CoughCough is the most common symptom reported at presentation by lung cancer patients. Cough is present at diagnosis in 50% or more of patients and eventually develops in nearly all patients who are not cured.¹⁰,¹¹ Cough in lung cancer may be related to many factors, including a central tumor, obstructive pneumonia, multiple parenchymal metastases, lymph node involvement, and pleural effusion. Even though cough is the most common symptom of lung cancer, it accounts as the only cause in about 2% of patients with chronic cough.¹²

Many lung cancer patients have underlying chronic obstructive pulmonary disease (COPD) and therefore may suffer from a chronic cough. Some smokers and former smokers also have a chronic cough referred to as smoker’s cough. Hence, the patient or the patient’s physician may ignore a gradual change in such a cough. A persistent change in the cough or acute exacerbation of COPD that fails to respond to therapy should prompt performance of a chest radiograph or even a CT scan. This evaluation is particularly important if the cough is not associated with fever or symptoms of upper respiratory tract infection or persists for longer than a week. Some of these patients are treated with multiple courses of antibiotics under the
presumption of bronchitis or pneumonia, thereby delaying the diagnosis of lung cancer.

Treatment of cough is most successful if the underlying etiology can be addressed. Thus, tumor-specific therapy is most successful in relieving lung cancer-related cough. In patients with airway involvement by the tumor, patients may also benefit from the addition of beta₂-agonists such as albuterol.

Many lung cancer patients continue to suffer from a persistent, distressing cough despite appropriate tumor-specific therapy. It is important to evaluate and treat other potential causes of cough such as postnasal drip, gastroesophageal reflux, and bronchospasm. Opiates have been used with some success for their antitussive properties.⁹ There is no evidence that one preparation of opiates is better than the other. Other antitussives such as guaifenesin, dextromethorphan, benzonatate, and levodropropizine may be tried, but they have had variable success in treating cancer-related cough.¹³,¹⁴,¹⁵,¹⁶

Inhaled lidocaine has been used to suppress cough.¹³,¹⁷,¹⁸,¹⁹ A starting dose of 5 mL of 2% lidocaine solution, via a nebulizer, every 4 to 6 hours may be used. The dose may be increased if required. Generally, dosages greater than 15 mL of 2% lidocaine solution are avoided to decrease the risk of seizures, from systemic absorption of lidocaine through the airways. Patients should be warned about the potential for aspiration resulting from oropharyngeal anesthesia. Corticosteroids can also be helpful in treating cough, particularly when the cough is related to underlying bronchitis, radiation-induced lung damage, or lymphangitic metastases. In addition, inhaled sodium cromoglycate may help cough of lung cancer through the inhibition of afferent unmyelinated C-fiber activation. C-fibers are involved in cancer-related cough, probably from the release of bradykinin by cancer cells and from the stimulation of the C-fibers by the cancer.²⁰

HemoptysisHemoptysis in lung cancer varies in severity but commonly consists of blood-streaked sputum. The most common description by the patient is that of coughing up blood-tinged sputum for several days in succession. Again, these patients are presumed to have bronchitis and are treated with antibiotics. The index of suspicion is raised if the symptom persists or recurs particularly in a patient who has a smoking history. It is prudent to initiate a workup immediately in a patient younger than 40 years with a smoking history who presents with hemoptysis. Although chest radiographs are usually abnormal in these patients, some may have a normal study. In these patients, further diagnostic studies such as sputum cytology, bronchoscopy,²¹ and CT scans should be considered. Detailed history of hemoptysis is essential because presence of hemoptysis is a contraindication for the use of bevacizumab. In the clinical trial, Eastern Cooperative Oncology Group phase III trial (ECOG 4599) that evaluated the role of bevacizumab, presence of half a teaspoon of hemoptysis per episode was an exclusion criteria.²²

The management of hemoptysis in lung cancer patients depends on the severity. Blood-streaked sputum does not require any specific therapy other than the therapy for lung cancer. More severe hemoptysis requires use of antitussives and advising the patient to sleep with the affected lung in the dependent position. In patients with advanced lung cancer, chest radiotherapy is the preferred treatment for moderate hemoptysis. In patients who have received prior radiotherapy, management of hemoptysis can be challenging.²³

In certain cases, emergent thoracotomy with resection of the affected area could be considered. However, technical difficulties or the general condition of the patient may preclude such an approach. Endobronchial brachytherapy is another alternative for control of hemoptysis in patients who have received prior external beam radiotherapy. Selective embolization of bronchial arteries feeding the hemorrhagic area can also be considered in settings where such expertise exists.²⁴,²⁵

Massive hemoptysis, which is fairly uncommon in lung cancer patients, is immediately fatal in many cases. The initial management of these patients is securing the airway with intubation or emergent tracheostomy to allow efficient suctioning of the blood that floods the alveoli, leading to respiratory failure. Bronchoscopy can be performed for both diagnostic and therapeutic purposes. Bronchoscopic instillation of cold saline solution or vasoconstrictive agents and bronchial balloon tamponade are some of the therapeutic interventions that could be implemented.²⁶ Further management of hemorrhage should proceed based on the clinical condition of the patient. Management of hemoptysis in lung cancer patients requires sound clinical judgment. Many patients with this problem have a poor prognosis, and any interventions chosen for the hemoptysis must be consistent with the patient’s prognosis.

Chest PainChest pain or discomfort is a common symptom that may occur even in early stage lung cancer, without frank evidence of invasion of the pleura, chest wall, or mediastinum. The origin of such discomfort is unclear because the lung parenchyma is not supplied with pain fibers. Patients may develop retrosternal pain from hilar and mediastinal adenopathy or at times from pericardial involvement. Pain from pleural involvement or rib metastasis is usually more localized
and severe than the nonspecific chest pain associated with lung cancer. Appropriate analgesics, including narcotics, should be used along with definitive antitumor therapy.

It is not unusual for patients with chest pain to undergo evaluation for coronary artery disease, including cardiac catheterization. Given the prevalence of coronary artery disease among smokers, it is not surprising that such patients have been discovered to have lung cancer from a chest radiograph performed prior to or after coronary artery bypass surgery.

DyspneaDyspnea is a fairly common symptom in patients with lung cancer. Most lung cancer patients have dyspnea during the course of their disease.²⁷ Dyspnea could be from various causes, including the tumor itself or the underlying chronic lung disease, and/or could be multifactorial (Table 23.2). Patients could also experience dyspnea from the complications of radiation therapy administered with or without chemotherapy. Incidence of dyspnea is often higher when pain and anxiety are high.²⁸

Management of dyspnea requires proper identification and treatment of the underlying etiology, with recognition that the tumor is not always the primary cause of the dyspnea. Symptomatic management of dyspnea includes judicious use of oxygen, opioids, and sedatives. Use of oxygen is clearly beneficial in the treatment of hypoxic patients with dyspnea.²⁹,³⁰ The role of oxygen, in treating dyspnea in patients who are not hypoxic, is unclear. There are studies that suggest that oxygen may be helpful in patients with nonhypoxic dyspnea,³¹,³² and based on this limited data, it is appropriate to offer a trial of oxygen in all cancer patients with dyspnea.

Opioids have been used to relieve dyspnea for many years. There is a concern about the potential of inducing respiratory failure with opioid use, particularly in patients with preexisting respiratory impairment.³³ However, studies in cancer patients suggest that opioids do not compromise respiratory function when titrated correctly.³⁴,³⁵ Respiratory depression is more a function of rate of change of the dose of opioids and the history of previous exposure to opioids.³⁶ Opioids administered through both parenteral and oral routes appear to be beneficial in relieving dyspnea.³⁷ Nebulized morphine was also assessed but was found to be no better than nebulized saline, when the data of randomized trials were analyzed.³⁷ Sedatives and tranquilizers have also been used to relieve dyspnea. Evidence supports the use of promethazine or chlorpromazine alone or in combination with morphine for the treatment of dyspnea, but the evidence for the use of benzodiazepines is lacking.³⁸,³⁹,⁴⁰,⁴¹ Systemic steroids should be considered in patients with acute exacerbation of COPD and in patients with treatment-related lung toxicity.

Dyspnea is an extremely distressing symptom for the patient and the family. Relief of dyspnea to the maximum extent possible should be a primary goal of the treating physician. Education regarding complimentary methods such as breathing and relaxation techniques has been shown to be helpful for patients dealing with dyspnea.⁴² It is also important to educate the patient and the family about measures that can be taken to relieve dyspnea such as anticipatory administration of opioids, taking frequent rests during physical activities, and sitting near an open window or in front of a fan.

WheezingLocalized wheezing may be the presenting symptom in patients with disease in the major airways, particularly in the mainstem bronchi. This symptom should be distinguished from the generalized wheezing of bronchospasm. The patient is often able to tell from where the wheezing is emanating. This type of localized wheezing is often associated with cough.

Lesions that are primarily endobronchial, but are too proximal for resection, often require special management techniques. Newer techniques have improved the ability to control such cancers and thus the symptoms from these lesions. High-dose brachytherapy, either alone or in combination with external beam radiation, can be highly effective in palliating such lesions.⁴³ Photodynamic therapy techniques have improved recently with the development of better photosensitizing agents and can be effectively employed in this setting.⁴⁴ Laser therapy can also be useful for this problem, particularly when other treatments have failed.⁴⁵ Stents made of different materials have been used, following tumor debridement to relieve airway obstruction, primarily when the obstruction is in central airways.⁴⁶,⁴⁷

PneumoniaPneumonia can be a common presentation of lung cancer. Patients may not have the classical symptoms of pneumonia such as high fever, pleuritic chest pain, cough, and dyspnea but may have more generalized symptoms such as fatigue. A chest x-ray performed for evaluation may reveal lobar consolidation or atelectasis. These patients may not necessarily have pneumonia but are treated for pneumonia based on chest x-ray findings and despite lack of resolution are continued on different antibiotics. It is essential that follow-up x-rays are performed for evaluating resolution of the original findings.

HoarsenessHoarseness in lung cancer patients is almost always caused by the involvement of the left recurrent laryngeal nerve resulting in left vocal cord paralysis. Because the left recurrent laryngeal nerve passes under the arch of the aorta, it is susceptible to involvement by primary tumors or lymphadenopathy in the aortopulmonary window. It is not unusual for patients with hoarseness to have had laryngoscopy and CT scans of the neck performed and then told that they have vocal cord paralysis, without any chest evaluation. New-onset hoarseness caused by involvement of the left recurrent laryngeal nerve is usually indicative of surgically unresectable lung cancer. Hoarseness may also be observed after surgery for lung cancer, because the recurrent laryngeal nerve may have to be sacrificed for complete resection of the tumor.

Vocal cord paralysis leads to voice change, in addition to hoarseness, and could also cause aspiration, dyspnea, and/or dysphagia. Hoarseness may improve with treatment of lung cancer, but more often it is persistent because of inadequate control of the primary tumor or irreversible damage to the nerve. Management of vocal cord paralysis includes Teflon or Gore-Tex injection of the vocal cord or phonosurgery.⁴⁸,⁴⁹ These procedures can improve the vocal quality, as well as improve other symptoms such as dysphagia and aspiration. Some patients may require feeding tubes to prevent aspiration pneumonia.

Phrenic Nerve ParalysisThe phrenic nerve courses along the pericardium bilaterally and is subject to injury caused by invasion from the primary tumor or bulky adenopathy. The left phrenic nerve is more commonly affected than the right, probably because of the relatively greater proximity of the left phrenic nerve to lymph nodes of the aortopulmonary window. Damage to the left phrenic nerve results in paralysis of the left hemidiaphragm, with consequent volume loss in the left hemithorax. Because the left hemidiaphragm is normally lower than the right, this condition has a rather characteristic x-ray appearance. The proximity of the left recurrent laryngeal nerve to the phrenic nerve in the aortopulmonary window occasionally results in coexisting hoarseness and left diaphragmatic paralysis. Phrenic nerve paralysis is always indicative of locally advanced disease. This condition is generally not reversible.

DysphagiaDysphagia can result from esophageal obstruction by bulky mediastinal adenopathy. Although bulky adenopathy is a relatively common occurrence, this symptom is surprisingly uncommon. Another potential cause of dysphagia is recurrent laryngeal nerve damage that can lead to dysfunction of the pharyngeal swallowing mechanism. This problem may be associated with aspiration as well (see preceding discussion under “Hoarseness”). Treatment of the mediastinal adenopathy with radiotherapy (with or without concurrent chemotherapy) may improve dysphagia caused by this mechanism. However, radiation-induced esophagitis could lead to acute odynophagia and dysphagia with a few patients developing chronic dysphagia from esophageal strictures. Selected patients may require nutritional support until effective swallowing is reestablished.

StridorStridor results from compromise of the lumen of the trachea. It can be caused by invasion of the trachea by tumor, or less commonly, bilateral vocal cord paralysis. An aggressive approach to management of stridor is necessary, because this problem is life threatening and extremely distressing. Prompt initiation of treatment, including radiotherapy or brachytherapy, with or without chemotherapy, is essential. For lesions located high in the trachea, or stridor caused by vocal cord paralysis, a tracheostomy may permit placement of a rigid canula beyond the obstruction. Considerations could be given to treatments, such as photodynamic therapy or laser therapy, to improve the airways prior to proceeding with more definitive therapy. Because flow is related to diameter in an exponential fashion, a small increase in diameter can result in a dramatic improvement in symptoms. This increase can sometimes be accomplished via laser fulguration.⁵⁰,⁵¹

Symptoms can be eased by the use of a helium-oxygen mixture (70:30), in place of room air or oxygen alone. Helium has a much lower viscosity than nitrogen, thus reducing obstruction to flow.⁵² Patients whose disease progresses despite therapy may require significant doses of morphine for control of symptoms.

Superior Vena Cava SyndromeSuperior vena cava (SVC) syndrome is a relatively common complication of lung cancer.⁵³,⁵⁴ It is generally a consequence of obstruction of the SVC by right paratracheal adenopathy or central extension of primary tumor in the right upper lobe. The syndrome is characterized by facial swelling, flushing, cough, and neck and chest wall vein distention. The extent and severity of symptoms greatly depends on how rapidly the obstruction progresses and on the speed and extent of the development of collateral circulation. Rapidly developing obstruction is most dangerous because it can result in central nervous system symptoms, including coma and death. Much more commonly, the onset is insidious, with swelling of the face, upper extremities, and breasts, causing the patient to seek medical attention.

In the undiagnosed patient, the principal differential diagnosis is between lung cancer and lymphoma. Approximately 80% of patients with SVC syndrome in the United States have an underlying diagnosis of lung cancer, divided approximately equally between small cell and non-small cell histologies. Once considered an emergency, current practice is to obtain a tissue diagnosis expeditiously prior to the initiation of appropriate therapy.⁵⁵ Bronchoscopy, mediastinoscopy, or mediastinotomy usually yield a diagnosis with little risk to the patient. Radiotherapy remains the preferred treatment for non-small cell lung cancer (NSCLC) and in selected situations, concurrent chemotherapy may be appropriate. Percutaneous stenting of the SVC is being increasingly used as the first treatment
modality.⁵⁶,⁵⁷ Stents are also considered in patients who have not responded to other treatment modalities. In uncommon circumstances, surgery could be considered for bypass or replacement of the SVC.

Pleural EffusionApproximately 15% of lung cancer patients present with pleural effusion. Although most of these effusions are ultimately determined to be malignant, about one half are initially cytologically negative. Diagnostic thoracentesis should be performed to determine the origin of the effusion, with an adequate amount of fluid sent for cytology. The differential diagnosis for causes of effusion can include atelectasis, pneumonia, lymphatic obstruction from enlarged lymph nodes, and congestive heart failure, among others. It is important to identify malignant effusion if possible. Proper classification of an effusion can both prevent the application of ineffective local measures (i.e., surgery or radiotherapy) as well as ensure that resectable patients are not denied the benefits of surgery.

The management of malignant pleural effusion varies greatly, depending on the clinical situation. Patients with good performance status and reasonable life expectancy can benefit from aggressive interventions such as video-assisted thoracoscopy and talc insufflation. Traditional thoracostomy tube placement can also be beneficial to patients who are in good physical condition.⁵⁸,⁵⁹ Patients with more advanced stages of disease are better served by placement of a flexible small-bore catheter, which does not require hospitalization. It is also important to understand that patients with trapped lung caused by parenchymal or pleural disease will not benefit from pleural fluid drainage.

Pleural effusions may resolve with effective chemotherapy, especially in patients with small cell lung cancer (SCLC). In NSCLC patients who are not symptomatic from the effusion and do not have a large effusion, chemotherapy may be tried as the initial management, but most patients in this category eventually require more aggressive local measures.

Pericardial EffusionPericardial effusion develops in 5% to 10% of lung cancer patients. At autopsy, cardiac involvement occurs in approximately 15% of cases.⁶⁰,⁶¹ Pericardial effusion typically occurs in the setting of locally advanced disease. Patients usually have dyspnea and orthopnea as the initial symptoms. The other symptoms and signs associated with pericardial effusion are anxiety, substernal chest tightness, jugular venous distension, and hepatomegaly.

Pericardial effusion causing cardiac tamponade is missed in up to one third of patients. The symptoms can be only dyspnea and anxiety and are often attributed to progression of parenchymal lung disease. The finding of dyspnea without concurrent hypoxia in an anxious, dyspneic patient with locally advanced lung cancer should prompt an investigation for pericardial disease.

Management of pericardial disease is dependent on whether the patient has cardiac tamponade. Patients with tamponade require immediate intervention with the preferred treatment being pericardiotomy (pericardial window) via a subxiphoid approach.⁶² Patients with very short expected survival or patients who do not have tamponade could be treated with pericardiocentesis. If appropriate expertise is available, placement of a small bore pericardial catheter can be effective. Such a catheter could be used to instill a sclerosing agent, which may help achieve long-term control of the effusion in many patients.⁶³

Pericardial effusion can be a late complication of chest radiation therapy (with or without chemotherapy) when significant portions of the pericardium are included in the radiation field.⁶⁴ Therefore, occurrence of pericardial effusion in a patient who has received chest radiation should not be assumed to be tumor recurrence.