Chapter 3: Pulmonology

A 42-year-old male who works in a hog confinement area presents to your office complaining of cough, fever, wheeze, and dyspnea. He and some other workers were cleaning the confinement area with high-pressure hoses (which aerosolized hog waste), and they all developed the same symptoms, which started between 4 and 8 hours after work. On examination, he is febrile with a respiratory rate of 28. He is able to talk in complete sentences. There are slight crackles when you auscultate the lungs. His chest x-ray is normal.

Question 3.1.1 The most likely diagnosis is:

A) "Farmer's lung" (hypersensitivity pneumonitis).

B) Organic dust toxicity syndrome.

C) Reactive airway disease.

D) Hydrogen sulfide poisoning.

E) Bronchiolitis obliterans.

Answer 3.1.1 The correct answer is "B." Organic dust toxicity syndrome (ODTS) occurs when moldy or decomposed hay and other organic material (such as hog manure) is moved. Endotoxins are aerosolized and inhaled, leading to the symptoms. The tip off here is that everyone on the job site was affected. Since hypersensitivity pneumonitis ("A") is specific to the individual, generally only one worker at the site will have symptoms. Compared with ODTS, hypersensitivity pneumonitis may present with an abnormal chest x-ray with micronodular or reticular opacities. "C" is incorrect because everyone is involved and febrile, which is not consistent with reactive airway disease. "D" is not correct. Hydrogen sulfide poisoning presents as a toxic pneumonitis with pulmonary edema, dyspnea, hypoxia, and loss of consciousness. Hydrogen sulfide also acts as a direct cellular toxin that binds to cytochrome oxidase system, similar to cyanide. In addition, hydrogen sulfide exposure comes from cleaning manure pits (as anyone in Iowa would know). Finally, "E," bronchiolitis obliterans, is a chronic illness rather than an acute one. Of note, there is a strong association between ODTS and development of chronic bronchitis.

Question 3.1.2 Appropriate treatment for this patient includes:

A) Antibiotics.

B) Intubation and mechanical ventilation.

C) Supportive care.

D) A and B.

E) A and C.

Answer 3.1.2 The correct answer is "C." Supportive care is the usual treatment of ODTS. Antibiotics are not needed because the syndrome is mediated by endotoxins rather than direct infection. "B" is incorrect because this patient is not in significant respiratory distress.

Keep reading to get to the objectives for this case.

This patient's brother, who also works on a farm, notes that every time he unloads hay he has fever, cough, dyspnea, and sputum production. It tends to resolve in 2 to 5 days but reoccurs when he is re-exposed to hay. Does he wear a mask? Well, no. He would look silly and the guys would poke fun at him. Besides, none of the other workers on the farm are affected, and they are beginning to wonder if he is malingering. His examination reveals tachypnea and fine rales. There is no wheezing present. A chest radiograph shows bilateral interstitial opacities.

Question 3.2.1 The most likely cause of this patient's symptoms is:

A) Thermoactinomyces candidus (an actinomyces species).

B) T. sacchari.

C) Botrytis cinerea.

D) Cryptostroma corticale.

E) None of the above.

Answer 3.2.1 The correct answer is "A." This patient presents with classic symptoms of hypersensitivity pneumonitis or, in this case, "Farmer's lung." This is caused by exposure to the Actinomyces species. Acute findings include fever, chills, cough, dyspnea, and chest tightness. Occasionally, the radiograph is normal. High-resolution chest computed tomography (CT) should then be obtained, which commonly shows centrilobular micronodules and ground-glass opacification. "B," T. sacchari, is involved in hypersensitivity pneumonitis from sugarcane (so-called Bagassosis). "C," Botrytis cinerea, is involved in hypersensitivity pneumonitis from grapes (so-called Spatlese lung). Finally, "D," Cryptostroma corticale, is involved in "Maple bark stripper's lung," another type of hypersensitivity pneumonitis.

Question 3.2.2 The correct treatment for this patient with Farmer's lung includes:

A) Antibiotics.

B) Inhaled steroids.

C) Oral steroids.

D) Leukotriene inhibitors.

E) Bronchoalveolar lavage (BAL).

Answer 3.2.2 The correct answer is "C." Oral steroids are effective in the treatment of hypersensitivity pneumonitis. Neither antibiotics ("A") nor inhaled steroids ("B") are of any benefit. "E," bronchoalveolar lavage, is not a treatment. However, it can be used as a diagnostic tool. One would expect to see lymphocytes on BAL.

Question 3.2.3 You would advise this patient to:

A) Get a new job.

B) Apply for disability.

C) Use a respirator at work and avoid exposure to this toxin if possible.

D) Sue the employer.

E) Take up worm farming or monoculture in rhubarb.

Answer 3.2.3 The correct answer is "C." Wearing an appropriate respirator at work can be beneficial. Avoiding exposure is even better. As for the other answers, you are a doctor not a lawyer or career counselor. Stick with what you know!

The patient is unable to change jobs or wear a respirator because it itches and he "keeps forgetting it." But he's persistent (or brave or thickheaded or unable to learn a new skill), and keeps farming. Three years later, he returns with a chronic cough, weight loss, dyspnea, fatigue, and clubbing of the fingers.

Question 3.2.4 Further evaluation will most likely reveal:

A) Bronchogenic carcinoma.

B) Air space disease (e.g., a pneumonia-like picture).

C) Decreased carbon monoxide diffusing capacity (decreased DLCO).

D) Markedly abnormal bronchoalveolar lavage (BAL) with lymphocytosis.

E) Obstructive changes on pulmonary function testing.

Answer 3.2.4 The correct answer is "C." Hypersensitivity pneumonitis can become chronic if exposure is not limited. In these cases, patients will generally have systemic complaints such as fatigue and possibly weight loss; fever will be absent. Dyspnea and clubbing of the fingers are also generally noted, reflecting chronic pulmonary disease. Along with this finding, pulmonary fibrosis can occur and the DLCO may be decreased. "A" is incorrect. Hypersensitivity pneumonitis does not lead to lung cancer. "B" is incorrect. While acute hypersensitivity pneumonitis causes an alveolitis, chronic hypersensitivity pneumonitis causes pulmonary fibrosis with an occasional micronodular pattern. "D" is incorrect. BAL in chronic hypersensitivity pneumonitis does not contain the markedly elevated lymphocyte count that is seen with acute hypersensitivity pneumonitis. Finally, "E" is incorrect. One would see a restrictive pattern on pulmonary function testing reflecting the fibrosis and not an obstructive pattern.

Objectives: Did you learn to…

• Recognize the clinical presentations of ODTS and hypersensitivity pneumonitis?

• Manage patients with lung disease related to agricultural exposures?

All of the following populations are at increased risk for developing asthma EXCEPT:

A) Obese children.

B) Female children.

C) Children exposed to tobacco.

D) Children with atopy.

E) City children.

The correct answer is "B." Male children have a greater prevalence of asthma. Interestingly, adult women "catch up" so that there is gender equity in young adulthood. After age 40, the prevalence is higher in females. Of note, frequent respiratory infections seem to be protective. There is an inverse association between children living on farms and asthma incidence (another feather in the cap of Iowa). Presumably, this is related to the greater variety of antigen exposure.

A 20-year-old woman with no significant past medical history presents with a 2-month history of episodic shortness of breath. These symptoms began with an upper respiratory tract infection. She has fits of coughing and trouble catching her breath with exertion. She states that her breath "sounds like whistles" at times. She tried a friend's albuterol inhaler with some improvement and wonders if she has asthma. On examination, she is breathing comfortably at 16 times per minute and her oxygen saturation is 96% on room air. Her lungs are clear to auscultation, and the remainder of her examination is unremarkable. You want to better categorize this patient's disease.

Question 3.3.1 Which of the following tests is most appropriate to order now?

A) Spirometry.

B) Chest x-ray.

C) Arterial blood gas (ABG).

D) Methacholine challenge.

E) Chest CT.

Answer 3.3.1 The correct answer is "A." Since this patient has symptoms of bronchospasm, spirometry will be essential in determining if there is objective evidence of obstructive lung disease. However, spirometry results are often normal in mild cases of asthma, especially when the patient is asymptomatic. Bronchoprovocation testing, with methacholine or histamine, may be useful in such cases, but should follow basic spirometry. Although chest radiography (x-ray or CT) may reveal an unsuspected process, it is not indicated in otherwise healthy patients with symptoms of bronchospasm. Bacterial pneumonia is a potential precipitant of bronchospasm that may be diagnosed on chest x-ray, but this patient has no constitutional symptoms (like fever) associated with serious bacterial infection. Obtaining an ABG may be helpful when a patient presents with respiratory distress but certainly not in the office setting.

Question 3.3.2 If this patient has mild asthma, which of the following pulmonary function test results would you expect to find?

A) Forced vital capacity (FVC) 50% of predicted.

B) Forced expiratory volume in 1 second (FEV₁) 100% of predicted.

C) FEV₁/FVC ratio <0.7.

D) Total lung capacity (TLC) 50% of predicted.

E) FEV₁/TLC <0.7.

Answer 3.3.2 The correct answer is "C." Patients with asthma will have a decreased FEV₁. The FVC may fall as well, but FEV₁ falls first and to a greater degree as the lung becomes obstructed. The ratio of FEV₁/FVC is very sensitive to airflow limitations, and FEV₁/FVC <0.7 (not predicted, just the ratio of the two numbers) is generally considered diagnostic of obstructive airway disease. The rest are incorrect. TLC is not measured by spirometry (which is why "E" is incorrect); but if it were, TLC may be increased in patients with obstructive airway disease due to air trapping.

Your patient's office spirometry shows the following:

• Normal FVC.

• FEV₁ 82% predicted.

• FEV₁/FVC 0.68.

Question 3.3.3 These findings are most consistent with which of the following?

A) Normal spirometry.

B) Obstructive lung disease.

C) End-stage emphysema.

D) Interstitial fibrosis.

E) Obesity-hypoventilation syndrome.

Answer 3.3.3 The correct answer is "B." Always go first to the FEV₁/FVC ratio. In this case, it is <0.70, which is suggestive of airway obstruction. The information provided here lacks data regarding reversibility, so you could not really differentiate between chronic obstructive pulmonary disease (COPD) and asthma. But this is clearly not end-stage emphysema, so "C" is incorrect. "D" is incorrect. Interstitial fibrosis is generally marked by a restrictive pattern on spirometry and decreased TLC. Both flow rate (e.g., FEV₁) and FVC are decreased in interstitial lung diseases but in proportion to each other. Thus, the FEV₁/FVC is often normal or elevated. See Table 3-1 for more on interpreting spirometry results.

Six months after you discuss her findings and prescribe inhaled beta-agonist therapy, she returns with complaints of continued wheezing and difficulty breathing. Her symptoms are brought on by cold weather and exercise and she uses her inhaler two times per week or less. She woke up two nights over the last 6 months with shortness of breath and coughing. Her albuterol still works for these symptoms, but she finds them bothersome and asks, "Why haven't I gotten over this?"

Question 3.3.4 How would you categorize this patient's respiratory state?

A) Intermittent asthma.

B) Mild persistent asthma.

C) Moderate persistent asthma.

D) Severe persistent asthma.

E) Recurrent lower respiratory tract infections.

Answer 3.3.4 The correct answer is "A." According to the National Asthma Education and Prevention Program (2007 NHLBI/NAEPP guidelines; Table 3-2), your patient meets the criteria for intermittent asthma. In such patients, mild symptoms correspond to an FEV₁ (not an FEV₁/FVC ratio) that is greater than 80% predicted.

Question 3.3.5 Which of the following is most appropriate for this patient given that she has intermittent asthma?

A) Add theophylline.

B) Add montelukast.

C) Continue albuterol as needed.

D) Schedule albuterol every 4 hours.

E) Prednisone 5 mg daily.

Answer 3.3.5 The correct answer is "C." As already discussed, this patient appears to have intermittent asthma. She is in no respiratory distress, is oxygenating normally, and is still responding well to albuterol by her report. Although there is some debate about the role of inhaled steroids in intermittent asthma, the NAEPP and most experts do not recommend their use. Oral prednisone is certainly not indicated in this case. She should be continued on a short-acting inhaled beta-2 agonist, such as albuterol, without the addition of another medication. "D" is incorrect. Scheduled albuterol actually yields less effective symptom control than does PRN use.

Your patient goes on to develop more frequent recurrent symptoms, such that she is using her albuterol inhaler more than three times per week, although her nighttime symptoms are rare.

Question 3.3.6 Which medication is the most appropriate next step in treating this patient's asthma?

A) Inhaled triamcinolone.

B) Inhaled salmeterol.

C) Inhaled cromolyn sodium.

D) Inhaled ipratropium.

E) Oral montelukast.

Answer 3.3.6 The correct answer is "A." Your patient now has mild persistent asthma and should be started on an inhaled steroid. When asthma symptoms become more persistent (i.e., when they occur >2 days per week or the patient awakens from sleep >2 times per month), the inflammatory component of the disease should be addressed while simultaneously treating the bronchospastic component with short-acting beta-2 agonists. Anti-inflammatory drugs are the mainstay of chronic asthma therapy, and inhaled corticosteroids are the most efficacious with the fewest side effects. Although ipratropium, cromolyn sodium, and montelukast have a place in asthma treatment, none of these medications is a first-line agent. Ipratropium works through its bronchodilatory effects, while cromolyn sodium is a mast cell stabilizer. Montelukast is a leukotriene inhibitor. The long-acting inhaled beta-2 agonists, such as salmeterol, are only recommended at Steps 3 and higher of persistent asthma control (Table 3-2, Fig. 3-1; NHLBI recommendations, 2007).

Your patient does quite well over the next year, having very few exacerbations. During one of her visits, you note slightly edematous nasal mucosa and nasal polyps. You prescribe intranasal steroids.

FIGURE 3-1. Taking a stepwise treatment approach to asthma.

One night when you are on call, she comes in severely dyspneic with audible wheezing. She talks in two- or three-word phrases. She reports a headache today, which she treated with aspirin (something she never takes but a friend gave it to her thinking it was acetaminophen). Her asthma attack started about an hour after the aspirin dose. She has been otherwise well. She denies fever, rhinorrhea, nasal congestion, and sore throat. Her respiratory rate is 40, heart rate 120 bpm, and oxygen saturation 88% on room air. She has poor air movement on auscultation of her lung fields.

Question 3.3.7 Which of the following is the most likely reason for this patient's acute exacerbation of asthma?

A) Viral upper respiratory infection (URI).

B) Sinusitis.

C) Noncompliance with inhaled albuterol.

D) Sensitivity to aspirin.

E) Noncompliance with nasal steroids.

Answer 3.3.7 The correct answer is "D." It is likely that this patient has aspirin sensitivity. Up to 10% of adults with asthma have the clinical triad of asthma, aspirin sensitivity, and nasal polyposis. Patients with asthma should be warned about the potential for exacerbations resulting from consumption of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). The drug-induced bronchial constriction caused by these medications can have an abrupt onset with severe symptoms. Patients with aspirin sensitivity can be desensitized with daily administration of small amounts of aspirin, but this should be done carefully with close supervision. Although viral URIs frequently cause exacerbations of asthma, your patient did not report antecedent symptoms of such an infection. Further discussion of the treatment of an acute asthma exacerbation can be found in Chapter 1, "Emergency Medicine."

After a brief hospitalization, your patient recovers nicely. Prior to this incident involving aspirin, she had been free of exacerbations for about a month.

Question 3.3.8 In addition to a short course of oral steroids, which of the following medication regimens do you prescribe for this patient with aspirin sensitive asthma at discharge?

A) Inhaled triamcinolone and inhaled albuterol as a "rescue."

B) Inhaled triamcinolone, oral montelukast, and inhaled albuterol as a "rescue."

C) Oral montelukast and inhaled albuterol as a "rescue."

D) Inhaled albuterol as a "rescue."

E) Inhaled salmeterol and inhaled triamcinolone.

Answer 3.3.8 The correct answer is "B." Leukotriene inhibitors (e.g., montelukast, zafirlukast) have demonstrated effectiveness in reducing symptoms and improving peak flow in patients with aspirin sensitive asthma. Leukotriene inhibitors should be used only in asthma patients who are already using a corticosteroid inhaler—or those who cannot tolerate inhaled corticosteroid therapy. Therefore, "C" is not an appropriate choice. "D" is incorrect because there is no anti-inflammatory. Although "E" offers an anti-inflammatory agent, there is no rescue inhaler, and patients with asthma must always have access to a short-acting inhaled bronchodilator.

Question 3.3.9 Which of the following medications, when used alone as maintenance therapy in persistent asthma, is associated with an increased risk of asthma-related mortality?

A) Inhaled fluticasone.

B) Inhaled salmeterol.

C) Oral zafirlukast.

D) Oral prednisone.

Answer 3.3.9 The correct answer is "B." Inhaled salmeterol, when used alone as a controller agent for asthma, has been associated with a two- to four-fold increase in the risk of death related to asthma or other respiratory conditions. Thus, the Food and Drug Administration (FDA) has mandated a "black box" warning be applied to salmeterol-containing products. It is not known whether inhaled steroid therapy is protective, but NHLBI/NAEPP guidelines recommend adding long-acting inhaled beta-agonists only after inhaled steroids are already in use.

Objectives: Did you learn to…

• Identify triggers of bronchospasm?

• Evaluate symptoms of wheezing and dyspnea?

• Classify asthma?

• Prescribe appropriate medications for intermittent and mild persistent asthma?

• Describe the triad of asthma, aspirin sensitivity, and nasal polyposis?

A 60-year-old female who smokes two packs of cigarettes per day complains of shortness of breath and fullness in her throat. You obtain spirometry in the office and the results are given above along with the flow/volume loop (Fig. 3-2).

FIGURE 3-2. Spirometery results.

How do you interpret these findings?

A) Chronic obstructive lung disease.

B) Restrictive lung disease.

C) Fixed upper airway obstruction.

D) Poor patient effort.

E) Within normal range.

The correct answer is "C." The flattened flow/volume loop is consistent with a fixed upper airway obstruction. In this case, FEV₁ and the FEV₁/FVC ratio may look like other obstructive diseases (i.e., asthma, COPD), so you have to look at the flow/volume loop (always a good idea). Some examples of flow/volume loops are given below (Fig. 3-3).

FIGURE 3-3. Spirometery results.

You are seeing a 65-year-old male in the emergency department (ED) where he presented with complaint of increasing shortness of breath. He has obvious difficulty breathing and cannot speak in full sentences. However, you are able to elicit that he has been having increasing respiratory problems over the last 3 to 4 days. He has known COPD with FEV₁ of "less than one" (normal FEV₁ is about 4 L for a 50-year-old male and 3 L for a 50-year-old female—for the calculations based on age, etc., see www.hankconsulting.com/RefCal.html). He has been using his inhalers much more than usual but with minimal improvement. He has smoked one pack per day since age 18 (but proudly points out he quit 2 days ago) and has a past medical history of high cholesterol, obesity, and hypertension.

On examination, he has a respiratory rate of 26 to 28, heart rate of 100 bpm, blood pressure of 130/90 mm Hg, and temperature of 37.7°C. His O₂ saturation is 84% on room air. On auscultation, you do not appreciate much due to his body habitus but you still manage to hear some wheezing. He has a normal cardiac examination and no lower extremity edema.

Question 3.4.1 What is the next best step to help this patient?

A) Perform emergent endotracheal intubation.

B) Administer supplemental O₂ via nasal cannula.

C) Administer Solu-Medrol, 1 g IV.

D) Start antibiotics IV.

E) Obtain a chest x-ray.

Answer 3.4.1 The correct answer is "B." This patient is hypoxic, and your first priority should be to improve his oxygenation. There exists a theory that oxygenating patients with COPD will suppress their respiratory drive. The classical teaching (mostly incorrect) is that COPD causes a switch from carbon dioxide levels driving respiration to oxygen levels driving respiration. While this may be partly true, further study has suggested that the main reason COPD patients are at risk of worsening hypercapnia is due to loss of hypoxic pulmonary vasoconstriction and worsening ventilation–perfusion mismatch that occurs with excess oxygen delivery. Regardless of that, you need to first worry about this patient's oxygenation.

"A" is incorrect. The patient is protecting his airway and you have not attempted improving his oxygenation with less invasive methods yet. Administering steroids, IV or PO, will have no immediate effect on his respiratory status. In fact, IV steroids might be worse than PO steroids (there is question of whether higher IV doses cause immunosuppression and subclinical myopathy; see Am J Respir Crit Care Med. 2014;189:1052). Antibiotics and a chest x-ray may be reasonable, but with low O₂ saturations, your priority is to quickly improve your patient's oxygen status.

Question 3.4.2 When initiating supplemental oxygen by nasal cannula, you instruct the nurse to keep the patient's oxygen saturation:

A) Between 96% and 100%.

B) Between 90% and 95%.

C) Between 85% and 89%.

D) At whatever saturation he looks most comfortable.

Answer 3.4.2 The correct answer is "B." The primary goal of supplemental oxygen is to reduce the risk of tissue hypoxia. Maintaining oxygen saturations above 90% (or PaO₂ 60–65 mm) will ensure tissue oxygenation. Higher oxygen saturations may result in CO₂ retention and hypercapnia, as noted earlier. Also, aiming at 100% with excessive levels of O₂ supplementation takes away an important patient assessment parameter because now you cannot tell easily whether his O₂ needs are going up or down. "D" is of special note. Patients with COPD who look comfortable may be becoming hypercapnic and developing CO₂ narcosis. Thus, while comfort is a goal, it may not be the best judge of clinical status in patients with COPD exacerbations. To assess CO₂ levels, you will need an ABG or VBG.

Your patient is now on 5 liters per minute (LPM) of oxygen via nasal cannula. You obtain an ABG: pH 7.29, PCO₂ 74 mm Hg, PO₂ 58 mm Hg. The patient is awake and alert but says that he still feels "like dirt." He remains tachypneic, in obvious respiratory distress, with a respiratory rate of 28. Albuterol and ipratropium are given via nebulizer.

Question 3.4.3 What is the best next step?

A) Clearly, he is failing therapy—emergently intubate.

B) Increase his O₂ to 100% via face mask.

C) Initiate noninvasive positive pressure ventilation (e.g., BiPAP).

D) Start IV antibiotics.

E) Obtain a chest CT with PE protocol (you are barking up the wrong bronchial tree).

Answer 3.4.3 The correct answer is "C." This patient is retaining CO₂ despite tachypnea and is in impending respiratory failure. He is also not oxygenating well despite low-flow oxygen. Noninvasive positive pressure support (BIPAP) can relieve hypercapnia and improve oxygenation by decreasing work of breathing without requiring intubation and its associated morbidity. Often IV antibiotics ("D") are used for empiric therapy in severe exacerbations of COPD, but again, improving the respiratory status comes first. He is hypoxic, but his main problem is CO₂ retention—increasing his O₂ delivery will not alleviate that (thus, "B" is incorrect). Although his respiratory status is tenuous, he is not in imminent respiratory failure, and intubation ("A") is not warranted at this time. Chest CT ("E") can rule out a PE in this hypoxic patient and may confirm COPD changes including emphysema but will greatly delay treatment and would not change your immediate course of action.

After several hours of noninvasive positive pressure ventilation, your patient is doing well and he is transferred out of the intensive care unit (ICU). When you see him the next day, his medications include inhaled bronchodilators, ceftriaxone, azithromycin, and prednisone. A chest x-ray shows no evidence of infiltrate. He is weaned from the positive pressure support and is now on 2 LPM of oxygen by nasal cannula. He appears comfortable, with a respiratory rate of 14 and an oxygen saturation of 95%.

Question 3.4.4 Now you know that he has COPD, what would be the best treatment for him?

A) Inhaled long-acting beta-agonist (LABA) + albuterol.

B) Inhaled steroid + albuterol.

C) Inhaled steroid + LABA + albuterol as needed.

D) Albuterol.

E) Albuterol and theophylline.

Answer 3.4.4 The correct answer is "C." This is a bit tricky, but due to the severity of his exacerbation, "C" is the best choice. Compared with patients with asthma, where long acting bronchodilators are not indicated as first-line therapy, COPD patients have a clear symptomatic benefit from long-acting bronchodilators. The two available choices are anticholinergics (e.g., tiotropium) or LABAs (e.g., salmeterol or formoterol). Either choice is fine. An inhaled steroid does not modify the long-term decline in FEV₁ in patients with COPD. However, it will reduce the frequency of exacerbations and thus improve health status. Current guidelines recommend addition of inhaled steroids with FEV₁< 50% predicted and frequent exacerbations (e.g., three in the last 3 years), see Figure 3-4.

FIGURE 3-4. Global obstructive lung disease COPD score and therapy.

Holding his inhalers and smiling toothlessly, your patient asks, "Which of these is going to keep me alive—just in case I can't afford both?"

Question 3.4.5 Which of the following medication regimens has demonstrated decreased mortality in the treatment of stable COPD?

A) Inhaled tiotropium (a long-acting anticholinergic).

B) Inhaled salmeterol (LABA).

C) Inhaled ipratropium (a short-acting anticholinergic).

D) Inhaled corticosteroid.

E) None of the above.

Answer 3.4.5 The correct answer is "E." Aside from oxygen, no medical therapy has clearly demonstrated a mortality benefit for stable COPD (see Fig. 3-4 for stage of COPD and appropriate treatment). Another therapy to consider in advanced COPD is pulmonary rehabilitation (PR). While having no definite effect on survival, PR improves dyspnea and quality of life scores while reducing the number of hospitalizations and days in hospital. Finally, there is a new oral phosphodiesterase inhibitor, roflumilast (Dalisrep), for severe COPD. As you probably already know, your authors are curmudgeons who don't like anything new. But roflumilast is particularly on our bad list. It increases FEV₁ by 45 mL over placebo. It has no effect on quality of life and exacerbations are 1.3/year with placebo and 1.2/year with rolfumilast. It also causes diarrhea and depression/suicidality. Nonetheless, you should know about it.

Note: Long-acting bronchodilators can be either a beta agonist or an anticholinergic.

Later that year, the same patient gets admitted to the hospital for community-acquired pneumonia. During his stay in the hospital, the hospitalist orders a CT chest "to rule out other things." The patient recovers from his infection and returns to you with the CD of his CT chest images. The reading of the CT chest describes a 2-cm pulmonary nodule in the right upper lobe along with extensive subcarinal lymphadenopathy.

Question 3.4.6 What is the next best step in management of this patient?

A) Repeat CT chest in 3 months.

B) Repeat CT chest in 6 months.

C) Refer for bronchoscopy with endobronchial ultrasound-guided biopsy.

D) Refer to an oncologist.

E) Refer for a mediastinoscopy.

Answer 3.4.6 The correct answer is "C." This patient probably has a malignant disease and tissue is needed to either diagnose it or rule it out. Bronchoscopy with endobronchial ultrasound (EBUS)-guided fine-needle biopsies is a minimally invasive procedure that can relatively safely obtain a tissue sample for the pathologist. There is good evidence that EBUS has high sensitivity and specificity compared with PET scanning. "A" and "B" are incorrect as this patient has a nodule that is larger than 1 cm along with mediastinal lymphadenopathy. This needs to be worked up and cannot wait 3 to 6 months. "D" is incorrect. Your patient will likely need to see an oncologist, but you need to first provide a tissue diagnosis. "E," mediastinoscopy, would likely provide you with the diagnosis, but it is a far more invasive procedure than bronchoscopy and carries higher mortality and morbidity.

Your patient returns with increasing dyspnea now at rest. His biopsy was negative. Despite both of you being blue in the face, he has not quit smoking.

Question 3.4.7 Criteria for the use of continuous low-flow oxygen in those with COPD include all of the following EXCEPT:

A) PO₂ <55 mm Hg.

B) Oxygen saturation <88%.

C) PO₂ of <59 mm Hg with evidence of cor pulmonale.

D) Episodic sleep apnea-related desaturations at night.

Answer 3.4.7 The correct answer is "D." Episodic sleep apnea–related oxygen desaturations, while a cause for concern and amenable to treatment (e.g., CPAP), is not one of the criteria for the use of continuous low-flow oxygen. The other choices are correct. "C" deserves some special attention. Evidence of cor pulmonale can include "p-pulmonale" on ECG, peripheral edema, or a hematocrit >55%.

Question 3.4.8 Concerning hypoxemic patients with COPD, which of the following is true?

A) Patients on continuous, low-flow O₂ become oxygen dependent and cannot function without it.

B) Continuous low-flow O₂ used for at least 8 hours a day helps to reverse pulmonary hypertension.

C) Concurrent smoking is a contraindication to the prescribing continuous low-flow home O₂ because patients are spontaneously combusting right and left (like Spinal Tap drummers).

D) Low-flow O₂ used at least 15 hours a day significantly enhances survival.

E) Low-flow O₂ is a well-tolerated and effective treatment for obstructive sleep apnea.

Answer 3.4.8 The correct answer is "D." Patients who use low-flow O₂ at home for 24 hours a day have an improved rate of survival. Patients should be encouraged to use O₂ at least 15 hours a day if possible. "B" is incorrect because patients need at least 15 hours of O₂ per day to have any significant benefit with regard to pulmonary hypertension. "C" is incorrect. Clearly, smoking while on O₂ is not a good idea, but patients can turn off their O₂ supply while smoking.

Objectives: Did you learn to…

• Recognize a patient presenting with signs and symptoms of COPD?

• Describe diagnostic and staging criteria for COPD?

• Develop a plan to manage hypoxemia and hypercapnia?

• Manage medications for acute exacerbations of COPD?

• Direct therapy for chronic COPD?

• Identify causes of dyspnea other than COPD presenting in a patient with known COPD?

In a patient with COPD, a lung transplantation referral can be considered:

A) Once the patient requires oxygen.

B) When you feel you have run out of interventions.

C) Once insurance accepts your referral.

D) After the patient meets strict criteria for the referral.

E) If the patient's family keeps asking for the referral.

The correct answer is "D." The International Society for Heart and Lung Transplantation created a set of criteria for when to consider transplantation and, more importantly, when should you consider referral for a lung transplant consultation. In COPD patients, the indication for referral is easy to remember and consists of BODE index >5 (BODE stands for Body-mass-index, airflow Obstruction, Dyspnea, and Exercise, which are the characteristics used in the index). The BODE index is an alternative to the GOLD criteria. The BODE index incorporates functional criteria such as breathlessness and 6-minute walking distance. Find a BODE calculator here: http://www.qxmd.com/calculate-online/respirology/bode-index. Criteria for transplantation in COPD are more complex and are beyond the scope of this book.

Ms. Sarah Bellum (if you're not smiling, try saying the name out loud or the joke is just lame …) is a 32-year-old Caucasian female who presents to your ED with shortness of breath. She just returned home after the International Conference on Coordination in London. Immediately after walking through her front door, she became acutely short of breath (not attributable to the Justin Bieber poster in her living room). This is associated with some moderately sharp chest pain located along the left side of her chest. The pain seems worse when she attempts to breathe deeply.

Question 3.5.1 Which important question(s) do you next ask Ms. Bellum?

A) Do you smoke cigarettes?

B) When was your last menstrual period?

C) Have you had surgery recently?

D) Do you have a history of kidney disease?

E) All of the above.

Answer 3.5.1 The correct answer is "E." Each of these questions addresses risk factors associated with pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Smoking cigarettes and recent surgery are strong risk factors, as is an active pregnancy. Addressing a patient's menstrual cycle serves as a natural segue to a discussion about the use of oral contraceptives, which, too, is a prominent risk factor. As for renal disease, nephrotic syndrome has been associated with an increased risk of PE.

After further verbal probing, you discover that Ms. Bellum recently completed her menstrual cycle and the other presented questions turned up no risk factors. However, your smooth segue did reveal that she takes low-dose estrogen for birth control. During this discourse, you also learn that her aunt had a blood clot in her leg once. She has no further details but does not think that her aunt had any further complications from this condition. Regardless, PE just took a violent leap to the top of your differential. You glance at her vitals (temperature 37.1°C, heart rate 92 bpm, blood pressure 129/68 mm Hg, respiratory rate 21, SpO₂ 95% on room air) and notice that she appears mildly uncomfortable but not in any acute distress. Her physical examination is entirely unremarkable. You order an ECG on the patient to evaluate for potential cardiac etiologies for her symptoms.

Question 3.5.2 Assuming Ms. Bellum does have a PE, what is her ECG most likely to show?

A) S₁Q₃T₃.

B) Nonspecific ST-T wave changes.

C) Sinus tachycardia.

D) Normal sinus rhythm.

E) Multifocal atrial tachycardia.

Answer 3.5.2 The correct answer is "D." The most common ECG finding associated with the diagnosis of PE remains normal sinus rhythm. With that said, the most common arrhythmia found in patients with a PE is sinus tachycardia. But alas, Sarah had a normal heart rate. The other choices can certainly be found with this condition but are far less frequent. Of note, the "textbook" S₁Q₃T₃ ECG rarely occurs and historically traces back to a handful of patients in the 1930s that had massive pulmonary emboli. Even if you do spot this pattern on an ECG, it is not specific enough to confirm the diagnosis. In the end, the clinical signs attributed to pulmonary emboli (such as the shortness of breath and chest pain) are frequently more valuable than any abnormal ECG finding.

As you attempt to rule out other potential etiologies for the patient's symptoms (e.g., pneumonia, atelectasis, and pneumothorax), you order a trusty chest radiograph.

Question 3.5.3 What is the most common radiographic finding in a patient with a PE?

A) Pleural effusion.

B) No acute cardiopulmonary processes.

C) Westermark sign.

D) Hilar/mediastinal enlargement.

E) Hampton hump.

Answer 3.5.3 The correct answer is "B." Admittedly, this one is a bit tricky. Approximately 75% of the chest radiographs in the setting of PE are abnormal. However, there are numerous causes for these abnormalities and none of them individually surpass the frequency of the normal chest radiographs. Specifically, the "textbook" findings of Westermark sign (loss of peripheral vascular markings) and Hampton hump (a wedge-shaped opacity due to pulmonary infarction) are infrequent, and both have a low sensitivity and low specificity. In short, all the other options can be seen as the result of a PE but none are more frequent than a normal chest radiograph.

ECG and chest radiograph in hand, you turn your attention toward ordering the appropriate laboratory tests to solidify your presumptive diagnosis. You are working with a medical student who suggests a number of lab tests. You agree with most of them, but shoot him down on one.

Question 3.5.4 Which test should you AVOID ordering?

A) CBC.

B) D-dimer.

C) PT/PTT.

D) Basic metabolic panel (Na⁺, K⁺, Cl^–, CO₂^–, BUN, Cr^–, and glucose).

E) Urine pregnancy test.

Answer 3.5.4 The correct answer is "B." The D-dimer can be a blessing for some but is the bane of existence for others. In this patient, a D-dimer is not useful. This test has great sensitivity but poor specificity. It is positive in far more conditions than PE. Used as a "rule-out" test for PE, it only applies in low-risk patients. Ms. Bellum is not a low-risk patient as suggested by the pulmonary embolism rule-out criteria (PERC) rules (see Helpful Tip) due to her use of exogenous estrogen. The Wells criteria for PE place her in the moderate-risk group (16.2% risk of PE). As such, even a negative D-dimer is insufficient for ruling out the diagnosis. As for the other tests, they all serve a valuable role in her evaluation. For instance, the CBC could provide evidence of anemia, while the PT/PTT may reveal a coagulopathy. Assessing her renal function may be needed for her evaluation moving forward, and the same can be said for verifying her nongestational status. Plus, a urine pregnancy test is performed on almost every woman in an ED. It might as well be part of the triage process.

That pesky med student seemed to know a lot about the PERC rules and Wells criteria. But when he listed the Wells criteria, he got one wrong.

Question 3.5.5 The Wells criteria for PE include all of the following EXCEPT:

A) Estrogen use.

B) Pulse >100.

C) Previous history of venous thromboembolism.

D) Clinical symptoms and signs consistent with PE.

E) Hemoptysis.

Answer 3.5.5 The correct answer is "A." While an important risk factor for PE, estrogen use is not included in the Wells criteria. All the others count in the Wells criteria (Table 3-3). Using a medical calculator website, such as www.medcalc.com, is most helpful.

The CBC, coagulation studies, and basic metabolic panel all return within normal limits. In addition, Ms. Bellum is not pregnant. Thus, you wish to (finally) solidify that diagnosis you have suspected for quite some time.

Question 3.5.6 Since you do not put her in the low-risk category by your clinical judgment, what diagnostic study should you order?

A) VQ (ventilation–perfusion) scan.

B) CT scan of the chest without contrast.

C) CT scan of the chest with contrast.

D) Pulmonary angiogram.

E) Compressive Dopplers of the lower extremities.

Answer 3.5.6 The correct answer is "C." The American College of Radiology (ACR) lists the CT scan of the chest with contrast (i.e., CT angiography or CTA) as the modality of choice in stable patients with a suspected PE. The CTA is considered to be the standard of care. Its benefits include the fact that it is noninvasive, cheaper than pulmonary angiography, and far more available than VQ scans. It should be noted that pulmonary angiography still remains the "gold standard" for diagnosing pulmonary emboli, but that is more of an academic point. As for VQ scans, they are not available in many locales and often return nondiagnostic. However, they can be used in a patient with a normal chest x-ray. A chest CT without contrast ("B") will not enhance the pulmonary arteries, making the diagnosis of a PE far more difficult, if not impossible. Since most pulmonary emboli are believed to arise from the lower extremity venous system, "E," Dopplers of the legs, could be considered if the patient was a poor candidate for both CTA and VQ scan (e.g., COPD and Stage 4 chronic kidney disease). But this approach is obviously not diagnostic of PE; it would just help you determine if the patient has an active thrombosis, and you would manage the same whether she has a PE or DVT or both.

As keenly suspected, Ms. Bellum's CTA of the chest reveals a moderate-sized pulmonary embolus in the left pulmonary artery. Her vital signs are still stable and her pain is well-controlled with intravenous morphine. She is surprised by the diagnosis you give her but appears to be taking it in stride.

Question 3.5.7 What is the optimal management plan for the patient moving forward?

A) Bolus her with unfractionated heparin (UFH), start her on oral warfarin, and discharge her to home.

B) Administer a dose of enoxaparin in the ED, provide education, and discharge the patient to home with primary care follow-up in the next 2 to 3 days.

C) Start the patient on low–molecular-weight heparin (LMWH), initiate oral warfarin therapy, and admit the patient to the family medicine service.

D) Bolus her with UFH, initiate a UFH drip, and admit the patient to the family medicine service.

E) Start her on oral warfarin and discharge her to home with primary care follow-up in the next 2 to 3 days.

Answer 3.5.7 The correct answer is "C." Full anticoagulation is considered mandatory for all patients with a PE. While discharging a patient with only a DVT is considered standard of care, this is not (yet) true for PE. Thus, any plan that centers on a discharge to home is incorrect (a 2014 Cochrane Database review concluded that the available evidence is insufficient to recommend outpatient therapy and that more studies are needed). With regard to selecting an anticoagulant, current evidence does not support the use of one agent over another; UFH, LMWH, and fondaparinux are all appropriate. Regardless of the selected anticoagulant, the current recommendations stipulate the initiation of warfarin at the time of diagnosis as well. The UFH, LMWH, or fondaparinux should be continued until the patient's INR has been therapeutic (2–3) for at least 24 hours and at least 5 days. Note that apixaban, dabigatran, and rivaroxaban can all be used to treat and prevent PE. Like warfarin, dabigatran requires 5 days of overlap with LMWH when used as treatment. Avoid edoxaban (Savaysa) if possible. It can only be used in those with a CrCl of less than 95 mL/min. And, it requires dose adjustment for those with a CrCl of between 50 and 15 mL/min (do not use under CrCl 15 mL/min). Note that the most recent available guideline from the American College of Chest Physicians (ACCP), published online in January 2016, recommends novel oral anticoagulants (e.g., dabigatran, apixaban, and others) over warfarin for treatment of PE in patients without cancer; however, the ACCP grades this recommendation as "weak with moderate quality evidence." Continue to look at the whole patient when making anticoagulation decisions.

Question 3.5.8 How long are you going to maintain this patient on anticoagulation?

A) 3 months.

B) 6 months.

C) 9 months.

D) Lifetime.

Answer 3.5.8 The correct answer is "A." For a PE that has a reversible cause (oral contraceptive pills in this patient with a long airplane trip), 3 months of anticoagulation is adequate. For those with a second PE, lifetime anticoagulation is warranted. For those with a cryptogenic PE or PE from an acquired or inherited thrombophilia (e.g., Factor V Leiden), recommendations are all over the place from 3 months to life. Nine months is likely adequate for a patient with a PE from an irreversible cause, although patients go back to their pre-treatment risk as soon as you stop anticoagulation. And, a first PE trumps everything else in terms for risk factors for a second PE—including all those fancy thrombophilia tests! So, finding that thrombophilia does not necessarily help your decision-making process. Note that some guidelines suggest anticoagulation for life after a first cryptogenic/unprovoked PE if benefit seems to outweigh risks. This should be decided after 3 months of anticoagulation. (Chest. 2012;141(2)(Suppl):7S–47S.)

Your patient does well, completes her course of warfarin, and has no further episodes over the next 2 years. She develops gallstones and plans to have an elective laparoscopic cholecystectomy. A surgeon colleague sends her back to see you for a preoperative evaluation. You find no evidence of cardiac, pulmonary, or hematologic disease. She is no longer on warfarin and is doing well.

Question 3.5.9 Which of the following postoperative management strategies do you recommend?

A) Aspirin 81 mg PO daily.

B) Warfarin 5 mg PO daily.

C) UFH 5,000 units subcutaneously daily.

D) Enoxaparin 40 mg subcutaneously daily.

E) No antiplatelet or anticoagulant drugs.

Answer 3.5.9 The correct answer is "D." Even for a relatively minor surgical procedure where anesthesia is used for 30 minutes or less and the postoperative recovery is usually quick, your patient is at moderate risk for venous thromboembolism. Her history of PE puts her in a higher risk category, and she requires prophylaxis. Of the choices available, enoxaparin would be the most appropriate. LMWH and UFH are both acceptable for prevention of DVT/PE in the postoperative period, but "C" is wrong because UFH must be dosed every 8 to 12 hours rather than daily. "A" is incorrect. Aspirin is sometimes used postoperatively, but the dose should be 160 mg/day or greater. Also, compared with heparin and its derivatives, aspirin is less efficacious in the prevention of thrombus. "B" is incorrect. Warfarin alone is not appropriate in this setting due to its slow onset of action.

Objectives: Did you learn to…

• Recognize risk factors for a PE?

• Understand the variability of symptoms and signs in PE?

• Appreciate the PERC rules and Wells criteria and how they can be used to rule out a PE?

• Implement treatment and prevention for PE?

• Understand the A–a gradient?

Which statement best describes the use of vena caval filters in preventing PE?

A) They reduce the risk of PE but only in patients who are maintained on anticoagulation.

B) Retrievable vena caval filters have been shown to have a short-term advantage while the patient is in the hospital; they should be removed as soon as possible.

C) They unequivocally reduce PE risk in both anticoagulated and nonanticoagulated patients.

D) One need not work-up a patient for a PE in the presence of a vena caval filter since they are close to 100% effective.

The correct answer is "B." All of the rest are wrong. All evidence suggests that vena caval filters are essentially useless in preventing PE (e.g., JAMA. 2015:28;313(16):1627–1635). In addition, they can break with strut migration to the heart or through the vena cava. 2016 ACCP guidelines recommend against vena caval filters in patients who can be anticoagulant even aster a recurrent PE. They may have some short-term benefit for inpatients such as with trauma.

A 50-year-old male who is a heavy drinker with a history of squamous cell carcinoma of the neck presents to your office complaining of abdominal pain. He has been coughing and expectorating bloody sputum and notes a low grade fever, chills, and mild dyspnea starting about 1 week ago. He denies nausea, emesis, and chest pain. His squamous cell carcinoma was treated with external beam radiation several years ago. Examination reveals an afebrile male in mild distress. His vital signs are normal, and his lungs sound clear. The abdominal examination reveals only mild epigastric tenderness.

The chest x-ray is available for your review (see Fig. 3-5). Your colleague, who is on call today, walks by and asks if you have any admissions for her.

FIGURE 3-5. Patient's chest x-ray.

Question 3.6.1 You consider this 50-year-old with a cough and reply:

A) "Yes. This gentleman will need the ICU."

B) "Yes. This gentleman will need a respiratory isolation room."

C) "No. I'm sending this gentleman home with metronidazole."

D) "No. I'll work-up this gentleman as an outpatient."

Answer 3.6.1 The correct answer is "B." Because he is expectorating bloody sputum and has a cavitary lesion on chest x-ray (right upper lobe), this patient should be admitted to a respiratory isolation room until tuberculosis is ruled out. He will need further evaluation and possibly intravenous antibiotic therapy, both of which may be accomplished during his hospitalization. "A" is incorrect. There is no need to send this patient to the ICU based on his current picture. "C" is also incorrect. Metronidazole alone is not an appropriate therapy for this patient even if this is bacterial (see below).

Question 3.6.2 What is the best next step in the diagnosis of this process?

A) Bronchoscopy.

B) Sputum cultures.

C) Blood cultures.

D) Chest CT.

E) Open-lung biopsy.

Answer 3.6.2 The correct answer is "D." The chest x-ray demonstrates a cavitary lesion in the right upper lobe. Chest CT is warranted for further characterization of the lesion. From history, examination, and chest x-ray, it is not possible to determine whether the lesion is an abscess or a malignant process. An indolent course with low-grade fever is characteristic of lung abscess. However, the pre-existing squamous cell carcinoma has potential to have spread to the lungs, and squamous cell carcinoma is known to cause cavitations. Culture of sputum and blood, including evaluation of first morning sputum for acid-fast bacilli (AFB), will be an essential part of the assessment but may not yield as much information as chest CT, and sputum culture should be done in conjunction with cytology and Gram stain. Bronchoscopy should be postponed until CT results are available. Bronchoscopic biopsy is potentially detrimental if the lesion is an abscess since the airway could flood with pus if the entire cavity wall is penetrated.

Chest CT further confirms a parenchymal abscess in the right upper lobe with cavitation and air within the cavity. Bronchoscopy reveals pus in the airway and extrinsic compression of the bronchi. A lavage sample is obtained, but biopsies are not taken due to the clinical impression that this is a lung abscess.

Question 3.6.3 What organisms are most commonly isolated in lung abscesses?

A) Anaerobic bacteria.

B) Aerobic bacteria.

C) Tuberculosis.

D) Mixed aerobic/anaerobic bacteria.

Answer 3.6.3 The correct answer is "A." Anaerobes are isolated most often, followed by mixed anaerobic/aerobic bacteria, followed by aerobic bacteria alone (especially staphylococci).

Gram stain of sputum demonstrates Gram-positive cocci and Gram-negative rods. Cultures are pending. Tuberculin skin test is negative.

Question 3.6.4 What is the most appropriate therapy for this patient?

A) Refer for surgical drainage.

B) Oral levofloxacin.

C) Intravenous clindamycin.

D) Intravenous metronidazole.

E) Intravenous ceftriaxone.

Answer 3.6.4 The correct answer is "C." Most lung abscesses are polymicrobial, but the most important aspect in treatment appears to be the use of an antibiotic active against anaerobes. Intravenous clindamycin is the usual choice for lung abscess due to its coverage of anaerobes and Streptococcus pneumoniae. Metronidazole is less effective, failing in up to 50% of cases of putrid lung abscess. A beta-lactam with beta-lactamase inhibitor (e.g., piperacillin/tazobactam) is another good choice. Ceftriaxone and levofloxacin offer poor coverage of anaerobes. Surgical drainage of lung abscesses is needed in only 5% to 10% of cases. Most resolve with just antibiotics.

Objectives: Did you learn to…

• Recognize the presence of a cavitary lesion on chest x-ray?

• Identify the common causes of cavitary lesions?

• Decide when to place a patient in respiratory isolation?

• Manage a patient with a lung abscess?

A 53-year-old male is accompanied by his wife to your office and complains of a cough for 6 weeks. It is worse at night and any time he lies down. He denies sputum production, shortness of breath, chest pain, and wheezing. He takes an antacid once or twice per day to settle his stomach and notes very bad heartburn. He smoked three packs of cigarettes per day until 1 year ago, when he quit "cold turkey." He takes only hydrochlorothiazide for hypertension and a daily aspirin. He has no cardiac disorders. His wife reports that he snores at night, and she adds, "He's always hacking and clearing his throat—all night." The review of systems is negative. In order to sleep better, he has recently started having a shot (or 2 … or 3 …) of whiskey before going to bed.

Question 3.7.1 What is the most likely cause for the cough?

A) Gastroesophageal reflux.

B) Lung cancer.

C) Antihypertensive medication.

D) Alcohol abuse.

E) Congestive heart failure (CHF).

Answer 3.7.1 The correct answer is "A." This patient appears to have a chronic cough that is most likely due to gastroesophageal reflux disease (GERD). He takes antacids and exhibits throat clearing, which can be a subtle sign and is not typically identified by patients as reflux. In addition, he drinks alcohol at bedtime, further predisposing to reflux. He has a history of smoking, which does place him at increased risk for developing a bronchogenic carcinoma, but a lung mass would not be a common cause for cough. Aspirin is associated with bronchospasm in some people, but it would not usually present as cough in a patient with no history of asthma. Hydrochlorothiazide is not known to cause cough (although angiotensin-converting enzyme [ACE] inhibitors are). Also, it is unlikely that symptoms would be isolated to nighttime if his cough were medication-related.

On physical examination, you note a mildly overweight male in no distress. His vital signs are normal. His lungs are clear to auscultation. The nasal and oropharyngeal mucosae are intact, moist, and not inflamed. The remainder of the examination is unremarkable. Chest x-ray shows flattened diaphragms but is otherwise negative. You suspect GERD, but also entertain other diagnoses.

Question 3.7.2 Which of the following is your next step in managing this patient's cough?

A) Start a proton pump inhibitor.

B) Start an inhaled steroid.

C) Order 24-hour esophageal pH monitoring.

D) Obtain spirometry.

E) Obtain a chest CT.

Answer 3.7.2 The correct answer is "A." An empiric trial of an effective gastric acid-suppressing medication in this symptomatic patient is likely to relieve the cough if the diagnosis is accurate. The ACCP recommends starting therapy with a proton pump inhibitor rather than an H₂-blocker. The usual anti-reflux measures, such as avoiding fatty foods, alcohol, and food before bedtime, should be instituted as well. Prescribers must be aware that sometimes a complete resolution of cough takes months. A 24-hour pH monitor ("C") is invasive and often not necessary if an empiric trial of gastric acid suppression resolves the problem. Starting the evaluation of chronic cough with a chest x-ray is part of the ACCP recommendations, but CT scan ("E") is not indicated with a negative chest x-ray. If the cough does not resolve with empiric therapy, spirometry should be considered.

He does not respond after 2 months of empiric treatment, and he is becoming more concerned. The examination is unchanged. Spirometry is normal with a normal flow volume loop.

Question 3.7.3 Which of the following management options is LEAST likely to benefit this patient?

A) Combination antihistamine and decongestant.

B) Inhaled corticosteroid.

C) Inhaled beta-2 agonist.

D) Antibiotics.

Answer 3.7.3 The correct answer is "D." This patient has no signs or symptoms of sinusitis or bacterial pulmonary infection, so treating with an antibiotic is inappropriate and unlikely to help. However, some form of empiric therapy might be tried. He could have postnasal drainage without signs on physical examination, and empiric therapy with combination antihistamine and decongestant may improve the cough. Inhaled corticosteroids and beta-2 agonists are the mainstay of chronic asthma therapy and may help relieve this patient's chronic cough. This patient could yet have "cough-variant asthma" despite normal spirometry results.

Question 3.7.4 The three most common causes of chronic cough (cough lasting longer than 8 weeks) are:

A) Postnasal drip, asthma, GERD.

B) GERD, COPD, congenital lung disease.

C) Lung cancer, postnasal drip, COPD.

D) Obstructive sleep apnea, respiratory infections, asthma.

Answer 3.7.4 The correct answer is "A." Epidemiologic studies have demonstrated that most cases of chronic cough are due to postnasal drainage (often termed "upper airway cough syndrome"), asthma, or symptomatic GERD. Most cases of chronic cough seem to have only a single cause, although some will have more than one cause. Empiric therapy should be aimed at these top three causes. Of course, infection (pertussis in particular), malignancy, and other causes of cough are important to consider—and potentially rule out—as well.

The evaluation of chronic cough should proceed in a logical manner. Usually, history and physical examination will find the cause. If this is unrevealing, consider a stepwise evaluation addressing each of the chronic etiologies in Table 3-4 in order. If this still does not give you an answer, consider a methacholine challenge test to see if you can reproduce the symptoms that would lead you to a presumptive diagnosis of asthma with normal spirometry.

Objectives: Did you learn to…

• Recognize the most common causes of chronic cough?

• Evaluate a patient with chronic cough?

• Develop a management plan for chronic cough?

You see a 38-year-old female in follow-up for a recent episode of sinusitis. The illness has been present for about 6 weeks and has not responded to 2 weeks of appropriate antibiotics. She continues to have intermittent nosebleeds, fatigue, arthralgias, low grade fevers, and night sweats. Two new complaints have surfaced: she has a cough productive of white sputum and she occasionally expectorates quarter-sized clots of blood. She has pleuritic chest pain, but denies dyspnea, tobacco use, and cardiac or pulmonary disease.

She is afebrile with a respiratory rate of 16, blood pressure 120/74 mm Hg, and pulse rate 92 bpm. Her oxygen saturation is 98% on room air. There is dried blood in the nares, but the oropharynx is clear. Cardiac and pulmonary examinations are unremarkable.

Question 3.8.1 Which initial test is most appropriate?

A) Chest x-ray.

B) Sputum cytologic analysis.

C) Bronchoscopy.

D) Chest CT.

E) CBC.

Answer 3.8.1 The correct answer is "A." Hemoptysis is alarming to the patient and the physician—we hope. A stepwise approach is warranted with chest x-ray as the first step. Sputum for cytology might help if the suspicion for lung cancer was substantial, but the yield is likely to be low here. She may eventually require bronchoscopy if suggested by initial studies. Chest CT is likely to be part of the evaluation, but a chest x-ray should be performed first. Obtaining blood for a CBC is also important, although likely to be normal in the setting of minor hemoptysis.

You obtain the chest x-ray pictured in Figure 3-6.

FIGURE 3-6. Patient's chest x-ray.

You get the following laboratory results back:

• CBC: Leukocytosis, thrombocytosis and normochromic, normocytic anemia.

• ESR: 70 mm/hr.

• Urine dipstick: Positive for protein, heme, and red cells.

Question 3.8.2 Which of the following tests will best assist you in the diagnosis of this patient?

A) Antineutrophil cytoplasmic antibody (ANCA).

B) Antiglomerular basement membrane antibody.

C) Antinuclear antibody (ANA).

D) A and B.

E) A and C.

Answer 3.8.2 The correct answer is "D." This patient is presenting with the classic triad of granulomatosis with polyangiitis (GPA), a disease of the upper respiratory tract, lower respiratory tract, and kidneys. (This disease was formerly known as Wegener's granulomatosis. As a response to Wegener's association with the Nazi Party, professional bodies and journals have replaced his name with a descriptive name.) She has some of the additional signs and symptoms associated with GPA, as well. Common findings include: pleuritic chest pain, myalgias, arthralgias, ptosis, fever, weight loss, and purpuric skin lesions, among others.

ANCA, and especially c-ANCA that is more specific for GPA, is present in up to 90% of patients with GPA. An ANA is not helpful in diagnosing GPA. An antiglomerular basement membrane antibody (anti-GBM) may be helpful in diagnosing Goodpasture syndrome (named for an American pathologist—not a Nazi—so he gets to keep the eponym). Goodpasture syndrome can be clinically easily confused with GPA; they both present with respiratory and renal involvement. Thus, anti-GBM antibody will be helpful in differentiating these two (but about 10% of patients with Goodpasture syndrome will also have GPA—just to add to the confusion). For a partial list of causes of hemoptysis, see Table 3-5.

Question 3.8.3 Which of the following is NOT a radiographic finding of granulomatosis with polyangiitis?

A) Nodules that may be cavitary.

B) Alveolar opacification.

C) Pleural opacities.

D) Widened mediastinum.

Answer 3.8.3 The correct answer is "D." A widened mediastinum is not one of the classic findings in GPA. However, one may, on occasion, see hilar adenopathy. All of the other choices can be found in GPA. In the patient's x-ray (Fig. 3-6), a right upper lobe mass is easily distinguished. In a young, nonsmoking female presenting with these symptoms, such a lung mass should lead to the consideration of GPA or possibly an infectious process. She is less likely to have a malignant process.

The diagnostic evaluation is in progress. Laboratory tests are pending, and a chest CT is scheduled. You have arranged for a pulmonologist to see her. When you are on call, the physician covering the ED calls you to admit her for "massive hemoptysis." When you arrive, the patient looks comfortable and has normal vital signs. She begins a fit of coughing, expectorating several ounces of bright red blood. Her systolic blood pressure falls to 80 mm Hg. Her respiratory rate is 40. Her work of breathing has increased considerably. The situation does not improve after 5 minutes of observation, and her O₂ saturation is now 83%.

Question 3.8.4 Remembering the movie Moulin Rouge (which has nothing to do with this case except for hemoptysis), what is your first action in this situation?

A) Arrange emergent bronchoscopy.

B) Transfuse 2 units of blood.

C) Perform endotracheal intubation.

D) Provide bolus IV normal saline.

E) Tell her, "The show must go on!"

Answer 3.8.4 The correct answer is "C." Massive hemoptysis is variably defined as 100 to 600 mL of blood expectorated per day, and it can result in hemodynamic compromise and asphyxiation. Quantification of the blood loss by the patient is usually unreliable. The main cause of mortality with hemoptysis is not hypovolemia but rather asphyxiation from blood in the lungs. As with any patient in acute respiratory distress, the airway must be controlled first. The best choice here is to perform intubation. Since this patient is known to have a potential source for bleeding in the right lung, intubation of the left mainstem bronchus may protect the left lung from the blood. Also, placing this patient on her right side (so that the bleeding source is dependent) may protect the left lung. If available, emergent bronchoscopy may allow identification of the bleeding site and selective lung intubation. However, bronchoscopy is not well suited for stopping the hemorrhage. The most that a bronchoscopist can do is place an endobronchial blocker and seal off the bleeding lobe. Interventional radiology should usually be the first treatment once the bleeding site has been localized. Emergent surgery is indicated if the bleeding remains brisk and not responsive to other interventions. Fluid resuscitation is important. However, before any of these other measures is undertaken, the airway must be protected.

The patient stabilizes in the ICU. You plan to start treatment for her granulomatosis with polyangiitis. She does better and is discharged in 2 days.

Objectives: Did you learn to…

• Perform an appropriate evaluation on a patient with hemoptysis?

• Recognize the major causes of hemoptysis?

• Diagnose granulomatosis with polyangiitis?

• Identify and treat massive hemoptysis?

A 35-year-old African-American female presents with dyspnea worsening over the last 2 months. She also complains of cough, generalized fatigue, and intermittent low-grade fevers. She does not smoke. Chest x-ray shows hilar adenopathy and small bilateral pleural effusions. Spirometry is consistent with a restrictive pattern.

Question 3.9.1 Of the following, which is the most likely diagnosis?

A) Granulomatosis with polyangiitis.

B) Sarcoidosis.

C) Bronchogenic carcinoma.

D) Pneumonia.

E) Microscopic polyangiitis.

Answer 3.9.1 The correct answer is "B." The findings of hilar lymphadenopathy and a restrictive pattern on spirometry are most consistent with sarcoidosis. The chest x-ray findings do not support the diagnosis of granulomatosis with polyangiitis. Besides, it can't be "A"—we just did that case (and when would you see two GPA cases in a row on a test—let alone in your career?). "E" is incorrect. Microscopic polyangiitis is a systemic vasculitis related to GPA, presenting with similar features as GPA but without granulomatous disease. Bronchogenic carcinoma is unlikely in this relatively young nonsmoker who does not demonstrate findings of carcinoma on x-ray. The clinical history is not typical of pneumonia, and chest x-ray shows no infiltrate. Tuberculosis (TB), although not an answer option, should also be considered, and the appropriate history and testing should be completed. In fact, TB and sarcoidosis often present in a similar fashion.

Question 3.9.2 Which of the following is NOT commonly associated with sarcoidosis?

A) Hypercalcemia.

B) Elevated ACE levels.

C) Reduced diffusion capacity.

D) Hypothyroidism.

E) Facial or peripheral nerve palsy.

Answer 3.9.2 The correct answer is "D." Sarcoidosis is marked by the presence of noncaseating granulomas. While sarcoid can infiltrate the thyroid, it rarely, if ever, causes hypothyroidism. Pulmonary sarcoidosis includes a decreased diffusion capacity and decreased vital capacity. Other laboratory findings include hypercalcemia, hypercalciuria, elevated liver and pancreatic enzymes, and elevated ACE levels. Neurologic involvement occurs in up to 5% of patients and frequently presents as facial paralysis but may present as any central nervous system lesion. Peripheral nerves may also be involved.

Question 3.9.3 Which of the following is NOT found as a part of sarcoidosis?

A) Erythema nodosum.

B) Myocardial infarction.

C) Cardiac arrhythmias.

D) Elevated liver enzymes.

E) Vision loss.

Answer 3.9.3 The correct answer is "B." Sarcoidosis does not cause myocardial infarctions. While there is cardiac involvement with sarcoidosis, the manifestations are bundle branch block, cardiac arrhythmias, and sudden death. Many organs can be affected by sarcoidosis, including the skin, eye (iritis), heart, lung, liver, nervous system—essentially anywhere granulomas form.

Question 3.9.4 Which of the following is true about ACE levels in sarcoidosis?

A) An elevated ACE level is specific for sarcoidosis.

B) ACE levels often correlate with disease severity in sarcoidosis.

C) ACE inhibitors are effective in the treatment of sarcoidosis.

D) All of the above.

Answer 3.9.4 The correct answer is "B." One can follow ACE levels to track the progress of the disease. However, since treatment is based on symptoms, following ACE levels is not recommended. "A" is incorrect. ACE levels may be elevated in silicosis, miliary TB, and asbestosis, among others. "C" is incorrect. ACE inhibitors are not used to treat sarcoidosis.

This patient is found to have only pulmonary sarcoidosis with some mild systemic symptoms.

Question 3.9.5 Which of the following is the best initial choice for management?

A) Observation.

B) Oral corticosteroids.

C) Oral antibiotics.

D) Inhaled corticosteroids.

E) Methotrexate.

Answer 3.9.5 The correct answer is "A." This patient has apparent pulmonary-limited disease and has minimal systemic symptoms. Nearly 50% of patients with sarcoidosis may have spontaneous resolution of their symptoms without treatment. In fact, treatment may actually prolong the disease process. If her pulmonary or systemic symptoms worsen or are causing major life problems, she should be started on oral steroids. Systemic corticosteroid therapy is the mainstay of treatment for sarcoidosis. Methotrexate and other immune-modulating drugs may be employed as well and offer a steroid-sparing effect, but these are not first-line agents. Evidence for the use of inhaled corticosteroids is lacking. Antibiotics are not effective.

Objectives: Did you learn to…

• Recognize the clinical manifestations of sarcoidosis?

• Manage a patient with mild sarcoidosis?

A 57-year-old male with no prior medical history comes in to clinic with a 1-week history of right rib pain and low-back pain. The rib pain is worse with deep breaths and especially bothers him at night. There has been no trauma. He has lost 20 lb in the last 3 months. He has a cough productive of white sputum. He denies any other symptoms. He smokes one to two packs of cigarettes per day but does not drink alcohol.

Vital signs: temperature 36.5°C, pulse rate 95 bpm, blood pressure 110/70 mm Hg, respiratory rate 16. On room air, his oxygen saturation is 96%. There is no adenopathy. His lung sounds are clear on the left and decreased on the right. There is dullness to percussion and decreased tactile fremitus over the right lower lung field.

Question 3.10.1 Based on this patient's history and physical examination, what do you expect to find on chest x-ray?

A) Normal chest x-ray.

B) Cavitary lung lesion.

C) Pleural effusion.

D) Expanded lung fields.

E) Pneumothorax.

Answer 3.10.1 The correct answer is "C." This patient's findings suggest pleural effusion. Everything is diminished in pleural effusion: there is dullness to percussion, decreased breath sounds, decreased tactile fremitus, and decreased voice transmission. A cavitary lung lesion presents with either a normal examination or findings similar to an infiltrate (e.g., crackles, increased fremitus, and dullness to percussion). Expanded lung fields on chest x-ray are often seen in patients with COPD or asthma, and examination findings include prolonged expiratory phase, wheezing, and resonance to percussion. Pneumothorax presents with hyperresonance to percussion, decreased breath sounds, and decreased fremitus.

Your suspicions are confirmed. The chest x-ray shows obliteration of the right hemidiaphragm, and the posterior costophrenic angle is obscured on the lateral view, consistent with pleural effusion. There is also a right upper lobe lung mass.

Question 3.10.2 Which of the following will provide the most information and guidance for your thoracentesis?

A) Supine chest x-ray.

B) Chest CT.

C) Lateral decubitus chest x-ray.

D) Chest ultrasound.

E) Apical view chest radiograph.

Answer 3.10.2 The correct answer is "D." Prior to performing a thoracentesis, you must know whether the effusion is loculated or freely flowing. Portable ultrasound has become a validated and widely accepted modality to diagnose and access a pleural effusion. Also, ultrasonography has been found to be more sensitive for detection of pleural fluid than a chest radiograph. Chest CT is somewhat more sensitive but far more cumbersome and does not allow a bedside diagnosis and treatment. A decubitus film, with the affected side down, would allow you see the effusion "layer out" unless it is loculated but again is less sensitive. A supine chest x-ray may cause the effusion to "layer out" too, but you will not be able to see it as well, which is why effusions may be missed when a patient is unable to stand or sit upright for his x-ray.

Question 3.10.3 Relative and absolute contraindications to thoracentesis include all of the following EXCEPT:

A) Herpes zoster in the area of needle placement.

B) Coagulopathy.

C) Diaphragmatic rupture.

D) Positive pressure ventilation.

E) History of recurrent laryngeal nerve injury or compromise.

Answer 3.10.3 The correct answer is "E." Absolute contraindications include chest wall compromise (e.g., burn, cellulitis, herpes zoster, ruptured diaphragm) and cases where chest tube thoracostomy would be more appropriate. Relative contraindications are poor patient cooperation, coagulopathy, anticoagulation therapy, very small effusions (<10 mm on decubitus film view), positive pressure ventilation, and pleural adhesions.

Question 3.10.4 On ultrasound, the effusion appears free flowing and not loculated. What is the most appropriate next step?

A) Referral for surgical drainage.

B) Place a chest tube to drain the effusion.

C) Perform an ultrasound-guided diagnostic thoracentesis at the bedside.

D) Order two pizzas, one for you and one for the patient (you have both had a long day and are hungry).

Answer 3.10.4 The correct answer is "C." The patient has a relatively large pleural effusion. Ultrasound-guided thoracentesis is a good first step in evaluating this effusion. Ultrasound guidance is quickly becoming the standard of care as it has been shown to decrease complications of pneumothorax as well as the number of unsuccessful clinical attempts or "dry taps." Referral to a thoracic surgeon may eventually be necessary, but this would not be the first step. Placing a chest tube into an effusion is not recommended at this point, and the diagnostic study should be obtained first.

Ultrasound-guided thoracentesis is successful in obtaining fluid. The fluid is amber and cloudy, with a pH 7.3, lactate dehydrogenase (LDH) 800 IU/L, glucose 65 mg/dL, total protein 5.5 g/dL, WBC 1,300/mm³, RBC 50,000/mm³. Serum studies done the same day include LDH 155 IU/L, glucose 99 mg/dL, and total protein 7.0 g/dL. Cytology, Gram stain, and culture of the pleural fluid are pending.

Question 3.10.5 Which of the following is the most accurate statement regarding the pleural fluid analysis?

A) The fluid is due to infection.

B) The fluid is due to cancer.

C) The fluid is a transudate.

D) The fluid is an exudate.

Answer 3.10.5 The correct answer is "D." Pleural effusions are broadly categorized as exudates and transudates (see Tables 3-6 and 3-7). Such a categorization helps to narrow the differential diagnosis. In this case, several elements of the pleural fluid are consistent with an exudate. LDH and protein can be used to determine whether the pleural fluid is transudative or exudative. Per Light's criteria, a pleural effusion is suggestive of an exudative process if two of any of the following criteria are met: pleural fluid LDH > 2/3 the upper limit of normal serum LDH, a pleural LDH:serum LDH ratio of >0.6, and a pleural protein:serum protein ratio of >0.5. All three of these indicators point to an exudate in this case. Also, exudative effusions tend to have a higher degree of cellularity than transudative effusions. With the information given, it is difficult to determine if the effusion is related to infection, cancer, or some other process.

The pleural fluid cytology comes back negative. The patient's symptoms and examination have not changed. Repeat radiograph still shows an upper lobe mass.

Question 3.10.6 What is the most appropriate next step in approaching this pleural effusion?

A) Await pleural fluid culture results.

B) Perform bedside chest tube drainage of the effusion.

C) Refer for surgical evacuation of the effusion.

D) Refer for bronchoscopy.

E) Place a chest tube for chemical pleurodesis.

Answer 3.10.6 The correct answer is "D." The effusion is clearly exudative, and the patient appears to have a lung mass. Biopsy of the lung mass via bronchoscopy is indicated. A negative pleural fluid cytology does not rule out lung cancer. Positive cytology indicates advanced stage lung cancer. Chest tube drainage of a pleural effusion is not recommended except under extraordinary circumstances. Intermittent thoracentesis is preferred and has lower morbidity. Surgical evacuation of the fluid would be indicated if the patient were symptomatic, the effusion was loculated and/or related to infection. If the effusion grows, or is drained and recurs, it may respond to pleurodesis. Otherwise, pleurodesis is not indicated at this time.

Now that you have gained expertise with ultrasound of a pleural effusion, your colleague sends you a patient that has a pleural effusion on chest x-ray. Your colleague asks you whether you could "tap" the fluid for him as he does not feel comfortable with the portable ultrasound. Also, he has a tee time in 30 minutes.

Question 3.10.7 On ultrasound, you quickly visualize the chest and see a septated and loculated pleural effusion. What is the best next step?