Congenital bronchiectasis in an adult

BRIEF CLINICAL

OBSERVATIONS

enzyme levels rapidly increased. Ten days after the operation, the arterial PO2 was 99.8 mm Hg, PC02 was 23.8 mm Hg, and pH was 7.25. Lactate levels were initially not measured but a lactate level of 23.6 mmol/L was determined on the following day. The patient was treated with 700 mmol of sodium bicarbonate over 12 hours and chemotherapy with MACOP-B [5] was instituted, which normalized the pH. The tumor rapidly regressed and the chemotherapy could be completed. There was no recurrence of acidosis. Four years after completion of therapy, the patient’s condition is in continued remission. Three patients with nonHodgkin’s lymphoma of intermediate- to high-grade malignancy involving the liver developed LA during the diagnostic work-up. Their circulatory status was not impaired at that time, and therefore increased lactate production by the tumor and/or impaired lactate metabolism by the liver has to be postulated. Since the normal liver is able to increase lactate utilization via gluconeogenesis and oxidation up to lofold, enhanced production of lactate by the tumor can alone hardly explain the marked lactacidemia in these cases. Thus, impairment of liver function by tumor infiltration and/or inhibition of enzymes by tumor products probably contributed to LA. The hypoglycemic episode in Patient 1 is most likely a consequence of impairment of gluconeogenesis due to the replacement of liver cells by lymphoma. Enhanced lactate formation by the tumor seems also to play a role since kinetic considerations suggest that cessation of a supposed hepatic lactate clearance of 40% is not followed by an enhanced lactate level, if lactate production remains constant [6]. The value of symptomatic therapy in LA is questionable. A 199

August

1991 The American

Journal

recent clinical study showed no difference in hemodynamic response to sodium bicarbonate and sodium chloride in critically ill patients with LA [7]. Impaired cardiac function has been observed after the administration of sodium bicarbonate in some patients and may be due to lowered intracellular pH. Another therapeutic option would be dichloroacetate, which has been successfully used to reverse LA [8]. However, no apparent benefit on overall survival could be demonstrated in patients with shock, sepsis, or liver failure. The usefulness of dichloroacetate in patients developing LA while being prepared for chemotherapy remains to be established. Although we did not observe any clinically apparent adverse effects of bicarbonate, the major improvement seen in our two patients that received bicarbonate was most likely due to the rapid cytoreduction achieved by simultaneously administered chemotherapy.

CONGENITAL BRONCHIECTASISIN AN ADULT

The possibility of a genetic disorder must always be considered in adult patients with pulmonary disease. In cases of generalized bronchiectasis, the possible congenital etiologies include cystic fibrosis, Kartagener’s syndrome, yellow nail syndrome, combined immunodeficiency, congenital tracheobronchomegaly, and Williams-Campbell syndrome. The last of these produces generalized thin-walled bronchiectasis as a result of a deficiency of bronchial cartilage. This report describes a 23-year-old patient with typical findings of this rare syndrome. The patient was the product of an uncomplicated pregnancy at 38% weeks’ gestation. He had an uneventful postnatal course and infancy. However, he was hospitalized for pneumonia at age 3, and again at age 3’%. As a small child, he noted the onset of dyspnea on exertion, which became CLEMENSB. CASPAR,M.D. more pronounced while he was in OSWALDOEL2,M.D. junior high school. The subseUniversity Hospital quent year, his symptoms proZurich, Switzerland gressed to the point where he was 1. Cohen RD, Woods HF. Clinical and biochemical aspects of lactic acidosis. Boston: Blackwell Scienable to ambulate only 100 yards tific Publications, 1976. without stopping. Despite his se2. Huckabee WE. Abnormal resting blood lactate. vere exercise limitation, he reAm J Med 1970; 30: 833-48. fused medical attention until age 3. Oliva PB. Lactic acidosis. Am J Med 1979; 48: 209-25. 23. He was referred to the Na4. Klimo P. Connors JM. MACOP-B chemotherapy tional Jewish Center for Immufor the treatment of diffuse large-cell lymphoma. nology and Respiratory Medicine Ann Intern Med 1985; 102: 596602. for further evaluation. 5. VanderMolen LA, Swain S. Lactic acidosis in lymphoma: prompt resolution of acidosis with therapy On examination, he was cyadirected at the lymphoma. J Natl Cancer lnst 1988; notic and moderately obese. The 80: 1077-8. result of head, eyes, ears, nose, 6. Woods HF, Connor H, Tucker GT. The role of aland throat examination was untered lactate kinetics in the pathogenesis of type B lactic acidosis. In: Metabolic acidosis. London: Pitremarkable except for mild nasal man Books Ltd. (Ciba Foundation Symposium 87). erythema and edema. Lung ex1982: 307-23. amination showed no rales, rhon7. Cooper DJ, Walley KR, Wiggs BR, Russell JA. Bichi, or wheezes except on forced carbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. Ann Intern expiration, when soft wheezes Med 1990; 112: 492-8. were heard. Cardiac examination 8. Stacpool PW, Lorenz AC, Thomas RG, Harman revealed no gallops, heaves, or EM. Dichloroacetate in the treatment of lactic acimurmurs. Extremities demondosis. Ann Intern Med 1988; 108: 58-63. strated If edema, but no clubSubmitted August 1. 1990, and accepted in revised form November 16. 1990 bing. of Medicine

Volume

91

BRIEF CLINICAL

Flgure 1. Posteroanterior demonstrating presence thin-walled cysts.

OBSERVATIONS

radiograph of multiple

Laboratory findings included the following arterial blood gas values: oxygen tension 36 mm Hg, carbon dioxide tension 57 mm Hg. A chest radiograph (Figure 1) revealed the presence of multiple thin-walled cysts, especially in the perihilar region. A sweat chloride level was 19.1 mEq/L, cul-antitrypsin level was 159 mg/dL (normal, 90 to 176 mg/dL), total hemolytic complement was 48 U/mL (normal, 22 to 43 U/mL), and Aspergillus titers were negative. A complete blood count showed a hemoglobin value of 14.7 g/dL and a hematocrit of 45.7%, with 56% neutrophils, 30% lymphocytes, 8% eosinophils, and 6% monocytes. Pulmonary function tests revealed a forced expiratory volume in 1 second of 1.01 L (22% of predicted), and a forced vital capacity of 2.50 L (30% of predicted). These improved after bronchodilator therapy to 1.27 L and 2.63 L, respectively. Total lung capacity was 113% of predicted, with a residual volume of 394% of predicted. Diffusing lung capaci-

ty for carbon monoxide was 28% of predicted. A pressure-volume curve showed a reduced coefficient of retraction of 1.8 cm water/L. An exercise study demonstrated that the patient was only able to exercise to 35 W. The dead space to tidal volume ratio was elevated at rest to 53% and rose during exercise to 58%. There was a slight decrease in the alveolar-arterial gradient, with an increase in arterial carbon dioxide tension from 63 mm Hg to 71 mm Hg. The minute ventilation approached the ventilatory ceiling. The cardiovascular response to exercise was normal. Bronchoscopy was performed and revealed markedly collapsible airways, with near total collapse on expiration. Bronchoal veolar lavage was performed with a yield of 9.59 X lo6 white blood cells. The differential showed 52.7% macrophages, 36% neutrophils, 7% eosinophils, and 5% lymphocytes. Transbronchial biopsy specimens demonstrated a nonspecific chronic bronchitis with basement membrane thickAugust

1991

The American

ening. The alveolar interstitial architecture was normal. A computed tomographic (CT) scan of the chest (Figure 2) revealed that the cystic changes were bronchocentric with initial narrowing and verrucous changes of the central bronchi, with subsequent marked cystic peripheral changes. High-resolution slices of the right lung demonstrated the extensive cystic dilatation of the airways. A CT scan of the chest performed on expiration (Figure 3) revealed significant collapse of the right and left mainstem bronchi, as well as the origins of all the central bronchi. There was also loss of volume in the peripheral bronchiectatic segments. Inferior lung fields had marked air trapping, and were unable to completely expire. This was believed to be diagnostic of WilliamsCampbell syndrome. As there is no specific treatment, the patient was placed on home oxygen and was taught postural drainage and chest percussion. He was unable to tolerate a continuous positive airway presJournal

of Medicine

Volume

91

199

BRIEF CLINICAL

OBSERVATIONS

Figure 2. Chest chocentric cystic

CT scan changes

showing

br ‘on-

Figure 3. Chest CT scan performed on expiration, at the same level as Figure 2. Significant collapse of mainstem and central bronchi with volume loss in peripheral bronchiectatic segments is demonstrated.

sure mask. He was also placed on the list of patients for possible lung transplantation. In 1960, Williams and Campbell [l] reported five children 200

August

1991

The American

Journal

with generalized bronchiectasis, the remarkable feature being soft, compliant bronchi that dilated and collapsed during inspiration and expiration. The cliniof Medicine

Volume

91

cal course of the children varied, with death occurring in two of the five during follow-up periods of up to 9 years. A subsequent autopsy of one of these children

BRIEF CLINICAL

showed an extensive deficiency of cartilage distal to the first division of the segmental bronchi, in a symmetric pattern, resulting in thin-walled bronchiectasis. Williams and Campbell postulated that the bronchiectasis was developmental due to its uniform symmetry and lack of inflammation in adjacent noncartilaginous structures. In 1976, Wayne and Taussig [2] reported the familial occurrences of this syndrome in two siblings. The familial pattern, early onset of symptoms, and similarity in the distribution of lesions support the theory of a congenital basis for this variety of bronchiectasis. In 1972,ll more children with the syndrome were described by Williams et al [3]. The clinical features of these children included chronic cough, episodic wheezing, dyspnea, and recurrent respiratory infections. Pulmonary function testing revealed hyperinflation with obstruction to airflow and decreased conductance. Additionally, pressure-volume curves demonstrated loss of elastic recoil. Pulmonary function testing in our patient yielded similar results. Last, bronchography demonstrated dilated bronchi with cystic cavities and alternating ballooning and collapse with respiration. Chest radiographs typically show hyperinflated lung fields with cystic dilatation of bronchi and, less commonly, associated segmental or lobar atelectasis. A case report of an adult with the syndrome describes CT scan findings of saccular dilatation of bronchi with expiratory collapse [4]. This phenomenon was also demonstrated in our patient. This pattern of expiratory bronchial collapse is an extremely rare finding in postinfective cystic bronchiectasis [5]. In summary, we report a case of congenital bronchiectasis, known as Williams-Campbell syndrome, diagnosed in adulthood. This is

the first report of a complete evaluation of such a patient including physiologic, radiologic, bronchoscopic, and bronchoalveolar lavage results. Currently, there is no pathologic approach to diagnosis, except for autopsy. The diagnosis of WilliamsCampbell syndrome must be considered in adults who present with thin-walled bronchiectasis. KENNETH B. NEWMAN,M.D. National Jewish Center for Immunology and Respiratory Medicine

WILLIAMR. BEAM,M.D.

University

of

Colorado Health Sciences Center Denver, Colorado

1. Williams H, Campbell P. Generalized bronchiectasis associated with deficiency of cartilage in the bronchial tree. Arch Dis Child 1960; 35: 182-91. 2. Wayne KS, Taussig LM Probably familial congenital bronchiectasis due to cartilage deficiency (Williams-Campbell syndrome). Am Rev Respir Dis 1976; 114: 15-22. 3. Williams HE, Landau LI, Phelan PD. Generalized bronchiectasis due to extensive deficiency of bronchial cartilage. Arch Dis Child 1972; 47: 423-8. 4. Watanabe Y. Nishiyama Y. Kanayama H. Enomoto K, Kato K, Takeichi M. Congenital bronchiectasis due to cartilage deficiency: CTdemonstration. J Comput Assist Tomogr 1987; 11: 701-3. 5. Fraser RG. Macklem PT, Brown WG. Airway dynamics in bronchiectasis. A combined cinefluorographic-manometric study. Am J Roentgen01 Radium Ther Nucl Med 1965; 93: 821-35. Submitted

November 7, 1990, and accepted in revised form February 25, 1991

EXCESSIVESALIVATIONAS AN ANGINAL EQUIVALENT:A SEQUELATO RAMSAY HUNT SYNDROME Signs of autonomic disturbance are common during acute myocardial infarction. Webb et al [l] found excessive vagal activity in 41 of their series of 71 patients with acute infarction. Bradyarrhythmias and hypotension are frequently seen in acute inferoposterior wall infarction and are thought to result from stimulation of sensory receptors in this region of myocardium. The Bezold-Jarisch reflex results from stimulation of these sensory receptors, with impulses traveling afferently along the vagus August

1991 The American

OBSERVATIONS

nerve and efferently along the parasympathetic vasodilators and visceral motor nerves of the thorax and abdomen, also along the vagus nerve [2]. We describe a patient with excessive parasympathetic activity, hypersalivation, as an unusual anginal equivalent at presentation with acute myocardial infarction. A 71-year-old male psychiatrist was admitted to the hospital with complaints of excessive salivation and chest pain. Ten years prior to admission, the patient had a myocardial infarction and three-vessel revascularization surgery. Over the next 8 years, the patient was without cardiac symptoms. Three years before admission, the patient was evaluated by a neurologist for a right facial palsy associated with herpetit lesions on the right forehead and right posterior pharynx. The patient was given the diagnosis of Bamsay Hunt syndrome. Except for a slight right facial droop, these symptoms promptly resolved. Approximately 18 months prior to admission, the patient developed “chest heaviness” on exertion. Evaluation included thallium treadmill testing showing 3-mm ST depression in anterolateral leads associated with a reversible septal perfusion defect. Coronary angiography revealed diffuse atherosclerotic obstruction in the saphenous vein grafts and native coronary arteries. Medical management was advised and the patient’s symptom of “chest heaviness” on exertion resolved with oral nitrates and a calcium channel blocker. One year before admission, the patient began experiencing episodes of hypersalivation associated with heavy exertion. Whether running to catch a bus, playing tennis, or climbing stairs, the patient would experience excessive salivation, sometimes associated with nausea and emesis, lasting 5 to 10 minutes and resolving with Journal

of Medicine

Volume

91

201