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Mayo Clin Proc. 2010 June; 85(6): e36–e39.
PMCID: PMC2878262

68-Year-Old Man With Chronic Cough and Weight Loss

A 68-year-old man presented to the pulmonary clinic at Mayo Clinic for evaluation of chronic cough and weight loss. He had a medical history of stroke, insomnia, chronic mucocutaneous candidiasis, spontaneous left-sided pneumothorax, and pneumonia. He had been in good health until experiencing a left pontine stroke in 2006, which caused transient right-sided weakness and dysphagia. Although these symptoms resolved, a cough continued for 18 months before evaluation. Findings on chest radiography and a pulmonary function test were normal 5 months before evaluation. The cough had recently become productive, and the sputum was occasionally red. The patient thought the cough was worse when he was in certain positions. His cough was not triggered by exertion or fumes. He denied sinus disease, postnasal drip, gastroesophageal reflux, and asthma. He had never been a smoker. He had no relevant chemical, occupational, or animal exposures. He reported fever, chills, and a weight loss of 13.6 kg (30 lbs) during the previous 2 months. One month before evaluation, he developed hemoptysis. He was found to have a pleural effusion and was treated for pneumonia at another hospital. Cultures from a bronchoscopy and thoracentesis were reportedly negative. He did not complete the antibiotic course because of mucocutaneous candidiasis.

  1. On the basis of the available clinical information, which one of the following conditions is the least likely explanation?
    1. Chronic obstructive pulmonary disease (COPD)
    2. Mycobacterium tuberculosis infection
    3. Lung cancer
    4. Aspiration pneumonia
    5. Human immunodeficiency virus (HIV)
    Chronic cough is defined as a cough lasting more than 8 weeks.1 Asthma, gastroesophageal reflux, and postnasal drip are the most common causes of cough. This patient denied having a history or symptoms of these diseases. Chronic obstructive pulmonary disease is also a well-known cause of chronic cough, with 70% of patients with COPD reporting coughing.1 Chronic obstructive pulmonary disease is highly associated with cigarette smoking. The patient denied any occupational exposures that would put him at risk of COPD. Hemoptysis is not associated with COPD.2 Common causes of hemoptysis include pulmonary infection, bronchiectasis, lung cancer, pulmonary or gastrointestinal hemorrhage, bronchitis, and chronic heart failure.2 Pulmonary function studies show airflow obstruction in patients with COPD. Because the patient had never smoked, had hemoptysis, and did not have airway obstruction as evidenced by normal findings on a pulmonary function test, COPD is the least likely diagnosis. Mycobacterium tuberculosis is commonly in the differential diagnosis of patients with cough, hemoptysis, fever, and weight loss. This infection is a public health risk and a treatable disease. Because the patient had all of these symptoms, this diagnosis was important to exclude. On the basis of these findings, tuberculosis cannot be ruled out. Lung cancer is also a concern in any patient who presents with these symptoms. Having experienced dysphagia after his stroke in 2006, the patient was at risk of aspiration and aspiration pneumonia. Although he was not at high risk of HIV, his weight loss, fever, and chills could be due to HIV. His history of chronic mucocutaneous candidiasis increased the possibility that he was immunosuppressed, supporting a diagnosis of HIV.
    For a month after the cessation of antibiotic treatment, the patient continued to experience daily fevers, diaphoresis, and weight loss, prompting a visit to the outpatient pulmonary clinic at Mayo Clinic. Computed tomography performed elsewhere showed a left lower lobe consolidation with a pleural effusion. Computed tomography of the chest was ordered to reassess the extent of the patient's lung disease and revealed persistent left lower lobe consolidation and a loculated effusion on the left side measuring 6 cm × 9 cm. There was also evidence of left hilar and mediastinal adenopathy. Laboratory studies revealed negative findings on HIV serology and on the interferon-γ assay for M tuberculosis, an elevated C-reactive protein, and an elevated white blood cell count.
  2. Which one of the following tests would be the most helpful at this time?
    1. Pulmonary function test
    2. Thoracentesis
    3. Bronchoscopy
    4. Sputum culture
    5. No further testing needed; initiate antibiotic therapy
    A pulmonary function test would likely reveal a restrictive pattern due to the effusion. It would not change the current management or help establish a diagnosis at this stage. Diagnostic thoracentesis can aid in establishing a diagnosis and can affect the treatment plan in patients with new pleural effusions because some patients may require chest tube placement for drainage. Almost all patients who present with a new pleural effusion should have a diagnostic thoracentesis.3 Thoracentesis is the test that would be most helpful at this time to determine the diagnosis and need for drainage. Bronchoscopy may have a role in the evaluation of this patient to determine the etiology of his effusion. Bronchoalveolar lavage can help to identify malignancy or infection. It is not the best next test at this time because the initial primary concern in patients with pleural effusion is the need for chest tube placement for drainage. Findings on sputum culture would help guide therapy but would not identify a malignancy or establish whether chest tube drainage is needed. Although antibiotics should be initiated if an infection is identified, not all pleural effusions are due to infection and so further evaluation and testing are needed.
    Diagnostic ultrasonography-guided thoracentesis showed 45 mL of whitish-brown viscous fluid, which was cytologically negative for malignant cells and which had a glucose level of 41 mg/dL and a lactate dehydrogenase (LDH) level of 13,640 U/L.
  3. Which one of the following is the most likely diagnosis on the basis of the pleural fluid sample analysis?
    1. Transudative effusion
    2. Simple parapneumonic effusion
    3. Complicated parapneumonic effusion
    4. Empyema
    5. Malignant effusion
    The first step in evaluating pleural fluid is to determine whether it is transudative or exudative. Exudative fluid is defined by a ratio of pleural fluid to serum total protein of greater than 0.5, a ratio of pleural fluid to serum pleural fluid LDH of greater than 0.6, or a pleural fluid LDH that is greater than 0.67 of the upper limit of normal for serum LDH levels.3 If none of these criteria are met, the effusion is most likely a transudate.3 If infection is a concern, pH, LDH levels, glucose, nucleated cell count, cytology, Gram stain, and culture are helpful. Unfortunately, serum LDH and protein levels were not obtained to compare to the pleural fluid levels because the tests were ordered in the outpatient setting and the patient was directly admitted to the hospital before his blood draw. The pH was not reported for the fluid. Fortunately, this was unnecessary for diagnosis, as evidenced by the definitions of the various types of effusions. Simple parapneumonic effusions are sterile exudative effusions.4 Complicated parapneumonic effusions are diagnosed when fluid analysis demonstrates a pH of less than 7.2, a glucose level of less than 35 mg/dL, and an LDH level greater than 1000 U/L.4,5 Empyema is defined by accumulation of pus in the pleural space as a result of pleural infection.5 The evidence of frank pus from the thoracentesis confirmed the diagnosis of empyema. Although serum LDH levels, serum protein levels, and the pleural fluid pH would have been helpful, they were not necessary for diagnosis once the pus was obtained during the thoracentesis. This effusion was unlikely to be malignant because the fluid analysis strongly supported an infectious process.
  4. Which one of the following is the next best step in the treatment of this patient?
    1. Chest tube placement
    2. Antibiotic therapy
    3. Antibiotic therapy and chest tube placement
    4. Antibiotic therapy, chest tube placement, and therapy with intrapleural thrombolytic agents
    5. Antibiotic therapy and thoracotomy with decortication
    Complicated parapneumonic effusions and empyema require drainage with a chest tube.4 Chest tube placement alone is not an adequate therapy. All patients with pleural effusion due to infection require antibiotic therapy. Empiric antibiotics should be started until culture results are available.4 Antibiotic choice should be guided by concern for community-acquired infection vs hospital-acquired infection. Alone, neither chest tube placement nor antibiotic therapy is sufficient; however, together they represent the next best step in the treatment of this patient. Intrapleural fibrinolytic therapy is controversial and is not recommended as an initial treatment for empyema.4,6-8 Thoracotomy with decortication may be necessary if the patient is not clinically and radiologically improving with standard treatment but is not an initial treatment of empyema.4
  5. Which one of the following organisms is most commonly identified as the cause of community-acquired empyema?
    1. Streptococcus pneumoniae
    2. Staphylococcus aureus
    3. Streptococcus milleri
    4. Pseudomonas species
    5. Methicillin-resistant S aureus (MRSA)
    Gram-positive aerobic bacteria are the most common cause of pleural infection in community- and hospital-acquired pulmonary infections. S pneumoniae represents approximately 10% to 25% of cases with pleural infection.4 Staphylococci have been found to constitute 11% of pathogens in community-acquired pleural infections4 and 18% of pathogens in hospital-acquired pleural infections in the Multicenter Intrapleural Sepsis Trial 1 (MIST1).7 The S milleri group is the most common pathogen identified in culture in 32% of community-acquired pleural infections.4 Pseudomonas species occur more frequently in hospital-acquired pleural infections.4 Representing 28% of positive cultures, MRSA is one of the most common causes of hospital-acquired pleural infection.4
    Our patient was admitted by the outpatient pulmonologist to the general medicine service for chest tube placement and intravenous antibiotics because the effusion could not be completely drained with thoracentesis. Vancomycin and piperacillin-tazobactam were initiated pending culture results. A chest tube was placed by interventional radiology for drainage of the pleural fluid. The cultures subsequently grew Streptococcus viridians, a common oral bacterium. The bacteria were susceptible to penicillin, ceftriaxone, vancomycin, and erythromycin. Concern for aspiration prompted a swallow study, the findings on which were normal. Infectious disease consultation suggested that the patient may have been experiencing chronic microaspiration that led to pneumonia and empyema. His medication was switched to intravenous ertapenem daily in preparation for intravenous antibiotic treatment at home. Ertapenem was selected because the infection could be polymicrobial, necessitating anaerobic coverage. Follow-up computed tomography of the chest showed that he continued to have a loculated pleural effusion and consolidation despite the drainage. Due to the persistent effusion, the thoracic surgery service proceeded to administer fibrinolytic agents through the chest tube, resulting in marked increase in chest tube output. Chest radiography showed improvement, and the patient was discharged with a catheter for continued drainage and instructions to complete a 6-week course of intravenous antibiotic therapy at home. He returned to Mayo Clinic 1 month later. The pleural effusion had completely resolved, and his infiltrates were improved. His appetite had improved, and he had gained 1 kg. He has continued to do well since that time.

DISCUSSION

Pleural effusions are frequently seen in hospitalized patients, and almost all of these patients should undergo a diagnostic thoracentesis for further evaluation.3 Effusions can evolve into empyema, which has considerable morbidity and mortality.4 The annual incidence in the United States is 60,000 cases,4 and mortality rates of 10% to 20% have been reported.4,5 Thus, performing a thoracentesis and analyzing the pleural fluid is of paramount importance.

The causes of empyema include bronchopulmonary infection, thoracic or esophageal surgery, infradiaphragmatic sepsis, and idiopathic causes. Bronchopulmonary infection may be due to pneumonia, aspiration, or bronchopleural fistulas.4,9 In one study, neurologic injury or illness was the contributing cause of empyema in 13 (18%) of 71 patients; in 7 of the 13 patients, empyema was caused by aspiration.10 Other risk factors for empyema include diabetes mellitus, alcohol abuse, gastroesophageal reflux disease, intravenous drug use, carcinoma, cirrhosis of the liver, malnutrition, bronchiectasis, and HIV.4,9 Up to one-third of cases occur with no identified risk factor.4

Diagnostic thoracentesis can aid in the diagnosis and the treatment plan for almost all pleural effusions. The exceptions to this rule are patients with typical chronic heart failure or patients with a very small effusion (<10 mm on lateral decubitus chest radiography).1,4 Pleural fluid analysis can be the basis of a definitive diagnosis if cytology is positive or an organism is isolated.1 It is especially helpful in determining if an effusion will require drainage because radiologic findings and an elevated white blood cell count cannot reliably predict who will need this intervention.4 Antibiotic therapy and chest tube placement are the initial treatment measures for patients with a complicated parapneumonic effusion and empyema.4 Some evidence supports that a pleural fluid pH of less than 7.2 is the best predictor of effusions requiring chest tube drainage.4 How long the chest tube should remain in place for optimal treatment remains unclear, but removal of the chest tube can be considered when the patient has clinically improved and output has markedly decreased.4 Empiric antibiotics should be initiated while waiting for culture results. Community-acquired infections should have coverage for gram-positive cocci such as Streptococcus species with a second-generation cephalosporin or an aminopenicillin with a β-lactamase inhibitor plus anaerobic coverage.4 Hospital-acquired infections require broad-spectrum antibiotics with coverage for MRSA.4 The duration of therapy has not been adequately studied, but most information recommends at least 3 weeks of antibiotic therapy with at least 1 week of intravenous antibiotics.4

If antibiotic therapy and chest tube placement fail, the next best step in management remains controversial. Some randomized controlled trials have demonstrated a high success rate with the use of fibrinolytic agents.4,6,8,11 One study of 53 patients by Diacon et al11 showed a higher clinical success rate with intrapleural streptokinase vs intrapleural saline, with 9% vs 45% of patients requiring surgical intervention, respectively. However, this advantage for intrapleural streptokinase was brought into question by a 2006 meta-analysis showing that the benefits associated with its use (eg, decreased hospital stay, improved radiographic appearance, and decreased rate of surgery) were inconsistent across studies.4,6 The controversy developed after the MIST1 study, which included 454 patients with empyema who were randomized to receive intrapleural fibrinolytic therapy or intrapleural saline in addition to antibiotics and chest tube drainage, showed no difference in the rates of death or surgery at 3 or 12 months.4,6,7 This has been the only study powered to address mortality and the need for surgery.4 Although fibrinolytic agents are not part of the initial management of empyema, they have been found to aid in thoracic decompression; thus, they may have a role in the treatment of selected patients.4,6 More studies are needed to determine the utility of fibrinolytic agents. Patients whose condition does not clinically and radiographically improve after 7 days of standard treatment should have a consultation to determine if they are candidates for surgical intervention. Video-assisted thoracoscopic surgery can be used to divide adhesions and septae to allow for better drainage through the chest tube.4,8 However, this procedure may not be sufficient, and thoracotomy with decortication may be needed.4 Thoracotomy with decortication has been reported to have a 95% success rate in certain groups with associated decreases in length of stay and drainage times.4 This surgical treatment may aid in the recovery of lung function and in the prevention of sepsis.4

When evaluating a patient with chronic cough, fever, and weight loss, the differential diagnosis commonly includes lung cancer, M tuberculosis infection, HIV, COPD, and interstitial lung disease. In this case, chronic aspiration with empyema was the cause. Aspiration is a known risk factor for empyema, and patients with dysphagia after stroke are at risk of aspiration. Recognition of this risk and appropriate diagnostic work-up can help prevent morbidity and mortality. This case demonstrates the potential long-term risks of chronic aspiration and the importance of performing a diagnostic thoracentesis in patients with significant effusions.

Notes

See end of article for correct answers to questions.

correct answers: 1. a, 2. b, 3. d, 4. c, 5. c

REFERENCES

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3. Sahn SA. The value of pleural fluid analysis. Am J Med Sci. 2008;335(1):7-15 [PubMed]
4. Rahman NM, Chapman SJ, Davies RJ. The approach to the patient with a parapneumonic effusion. Clin Chest Med. 2008;27(2):253-266 [PubMed]
5. Ahmed RA, Marrie TJ, Huang JQ. Thoracic empyema in patients with community-acquired pneumonia. Am J Med. 2006;119(10):877-883 [PubMed]
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8. Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment of parapneumonic effusion: an evidence-based guideline [published correction appears in Chest. 2001;119(1):319] Chest 2000;118(4):1158-1171 [PubMed]
9. Alfageme I, Munoz F, Pena N, Umbria S. Empyema of the thorax in adults: etiology, microbiologic findings, and management. Chest 1993;103(3):839-843 [PubMed]
10. Ashbaugh DG. Empyema thoracis: factors influencing morbidity and mortality. Chest 1991;99(5):1162-1165 [PubMed]
11. Diacon AH, Theron J, Schuurmans MM, Van de Wal BW, Bollinger CT. Intrapleural streptokinase for empyema and complicated parapneumonic effusions. Am J Respir Crit Care Med. 2004;170(1):49-53 [PubMed]

Articles from Mayo Clinic Proceedings are provided here courtesy of The Mayo Foundation for Medical Education and Research