Chronic Cough

2 Pearce SJ. Fiberoptic bronchoscopy: is sedation necessary? Br J Med 1980; 281:779-80 3 Bees PJ, Hay JG, Webb JR. Premedication for fiberoptic bronchoscop~ Thorax 1983; 38:624-27 4 Shelley Me Wdson e Norman J. Sedation for fiberoptic bronchoscopy. Thorax 1989; 44:769-75 7b the Editor: The comments by Dr Mehta and Dr Stubbs are welcome, and we emphasize again the diverse opinions regarding preparation for 8beroptic bronchoscopy with the patient under local anesthesia. We agree that maximum comfort and cooperation must be ensured for patients undergoing invasive procedures. This element could not be precisely assessed because of the retrospective nature ofour stud~ After 20 years of experience, however, we have not been impressed by the effects of --routine premedication·' on patient comfort and cooperation regardless of age, sex, or indication. No patient has refused a second bronchoscopic procedure when informed of the necessity. We suspect that confident reassurance, kind and considerate nursing care, and a gentle, experienced endoscopist contribute significantly to a smooth procedure. Coping mechanisms are probably important as well, and may differ in regard to sex, age, race, or nationality. Prospective studies that focus on these multiple facets and compare them with premedication alone may be desirable. Cen~ l&er et

Henri G. Colt, M.D., Seroice d·Endoscopie 1Jwracique, H6pital Ste. Marguerite, Marseille, France; and }ames F. Morris, M.D., F.C.C.l, Pulmonary Disease Section, Portland VA Medical Center, Portland, ~gon

Chronic Cough Sometimes You Have to Look at a Tree

to See the Forest

lenge testing failed to reveal an obstructive ventilatory pattern. Two patients with LD had normal flow-volume loops at rest. In each patient, bronchoscopy showed paradoxic adduction of the vocal cords during inspiration, either at rest or after an exercise challenge that reproduced their symptoms. In our evaluation of chronic cough, we utilize the anatomic diagnostic protocol. 5 It is important to separate pulmonary from nonpulmonary causes of cough and differentiate upper airway from lower airway disease to initiate the appropriate thera~ Patients with LD would be expected to have a negative result on a methacholine challenge study and, in some cases, a normal flowvolume loop. Therefore, it is critical to include the evaluation of the upper airway and vocal cords during bronchoscopy as part of the anatomic diagnostic protocol to diagnose LD. We believe that milder forms of LD are responsible for the symptoms of chronic cough in more patients than has been previously recognized. Indirect laryngoscopy may be inadequate to diagnose LD, and these patients have indications for both a lower and an upper airway examination. Therapy for patients with LD concentrates on speech and psychotherapy at the present time. We are prospectively evaluating patients with chronic cough to determine the actual incidence of LD in this patient population. Laryngeal dyskinesia may be poorly recognized because many bronchoscopists, in their haste to "rule out an endobronchial lesion;· bypass appropriate vocal cord evaluation. Bronchoscopic training should include a careful examination of the upper airway and dynamic vocal cord movement. We must be vigilant during bronchoscopy to perform evaluation of both the upper and the lower airways, and be able to recognize a tree before we characterize the forest.

71wmas M. FUzpatnck, Ph.D., M.D., and Wanm L. Whitlock, M.D., F.C.C.l, Pulmonary Disease Seroice, Letterman Anny Medical Center, Presidio o/San Francisco, Cali.forma

The opinions or Q88ertions contained herein are the private views of the authors and are not to be comtnIed as of/icjal or as rejlecHng the views of the Department of the Anny, the Department Of Defetve, or the US government.

7b the Editor: In the January 1991 issue of Chest, Drs Sen and Walsh expended considerable effort to demonstrate the diagnostic yield of 8beroptic bronchoscopy (FB) in a select group of chronic coughers and concluded that, --in patients refractory to.therapy based on clinical evaluation, FB may have a significant diagnostic yield:'l However, 72 percent (18125) of their patients are left: with an undefined cause for their chronic cough. This is significant when compared with the findings in a recent report by Poe et al,· in which no diagnosis was arrived at for 20 percent (16178) of their patients with negative results on a provocative airway challenge stud~ Typically, these patients are labeled with a diagnosis of exclusion, such as "psychogenic cough" or malingering. We speculate that a significant number of these patients who present with chronic cough and/or dyspnea on exertion have laryngeal dyskinesia (LD). This is an ill-defined syndrome that is characterized by paradoxic adduction of the vocal cords during inspiration. Laryngeal dyskinesia is reported to mimic asthmatic exacerbations, 3.4 but may also present with milder symptomatol~ such as chronic cough. Sen and Walsh reported the case of one patient with an abnormal flow-volume loop who was later found at bronchoscopy to have LD.l Over the past two years, we have evaluated six patients with unexplained cough or wheezing and found five of them to have LD. In each case, pulmonary function studies and methacholine chal-

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REFERENCES 1 Sen ~ Walsh TE. Fiberoptic bronchoscopy for refractory cough.

Chest 1991; 99:33-35

2 Poe RH, Harder R~ Israel RH, Kallay MC. Chronic persistent

cough: experience in diagnosis and outcome using an anatomic diagnostic protocol. Chest 1989; 95:723-28 3 Christopher KL, Wood He Eckert RC, Blager FB, Raney RA, Souhrada JF. Vocal-cord dysfunction presenting as asthma. N Eng) J Med 1983; 308:1566-70 4 Ramirez J, Leon I, Rivera LM. Episodic laryngeal dyskinesia: clinical and psychiatric characterization. Chest 1986; 90:716-21 5 Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy. Am Rev Respir Dis 1981; 123:413-17

Coronary Arterial Spasm and Cardiac Arrest following Mediastinal Radiation Therapy for Hodgkin'S Disease 7b the Editor: Coronary artery disease following high-dose radiation therapy for Hodgkin·s disease has been previously reported. l We report the case of a patient who presented with episodes of angina associated

with cardiac arrest due to coronary artery spasm following mediastinal irradiation. In November 1985, stage IIIAS nodular sclerosis Hodgkin's disease was diagnosed in a 49-yeaN>ld man. The patient was treated with a course of total nodal irradiation (cobalt 60). A total of 45 Gy (4,500 rad) was delivered in the midplane of the mediastinum via anterior and posterior ports. The patient's condition is presently in remission 41 months later. No family history or risk factors for coronary heart disease were detected. Three months before admission, the patient was admitted to another hospital because of chest pain, which increased with deep breathing. An echocardiogram showed mild pericardial effusion, and acute pericarditis was diagnosed. Acetylsalicylic acid was administered, and the patient was discharged 48 h later. Three months later, he was referred to our hospital because of seven episodes of chest pain of a few seconds' duration while at rest, followed by loss of consciousness. The patient also complained of progressive asthenia and dyspnea during exercise. There was no exertional chest pain. On admission, blood pressure was normal, and a paradoxical arterial pulse was palpable. The neck veins were distended to the angles of the jaw with the patient sitting. There were no murmurs, but a third heart sound was heard. The liver was enlarged, and mild edema was seen in the inferior extremities. There were no enlarged lymph nodes. The ECG showed a sinus rhythm and inverted T waves in precordial leads (Fig 1, A). Chest radiography revealed mild cardiomegaly, mild right pleural effusion, and lung changes probably secondary to radiation 6brosis. A two-dimensional echocardiogram showed a mild posterior pericardial effusion, thickening of the anterior pericardial wall, early interventricular septal diastolic motion, and enlargement of the superior vena cava. A Holter

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FIGURE 1. A: A 12-lead ECG obtained before the anginal episode shows sinus rhythm and inverted T waves in precordial leads. B: A 12-lead ECG obtained during an episode of angina at rest shows ST elevation in leads II, III, and aVF.

recording disclosed paroxysms of atrial Hutter and atrial fibrillation. No clinical symptoms of angina or low cardiac output appeared during these episodes of supraventricular arrhythmias. Three days after admission, the patient experienced chest pain at rest. The ECG showed ST segment elevation in leads II, III, and aVF (Fig 1, B) associated with complete atrioventricular block. Severe hypotension and transient loss of consciousness followed. Both ECG abnormalities and arterial pressure recovered immediately upon resolution of the anginal attack. Right and left heart catheterization and coronary angiography were performed. The mean right atrial pressure was 18 mm Hg and showed a characteristic ccdip-plateau" pattern. The cardiac output was 3.6 Umin. Both left and right coronary arteries were angiographically normal. Constrictive pericarditis was diagnosed. Twelve hours later the patient experienced a new episode of chest pain at rest with ST segment elevation in the inferior leads and complete atrioventricular block associated with severe sinus bradyarrhythmia, which progressed quickly to atrial standstill and further respiratory arrest. Sinus rhythm and spontaneous ventilation recovered after standard resuscitation maneuvers. Ten days after the cardiac arrest, a pericardiectomy was performed. At surgery, extensive adherences of pericardium to the mediastinal structures and to myocardium were found. Pathologic study of the pericardium revealed severe interstitial 6brosis. In the early postoperative period the patient suffered another episode of angina with ST segment elevation in the inferior leads, which progressed to atrial standstill. Sinus rhythm recovered after external cardiac massage. Nifedipine at 40 mwday was started. One month later the patient was discharged, and after a 14-month follow-up the patient remains angina-free with good exercise tolerance. Coronary arterial spasm may produce severe myocardial ischemia in patients with obstructive arteriosclerotic coronary lesions or with normal coronary arteries. 2 The speci6c mechanisms that have been implicated are local abnormality of vascular smooth muscle, metabolic or hormonal imbalance, circulating catecholamines, and alteration of the autonomic nervous system. 3 Coronary arterial spasm is an exceptional event following mediastinal irradiation. We found in the literature only the report of Miller et al4 of a patient who presented with angina at rest four years after mediastinal irradiation. At coronary arteriography, a coronary spasm over a &xed coronary stenosis in the left coronary artery was induced by ergonovine. Ionizing irradiation may produce histologic changes in the arterial wall, such as adventitial and intimal 6brosis followed by medial atrophy. 5 In our patient, mediastinal irradiation probably injured the arterial wall without causing angiographic coronary arterial stenosis, but probably triggered local mechanisms that led to coronary arterial spasm. In summary, symptomatic coronary spasm may be a secondary effect of mediastinal radiation therapy. Due to the potential risk of cardiac arrest, an early diagnosis should be made in order to de6ne a speci6c treatment. Vacens Mart!, M.D., Juan Garda, M.D., jose Maria Auge, M.D., Damid Obradm; M.D., and Manel Ballester; M.D., Department of Cardiology, Hospital de la Santa Cmu i Sant Hzu, Barcelona, Spain Reprint requests: Dr Mart!, Department of Cardiology, Hospital de la Santa Cmu i Sant lhu, Avenida Antonio M. Claret 167, 08025 Barcelona, Spain

REFERENCES 1 Fajardo LF, Stewart JR, Cohn KE. Morphology of radiationinduced heart disease. Arch Patholl968; 86:512-19 CHEST I 100 I 4 I OCTOBER, 1991

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2 Selzer A, Langstom M, Ruggeroli C, Cohn K. Clinical syndrome of variant angina with normal coronary arteriogram. N Engl J Med 1976; 295:1343-47 3 Yasue H. Pathophysiology and treatment of coronary arterial spasm. Chest 1980; 78 (suppl):216-23 4 Miller DD, Waters DD, Dangoisse ~ David PRo Symptomatic coronary artery spasm following radiotherapy for Hodgkin disease. Chest 1983; 83:284-85 5 Brosius FC, Waller BF, Roberts WC. Radiation heart disease: analysis of 16 young (aged 15 to 33 years) necropsy patients who received over 3,500 rads to the heart. Am J Med 1981; 70:519-30

It has been stated that an elevated serum lactate dehydrogenase (LDH) concentration in the setting of diffuse lung disease should suggest the diagnosis of pulmonary alveolar proteinosis 1 or Pneumocystis carinii pneumonia. W However, we suspected that elevations in serum LDH may be nonspecific and simply reflect diffuse lung injury. We prospectively evaluated 81 patients with various forms of interstitial lung disease; all patients had at least two of the following characteristics: (a) radiographic evidence of bilateral interstitial-alveolar chest in6ltrates, (b) static lung volumes <80 percent of predicted, and (c) diffusing capacity for carbon monoxide <75 percent of predicted. In 38 (47 percent) patients a de6nitive diagnosis was established by biopsy. All patients were followed up for an average of 24 months (range, three to 52 months). Elevated serum LDH values (>425 UIL) were found in 35 (43 percent) patients. Most of these patients had cryptogenic 6brosing alveolitis, but an elevated serum LDH concentration was also seen in cases ofbleomycin pneumonitis, sarcoidosis, lymphoid interstitial pneumonia, and lung disease associated with rheumatoid arthritis and systemic sclerosis. Although a high serum LDH level did not appear useful in predicting the cause of interstitial lung disease, it did appear to have some prognostic value. Of the 46 patients with a normal serum LDH level, only four (9 percent) died within the follow-up period (Fig 1). In contrast, 16 (46 percent) of the patients with a high serum LDH level died (p<0.01). Particularly striking was the mortality rate (83 percent) in patients with a serum LDH concentration greater than 650 UIL (Fig 1). In summary, we found that an elevated serum LDH concentration was of no help in predicting the cause of interstitial lung disease,

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SERUM LDH FIGURE

1. Survival of patients with interstitial lung disease relative

to serum LDH level on presentation.

1182

UIwrie D. Oliphant, M.D., EC.C.l, St. Josephs Health Cenm, London, Ontario, Canada

REFERENCES

1b the Editor:

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Robin G. McRu:lden, M.D., EC.C.l, and

Reprint requests: Dr McRu:lden, Department of Medicine, St. josephs Health Centre, 268 Grosvenor Street, LOndon, Ontario, Canada N6H 486

serum Lactate Dehydrogenase in Interstitial Lung Disease

E-4

but was of unexpected prognostic significance. We suspect that an elevated serum LDH concentration in these patients reflects cellular hypoxia and tissue necrosis, and is a marker of acute and severe lung damage. A high serum LDH level also predicts a poor prognosis in patients with acquired immunodeficiency syndrome and P carin" pneumonia. 4.5

1 Martin RJ, Rogers RM, Myers NM. Pulmonary alveolar proteinosis: shunt fraction and lactic acid dehydrogenase concentration as aids to diagnosis. Am Rev Respir Dis 1978; 117:1059-62 2 Kagawa IT, Kirsch CM, Yenokida GG, Levine ML. Serum lactate dehydrogenase activity in patients with AIDS and Pneumocy8tis carinii pneumonia: an adjunct to diagnosis. Chest 1988; 94:103133

3 Smith RL, Ripps CS, Lewis ML. Elevated lactate dehydrogenase values in patients with Pneumocyatia carinii pneumonia. Chest 1988; 93:987-92 4 Zaman MK, White DA. Serum lactate dehydrogenase levels and Pneumocystis carinii pneumonia: diagnostic and prognostic significance. Am Rev Respir Dis 1988; 137:796-800 5 Garay SM, Greene J. Prognostic indicators in the initial presentation of Pneumocystis carinii pneumonia. Chest 1989; 95:769-72 1b the Editor: The observations of Drs McFadden and Oliphant on serum LDH levels in interstitial lung disease are interesting, but somewhat ambiguous. The study group of 81 patients is not well characterized in that fewer than half the patients had a definitive diagnosis established by biop~ Was the diagnosis in the remaining patients established by radiologic and physiologic criteria only? The uncertainty of diagnosis in the majority of cases weakens the authors' statement that serum LDH values are not useful in predicting the cause of interstitial lung disease. The authors then analyze the prognostic value ofserum LDH for all 81 patients, lumped together, irrespective of specific cause. Such an analysis, by definition, does not distinguish patients with cryptogenic fibrosing alveolitis or lung disease with a poor prognosis from patients with sarcoidosis or other lung diseases. It would be more useful to know the prognostic value of the serum LDH level, or any other serum marker for that matter, in patients within a specific disease category. The serum LDH level in patients with Pneumocystis pneumonia, on the other hand, is a useful prognostic marker, precisely because it is being applied to a single disease. Moreover, the changes in serum LDH levels are also useful prognostically as applied to Pneumocystis pneumonia specifically. The speculation that elevated serum LDH values reflect cellular hypoxia might have been supported by relating the LDH levels to the presence of hypoxemia or a widened a1veo~arterial Po. gradient. Is there a correlation between the degree of hypoxemia and the elevation of serum LDH concentration? Are the patients with LDH values greater than 650 UIL distinctive with regard to degree of hypoxemia? It may be that hypoxemia better correlates with prognosis in specific groups of patients.

Robert L. Smith, M.D., F.C.C.l, New York ~ans Affairs Medical Center; New York Communications to the EcItor