Chapter 41: Hemoptysis¶

Part 2: Cardinal Manifestations and Presentation of Diseases · Part 2 – Cardinal Manifestations & Presentation

Detailed clinical reference synthesised from Harrison's Principles of Internal Medicine, 22nd Edition

🔑 Key Clinical Points¶

Hemoptysis is defined as the expectoration of blood originating from the lower respiratory tract.
Massive hemoptysis is commonly defined as expectorating >150 mL in 24 hours or a bleeding rate of ≥100 mL/h.
Life-threatening hemoptysis is defined by abnormal gas exchange, hemodynamic compromise, or threat for airway obstruction.
Most hemoptysis originates from the bronchial circulation (high-pressure system from the aorta), making it difficult to control.
In the United States, the most common causes remain viral bronchitis, bronchiectasis, or malignancy.
In other parts of the world, infections such as tuberculosis are the most common causes.
Rasmussen's aneurysm (erosion of a pulmonary artery aneurysm into a preexisting cavity) is a rare but significant cause of massive hemoptysis in tuberculosis.
Pulmonary emboli do not commonly cause hemoptysis; frank blood is not a typical presentation.
Diffuse alveolar hemorrhage (DAH) typically presents with diffuse ground-glass opacities and is not often associated with hemoptysis.
Patients with chronic cough who have normal findings on chest CT can be reassured as to the absence of serious pulmonary pathology.
Bronchogenic carcinoma of any histology is a common cause of hemoptysis, with small-cell and squamous cell carcinomas frequently central and more likely to erode into major pulmonary vessels.
Kaposi's sarcoma is very vascular and can develop anywhere along the respiratory tract, from the bronchi to the oral cavity.

📑 Table of Contents¶

1. DEFINITION & OVERVIEW
1.1 Definition of Massive Hemoptysis
2. EPIDEMIOLOGY
2.1 Global Considerations
3. ETIOLOGY & PATHOPHYSIOLOGY
3.1 Anatomical Basis
3.2 Infectious Etiologies
3.3 Malignancy
3.4 Vascular & Mechanical Causes
4. CLINICAL FEATURES
4.1 History Taking
4.2 Physical Examination
5. DIFFERENTIAL DIAGNOSIS
5.1 Systematic Differential Diagnosis
6. INVESTIGATIONS & DIAGNOSIS
6.1 Diagnostic Workup
6.2 Diagnostic Algorithm
7. MANAGEMENT & TREATMENT
7.1 Management Algorithm
7.2 Cough Management (Contextual)
8. PROGNOSIS & COMPLICATIONS
8.1 Mortality Risk
9. SPECIAL CONSIDERATIONS
9.1 Global & Environmental
9.2 Coagulopathy & Procedures
10. KEY PEARLS & CLINICAL TRAPS
10.1 Board Exam Favorites
Flowcharts & Algorithms

📋 Figures in This Chapter¶

#	Type	Description
1	🔀 Flowchart	Approach to the management of hemoptysis

1. DEFINITION & OVERVIEW¶

Hemoptysis is the expectoration of blood originating from the lower respiratory tract.
It can be confused initially with bleeding from the gastrointestinal tract (hematemesis) or nasal cavities (epistaxis).
The amount of blood that is being expectorated (volume and frequency) is the most important information to gather.
Massive or life-threatening hemoptysis requires emergent intervention.
This chapter focuses on non-life-threatening hemoptysis, which is more common.
Diseases causing cough that may be missed on chest x-ray include tumors, early interstitial lung disease, bronchiectasis, and atypical mycobacterial pulmonary infection.
Patients with chronic cough who have normal findings on chest examination, lung function testing, oxygenation assessment, and chest CT can be reassured as to the absence of serious pulmonary pathology.

1.1 Definition of Massive Hemoptysis¶

Massive hemoptysis is defined by variable definitions but commonly expectorating >150 mL in 24 hours.
Alternatively, a bleeding rate of ≥100 mL/h is considered massive.
Life-threatening hemoptysis is defined by the presence of significantly abnormal gas exchange, hemodynamic compromise, or threat for airway obstruction.
Patients rarely die of exsanguination but, rather, are at risk of death due to asphyxiation from blood filling the airways and airspaces.
This can occur with blood loss of >400 mL within 24 hours or >150 mL at one time.
Fortunately, life-threatening hemoptysis only accounts for 5–15% of cases of hemoptysis.

Table 1 — Table 41-1: Definition of Massive vs. Life-Threatening Hemoptysis¶

Parameter	Non-Massive	Massive / Life-Threatening
Volume (24h)	< 150 mL	> 150 mL
Bleeding Rate	< 100 mL/h	≥ 100 mL/h
Clinical Status	Stable	Abnormal gas exchange, hemodynamic compromise, or threat for airway obstruction
Mortality Risk	Low	High (Asphyxiation > Exsanguination)

2. EPIDEMIOLOGY¶

In the United States, the most common causes remain viral bronchitis, bronchiectasis, or malignancy.
In other parts of the world, infections such as tuberculosis are the most common causes.
Tuberculosis used to be the most common cause of hemoptysis worldwide, but in industrialized countries, bronchitis and bronchiectasis are more common.
Regular exposure to air pollution can cause chronic cough and throat clearing, as well as lower respiratory tract disease.
Smoke from cooking and heating fuels in poorly ventilated homes; toxic exposures in work settings lacking implementation of occupational safety standards; and the ambient chemicals and particulates in highly polluted outdoor air are all forms of air pollution causing cough.
Limited therapeutic options are available; treatment focuses on improving environmental air quality (e.g., use of a stove chimney in the home), removal from the exposure, and use of an appropriate face mask.

2.1 Global Considerations¶

In areas of the world where tuberculosis is endemic, chronic cough conjures the possibility of active pulmonary tuberculosis and mandates appropriate evaluation, including chest imaging and sputum analysis.
Paragonimiasis can mimic tuberculosis and is another significant cause of hemoptysis seen globally.
It is common in Southeast Asia and China, although cases have been reported in North America from raw crayfish ingestion.
It should be considered as a cause of hemoptysis in recent immigrants from endemic areas.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

Infection, malignancy, and vascular disease are some of the common causes of hemoptysis, but the differential is quite broad.
In addition to infection, vascular disease, and malignancy, other insults underlying disease (usually coagulation to the pulmonary system) can cause hemoptysis.
In patients with tuberculosis, development of cavitary disease is frequently the source of bleeding, but rarer complications such as erosion of a pulmonary artery aneurysm into a preexisting cavity (i.e., Rasmussen's aneurysm) can also be the source.
Other infectious agents such as endemic fungi, Nocardia, and non-tuberculous mycobacteria can present as cavitary lung disease complicated by hemoptysis.
In addition, Aspergillus species can develop into mycetomas within preexisting cavities, with neovascularization to these inflamed spaces leading to bleeding.
Pulmonary abscesses and necrotizing pneumonia can cause bleeding by devitalizing lung parenchyma.
Common responsible organisms include Staphylococcus aureus, Klebsiella pneumoniae, and oral anaerobes.
The blood supply to the lungs is available from both the pulmonary and bronchial circulations.
The pulmonary circulation is a low-pressure system that is essential for gas exchange at the alveoli.
In contrast, the bronchial circulation originates from the aorta and, thus, is a higher-pressure system.
The bronchial arteries supply the airways and can neovascularize tumors, dilated airways in bronchiectasis, and cavitary lesions.
Most hemoptysis originates from the bronchial circulation, the higher-pressure system, which can make it difficult to control.
Pulmonary endometriosis causes cyclical bleeding known as catamenial hemoptysis.
Foreign body aspiration can lead to airway irritation and bleeding.
Diagnostic and therapeutic procedures are also potential offenders: pulmonary vein stenosis can result from left atrial procedures, such as pulmonary vein isolation, and pulmonary artery catheters can lead to rupture of the pulmonary artery if the distal balloon is kept inflated.
Finally, in the setting of thrombocytopenia, even minor insults can cause hemoptysis.

3.1 Anatomical Basis¶

Hemoptysis originates in the lower respiratory tract, anywhere from the glottis to the alveolus.
The bleeding most commonly arises from the bronchi or medium-sized airways, but a thorough evaluation of the entire respiratory tree is important.
The blood supply to the lungs is available from both the pulmonary and bronchial circulations.
The pulmonary circulation is a low-pressure system that is essential for gas exchange at the alveoli.
In contrast, the bronchial circulation originates from the aorta and, thus, is a higher-pressure system.
The bronchial arteries supply the airways and can neovascularize tumors, dilated airways in bronchiectasis, and cavitary lesions.
Most hemoptysis originates from the bronchial circulation, the higher-pressure system, which can make it difficult to control.

3.2 Infectious Etiologies¶

Viral bronchitis is the most common cause of small-volume hemoptysis.
Patients with chronic bronchitis are at risk for bacterial superinfection.
Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the more common bacteria involved.
These infections can increase airway inflammation that leads to bleeding.
Patients with bronchiectasis, including those with cystic fibrosis, can have hemoptysis during exacerbations.
Due to recurrent bacterial infection, bronchiectatic airways are dilated, inflamed, and highly vascular, supplied by the bronchial circulation.
This can cause bronchiectasis to also be a significant cause of massive hemoptysis and subsequent death.
Tuberculosis used to be the most common cause of hemoptysis worldwide.
In patients with tuberculosis, development of cavitary disease is frequently the source of bleeding.
Rarer complications such as erosion of a pulmonary artery aneurysm into a preexisting cavity (i.e., Rasmussen's aneurysm) can also be the source.
Other infectious agents such as endemic fungi, Nocardia, and non-tuberculous mycobacteria can present as cavitary lung disease complicated by hemoptysis.
Aspergillus species can develop into mycetomas within preexisting cavities, with neovascularization to these inflamed spaces leading to bleeding.
Pulmonary abscesses and necrotizing pneumonia can cause bleeding by devitalizing lung parenchyma.
Common responsible organisms include Staphylococcus aureus, Klebsiella pneumoniae, and oral anaerobes.
Paragonimiasis can mimic tuberculosis and is another significant cause of hemoptysis seen globally.
It is common in Southeast Asia and China, although cases have been reported in North America from raw crayfish ingestion.
It should be considered as a cause of hemoptysis in recent immigrants from endemic areas.

3.3 Malignancy¶

Bronchogenic carcinoma of any histology is a common cause of hemoptysis (both massive and nonmassive).
Hemoptysis can indicate airway involvement of the tumor and can be a presenting symptom of carcinoid tumors.
Small-cell and squamous cell carcinomas are frequently central in nature and more likely to erode into major pulmonary vessels, resulting in massive hemoptysis.
Pulmonary metastases from distant tumors (e.g., melanoma, sarcoma, adenocarcinomas of the breast and colon) can also cause bleeding.
Kaposi's sarcoma, seen in advanced acquired immunodeficiency syndrome, is very vascular and can develop anywhere along the respiratory tract, from the bronchi to the oral cavity.

3.4 Vascular & Mechanical Causes¶

Pulmonary embolism with parenchymal infarction can present with hemoptysis, but pulmonary emboli do not commonly cause hemoptysis.
An ectatic vessel in an airway or a pulmonary arteriovenous malformation can be a source of bleeding.
A rare vascular cause of hemoptysis is the rupture of an aortobronchial fistula.
These fistulae arise in the setting of aortic pathology such as aneurysm or pseudoaneurysm and can cause small bleeding episodes that result in massive hemoptysis.
DAH causes significant bleeding into the lung parenchyma but, interestingly, is not often associated with hemoptysis.
DAH typically presents with diffuse ground-glass opacities on chest imaging.
A range of insults cause DAH, including immune-mediated capillaritis from diseases such as systemic lupus erythematosus, toxicity from cocaine and other inhalants, and stem cell transplantation.
The so-called "pulmonary-renal" syndromes, including granulomatosis with polyangiitis and anti–glomerular basement membrane (anti-GBM) disease, may lead to both hemoptysis and hematuria (though one manifestation may be present without the other).
A recently identified cause of hemoptysis and DAH is vaping-induced lung injury.
Pulmonary endometriosis causes cyclical bleeding known as catamenial hemoptysis.
Foreign body aspiration can lead to airway irritation and bleeding.
Diagnostic and therapeutic procedures are also potential offenders: pulmonary vein stenosis can result from left atrial procedures, such as pulmonary vein isolation, and pulmonary artery catheters can lead to rupture of the pulmonary artery if the distal balloon is kept inflated.
Finally, in the setting of thrombocytopenia, even minor insults can cause hemoptysis.

4. CLINICAL FEATURES¶

The initial history should be directed at assessing the pattern, severity, and quantity of hemoptysis.
An approach to management of hemoptysis is outlined in Fig. 41-1.
A patient's description of the sputum expectorated (e.g., flecks of blood, pink-tinged, frank blood or clot) is helpful if you cannot examine it.
Quantification is often challenging for patients, so using references like cups (one U.S. cup is 236 mL) can be helpful.
Further history may help define the etiology of hemoptysis.
Smoking history and/or unintentional weight loss may point to possible malignancy.
Preceding fevers, cough, and/or sputum production may suggest infection.
A history of prior diagnosed chronic lung conditions, especially cystic fibrosis or other chronic bronchiectatic diseases, is important to note.
Screening for causes of pseudohemoptysis (i.e., other upper airway or gastrointestinal) is also helpful.
Patients should initially be assessed for signs of life-threatening hemoptysis including hypoxemia, tachycardia, and hemodynamic instability.
Examination should include possible sites of extrapulmonary bleeding such as the nasal and oral cavities.
Auscultation of the lungs may suggest a laterality.
Other relevant physical findings may suggest other etiologies of the hemoptysis and include clubbing, signs of a bleeding diathesis (e.g., skin or mucosal ecchymoses and petechiae), telangiectasias, or skin rash.

4.1 History Taking¶

Pattern, severity, and quantity of hemoptysis.
Sputum description: flecks of blood, pink-tinged, frank blood or clot.
Quantification: Use references like cups (one U.S. cup is 236 mL).
Risk factors: Smoking history, unintentional weight loss (malignancy).
Infection signs: Preceding fevers, cough, sputum production.
Chronic lung conditions: Cystic fibrosis, chronic bronchiectatic diseases.
Pseudohemoptysis screening: Other upper airway or gastrointestinal sources.

4.2 Physical Examination¶

Life-threatening signs: Hypoxemia, tachycardia, hemodynamic instability.
Extrapulmonary bleeding sites: Nasal and oral cavities.
Lung auscultation: Suggests laterality.
Clubbing: Suggests chronic lung disease or malignancy.
Bleeding diathesis signs: Skin or mucosal ecchymoses and petechiae.
Telangiectasias or skin rash: Suggests vasculitis or other systemic disease.

5. DIFFERENTIAL DIAGNOSIS¶

Infection: Viral bronchitis, bacterial superinfection, tuberculosis, fungal infections, paragonimiasis, abscesses.
Malignancy: Bronchogenic carcinoma, carcinoid tumors, metastases, Kaposi's sarcoma.
Vascular: Pulmonary embolism, arteriovenous malformation, diffuse alveolar hemorrhage, aortobronchial fistula.
Mechanical/Other: Pulmonary endometriosis, foreign body aspiration, procedural complications (pulmonary vein isolation, PA catheter), vaping-induced lung injury.

5.1 Systematic Differential Diagnosis¶

Infection
Viral bronchitis
Bacterial superinfection (S. pneumoniae, H. influenzae, M. catarrhalis)
Tuberculosis (cavitary disease, Rasmussen's aneurysm)
Fungal infections (Aspergillus mycetoma, endemic fungi, Nocardia)
Paragonimiasis
Abscesses/Necrotizing pneumonia (S. aureus, K. pneumoniae, oral anaerobes)
Malignancy
Bronchogenic carcinoma (central, erodes vessels)
Carcinoid tumors
Metastases (melanoma, sarcoma, breast, colon)
Kaposi's sarcoma
Vascular
Pulmonary embolism (infarction)
Arteriovenous malformation
Diffuse alveolar hemorrhage
Aortobronchial fistula
Mechanical/Other
Pulmonary endometriosis
Foreign body aspiration
Procedural complications
Vaping-induced lung injury

6. INVESTIGATIONS & DIAGNOSIS¶

Patients should initially be assessed for signs of life-threatening hemoptysis including hypoxemia, tachycardia, and hemodynamic instability.
Examination should include possible sites of extrapulmonary bleeding such as the nasal and oral cavities.
Quantification is often challenging for patients, so using references like cups (one U.S. cup is 236 mL) can be helpful.
A patient's description of the sputum expectorated (e.g., flecks of blood, pink-tinged, frank blood or clot) is helpful if you cannot examine it.
Screening for causes of pseudohemoptysis (i.e., other upper airway or gastrointestinal) is also helpful.
Diseases causing cough that may be missed on chest x-ray include tumors, early interstitial lung disease, bronchiectasis, and atypical mycobacterial pulmonary infection.
On the other hand, patients with chronic cough who have normal findings on chest examination, lung function testing, oxygenation assessment, and chest CT can be reassured as to the absence of serious pulmonary pathology.
Pulmonary embolism with parenchymal infarction can present with hemoptysis, but pulmonary emboli do not commonly cause hemoptysis.
DAH typically presents with diffuse ground-glass opacities on chest imaging.
A range of insults cause DAH, including immune-mediated capillaritis from diseases such as systemic lupus erythematosus, toxicity from cocaine and other inhalants, and stem cell transplantation.
The so-called "pulmonary-renal" syndromes, including granulomatosis with polyangiitis and anti–glomerular basement membrane (anti-GBM) disease, may lead to both hemoptysis and hematuria (though one manifestation may be present without the other).
A recently identified cause of hemoptysis and DAH is vaping-induced lung injury.

6.1 Diagnostic Workup¶

Initial Assessment
Assess for life-threatening hemoptysis (hypoxemia, tachycardia, hemodynamic instability).
Examine extrapulmonary bleeding sites (nasal, oral cavities).
Quantify bleeding (cups, mL).
Describe sputum (flecks, pink-tinged, frank blood, clot).
Screen for pseudohemoptysis (upper airway, GI).
Imaging
Chest X-ray (CXR)
Computed Tomography (CT)
Note: Diseases causing cough that may be missed on chest x-ray include tumors, early interstitial lung disease, bronchiectasis, and atypical mycobacterial pulmonary infection.
Note: Patients with chronic cough who have normal findings on chest CT can be reassured.
Laboratory
Complete Blood Count (CBC)
Urinalysis (UA)
Creatinine
Coagulation studies (infection, coagulopathy, anticoagulation, antiplatelet therapy)
Procedures
Bronchoscopy
Embolization
Resection

6.2 Diagnostic Algorithm¶

Step 1: Assess for life-threatening hemoptysis.
If life-threatening: Protect airway.
If non-life-threatening: Quantify amount of bleeding.
Step 2: Perform initial investigations.
Treat CXR, CBC, UA, infection studies, creatinine.
Step 3: Evaluate bleeding status.
If bleeding stops: Treat underlying disease.
If bleeding continues: Embolization or resection.
Step 4: Persistent bleeding.
Persistent CT scan.
Bronchoscopy.
Treat underlying disease.
Step 5: Life-threatening hemoptysis.
Defined by significantly abnormal gas exchange, hemodynamic compromise, or threat for airway obstruction.
Can occur with blood loss of >400 mL within 24 h or >150 mL at one time.

7. MANAGEMENT & TREATMENT¶

An approach to management of hemoptysis is outlined in Fig. 41-1.
Patients should initially be assessed for signs of life-threatening hemoptysis including hypoxemia, tachycardia, and hemodynamic instability.
Examination should include possible sites of extrapulmonary bleeding such as the nasal and oral cavities.
Quantification is often challenging for patients, so using references like cups (one U.S. cup is 236 mL) can be helpful.
A patient's description of the sputum expectorated (e.g., flecks of blood, pink-tinged, frank blood or clot) is helpful if you cannot examine it.
Screening for causes of pseudohemoptysis (i.e., other upper airway or gastrointestinal) is also helpful.
Life-threatening hemoptysis is defined by the presence of significantly abnormal gas exchange, hemodynamic compromise, or threat for airway obstruction.
Patients rarely die of exsanguination but, rather, are at risk of death due to asphyxiation from blood filling the airways and airspaces.
This can occur with blood loss of >400 mL within 24 h or >150 mL at one time.
Fortunately, life-threatening hemoptysis only accounts for 5–15% of cases of hemoptysis.
Further history may help define the etiology of hemoptysis.
Smoking history and/or unintentional weight loss may point to possible malignancy.
Preceding fevers, cough, and/or sputum production may suggest infection.
A history of prior diagnosed chronic lung conditions, especially cystic fibrosis or other chronic bronchiectatic diseases, is important to note.
Screening for causes of pseudohemoptysis (i.e., other upper airway or gastrointestinal) is also helpful.
Patients should initially be assessed for signs of life-threatening hemoptysis including hypoxemia, tachycardia, and hemodynamic instability.
Examination should include possible sites of extrapulmonary bleeding such as the nasal and oral cavities.
Auscultation of the lungs may suggest a laterality.
Other relevant physical findings may suggest other etiologies of the hemoptysis and include clubbing, signs of a bleeding diathesis (e.g., skin or mucosal ecchymoses and petechiae), telangiectasias, or skin rash.
In addition to infection, vascular disease, and malignancy, other insults underlying disease (usually coagulation to the pulmonary system) can cause hemoptysis.
Pulmonary endometriosis causes cyclical bleeding known as catamenial hemoptysis.
Foreign body aspiration can lead to airway irritation and bleeding.
Diagnostic and therapeutic procedures are also potential offenders: pulmonary vein stenosis can result from left atrial procedures, such as pulmonary vein isolation, and pulmonary artery catheters can lead to rupture of the pulmonary artery if the distal balloon is kept inflated.
Finally, in the setting of thrombocytopenia, even minor insults can cause hemoptysis.
Empiric treatment of chronic idiopathic cough with inhaled corticosteroids, inhaled anticholinergic bronchodilators, and macrolide antibiotics has been tried without consistent success.
Currently available cough suppressants are only modestly effective.
Most potent are narcotic cough suppressants, such as codeine, hydrocodone, or morphine, which are thought to act in the "cough center" in the brainstem.
The tendency of narcotic cough suppressants to cause drowsiness and constipation and their potential for addictive dependence limit their appeal for long-term use.
Dextromethorphan is an over-the-counter, centrally acting cough suppressant with fewer side effects and less efficacy than the narcotic cough suppressants.
Dextromethorphan is thought to have a different site of action than narcotic cough suppressants and can be used in combination with them if necessary.
Benzonatate is thought to inhibit neural activity of sensory nerves in the cough-reflex pathway.
It is generally free of side effects; however, its effectiveness in suppressing cough is variable and unpredictable.
Inhaled lidocaine, an inhibitor of voltage-gated sodium channels, provides transient cough suppression, but because of associated oropharyngeal anesthesia, it poses an increased risk of aspiration.
Attempts to treat cough hypersensitivity syndrome have focused on inhibition of neural pathways.
Small case series and randomized clinical trials have indicated benefit from off-label use of gabapentin, pregabalin, or amitriptyline.
Recent studies suggest a role for behavioral modification using specialized speech therapy techniques, but widespread application of this modality is currently not practical.
Novel cough suppressants without the limitations of currently available agents are greatly needed.
Approaches that are being explored include the development of neurokinin-1 receptor antagonists, transient receptor protein vanilloid-1 (TRPV1) channel antagonists, P2X3 channel antagonists, and novel opioid and opioid-like receptor agonists.

7.1 Management Algorithm¶

Step 1: Assess life-threatening status.
If life-threatening: Protect airway.
If non-life-threatening: Quantify amount of bleeding.
Step 2: Initial Investigations.
Treat CXR, CBC, UA, infection studies, creatinine.
Step 3: Evaluate bleeding status.
If bleeding stops: Treat underlying disease.
If bleeding continues: Embolization or resection.
Step 4: Persistent bleeding.
Persistent CT scan.
Bronchoscopy.
Treat underlying disease.
Step 5: Life-threatening hemoptysis.
Defined by significantly abnormal gas exchange, hemodynamic compromise, or threat for airway obstruction.
Can occur with blood loss of >400 mL within 24 h or >150 mL at one time.

7.2 Cough Management (Contextual)¶

Empiric treatment of chronic idiopathic cough with inhaled corticosteroids, inhaled anticholinergic bronchodilators, and macrolide antibiotics has been tried without consistent success.
Currently available cough suppressants are only modestly effective.
Most potent are narcotic cough suppressants, such as codeine, hydrocodone, or morphine, which are thought to act in the "cough center" in the brainstem.
The tendency of narcotic cough suppressants to cause drowsiness and constipation and their potential for addictive dependence limit their appeal for long-term use.
Dextromethorphan is an over-the-counter, centrally acting cough suppressant with fewer side effects and less efficacy than the narcotic cough suppressants.
Dextromethorphan is thought to have a different site of action than narcotic cough suppressants and can be used in combination with them if necessary.
Benzonatate is thought to inhibit neural activity of sensory nerves in the cough-reflex pathway.
It is generally free of side effects; however, its effectiveness in suppressing cough is variable and unpredictable.
Inhaled lidocaine, an inhibitor of voltage-gated sodium channels, provides transient cough suppression, but because of associated oropharyngeal anesthesia, it poses an increased risk of aspiration.
Attempts to treat cough hypersensitivity syndrome have focused on inhibition of neural pathways.
Small case series and randomized clinical trials have indicated benefit from off-label use of gabapentin, pregabalin, or amitriptyline.
Recent studies suggest a role for behavioral modification using specialized speech therapy techniques, but widespread application of this modality is currently not practical.
Novel cough suppressants without the limitations of currently available agents are greatly needed.
Approaches that are being explored include the development of neurokinin-1 receptor antagonists, transient receptor protein vanilloid-1 (TRPV1) channel antagonists, P2X3 channel antagonists, and novel opioid and opioid-like receptor agonists.

8. PROGNOSIS & COMPLICATIONS¶

Patients rarely die of exsanguination but, rather, are at risk of death due to asphyxiation from blood filling the airways and airspaces.
This can occur with blood loss of >400 mL within 24 h or >150 mL at one time.
Fortunately, life-threatening hemoptysis only accounts for 5–15% of cases of hemoptysis.
Due to recurrent bacterial infection, bronchiectatic airways are dilated, inflamed, and highly vascular, supplied by the bronchial circulation.
This can cause bronchiectasis to also be a significant cause of massive hemoptysis and subsequent death.

8.1 Mortality Risk¶

Life-threatening hemoptysis accounts for 5–15% of cases of hemoptysis.
Death is typically due to asphyxiation rather than exsanguination.
Massive hemoptysis can lead to subsequent death in the setting of bronchiectasis due to recurrent bacterial infection.

9. SPECIAL CONSIDERATIONS¶

In areas of the world where tuberculosis is endemic, chronic cough conjures the possibility of active pulmonary tuberculosis and mandates appropriate evaluation, including chest imaging and sputum analysis.
Regular exposure to air pollution can cause chronic cough and throat clearing, as well as lower respiratory tract disease.
Smoke from cooking and heating fuels in poorly ventilated homes; toxic exposures in work settings lacking implementation of occupational safety standards; and the ambient chemicals and particulates in highly polluted outdoor air are all forms of air pollution causing cough.
Limited therapeutic options are available; treatment focuses on improving environmental air quality (e.g., use of a stove chimney in the home), removal from the exposure, and use of an appropriate face mask.
In addition to infection, vascular disease, and malignancy, other insults underlying disease (usually coagulation to the pulmonary system) can cause hemoptysis.
In the setting of thrombocytopenia, even minor insults can cause hemoptysis.
Coagulopathy, anticoagulation, or antiplatelet therapy can cause hemoptysis.
Pulmonary endometriosis causes cyclical bleeding known as catamenial hemoptysis.
Foreign body aspiration can lead to airway irritation and bleeding.
Diagnostic and therapeutic procedures are also potential offenders: pulmonary vein stenosis can result from left atrial procedures, such as pulmonary vein isolation, and pulmonary artery catheters can lead to rupture of the pulmonary artery if the distal balloon is kept inflated.
A recently identified cause of hemoptysis and DAH is vaping-induced lung injury.

9.1 Global & Environmental¶

Tuberculosis endemic areas: Chronic cough mandates evaluation (chest imaging, sputum analysis).
Air pollution: Regular exposure causes chronic cough and lower respiratory tract disease.
Treatment: Improve environmental air quality (stove chimney, removal from exposure, face mask).

9.2 Coagulopathy & Procedures¶

Coagulopathy, anticoagulation, or antiplatelet therapy can cause hemoptysis.
In the setting of thrombocytopenia, even minor insults can cause hemoptysis.
Pulmonary vein stenosis can result from left atrial procedures, such as pulmonary vein isolation.
Pulmonary artery catheters can lead to rupture of the pulmonary artery if the distal balloon is kept inflated.

10. KEY PEARLS & CLINICAL TRAPS¶

Hemoptysis is the expectoration of blood originating from the lower respiratory tract.
It can be confused initially with bleeding from the gastrointestinal tract (hematemesis) or nasal cavities (epistaxis).
The amount of blood that is being expectorated (volume and frequency) is the most important information to gather.
Massive or life-threatening hemoptysis requires emergent intervention.
This chapter focuses on non-life-threatening hemoptysis, which is more common.
Diseases causing cough that may be missed on chest x-ray include tumors, early interstitial lung disease, bronchiectasis, and atypical mycobacterial pulmonary infection.
Patients with chronic cough who have normal findings on chest examination, lung function testing, oxygenation assessment, and chest CT can be reassured as to the absence of serious pulmonary pathology.
In the United States, the most common causes remain viral bronchitis, bronchiectasis, or malignancy.
In other parts of the world, infections such as tuberculosis are the most common causes.
Tuberculosis used to be the most common cause of hemoptysis worldwide, but in industrialized countries, bronchitis and bronchiectasis are more common.
Regular exposure to air pollution can cause chronic cough and throat clearing, as well as lower respiratory tract disease.
Smoke from cooking and heating fuels in poorly ventilated homes; toxic exposures in work settings lacking implementation of occupational safety standards; and the ambient chemicals and particulates in highly polluted outdoor air are all forms of air pollution causing cough.
Limited therapeutic options are available; treatment focuses on improving environmental air quality (e.g., use of a stove chimney in the home), removal from the exposure, and use of an appropriate face mask.
In areas of the world where tuberculosis is endemic, chronic cough conjures the possibility of active pulmonary tuberculosis and mandates appropriate evaluation, including chest imaging and sputum analysis.
Hemoptysis from a vascular cause can be associated with cardiac disease, pulmonary embolism, arteriovenous malformation, or diffuse alveolar hemorrhage (DAH).
While the classic description of the sputum expectorated in pulmonary edema (from elevated left end-diastolic pressure) is "pink and frothy," a spectrum of hemoptysis including frank blood can be seen.
This observation is particularly true now with the more widespread use of anticoagulants and antiplatelet medications.
Pulmonary embolism with parenchymal infarction can present with hemoptysis, but pulmonary emboli do not commonly cause hemoptysis.
An ectatic vessel in an airway or a pulmonary arteriovenous malformation can be a source of bleeding.
A rare vascular cause of hemoptysis is the rupture of an aortobronchial fistula.
These fistulae arise in the setting of aortic pathology such as aneurysm or pseudoaneurysm and can cause small bleeding episodes that result in massive hemoptysis.
DAH causes significant bleeding into the lung parenchyma but, interestingly, is not often associated with hemoptysis.
DAH typically presents with diffuse ground-glass opacities on chest imaging.
A range of insults cause DAH, including immune-mediated capillaritis from diseases such as systemic lupus erythematosus, toxicity from cocaine and other inhalants, and stem cell transplantation.
The so-called "pulmonary-renal" syndromes, including granulomatosis with polyangiitis and anti–glomerular basement membrane (anti-GBM) disease, may lead to both hemoptysis and hematuria (though one manifestation may be present without the other).
A recently identified cause of hemoptysis and DAH is vaping-induced lung injury.
Bronchogenic carcinoma of any histology is a common cause of hemoptysis (both massive and nonmassive).
Hemoptysis can indicate airway involvement of the tumor and can be a presenting symptom of carcinoid tumors.
Small-cell and squamous cell carcinomas are frequently central in nature and more likely to erode into major pulmonary vessels, resulting in massive hemoptysis.
Pulmonary metastases from distant tumors (e.g., melanoma, sarcoma, adenocarcinomas of the breast and colon) can also cause bleeding.
Kaposi's sarcoma, seen in advanced acquired immunodeficiency syndrome, is very vascular and can develop anywhere along the respiratory tract, from the bronchi to the oral cavity.
In addition to infection, vascular disease, and malignancy, other insults underlying disease (usually coagulation to the pulmonary system) can cause hemoptysis.
Pulmonary endometriosis causes cyclical bleeding known as catamenial hemoptysis.
Foreign body aspiration can lead to airway irritation and bleeding.
Diagnostic and therapeutic procedures are also potential offenders: pulmonary vein stenosis can result from left atrial procedures, such as pulmonary vein isolation, and pulmonary artery catheters can lead to rupture of the pulmonary artery if the distal balloon is kept inflated.
Finally, in the setting of thrombocytopenia, even minor insults can cause hemoptysis.
The initial history should be directed at assessing the pattern, severity, and quantity of hemoptysis.
An approach to management of hemoptysis is outlined in Fig. 41-1.
A patient's description of the sputum expectorated (e.g., flecks of blood, pink-tinged, frank blood or clot) is helpful if you cannot examine it.
Quantification is often challenging for patients, so using references like cups (one U.S. cup is 236 mL) can be helpful.
Further history may help define the etiology of hemoptysis.
Smoking history and/or unintentional weight loss may point to possible malignancy.
Preceding fevers, cough, and/or sputum production may suggest infection.
A history of prior diagnosed chronic lung conditions, especially cystic fibrosis or other chronic bronchiectatic diseases, is important to note.
Screening for causes of pseudohemoptysis (i.e., other upper airway or gastrointestinal) is also helpful.
Patients should initially be assessed for signs of life-threatening hemoptysis including hypoxemia, tachycardia, and hemodynamic instability.
Examination should include possible sites of extrapulmonary bleeding such as the nasal and oral cavities.
Auscultation of the lungs may suggest a laterality.
Other relevant physical findings may suggest other etiologies of the hemoptysis and include clubbing, signs of a bleeding diathesis (e.g., skin or mucosal ecchymoses and petechiae), telangiectasias, or skin rash.
Patients rarely die of exsanguination but, rather, are at risk of death due to asphyxiation from blood filling the airways and airspaces.
This can occur with blood loss of >400 mL within 24 h or >150 mL at one time.
Fortunately, life-threatening hemoptysis only accounts for 5–15% of cases of hemoptysis.
In addition to infection, vascular disease, and malignancy, other insults underlying disease (usually coagulation to the pulmonary system) can cause hemoptysis.
Pulmonary endometriosis causes cyclical bleeding known as catamenial hemoptysis.
Foreign body aspiration can lead to airway irritation and bleeding.
Diagnostic and therapeutic procedures are also potential offenders: pulmonary vein stenosis can result from left atrial procedures, such as pulmonary vein isolation, and pulmonary artery catheters can lead to rupture of the pulmonary artery if the distal balloon is kept inflated.
Finally, in the setting of thrombocytopenia, even minor insults can cause hemoptysis.
Empiric treatment of chronic idiopathic cough with inhaled corticosteroids, inhaled anticholinergic bronchodilators, and macrolide antibiotics has been tried without consistent success.
Currently available cough suppressants are only modestly effective.
Most potent are narcotic cough suppressants, such as codeine, hydrocodone, or morphine, which are thought to act in the "cough center" in the brainstem.
The tendency of narcotic cough suppressants to cause drowsiness and constipation and their potential for addictive dependence limit their appeal for long-term use.
Dextromethorphan is an over-the-counter, centrally acting cough suppressant with fewer side effects and less efficacy than the narcotic cough suppressants.
Dextromethorphan is thought to have a different site of action than narcotic cough suppressants and can be used in combination with them if necessary.
Benzonatate is thought to inhibit neural activity of sensory nerves in the cough-reflex pathway.
It is generally free of side effects; however, its effectiveness in suppressing cough is variable and unpredictable.
Inhaled lidocaine, an inhibitor of voltage-gated sodium channels, provides transient cough suppression, but because of associated oropharyngeal anesthesia, it poses an increased risk of aspiration.
Attempts to treat cough hypersensitivity syndrome have focused on inhibition of neural pathways.
Small case series and randomized clinical trials have indicated benefit from off-label use of gabapentin, pregabalin, or amitriptyline.
Recent studies suggest a role for behavioral modification using specialized speech therapy techniques, but widespread application of this modality is currently not practical.
Novel cough suppressants without the limitations of currently available agents are greatly needed.
Approaches that are being explored include the development of neurokinin-1 receptor antagonists, transient receptor protein vanilloid-1 (TRPV1) channel antagonists, P2X3 channel antagonists, and novel opioid and opioid-like receptor agonists.

10.1 Board Exam Favorites¶

Massive hemoptysis definition: >150 mL in 24 hours or ≥100 mL/h.
Life-threatening hemoptysis definition: Abnormal gas exchange, hemodynamic compromise, or threat for airway obstruction.
Bronchial circulation is the source of most hemoptysis (high-pressure system from aorta).
Rasmussen's aneurysm: Erosion of a pulmonary artery aneurysm into a preexisting cavity in TB.
Pink and frothy sputum: Classic description of pulmonary edema, but spectrum of hemoptysis including frank blood can be seen.
Pulmonary emboli do not commonly cause hemoptysis.
DAH typically presents with diffuse ground-glass opacities on chest imaging.
Kaposi's sarcoma is very vascular and can develop anywhere along the respiratory tract.
Smoking history and/or unintentional weight loss may point to possible malignancy.
Preceding fevers, cough, and/or sputum production may suggest infection.
Screening for causes of pseudohemoptysis (i.e., other upper airway or gastrointestinal) is also helpful.

Flowcharts & Algorithms¶

Reproduced from Harrison's 22nd Edition.

Flowchart 1¶

Approach to the management of hemoptysis

Caption: FIGURE 41-1 Approach to the management of hemoptysis. CBC, complete blood count; chest x-ray; UA, urinalysis.

Generated from Harrison's Principles of Internal Medicine, 22nd Edition.