Older Man With Worsening Dyspnea,Chest Discomfort, and Cough

For the past 3 months, a 72-year-old man has had progressively worsening dyspnea on exertion and constant vague discomfort in the left chest that appears to have a pleuritic component. He denies paroxysmal nocturnal dyspnea and has no history of chest trauma. However, he has a chronic cough that sometimes produces purulent sputum-although it is not associated with hemoptysis. His feet swell occasionally, and he has mild anorexia and has lost 20 lb in 6 months.

HISTORY
Mild chronic obstructive pulmonary disease and congestive heart failure (CHF) were diagnosed 1 year earlier. His regimen includes theophylline, several different aerosolized medications, and an angiotensin-converting enzyme inhibitor. The patient is a former heavy smoker (80 pack-year history), but he has not smoked during the previous year. Six months earlier, a chest radiograph showed mild cardiomegaly and flattened diaphragms, and an echocardiogram revealed an ejection fraction of 40%.

PHYSICAL EXAMINATION
The patient appears his age and is in no acute distress. Temperature is 37^oC (98.6^oF); respiration rate, 22 breaths per minute; and blood pressure, 110/70 mm Hg.No adenopathy is evident in the neck, supraclavicular region, or axillae. Heart tones are distant. Breath sounds are normal in the right chest but markedly diminished in the left; the left chest is also dull to percussion and tactile fremitus is decreased. There is no peripheral edema. The remainder of the physical examination is normal.

LABORATORY AND IMAGING RESULTS
Results of a hemogram and serum chemistry panel are normal. A chest radiograph reveals a large left pleural effusion. Thoracentesis is performed, and the removal of pleural fluid significantly alleviates the patient’s respiratory symptoms. The fluid is grossly bloody. Analysis of the fluid reveals a red blood cell count of 300,000/μL; a hematocrit of 4%; and a white blood cell (WBC) count of 6000/μL with 60% lymphocytes, 35% polymorphonuclear neutrophils (PMNs), and 5% other leukocytes. Protein level is 4.2 g/dL (serum protein, 6.2 g/dL); lactate dehydrogenase (LDH), 200 IU/L (serum, 315 IU/L); and pH, 7.15.

Which of the following represents the most likely cause of the pleural effusion and the most appropriate next step and/or probable outcome?A. The effusion is related to CHF and will respond to diuretics.
B. The effusion represents tuberculosis, which can best be confirmed by a pleural fluid culture for Mycobacterium tuberculosis.
C. The effusion is the result of a pyogenic infection and will respond to parenteral antibiotics.
D. The effusion is attributable to a malignancy and will respond poorly to pleurodesis.
E. The effusion results from a pulmonary embolism, which can be confirmed by pleural fluid D-dimer assay. CORRECT ANSWER: D
The history is highly useful in the creation of a reasonable differential diagnosis for this patient. He has sustained no trauma, is afebrile, has mild CHF, and has a significant smoking history. Thus, tumor and CHF are more likely causes of the pleural effusion than trauma and pyogenic infection.

Thoracentesis is helpful in this setting. The patient meets at least 2 criteria for the procedure. He has a pleural effusion of substantial size (more than 10 mm thick) that is causing significant respiratory compromise. This alone is sufficient indication for fluid removal. In addition, he is symptomatic. Although the patient has a history of CHF (typically associated with bilateral effusions), his effusion is asymmetric; this suggests other causes.

Analysis of the pleural fluid further narrows the differential.Gross blood in the fluid indicates that cancer is by far the most likely diagnosis, followed by pulmonary embolism, trauma,and pneumonia.^1,2The fluid hematocrit is in a range (1% to 20%) that suggests a tumor, pulmonary embolism, or trauma. The Ddimer assay (choice E) is a reasonable screening study for patients with suspected pulmonary embolism.³However, the D-dimer assay discussed in the literature uses serum, not pleural fluid. Moreover, this patient’s symptoms are chronic rather than acute and are not typical of pulmonary embolism; the dyspnea is disproportionate to the size of the effusion, and he has not had hemoptysis. Thus, choice E is likely incorrect on clinical grounds as well.

The fluid protein and LDH values show this to be an exudative rather than a transudative effusion by traditional Light criteria.^1,2This rules out CHF (choice A), which causes a transudative effusion.

The fluid cell count-particularly the WBC differential- also narrows the differential. Although not pathognomonic, the lymphocytic predominance implies a chronic process. PMNs are predominant in most acute pyogenic effusions. Even if this were a chronic pyogenic process of some sort, the low pH suggests that antibiotics alone would be ineffective and that drainage would be required.⁴ Thus, choice C is incorrect on several counts.

Tuberculosis can cause an exudative effusion with lymphocytic predominance. However, culture of pleural fluid (choice B) is a relatively poor confirmatory study; the diagnostic accuracy is only 40%. Newer, better methods of confirming tuberculous pleurisy use pleural fluid adenosine deaminase measurements and detection of M tuberculosis DNA by polymerase chain reaction, which are more than 95% accurate.⁵

The clinical findings and the grossly bloody appearance, exudative nature, and small-cell predominance of the pleural effusion point to a tumor as the most likely cause. Cytology is confirmatory in about 70% of patients. A chest CT scan can reveal any nodules or primary lesions in the underlying lung that warrant further studies, such as bronchoscopy or thoracoscopy.

The low pH here indicates an ominous prognosis. A pH of less than 7.2 in cancerous effusions is associated with very short survival and with failure of pleurodesis maneuvers to provide relief.²Thus, choice D is correct.

Outcome of this case. The cytology showed class V adenocarcinoma. The patient died of respiratory failure several weeks later.

References:

REFERENCES:

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Light RW, Erozan YS, Ball WC Jr. Cells in pleural fluid: their value in differentialdiagnosis.

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Light RW. Pleural effusion.

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Ahearn GS, Boundmeaux H. The role of D-dimer in the diagnosis of venousthromboembolism.

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Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment ofparapneumonic effusions: an evidence-based guideline.

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Lee YC, Rogers JT, Rodriguez RM, et al. Adenosine deaminase levels in nontuberculouslymphocytic pleural effusions.

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