Chapter 48 - Cough and Hemoptysis

Question 1

Exemplify how cough can be perceived as a physiologic and a pathologic process.

Answer 1

“Cough performs an essential protective function for human airways and lungs. Without an effective cough reflex, we are at risk for retained airway secretions and aspirated material predisposing to infections, atelectasis, and respiratory compromise. At the other extreme, excessive coughing can be exhausting; can be complicated by emesis, syncope, muscular pain, or rib fractures; and can aggravate abdominal or inguinal hernias and urinary incontinence.”

Question 2

How is it that capsaicin is related to cough?

Answer 2

Capsaicin might stimulate the cough reflex by chemical sensing. Also, a “cationic ion channel - the type 1 vanilloid receptor - found on rapidly adapting receptors and C fibers is the receptor for capsaicin, and its expression is increased in patients with chronic cough.”

Question 3

Summarize the afferent pathways that might trigger the cough reflex.

Answer 3

“Afferent nerve endings richly iinvervate the pharynx, larynx, and airways to the level of the terminal bronchioles and extend into the lung parenchyma. They may also be located in the external auditory meatus (the auricular branch of the vagus nerve, or the Arnold nerve) and in the esophagus. Sensory signals travel via the vagus and superior laryngeal nerves to a region of the brainstem in the nucleus tractus solitarius vaguely identified as the “cough center”.”

Question 4

Explain the physiologic process of cough.

Answer 4

“The vocal cords adduct, leading to transient upper-airway occlusion. Expiratory muscles contract, generating positive intrathoraci pressures as high as 300mmHg. With sudden release of the laryngeal contraction, rapid expiratory flows are generated, exceeding the normal “envelope” of maximal expiratory flow seen on the flow-volume curve.”

Question 5

A series of repetitive coughs at successively lower lung volumes sweeps the point of maximal expiratory velocity progressively further into the lung periphery.
True or False?

Answer 5

True.

Question 6

Name the major causes of impaired cough.

Answer 6

“Weakness, paralysis, or pain of the expiratory (abdominal and intercostal) muscles is foremost on the list of causes of impaired cough.”

Question 7

Impaired cough might occur with preserved expiratory muscle force.
True or False?

Answer 7

True.
“Cough may fail to clear secretions despite a preserved ability to generate normal expiratory velocities; such failure may be due to either abnormal airway secretions (e.g., bronchiectasis due to cystic fibrosis) or structural abnormalities of the airways (e.g., tracheomalacia with expiratory collapse during cough).”

Question 8

Which parameters might be used to quantify the impairment of cough?

Answer 8

Peak expiratory flow or maximal expiratory pressure.

Question 9

Name all the causes of impaired cough.

Answer 9

• Decreased expiratory-muscle strenght
• Decreased inspiratory-muscle strenght
• Chest wall deformity
• Impaired glottic closure or tracheostomy
• Tracheomalacia
• Abnormal airway secretions
• Central respiratory depression (e.g., anesthesia, sedation, or coma)

Question 10

What are the features of chronic bronchitis cough?

Answer 10

“The cough of chronic bronchitis in long-term cigarette smokers rarely leads the patient to seek medical advice. It lasts for only seconds to a few minutes, is productive of bening-appearing mucoid sputum, and generally does not cause discomfort.”

Question 11

Name causes of the following: (i) acute cough; (ii) subacute cough; (iii) chronic cough.

Answer 11

(i) acute cough (less then 3 weeks): respiratory tract infection, aspiration, or inhalation of noxious chemicals or smoke.
(ii) subacute cough (3-8 weeks): residdum of tracheobronchitis, as in pertussis or “postviral tussive syndrome”.
(iii) chronic cough (>8 weeks) inflammatory, infectious, neoplastic and cardiovascular etiologies.

Question 12

When one investigates chronic cough, which differential diagnosis should be considered if chest examination and radiography are both normal?

Answer 12

One should consider cough-variant asthma, gastroesophageal reflux, nasopharyngeal drainage, and medications (angiotensin-converting enzyme inhibitors).
Some authors argue that these causes account for more than 90% of chronic cough with a normal or noncontributory chest radiograph. “However, clinical experience does not support this contention, and strict adherence to this concept discourages the search for alternatives explanations by both clinicians and researchers.”

Question 13

Are there any aggravating or improving factors for cough?

Answer 13

Yes.
“Regardless of cause, cough often worsens upon first lying down at night, with talking, or with the hyperpnea of exercise; it frequently improves with sleep. An exception may involve the cough that occurs only with certain allergic exposures or exercise in cold air, as in asthma.”

Question 14

Cough might be a manifestation of systemic disease such as sarcoidosis or vasculitis.
True or False?

Answer 14

True.

Question 15

In isolated acute media otitis, how can one explain the cough mechanism?

Answer 15

Stimulation of the Arnold nerve (a branch of the vagus nerve) by the inflammatory/infectious process.

Question 16

Name the serious causes of isolated chronic cough dependent on the patient’s age.

Answer 16

“The list of diseases that can cause persistent cough without other symptoms and without detectable abnormalities on physical examination is long. It includes serious illnesses such as sarcoidosis or Hodgkin’s diseases in young adults, lung cancer in older patients, and (worldwide) pulmonary tuberculosis.”

Question 17

What should one sough in sputum citology?

Answer 17

Malignant cells or eosinophils versus neutrophils regarding the type of inflammatory cells present in chronic bronchitis.

Question 18

Summarize the findings related to ACE inhibitor-induced chronic cough as well as its epidemiology and therapeuty.

Answer 18

“ACE inhibitor-induced cough occurs in 5-30% of patients taking these agents and is not dose dependent. ACE metabolizes bradykinin and other tachykinins, such as substance P. The mechanism of ACE inhibitor-associated cough may involve sensitization of sensory nerve endings due to accumulation of bradykinin. In support of this hypothesis, polymorphisms in the neurokinin-2 receptor gene are associated with ACE inhibitor-induced cough. Any patient with chronic unexplained cough who is taking an ACE inhibitor should have a trial period off the medication, regardless of the timing of onset of cough relative to the initiation of ACE inhibitor therapy. In most instances, a safe alternative is available; angiotensin-receptor blockers do not cause cough. Failure to observe a decrease in cough after 1 month off medication argues strongly against this etiology.”

Question 19

Summarize the characteristics of chronic cough related to postnasal drainge.

Answer 19

“Postnasal drainge of any etiology can cause cough as a response to stimulation of sensory receptors of the cough-reflex pathway in the hypopharynx or aspiration of draining secretions into the trachea. Clues suggesting this etiology include postnasal drip, frequent throat clearing, and sneezing and rhinorrhea. On speculum examination of the nose, excess mucoid or purulent secretions, inflamed and edematous nasal mucosa, and/or polyps may be seen; in addition, secretions or a cobblestoned appearance of the mucosa along theposterior pharyngeal wall may be noted. Unfortunately, there is no means by which to quantitate postnasal drainage. In many instances, this diagnosis must rely on subjective information provided by the patient. This assessment must also be counterbalanced by the fact that many people who have chronic postnasal drainage do not experience cough.”

Question 20

Summarize the findings in history and complementary examination in gastroesophageal reflux related to chronic cough.

Answer 20

“Linking gastroesophageal reflux to chronic cough poses similar challenges. It is thought that reflux of gastric contents into the lower esophagus may trigger cough via reflex pathways initiated in the esophageal mucosa. Reflux to the level of the pharynx (laryngopharyngeal reflux), with consequent aspiration of gastric contents, causes a chemical bronchitis and possibly pneumonits that can elicit cough for days afterward. Retrosternal burning after meals or on recmbency, frequent eructation, hoarseness, and throat pain may be indicative of gastroesophageal reflux. Nevertheless, reflux may also elicit minimal or no symptoms. Glottic inflammation detected on laryngoscopy may be a manifestation of recurrent reflux to the level of the throat, but it is a nonspecific fidings. Quantification of the frequency and level of reflux requieres a somewhat invasive procedure to measure esophageal pH directly (either nasopharyngeal placement of a catheter with a pH probe into the esophagus for 24 h or endoscopic placement of a radiotransmitter capsule into the esophagus). The precice interpretation of test results that permits an etiologic linking of reflux events and cough remains debated.”

Question 21

Cough alone as a manifestation of asthma is common among children but not among adults.
True or False?

Answer 21

True.

Question 22

How does one diagnose chronic eosinophilic bronchitis? What are its main features?

Answer 22

“Chronic eosinophilic bronchitis causes chronic cough with a normal chest radiograph. This condition is characterized by sputum eosinophilia in excess of 3% without airflow obstruction or bronchial hyperresponsiveness and is successfully treated with inhaled glucocorticoids.”

Question 23

Which treatments are there available for postnasal drainage?

Answer 23

“Therapy for postnasal drainage depends on the presumed etiology (infection, allergy, or vasomotor rhinitis) and may include systemic antihistamines; antibiotics; nasal saline irrigation; and nasal pump sprays with glucocorticoids, antihistamines, or anticholinergics.”

Question 24

If you consider a patient that does not respond to usual therapy for chronic cough with a clear radiography, which test would you ask for and which diseases would you want look for?

Answer 24

“Patients who fail to respond to treatment targeting the common causes of chronic cough or who have had these causes excluded by appropriate diagnostic testing should undergo chest CT. Diseases causing cough that may be missed on chest x-ray include tumors, early interstitial lung disease, bronchiectasis, and atypical mycobacterial pulmonary infection.”

Question 25

Which drugs are there available for symptom-based treatment of cough?

Answer 25

• Opioids, such as codeine and hydrocodone,
• Dextromethorphan, benzonatate, gabapentin and amytriptline
• Neurokinin receptor antagonists, type 1 vanilloid receptor antagonists, and novel opioid and opioid-like receptor agonists (under investigation).

Question 26

What are the main differential diagnosis for hemoptysis?

Answer 26

Epistaxis and hematemesis.

Question 27

Name the causes of difuse alveolar hemorrhage (DAH).

Answer 27

“Causes of DAH can be inflammatory or noninflammatory. Inflammatory DAH is due to small-vessel vasculitis/capillaritis from a variety of diseases, including granulomatosis with polyangiitis and microscopic polyangiitis. Similiarly, systemic autoimmune diseases such as systemic lupus erythematosus can manifest as pulmonary capillaritis. Antibodies to the alveolar basement membrane, as are seen in Goodpastures disease, can also result in alveolar hemorrhage. In the early period after bone marrow transplantation, patients can develop a form of inflammatory DAH that can be catastrophic and life-threatening. The exact pathophysiology of this process is not well understood, but DAH should be suspected in patients with sudden-onset dyspnea and hypoxemia in the first 100 days after bone marrow transplantation.”

Question 28

Which type of lesion would you expect to produce a higher-volume hemoptysis: bronchial vascular involvement versus smaller airway vascular involvement?

Answer 28

The first would be expected to lead to a higher-volume hemoptysis.
“Bleeding in hemoptysis most commonly arises from the small- to medium-sized airways. Irritation and injury of the bronchial mucosa can lead to small-volume bleeding. More significant hemoptysis can result from the proximity of the bronchial artery and vein to the airway, with these vessels and the bronchus running together in what is often referred to as the bronchovascular bundle. In the smaller airway, these blood vessels are close to the airspace, and lesser degrees of inflammation or injury can therefore result in their rupture into the airways. While alveolar hemorrhage aries from capillaries that are part of the low-pressure pulmonary circulation, bronchial bleeding generally originates from bronchial arteries, which are under systemic pressure and thus are predisposed to larger-volume bleeding.”

Question 29

Patients with bronchiectasis are particularly prone to hemoptysis.
True or False?

Answer 29

True.

Question 30

How do you designate the dilatation of a pulmonary artery branch in the context of cavity formed by previous tuberculous infection?

Answer 30

Rasmussen’s aneurysm.

Question 31

Name some of the organisms commonly associated with hemoptysis.

Answer 31

• Mycobacterium tuberculosis.
• Streptococcus pneumoniae, Haemophilus influenzae, or Moraxhella catarrhalis, especially in those with chronic bronchitis.
• Staphylococcus aureus and gram-negative rods (e.g., Klebsiella pneumoniae), which are likely to cause necrotizing lung infections and thus to be associated with hemoptysis.

Question 32

Describe the features of paragonimiasis.

Answer 32

“While not common in North America, pulmonary paragonimiasis (i.e., infection with the lung fluke Paragonimus westermani) often presents as fever, cough, and hemoptysis. This infection is a public health issue in Southeast Asia and China and is frequently confused with active tuberculosis, in which the clinical picture can be similar. Paragonimiasis should be considered in recent immigrants from endemic areas who have new or recurrent hemoptysis. In addition, pulmonary paragonimiasis has been reported secondary to ingestion of crayfish or small crabs in the United States.”

Question 33

How many patients with lung cancer present with hemoptysis?

Answer 33

~10%

Question 34

Which type of lung cancers are most often associated with hemoptysis? How would you explain this correlation?

Answer 34

“Because both squamous cell carcinomas and small-cell carcinomas are more commonly in or adjacent to the proximal airways, and large at presentation, they are more often a cause of hemoptysis.”

Question 35

Carcinoid tumors lead to hemoptysis due to erusion to the adjacent vessels.
True or False?

Answer 35

False.
“Carcinoid tumors, which are found almost exclusively as endobronchial lesions with friable mucosa, can also present with hemoptysis.”

Question 36

Explain the pathophysiology between heart failure and valvulopathies with hemoptysis.

Answer 36

“Perhaps most frequently, congestive heart failure with transmission of elevated left atrial pressures can lead to rupture of small alveolar capillaries. These patients rarely present with bright red blood but more commonly have pink, frothy sputum or blood-tinged secretions. Patients with a focal jet of mitral regurgitation can present with an upper-lobe opacity on chest radiography together with hemoptysis. This finding is thought to be due to focal increases in pulmonary capillary pressure due to regurgitant jet.”

Question 37

Primary pulmonary arterial hypertension rarely causes hemoptysis.
True or False?

Answer 37

True.
Most often, pulmonary embolism, which is associated with pulmonary arterial hypertension, leads to hemoptysis but due to pulmonary infarction.

Question 38

Monthly hemptysis in women suggest catamenial hemoptysis from pulmonary endometriosis.
True or False?

Answer 38

True.

Question 39

How does one define massive hemoptysis?

Answer 39

> 200-600mL/24h.

Question 40

Patients rarely exsanguinate from hemopysis but can effectively “drown” in aspirated blood.
True or False?

Answer 40

True.

Question 41

Summarize the steps of physical examination in hemoptysis.

Answer 41

“The physical examination begins with an assessment of vital signs and oxygen saturation to gauge whether there is evidence of life-threatening bleeding. Tachycardia, hypotension, and decreased oxygen saturation mandate a more expedited evaluation of hemoptysis. A specific focus on respiratory and cardiac examinations is important; these examinations should inlude inspection of the nares, auscultation of the lungs and heart, assessment of the lower extremities for symmetric or asymmetric edema, and evaluation for jugular venous distension. Clubbing of the digits may suggest underling lung diseases such as bronchogenic carcinoma or bronchiectasis, which predisposes to hemoptysis. Similarly, mucocutaneous telangiectasis should raise the specter of pulmonary arterial-venous malformations.”

Question 42

When should you suspect a pulmonary-renal syndrome? Which tests would you ask for to rule in or out these hypothesis?

Answer 42

“Renal function should be evaluated and urinalysis condutected because of the possibility of pulmonary-renal syndromes presenting with hemoptsys. The documentation of acute renal insufficiency or the detection of red blood cells or their casts on urinalysis should elevate suspicion of small-vessel vasculitis, and studies such as anti-neutrophil cytoplasmic antibody, antiglomerular basement membrane antibody, and antinuclear antibody should be considered.”

Question 43

Bronchoscopy should be considered when previous tests are unrevealling of the etiology of hemoptysis.
True or False?

Answer 43

True for patients with a history of cigarette smoking since endobronchial lesions are not reliably visualized on CT.

Question 44

Summarize the steps for intervention in large-volume, life-threatening hemoptysis.

Answer 44

The first step is to establish a patent airway, usually by endotraqueal intubation and subsequent emchanical ventilation. As large-volume hemoptysis usually arises from an airway lesion, it is ideal to identify the site of bleeding by either chest imaging or bronchoscopy (more commonly rigid rather than flexible). The goals are then to isolate the bleeding to one lung and not to allow the preserved airspaces in the other lung to be filled with blood so that gas exchange is further impiared. Patients should be placed with the bleeding lung in a dependent position (i.e., bleeding-side down), and, if possible, dual lumen endotracheal tubes or an airway blocker should be placed in the proximal airway of the bleeding lung. These intervetions generally require the assistance of anesthesiologists, interventional pulmonologists, or thoracic surgeons.”

Question 45

Angiographic embolization might be considered if bronchoscopically mediated therapies are not efficacious in stopping the bleeding lung. What is the major risk associated with the first intervention?

Answer 45

Embolization of the spinal artery and consequent paraplegia.