconstriction. Henry Gong, [r., M.D., and Donald P. Tashkin, M.D., F.C.C.P., Pulmonary Disease Division, Department of Medicine, UCLA School of Medicine, Los Angeles REFERENCE

1 Freedman BJ. Asthma induced by sulphur dioxide, benzoate and tartrazine contained in orange drinks. Clin Allergy 1977; 7:407-15

174 COMMUNICATIONS TO THE EDITOR

Ventilatory Effects of Beta-blockers and Characteristics of Patients with COPD To the Editor: The article of Chester and coworkers in Chest 1981; 79:540 gives us reason to make the following remarks. The patients involved in their trial meet the diagnostic standards of the American Thoracic Society regarding chronic bronchitis and/or emphysema, which, however, do not exclude an asthmatic component in their disease. The patients were regarded as not asthmatic because of: 1) negative skin tests, 2) absence of eosinophilia, and 3) absence of a major reversibility of obstruction of the bronchus with treatment over time. Regarding the first two criteria of the authors. it is well known to pulmonologists that patients not fulfilling these criteria can also be asthmatics (intrinsic asthma). Considering the third criterion and looking at the figures presented by the authors, it is easy to see that patients no. 2, 3, 5, 6, 9 and 12 show an improvement of their SRAW of more than 20 percent on stimulation with a FI-agonist drug, which is, to our knowledge, defined as a good reversibility of the obstruction. So classification of these patients as not asthmatic is misleading. In our opinion, six of 13 investigated patients have chronic obstructive pulmonary disease (COPD) with an asthmatic component. In patients with good reversibility of the bronchial obstruction on FI-agonist therapy one can expect a decrease in ventilatory indices with use of a nonselective FI-blocker such as propranolol, because the point of action of both agents is the FI-receptor influencing the tone of the smooth muscle in the airways. In patients in whom the bronchial obstruction is fixed, because it is only caused by increased mucus production andlor swelling of the mucous membrane, no reaction is to be expected using FI-agonist and FI-blockers, as is already pointed to by Perks and coworkers! and which is also our experience. The separation between the patients in reacting and not reacting to a FI-blocker, as the authors conclude, is probably predictable by their response on Fl 2-agonists. We support the conclusion of the authors that propranolol should not be used in patients with COPD, not only because a hidden asthmatic component can be present, but also because the bronchial obstruction induced by nonselective FI-blockade cannot be reversed by FI-agonist in a normal dose. Using Fl1-selective blockers, such as metoprolol and atenolol,. in patients with COPD and an asthmatic component, the mfluence on the airways is limited and can be easily antagonized by FI-agonists.2 AP.M. Greefhorst, M.D., and C.L.A van Herwaarden, M.D., Department of Pulmonary Diseases, University of Nijmegen, Medical Centre Dekkerswald, H. Landstichting, The Netherlands

Reprint requests: Dr. Greefhorst, Medisch Centrum Dekkerswald, Nymeegse baan 31,6564 C.A Groesbeek, The Netherlands REFERENCES

1 Perks WH, Chatterjee SS, Croxson RS, Cruickshank JM. Comparison of atenolol and oxprenolol in patients with angina or hypertension and co-existent chronic airways obstruction. Br J Clin Pharmacol 1978; 5: 101-06 2 Greefhorst APM van Herwaarden CLA. A comparative study on the ventilatory effects of three Fl1-selective blocking agents in asthmatic patients. Eur J Clin Pharmacol1981; 20:417-21

CHEST, 81: 6, JUNE, 1982