According to the National Cancer Institute and American Cancer Society, lung cancer was the second most common cancer identified in both men and women, second only to prostate cancer and breast cancer, respectively. Lung cancer, however, remains the most common cause of cancer-related mortality in the United States, claiming over 160,000 deaths in 2012 alone. Less than 20% are small cell in type, whereas over 80% are non-small cell. According to the CDC, 80% of mortality among men and ~50% of mortality among women from lung cancer can be directly attributable to smoking. Despite advances in radiologic imaging with low-dose computed tomography (CT) and positron emission tomography (PET) scanning, screening has not yet proved beneficial in decreasing mortality from lung cancer.

SCLC is considered a systemic disease, and thus surgery plays no part in the management of the disease. Multiple staging systems are used for SCLC, including the American Joint Cancer Commission (AJCC), the Veteran’s Administration Lung Study Group (VALG), and the International Association for the Study of Lung Cancer (IASLC). All of these classifications attempt to identify SCLC as either limited stage disease (those lesions that can be encompassed in a single radiation field) or extensive disease. Limited stage disease describes disease confined to one hemithorax that can be included in a reasonable thoracic radiation field. This includes extension to supraclavicular nodes on the same side as the sentinel lesion. Approximately 80% of patients respond to chemotherapy. Prophylactic cranial irradiation reduces the incidence of brain metastases, but has not been shown to prolong survival.

With currently available modalities in thoracic surgery, postoperative mortality rate is <5%. About 20% to 33% of patients are suitable for resection at the time of diagnosis, and lobectomy is the most commonly performed operation. Surgery offers the best chance of cure for non-small-cell lung Ca. Stages IA and IB diseases are associated with 5-year survival rates of 67% and 57%, respectively, whereas stages IIA, IIB, and IIIA have 5-year survival rates of 55%, 39%, and 26%, respectively. Advanced stages such as IIIB and IV have poor 5-year survival rates of 5% and 1%, respectively.

The overriding concern is to improve tissue oxygen delivery. Following are the current guidelines for long-term supplemental O₂ therapy based on the gold criteria: PaO₂ of 55 mmHg or less OR an SaO₂ of less than 88% confirmed twice over a 3-week period. Alternatively, supplemental O₂ is also indicated if one has a PaO₂ between 55 and 60 mmHg OR an SaO₂ of 88% if they have one of the following conditions: pulmonary hypertension, peripheral edema suggesting congestive heart failure, or hematocrit >55%. Although supplemental oxygen may contribute to hypercapnia (mostly by affecting ventilation-perfusion mismatching rather than the suppression of hypoxic drive), correcting hypoxemia is critical. The mechanism whereby chronic oxygen improves survival is probably by reducing pulmonary hypertension. The best way to reduce pulmonary artery pressures is to correct hypoxemia.

Asbestos exposure represents a spectrum of histopathologic and radiographic findings that are typically broken up into three major categories: pleural disease, interstitial disease, and malignancies.

Pleural disease is often considered the hallmark of asbestos exposure, and upwards of 50% of patients will have some pleural involvement. Pleural disease manifests as either pleural plaques, pleural adhesions causing rounded atelectasis, or benign asbestos pleural effusions (BAPEs). Pleural plaques preferentially involve the parietal pleura adjacent to the ribs. They are considerably less extensive in the visceral pleura and the intercostal space and are almost never seen in the costophrenic angles or the apices. Rounded atelectasis is a non-specific finding and can be seen with just about any type of pleural inflammation. BAPEs are typically very small and unilateral and can be seen before the interstitial disease. Pleural fluid analysis can be varied: up to one-third have increased pleural eosinophils and can be as high as 50% of the total nucleated cell count.

The interstitial process typically involves the lower lung zones and can be seen as non-specific imaging findings of haziness on CXR and ground glass opacities on CT scan early in the disease. This eventually progresses to honeycombing. Lymphadenopathy, either hilar or mediastinal, is not associated with asbestosis.

Asbestos is classically linked to mesothelioma, and along with smoking is a major risk factor for this malignancy. However, asbestos exposure has also been linked to both small- and non-small-cell lung cancers.

Sarcoidosis is an inflammatory condition marked by noncaseating granulomas of affected tissue without evidence of another identifiable etiology. Given that infection, particularly mycobacterial and fungal infections are on the differential, a travel and occupational history is important. Occupational history is also important, as there have been association with certain occupational irritants, specifically insecticides and building materials. Clinical presentation can vary substantially and can involve any organ systems. The most common organs involved are the lymphatic system, lungs, skin, and eyes. Up to 90% of patients with sarcoidosis will have some involvement from these systems. The most common presentation is a chest radiograph showing hilar lymphadenopathy or reticulonodular infiltrates in an asymptomatic patient. Angiotensin-converting enzyme (ACE) is produced by granulomas, and elevated levels can be seen in up to 60% of patients. However, genetic polymorphisms can lead to variable levels in individuals, leading to a lack of both sensitivity and specificity in the diagnosis of sarcoidosis. Currently, the role of ACE levels is controversial at best. Making a histologic diagnosis of sarcoidosis is not considered sufficient reason to treat with steroids. Commonly accepted indications for treatment include significant symptoms or progressive loss of lung function. Involvement of critical extrapulmonary organs, such as cardiac or renal sarcoid, also may prompt treatment.

This question is meant to emphasize the fact that the term asbestosis should be reserved for patients with evidence of pulmonary parenchymal scarring. Pleural disease does not merit the diagnosis of asbestosis. The clinical relevance of this distinction centers around two issues: increased symptoms in patients with asbestosis, as most pleural disease does not cause symptoms or impairment, as well as the increased risk of malignancy in patients with asbestosis versus asbestos associated with pleural disease. Patients with any asbestos exposure, even low level exposure without evidence of pleural or parenchymal disease are at increased risk for mesothelioma compared with the general population. Those patients with asbestos-associated pleural disease have a comparable risk of mesothelioma as those with asbestos exposure without pleural disease. However, asbestosis is associated with a higher risk of mesothelioma compared with those with pleural disease. This risk is further increased by concurrent smoking, and as such, all patients with asbestosis should be strongly discouraged against smoking. BAPEs are typically very small and unilateral and can be seen before the interstitial disease. Patients with evidence of pleural disease can develop rounded atelectasis, which can appear mass like on imaging and is often mistaken for malignancy.

Silicosis represents pulmonary manifestations after exposure to silica. Silica exposure is often seen in mining, glass manufacturing, sand blasting, and road and building construction. Silicosis manifests clinically along a spectrum of
simple chronic silicosis (most common), accelerated silicosis and acute silicosis, based on the chronicity of symptom development compared to exposure to silica. They all lead to increased inflammation in the pulmonary parenchyma and intrathoracic lymph nodes, predominantly in the upper lobes. Silicosis is associated with the following complications: progressive massive fibrosis, lung cancer, and respiratory failure. Silicosis is also associated with an increased risk of TB, and therefore, patients should get regular Tb testing. Silicosis has also been associated with higher incidence of autoimmune conditions such as rheumatoid arthritis, scleroderma, and systemic lupus erythematosus.

Pulmonary involvement is a major cause of mortality in connective tissue disease. Pulmonary involvement is most commonly ILD but can also involve pulmonary hypertension, pulmonary thromboembolic disease, and pulmonary nodules. As with many of the connective tissue disease-associated ILDs, there is no real correlation between the severity of the ILD and the extrapulmonary manifestations. It is generally more common in men with rheumatoid arthritis versus women with rheumatoid arthritis. To further underscore the disconnect between pulmonary and extrapulmonary manifestations of connective tissue disease, lupus pneumonitis can be seen in up to 50% of patients without any previous history of lupus. Jo-1 is associated with dermatomyositis/polymyositis and has a stronger association with ILD. ILD associated with Sjögren syndrome is associated with a lymphocytic infiltrate, not neutrophilic infiltration.

This question identifies a patient with diabetes and alcohol abuse who is at risk for complicated infections, and presenting with sepsis. The management of this patient must be prioritized based on the acuity of the patient. The patient is ill appearing, but is not in acute respiratory distress or in shock. He does not have any indications for urgent intubation and mechanical ventilation. Once emergent issues are addressed, source identification and control is paramount. Patient clearly has a respiratory focus for this infection evidenced by the symptoms of fever, productive cough, and pleuritic chest pain. This is further confirmed by infiltrates on imaging. However, he also has an effusion with pleural fluid analysis suggestive of a urea splitting organism leading to increased ammonia production and increased pH. Some gram-negative bacilli, specifically Proteus is associated with empyema with elevated pH. The mainstay of therapy for an empyema is drainage with tube thoracostomy. If this fails, then open thoracostomy is warranted. Given the overwhelming evidence of a pulmonary infection, management of this should not be delayed looking for other sources. With a chronic indwelling Foley catheter, he is at higher risk for colonization, and a urine culture without urinalysis is of limited utility. Also, EGD would not be warranted in this patient.

Pulmonary complications are a major cause of mortality of rheumatoid arthritis, however, pleural effusions is an uncommon manifestation. Pleural effusions associated with rheumatoid arthritis are more common in men (as are most pulmonary manifestations). Pleural fluid analysis classically shows a low pH, high LDH, low protein, and low glucose. The fluid is predominantly composed of PMNs, and pleural biopsy may show rheumatoid nodules. These last two findings are more specific findings, and the absence of these should not exclude rheumatoid effusion from the differential. This may be difficult to differentiate from empyema and parapneumonic effusion based on fluid analysis alone. However, in this patient, he had a previous pleural effusion and is non-toxic in appearance. He also has a history of articular symptoms, pointing toward underlying RA. He also had a negative PPD 3 months previously, making TB an unlikely etiology for the pleural effusion.

The mainstay of therapy for rheumatoid arthritis is immunosuppression, especially corticosteroids acutely. Corticosteroids have also been shown to be effective for rheumatoid effusions. There is no role for drainage of a rheumatoid effusion.

The identification of a young woman with a history of spontaneous pneumothorices and interstitial markings on CXR as concerning for LAM is the first step in answering this question. This is further confirmed by evidence of a chylothorax with high triglycerides and low cholesterol levels confirms this finding. Chylothoraces is associated with disruption of the thoracic duct or its tributaries and is classified as either a traumatic cause versus non-traumatic causes. The most common non-traumatic causes in younger patients are lymphoma and LAM. Lymphoma is not typically associated with interstitial markings on CXR and would not explain the pneumothoraces 1 year prior.

This is a cholesterol, also known as pseudochylothorax or chyliform effusion, as evidence by low triglycerides and elevated cholesterol in the pleural fluid. The presence of cholesterol crystals is also consistent with a cholesterol effusion. The rest of the pleural fluid is consistent with a rheumatoid effusion and high LDH and low glucose. This is also consistent
with the patient’s history of preexisting rheumatoid arthritis. Cholesterol effusion is associated with chronic inflammation or infection of the pleura, most commonly rheumatoid effusions and tuberculosis. The treatment for a cholesterol effusion is treatment of the underlying condition and conservative management. Medium-chain triglyceride diet is the appropriate diet for a chylothorax, not for a pseudochylothorax. Chylothorax is evidenced by fluid analysis high in triglycerides, and low in cholesterol, which is inconsistent with this patient. Chylothorax is caused by obstruction or damage to the lymphatic system. Lymphangiography would potentially be indicated for a chylothorax. Wuchereria bancrofti is a parasitic infection associated with lymphatic obstruction. It is responsible for up to 90% of lymphatic filariasis. This would present as a chylous effusion as well. Bilateral pleuroperitoneal shunt is a treatment for persistent chylothorax.

A thoracentesis is a relatively safe procedure. The major complications are pneumothorax, hemothorax, hemorrhage, and re-expansion pulmonary edema. This patient developed reexpansion pulmonary edema, presumed secondary to rapid change in intrathoracic pressure leading to microvascular injury. The patient develops pulmonary edema following drainage of a large volume of a chronic pleural effusion. Intrapleural pressure monitoring could be used to minimize the risk of this occurring. The physical examination findings are not consistent with hemothorax or pneumothorax.

The patient has signs of a left-sided tension pneumothorax on the left as evidenced by a rapid deterioration of respiratory and hemodynamic status, decreased air entry on the left and tracheal deviation to the right. Tension pneumothorax is a clinical diagnosis and does not require radiographic confirmation prior to intervention. Urgent decompression of the pneumothorax is essential and is achieved by needle thoracostomy in the second intercostal space on the side of the pneumothorax. No other intervention will correct the hemodynamic compromise and may actually worsen it.

Pericardiocentesis with drainage of effusion leads to cardiac tamponade. Recognition of the right-sided waveforms and their derangements in disease is useful when prioritizing diagnostic tests, when decisions must be made urgently, or when there are conflicting data. It is important to be familiar with expected values for filling pressure (typically 4 to 8 mmHg for CVP). The differential diagnosis for elevated CVP in the setting of shock includes acute right heart failure (massive pulmonary embolism, right ventricular infarction), pericardial disease, and acute left heart disease (large myocardial infarction, acute mitral regurgitation, acute ventricular septal defect). The finding of an attenuated y descent is characteristic of cardiac tamponade because there is equalization of pressures between the atria and ventricles, which impairs atrial emptying. In uremic pericarditis, the expected tachycardia may be absent due to autonomic insufficiency; likewise, the ECG may not reveal diffuse ST segment elevations. In the early stages of septic shock, there is usually hypovolemia, so the CVP should be low. Massive pulmonary embolism and acute mitral valve rupture may cause hypotension but should not preferentially affect the y descent.

It is important to recognize common complications of mechanical ventilation in patients with severe airways obstruction. Development of intrinsic positive end-expiratory pressure (PEEP; auto-PEEP, dynamic hyperinflation) is one of the most significant complications. Intrinsic PEEP can result in patient-ventilator dyssynchrony, agitation, difficulty weaning, ventilation/perfusion mismatch, barotrauma, and impairment of right-sided venous return leading to cardiovascular collapse. An important consideration is tension pneumothorax, but typically the patient will exhibit physical examination signs such as tracheal deviation, unilateral decrease of breath sounds, and hyperresonance on percussion. Prevention of intrinsic PEEP is achieved by maximizing alveolar emptying, either by decreasing airways resistance (bronchodilators) or by increasing expiratory time. Techniques to increase expiratory time include ensuring a low respiratory rate using sedatives and, if necessary, paralytics, decreasing the inspiratory time by adjusting the flow rate or the I:E ratio, and setting the mandatory rate on the ventilator as low as possible. Hypercapnia is acceptable to achieve this goal. However, none of these techniques is generally rapid enough to be helpful when hypotension is already established. Temporarily disconnecting the endotracheal tube from the ventilator circuit, and therefore the effects of positive-pressure ventilation, is the quickest way to effectively restore BP.

This question highlights an important topic in critical care medicine-drug interactions. An important effect of drug interaction in the critically ill patient is hypotension caused by partial adrenal insufficiency. This drug interaction occurs in patients receiving drugs that can increase the activity of the P450 system (e.g., phenytoin, phenobarbital). When the P450 system is activated, the metabolism of steroids increases, creating a state of partial adrenal insufficiency. This drug interaction should be suspected in patients receiving medication that can increase the metabolism of the P450 system and who present with persistent hypotension in the absence of other etiologies. An increasingly recognized offender is etomidate, a medication commonly used in rapid-sequence intubation, which blocks adrenal steroid production directly.

Macrolides and haloperidol, drugs commonly used in the intensive care unit, are known to increase the QT interval. Patients with underlying ischemic heart disease and electrolyte and acid-base abnormalities are more likely to develop this complication. Phenothiazines, antiarrhythmic medications, tricyclic antidepressants, and antipsychotic agents and cisapride can prolong the QT interval as well.

Interpretation of ABG abnormalities is a key skill in critical care medicine. Systematic evaluation of the ABG results often leads to unsuspected findings, such as triple acid-base disorders or respiratory insufficiency. In this case, use of “Winter formula” allows assessment of the adequacy of the respiratory response to the primary acidosis:

Expected, PCO₂ = ([1.5 × measured HCO₃] + 8) ± 2

To evaluate for the presence of two metabolic processes, one must compare the change in AG versus the change in bicarbonate. In the setting of hypoalbuminemia, the expected AG should be reduced by about 2.5 mEq/L for every 1 g/dL decrease in serum albumin, with normal AG in most laboratories ranging from 6 to 12 mEq/L.

Using 12 mEq/L as the AG normal value, in the previous example, the expected AG should be [12 mEq/L – (2.5 × 1.6 g/dL decrease of albumin)] = 8 mEq/L. However, the calculated gap is 23 mEq/L. Thus, the AG has increased by 15 mEq/L over the expected value. Has there been an equivalent (equimolar) change in the bicarbonate level? In this case, the bicarbonate has decreased from 24 mEq/L (normal) to 10 mEq/L = 14 mEq/L. Therefore, all the change in bicarbonate level can be explained by the unmeasured anions. If the change in bicarbonate were more severe than that predicted by the change in AG, a superimposed nongapped acidosis would be suspected; if less profound, then a concomitant metabolic alkalosis should be considered.

The correct answer depends on recognizing that the likely diagnoses are community-acquired pneumonia or aspiration pneumonitis with acute respiratory distress syndrome (ARDS). The development of pneumonia after 48 hours in the hospital, or within 3 months of a prior hospitalization, classifies as hospital-acquired pneumonia, mandating consideration of antipseudomonal antibiotics as part of the initial therapy. However, in community-acquired pneumonias, there are mitigating factors that may provide indications for more extensive antimicrobial coverage. In patients admitted to the intensive care unit, there is a high likelihood that resistant organisms will be present, including drug-resistant pneumococcus, Legionella species, and community-acquired methicillin-resistant Staphylococcus aureus (MRSA). Therefore, patients with severe community-acquired pneumonia should be treated with a combination of a potent antipneumococcal cephalosporin and either an advanced macrolide or quinolone. In patients with risk factors for Pseudomonas aeruginosa, including immunosuppression, significant structural lung disease [cystic fibrosis (CF), bronchiectasis, or repeated exacerbations of COPD that require frequent glucocorticoid and/or antibiotic use], probable aspiration, or multiple medical comorbidities, an antipseudomonal penicillin should be used. The use of vancomycin in severe community acquired pneumonia is hotly debated, but should generally be reserved for individuals with gram-positive organisms on sputum examination or risk factors for community-acquired MRSA (recent influenza-like illness, prior antibiotic therapy, end-stage renal disease, or injection drug abuse).

Although this individual may have AIDS, the onset of Pneumocystis pneumonia (PCP) is usually subacute. Although the sensitivity of bronchoalveolar lavage for diagnosing PCP is excellent in HIV (97% to 99%), it is less sensitive in the non-HIV population.

This man’s clinical picture suggests obstructive sleep apnea. Patients with unexplained excessive daytime sleepiness deserve further evaluation, and the diagnosis of obstructive sleep apnea requires examining a patient during sleep with a polysomnogram.

CF is a fatal autosomal recessive, multisystem disease that usually presents with persistent pulmonary infection, pancreatic insufficiency, and sinusitis. Additional features include pancreatitis, infertility, diabetes, deep vein thrombosis (DVT), and, rarely, biliary cirrhosis. Although CF is generally diagnosed in infants and children, patients may present later in life with atypical symptoms. One large retrospective cohort study of 1,051 patients with CF found that 7% received a diagnosis at age 18 years or older. Progressive lung disease and eventual respiratory failure continue to be the major causes of morbidity and mortality. The sweat chloride test is the gold standard for CF diagnosis, and a result of >70 mEq/L distinguishes CF from other lung diseases. More than 95% of men with CF are infertile, mostly due to incomplete development of the Wolffian structures, particularly the vas deferens. Digital clubbing is often seen in patients with moderate to severe disease.

Anaphylaxis can occur within 5 to 60 minutes after exposure to an allergen. This medical student is at risk for anaphylaxis and death. He needs a controlled and monitored environment. Epinephrine is the drug of choice; fatality rates are highest in patients in whom epinephrine administration is delayed. Severe airway edema, severe bronchospasm, or hypotension requires intravenous administration of 0.5 to 1.0 mL of epinephrine. Mild or moderate symptoms without laryngeal edema, bronchospasm, or hypotension should be treated with 0.3 to 0.5 mL of 1:1,000 epinephrine subcutaneously or intramuscularly.

A solitary pulmonary nodule is a lesion that is usually <3 cm and surrounded by pulmonary parenchyma. Larger lesions are more likely to be malignant than smaller lesions. Malignant lesions tend to have more irregular and spiculated borders as compared to the smooth and discrete border of benign lesions. Increased density on CT argues against malignancy with the cutoff of >164 Hounsfield units for benign and <164 Hounsfield units for malignant lesions. Certain patterns of calcification such as “popcorn” calcification, laminated (concentric) calcification, central calcification, and diffuse homogeneous calcification suggest that a lesion is benign, whereas reticular, punctate, amorphous, or eccentric calcifications raise the concern for malignancy. A nodule with a low probability of being malignant may be followed with serial chest CT scans. A nodule that is ≥1 cm and has an intermediate probability of being malignant should be evaluated by fluoro-2-deoxyglucose-PET. If the nodule is negative by PET, they too can be followed with serial chest CT scans; if the PET is positive, the nodule should be excised. A nodule that is <1 cm and has an intermediate probability of being malignant can be followed by serial chest CT scans. Any nodule that has a high probability of being malignant should be excised. For nodules ≥4 mm, serial CT scans are not required if the patient is at low risk. Patients who are at high risk or have nodules >4 mm should have follow-up chest CT scanning.

The pulmonary symptoms and signs are suggestive of bronchiectasis. Kartagener syndrome consists of dextrocardia, sinusitis, and bronchiectasis. Young syndrome is defined
as obstructive azoospermia; approximately 20% to 30% of patients have bronchiectasis. Early panacinar emphysema, as well as bronchiectasis, may develop in patients with α₁-antitrypsin deficiency. Yellow nail syndrome is characterized by the triad of lymphedema, pleural effusion, and yellow discoloration of the nails; 40% of patients have bronchiectasis. Patients with Williams-Campbell syndrome have a deficiency of the bronchial cartilage of medium-size airways, which dilate and can be complicated by bronchiectasis.

ARDS patients who are mechanically ventilated have an intensive care unit course complicated by barotrauma, nosocomial pneumonia, and multiple organ failure. Additional complications include deep vein thromboses, gastrointestinal bleeding, malnutrition, and side effects from sedatives and paralytics. Barotrauma occurs in a minority of ventilated patients (13% in one study), with barotrauma rarely directly causing death. The tissue breakdown seen in ARDS, high airway pressures, and high tidal volumes predisposes to barotrauma. Barotrauma is evidenced by the development of pneumothorax, subcutaneous emphysema, pneumomediastinum, and interstitial emphysema. Increased radiolucency at the lung bases and the presence of the deep sulcus sign on a chest radiograph are clues to barotrauma and pneumothorax. Nosocomial pneumonia is present in 55% of patients with ARDS and is accompanied by nonspecific findings. The combination of a corticosteroid and a neuromuscular blocking agent has been associated with a reversible myopathy that takes several months to resolve.

Infection is a frequent cause of COPD exacerbation. All patients with stable COPD should be offered pneumococcal vaccine, especially if they are 65 years or older, or with FEV₁ <40%. An influenza vaccine should be offered to all patients with COPD annually. All patients should be strongly encouraged to quit smoking because this can minimize exacerbations and retard the rate of FEV₁ decline. For all patients with COPD, a short-acting bronchodilator must be used on an as-needed basis and if that is insufficient to control symptoms, a regularly scheduled long-acting inhaled bronchodilator or a long-acting inhaled anticholinergic should be added. Patients who continue to have exacerbations despite being on optimal long-acting inhaled bronchodilators may require inhaled corticosteroids. Indications for continuous long-term oxygen therapy in COPD patients include an arterial partial pressure of oxygen (PaO₂) of ≤55 mmHg or arterial oxygen saturation (SaO₂) of ≤88%. If patients have cor pulmonale, right heart failure, or hematocrit >55%, oxygen is also warranted. Long-term oxygen therapy improves quality of life and increases survival in these patients.

Crack lung may occur within 48 hours of smoking of cocaine, which presents as diffuse alveolar infiltrates, eosinophilia, and fever. Patients may present with pleuritic chest pain, dyspnea with even mild exertion, dry or productive cough, wheezing, and hemoptysis. Melanoptysis or expectoration of black sputum is seen from inhalation of black carbonaceous residue from inflammable substances that are typically used to set fire to crack. Finger burns are seen from handling crack pipes. Cocaine users are at an increased risk for pulmonary infections, malnutrition, HIV, and TB. Crack smokers often perform Valsalva maneuver after inhalation or exhale vigorously into each other’s mouths to augment the uptake of the drug, which may lead to the development of pneumothorax, pneumomediastinum, and pneumopericardium.