When your patients are coughing up blood

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Hemoptysis can signal conditions ranging from the mild to life-threatening. Here's how to determine which cases demand immediate intervention.

Hemoptysis is frequently encountered by primary-care clinicians. Most cases are self-limiting or resolve with treatment of an underlying condition. But the expectoration of blood can also be a symptom of an acute or life-threatening illness, such as pneumonia, pulmonary embolism, or lung cancer. The challenge for the clinician is to separate the cases with a less serious etiology from those that demand immediate intervention.

Making that distinction requires interpretation of key history and physical exam findings, the ordering of appropriate diagnostic studies, formulating a differential diagnosis, and knowing when to refer to a specialist. The two patients described below illustrate the types of cases a clinician may see in a primary-care practice.

Patient 1

A 35-year-old overweight woman with diabetes and a history of chronic bronchitis complains that for several days she has had a worsening cough productive of greenish sputum containing streaks of blood. She had just recovered from the flu and was feeling somewhat better until the coughing started. While the patient has had bronchitis in the past, she has never had blood in her phlegm.

She does not smoke. Currently, she takes medication for diabetes and hyperlipidemia. Her vital signs are stable, and she does not appear to be in distress. Her lung exam is unremarkable except for a wet-sounding cough.

Patient 2

A 65-year-old man presents with a weeklong history of coughing up two to three teaspoons of blood daily. He cannot recall precisely when it started but says that he has also been “sick.” Over the past week or so, he has developed worsening shortness of breath and dyspnea on exertion.

His usually clear sputum has become purulent. The patient also reports night sweats and unintentional weight loss. For the past 40 years, he has smoked a pack of cigarettes a day. He takes medication for hypertension and uses inhalers for emphysema. Examination reveals low-grade fever and mild tachycardia. He is cachectic, has poor breath sounds throughout all lung fields, and has localized rhonchi in his mid-right back.

A review of the lung anatomy and the patient-evaluation process will help diagnose these patients.

Where the bleeding comes from

The lungs have two main blood supplies: the pulmonary arterial circulation and the bronchial circulation. Damage to the alveoli and the lungs' vascular bed can lead to hemoptysis. The airways are supplied by a branch of the aorta and branching intercostal arteries. Bleeding occurs within the airways, lung parenchyma, or pulmonary capillary bed after inflammation, trauma, or erosion in one or both of the two main blood supplies. Blood flowing through the pulmonary capillary bed is supplied by the relatively lower-pressure right ventricle and pulmonary arteries. Since the bronchial circulation is under systemic pressure, erosion there can be a source of more significant bleeding (Table 1).

Evaluation

Any patient presenting with hemoptysis requires an immediate evaluation of the ABCs—Airway, Breathing, and Circulation. Clinicians should be alert for any signs of cyanosis around the lips, mouth, and tongue (central cyanosis), as well as in the fingernail beds, hands, and feet (peripheral cyanosis). Central cyanosis typically corresponds to an oxygen saturation ≤75%-80%. Peripheral cyanosis may also be caused by anxiety or a cold examination room. A lower level of consciousness can indicate hypoxemia. A quick check for a patent airway and possible hemodynamic collapse is crucial in patients with serious bleeding, as is taking vital signs with pulse oximetry.

Hemoptysis can range from small flecks or streaks of blood in the sputum to frank blood or clots without sputum. Determining the amount of blood is a key diagnostic step. Most experts define “massive” hemoptysis as expectorating >200 cc per 24 hours1; any amount less than that is termed “nonmassive.” The patient should be asked to quantify the amount of bleeding. It can be helpful to use familiar measurements (e.g., teaspoons or cupfuls). Most outpatients will present with nonmassive hemoptysis. Any significant amount of bleeding over a short period of time (e.g., 60 cc over two hours) should be treated as massive hemoptysis.2

Next, distinguish between actual hemoptysis vs. bleeding from the upper airway or regurgitated blood from the upper GI tract. To this end, the history should focus on prior or current episodes of epistaxis, GI symptoms (e.g., nausea and vomiting), and pain associated with eating. Find out if the patient has been taking aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or warfarin.

Timing of the bleeding and the color and consistency of the blood can also be helpful in distinguishing hemoptysis from upper GI bleeding—blood that has been swallowed or digested is usually regurgitated as “coffee grounds.” Hemoptysis can be a presenting symptom of pulmonary embolism (PE), though this occurs in fewer than 20% of cases. The classic triad of PE symptoms consists of hemoptysis, dyspnea, and chest pain. Risk factors for thromboembolic disease should also be ascertained, such as prolonged immobilization from surgery or illness or recent travel.

Smoking history and use of illicit substances must be explored because smoking raises the risk of related lung disease. Inhaled substances, especially cocaine, are directly toxic to the lung parenchyma and vasculature. Malignancy is suggested by unintentional weight loss, unexplained fevers, and malaise.

Hemoptysis is also a possible complication of community-acquired pneumonia (CAP), but the bleeding usually resolves within a few days of antibiotic therapy. Presence of hemoptysis is typically associated with necrotizing pneumonia. A particularly virulent strain of methicillin-resistant Staphylococcus aureus (MRSA), the Panton-Valentine leukocidin (PVL) variant, has been recognized with increased frequency as the causative agent of necrotizing CAP. PVL-MRSA, which primarily affects children and young adults, is usually preceded by a viral syndrome, particularly influenza A. There is a 75% mortality rate associated with PVL-MRSA pneumonia, and the suspicion of the diagnosis, raised, for example, by infiltrates, warrants hospitalization3 (Figure 1).

Frequent or daily production of foul-smelling sputum may suggest bronchiectasis, a condition in which the bronchi and terminal bronchioles are chronically inflamed and permanently dilated (Figure 2). Their associated blood supplies have become remodeled and distorted. Patients with bronchiectasis typically produce copious sputum, especially in the morning. The sputum is often foul-smelling and streaked with blood. Bronchiectasis can be caused by repeated pulmonary infections leading to mucus plugging, immunoglobulin deficiencies, cystic fibrosis, and other less common conditions.4,5 In fact, bronchiectasis in an adult may be the only manifestation of a cystic fibrosis variant.6 Treatment often involves antibiotics and aggressive pulmonary hygiene.7,8

In patients with hemoptysis, sinus troubles (with or without epistaxis) and hematuria raise the suspicion of autoimmune disease, such as Wegener's granulomatosis, a form of vasculitis that affects the lungs and other organs. Goodpasture's syndrome (a rare autoimmune disease affecting the lungs and kidneys also known as anti-glomerular basement membrane disease) should be suspected in any patient with hemoptysis and glomerulonephritis.

The physical examination

Patient evaluation should include a thorough examination of the upper airway and teeth to determine if dental abscess or gum disease is the source of blood that is simply being spit out or perhaps has been aspirated and coughed back up. Neck, axillary, and supraclavicular lymph nodes should be palpated to check for swelling, which can be caused by an infection or a malignancy. Palpation and auscultation of the precordium will help detect a displaced point of maximal impulse as well as additional heart sounds and murmurs associated with congestive heart failure and mitral stenosis. The lungs should be auscultated for areas of diminished breath sounds and signs of consolidation. Pay special attention to areas of diffuse or localized wheezing suggestive of obstructive lung disease (i.e., chronic obstructive pulmonary disease [COPD], chronic bronchitis) or partial airway obstruction caused by foreign body or mass. Use of accessory muscles should be noted. If an upper GI source of bleeding is suspected, an abdominal exam with focus on epigastric pain is called for. Hands should be inspected for digital clubbing, which occurs with long-standing hypoxia or malignancy. Lower extremities should be examined for asymmetry or calf pain, which may be a clue to thromboembolic disease.

While most hemoptysis is caused by infectious or other serious conditions, there are instances in which this condition can be rather benign. One such cause would be airway microtrauma from repeated coughing episodes. Bacterial and viral syndromes frequently have an associated cough that can last for weeks.

Diagnostic studies

A complete blood count and coagulation studies should be ordered. Unless the history and physical exam suggest bronchitis with some degree of certainty, patients who have hemoptysis should undergo posteroanterior and lateral chest x-rays. Patients at risk for lung cancer should have sputum collected for cytology. Three early morning sputum samples are usually sufficient and in certain patients may decrease the need for invasive testing.9,10 Urinalysis should be done when there is a suspicion of autoimmune disease. Specific autoantibody assays may be appropriate, such as antineutrophilic cytoplasmic antibodies reactive to proteinase-3 for Wegener's granulomatosis or anti-glomerular basement membrane antibodies in Goodpasture's syndrome.

If the cause of hemoptysis is not apparent by history and chest x-ray or if the patient is at high risk for lung cancer, chest CT is warranted. Patients who do not respond to therapy or who have continued hemoptysis of at least 30 cc per day or for a week also warrant CT. Typically a scan without contrast will suffice. If the likelihood of cancer is high, a CT with contrast is needed to evaluate not only the lung parenchyma but any possible mediastinal lymphadenopathy. A specific spiral CT is used to evaluate for PE. CT is contraindicated in patients with contrast allergy or elevated serum creatinine.

Evaluations such as the one outlined led to diagnoses in the patients previously described:

Patient 1: Exacerbation of chronic bronchitis

This patient is suffering from an exacerbation of chronic bronchitis. In this case, a short course of antibiotics and follow-up on an as-needed basis would be appropriate. The hemoptysis associated with bronchitis is caused by airway inflammation and mechanical trauma stemming from repeated coughing. Therefore, it would also be reasonable to try antitussive therapy. Bronchospasm can be associated with bronchitis as well, so bronchodilators may be tried. This patient would not necessarily require follow-up unless the hemoptysis does not resolve within a few days or the patient becomes sicker despite the therapy. The precise role of antibiotics in acute bronchitis remains unclear, with the major benefit in studies being only a small reduction in the duration of symptoms.11 For exacerbations of chronic bronchitis, especially with chronic airway obstruction, i.e., COPD, antibiotics are often utilized along with corticosteroids since there is usually an underlying bacterial cause.

Patient 2: Lung cancer

Lung cancer is the No. 1 cause of cancer death in the United States. It was estimated that more than 213,000 new cases were diagnosed in 2007 and just over 160,000 would be fatal. Lung cancer kills more people each year than colon, breast, and prostate cancer combined. While exposure to pollution, radiation, and asbestos are associated with lung cancer, 90% of all cases are linked to cigarette smoking.3,12 Men older than 40 who smoke and have COPD are at even higher risk for lung cancer.

In this patient, chest radiography revealed a discrete mass with post-obstructive consolidation (Figure 3). Any radiograph with an unresolving pulmonary infiltrate despite previous therapy should raise suspicion for bronchogenic cancer. CT scanning with contrast in this situation can help define the extent or borders of masses and associated lymphadenopathy and whether there is airway compromise.

When to refer

As previously indicated, relatively minor hemoptysis caused by bronchitis warrants a trial of appropriate antibiotics with follow-up on an as-needed basis in otherwise low-risk patients. Bleeding in excess of 30 cc per day or hemoptysis that lasts longer than one week or is otherwise unexplained should prompt referral to a pulmonologist. And of course massive hemoptysis requires immediate attention and admission to an ICU.

When the evaluation is suggestive of an underlying autoimmune disorder, referral should be made to both a rheumatologist and a pulmonologist. In cases suspicious for cancer, the patient should be referred for fiberoptic bronchoscopy and tissue sampling.

There may be other reasons for referral as well, such as the need for imaging studies. Positron emission tomography may be employed after infections, such as pneumonia, have subsided. More specialized tests, such as magnetic resonance angiography and pulmonary angiography, may be required when pulmonary vascular malformations are suspected.

Hemoptysis severe enough to warrant referral or hospital admission sometimes requires surgical resection or selective bronchial artery embolization.

Summary

Hemoptysis is a serious and potentially life-threatening condition, but with prompt recognition, the clinician can start appropriate therapy, provide reassurance, ease symptoms, and avoid delay in recognizing underlying conditions that require specialized care.

Mr. Hochberg is a senior physician assistant for The Johns Hopkins University Division of Pulmonary and Critical Care Medicine in Baltimore.

References

1. Thompson AB, Teschler H, Rennard SI. Pathogenesis, evaluation and therapy for massive hemoptysis. Clin Chest Med. 1992;13:69-82.

2. Johnson JL. Manifestations of hemoptysis. Postgrad Med. 2002;112(4):101-113.

3. Hampson FG, Hancock SW, Primhak RA. Disseminated sepsis due to a Panton-Valentine leukocidin-producing strain of community-acquired methicillin-resistant Staphylococcus aureus and use of intravenous immunoglobulin therapy. Arch Dis Child. 2006;91:201.

4. Barker AF. Bronchiectasis. N Engl J Med. 2002;346:1383-1393.

5. Thickett KM, Kumararatne DS, Banerjee AK, et al. Common variable immune deficiency: respiratory manifestations, pulmonary function and high-resolution CT scan findings. QJM. 2002;95:655-662.

6. Gilljam M, Ellis L, Corey M, et al. Clinical manifestations of cystic fibrosis among patients with diagnosis in adulthood. Chest. 2004;126:1215-1224.

7. Watt AP, Brown V, Courtney J, et al. Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis. Thorax. 2004;59:231-236.

8. McCool FD, Rosen MJ. Nonpharmacologic airway clearance therapies: ACCP evidence-based clinical practice guidelines. Chest. 2006;129:250S-259S.

9. Ng AB, Horak GC. Factors significant in the diagnostic accuracy of lung cytology in bronchial washing and sputum samples. II. Sputum samples. Acta Cytol. 1983;27:397-402.

10. Raab SS, Hornberger J, Raffin T. The importance of sputum cytology in the diagnosis of lung cancer: a cost-effectiveness analysis. Chest. 1997;112; 937-945.

11. Smucny J, Fahey T, Becker L, Glazier R. Antibiotics for acute bronchitis. Cochrane Database Syst Rev. 1997;(4):CD000245.

12. Alberg AJ, Samet JM. Epidemiology of lung cancer. Chest. 2003;123(1 suppl):21S-49S.

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