Carbon Monoxide and Stress Testing

normal resulting from ventricular septal defects. Using a dosage of 1 mg/kg directly administered into the pulmonary artery, they reduced the resistance to normal in each case without adverse eHects. It is unlikely, in this case, that the exaggerated response to tolazoline was due to its administration via a peripheral IV line instead of the pulmonary artery. WeinerS states that the acute responses to toIazoline are variable but considerable in some patients with pulmonary hypertension, and a paradoxic increase in pulmonary resistance has been reported in a patient with mitral stenosis. In that situation, the obsbuction at the mitral valve was probably an important conbibuting factor.· Therapeutic doses of tolazoline may cause cardiac stimulation that is more than just a reflex response to peripheral vasodilatation and may be associated with arrhythmias possibly related to the histamine and acetylcholine-like properties described by Ahlquist in 1947.1 In addition, the discovery of catecholamine overflow in studies in vitro following administration of alpha-blockers such as phentolamine and phenoxybenzamine has led to the elucidation of the role of pre- and postsynaptic alpha adrenergic receptors. e This apparent paradoxic response can possibly also be explained by catecholamine excess with unopposed beta adrenergic stimulation. this unanticipated response to parenteral tolazoline in primary pulmonary hypertension is probably not paradoxic since explanations for the occurrence can be proposed. Additionally, discrepant responses to parenteral isoproterenol in pulmonary hypertension1 , 8 would also support the fact that unpredictable responses to catecholamine agonists and antagonists in primary pulmonary hypertenison may be more common than heretofore recognized. WiQiam H. Fennell, M.D.; John A. Farmer, M.D.; Roymond H. Graf, M.D.; and James B. Young, M.D., F.C.C.P., Cardiology Section, Ben Taub General Hospital, BtJfIlor College of Medicine, HOtI8tOn

Carbon Monoxide and Stress Testing To the Ed:tor:

In a previous issue of Chest (1981; 79:302-(5) Corbalan at present what appears to be a 6ne double-blind study demonstrating that nifedipine significantly improves the exercise tolerance of patients with stable angina pectoris. As the number oE studies utilizing an exercise-induced anginal end-point seems to be increasing, with major medical and even surgical decisions being predicated upon their data, it is most distressing to me that an obvious aspect of exercise physiology in these patients is being neglected: namely, carbon monoxide levels in the subjects tested. Decreased time to exercise-induced angina in the presence of very mild elevations in blood carbon monoxide has clearly been demonstrated. These levels were induced in doubleblind, controlled studies, both by exposure to cigarette smoke,1,2 and freeway air. S The physiology bas been weD worked out, and involves decreased myocardial oxygenation superimposed upon a vascular system inadequate to provide augmented perfusion. In that the half-life of carbon monoxide is approximately three and one-half to four hours, it is not inconceivable that any patient smoking and/or driving through heavy trafBc on his way to the test might have a high enough carbon monoxide level to affect his exercise-induced anginal endpoint. Sadly, as in most studies of this nature, not only do we not know the subjects' carbon monoxide levels, we don't even know who smokesl et

lohn M. MoorhetId, M.D.

DeptJrtment of Pulmot1tJf1l Medicine, Bt.IpIisI Medical Center, Jacbonoille HeGltJa Education ProgrtJfR8, Jacbonotlle, Florida Reprint requem: Dr. Moorhead, B~~ Medical Center, 800 Pn.ulential Drive, JtlCk8om>il1s, Florida 32201

Reprint requests: Dr. Young, 1200 Moursund, 512D, H0fJ8ton 77030

1 DresdaIe DT, Schultz M, Michtom RJ. Primary pulmonary hypertension: clinical and hemodynamic study. Am J Med 1951; 11:686-705 2 Grover RF, Reeves JT, Blount SG Jr. Tolazoline hydrochloride (Priscoline), an effective pulmonary vasodilator. Am Heart J 1961; 61:5-15 3 Wiener N. Drugs that inhibit adrenergic nerves and blodc adrenergic receptors. In: The pharmacological basis of therapeutics. (Goodman and Gilman eds) New York: McMillan, 1980; 183-84 4 Ahlquist BP, Huggins RA, Woodbury RA. The pharmacology of benzyl imidazoline ( Priscol). J Pharm Expt Ther 1947; 89:271-88 5 Brown GL, GilleSpie JS. The output of sympathetic transmitter from the spleen of the cat. J Physiol London 1975; 138:81-102 6 Shettigar UR, Hultgren HN, Specter M, et aL Primary pulmonary hypertension: Favorable effect of isoproterenol. N Eng! J Med 1976; 295:1414-15 7 Welton DE, Petrovich LJ, Adyanthaya A, Alexander JK. Primary pulmonary hypertension; detrimental effects of isoproterenol. Chest 1978; 74:353

CHEST, 81: 1, JANUARY, 1982

REFEBENCES 1 Aronow WS, Rokaw SN, Carboxyhemoglobin caused by smolcing nonnicotine cigarettes, effects in angina pectoris. Circulation 1971; 44:782-88 2 Aronow WS. Effect of passive smoking on angina pectoris. N Eng} J Moo 1978; 299:21-24 3 Aronow WS, Harris CN, Isbell MW, RODW SN, Imparato B. Effect of freeway travel on angina pectoris. Ann Intern Med 1972; 77:669-76 To the Ed:tor:

We thank Dr. Moorhead for his letter and agree that a number of factors can influence exercise performance in patients with chronic stable angina pectoris and, certainly, carbon monoxide levels is one of them. In our protocol, special efforts were made to keep some of them constant: several tests were performed consecutively to remove apprehension and to take into account the known adaptation to testing; tests were performed at the same hour of the day and with the same interval after a light breakfast, etc. Carbon monoxide levels were not monitored, but we hope Dr. Moorhead would agree that changes of CO levels are highly unlikely to explain the striking improvement in exercise performance that was observed in every patient

COIMUNICAnollS TO THE EDITOR 121

after administration of nifedipine. For this to be true, a significantly lower level of CO would have to be present in every or most every one of the subjects precisely on one of five consecutive days, the sequence of which was even changed at random. Ideally, every drug trial should include monitoring of all relevant factors that can inHuence the results . This is usually impossible from the practical standpoint. We were aware of the effects of CO in this setting, but thought that the design of the experiment, with multiple testing and double-blind random cross-over between placebo and nifedipine would malce monitoring of CO levels unnecessary for the purpose of the study. Ramon Corbalan, M.D. Department of Cardiovascular DUease, Pont;ficia Universidad CatoUca de Chile, Santiago

Langerhans Cells in Bronchoalveolar Lavage in the Late Stages of Pulmonary Histiocytosis X To the Editor:

The study of cells obtained by bronchoalveolar lavage ( BAL ) has helped in the understanding of inHammatory and immune processes of the lower respiratory traot.t Langerhans cells ( LC) are recognized by their specific granules, have been reported in lung biopsies from patients with pulmonary histiocytosis X (PHX) 2 and with lesser frequency in other lung disorders.s-! but their appearance in BAL has been described only in PHX.4,3 We report the electron microscopic findings in the BAL of two patients with PHX and honeycomb lungs.

CASE REPoRTS CASE

1

A 34-year-old man suffered from diabetes insipidus for 20 years and had had two previous episodes of pneumothorax, productive cough and moderate exertional dyspnea of increasing intensity in the last years. He was admitted to our hospital with a right pneumothorax and the chest x-ray film showed a bilateral honeycomb pattern. There was neither exophthalmos nor bone lesions and the dehydration test confirmed his inability to concentrate urine . Once the pneumothorax had subsided, pulmonary function tests revealed : Pa0 2 , 76 mm Hg; PaC02 , 32 mm Hg; pH, 7.43; VC, 2,400 ml (4,700); FEV t , 1,527 ml (3,715) ; TLC, 4,000 ml (5,800); DLco, 10.5 ml/min/mm Hg (30), (expected values in parentheses). CASE

2

A 17-year-old boy was admitted to the hospital with bilateral pneumothorax. He had been treated nine months earlier at another clinic for a previous unilateral episode, at which time the chest x-ray examination disclosed a honeycomb pattern; an open lung biopsy was reported as pulmonary eosinophilic granuloma. Physical and radiologic examinations revealed no extrathoracic lesions. In each patient 100 ml of saline solution was instilled into a lower lobe through a fiberoptic bronchoscope (Olympus BF B2) . The aspirated fluid was fixed in 3 percent glutaraldehyde, centrifuged and studied with a Phillips 301 TEM. Inflammatory cells with neutrophils, eosinophils and

130 COMMUNICanONS TO THE EDITOR

FIGURE 1. Histiocytosis X cell with multilobed nucleus and specific X granules ( EM stain, original magnification X 14,000) . Inset: (original magnification X 30,000). alveolar macrophages were abundant, and among them cells with multilobed nuclei and abundant cytoplasm containing characteristic pentalaminar structures were identified in both cases (Fig 1). "HX cells" are considered activated forms of Langerhans cells and are consistently reported in histiocytosis X, decreasing in number as the disease becomes chronic. Their exact origin and function is not well defined, but they probably belong to the mononuclear phagocytic system and are related to the immune response.! It is of interest to note that our two patients were in the late stages, when HX cells are less numerous in biopsies, and yet these were present in the BAL in sufficient number to suggest a specific diagnosis. Thus, this technique can be valuable both in early and advanced stages of PHX if these cells are not identified in the BAL of other lung conditions where LC do not migrate from the interstitium into the alveolar lumen, as reported by Kawanami et al.4 Hector Verea-Hemando, M.D.; Jose Fontan-Bueso, M.D.; M. Teresa Martin-Egana, M.D.; and Enmcisco Amal-Monreal, M.D., Ciudad Sanitaria 1. Canalejo, La Corona, Spain

fu:FERENCES 1 Hunninghalce GW, Gadek JE, Kawanami 0. Ferrans VJ, Crystal RG. Inflammatory and immune processes in human lung in health and disease: Evaluation by bronchoalveolar lavage . Am J Path 1979; 97 :149-209 2 Basset F, Corrin B, Spencer H, et al. Pulmonary histiocytosis X. Am Rev Respir Dis 1978; 118:811-20 3 Hamar SP, Bockus D, Remington F, et al, Langerbans cells and serum precipitating antibodies against fungal antigens in bronchoalveolar cell carcinoma: Possible association with pulmonary eosinophilic granuloma. Ultrastr Path 1980; 1:19-37 4 Kawanami 0, Basset F, Ferrans VJ. Soler P, Crystal RG. Pulmonary Langerhans' oeIIs in patients with fibrotic lung disorders . Lab Invest 1981; 44:227-33 5 Basset F, Soler P, Jaurant MC, Bignon J. Ultrastructural examination of bronchoalveolar lavage for diagnosis of pulmonary histiocytosis X: Preliminary report on 4 cases. Thorax 1977; 3.2:303-06

CHEST, 81: 1, JANUARY, 1982